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A markedly increased demand for vascular ultrasound laboratory and other imaging studies in COVID-19-positive patients has occurred, due to most of these patients having a markedly elevated D-dimer and a presumed prothrombotic state in many of the very ill patients.,In the present report, we have summarized a broad institutional consensus focusing on evaluation and recommended empirical therapy for COVID-19-positive patients.,We recommend following the algorithms with the idea that as more data becomes available these algorithms may well change. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
Supplemental Digital Content is available in the text.,Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality.,Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this.,We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities.,Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke.,We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year.,Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%-46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana.,Results compared with the prior year and time trend analyses were consistent.,Reperfusion treatments also appeared to decline by 31% (95% CI, 3%-51%), and specifically thrombolysis by 33% (95% CI, 4%-55%), but this finding had less precision.,Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly.,Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study.,Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19. | Stroke assistance is facing changes and new challenges since COVID‐19 became pandemic.,A variation on the patient influx might be one of the greater concerns, due to fewer people coming to emergency departments or coming too late.,However, no data quantifying this have been published until now.,The aim was to analyse the impact of the COVID‐19 epidemic outbreak on hospital stroke admissions and their characteristics in our region.,The data of every patient admitted to any hospital of our healthcare system with a diagnosis of ischaemic stroke between 30 December 2019 and 19 April 2020 were reviewed.,Demographic and clinical data were recorded and compared between periods before and after the setting of the state of emergency secondary to the COVID‐19 outbreak.,In total, 354 patients with ischaemic stroke were admitted in our study period.,There was a weekly average of 27.5 cases before the setting of the state of emergency against 12 afterwards (P < 0.001).,This drop in stroke cases occurred progressively from week 11, persisting in time despite the decrease in confirmed cases of COVID‐19.,No differences in the proportion of intravenous thrombolysis (21.1% vs.,21.5%, P = 0.935) or endovascular therapy (12.4% vs.,15.2%, P = 0.510) were found, nor in other demographic or clinical characteristics except for median onset‐to‐door time (102 vs. 183 min, P = 0.015).,This observational study offers the perspective of a whole region in one of the countries more heavily stricken by the SARS‐CoV‐2 epidemic and shows that the decrease of stroke events, since the beginning of the COVID‐19 outbreak, happened globally and without any specific patient distribution. | 1 |
What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. | Cardiac injury in patients infected with the novel Coronavirus (COVID-19) seems to be associated with higher morbimortality.,We provide a broad review of the clinical evolution of COVID-19, emphasizing its impact and implications on the cardiovascular system.,The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by overproduction of inflammatory cytokines (IL-6 and TNF-α) leading to systemic inflammation and multiple organ dysfunction syndrome, acutely affecting the cardiovascular system.,Hypertension (56.6%) and diabetes (33.8%) are the most prevalent comorbidities among individuals with COVID-19, who require hospitalization.,Furthermore, cardiac injury, defined as elevated us-troponin I, significantly relates to inflammation biomarkers (IL-6 and C-reactive protein (CRP), hyperferritinemia, and leukocytosis), portraying an important correlation between myocardial injury and inflammatory hyperactivity triggered by viral infection.,Increased risk for myocardial infarction, fulminant myocarditis rapidly evolving with depressed systolic left ventricle function, arrhythmias, venous thromboembolism, and cardiomyopathies mimicking STEMI presentations are the most prevalent cardiovascular complications described in patients with COVID-19.,Moreover, SARS-CoV-2 tropism and interaction with the RAAS system, through ACE2 receptor, possibly enhances inflammation response and cardiac aggression, leading to imperative concerns about the use of ACEi and ARBs in infected patients.,Cardiovascular implications result in a worse prognosis in patients with COVID-19, emphasizing the importance of precocious detection and implementation of optimal therapeutic strategies. | 1 |
The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic. | •There are anecdotal reports of lower stroke rates during the COVID-19 pandemic.,•Our center confirms a local fall in new acute stroke diagnoses during the pandemic.,•This fall is driven by fewer patients presenting with mild symptoms in our network.,•Mild stroke symptoms ought to not be ignored in community practices.,There are anecdotal reports of lower stroke rates during the COVID-19 pandemic.,Our center confirms a local fall in new acute stroke diagnoses during the pandemic.,This fall is driven by fewer patients presenting with mild symptoms in our network.,Mild stroke symptoms ought to not be ignored in community practices.,Although there is evidence to suggest a high rate of cerebrovascular complications in patients with SARS-CoV-2 infection, anecdotal reports indicate a falling rate of new ischemic stroke diagnoses.,We conducted an exploratory single-center analysis to estimate the change in number of new stroke diagnoses in our region, and evaluate the proximate reasons for this change during the COVID-19 pandemic at a tertiary care center in New Jersey.,A Comprehensive Stroke Center prospective cohort was retrospectively analyzed for the number of stroke admissions, demographic features, and short-term outcomes 5 months prior to 3/1/2020 (pre-COVID-19), and in the 6 weeks that followed (COVID-19 period).,The primary outcome was the number of new acute stroke diagnoses before and during the COVID-19 period, as well as the potential reasons for a decline in the number of new diagnoses.,Of the 328 included patients, 53 (16%) presented in the COVID-19 period.,There was a mean fall of 38% in new stroke diagnoses (mean 1.13/day [SD 1.07] from 1.82/day [SD 1.38], p<0.01), which was related to a 59% decline in the number of daily transfers from referral centers (p<0.01), 25% fewer telestroke consultations (p=0.08), and 55% fewer patients presenting directly to our institution by private vehicle (p<0.01) and 29% fewer patients through emergency services (p=0.09).,There was no significant change in the monthly number of strokes due to large vessel occlusion (LVO), however the proportion of new LVOs nearly doubled in the COVID-19 period (38% vs. 21%, p=0.01).,The observations at our tertiary care center corroborate anecdotal reports that the number of new stroke diagnoses is falling, which seems related to a smaller proportion of patients seeking healthcare services for milder symptoms.,These preliminary data warrant validation in larger, multi-center studies. | 1 |
Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario.,In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team.,Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis.,Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation.,A protected code stroke algorithm was developed.,Features specific to prenotification and clinical status of the patient were used to define precode screening.,These include primary infectious symptoms, clinical, and examination features.,A focused framework was then developed with regard to a protected code stroke.,We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke.,We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management.,These considerations and suggested algorithms can be utilized and adapted for local practice. | Acute stroke remains a medical emergency even during the COVID-19 pandemic.,Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations.,Here we present a series of four patients with COVID-19 that presented with acute stroke.,We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection.,All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study.,Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study.,Retrospective patient data were obtained from electronic medical records.,Informed consent was obtained.,We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection.,We elucidate the clinical characteristics, imaging findings, and the clinical course.,Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke.,Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient.,Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection. | 1 |
An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | 1 |
The association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown.,To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data.,A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020.,These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis.,The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve.,Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis.,The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively.,PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography.,DVT was present in 42.4% of patients with PE.,D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively).,Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT.,The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19.,© RSNA, 2020,Supplemental material is available for this article.,See also the editorial by Woodard in this issue. | Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19. | 1 |
The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic. | Patients with the Coronavirus Disease of 2019 (COVID-19) are at increased risk for thrombotic events and mortality.,Various anticoagulation regimens are now being considered for these patients.,Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared.,We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population.,Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study.,Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist.,Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications.,We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37-83 years), 21.2% of whom were female.,Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate.,Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small- moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation.,Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery.,Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen. | 1 |
Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden.,This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs).,This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia).,CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography.,The participants were divided into three groups based on TyG index tertiles.,The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001).,Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05).,The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001).,The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex.,TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy. | Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is the leading cause of morbidity and mortality from cardiovascular disease worldwide.,Several recent studies have shown the relationship between the triglyceride-glucose (TyG) index and vascular disease; however, the role of the TyG index in NSTE-ACS has not been extensively assessed.,Thus, we aimed to investigate the association of the TyG index with cardiovascular risk factors and outcomes in NSTE-ACS.,Overall, 438 patients with NSTE-ACS were enrolled to examine the association of the TyG index with the SYNTAX score and major adverse cardiovascular events (MACEs).,The TyG index was calculated as ln (fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2).,The severity of coronary lesions was quantified by the SYNTAX score.,MACEs included cardiac death, nonfatal myocardial infarction, target vessel revascularization, congestive heart failure, and nonfatal stroke.,All the patients underwent a 12-month follow-up for MACEs after admission.,Multivariate regression analysis identified metabolic risk factors as independent parameters correlated with the TyG index.,The prevalence of glucose metabolism disorder, metabolic syndrome, and MACEs increased with increasing TyG index.,The TyG index showed a strong diagnostic performance for cardiovascular risk factors and was independently associated with the SYNTAX score (OR 6.055, 95% CI 2.915-12.579, P < 0.001).,The risk of MACEs (12.8% and 22.8% for the low TyG index and high TyG index groups, respectively; adjusted HR = 1.791, 95% CI 1.045-3.068, P = 0.034) significantly increased in the high TyG index group as compared with the low TyG index group.,The multivariate Cox regression analysis further revealed that the TyG index was an independent predictor of MACEs (HR 1.878, 95% CI 1.130-3.121, P = 0.015).,In conclusion, the TyG index might be an independent predictor of coronary artery disease severity and cardiovascular outcomes in NSTE-ACS. | 1 |
•SARS-CoV-2 may impair host antiviral response, causing subsequent hyperinflammation.,•SARS-CoV-2 likely deranges the renin angiotensin aldosterone system (RAAS).,•Hyperinflammation and RAAS imbalance may drive acute lung injury and coagulopathy.,•RAAS imbalance impairs fibrinolysis, which can result in relative hypofibrinolysis.,•This can lead widespread immunothrombosis, contributing to multi-organ damage.,SARS-CoV-2 may impair host antiviral response, causing subsequent hyperinflammation.,SARS-CoV-2 likely deranges the renin angiotensin aldosterone system (RAAS).,Hyperinflammation and RAAS imbalance may drive acute lung injury and coagulopathy.,RAAS imbalance impairs fibrinolysis, which can result in relative hypofibrinolysis.,This can lead widespread immunothrombosis, contributing to multi-organ damage.,Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy.,In this paper, we present an immunothrombosis model of COVID-19.,We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
The study aimed to evaluate Choroidal Vascularity Index (CVI) of Haller’s and Sattler’s layers and their relationships with choroidal and retinal thickness, volumes measured on enhanced depth imaging-optical coherence tomography (OCT) scans in the eyes of patients without diabetes, patients with diabetes with no diabetic retinopathy (DR) and patients with diabetes and DR.,Retrospective analysis of 165 eyes from 84 Singapore Indian Eye Study-2 study participants (group 1: no diabetes, group 2: diabetes with no DR and group 3: with DR).,Groups 1 and 2 were matched by age and gender from group 3.,In the eyes of patients with diabetes without DR, the macular CVI of Haller’s but not Sattler’s layer was significantly reduced compared with eyes of patients without diabetes.,Eyes with >5 years of diabetes have significantly decreased CVI of Sattler’s layers (mean difference=0.06 ± 0.10, p=0.04) and also decreased subfoveal choroidal volume (mean difference=0.89 ± 0.16 mm3, p=0.02), compared with those with ≤5 years of diabetes.,Diabetic eyes without DR had significantly lower CVI of macular Haller’s layer than those of healthy controls.,With a longer duration of diabetes, CVI of subfoveal Sattler’s layer and choroidal volume continue to decrease, irrespective of diabetic control, suggesting that early diabetic choroidopathy mainly affects larger choroidal veins initially before medium-sized arterioles.,The CVI of macular Haller’s layer could potentially be used as a marker on spectral domain OCT imaging in newly diagnosed patients with diabetes for the onset of DR and as a possible prognostication tool in diabetic eyes.,Future prospective longitudinal studies in diabetic eyes would be useful in establishing the relationship between CVIs of Haller’s and Sattler’s layer with visual acuity as a marker of photoreceptor health and visual prognosis. | The relationships between changes in choroidal vasculature and the severity of diabetic retinopathy (DR) remain unclear.,We assessed choroidal changes in diabetic patients by measuring choroidal vascularity index (CVI) in conjunction with DR stage.,In this study, patients with diabetes and healthy controls were retrospectively analyzed.,Subjects were divided into seven groups as follows: Healthy controls, no DR, mild/moderate non-proliferative DR (NPDR), severe NPDR, proliferative DR (PDR), panretinal photocoagulation-treated DR, and clinically significant macular edema.,The mean CVI values in the above groups were 69.08, 67.07, 66.28, 66.20, 63.48, 65.38, and 66.28, respectively.,The eyes of diabetic patients exhibited a significantly lower CVI value than those of healthy controls even without DR.,The PDR group exhibited a significantly lower CVI value than the healthy control, no DR, and mild/moderate NPDR groups.,Age, sex, disease duration, glycated hemoglobin, fasting blood sugar, or intraocular pressure had no correlation with CVI.,In multivariate regression analysis, thicker subfoveal choroid and thinner central retina were significantly associated with higher CVI values.,These findings carefully suggest that changes in choroidal vasculature could be the primary event in diabetes even where there is no DR. | 1 |
The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches.,ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date.,This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data.,Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed.,Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided. | Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities.,Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation.,However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation.,Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise.,While algorithms have been developed to automate this process, the results often lack accuracy.,Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance.,Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata.,This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods.,We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods. | 1 |
Little is known about the effect of the Coronavirus disease 2019 pandemic on stroke care and the impact of the epidemic on acute stroke hospitalizations has not been described.,We analyze the stroke admission rate in three hospitals in New York City from January 1, 2020 through April 17, 2020, identifying all cases of acute ischemic stroke, intraparenchymal hemorrhage and subarachnoid hemorrhage.,We confirmed 518 cases of out-of-hospital stroke.,During the baseline period up to February 25, 2020, the daily stroke admission rate was stable, with the slope of the regression describing the number of admissions over time equal to -0.33 (se = 1.21), not significantly different from 0 (p = 0.79), with daily admissions averaging 41.,During the pandemic period, the slope was -4.4 (se = 1.00); i.e., the number of stroke admissions decreased an average of 4.4 per week, (p = 0.005), with weekly admissions averaging 23, a reduction of 44% versus baseline.,This general result was not different by patient age, sex, or race/ethnicity.,The weekly stroke admission rate started declining two weeks prior to the local surge of coronavirus admissions.,The consequences of lack of diagnosis and treatment of a large proportion of acute stroke patients are likely severe and lasting. | During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement.,Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion.,The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement.,In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States).,This study included 1600 patients treated by EVT for acute ischemic stroke.,Date of EVT and symptom onset-to-groin puncture time were collected.,Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures.,Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test.,The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001).,In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]).,Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place. | 1 |
The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI).,The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI.,A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies.,STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included.,A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3).,The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization.,As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients).,COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs).,COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients).,Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients).,The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients).,COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics.,PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
Triglyceride Glucose (TyG) index has been associated with an increased risk in cardiovascular events.,Silent coronary disease is common in patients with type 2 diabetes.,In Vietnam, a low-middle income country, the burden of cardiovascular disease is growing simultaneously with the epidemiologic transition.,Our aim was to assess the prevalence of coronary stenoses (CS) in patients with type 2 diabetes and no history or symptom of cardiovascular disease and to investigate the association between TyG index and cardiovascular risk factors and both the presence and severity of CS.,Futhermore, we assessed the value of TyG index in predicting subclinical CS.,This was a cross-sectional observational study.,We recruited 166 patients at Ninh Thuan General Hospital, Vietnam.,TyG index and HOMA-IR were calculated, and a coronary computed tomography angiography (CCTA) was performed.,The population was classified according to tertiles of TyG index.,The highest TyG values were associated with higher BMI, waist circumference, total cholesterol, LDL-cholesterol, triglycerides, plasma glucose, HbA1c levels and HOMA-IR, lower HDL-cholesterol, a higher incidence of metabolic syndrome and less frequent physical activity (p < 0.05 to < 0.0001).,TyG index correlated with logHOMA-IR (p < 0.0001).,CS ≥ 50% were present in 60 participants and 32 had coronary artery stenosis ≥ 70%.,TyG index and HOMA-IR were significantly higher in patients with CS ≥ 70%.,The number of narrowed coronary arteries and the degree of stenosis were associated with higher TyG index levels (p = 0.04 and < 0.005 respectively).,A TyG index ≥ 10 was significantly associated with an increased risk of multiple coronary artery disease and of more severe CS.,After adjusting for confounding factors, including logHOMA-IR, these risks remained mostly significant.,A TyG index threshold at 10 resulted in 57% sensitivity and 75% specificity for predicting the presence of CS ≥ 70%.,In subgroup analysis TyG index ≥ 10 was associated with an increased risk in CS ≥ 70% in patients treated with statin or antiplatelet therapy.,More than one third of asymptomatic patients with type 2 diabetes had significant CS on CCTA.,TyG index may be considered as a marker for insulin resistance and increased TyG index could identify patients with high risk of coronary artery stenoses and is associated with the number and the severity of artery stenoses. | The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes.,Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain.,The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.,A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study.,Patients were divided into tertiles according to their TyG index.,The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke.,The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2).,The incidence of MACE increased with TyG index tertiles at a 3-year follow-up.,The Kaplan-Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005).,Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201-1.746; P < 0.001).,The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001).,Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).,The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS. | 1 |
A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19.,The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE.,This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion.,Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients.,Ninety-two patients were included, 29 (32%) had PE.,PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years).,Clinical symptoms and COVID-19 CT features were similar in both groups.,PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms.,Corticosteroid boluses were more frequently used in PE patients (62% vs.,43%).,No patients met ISTH DIC criteria.,Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups.,Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01).,Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively.,Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE.,This difference is more pronounced when the fold increase between weeks 1 and 2 is compared. | While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse.,We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients.,In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19.,Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded.,Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA.,The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001).,In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively].,In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002).,PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.,Graphical Abstract | 1 |
The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. | Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system.,Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD).,We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity.,Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction).,We recruited 79 patients with obstructive coronary artery disease.,The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2-41.2].,Over a median follow up of 10.5 years [9.6-10.8years], MACE occurred in 46% of patients (36 events).,On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01).,After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24-4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42-11.5, p = 0.009).,Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD. | 1 |
COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None. | COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown. | 1 |
Supplemental Digital Content is available in the text.,Arterial hypertension and its organ sequelae show characteristics of T cell-mediated inflammatory diseases.,Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage.,Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk.,The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health.,Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis.,Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage.,To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout-deficient mice received propionate (200 mmol/L) or control in the drinking water.,To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg-1·d-1 subcutaneous) for 14 days.,To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg-1·d-1 subcutaneous) for 28 days.,Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry.,Blood pressure was measured by radiotelemetry.,Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate.,Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models.,Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II-infused wild-type NMRI mice.,Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout-deficient mice.,Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice.,Cardioprotective effects of propionate were abrogated in regulatory T cell-depleted angiotensin II-infused mice, suggesting the effect is regulatory T cell-dependent.,Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health.,The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease. | Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases.,Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown.,To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice.,Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations.,Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension.,The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis.,And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately.,Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated.,Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension.,And the significance of early intervention for pre-hypertension was emphasized.,The online version of this article (doi:10.1186/s40168-016-0222-x) contains supplementary material, which is available to authorized users. | 1 |
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of coronavirus disease 2019 (COVID-19) infection or affect disease severity.,Prior studies have not examined risks by medication dose.,This retrospective cohort study included people aged ≥18 years enrolled in a US integrated healthcare system for at least 4 months as of 2/29/2020.,Current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications.,COVID-19 infections and hospitalizations were identified through 6/14/2020 from laboratory and hospitalization data.,We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for race/ethnicity, obesity, and other covariates.,Among 322,044 individuals, 826 developed COVID-19 infection.,Among people using ACEI/ARBs, 204/56,105 developed COVID-19 (3.6 per 1,000 individuals) compared with 622/265,939 without ACEI/ARB use (2.3 per 1,000), yielding an adjusted OR of 0.91 (95% CI 0.74-1.12).,For use of <1 defined daily dose (DDD) vs. nonuse, the adjusted OR for infection was 0.92 (95% CI 0.66-1.28); for 1 to <2 DDDs, 0.89 (95% CI 0.66-1.19); and for ≥2 DDDs, 0.92 (95% CI 0.72-1.18).,The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 26% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.98 (95% CI 0.63-1.54), and there was no association with dose.,These findings support current recommendations that individuals on these medications continue their use. | A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19. | 1 |
Diabetic cardiomyopathy (DCM) is one of the leading causes of heart failure in patients with diabetes mellitus, with limited effective treatments.,The cardioprotective effects of sodium‐glucose cotransporter 2(SGLT2) inhibitors have been supported by amounts of clinical trials, which largely fills the gap.,However, the underlying mechanism still needs to be further explored, especially in terms of its protection against cardiac fibrosis, a crucial pathophysiological process during the development of DCM.,Besides, endothelial‐to‐mesenchymal transition (EndMT) has been reported to play a pivotal role in fibroblast multiplication and cardiac fibrosis.,This study aimed to evaluate the effect of SGLT2 inhibitor dapagliflozin (DAPA) on DCM especially for cardiac fibrosis and explore the underlying mechanism.,In vivo, the model of type 2 diabetic rats was built with high‐fat feeding and streptozotocin injection.,Untreated diabetic rats showed cardiac dysfunction, increased myocardial fibrosis and EndMT, which was attenuated after treatment with DAPA and metformin.,In vitro, HUVECs and primary cardiac fibroblasts were treated with DAPA and exposed to high glucose (HG).,HG‐induced EndMT in HUVECs and collagen secretion of fibroblasts were markedly inhibited by DAPA.,Up‐regulation of TGF‐β/Smad signalling and activity inhibition of AMPKα were also reversed by DAPA treatment.,Then, AMPKα siRNA and compound C abrogated the anti‐EndMT effects of DAPA in HUVECs.,From above all, our study implied that DAPA can protect against DCM and myocardial fibrosis through suppressing fibroblast activation and EndMT via AMPKα‐mediated inhibition of TGF‐β/Smad signalling. | To explore mechanisms by which SGLT2 inhibitors protect diabetic hearts from heart failure, we examined the effect of empagliflozin (Empa) on the ultrastructure of cardiomyocytes in the noninfarcted region of the diabetic heart after myocardial infarction (MI).,OLETF, a rat model of type 2 diabetes, and its nondiabetic control, LETO, received a sham operation or left coronary artery ligation 12 h before tissue sampling.,Tissues were sampled from the posterior ventricle (i.e., the remote noninfarcted region in rats with MI).,The number of mitochondria was larger and small mitochondria were more prevalent in OLETF than in LETO.,Fis1 expression level was higher in OLETF than in LETO, while phospho‐Ser637‐Drp1, total Drp1, Mfn1/2, and OPA1 levels were comparable.,MI further reduced the size of mitochondria with increased Drp1‐Ser616 phosphorylation in OLETF.,The number of autophagic vacuoles was unchanged after MI in LETO but was decreased in OLETF.,Lipid droplets in cardiomyocytes and tissue triglycerides were increased in OLETF.,Empa administration (10 mg/kg per day) reduced blood glucose and triglycerides and paradoxically increased lipid droplets in cardiomyocytes in OLETF.,Empa suppressed Fis1 upregulation, increased Bnip3 expression, and prevented reduction in both mitochondrial size and autophagic vacuole number after MI in OLETF.,Together with the results of our parallel study showing upregulation of SOD2 and catalase by Empa, the results indicate that Empa normalizes the size and number of mitochondria in diabetic hearts and that diabetes‐induced excessive reduction in mitochondrial size after MI was prevented by Empa via suppression of ROS and restoration of autophagy. | 1 |
Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients. | Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19. | 1 |
SARS-CoV-2 infection is associated with hypercoagulability which predisposes to venous thromboembolism (VTE).,We analyzed platelet and neutrophil activation in COVID-19 patients and their association with VTE.,Hospitalized COVID-19 patients and age- and sex-matched healthy controls were studied.,Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase-9 (MMP-9), a neutrophil-released enzyme, were measured.,Four patients were re-studied after recovery.,The activating effect of COVID-19 plasma on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied.,36 COVID-19 patients and 31 healthy controls were studied; 8/36 COVID-19 patients (22.2%) developed VTE.,Platelets and neutrophils were activated in COVID-19 patients.,NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis.,Plasmatic MMP-9 was significantly increased in COVID-19 patients.,Platelet and neutrophil activation markers, but less so NETs, normalized after recovery.,In vitro, plasma from COVID-19 patients triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic dose low-molecular weight heparin, but not by aspirin or dypiridamole.,Platelet and neutrophil activation are key features of COVID-19 patients.,NET biomarkers may help to predict clinical worsening and VTE, and may guide LMWH-treatment intensity. | The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19. | 1 |
Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart. | 1 |
On 11 March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a pandemic.,As of 22 April, more than 2.4 million cases have been confirmed worldwide [1].,In light of the widely documented lung injuries related to COVID-19 [2, 3], concerns have been raised regarding the assessment of lung injury for discharged patients.,A recent report portrayed that discharged patients with COVID-19 pneumonia still have residual abnormalities in chest computed tomography (CT) scans, with ground-glass opacity as the most common pattern [4].,Persistent impairment of pulmonary function and exercise capacity have been known to last for months or even years [5-8] in the recovered survivors from other coronavirus pneumonia (severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)).,However, until now, there is no report in regard to pulmonary function in discharged COVID-19 survivors.,This article aims to describe the characteristics of pulmonary function in these subjects.,In discharged survivors with COVID-19, impairment of diffusion capacity is the most common abnormality of lung function, followed by restrictive ventilatory defects, which are both associated with the severity of the diseasehttps://bit.ly/2yUaBaT | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
Cardiac Troponin (hs-TnT) elevation has been reported in unselected patients hospitalized with COVID-19 however the mechanism and relationship with mortality remain unclear.,Consecutive patients admitted to a high-volume intensive care unit (ICU) in London with severe COVID-19 pneumonitis were included if hs-TnT concentration at admission was known.,Kaplan-Meier survival analysis performed, with cohorts classified a priori by multiples of the upper limit of normal (ULN). 277 patients were admitted during a 7-week period in 2020; 176 were included (90% received invasive ventilation). hs-TnT at admission was 16.5 (9.0 to 49.3) ng/L, 56% had concentrations >ULN. 56 patients (31.8%) died during the index admission.,Admission hs-TnT level was lower in survivors (12.0 (8.0-27.8) vs 28.5 (14.0 to 81.0) ng/L, p = 0.001).,Univariate predictors of mortality were age, APACHE-II Score and admission hs-TnT (HR 1.73, p = 0.007).,By multivariate regression, only age (HR 1.33, CI: 1.16.to 1.51, p < 0.01) and admission hs-TnT (HR 1.94, CI: 1.22 to 3.10, p = 0.006) remained predictive.,Survival was significantly lower when admission hs-TnT was >ULN (log-rank p-value<0.001).,Peak hs-TnT was higher in those who died but was not predictive of death after adjustment for other factors.,In conclusion, in critically ill patients with COVID-19 pneumonitis, the hs-TnT level at admission is a powerful independent predictor of the likelihood of surviving to discharge from ICU.,In most cases, hs-TnT elevation does not represent major myocardial injury but acts as a sensitive integrated biomarker of global stress.,Whether stratification based on admission Troponin level could be used to guide prognostication and management warrants further evaluation. | Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19. | 1 |
Ambient air pollution is a leading cause of non-communicable disease globally.,The largest proportion of deaths and morbidity due to air pollution is now known to be due to cardiovascular disorders.,Several particulate and gaseous air pollutants can trigger acute events (e.g. myocardial infarction, stroke, heart failure).,While the mechanisms by which air pollutants cause cardiovascular events is undergoing continual refinement, the preponderant evidence support rapid effects of a diversity of pollutants including all particulate pollutants (e.g. course, fine, ultrafine particles) and gaseous pollutants such as ozone, on vascular function.,Indeed alterations in endothelial function seem to be critically important in transducing signals and eventually promoting cardiovascular disorders such as hypertension, diabetes, and atherosclerosis.,Here, we provide an updated overview of the impact of particulate and gaseous pollutants on endothelial function from human and animal studies.,The evidence for causal mechanistic pathways from both animal and human studies that support various hypothesized general pathways and their individual and collective impact on vascular function is highlighted.,We also discuss current gaps in knowledge and evidence from trials evaluating the impact of personal-level strategies to reduce exposure to fine particulate matter (PM2.5) and impact on vascular function, given the current lack of definitive randomized evidence using hard endpoints.,We conclude by an exhortation for formal inclusion of air pollution as a major risk factor in societal guidelines and provision of formal recommendations to prevent adverse cardiovascular effects attributable to air pollution. | Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden.,We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels.,We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements.,Using integrated exposure-response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure-response functions spanning the global range of exposure.,Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015.,Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia.,Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015.,Exposure to ozone caused an additional 254 000 (95% UI 97 000-422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015.,Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries.,Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction.,Bill & Melinda Gates Foundation and Health Effects Institute. | 1 |
Supplemental Digital Content is available in the text.,High blood pressure (BP) is a risk factor for cardiovascular morbidity and mortality.,While BP is regulated by the function of kidney, vasculature, and sympathetic nervous system, recent experimental data suggest that immune cells may play a role in hypertension.,We studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and used Mendelian randomization (MR) analyses using the ≈750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies to examine which leukocyte populations may be causally linked to BP.,A positive association between quintiles of lymphocyte, monocyte, and neutrophil counts, and increased systolic BP, diastolic BP, and pulse pressure was observed (eg, adjusted systolic BP mean±SE for 1st versus 5th quintile respectively: 140.13±0.08 versus 141.62±0.07 mm Hg for lymphocyte, 139.51±0.08 versus 141.84±0.07 mm Hg for monocyte, and 137.96±0.08 versus 142.71±0.07 mm Hg for neutrophil counts; all P<10-50).,Using 121 single nucleotide polymorphisms in MR, implemented through the inverse-variance weighted approach, we identified a potential causal relationship of lymphocyte count with systolic BP and diastolic BP (causal estimates: 0.69 [95% CI, 0.19-1.20] and 0.56 [95% CI, 0.23-0.90] of mm Hg per 1 SD genetically elevated lymphocyte count, respectively), which was directionally concordant to the observational findings.,These inverse-variance weighted estimates were consistent with other robust MR methods.,The exclusion of rs3184504 SNP in the SH2B3 locus attenuated the magnitude of the signal in some of the MR analyses.,MR in the reverse direction found evidence of positive effects of BP indices on counts of monocytes, neutrophils, and eosinophils but not lymphocytes or basophils.,Subsequent MR testing of lymphocyte count in the context of genetic correlation with renal function or resting and postexercise heart rate demonstrated a positive association of lymphocyte count with urine albumin-to-creatinine ratio.,Observational and genetic analyses demonstrate a concordant, positive and potentially causal relationship of lymphocyte count with systolic BP and diastolic BP. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
Myocarditis following mRNA COVID-19 vaccination has recently been reported to health authorities in the United States and other countries.,Cases predominately occur in young adult males within four days following the second dose of either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines.,Although the number of cases reported have been small in comparison with the large number of people vaccinated, myocarditis may be a rare adverse reaction to the COVID-19 vaccination that is now only becoming apparent due to the widespread use of the vaccine.,In this article, we present a case of a 20-year-old male with no prior medical history who presented to the emergency department (ED) with chest pain.,He had received the BNT162b2 vaccine two days prior to his presentation to the ED.,The patient had an elevated troponin at 89 ng/L which increased on repeat examination.,His electrocardiogram showed diffuse concave ST segment elevations and a later MRI confirmed the diagnosis of myocarditis.,Based on these findings, the patient was diagnosed with myocarditis.,The patient had a previous infection with SARS-CoV-2 approximately two months prior to the onset of his symptoms, but since he had fully recovered before the time of his presentation to the ED, it is unlikely that the infection caused the myocarditis.,To our knowledge, this is the first published case of myocarditis following BNT162b3 vaccination. | Human coronavirus-associated myocarditis is known, and a number of coronavirus disease 19 (COVID-19)-related myocarditis cases have been reported.,The pathophysiology of COVID-19-related myocarditis is thought to be a combination of direct viral injury and cardiac damage due to the host’s immune response.,COVID-19 myocarditis diagnosis should be guided by insights from previous coronavirus and other myocarditis experience.,The clinical findings include changes in electrocardiogram and cardiac biomarkers, and impaired cardiac function.,When cardiac magnetic resonance imaging is not feasible, cardiac computed tomographic angiography with delayed myocardial imaging may serve to exclude significant coronary artery disease and identify myocardial inflammatory patterns.,Because many COVID-19 patients have cardiovascular comorbidities, myocardial infarction should be considered.,If the diagnosis remains uncertain, an endomyocardial biopsy may help identify active cardiac infection through viral genome amplification and possibly refine the treatment risks of systemic immunosuppression.,Arrhythmias are not uncommon in COVID-19 patients, but the pathophysiology is still speculative.,Nevertheless, clinicians should be vigilant to provide prompt monitoring and treatment.,The long-term impact of COVID-19 myocarditis, including the majority of mild cases, remains unknown. | 1 |
The common reported adverse effects of COVID-19 vaccination consist of the injection site's local reaction followed by several non-specific flu-like symptoms.,However, rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) after viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.,COV2 vaccine) have been reported.,Herein we systemically reviewed the reported cases of CVST and VITT following the COVID-19 vaccination.,This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.,We searched PubMed until May 19, 2021, and the following Keywords were used: COVID Vaccine & Neurology, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, Janssen COVID vaccine, Johnson & Johnson COVID vaccine, Ad26.,COV2 COVID vaccine.,The authors evaluated the abstracts and titles of each article for screening and inclusion.,English reports about post-vaccine CVST and VITT in humans were collected.,Until May 19, we found 877 articles with the searched terms.,We found 12 articles, which overall present clinical features of 36 patients with CVST and VITT after the ChAdOx1 nCoV-19 vaccine.,Moreover, two articles were noted, which present 13 patients with CVST and VITT after Ad26.,COV2 vaccine.,The majority of the patients were females.,Symptom onset occurred within one week after the first dose of vaccination (Range 4-19 days).,Headache was the most common presenting symptom.,Intracerebral hemorrhage (ICH) and/or Subarachnoid hemorrhage (SAH) were reported in 49% of the patients.,The platelet count of the patients was between 5 and 127 cells×109/l, PF4 IgG Assay and d-Dimer were positive in the majority of the reported cases.,Among 49 patients with CVST, at least 19 patients died (39%) due to complications of CVST and VITT.,Health care providers should be familiar with the clinical presentations, pathophysiology, diagnostic criteria, and management consideration of this rare but severe and potentially fatal complication of the COVID-19 vaccination.,Early diagnosis and quick initiation of the treatment may help to provide patients with a more favorable neurological outcome. | The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Within a year, several vaccines have been developed and millions of doses delivered.,Reporting of adverse events is a critical postmarketing activity.,We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).,On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.,In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype.,All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation.,No evidence of thrombophilia or causative precipitants was identified.,Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient.,On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.,Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic.,A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine.,Rapid identification of this rare syndrome is important because of the therapeutic implications. | 1 |
Multiple myeloma (MM) is accompanied by heterogeneous somatic alterations.,The overall goal of this study was to describe the genomic landscape of myeloma using deep whole-genome sequencing (WGS) and develop a model that identifies patients with long survival.,We analyzed deep WGS data from 183 newly diagnosed patients with MM treated with lenalidomide, bortezomib, and dexamethasone (RVD) alone or RVD + autologous stem cell transplant (ASCT) in the IFM/DFCI 2009 study (ClinicalTrials.gov identifier: NCT01191060).,We integrated genomic markers with clinical data.,We report significant variability in mutational load and processes within MM subgroups.,The timeline of observed activation of mutational processes provides the basis for 2 distinct models of acquisition of mutational changes detected at the time of diagnosis of myeloma.,Virtually all MM subgroups have activated DNA repair-associated signature as a prominent late mutational process, whereas APOBEC signature targeting C>G is activated in the intermediate phase of disease progression in high-risk MM.,Importantly, we identify a genomically defined MM subgroup (17% of newly diagnosed patients) with low DNA damage (low genomic scar score with chromosome 9 gain) and a superior outcome (100% overall survival at 69 months), which was validated in a large independent cohort.,This subgroup allowed us to distinguish patients with low- and high-risk hyperdiploid MM and identify patients with prolongation of progression-free survival.,Genomic characteristics of this subgroup included lower mutational load with significant contribution from age-related mutations as well as frequent NRAS mutation.,Surprisingly, their overall survival was independent of International Staging System and minimal residual disease status.,This is a comprehensive study identifying genomic markers of a good-risk group with prolonged survival.,Identification of this patient subgroup will affect future therapeutic algorithms and research planning. | The multiple myeloma (MM) genome is heterogeneous and evolves through preclinical and post-diagnosis phases.,Here we report a catalog and hierarchy of driver lesions using sequences from 67 MM genomes serially collected from 30 patients together with public exome datasets.,Bayesian clustering defines at least 7 genomic subgroups with distinct sets of co-operating events.,Focusing on whole genome sequencing data, complex structural events emerge as major drivers, including chromothripsis and a novel replication-based mechanism of templated insertions, which typically occur early.,Hyperdiploidy also occurs early, with individual trisomies often acquired in different chronological windows during evolution, and with a preferred order of acquisition.,Conversely, positively selected point mutations, whole genome duplication and chromoplexy events occur in later disease phases.,Thus, initiating driver events, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of evolution that are biologically relevant but heterogeneous across patients.,Multiple myeloma evolves continuously.,Here the authors chronologically reconstruct driver events in multiple myeloma, noting a limited repertoire of initiating driver events that shape the evolutionary trajectory of the disease. | 1 |
Emerging evidence shows that severe coronavirus disease 2019 (COVID‐19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism.,The incidence of venous thromboembolism among COVID‐19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions.,D‐dimer might help in early recognition of these high‐risk patients and also predict outcome.,Preliminary data show that in patients with severe COVID‐19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis‐induced coagulopathy criteria or with markedly elevated d‐dimer.,Recent recommendations suggest that all hospitalized COVID‐19 patients should receive thromboprophylaxis, or full therapeutic‐intensity anticoagulation if such an indication is present. | Patients with COVID-19 have a coagulopathy and high thrombotic risk.,In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients.,Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially).,Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma.,In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients.,Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes. | 1 |
Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19).,There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care.,We estimated excess mortality in specific CVDs, both ‘direct’, through infection, and ‘indirect’, through changes in healthcare.,We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD.,We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).,Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14).,CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England.,In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England.,For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.,Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.,Graphical Abstract | CoV-19/SARS-CoV-2 is a highly pathogenic virus that is causing a global pandemic with a high number of deaths and infected people.,To contain the diffusion of infection, several governments have enforced restrictions on outdoor activities or even collective quarantine on the population.,The present commentary briefly analyzes the effects of quarantine on lifestyle, including nutrition and physical activity and the impact of new technologies in dealing with this situation.,Quarantine is associated with stress and depression leading to unhealthy diet and reduced physical activity.,A diet poor in fruit and vegetables is frequent during isolation, with a consequent low intake of antioxidants and vitamins.,However, vitamins have recently been identified as a principal weapon in the fight against the Cov-19 virus.,Some reports suggest that Vitamin D could exert a protective effect on such infection.,During quarantine, strategies to further increase home-based physical activity and to encourage adherence to a healthy diet should be implemented.,The WHO has just released guidance for people in self-quarantine, those without any symptoms or diagnosis of acute respiratory illness, which provides practical advice on how to stay active and reduce sedentary behavior while at home.,Quarantine carries some long-term effects on cardiovascular disease, mainly related to unhealthy lifestyle and anxiety.,Following quarantine, a global action supporting healthy diet and physical activity is mandatory to encourage people to return to a good lifestyle routine. | 1 |
We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images.,We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy.,Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated.,The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots.,Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image.,Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%).,Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%).,Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001).,RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01).,Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001).,RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images. | Only few studies have investigated the relationship between the histopathology of retrieved thrombi and clinical outcomes.,This study aimed to evaluate thrombus composition and its association with clinical, laboratory, and neurointerventional findings in patients treated by mechanical thrombectomy due to acute large vessel occlusion.,At our institution, 79 patients were treated by mechanical thrombectomy using a stent retriever and/or aspiration catheter between August 2015 and August 2016.,The retrieved thrombi were quantitatively analyzed to quantify red blood cells, white blood cells, and fibrin by area.,We divided the patients into two groups - a fibrin-rich group and an erythrocyte-rich group - based on the predominant composition in the thrombus.,The groups were compared for imaging, clinical, and neurointerventional data.,The retrieved thrombi from 43 patients with acute stroke from internal carotid artery, middle cerebral artery, or basilar artery occlusion were histologically analyzed.,Erythrocyte-rich thrombi were present in 18 cases, while fibrin-rich thrombi were present in 25 cases.,A cardioembolic etiology was significantly more prevalent among the patients with fibrin-rich thrombi than among those with erythrocyte-rich thrombi.,Attenuation of thrombus density as shown on computed tomography images was greater in patients with erythrocyte-rich thrombi than in those with fibrin-rich thrombi.,All other clinical and laboratory characteristics remained the same.,Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers, shorter procedure times, a shorter time interval between arrival and recanalization, and a higher percentage of stent retrievers in the final recanalization procedure.,The occluded vessels did not differ significantly.,In this study, erythrocyte-rich thrombus was associated with noncardioembolic etiology, higher thrombus density, and reduced procedure time. | 1 |
Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19.,However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression.,Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins.,Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58.,The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis.,These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.,•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits,Statin treatment among 13,981 patients with COVID-19 was retrospectively studied,Statin use in this cohort was associated with a lower risk of all-cause mortality,Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort,The benefit of statins among this cohort may be due to immunomodulatory benefits,Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19.,But statins may increase the expression of ACE2, the receptor for SARS-CoV-2.,Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality. | Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide, and novel clinical presentations of COVID‐19 are often reported.,The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown.,The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19.,We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts.,We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status.,ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells.,We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL, or blood.,Additionally, CD147‐related genes correlated positively with age and BMI.,Interestingly, we also observed higher expression of CD147‐related genes in the lesional skin of patients with atopic dermatitis.,Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells.,Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID‐19 morbidity and severity patterns.,ACE2 and TMPRSS2 expression is unique for the epithelial barrier sites, whereas CD147, cyclophilins, and CD26 are expressed in both, epithelial and immune cells.,Age is a factor associated with the differential expression profiles of ACE2‐, CD147‐ and CD26‐related genes in the PBMCs and naive CD4+ T cells from healthy children and adults.,Asthma, COPD, hypertension, smoking, obesity, and male gender generally lead to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood.,Abbreviations: ACE2, angiotensin‐converting enzyme 2; AD, atopic dermatitis; BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; CypA, cyclophilin A; CypB, cyclophilin B; GLUT1, glucose transporter 1; ILC, innate lymphoid cell; MCTs, monocarboxylate transporters; NF‐ATs, nuclear factor of activated T cells; PBMCs, peripheral blood mononuclear cells; SARS‐CoV‐2; severe acute respiratory syndrome coronavirus 2; SLC6A19, sodium‐dependent neutral amino acid transporter B(0)AT1; S100A9, protein S100‐A9; TMPRSS2, transmembrane protease serine. | 1 |
Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions.,We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020.,The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days.,Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days.,Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease.,In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients. | The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health.,This study was conducted to provide the international community with a deeper understanding of this new infectious disease.,Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study.,A total of 135 hospitalized patients with COVID‐19 were enrolled.,The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men).,The majority of patients had contact with people from the Wuhan area.,Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]).,Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]).,Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients.,All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]).,In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]).,It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines.,Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase.,This study demonstrates the clinic features and therapies of 135 COVID‐19 patients.,Kaletra and TCM played an important role in the treatment of the viral pneumonia.,Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.,Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.,Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.,Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.,All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | The novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury.,In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection.,COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation.,The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation, and intravascular coagulation, and ultimately contributes to multiple organ failure and death.,In this review, we discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multiorgan damage. | 1 |
The COVID-19 pandemic has had a profound effect on general health care.,We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic.,In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset.,We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown.,The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown.,Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests.,Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests.,Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion.,Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables.,The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.,Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study.,Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51-0·70]).,Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62-0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55-0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19.,A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19.,Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics.,Recherche Hospitalo-Universitaire en Santé iVasc. | To examine the impact of COVID‐19 on acute heart failure (AHF) hospitalization rates, clinical characteristics and management of patients admitted to a tertiary Heart Failure Unit in London during the peak of the pandemic.,Data from King's College Hospital, London, reported to the National Heart Failure Audit for England and Wales, between 2 March-19 April 2020 were compared both to a pre‐COVID cohort and the corresponding time periods in 2017 to 2019 with respect to absolute hospitalization rates.,Furthermore, we performed detailed comparison of patients hospitalized during the COVID‐19 pandemic and patients presenting in the same period in 2019 with respect to clinical characteristics and management during the index admission.,A significantly lower admission rate for AHF was observed during the study period compared to all other included time periods.,Patients admitted during the COVID‐19 pandemic had higher rates of New York Heart Association III or IV symptoms (96% vs.,77%, P = 0.03) and severe peripheral oedema (39% vs.,14%, P = 0.01).,We did not observe any differences in inpatient management, including place of care and pharmacological management of heart failure with reduced ejection fraction.,Incident AHF hospitalization significantly declined in our centre during the COVID‐19 pandemic, but hospitalized patients had more severe symptoms at admission.,Further studies are needed to investigate whether the incidence of AHF declined or patients did not present to hospital while the national lockdown and social distancing restrictions were in place.,From a public health perspective, it is imperative to ascertain whether this will be associated with worse long‐term outcomes. | 1 |
Rapid spread of coronavirus disease 2019 (COVID-19) in the United States, especially in New York City (NYC), led to a tremendous increase in hospitalizations and mortality.,There is very limited data available that associates outcomes during hospitalization in patients with COVID-19.,In this retrospective cohort study, we reviewed the health records of patients with COVID-19 who were admitted from March 9-April 9, 2020, to a community hospital in NYC.,Subjects with confirmed reverse transcriptase-polymerase chain reaction (RT-PCR) of the nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were included.,We collected data related to demographics, laboratory results, and outcome of hospitalization.,Outcome was measured based on whether the patient was discharged home or died during hospitalization.,There were 888 consecutive admissions with COVID-19 during the study period, of which 513 were excluded with pending outcome or incomplete information.,We included a total of 375 patients in the study, of whom 215 (57%) survived and 160 (43%) died during hospitalization.,The majority of patients were male (63%) and of Hispanic origin (66%) followed by Blacks (25%), and others (9%).,Hypertension (60%) stands out to be the most common comorbidity followed by diabetes mellitus (47%), cardiovascular disease (17%), chronic kidney disease (17%), and human immunodeficiency virus/acquired immunodeficiency syndrome (9%).,On multiple regression analysis, increasing odds of mortality during hospitalization was associated with older age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01-1.06 per year increase; p < 0.0001), admission D-dimer more than 1000 nanograms per milliliter (ng/mL) (OR 3.16; 95% CI, 1.75-5.73; p<0.0001), admission C-reactive protein (CRP) levels of more than 200 milligrams per liter (mg/L) (OR 2.43; 95% CI, 1.36-4.34; p = 0.0028), and admission lymphopenia (OR 2.63; CI, 1.47-4.69; p 0.0010).,In this retrospective cohort study originating in NYC, older age, admission levels of D-dimer of more than 1000 ng/mL, CRP of more than 200 mg/L and lymphopenia were associated with mortality in individuals hospitalized for COVID-19.,We recommend using these risk factors on admission to triage patients to critical care units or surge units to maximize the use of surge capacity beds. | We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China.,Clinical data on COVID-19 inpatients in Zengdu Hospital from January 27 to March 11, 2020 were collected; this is a community hospital in an area surrounding Wuhan and supported by volunteer doctors.,All hospitalized patients with COVID-19 were included in this study.,The epidemiological findings, clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of these patients were analyzed.,The patients were followed up for clinical outcomes until March 22, 2020.,Severe COVID-19 cases include severe and critical cases diagnosed according to the seventh edition of China’s COVID-19 diagnostic guidelines.,Severe and critical COVID-19 cases were diagnosed according to the seventh edition of China’s COVID-19 diagnostic guidelines.,All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients.,The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p < 0.01).,Approximately a quarter of the patients (24.6%) had at least one comorbidity, such as hypertension, diabetes, or cancer, and the proportion of patients with comorbidities was higher in the severe group (85.7%) than in the non-severe group (21.4%, p < 0.01).,Common symptoms included fever (82.2% [227/276]) and cough (78.0% [218/276]).,38.4% (106/276) of the patients had a fever at the time of admission.,Most patients (94.9% [204/276]) were cured and discharged; 3.6% (10/276) deteriorated to a critical condition and were transferred to another hospital.,The median COVID-19 treatment duration and hospital stay were 14.0 and 18.0 days, respectively.,Most of the COVID-19 patients in Zengdu had mild disease.,Older patients with underlying diseases were at a higher risk of progression to severe disease.,The length of hospital-stay and antiviral treatment duration for COVID-19 were slightly longer than those in Wuhan.,This work will contribute toward an understanding of COVID-19 characteristics in the areas around the core COVID-19 outbreak region and serve as a reference for decision-making for epidemic prevention and control in similar areas. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases.,Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.,The study sought to assess COVID-19’s impact on global cardiovascular diagnostic procedural volumes and safety practices.,The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19.,Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019.,Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.,Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries.,Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020.,Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities.,Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure).,In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product.,Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.,COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world’s economically challenged.,Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. | To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects.,Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019.,We analysed aggregate data for selected cardiovascular diseases before and during the epidemic.,We produced an online visualisation tool to enable near real-time monitoring of trends.,Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year.,Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures.,Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60).,There was limited recovery towards usual levels of some activities from mid-April 2020.,Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently. | 1 |
Higher rates of strokes have been observed in patients with coronavirus disease 2019 (COVID-19), but data regarding the outcomes of COVID-19 patients suffering from acute ischemic stroke due to large vessel occlusion (LVO) are lacking.,We report our initial experience in the treatment of acute ischemic stroke with LVO in patients with COVID-19.,All consecutive patients with COVID-19 with acute ischemic stroke due to LVO treated in our institution during the 6 first weeks of the COVID-19 outbreak were included.,Baseline clinical and radiological findings, treatment, and short-term outcomes are reported.,We identified 10 patients with confirmed COVID-19 treated for an acute ischemic stroke due to LVO.,Eight were men, with a median age of 59.5 years.,Seven had none or mild symptoms of COVID-19 at stroke onset.,Median time from COVID-19 symptoms to stroke onset was 6 days.,All patients had brain imaging within 3 hours from symptoms onset.,Five patients had multi-territory LVO.,Five received intravenous alteplase.,All patients had mechanical thrombectomy.,Nine patients achieved successful recanalization (mTICI2B-3), none experienced early neurological improvement, 4 had early cerebral reocclusion, and a total of 6 patients (60%) died in the hospital.,Best medical care including early intravenous thrombolysis, and successful and prompt recanalization achieved with mechanical thrombectomy, resulted in poor outcomes in patients with COVID-19.,Although our results require further confirmation, a different pharmacological approach (antiplatelet or other) should be investigated to take in account inflammatory and coagulation disorders associated with COVID-19. | The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic. | 1 |
Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.,In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation.,Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis).,The median value for organ support-free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%).,The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11).,Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.,In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.,(REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.) | Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19. | 1 |
Highly sensitive troponin (hs-TnI) levels are frequently elevated in COVID-19 patients and are associated with increased cardiovascular mortality during hospitalization.,However, no data exists on cardiac involvement in patients recovered from COVID-19 infection.,We aimed to evaluate by global longitudinal strain (LV-GLS) whether there is subclinical myocardial deformation after COVID-19 infection.,Two-dimensional speckle tracking echocardiography (2D-STE) was performed within 29.5 ± 4.5 days after COVID-19 treatment.,The standard GLS limit was identified at < −18%.,The patients were divided into two groups according to their hs-TnI levels during hospitalization as with (> 11.6 ng/dl) and without (< 11.6 ng/dl) myocardial injury.,Patients’ (n = 74) mean age was 59.9 years, and women were in the majority (60.8%).,Of the patients, 43.2% of them were hypertensive, and 10.9% were diabetic.,Abnormal LV-GLS values (> −18) were measured in 28 patients (37.8%).,While 16 (57.1%) of these patients were in the group with myocardial injury, 12 (26.1%) of them were in the group without myocardial injury (p = 0.014).,D-dimer, C reactive protein, white blood cell levels were higher in the group with myocardial injury (All p values < 0.05).,Electrocardiographically, 9 (12.2%) patients had T wave inversion, while two patients had a bundle branch block.,Subclinical left ventricular dysfunction was observed in approximately one-third of the patients at the one-month follow-up after COVID-19 infection.,This rate was higher in those who develop myocardial injury during hospitalization.,This result suggests that patients recovered from COVID-19 infection should be evaluated and followed in terms of cardiac involvement.,The online version contains supplementary material available at 10.1007/s10554-021-02211-5. | Supplemental Digital Content is available in the text.,Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce.,We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection.,One hundred consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared with reference values.,Echocardiographic studies included left ventricular (LV) systolic and diastolic function and valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound.,A second examination was performed in case of clinical deterioration.,Thirty-two patients (32%) had a normal echocardiogram at baseline.,The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%).,Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared with patients with normal troponin or better clinical condition, but they had worse RV function.,Clinical deterioration occurred in 20% of patients.,In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients).,Femoral deep vein thrombosis was diagnosed in 5 of 12 patients with RV failure.,In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic function and RV function are impaired.,Elevated troponin and poorer clinical grade are associated with worse RV function.,In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without deep vein thrombosis, is more common, but acute LV systolic dysfunction was noted in ≈20%. | 1 |
Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19.,We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.,The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide.,Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission.,Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded.,Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system.,The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation.,Primary analyses were done in the intention-to-treat population.,The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.,Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77).,Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes.,Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]).,There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77).,There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.,Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.,REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants. | Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19).,However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.,We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing.,We further validated some of the key observations in other human tissues and/or a controlled experimental model.,Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney.,We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs.,We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.,Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney.,Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.,Graphical Abstract | 1 |
To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19).,We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years.,Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors.,Risk factors of death and myocardial injury were analysed using multivariable regression models.,A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs.,9.7%; P < 0.001) than survivors.,The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001].,The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively.,In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury.,The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities. | A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community.,Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients.,Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19.,We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes.,Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis.,112 COVID-19 patients were enrolled in our study.,There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis.,Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died.,Troponin levels were significantly increased in the week preceding the death.,15 (13.4%) patients have presented signs of pulmonary hypertension.,Typical signs of myocarditis were absent on echocardiography and electrocardiogram.,The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus.,The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.,•The evidence from clinical standpoint and front-line data in Wuhan for COVID-19.,•The novel coronavirus in COVID-19 less likely caused myocardial injury directly.,•Elevation in cardiac markers is the warning sign of adverse outcomes for COVID-19.,The evidence from clinical standpoint and front-line data in Wuhan for COVID-19.,The novel coronavirus in COVID-19 less likely caused myocardial injury directly.,Elevation in cardiac markers is the warning sign of adverse outcomes for COVID-19. | 1 |
Supplemental Digital Content is available in the text.,RAASi (renin-angiotensin-aldosterone system inhibitors) are suggested as possible treatment option in the early phase of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.,A meta-analysis investigating the possible detrimental effects of RAASi on the severity of (SARS-CoV-2) infection showed that ambulatory use of RAASi, by hospitalized patients, has a neutral effect.,It is, however, conceivable that this observation is biased by the fact that antihypertensive medications, are often discontinued at or during admission in hospitalized patients with SARS-CoV-2.,We, therefore, investigated the effect of discontinuation of antihypertensive medications, in hospitalized patients with SARS-CoV-2.,We performed a retrospective observational study on 1584 hospitalized patients with SARS-CoV-2 from 10 participating hospitals in the Netherlands.,Differences in the outcome (severity of disease or death) between the groups in which medications were either continued or discontinued during the course of hospitalization were assessed using logistic regression models.,Discontinuation of angiotensin receptor blockers, ACE (angiotensin-converting enzyme) inhibitors and β-blockers, even when corrected for sex, age, and severity of symptoms during admission, resulted in a 2 to 4× higher risk of dying from SARS-CoV-2 infection (odds ratio [95% CI]); angiotensin receptor blockers 2.65 [1.17-6.04], ACE inhibitor (2.28 [1.15-4.54]), and β-blocker (3.60 [1.10-10.27]).,In conclusion, discontinuation of at-home ACE inhibitor, angiotensin receptor blockers, or β-blocker in patients hospitalized for a SARS-CoV-2 infection was associated with an increased risk of dying, whereas discontinuation of calcium channel blockers and diuretics was not. | •We evaluated ECG features of patients hospitalized for COVID-19 pneumonia.,•New ECG abnormalities reflected a wide spectrum of cardiovascular complications.,•The most common manifestations were signs of pericarditis and atrial fibrillation.,•ECG abnormalities showed a late onset from hospitalization.,•ECG abnormalities seem to follow a separate course from the respiratory infection.,We evaluated ECG features of patients hospitalized for COVID-19 pneumonia.,New ECG abnormalities reflected a wide spectrum of cardiovascular complications.,The most common manifestations were signs of pericarditis and atrial fibrillation.,ECG abnormalities showed a late onset from hospitalization.,ECG abnormalities seem to follow a separate course from the respiratory infection.,.,The electrocardiographic (ECG) changes which may occur during hospitalization for COVID-19 have not yet been comprehensively assessed.,.,We examined 50 patients admitted to hospital with proven COVID-19 pneumonia.,At entry, all patients underwent a detailed clinical examination, 12-lead ECG, laboratory tests and arterial blood gas test.,ECG was also recorded at discharge and in case of worsening clinical conditions.,.,Mean age of patients was 64 years and 72% were men.,At baseline, 30% of patients had ST-T abnormalities, and 33% had left ventricular hypertrophy.,During hospitalization, 26% of patients developed new ECG abnormalities which included atrial fibrillation, ST-T changes, tachy-brady syndrome, and changes consistent with acute pericarditis.,One patient was transferred to intensive care unit for massive pulmonary embolism with right bundle branch block, and another for non-ST segment elevation myocardial infarction.,Patients free of ECG changes during hospitalization were more likely to be treated with antiretrovirals (68% vs 15%, p = 0.001) and hydroxychloroquine (89% vs 62%, p = 0.026) versus those who developed ECG abnormalities after admission.,Most measurable ECG features at discharge did not show significant changes from baseline (all p>0.05) except for a slightly decrease in Cornell voltages (13±6 vs 11±5 mm; p = 0.0001) and a modest increase in the PR interval.,The majority (54%) of patients with ECG abnormalities had 2 prior consecutive negative nasopharyngeal swabs.,ECG abnormalities were first detected after an average of about 30 days from symptoms’ onset (range 12-51 days).,.,ECG abnormalities during hospitalization for COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, exhibit a late onset, do not progress in parallel with pulmonary abnormalities and may occur after negative nasopharyngeal swabs. | 1 |
Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease.,To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19.,The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients.,This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020.,Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein.,There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration.,Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI.,Higher doses of heparin to achieve therapeutic activated clotting times were also noted.,Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission.,In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes.,This supports the need for establishing COVID-19 status in all STEMI cases.,Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases. | Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients.,We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.,Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments).,Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017.,Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded.,Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias.,We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.,Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores.,The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management.,During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died.,The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84).,Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93).,The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.,NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative. | 1 |
Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | •COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,•Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,•Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.,COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low. | 1 |
The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is responsible for the global coronavirus disease 2019 pandemic.,Small studies have shown a potential benefit of chloroquine/hydroxychloroquine±azithromycin for the treatment of coronavirus disease 2019.,Use of these medications alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the risk of Torsade de pointes and sudden cardiac death.,Hospitalized patients treated with chloroquine/hydroxychloroquine±azithromycin from March 1 to the 23 at 3 hospitals within the Northwell Health system were included in this prospective, observational study.,Serial assessments of the QT interval were performed.,The primary outcome was QT prolongation resulting in Torsade de pointes.,Secondary outcomes included QT prolongation, the need to prematurely discontinue any of the medications due to QT prolongation, and arrhythmogenic death.,Two hundred one patients were treated for coronavirus disease 2019 with chloroquine/hydroxychloroquine.,Ten patients (5.0%) received chloroquine, 191 (95.0%) received hydroxychloroquine, and 119 (59.2%) also received azithromycin.,The primary outcome of torsade de pointes was not observed in the entire population.,Baseline corrected QT interval intervals did not differ between patients treated with chloroquine/hydroxychloroquine (monotherapy group) versus those treated with combination group (chloroquine/hydroxychloroquine and azithromycin; 440.6±24.9 versus 439.9±24.7 ms, P=0.834).,The maximum corrected QT interval during treatment was significantly longer in the combination group versus the monotherapy group (470.4±45.0 ms versus 453.3±37.0 ms, P=0.004).,Seven patients (3.5%) required discontinuation of these medications due to corrected QT interval prolongation.,No arrhythmogenic deaths were reported.,In the largest reported cohort of coronavirus disease 2019 patients to date treated with chloroquine/hydroxychloroquine±azithromycin, no instances of Torsade de pointes, or arrhythmogenic death were reported.,Although use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue therapy.,Further study of the need for QT interval monitoring is needed before final recommendations can be made.,A visual overview is available for this article. | Chloroquine and hydroxychloroquine are now being widely used for treatment of COVID-19.,Both medications prolong the QT interval and accordingly may put patients at increased risk for torsades de pointes and sudden death.,Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects.,Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine.,We searched on MEDLINE and Embase, as well as in the gray literature up to April 17, 2020, for the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage.,This search resulted in 390 unique records, of which 41 were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients.,Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation.,We found evidence of ventricular arrhythmia in 2 COVID-19 patients from a group of 28 treated with high-dose chloroquine.,Limitations of these results are unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT-interval prolongation and potentially increase the risk of arrhythmia.,Daily electrocardiographic monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy. | 1 |
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19. | Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19. | 1 |
The outbreak of a novel coronavirus since December 2019, became an emergency of major international concern.,As of June 21, 2020, the SARS-CoV-2 pandemic has caused 8,769,844 confirmed infections with 463,745 fatal cases worldwide.,The SARS-CoV-2 outbreak is a major challenge for clinicians.,In our clinic, we found a rare case that a COVID-19 patient combined with ischemic stroke.,A 79-year-old man was admitted to the Hubei Provincial Hospital of Traditional Chinese Medicine due to right limb weakness for 1 day and slight cough for 1 week.,At presentation, his oxygen saturation was 94.2% on room air and body temperature was 37.3 °C (99.0 °F) with some moist rales.,Neurological examination showed right limb weakness, and the limb muscle strength was grade 4.,The left leg and arms were unaffected.,In addition, runs of speech were not fluent enough with tongue deviation.,Laboratory studies showed lymphopenia and eosinophilic granulocytopenia.,Chest CT revealed bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, with a peripheral lung distribution.,Real-time polymerase chain reaction (RT-PCR) from throat swab sample was positive for SARS-CoV-2 nucleic acid.,This patient was treated with antiviral drugs and anti-inflammatory drugs with supportive care until his discharge.,Clopidogrel (75 mg) and atorvastatin (20 mg) were administered orally to treat acute ischemic stroke.,After 12 days of treatment, he can walk normally and communicate with near fluent language.,We report an even more unusual case, a patient who was hospitalized for right limb weakness and was later diagnosed with COVID-19.,Here, SARS-CoV-2 infection caused hypoxemia and excessive secretion of inflammatory cytokines, which contribute to the occurrence and development of ischemic stroke.,Once COVID-19 patients show acute ischemic stroke, neurologists should cooperate with infectious disease doctors to help patients. | •Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,•Most neurological diseases could be caused by coronoviruses invasion.,•Coronoviruses cause nerve damage via diverse pathways.,Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system.,Most neurological diseases could be caused by coronoviruses invasion.,Coronoviruses cause nerve damage via diverse pathways.,Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage.,Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases.,It is reported that CoV can be found in the brain or cerebrospinal fluid.,The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system.,Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system. | 1 |
We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses nationwide from 2012 to 2014 and compared this to the incidence among patients hospitalized with COVID-19 at a large health system in New York.,Non-COVID-19 viral respiratory illness was complicated by acute MI in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%.,The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (5% vs 16%; P< .001).,Thrombosis is a prominent feature of the novel Coronavirus disease 2019 (COVID-19).,The incidence of thrombosis during hospitalization for non-COVID-19 viral respiratory infections is uncertain.,We evaluated the incidence of thrombosis in patients hospitalized with non-COVID-19 acute viral respiratory illnesses compared to COVID-19.,Adults age >18 years hospitalized with a non-COVID-19 viral respiratory illness between 2002 and 2014 were identified.,The primary study outcome was a composite of venous and arterial thrombotic events, including myocardial infarction (MI), acute ischemic stroke, and venous thromboembolism (VTE), as defined by ICD-9 codes.,The incidence of thrombosis in non-COVID-19 viral respiratory illnesses was compared to the recently published incidence of thrombosis in COVID-19 from 3,334 patients hospitalized in New York in 2020.,Among 954,521 hospitalizations with viral pneumonia from 2002 to 2014 (mean age 62.3 years, 57.1% female), the combined incidence of arterial and venous thrombosis was 5.0%.,Acute MI occurred in 2.8% of hospitalizations, VTE in 1.6%, ischemic stroke in 0.7%, and other systemic embolism in 0.1%.,Patients with thrombosis had higher in-hospital mortality (14.9% vs 3.3%, P< .001) than those without thrombosis.,The proportion of hospitalizations complicated by thrombosis was lower in patients with viral respiratory illness in 2002-2014 than in COVID-19 (median age 64; 39.6% female) in 2020 (5% vs 16%; P< .001),In a nationwide analysis of hospitalizations for viral pneumonias, thrombosis risk was lower than that observed in patients with COVID-19.,Investigations into mechanisms of thrombosis and risk reduction strategies in COVID-19 and other viral respiratory infections are necessary.,Image, graphical abstract | Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19. | 1 |
Coronavirus-2019 (COVID-19) predisposes patients to arterial and venous thrombosis commonly complicating the clinical course of hospitalized patients and attributed to the inflammatory state, endothelial dysfunction, platelet activation and blood stasis.,This viral coagulopathy may occur despite thromboprophylaxis and raises mortality; the risk appears highest among critically ill inpatients monitored in the intensive care unit.,The prevalence of venous thromboembolism in COVID-19 patients has been reported to reach ∼10-35%, while autopsies raise it to nearly 60%.,The most common thrombotic complication is pulmonary embolism, which though may occur in the absence of a recognizable deep venous thrombosis and may be due to pulmonary arterial thrombosis rather than embolism, resulting in thrombotic occlusion of small- to mid-sized pulmonary arteries and subsequent infarction of lung parenchyma.,This micro-thrombotic pattern seems more specific for COVID-19 and is associated with an intense immuno-inflammatory reaction that results in diffuse occlusive thrombotic micro-angiopathy with alveolar damage and vascular angiogenesis.,Furthermore, thrombosis has also been observed in various arterial sites, including coronary, cerebral and peripheral arteries.,Biomarkers related to coagulation, platelet activation and inflammation have been suggested as useful diagnostic and prognostic tools for COVID-19-associated coagulopathy; among them, D-dimer remains a key biomarker employed in clinical practice.,Various medical societies have issued guidelines or consensus statements regarding thromboprophylaxis and treatment of these thrombotic complications specifically adapted to COVID-19 patients.,All these issues are detailed in this review, data from meta-analyses and current guidelines are tabulated, while the relevant mechanisms of this virus-associated coagulopathy are pictorially illustrated. | An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | 1 |
Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival. | Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients. | 1 |
Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients. | Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology.,Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways.,While a “cytokine storm” involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection.,C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients.,Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101. | 1 |
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initially most appreciated for its pulmonary symptoms, is now increasingly recognized for causing multi-organ disease and stroke in the setting of a hypercoagulable state.,We report a case of 33-year-old African American woman with COVID-19 who developed acute malignant middle cerebral artery infarction due to thromboembolic occlusion of the left terminal internal carotid artery and middle cerebral artery stem.,Mechanical thrombectomy was challenging and ultimately unsuccessful resulting in limited reperfusion of <67% of the affected vascular territory, and thrombectomized clot was over 50 mm in length, at least three times the average clot length.,The final stroke size was estimated at 224 cubic centimeters.,On admission her D-dimer level was 94,589 ng/mL (normal 0-500 ng/ml).,Throughout the hospitalization D-dimer decreased but never reached normal values while fibrinogen trended upward.,Hypercoagulability panel was remarkable for mildly elevated anticardiolipin IgM of 16.3 MPL/mL (normal: 0-11.0 MPL/mL).,With respect to remaining stroke workup, there was no evidence of clinically significant stenosis or dissection in the proximal internal carotid artery or significant cardioembolic source including cardiomyopathy, atrial fibrillation, cardiac thrombus, cardiac tumor, valvular abnormality, aortic arch atheroma, or patent foramen ovale.,She developed malignant cytotoxic cerebral edema and succumbed to complications.,This case underscores the importance of recognizing hypercoagulability as a cause of severe stroke and poor outcome in young patients with COVID-19 and highlights the need for further studies to define correlation between markers of coagulopathy in patients with COVID-19 infection and outcome post stroke. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
Risk factors for pulmonary embolism in patients with coronavirus disease 2019 include obesity, an elevated d-dimer value, elevated C-reactive protein level, and a rising d-dimer value over time. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide.,Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women.,Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease.,We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19.,We analyzed information from 2378 charts of Italian patients certified for COVID-19 admitted in 26 hospitals.,Three hundred ninety-five patients (16.6%) required ICU admission due to COVID19 infection, more frequently men (74%), with a higher prevalence of comorbidities (1,78±0,06 vs 1,54±0,03 p<0.05).,In multivariable regression model main predictors of admission to ICU are male gender (OR 1,74 95% CI 1,36-2,22 p<0.0001) and presence of obesity (OR 2,88 95% CI 2,03-4,07 p<0.0001), chronic kidney disease (OR: 1,588; 95%, 1,036-2,434 p<0,05) and hypertension (OR: 1,314; 95% 1,039-1,662; p<0,05).,In gender specific analysis, obesity, chronic kidney disease and hypertension are associated with higher rate of admission to ICU among men, whereas in women, obesity (OR: 2,564; 95% CI 1,336-4.920 p<0.0001) and heart failure (OR: 1,775 95% CI: 1,030-3,057) are associated with higher rate of ICU admission.,Our study demonstrates that gender is the primary determinant of the disease’s severity among COVID-19.,Obesity is the condition more often observed among those admitted to ICU within both genders.,Clinicaltrials.gov: NCT04331574. | There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications. | 1 |
Standard evaluation and management of the patient with suspected or proven cardiovascular complications of coronavirus disease-2019 (COVID-19), the disease caused by severe acute respiratory syndrome related-coronavirus-2 (SARS-CoV-2), is challenging.,Routine history, physical examination, laboratory testing, electrocardiography, and plain x-ray imaging may often suffice for such patients, but given overlap between COVID-19 and typical cardiovascular diagnoses such as heart failure and acute myocardial infarction, need frequently arises for advanced imaging techniques to assist in differential diagnosis and management.,This document provides guidance in several common scenarios among patients with confirmed or suspected COVID-19 infection and possible cardiovascular involvement, including chest discomfort with electrocardiographic changes, acute hemodynamic instability, newly recognized left ventricular dysfunction, as well as imaging during the subacute/chronic phase of COVID-19.,For each, the authors consider the role of biomarker testing to guide imaging decision-making, provide differential diagnostic considerations, and offer general suggestions regarding application of various advanced imaging techniques. | To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates. | 1 |
Non-communicable diseases (NCDs) are the second common cause of death in sub-Saharan Africa (SSA) accounting for about 35% of all deaths, after a composite of communicable, maternal, neonatal, and nutritional diseases.,Despite prior perception of low NCDs mortality rates, current evidence suggests that SSA is now at the dawn of the epidemiological transition with contemporary double burden of disease from NCDs and communicable diseases.,In SSA, cardiovascular diseases (CVDs) are the most frequent causes of NCDs deaths, responsible for approximately 13% of all deaths and 37% of all NCDs deaths.,Although ischemic heart disease (IHD) has been identified as the leading cause of CVDs mortality in SSA followed by stroke and hypertensive heart disease from statistical models, real field data suggest IHD rates are still relatively low.,The neglected endemic CVDs of SSA such as endomyocardial fibrosis and rheumatic heart disease as well as congenital heart diseases remain unconquered.,While the underlying aetiology of heart failure among adults in high-income countries (HIC) is IHD, in SSA the leading causes are hypertensive heart disease, cardiomyopathy, rheumatic heart disease, and congenital heart diseases.,Of concern is the tendency of CVDs to occur at younger ages in SSA populations, approximately two decades earlier compared to HIC.,Obstacles hampering primary and secondary prevention of CVDs in SSA include insufficient health care systems and infrastructure, scarcity of cardiac professionals, skewed budget allocation and disproportionate prioritization away from NCDs, high cost of cardiac treatments and interventions coupled with rarity of health insurance systems.,This review gives an overview of the descriptive epidemiology of CVDs in SSA, while contrasting with the HIC and highlighting impediments to their management and making recommendations.,- The burden of non-communicable diseases including cardiovascular diseases is rising in SSA.,- Levels of hypertension diagnosis, treatment, and control are low at <40%, <35%, and 10-20%, respectively, and more than 40% of patients with diabetes are not aware of their diagnosis in SSA.,- SSA has 23% of the world’s prevalent rheumatic heart disease cases.,- The leading causes of heart failure in SSA are hypertensive heart disease, cardiomyopathy, and rheumatic heart disease, with ischemic heart disease accounting for <10% of cases compared to >50% in high-income countries. | The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.,The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.,CVD mortality was estimated from vital registration and verbal autopsy data.,CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries.,Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights.,Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy.,A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.,In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths).,Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries.,Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke.,As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men.,CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.,CVDs remain a major cause of health loss for all regions of the world.,Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions.,Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD. | 1 |
Supplemental Digital Content is available in the text.,Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males.,According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age.,In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels.,ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients.,There was no evidence of acute COVID-19 or other viral infections.,In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased.,Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed.,The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women.,Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.,Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age. | What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. | 1 |
COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown. | Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | 1 |
Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.,All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020.,Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.,In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died.,Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia.,In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.,We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1.,The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.,These data showed that age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 were four risk factors predicting high mortality of COVID-19 pneumonia patientshttps://bit.ly/2Rh6Nqv | 1 |
COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak. | When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted.,In this study, we investigated the impact of the COVID-19 outbreak on stroke care across China.,Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy.,We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes.,The survey was distributed to the leaders of stroke centers in these 280 hospitals.,From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% (P<0.0001) and 25.3% (P<0.0001), respectively, in February 2020 as compared with February 2019.,We retrieved 227 valid complete datasets from the 280 stroke centers.,Nearly 50% of these hospitals were designated hospitals for COVID-19.,The capacity for stroke care was reduced in the majority of the hospitals.,Most of the stroke centers stopped or reduced their efforts in stroke education for the public.,Hospital admissions related to stroke dropped ≈40%; thrombolysis and thrombectomy cases dropped ≈25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019.,Many factors contributed to the reduced admissions and prehospital delays; lack of stroke knowledge and proper transportation were significant limiting factors.,Patients not coming to the hospital for fear of virus infection was also a likely key factor.,The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy.,Although many factors contributed, patients not coming to the hospital was probably the major limiting factor.,Recommendations based on the data are provided. | 1 |
The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.,We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States.,The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.,Clinicians abstracted the data onto standardized forms.,We report on 186 patients with MIS-C in 26 states.,The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.,Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).,The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died.,Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease-like features were documented in 74 (40%).,Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation.,The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).,Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.,(Funded by the Centers for Disease Control and Prevention.) | Kawasaki disease (KD) is a systemic form of self-limited vasculitis in children less than five years old, and the main complication is coronary artery injury.,However, the etiology of KD remains unclear.,The IL-1B polymorphisms rs16944 GG and rs1143627 AA and their diplotype GA/GA have been associated with significantly increased risk of intravenous immunoglobulin (IVIG) resistance in a Taiwanese population, but the relationship between rs16944 A/G and rs1143627 G/A and coronary artery lesions (CALs) in patients with KD has not been investigated.,The present study is aimed at investigating whether the rs16944 A/G and rs1143627 G/A polymorphisms in IL-1B were associated with KD susceptibility and CALs in a southern Chinese population.,We recruited 719 patients with KD and 1401 healthy children.,Multiplex PCR was used to assess the genotypes of single nucleotide polymorphisms (SNPs), including two SNPs of IL-1B, rs16944 A/G and rs1143627 G/A.,According to the results, no significant association was observed between the IL-1B (rs16944 and rs1143627) polymorphisms and KD risk in the patients compared with the healthy controls in our southern Chinese population.,However, in further stratified analysis, we found that children younger than 12 months with the rs16944 GG and rs1143627 AA genotypes of IL-1B had a higher risk of CALs than those with the AA/AG genotypes of rs16944 and GG/AG genotypes of rs1143627 (OR = 2.28, 95% CI = 1.32-3.95, P = 0.0032, adjusted OR = 2.33, 95% CI = 1.34-4.04, P = 0.0027).,Our results indicated that there was no association between the rs16944 A/G and rs1143627 G/A gene polymorphisms and KD susceptibility.,However, the rs16944 GG and rs1143627 AA genotypes of IL-1B may significantly impact the risk of CAL formation in children younger than 12 months, which may contribute to the pathogenesis of KD.,These findings need further validation in multicenter studies with larger sample sizes. | 1 |
Women with hypertensive pregnancy disorders have adverse levels of cardiovascular risk factors.,It is unclear how this adverse risk factor profile evolves during adult life.,We compared life course trajectories of cardiovascular risk factors in women with preeclampsia or gestational hypertension in their first pregnancy to normotensive women.,We linked information on cardiovascular risk factors from the population‐based HUNT (Nord‐Trøndelag Health Study) surveys with pregnancy information from the Medical Birth Registry of Norway.,Trajectories of cardiovascular risk factors were constructed for 22 308 women with a normotensive first pregnancy; 1092 with preeclampsia, and 478 with gestational hypertension in first pregnancy.,Already before first pregnancy, women with preeclampsia in their first pregnancy had higher measures of adiposity, blood pressure, heart rate, and serum lipids and glucose compared with women with a normotensive first pregnancy.,After first pregnancy, there was a parallel development in cardiovascular risk factor levels, but women with a normotensive first pregnancy had a time lag of >10 years compared with the preeclampsia group.,There were no clear differences in risk factor trajectories between women with gestational hypertension and women with preeclampsia.,Women with hypertensive pregnancy disorders in their first pregnancy had an adverse cardiovascular risk factor profile before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age.,Hypertensive disorders in pregnancy signal long‐term increases in modifiable cardiovascular risk factors, and may be used to identify women who would benefit from early prevention strategies. | Objectives To determine how soon after delivery the risk of post-pregnancy hypertension increases in women with hypertensive disorders of pregnancy and how the risk evolves over time.,Design Nationwide register based cohort study.,Setting Denmark.,Populations 482 972 primiparous women with a first live birth or stillbirth between 1995 and 2012 (cumulative incidence analyses), and 1 025 118 women with at least one live birth or stillbirth between 1978 and 2012 (Cox regression analyses).,Main outcome measures 10 year cumulative incidences of post-pregnancy hypertension requiring treatment with prescription drugs, and hazard ratios estimated using Cox regression.,Results Of women with a hypertensive disorder of pregnancy in a first pregnancy in their 20s, 14% developed hypertension in the first decade post partum, compared with 4% of women with normotensive first pregnancies in their 20s.,The corresponding percentages for women with a first pregnancy in their 40s were 32% and 11%, respectively.,In the year after delivery, women with a hypertensive disorder of pregnancy had 12-fold to 25-fold higher rates of hypertension than did women with a normotensive pregnancy.,Rates in women with a hypertensive disorder of pregnancy were threefold to 10-fold higher 1-10 years post partum and remained twice as high even 20 or more years later.,Conclusions The risk of hypertension associated with hypertensive disorders of pregnancy is high immediately after an affected pregnancy and persists for more than 20 years.,Up to one third of women with a hypertensive disorder of pregnancy may develop hypertension within a decade of an affected pregnancy, indicating that cardiovascular disease prevention in these women should include blood pressure monitoring initiated soon after pregnancy. | 1 |
Previous studies suggested a possible gut microbiota dysbiosis in chronic heart failure (CHF).,However, direct evidence was lacking.,In this study, we investigated the composition and metabolic patterns of gut microbiota in CHF patients to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF.,We enrolled 53 CHF patients and 41 controls.,Metagenomic analyses of faecal samples and metabolomic analyses of faecal and plasma samples were then performed.,We found that the composition of gut microbiota in CHF was significantly different from controls.,Faecalibacterium prausnitzii decrease and Ruminococcus gnavus increase were the essential characteristics in CHF patients’ gut microbiota.,We also observed an imbalance of gut microbes involved in the metabolism of protective metabolites such as butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients.,Metabolic features of both faecal and plasma samples from CHF patients also significantly changed.,Moreover, alterations in faecal and plasma metabolic patterns correlated with gut microbiota dysbiosis in CHF.,Taken together, we found that CHF was associated with distinct gut microbiota dysbiosis and pinpointed the specific core bacteria imbalance in CHF, along with correlations between changes in certain metabolites and gut microbes. | The human gut is heavily colonized by a community of microbiota, primarily bacteria, that exists in a symbiotic relationship with the host and plays a critical role in maintaining host homeostasis.,The consumption of a high-fat (HF) diet has been shown to induce gut dysbiosis and reduce intestinal integrity.,Recent studies have revealed that dysbiosis contributes to the progression of cardiovascular diseases (CVDs) by promoting two major CVD risk factors-atherosclerosis and hypertension.,Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression.,Dysbiosis has been implicated in the development of atherosclerosis through metabolism-independent and metabolite-dependent pathways.,This review will illustrate how these pathways contribute to the various stages of atherosclerotic plaque progression.,In addition, dysbiosis can promote hypertension through vascular fibrosis and an alteration of vascular tone.,As CVD is the number one cause of death globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research, with vast therapeutic potential. | 1 |
Acute myocardial infarction is a common condition responsible for heart failure and sudden death.,Here, we show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardial function.,Depletion of CD8+ T lymphocytes decreases apoptosis within the ischemic myocardium, hampers inflammatory response, limits myocardial injury and improves heart function.,These effects are recapitulated in mice with Granzyme B-deficient CD8+ T cells.,The protective effect of CD8 depletion on heart function is confirmed by using a model of ischemia/reperfusion in pigs.,Finally, we reveal that elevated circulating levels of GRANZYME B in patients with acute myocardial infarction predict increased risk of death at 1-year follow-up.,Our work unravels a deleterious role of CD8+ T lymphocytes following acute ischemia, and suggests potential therapeutic strategies targeting pathogenic CD8+ T lymphocytes in the setting of acute myocardial infarction.,Immune cells contribute to adverse remodeling following myocardial infarction.,Here the authors show in mice and pigs that CD8+ lymphocytes release Granzyme B in the infarcted heart leading to cardiomyocyte death, enhanced inflammation and deterioration of cardiac function. | Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction.,B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes.,The animal experiment used ligation of the left anterior descending (LAD) artery of C57BL/6 mice to establish a mouse acute myocardial infarction (AMI) model to observe changes in activated B cells and cytokines at different time points.,Twelve-week-old C57BL/6 male mice were randomly divided into the Sham group (24 mice) (thread under the LAD artery without ligation) and the AMI group (64 mice).,In addition, C57BL/6 B-cell knockout (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte cytokines, such as TNF-α IL-1β, IL-6, TGF-β1, COL1-A1, COL3-AIII, TIMP, and MMP9.,Moreover, pathological and collagen changes in the myocardium were analysed.,One-way ANOVA and LSD method was used for comparisons of multiple and pairwise groups respectively.,P < 0.05 indicated significant differences.,An AMI model of C57BL/6 mice was established successfully.,The ratio of activated B cells and the expression of TNF-α, IL-1β, IL-6, TGF-β1, and B cell activating factor (BAFF) in the 5-day subgroup were the highest in the myocardium, spleen and peripheral blood with the most obvious myocardial inflammatory cell infiltration.,The cytokines mRNA expression levels in the 5-day subgroup of the BKO group were decreased compared with those in the WT group (P < 0.05).,Among the 2-week subgroups of the Sham, WT and BKO groups, the the LVEDd and LVESd of the BKO group were lower than those of the WT group (P < 0.05), and the left ventricular ejection fraction was higher than that of the WT group (P < 0.05).,Activated B cells participate in the sustained state of myocardial inflammation and immune system activation after AMI, and may affect the metabolism of myocardial collagen after AMI by secreting cytokines.,Moreover, B cells promote the expression of myocardial collagen Type I and Type III and damage the left ventricular ejection function. | 1 |
Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection.,Mechanisms remain unclear.,The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.,From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry.,Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS.,Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis).,Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).,In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs.,BCIS: median 339.0 min vs.,173.0 min; p < 0.001; COVID NSTE-ACS vs.,MINAP: 417.0 min vs.,295.0 min; p = 0.012).,Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs.,5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs.,1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]).,Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).,In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population.,Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients. | The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.,The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment.,This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020.,Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality.,A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries.,In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001).,The heterogeneity among centers was not related to the incidence of death due to COVID-19.,A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019.,Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.,The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic.,(Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655). | 1 |
Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
Supplemental Digital Content is available in the text.,Type 2 myocardial infarction and myocardial injury are common in clinical practice, but long-term consequences are uncertain.,We aimed to define long-term outcomes and explore risk stratification in patients with type 2 myocardial infarction and myocardial injury.,We identified consecutive patients (n=2122) with elevated cardiac troponin I concentrations (≥0.05 µg/L) at a tertiary cardiac center.,All diagnoses were adjudicated as per the universal definition of myocardial infarction.,The primary outcome was all-cause death.,Secondary outcomes included major adverse cardiovascular events (eg, nonfatal myocardial infarction or cardiovascular death) and noncardiovascular death.,To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models.,The adjudicated index diagnosis was type 1 or 2 myocardial infarction or myocardial injury in 1171 (55.2%), 429 (20.2%), and 522 (24.6%) patients, respectively.,At 5 years, all-cause death rates were higher in those with type 2 myocardial infarction (62.5%) or myocardial injury (72.4%) compared with type 1 myocardial infarction (36.7%).,The majority of excess deaths in those with type 2 myocardial infarction or myocardial injury were because of noncardiovascular causes (hazard ratio, 2.32; 95% confidence interval, 1.92-2.81 versus type 1 myocardial infarction).,Despite this finding, the observed crude major adverse cardiovascular event rates were similar between groups (30.6% versus 32.6%), with differences apparent after adjustment for covariates (hazard ratio, 0.82; 95% confidence interval, 0.69-0.96).,Coronary heart disease was an independent predictor of major adverse cardiovascular events in those with type 2 myocardial infarction or myocardial injury (hazard ratio, 1.71; 95% confidence interval, 1.31-2.24).,Despite an excess in noncardiovascular death, patients with type 2 myocardial infarction or myocardial injury have a similar crude rate of major adverse cardiovascular events as those with type 1 myocardial infarction.,Identifying underlying coronary heart disease in this vulnerable population may help target therapies that could modify future risk. | Elucidation of the physiologically distinct subunits of troponin in 1973 greatly facilitated our understanding of cardiac contraction.,Although troponins are expressed in both skeletal and cardiac muscle, there are isoforms of troponin I/T expressed selectively in the heart.,By exploiting cardiac-restricted epitopes within these proteins, one of the most successful diagnostic tests to date has been developed: cardiac troponin (cTn) assays.,For the past decade, cTn has been regarded as the gold-standard marker for acute myocardial necrosis: the pathological hallmark of acute myocardial infarction (AMI).,Whilst cTn is the cornerstone for ruling-out AMI in patients presenting with a suspected acute coronary syndrome (ACS), elevated cTn is frequently observed in those without clinical signs indicative of AMI, often reflecting myocardial injury of ‘unknown origin’. cTn is commonly elevated in acute non-ACS conditions, as well as in chronic diseases.,It is unclear why these elevations occur; yet they cannot be ignored as cTn levels in chronically unwell patients are directly correlated to prognosis.,Paradoxically, improvements in assay sensitivity have meant more differential diagnoses have to be considered due to decreased specificity, since cTn is now more easily detected in these non-ACS conditions.,It is important to be aware cTn is highly specific for myocardial injury, which could be attributable to a myriad of underlying causes, emphasizing the notion that cTn is an organ-specific, not disease-specific biomarker.,Furthermore, the ability to detect increased cTn using high-sensitivity assays following extreme exercise is disconcerting.,It has been suggested troponin release can occur without cardiomyocyte necrosis, contradicting conventional dogma, emphasizing a need to understand the mechanisms of such release.,This review discusses basic troponin biology, the physiology behind its detection in serum, its use in the diagnosis of AMI, and some key concepts and experimental evidence as to why cTn can be elevated in chronic diseases. | 1 |
Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis.,However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data.,This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19.,We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization.,Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization.,A total of 305 patients were included.,Mean age was 63 years and 205 patients (67.2%) were male.,Overall, myocardial injury was observed in 190 patients (62.3%).,Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions.,Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.,Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities.,Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury.,Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present. | Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19.,However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression.,Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins.,Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58.,The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis.,These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.,•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits,Statin treatment among 13,981 patients with COVID-19 was retrospectively studied,Statin use in this cohort was associated with a lower risk of all-cause mortality,Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort,The benefit of statins among this cohort may be due to immunomodulatory benefits,Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19.,But statins may increase the expression of ACE2, the receptor for SARS-CoV-2.,Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality. | 1 |
An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | 1 |
Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.,We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).,Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers.,The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.,The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively.,The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers.,High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p < 0.0001).,There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations.,SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.,The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes.,Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes. | Spain has been one of the countries heavily stricken by COVID-19.,But this epidemic has not affected all regions equally.,We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain.,Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network.,We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality.,In the study period, 2737 patients were admitted with ischemic stroke.,There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001).,In-hospital mortality of stroke patients increased significantly (9.9% vs.,6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs.,16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504).,We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain.,There were regional changes within the network, not fully explained by the severity of the pandemic in different regions. | 1 |
Thromboembolic disease is common in coronavirus disease-2019 (COVID-19).,There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.,The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.,This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding.,Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission.,Thromboembolic disease was contextualized by premortem AC among consecutive autopsies.,Among 4,389 patients, median age was 65 years with 44% women.,Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively).,When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08).,Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC.,Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC.,AC was associated with lower mortality and intubation among hospitalized COVID-19 patients.,Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant.,Autopsies revealed frequent thromboembolic disease.,These data may inform trials to determine optimal AC regimens. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component.,While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study.,A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients.,The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities.,Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%).,At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases.,Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting.,In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare. | We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock.,The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation.,Cardiac function fully recovered in 5 days and ECMO was removed.,Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung. | 1 |
To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection.,Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019.,What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities.,Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality.,The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body’s innate immune response, and the vascular response to cytokine production.,The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.,•The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,•Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,•Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress.,The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress. | Supplemental Digital Content is available in the text.,Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce.,We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection.,One hundred consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared with reference values.,Echocardiographic studies included left ventricular (LV) systolic and diastolic function and valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound.,A second examination was performed in case of clinical deterioration.,Thirty-two patients (32%) had a normal echocardiogram at baseline.,The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%).,Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared with patients with normal troponin or better clinical condition, but they had worse RV function.,Clinical deterioration occurred in 20% of patients.,In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients).,Femoral deep vein thrombosis was diagnosed in 5 of 12 patients with RV failure.,In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic function and RV function are impaired.,Elevated troponin and poorer clinical grade are associated with worse RV function.,In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without deep vein thrombosis, is more common, but acute LV systolic dysfunction was noted in ≈20%. | 1 |
What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer.,Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19.,To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE.,We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19.,Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR).,There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care.,The diagnostic yield for PE was 37%.,The overall proportion of PE in patients with COVID-19 was 5.4%.,The proportions with Wells score of ≥4 (‘PE likely’) was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951).,The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133).,D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001).,In the ‘low probability’ group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE.,Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common.,Of note, approaching half of PE events were diagnosed on hospital admission.,More data are needed to identify an optimal diagnostic pathway in patients with COVID-19.,Randomised controlled trials of intensified thromboprophylaxis are urgently needed.,•COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients•Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19•Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19•37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,•Clinicians should have high index of suspicion for PE in COVID-19,COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients,Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19,Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19,37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,Clinicians should have high index of suspicion for PE in COVID-19 | Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | 1 |
The association between underlying comorbidities and cardiac injury and the prognosis in coronavirus disease 2019 (COVID‐19) patients was assessed in this study.,The underlying comorbidities and cardiac injury may be associated with the prognosis in COVID‐19 patients.,A systematic search was conducted in PubMed, EMBASE, Web of science, and The Cochrane library from December 2019 to July 2020.,The odds ratio (OR) and 95% confidence intervals (95% CI) were used to estimate the probability of comorbidities and cardiac injury in COVID‐19 patients with or without severe type, or in survivors vs nonsurvivors of COVID‐19 patients.,A total of 124 studies were included in this analysis.,A higher risk for severity was observed in COVID‐19 patients with comorbidities.,The pooled result in patients with hypertension (OR 2.57, 95% CI: 2.12‐3.11), diabetes (OR 2.54, 95% CI: 1.89‐3.41), cardiovascular diseases (OR 3.86, 95% CI: 2.70‐5.52), chronic obstractive pulmonary disease (OR 2.71, 95% CI: 1.98‐3.70), chronic kidney disease (OR 2.20, 95% CI: 1.27‐3.80), and cancer (OR 2.42, 95% CI: 1.81‐3.22) respectively.,All the comorbidities presented a higher risk of mortality.,Moreover, the prevalence of acute cardiac injury is higher in severe group than in nonsevere group, and acute cardiac injury is associated with an increased risk for in‐hospital mortality.,Comorbidities and acute cardiac injury are closely associated with poor prognosis in COVID‐19 patients.,It is necessary to continuously monitor related clinical indicators of organs injury and concern comorbidities in COVID‐19 patients. | The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients. | 1 |
Estimating the risk of pre-existing comorbidities on coronavirus disease 2019 (COVID-19) mortality may promote the importance of targeting populations at risk to improve survival.,This systematic review and meta-analysis aimed to estimate the association of pre-existing comorbidities with COVID-19 mortality.,We searched MEDLINE, SCOPUS, OVID, and Cochrane Library databases, and medrxiv.org from December 1st, 2019, to July 9th, 2020.,The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing comorbidities.,We analyzed 11 comorbidities: cardiovascular diseases, hypertension, diabetes, congestive heart failure, cerebrovascular disease, chronic kidney disease, chronic liver disease, cancer, chronic obstructive pulmonary disease, asthma, and HIV/AIDS.,Two reviewers independently extracted data and assessed the risk of bias.,All analyses were performed using random-effects models and heterogeneity was quantified.,Eleven pre-existing comorbidities from 25 studies were included in the meta-analysis (n = 65, 484 patients with COVID-19; mean age; 61 years; 57% male).,Overall, the between-study heterogeneity was medium, and studies had low publication bias and high quality.,Cardiovascular disease (risk ratio (RR) 2.25, 95% CI = 1.60-3.17, number of studies (n) = 14), hypertension (1.82 [1.43 to 2.32], n = 13), diabetes (1.48 [1.02 to 2.15], n = 16), congestive heart failure (2.03 [1.28 to 3.21], n = 3), chronic kidney disease (3.25 [1.13 to 9.28)], n = 9) and cancer (1.47 [1.01 to 2.14), n = 10) were associated with a significantly greater risk of mortality from COVID-19.,Patients with COVID-19 with cardiovascular disease, hypertension, diabetes, congestive heart failure, chronic kidney disease and cancer have a greater risk of mortality compared to patients with COVID-19 without these comorbidities.,Tailored infection prevention and treatment strategies targeting this high-risk population might improve survival. | To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography.,In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020.,Patient characteristics, indications, findings, and impact of echocardiography on management were recorded.,Multivariable logistic regression identified predictors of echocardiographic abnormalities.,A total of 1216 patients [62 (52-71) years, 70% male] from 69 countries across six continents were included.,Overall, 667 (55%) patients had an abnormal echocardiogram.,Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%).,Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients.,In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease.,Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75-5.05) and cardiac troponin (OR 1.69, 95% CI 1.13-2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73-6.10) for the latter.,Echocardiography changed management in 33% of patients.,In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography.,Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients. | 1 |
The impact of atrial arrhythmias on coronavirus disease 2019 (COVID‐19)‐associated outcomes are unclear.,We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID‐19.,An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted.,Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL).,The association between atrial arrhythmias and 30‐day mortality was assessed with multivariable analysis.,Mean age of patients was 62 ± 17 years and 62% were men.,Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients.,Newly detected atrial arrhythmias occurred in 101 (9.6%) patients.,Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence.,Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B‐type natriuretic peptide, C‐reactive protein, ferritin and d‐dimer.,Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001).,After adjustment for age and co‐morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30‐day mortality.,Atrial arrhythmias are common among patients hospitalized with COVID‐19.,The presence of AF/AFL tracked with markers of inflammation and cardiac injury.,Atrial arrhythmias were independently associated with increased mortality. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients.,Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed.,To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization.,Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups.,However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187-.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101-.455) compared to patients who discontinued ACEi/ARB.,The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI.,These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.,In hypertensive patients with COVID-19, in-hospital continuation of ACE inhibitors or ARBs is associated with lower rates of mortality and intensive care admission in the absence of hypotension or acute kidney injury. | Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart. | 1 |
Cardiovascular involvement in coronavirus disease 2019 (COVID‐19) is common and leads to worsened mortality.,Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death.,We analyzed 887 patients (aged 64±17 years) admitted with COVID‐19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis.,Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs‐cTnT), were abstracted.,At 30 days follow‐up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired.,Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST‐T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non‐life‐threatening rhythms (P<0.001).,Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST‐T wave changes, and initial hs‐cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs‐cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality.,Myocardial injury with hs‐cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID‐19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone. | the SARS-CoV-2 infection ranges from asymptomatic to critical forms and several prognostic factors have been described.,Atrial fibrillation (AF) is common in acute situations where it is linked with more complications and mortality.,We aimed to evaluate the prognostic information of AF in this population.,retrospective analysis of a cohort of 517 patients consecutively admitted in a tertiary hospital due to SARS-CoV-2 infection.,We divided the patients in two groups according the development of AF and compared the main features of both groups.,An univariable and multivariable analysis of mortality were also performed.,among 517 patients with SARS-CoV-2 infection admitted in a tertiary center, 54 (10.4%) developed AF.,These patients are older (81.6 vs 66.5 years old, p < 0.001) and present more hypertension (74% vs 47%, p < 0.001), cardiomyopathy (9% vs 1%, p = 0.002), previous heart failure admission (9% vs 0.4%, p < 0.001), previous episodes of AF (83% vs 1%, p < 0.001) and bigger left atrium (47.8 vs 39.9 mm, p < 0.001).,AF COVID-19 patients present more acute respiratory failure (72% vs 40%, p < 0.001) and higher in-hospital mortality (50% vs 22%, p < 0.001).,Predictors of AF development are age and previous AF.,AF is not an independent predictor of in-hospital mortality.,Predictors are age, creatinine > 1.5 mg/dL at admission, LDH > 250 UI/L at admission and acute respiratory failure.,Atrial fibrillation appears in 10% of hospitalized patients with SARS-CoV-2 infection.,These patients present more comorbidities and two-fold increase in hospital mortality.,Atrial fibrillation is not an independent prognostic factor. | 1 |
Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19. | Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | 1 |
The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19. | Evidence about COVID-19 on cardiac injury is inconsistent.,We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak.,We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase-MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection.,We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection.,Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI).,We included 4189 confirmed COVID-19 infected patients from 28 studies.,More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase-MB, myoglobin, and NT-proBNP.,Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001).,Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030).,Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors.,The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death.,Cardiac injury biomarkers mainly increase in non-survivors.,This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.,Unlabelled Image | 1 |
We present the case of a 76-year-old woman who underwent left upper lobectomy for lung adenocarcinoma.,Three days after the surgery, a thrombus was observed in the pulmonary vein (PV) stump.,Four months after the surgery, we performed 4D flow MRI, which revealed decreased blood flow, not only in the left superior PV stump, but also over a widespread region around the left atrium-left superior PV junction.,4D flow MRI can clarify the altered hemodynamics underlying thrombus formation. | We aimed to evaluate the incidence and clinical features of vascular stump thrombus after oncologic lung surgery.,A retrospective analysis of records from our institutional database dated between 2009 and 2016 was performed.,Data regarding demographics, clinical presentation, medication use, operative findings, pathology, and radiologic findings were retrieved.,The study cohort consisted of 648 oncologic surgeries for primary lung cancer.,The incidence of thrombus in the entire population was 5.7% (37/648).,Most thrombi were incidentally found on follow-up chest computed tomography scans.,Univariate Cox proportional hazard analysis showed that age (p = 0.02), adjuvant therapy (p <0.001), neoadjuvant therapy (p = 0.04), left-sided surgery (p = 0.02), complex surgery greater than simple lobectomy or segmentectomy (p <0.001), advanced stages (p <0.001), non-adenocarcinoma (p = 0.003), and thoracotomy approach (p = 0.009) were associated with an increased risk of vascular stump thrombus.,There were no embolic events in our cohort, except for a case of pulmonary thromboembolism.,During follow-up, 43.2% (16/37) of thrombi had completely resolved, 48.6% (18/37) showed partial regression and stabilization, and 8.1% (3/37) had progressed.,The incidence of vascular stump thrombus in our study was not negligible.,The clinical course of stump thrombus appears to be benign in most cases.,Anticoagulation may be used with caution based on an individual basis depending on each patient’s risk factors. | 1 |
Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI).,We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI.,Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE.,T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium.,Average T1 in the MI core was higher than in the MI border zone and remote myocardium.,However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02).,MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p<0.001).,The presence of MVI profoundly affects MOLLI-measured native T1 values.,T2* mapping suggested that this may be the result of intramyocardial haemorrhage.,These findings have important implications for the interpretation of native T1 values shortly after AMI.,• Microvascular injury after acute myocardial infarction affects local T1 and T2* values.,• Infarct zone T1 values are lower if microvascular injury is present.,• T2* mapping suggests that low infarct T1 values are likely haemorrhage.,• T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.,The online version of this article (doi:10.1007/s00330-017-5010-x) contains supplementary material, which is available to authorized users. | Supplemental Digital Content is available in the text.,CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment-elevation myocardial infarction.,We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling.,Sixty ST-segment-elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement.,T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%).,Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=−0.73).,Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement.,Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment-elevation myocardial infarction.,A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment.,Further confirmatory studies will be needed. | 1 |
Coronavirus Disease 2019 (COVID‐19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality.,The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID‐19 patients.,Information on the benefit/risk ratio of this approach is still lacking.,To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug.,Consecutive COVID‐19 patients admitted between February and April 2020 were included in a retrospective analysis.,Major bleedings (MB) and clinically relevant non‐major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee.,Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants.,The rate of the composite endpoint of MB or CRNMB was 6.9 per 100‐person/months in patients who had been given prophylactic doses, and 26.4 per 100‐person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90‐7.97).,The corresponding rates for overall mortality were 12.2 and 20.1 per 100‐person/months, respectively.,The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants.,In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher.,Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non‐critically ill patients with COVID‐19. | Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | 1 |
Spain has been one of the countries heavily stricken by COVID-19.,But this epidemic has not affected all regions equally.,We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain.,Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network.,We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality.,In the study period, 2737 patients were admitted with ischemic stroke.,There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001).,In-hospital mortality of stroke patients increased significantly (9.9% vs.,6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs.,16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504).,We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain.,There were regional changes within the network, not fully explained by the severity of the pandemic in different regions. | The COVID-19 pandemic has disrupted established care paths worldwide.,Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases.,We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US.,The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database.,We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020.,There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March).,There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period.,The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02).,We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center. | 1 |
To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19).,This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE).,Patients with poor acoustic window (n=11) were excluded.,Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion <17 mm or S wave <9.5 cm/s).,The primary endpoint was in-hospital death or ICU admission.,A total of 200 patients were included in the final analysis (median age 62 (IQR 52-74) years, 65.5% men).,The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively.,Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH.,Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD.,The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, p<0.001), while the presence of RVD was not (17.2 vs 11.7%, p=0.404).,Among hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome.,NCT04318366 | This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).,Myocardial injury caused by COVID-19 was previously reported in hospitalized patients.,It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.,Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included.,CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping).,Edema ratio and LGE were assessed in post-COVID-19 patients.,Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.,Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients.,Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings.,Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs.,38.1 ms ± 2.4 vs.,39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs.,24.8% [23.1% to 25.4%] vs.,23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).,Cardiac involvement was found in a proportion of patients recovered from COVID-19.,CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function.,Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms. | 1 |
Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed.,SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models.,Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients.,Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans.,Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far.,Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19.,Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi.,Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations.,In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi.,Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis. | Supplemental Digital Content is available in the text.,The full spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic to acute respiratory distress syndrome, characterized by hyperinflammation and thrombotic microangiopathy.,The pathogenic mechanisms are poorly understood, but emerging evidence suggest that excessive neutrophil extracellular trap (NET) formation plays a key role in COVID-19 disease progression.,Here, we evaluate if circulating markers of NETs are associated with COVID-19 disease severity and clinical outcome, as well as to markers of inflammation and in vivo coagulation and fibrinolysis.,One hundred six patients with COVID-19 with moderate to severe disease were enrolled shortly after hospital admission and followed for 4 months.,Acute and convalescent plasma samples as well as plasma samples from 30 healthy individuals were assessed for markers of NET formation: citrullinated histone H3, cell-free DNA, NE (neutrophil elastase).,We found that all plasma levels of NET markers were elevated in patients with COVID-19 relative to healthy controls, that they were associated with respiratory support requirement and short-term mortality, and declined to those found in healthy individuals 4 months post-infection.,The levels of the NET markers also correlated with white blood cells, neutrophils, inflammatory cytokines, and C-reactive protein, as well as to markers of in vivo coagulation, fibrinolysis, and endothelial damage.,Our findings suggest a role of NETs in COVID-19 disease progression, implicating their contribution to an immunothrombotic state.,Further, we observed an association between circulating markers of NET formation and clinical outcome, demonstrating a potential role of NET markers in clinical decision-making, as well as for NETs as targets for novel therapeutic interventions in COVID-19. | 1 |
The purpose of this study was to identify patients at higher risk of deep venous thrombosis (DVT) in the uninjured lower extremity both preoperatively and postoperatively in patients with lower extremity fractures.,We collected the clinical data of patients with lower extremities fractures who presented at Xi’an Honghui Hospital between 1 July, 2015 and 31 October, 2017.,Doppler ultrasonography was used to diagnose the DVT.,Patients were examined pre- and postoperatively.,The patients were divided into thrombosis group and no thrombosis group according to the preoperative and postoperative ultrasonography results.,The thrombosis group was defined as patients with DVT in the uninjured lower extremity and the no thrombosis group was defined as patients without DVT in the uninjured lower extremity.,This study enrolled 1454 patients who met the inclusion criteria.,The incidence of preoperative DVT in the uninjured lower extremity was 9.63% whereas the postoperative incidence was 20.29%.,Age (OR = 0.965, 95 CI%: 0.954-0.977; P ≤ 0.001) and female (OR = 0.667, 95% CI: 0.451-0.986, P = 0.042) were independent risk factors for preoperative DVT in the uninjured lower extremity.,Blood loss (OR = 0.997, 95 CI%: 0.995-1.000; P = 0.020), D-dimer level at admission (OR = 0.941, 95 CI%: 0.887-0.999; P = 0.045), and postoperative day 5 D-dimer level (OR = 0.889, 95 CI%: 0.819-0.965; P = 0.005), were independent risk factors for postoperative DVT in the uninjured lower extremity.,For the patients with lower extremity fractures, age and female were associated with the preoperative DVT in the uninjured lower extremity.,Blood loss, D-dimer at admission and postoperative day 5 D-dimer were associated with the postoperative DVT in the uninjured lower extremity. | In this study, we investigated the epidemiological characteristics and predictors of preoperative new-onset deep vein thrombosis (DVT) in adult patients with closed distal femur fractures (DFFs).,The study was designed as a prospective cohort trial at the Third Hospital of Hebei Medical University.,From October 2018 to June 2020, a total of 160 patients with closed DFFs were enrolled to assess the location and prognosis of preoperative DVT.,The patients were followed up for 2 months.,Duplex ultrasonography (DUS) was used to diagnose patients with DVT.,The patients were divided into two groups (DVT group and non-DVT group).,The DVT was then classified into proximal, distal, and mixed thromboses.,The Mann-Whitney U test or t test, receiver operating characteristic (ROC) analyses, univariate Chi-square analyses, and multiple logistic regression analyses were used to analyze the adjusted predictors of DVT.,The overall incidence of preoperative DVTs was 52.5% (n = 84), which was diagnosed at a mean period of 3.1 days after injury.,Among patients diagnosed with DVTs, 50.0% (n = 42) had distal thrombosis while 47.6% (n = 40) had mixed thrombosis.,The calf muscle veins were the most common sites of DVTs (90.5%, n = 76).,Of note, 45.2% (n = 38) of diagnosed DVTs were completely recanalized at a mean period of 12.0 days after the initial (first) diagnosis.,Multivariate analysis revealed that age of ≥ 65 years of age (odds ratio [OR], 4.390; 95% confidence interval [CI] 1.727-11.155; p = 0.002), C-reactive protein (CRP) levels exceeding 11 mg/L (OR 4.158; 95% CI 1.808-11.289; p = 0.001), platelet (PLT) levels over 217 × 109/L (OR, 2.55; 95% CI 1.07-6.07; p = 0.035), D-dimer levels over 1.0 mg/L (OR 3.496; 95% CI 1.483-8.237; p = 0.004), and an American Society of Anesthesiologists (ASA) score of III-V (OR 2.753; 95% CI 1.216-6.729; p = 0.026) were the independent risk factors of preoperative DVT.,High levels of CRP, PLT, D-dimer, ASA, and ≥ 65 years of age increase the risk of preoperative DVTs in adult patients with closed DFFs.,Thus, the prediction of preoperative DVTs can significantly be improved by identifying older patients over the age of 65, and establishing the biochemical cut-off values of CRP, PLT, ASA, and D-dimer.,No.,2018-026-1, 24 October 2018, prospectively registered.,This trial was registered prospectively on 24 October 2018 before the first participant was enrolled.,This study protocol conformed to the Declaration of Helsinki and approved by the Institutional Review Board.,The ethics committee approved the study on the factors of prognosis for patients with fractures.,Data used in this study were obtained from the patients who underwent orthopedic surgery between October 2018 and June 2020. | 1 |
Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
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