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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%. | 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 |
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. | 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 |
Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI).,How they impact remote organs is however largely unknown.,Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM).,In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component.,Myo-miRs are imported selectively to peripheral organs and preferentially to the BM.,Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression.,Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells.,Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.,During myocardial infarction, microRNAs (myo-miRs) are released into the circulation.,Here Cheng et al. show that myo-miRs carried in exosomes are transferred to the bone marrow (BM), downregulate expression of CXCR4 in mononuclear cells, and increase the number of circulating BM progenitor cells, thus orchestrating a systemic response to myocardial injury. | Rationale: Cardiac stem cell-derived exosomes have been demonstrated to promote cardiac regeneration following myocardial infarction in preclinical studies.,Recent studies have used intramyocardial injection in order to concentrate exosomes in the infarct.,Though effective in a research setting, this method is not clinically appealing due to its invasive nature.,We propose the use of a targeting peptide, cardiac homing peptide (CHP), to target intravenously-infused exosomes to the infarcted heart.,Methods: Exosomes were conjugated with CHP through a DOPE-NHS linker.,Ex vivo targeting was analyzed by incubating organ sections with the CHP exosomes and analyzing with fluorescence microscopy.,In vitro assays were performed on neonatal rat cardiomyocytes and H9C2 cells.,For the animal study, we utilized an ischemia/reperfusion rat model.,Animals were treated with either saline, scramble peptide exosomes, or CHP exosomes 24 h after surgery.,Echocardiography was performed 4 h after surgery and 21 d after surgery.,At 21 d, animals were sacrificed, and organs were collected for analysis.,Results: By conjugating the exosomes with CHP, we demonstrate increased retention of the exosomes within heart sections ex vivo and in vitro with neonatal rat cardiomyocytes.,In vitro studies showed improved viability, reduced apoptosis and increased exosome uptake when using CHP-XOs.,Using an animal model of ischemia/reperfusion injury, we measured the heart function, infarct size, cellular proliferation, and angiogenesis, with improved outcomes with the CHP exosomes.,Conclusions: Our results demonstrate a novel method for increasing delivery of for treatment of myocardial infarction.,By targeting exosomes to the infarcted heart, there was a significant improvement in outcomes with reduced fibrosis and scar size, and increased cellular proliferation and angiogenesis. | 1 |
The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease.,Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors.,Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses.,Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors.,We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort).,Results were validated in 1123 men and 575 women (validation cohort).,The median age was 69 years for men and 75 years for women.,The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively).,In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2.,In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations.,In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations.,These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations. | 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 potential beneficial effect of ozone (O3) on stroke had been identified experimentally and clinically, but these effects remain controversial in population-based studies.,This study aimed to explore the epidemiological association between O3 and risk of ischemic stroke.,Ischemic stroke related health data and air pollution data were obtained from the Center for Disease Control and Prevention and Environmental Monitoring Center in Changzhou between 2015 and 2016, respectively.,The associations between the short-term exposure to O3 and daily ischemic stroke onsets and deaths were examined based on time-series generalized additive Poisson model.,During the study period, daily ischemic stroke onsets and deaths decreased 0.340% (95% confidence interval (CI) −0.559% to −0.120%) and 0.697% (95% CI −1.103% to −0.290%) with an interquartile range (IQR) (41.1 µg/m3) increase in levels of ambient O3, respectively.,The protective effects of O3 were more significant in men and elders and in the cool season than those in women and young people and in the warm season, respectively.,The negative association was independent of PM2.5, PM10, SO2, NO2 or CO exposure.,Acute O3 exposure was associated with decreased risk of ischemic stroke.,These findings will help provide new insights into the relationship between ischemic stroke and ambient O3 concentrations. | Background: Though increasing evidence supports association between gaseous air pollution and stroke, it remains unclear whether the effects differ in season, sex and age.,The aim of this study was to examine the associations of gaseous air pollution with stroke admissions in Beijing, 2013-2014 in different subgroups.,Methods: Case-crossover design and conditional logistic regression were used to perform the analyses.,We examined the exposure-response relationship between air pollution and stroke.,Stratified analyses were performed in different seasons, sex, and age groups.,Results: There were 147,624 stroke admissions during the study period.,In the whole study period, percent changes of stroke admissions were 0.82% (95% CI: 0.52% to 1.13%) and 0.73% (95% CI: 0.44% to 1.03%) per 10 μg/m3 increase in the same day conentration of nitrogen dioxide (NO2) and sulfur dioxide (SO2).,The positive associations were higher in warm seasons and with patients >65 years (p < 0.05).,Contrary effects of carbon monoxide (CO) and ozone on stroke admissions were observed in different seasons.,Conclusions: NO2 and SO2 were positively associated with stroke admissions, with stronger effects in warm seasons and with patients >65 years.,The associations of CO and ozone with stroke admissions differed across seasons. | 1 |
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. | Acute respiratory distress syndrome development in patients with coronavirus disease 2019 (COVID-19) pneumonia is associated with a high mortality rate and is the main cause of death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1].,Myocardial injury has also been reported to be significantly associated with fatal outcome, with a 37% mortality rate in patients without prior cardiovascular disease but elevated troponin levels [2].,A D-dimer level of >1 μg·mL−1 has been clearly identified as a risk factor for poor outcome in SARS-Cov-2 infection [3], with recent reports highlighting a high incidence of thrombotic events in intensive care unit (ICU) patients [4].,A normal D-dimer level allows the safe exclusion of pulmonary embolism (PE) in outpatients with a low or intermediate clinical probability of PE, but there is no recommendation to use D-dimer as a positive marker of thrombosis because of lack of specificity.,This study reports an overall 24% (95% CI 17-32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30-70%) in ICU and 18% (12-27%) in other patientshttps://bit.ly/35s7hjm | 1 |
Giant cell arteritis (GCA) can be classified into Cranial(C)-GCA and Large Vessel(LV)-GCA.,Based on analysis of temporal arteries, GCA is postulated to be T-cell-mediated.,Recently, a disturbed B-cell homeostasis was documented in newly diagnosed GCA patients.,In the current study, we assessed the presence of B-cells and their level of ectopic organization in the aorta of LV-GCA patients.,Aorta tissue samples of 9 histologically-proven LV-GCA patients and 22 age- and sex-matched atherosclerosis patients who underwent aortic aneurysm surgery were studied by immunohistochemistry.,Sections were stained for B-cells, T-cells, follicular dendritic cells, high endothelial venules, germinal center B-cells, proliferating B-cells, macrophages, and plasma cells.,Aortas of LV-GCA patients showed massive infiltration of B-cells, which clearly outnumbered T-cells, as opposed to C-GCA patients where, as previously reported, T-cells outnumber B-cells.,B-cells were mainly found in the adventitia of the vessel wall and were organized into artery tertiary lymphoid organs.,These tertiary lymphoid organs had germinal centers, proliferating B-cells and plasma cell niches.,In conclusion, we found massive and organized B-cell infiltrates in the aorta of LV-GCA patients, which is in line with the previously documented decrease of circulating B-cells in active GCA.,Our data indicate a role for B-cells in the pathogenesis of GCA and thus evoke further investigation into the factors determining the tissue tropism and organization of B-cells in GCA. | While clinical signs and symptoms of giant cell arter it is improve promptly after starting glucocorticoid therapy, reports have suggested that the vascular inflammation may persist.,To assess the duration and quality of his to pathologic changes in treated patients, we prospectively obtained second temporal artery biopsies in patients treated for 3 to 12 months after their first diagnostic biopsy. 40 patients (28 women, 12 men, median age 77 years) agreed to have a second temporal artery biopsy randomly assigned to 3, 6, 9, or 12 months subsequent to the first.,Clinical and laboratory evaluation of the patient cohort revealed a typical rapid response and continued suppression of clinical manifestations as a result of glucocorticoid treatment.,His to pathologic findings, evaluated in a blinded fashion by a cardiovascular pathologist, showed unequivocal findings of vasculitis in 7/10 patients with second temporal artery biopsy at 3 months, 9/12 at 6 months, 4/9 at 9 months, and 4/9 at 12 months.,Lymphocytes were present in all positive initial biopsies and remained the dominant cell population in chronically treated patients.,Granulomatous inflammation decreased in a time-dependent fashion from 78%-100% at initial biopsy to 50% at 9 months and 25% at 12 months.,The increased medial fibrosis noted in the second biopsies (60% vs. 33% in primary temporal artery biopsies) suggested that the finding may represent a chronic finding in arteritis.,In summary, the response to glucocorticoids in giant cell arteritis was frequently discordant.,Clinical manifestations were readily suppressed, but vascular changes were gradual and often incomplete. | 1 |
Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people.,However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.,We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.,Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020).,The review protocol was previously registered (PROSPERO ID = CRD42020185476).,Data were extracted from articles reporting ≥5 stroke cases in COVID-19.,We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality.,Data were pooled using a random-effect model.,Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis.,Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9).,The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%).,Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54).,Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90).,Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors.,The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease. | Italy is one of the most affected countries by the coronavirus disease 2019 (COVID-19).,The responsible pathogen is named severe acute respiratory syndrome coronavirus (SARS-CoV-2).,The clinical spectrum ranges from asymptomatic infection to severe pneumonia, leading to intensive care unit admission.,Evidence of cerebrovascular complications associated with SARS-CoV-2 is limited.,We herein report six patients who developed acute stroke during COVID-19 infection.,A retrospective case series of patients diagnosed with COVID-19 using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs, who developed clinical and neuroimaging evidence of acute stroke during SARS-CoV-2 infection.,Six patients were identified (5 men); median age was 69 years (range 57-82).,Stroke subtypes were ischemic (4, 67%) and hemorrhagic (2, 33%).,All patients but one had pre-existing vascular risk factors.,One patient developed encephalopathy prior to stroke, characterized by focal seizures and behavioral abnormalities.,COVID-19-related pneumonia was severe (i.e., requiring critical care support) in 5/6 cases (83%).,Liver enzyme alteration and lactate dehydrogenase (LDH) elevation were registered in all cases.,Four patients (67%) manifested acute kidney failure prior to stroke.,Four patients (67%) had abnormal coagulation tests.,The outcome was poor in the majority of the patients: five died (83%) and the remaining one (17%) remained severely neurologically affected (mRS: 4).,Both ischemic and hemorrhagic stroke can complicate the course of COVI-19 infection.,In our series, stroke developed mostly in patients with severe pneumonia and multiorgan failure, liver enzymes and LDH were markedly increased in all cases, and the outcome was poor. | 1 |
Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.,In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.,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.,This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.,The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met.,Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58).,The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2).,The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort.,Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.,In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis.,(ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.) | 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 |
Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles. | The aim of this study was to characterize the echocardiographic phenotype of patients with COVID-19 pneumonia and its relation to biomarkers.,Seventy-four patients (59 ± 13 years old, 78% male) admitted with COVID-19 were included after referral for transthoracic echocardiography as part of routine care.,A level 1 British Society of Echocardiography transthoracic echocardiography was used to assess chamber size and function, valvular disease, and likelihood of pulmonary hypertension.,The chief abnormalities were right ventricle (RV) dilatation (41%) and RV dysfunction (27%).,RV impairment was associated with increased D-dimer and C-reactive protein levels.,In contrast, left ventricular function was hyperdynamic or normal in most (89%) patients. | 1 |
Supplemental Digital Content is available in the text,Coronavirus disease 2019 (COVID-19) has been associated with increased incidence of venous thromboembolic events (VTE) as well as mortality.,D-dimer is a marker of fibrinolysis and has been used as a diagnostic and prognostic marker in VTE among other diseases.,The purpose of our study is to describe outcomes from out center and to examine trends in D-dimer levels as it relates to VTE and mortality.,Patients admitted with confirmed COVID-19 cases to Emory Healthcare from March 12, 2020 through April 6, 2020 with measured plasma D-dimer levels were included in our retrospective analysis.,Relevant data about comorbidities, hospitalization course, laboratory results, and outcomes were analyzed.,One hundred fifteen patients were included in our study.,Mean age was 64 ± 15 years, 47 (41%) females and 84 (73%) African-American.,Hypertension was present in 83 (72%) and diabetes in 60 (52%).,Mean duration of hospitalization was 19 ± 11 days with 62 (54%) patients intubated (mean duration of 13 ± 8 days).,VTE was diagnosed in 27 (23%) patients (mean time to diagnosis 14 ± 9 days).,Median D-dimer within the first 7 days of hospitalization was higher (6450 vs. 1596 ng/mL, p < 0.001) in VTE cases compared to non-VTE cases, and was predictive of VTE (area under the curve [AUC] = 0.72, optimal threshold 2500 ng/mL) although not of mortality (AUC 0.55, P = .34).,Change in D-dimer level (AUC = 0.72 P = .004) and rate of D-dimer rise (AUC = 0.75 P = .001) were also predictive of VTE, though neither predicted death (P > .05 for all).,Within the first 7 days of hospitalization, peak D-dimer level of >2500 ng/mL and a rate of change exceeding 150 ng/mL/d were predictive of future diagnosis of VTE.,Rise in D-dimer >2000 ng/mL within any 24 hour period through hospital day 10 had 75% sensitivity and 74% specificity for diagnosis of VTE.,We found that both magnitude and rate of rise in d-dimer within the first 10 days of hospitalization are predictive of diagnosis of VTE but not mortality.,These parameters may aid in identifying individuals with possible underlying VTE or at high risk for VTE, thereby guiding risk stratification and anticoagulation policies in COVID-19 patients. | 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 |
Magnetic resonance (MR) studies suggested cardiac involvement post‐Covid‐19 in a significant subset of affected individuals, including athletes.,This brings serious clinical concerns regarding the potential need for in‐depth cardiac screening in athletes after Covid‐19 before return to play.,The aim of this study was to gain further insight into the relation between Covid‐19 and cardiac involvement in professional athletes.,This was a retrospective cohort study, in which 26 consecutive elite athletes (national team, Olympians, top national league players; median age 24 years, interquartile range [IQR] 21-27, 81% female) were included.,At 1.5 T including balanced steady‐state free precession cine imaging, T1 and T2‐mapping using Myomaps software (Siemens), dark‐blood T2‐weighted images with fat suppression, and late gadolinium enhancement (LGE) with phase‐sensitive inversion recovery sequence were used.,The athletes had mainly asymptomatic or mild course of the disease (77%).,They were scanned after a median of 32 days (IQR 22-62 days) from the diagnosis.,MR data were reviewed by three independent observers, each with >10 years cardiac MR experience.,Native T1, T2, extracellular volume, and T2 signal intensity ratio were calculated.,Diagnosis of acute myocarditis was based on modified Lake Louise criteria.,Statistical analyses used were Pearson correlation and Bland-Altman repeatability analysis.,At the time of MR the athletes had no pathologic electrocardiogram abnormalities or elevated troponin levels.,MR did not reveal any case of acute myocarditis.,Cardiac abnormalities were found in five (19%) athletes, including four athletes presenting borderline signs of isolated myocardial edema and one athlete showing nonischemic LGE with pleural and pericardial effusion.,Another athlete had signs of persistent lung congestion without cardiac involvement.,We have shown that in a small group of elite athletes with mainly asymptomatic to mild Covid‐19, lack of electrocardiographic changes, and normal troponin concentration 1-2 months after the diagnosis, there were no signs of acute myocarditis, but 19% of athletes had some abnormalities as assessed by cardiac MR.,4,3 | As our understanding of the complications of coronavirus disease-2019 (COVID-19) evolve, subclinical cardiac pathology such as myocarditis, pericarditis, and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern.,The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias.,Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return to play.,Cardiac imaging is at the center of these evaluations.,This review seeks to evaluate the current evidence regarding COVID-19-associated cardiovascular disease and how multimodality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection.,Guidance is provided with diagnostic “red flags” that raise the suspicion of pathology.,Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from subclinical cardiac disease.,The strengths and limitations of different imaging modalities are discussed and an approach to return to play decision making for athletes post-COVID-19, as informed by multimodality imaging, is provided. | 1 |
Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide.,Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear.,A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.,Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6).,Salient information was abstracted from the medical record.,Light microscopic findings were recorded.,An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases.,Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.,Male sex was more common in the COVID-19 group (P=0.05).,Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006).,Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease.,Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004).,Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively).,SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence.,Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis.,Cases with cleared infection had variable presentations.,This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection.,COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury.,Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent.,Histological features of resolved infection are variable.,Cardiac amyloidosis may be an additional risk factor for severe disease. | 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 |
Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected.,Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered.,Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19.,A key role may be that of the renin-angiotensin-aldosterone system.,Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti‐inflammatory effects.,Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19.,On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers.,ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation.,Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity.,Prospective trials are needed to ascertain whether these drugs may have protective effects. | 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 |
•Acute suppurative bronchopneumonia is a frequent complication in patients with COVID-19 and may be the major cause of death.,•A high incidence of thrombotic/thromboembolic vascular occlusions is seen in COVID-19 decedents.,•COVID-19 increases the risk of thrombotic/thromboembolic events and cardiac complications.,Acute suppurative bronchopneumonia is a frequent complication in patients with COVID-19 and may be the major cause of death.,A high incidence of thrombotic/thromboembolic vascular occlusions is seen in COVID-19 decedents.,COVID-19 increases the risk of thrombotic/thromboembolic events and cardiac complications.,Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades.,The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents.,Bilateral diffuse alveolar damage (DAD) was found in all patients.,Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients.,A key finding was the presence of thrombotic/thromboembolic vascular occlusions.,We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%).,Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage.,All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%).,Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis.,The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events.,Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death. | The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality. | 1 |
Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients.,In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE).,Among adipokines, omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity.,To study the relationship between omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).,We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization.,Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months.,Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 vs 30.82 ± 5.48 ng/mL, p < 0.001).,Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up.,We observed that omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 vs 31.34 ± 5.54 ng/mL, p < 0.001).,The association between omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis.,Receiver operating characteristics (ROC) curve using omentin-1 levels predicted incidence events (area under the curve = 0.80).,We demonstrated that reduced omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure. | Sortilin is a 95-kDa protein which has recently been linked to circulating cholesterol concentration and lifetime risk of developing significant atherosclerotic disease.,Sortilin is found inside different cell types and circulating in blood.,Higher circulating sortilin concentration has been found in patients with coronary atherosclerosis compared to control subjects.,Sortilin concentration is influenced by statin therapy.,We enrolled statin-naïve subjects with type 2 diabetes mellitus and we performed a cross-sectional study to evaluate the association between sortilin levels and the presence of clinically significant lower limb peripheral artery disease (PAD) in a population of statin-free diabetic subjects.,Out of the 154 patients enrolled in our study, 80 patients were free from PAD, while 74 had clinically significant PAD.,Sortilin concentration was significantly higher in the latter group compared to the former (1.61 ± 0.54 ng/mL versus 0.67 ± 0.30 ng/mL, P < 0.01) and there was a trend toward increased sortilin levels as disease severity increased.,The association of sortilin levels with PAD remained after adjusting for major risk factors in a multivariate analysis.,We showed that sortilin is significantly and independently associated with the presence of lower limb PAD in a statin-free diabetic population and it may be a promising marker for clinically significant atherosclerosis of the lower limbs.,Further studies are needed to confirm this finding and to evaluate its clinical usefulness. | 1 |
Covid‐19 can involve multiple organs including the nervous system.,We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid‐19.,We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid‐19 within a hospital network in Chicago, Illinois.,We compared the severity of Covid‐19 and outcomes in patients with and without neurologic manifestations.,We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression.,Neurologic manifestations were present at Covid‐19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%).,The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%).,Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each).,Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%).,Independent risk factors for developing any neurologic manifestation were severe Covid‐19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014).,Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2).,However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs.,11 [3.2%] patients; P < 0.001).,Neurologic manifestations occur in most hospitalized Covid‐19 patients.,Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity. | Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series.,Larger studies have been limited by both geography and specialty.,Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies.,The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.,During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care.,Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations).,Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available.,Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.,The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020.,Data lock for this report was on April 26, 2020.,During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies.,Median patient age was 71 years (range 23-94; IQR 58-79).,Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis.,The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses.,Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.,To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19.,Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.,This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.,None. | 1 |
To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice.,Cohort study using data from nationwide registers and an active-comparator new-user design.,Denmark, Norway, and Sweden, from April 2013 to December 2016.,20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score.,Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure).,Secondary outcomes were the individual components of the cardiovascular composite and any cause death.,In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition.,Cox regression was used to estimate hazard ratios.,Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease.,Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin.,During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively.,Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure.,Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure.,Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death.,In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death.,In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis.,In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed.,These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice. | To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice.,Population based retrospective cohort study.,Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart).,Three pairwise 1:1 propensity score matched cohorts of patients with type 2 diabetes 18 years and older who initiated canagliflozin or a comparator non-gliflozin antidiabetic agent (ie, a DPP-4i, a GLP-1RA, or a sulfonylurea) between April 2013 and September 2015.,The primary outcomes were heart failure admission to hospital and a composite cardiovascular endpoint (comprised of being admitted to hospital for acute myocardial infarction, ischemic stroke, or hemorrhagic stroke).,Hazard ratios and 95% confidence intervals were estimated in each propensity score matched cohort controlling for more than 100 baseline characteristics.,During a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ).,The hazard ratio for the composite cardiovascular endpoint associated with canagliflozin was 0.89 (0.68 to 1.17) versus a DPP-4i, 1.03 (0.79 to 1.35) versus a GLP-1RA, and 0.86 (0.65 to 1.13) versus a sulfonylurea.,Results were similar in sensitivity analyses further adjusting for baseline hemoglobin A1c levels and in subgroups of patients with and without prior cardiovascular disease or heart failure.,In this large cohort study, canagliflozin was associated with a lower risk of heart failure admission to hospital and with a similar risk of myocardial infarction or stroke in direct comparisons with three different classes of non-gliflozin diabetes treatment alternatives as used in routine care. | 1 |
Runt-related transcription factor-1 (RUNX1), also known as acute myeloid leukaemia 1 protein (AML1), is a member of the core-binding factor family of transcription factors which modulate cell proliferation, differentiation, and survival in multiple systems.,It is a master-regulator transcription factor, which has been implicated in diverse signalling pathways and cellular mechanisms during normal development and disease.,RUNX1 is best characterized for its indispensable role for definitive haematopoiesis and its involvement in haematological malignancies.,However, more recently RUNX1 has been identified as a key regulator of adverse cardiac remodelling following myocardial infarction.,This review discusses the role RUNX1 plays in the heart and highlights its therapeutic potential as a target to limit the progression of adverse cardiac remodelling and heart failure. | Supplemental Digital Content is available in the text.,Myocardial infarction (MI) is a leading cause of heart failure and death worldwide.,Preservation of contractile function and protection against adverse changes in ventricular architecture (cardiac remodeling) are key factors to limiting progression of this condition to heart failure.,Consequently, new therapeutic targets are urgently required to achieve this aim.,Expression of the Runx1 transcription factor is increased in adult cardiomyocytes after MI; however, the functional role of Runx1 in the heart is unknown.,To address this question, we have generated a novel tamoxifen-inducible cardiomyocyte-specific Runx1-deficient mouse.,Mice were subjected to MI by means of coronary artery ligation.,Cardiac remodeling and contractile function were assessed extensively at the whole-heart, cardiomyocyte, and molecular levels.,Runx1-deficient mice were protected against adverse cardiac remodeling after MI, maintaining ventricular wall thickness and contractile function.,Furthermore, these mice lacked eccentric hypertrophy, and their cardiomyocytes exhibited markedly improved calcium handling.,At the mechanistic level, these effects were achieved through increased phosphorylation of phospholamban by protein kinase A and relief of sarco/endoplasmic reticulum Ca2+-ATPase inhibition.,Enhanced sarco/endoplasmic reticulum Ca2+-ATPase activity in Runx1-deficient mice increased sarcoplasmic reticulum calcium content and sarcoplasmic reticulum-mediated calcium release, preserving cardiomyocyte contraction after MI.,Our data identified Runx1 as a novel therapeutic target with translational potential to counteract the effects of adverse cardiac remodeling, thereby improving survival and quality of life among patients with MI. | 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. | 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 |
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. | 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 |
An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients. | 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 |
Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID‐19).,Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation.,We analyzed a case series of COVID‐19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs.,We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12‐lead ECGs.,Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms.,Tisdale score and Elixhauser comorbidity index were calculated.,Of 490 COVID‐19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID‐19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men).,Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%.,Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications.,Significant prolongation was observed only in men (18±43 ms versus −0.2±28 ms in women; P=0.02).,A total of 12% of patients reached critical QTc prolongation.,Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07).,No patients manifested torsades de pointes.,Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone.,The balance between uncertain benefit and potential risk when treating COVID‐19 patients should be carefully assessed. | Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID‐19)‐related pneumonia as well as multiple organ injuries.,COVID‐19 infection may result in cardiovascular manifestations leading to worse clinical outcome.,Fifty four severe and critical patients with confirmed COVID‐19 were enrolled.,Risk factors predicting the severity of COVID‐19 were analyzed.,Of the 54 patients (56.1 ± 13.5 years old, 66.7% male) with COVID‐19, 39 were diagnosed as severe and 15 as critical cases.,The occurrence of diabetes, the level of D‐dimer, inflammatory and cardiac markers in critical cases were significantly higher.,Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients.,Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently.,Hypotension was found in one severe case and seven critical cases during hospitalization.,Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients.,Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common.,Mild pericardial effusion was observed in one severe case and five critical cases.,Three critical cases suffered new onset of heart failure.,Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID‐19 infection.,This study has systemically observed the impact of COVID‐19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases.,Monitoring of vital signs and cardiac function of COVID‐19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance. | 1 |
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. | 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 |
Previous studies have investigated the relationship of the triglyceride glucose (TyG) index with the incidence of cardiovascular events.,However, to date, there have been no studies comparing the predictive values of fasting plasma glucose (FPG), glycosylated hemoglobin A (HbA1C) and the TyG index for the risk of cardiovascular events.,This study aimed to use discordance analysis to evaluate and compare the effectiveness of FPG, HbA1C and the TyG index to predict the risk of cardiovascular events.,Patients diagnosed with acute coronary disease (ACS) undergoing percutaneous coronary intervention (PCI) were enrolled in this study.,The TyG index was computed using the following formula: ln [fasting triglycerides (mg/dL) × FPG (mg/dL)/2].,We categorized patients into 4 concordance/discordance groups.,Discordance was defined as a TyG index equal to or greater than the median and an FPG or HbA1C less than the median, or vice versa.,The primary outcome was the composite of death, nonfatal myocardial infarction, nonfatal stroke and unplanned repeat revascularization.,A Cox proportional hazards regression model was performed to estimate the risk of cardiovascular events according to the concordance/discordance groups.,Sensitivity analysis was performed on each patient group divided into high or low categories for HbA1C or FPG and were repeated according to diabetes status.,In total, 9285 patients were included in the final statistical analysis (male: 75.3%, age: 59.9 ± 10.05 years, BMI: 26.2 ± 9.21 kg/m2, diabetes: 43.9% and dyslipidemia: 76.8%).,The medians defining concordance/discordance were 6.19 mmol/L for FPG, 6.1% for HbA1C and 8.92 for the TyG index.,The TyG index was strongly related to triglycerides and HDL-C (r = 0.881 and -0.323, respectively; both P < 0.001).,During the 17.4 ± 2.69 months of follow-up, there were 480 (5.1%) incident cardiovascular events.,Among patients with a lower HbA1C or FPG, 15.6% and 16.3%, respectively, had a discordantly high TyG index and a greater risk of cardiovascular events compared with patients with a concordantly low TyG index after full adjustment (HR: 1.92, 95% CI 1.33-2.77; HR: 1.89, 95% CI 1.38-2.59; for HbA1C and FPG, respectively).,Repeat risk estimation using high or low categories for FPG or HbA1C and diabetes status confirmed the results.,Patients with a discordantly high TyG index had a significantly greater risk of cardiovascular events regardless of diabetes status.,The TyG index might be a better predictor of cardiovascular risk than FPG or HbA1C for patients with ACS undergoing PCI.,This discordance may support better cardiovascular risk management regardless of diabetes status. | The triglyceride glucose (TyG) index, a simple surrogate estimate of insulin resistance, has been demonstrated to predict cardiovascular (CV) disease morbidity and mortality in the general population and many patient cohorts.,However, to our knowledge, the prognostic usefulness of the TyG index after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) has not been determined.,This study aimed to evaluate the association of the TyG index with adverse CV outcomes in patients with T2DM and ACS who underwent PCI.,The TyG index was calculated using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2].,The primary endpoint was the composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization.,The association between the TyG index and adverse CV outcomes was assessed by Cox proportional hazards regression analysis.,In total, 776 patients with T2DM and ACS who underwent PCI (mean age, 61 ± 10 years; men, 72.2%) were included in the final analysis.,Over a median follow-up of 30 months, 188 patients (24.2%) had at least 1 primary endpoint event.,The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles.,The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.17 (95% CI 1.45-3.24; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared.,The TyG index was significantly and positively associated with adverse CV outcomes, suggesting that the TyG index may be a valuable predictor of adverse CV outcomes after PCI in patients with T2DM and ACS. | 1 |
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. | Ever since the first case was reported at the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) has become a serious threat to public health globally in short time.,At this point in time, there is no proven effective therapy.,The interactions with concomitant disease are largely unknown, and that may be particularly pertinent to inherited arrhythmia syndrome.,An arrhythmogenic effect of COVID-19 can be expected, potentially contributing to disease outcome.,This may be of importance for patients with an increased risk of cardiac arrhythmias, either secondary to acquired conditions or comorbidities or consequent to inherited syndromes.,Management of patients with inherited arrhythmia syndromes such as long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia in the setting of the COVID-19 pandemic may prove particularly challenging.,Depending on the inherited defect involved, these patients may be susceptible to proarrhythmic effects of COVID-19-related issues such as fever, stress, electrolyte disturbances, and use of antiviral drugs.,Here, we describe the potential COVID-19-associated risks and therapeutic considerations for patients with distinct inherited arrhythmia syndromes and provide recommendations, pending local possibilities, for their monitoring and management during this pandemic. | 1 |
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. | 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.,The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic.,Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy.,The incidence of torsade de pointes remains unknown.,Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment.,Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study.,A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest.,The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin.,Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms.,Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%).,A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5.,There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced.,The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy. | We report on a case of a 57-year-old male patient, who underwent full root replacement in 2005 and now presented with high grade aortic insufficiency.,On admission, the patient underwent a computed tomography scan which demonstrated interstitial infiltration in the left lung, highly suspicious for a COVID-19 infection that could not be confirmed by reverse transcription polymerase chain reaction (RT-PCR) testing.,As there usually is a delay between infection and positive RT-PCR test results, the initial decision was to perform additional testing.,However, the patient deteriorated quickly in spite of optimal medical therapy making urgent aortic valve replacement necessary.,We decided to perform transcatheter aortic valve replacement to avoid cardiopulmonary bypass with shorter operative times, presumably shorter ventilation times and duration of intensive care unit stay, and thus a lesser risk for pulmonary complications. | 1 |
Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19).,We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.,Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020.,COVID‐19 cases were defined based on hospitalization/death for COVID‐19.,Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases.,We performed consistency analysis to quantify the impact of potential unmeasured confounding.,Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19.,After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96).,MRA use was not associated with risk of any outcome.,Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.,In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19. | Angiotensin-converting enzyme 2 is the receptor that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses for entry into lung cells.,Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia.,This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs.,We retrospectively reviewed 684 consecutive patients hospitalized for suspected COVID-19 pneumonia and tested by polymerase chain reaction assay.,Patients were split into two groups, according to whether (group 1, n = 484) or not (group 2, n = 250) COVID-19 was confirmed.,Multivariable adjusted comparisons included a propensity score analysis.,The mean age was 63.6 ± 18.7 years, and 302 patients (44%) were female.,Hypertension was present in 42.6% and 38.4% of patients in groups 1 and 2, respectively (P = 0.28).,Treatment with ARBs was more frequent in group 1 than group 2 (20.7% vs.,12.0%, respectively; odds ratio [OR] 1.92, 95% confidence interval [CI] 1.23-2.98; P = 0.004).,No difference was found for treatment with ACEIs (12.7% vs.,15.7%, respectively; OR 0.81, 95% CI 0.52-1.26; P = 0.35).,Propensity score-matched multivariable logistic regression confirmed a significant association between COVID-19 and previous treatment with ARBs (adjusted OR 2.36, 95% CI 1.38-4.04; P = 0.002).,Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients.,This study suggests that ACEIs and ARBs are not similarly associated with COVID-19.,In this retrospective series, patients with COVID-19 pneumonia more frequently had previous treatment with ARBs compared with patients without COVID-19. | 1 |
We describe a case of a 20‐year‐old healthy man developing chest pain and classical symptoms of vaccine reactogenicity 12 h after receiving the first dose of mRNA‐1273 (Moderna).,Cardiac troponin T was increased, and subepicardial inflammation and focal contractile dysfunction were detected by cardiac magnetic resonance imaging and echocardiography.,We confirmed the diagnosis of acute myocarditis by endomyocardial biopsy demonstrating significant infiltration of monocytes and T lymphocytes.,Although we detected IgG against nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) indicating prior infection, the patient repeatedly tested negative for SARS‐CoV‐2 and had been asymptomatic for several months.,Furthermore, viral genome analysis of endomyocardial biopsy samples was negative for SARS‐CoV‐2 and other potential cardiotropic viruses.,These findings and the strong temporal relation between the vaccination and the symptom onset imply a potential side effect of mRNA‐1273. | Half of U.S. adults have received at least one dose of the COVID-19 vaccines produced by either Pfizer, Moderna, or Johnson and Johnson, which represents a major milestone in the ongoing pandemic.,Given the emergency use authorizations for these vaccines, their side effects and safety were assessed over a compressed time period.,Hence, ongoing monitoring for vaccine-related adverse events is imperative for a full understanding and delineation of their safety profile.,An 22-year-old Caucasian male presented to our hospital center complaining of pleuritic chest pain.,Six months prior he had a mild case of COVID-19, but was otherwise healthy.,He had received his first dose of the Moderna vaccine three days prior to developing symptoms.,Laboratory analysis revealed a markedly elevated troponin and multiple imaging modalities during his hospitalization found evidence of wall motion abnormalities consistent with a diagnosis of perimyocarditis.,He was started on aspirin and colchicine with marked improvement of his symptoms prior to discharge.,We present a case of perimyocarditis that was temporally related to COVID-19 mRNA vaccination in an young male with prior COVID-19 infection but otherwise healthy.,Our case report highlights an albeit rare but important adverse event for clinicians to be aware of.,It also suggests a possible mechanism for the development of myocardial injury in our patient.,The online version contains supplementary material available at 10.1186/s12872-021-02183-3. | 1 |
•Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,•Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,•Left ventricular dysfunction and hypokinesis was common and should be managed.,•Steroids were often used but implications on viral clearance should be considered.,Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,Left ventricular dysfunction and hypokinesis was common and should be managed.,Steroids were often used but implications on viral clearance should be considered.,Myocarditis caused by SARS-CoV-2 infection was proposed to account for a proportion of cardiac injury in patients with COVID-19.,However, reports of coronavirus-induced myocarditis were scarce.,The aim of this review was to summarise the published cases of myocarditis and describe their presentations, diagnostic processes, clinical characteristics and outcomes.,A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL and OpenGrey on was performed on 3 June 2020.,Studies of myocarditis in patients with COVID-19 were included, and those only reporting cardiac injury or heart failure were excluded.,Cases were “confirmed” myocarditis if diagnosed on cardiac magnetic resonance imaging (CMR) or histopathology.,Those without were grouped as “possible” myocarditis.,A total of 31 studies on 51 patients were included; 12 cases were confirmed myocarditis while 39 had possible myocarditis.,The median age was 55 and 69% were male.,The most common presenting symptoms were fever, shortness of breath, cough and chest pain.,Electrocardiogram changes included non-specific ST-segment and T-wave changes and ventricular tachycardia.,Most patients had elevated cardiac and inflammatory biomarkers.,Left ventricular dysfunction and hypokinesis was common.,CMR established the diagnosis in 10 patients, with features of cardiac oedema and cardiac injury.,Five patients had histopathological examination.,Some cases required mechanical ventilation and extracoporeal membrane oxygenation, and 30% of patients recovered but 27% died.,COVID-19 myocarditis was associated with ECG, cardiac biomarker and echocardiographic changes, and the manifestation could be severe leading to mortality.,Endomyocardial biopsy was not available in most cases but CMR was valuable. | Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense.,Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported.,SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated.,Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed.,EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany.,Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction.,We describe patients of different history of symptoms and time duration.,Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage.,This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs.,In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases.,EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies. | 1 |
Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance.,We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort.,A total of 97,653 participants free of history of stroke in the Kailuan Study were included.,TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2).,Baseline TyG index was measured during 2006-2007.,Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up.,The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage.,The associations of TyG index with outcomes were explored with Cox regression.,During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage.,After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12-1.33, and adjusted HR 1.32, 95% CI 1.21-1.44, respectively, P for trend < 0.001).,We also found a linear association between baseline TyG index with stroke.,Similar results were found for ischemic stroke.,However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage.,Parallel results were observed for the associations of updated cumulative average TyG index with outcomes.,Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up. | The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases.,However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD).,In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH).,We assessed health check-up participants aged 40-79 years from 2006 to 2013.,The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2.,The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated.,This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD.,SBI was measured for both prevalence and burden.,The WMH volume was quantitatively rated using a computer-assisted semi-automated technique.,A total of 2615 participants were evaluated (median age: 56 years, male sex: 53%).,In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06-1.81).,Further quantitative analyses showed a positive dose-response relationship between the TyG index and SBI burden (P for trend = 0.006).,In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154).,Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR.,A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population.,This marker of IR could be a convenient and useful predictor of cSVD. | 1 |
Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19).,We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.,Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020.,COVID‐19 cases were defined based on hospitalization/death for COVID‐19.,Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases.,We performed consistency analysis to quantify the impact of potential unmeasured confounding.,Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19.,After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96).,MRA use was not associated with risk of any outcome.,Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.,In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19. | Although attention is focused on addressing the acute situation created by the COVID-19 illness, it is imperative to continue our efforts to prevent cardiovascular morbidity and mortality, particularly during a period of prolonged social isolation which may limit physical activity, adversely affect mental health and reduce access to usual care.,One option may be to deliver healthcare interventions remotely through digital healthcare solutions.,Therefore, the aim of this paper is to bring together the evidence for remote healthcare during a quarantine situation period to support people living with cardiovascular disease during COVID-19 isolation.,The PubMed, CINAHL and Google Scholar were searched using telehealth OR digital health OR mHealth OR eHealth OR mobile apps AND COVID-19 OR quarantine search terms.,We also searched for literature relating to cardiovascular disease AND quarantine.,The literature search identified 45 potentially relevant publications, out of which nine articles were included.,Three overarching themes emerged from this review: (1) preparing the workforce and ensuring reimbursement for remote healthcare, (2) supporting mental and physical health and (3) supporting usual care.,To support people living with cardiovascular disease during COVID-19 isolation and to mitigate the effects of quarantine and adverse effect on mental and physical well-being, we should offer remote healthcare and provide access to their usual care. | 1 |
•Diabetes mellitus is a frequent comorbidity in patients with COVID-19 infection•Diabetic patients with COVID-19 infection are at higher risk to be admitted to intensive care unit•Diabetic patients with COVID-19 infection have an higher mortality risk,Diabetes mellitus is a frequent comorbidity in patients with COVID-19 infection,Diabetic patients with COVID-19 infection are at higher risk to be admitted to intensive care unit,Diabetic patients with COVID-19 infection have an higher mortality risk,The prognostic significance of diabetes mellitus (DM) in patients with coronavirus 2019 disease (COVID-19) remains unknown.,To assess the risk of ICU admission and morality risk in diabetic COVID-19 patients.,A database search was conducted to identify studies comparing diabetic COVID-19 patients hospitalized in intensive care unit (ICU) and those reporting the overall mortality of these patients published up to March 25, 2020 within MEDLINE, Scopus and Web of Science.,Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity.,Quality assessment was performed using the Newcastle-Ottawa quality assessment scale.,The main outcome was the risk of ICU admission in diabetic patients with COVID-19 infection while the second was the mortality risk in overall diabetic COVID-19 patients.,Data were pooled using the Mantel-Haenszel random effects models with odds ratio (OR) as the effect measure with the related 95 % confidence interval (CI).,Statistical heterogeneity between groups was measured using the Higgins I2 statistic.,Among 1382 patients (mean age 51.5 years, 798 males), DM resulted to be the second more frequent comorbidities.,Diabetic patients resulted to have a significant increased risk of ICU admission (OR: 2.79, 95 % CI 1.85-4.22, p < 0.0001, I2 = 46 %).,In 471 patients (mean age 56.6 years, 294 males) analysed for the secondary outcome diabetic subjects resulted to be at higher mortality risk (OR 3.21, 95 % CI 1.82-5.64, p < 0.0001, I2 = 16 %).,Diabetic patients with COVID-19 patients are at higher risk of ICU admission and show an higher mortality risk. | The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19. | 1 |
Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation.,Minority populations are disproportionately impacted by COVID-19.,This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients.,We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY).,We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias.,One hundred five patients (mean age 67 years; 44.8% F) were analyzed.,The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3).,QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001).,The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities.,The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs.,4.8%, p < 0.01).,Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs.,22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7).,Adjusting for race/ethnicity yielded no significant associations.,Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias.,Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment.,Careful risk-benefit analyses for individual patients should guide the use of these medications.,Randomized control trials are necessary to evaluate their efficacies. | 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 |
Achieving the blood pressure treatment target in individuals with hypertension is a serious global health challenge.,Furthermore, the actual burden of uncontrolled hypertension is poorly understood, especially in the developing countries.,Therefore, this study comprehensively examined the prevalence and factors associated with uncontrolled hypertension in individuals receiving care at the primary healthcare facilities in the rural areas of Mkhondo Municipality in the Mpumalanga Province, South Africa.,In this cross-sectional study, 329 individuals attending care for hypertension were recruited from January 2019 to June 2019 at three primary healthcare centres, namely, Piet Retief hospital, Mkhondo town clinic and Thandukukhanya community health centre.,Uncontrolled hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg in accordance with the South African Hypertension Society guideline (2014).,Multiple logistic regression (Forward LR method) analysis was used to identify the significant determinants of uncontrolled hypertension.,The majority of the participants were 55 years old and above (69.0%), Zulus (81.2%), non-smokers (84.19%) and had been diagnosed with hypertension for more than a year prior to the study (72.64%).,The overall prevalence of uncontrolled hypertension was 56.83% (n = 187) with no significant difference between sexes, 57.38% male versus 56.88% female, respectively.,In the multiple logistic regression model analysis after adjusting for confounding variables, obesity (AOR = 2.90; 95% CI 1.66-5.05), physical activity (AOR = 4.79; 95% CI 2.15-10.65) and HDL-C (AOR = 5.66; 95% CI 3.33-9.60) were the significant and independent determinants of uncontrolled hypertension in the cohort.,The high prevalence of uncontrolled hypertension in the study setting can be largely attributed to obesity, physical activity and dyslipidaemia.,Treatment will require the collaborative efforts of individuals, clinicians and health authorities.,All these determinants should be addressed decisively so as to achieve the treatment blood pressure targets in the study population. | The objective of this study was to examine the impact of smoking on respiratory diseases, hypertension and myocardial infarction, with a particular focus from a life-course perspective.,In this study, 28,577 males from a Chinese longitudinal survey were analysed.,The effects of smoking on the risk of respiratory diseases, hypertension and myocardial infarction were assessed from a life-course perspective and a current view separately.,No significant associations were found between smoking and the risk of incident respiratory diseases, hypertension and myocardial infarction in the group younger than 35.,Among study participants aged between 36-55 and 56-80, smoking was positively associated with the risk of incident respiratory diseases, hypertension and myocardial infarction from the life-course perspective, and the risk increased with age.,In contrast, the results from a current view showed inverse associations between smoking and the risk of the diseases mentioned above.,Our findings highlight that it is essential to quantify the effects of smoking from a life-course perspective in future research and to suggest that smokers quit smoking as soon as possible, regardless of the temporary side effects of quitting. | 1 |
Cellular defense mechanisms, intracellular signaling, and physiological functions are regulated by electrophiles and reactive oxygen species (ROS).,Recent works strongly considered imbalanced ROS and electrophile overabundance as the leading cause of cellular and tissue damage, whereas oxidative stress (OS) plays a crucial role for the onset and progression of major cerebrovascular and neurodegenerative pathologies.,These include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), stroke, and aging.,Nuclear factor erythroid 2-related factor (NRF2) is the major modulator of the xenobiotic-activated receptor (XAR) and is accountable for activating the antioxidative response elements (ARE)-pathway modulating the detoxification and antioxidative responses of the cells.,NRF2 activity, however, is also implicated in carcinogenesis protection, stem cells regulation, anti-inflammation, anti-aging, and so forth.,Herein, we briefly describe the NRF2-ARE pathway and provide a review analysis of its functioning and system integration as well as its role in major CNS disorders.,We also discuss NRF2-based therapeutic approaches for the treatment of neurodegenerative and cerebrovascular disorders. | Electrophiles and reactive oxygen species (ROS) play a major role in modulating cellular defense mechanisms as well as physiological functions, and intracellular signaling.,However, excessive ROS generation (endogenous and exogenous) can create a state of redox imbalance leading to cellular and tissue damage (Ma and He, 2012) [1].,A growing body of research data strongly suggests that imbalanced ROS and electrophile overproduction are among the major prodromal factors in the onset and progression of several cerebrovascular and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), stroke, Alzheimer's disease (AD), Parkinson's disease (PD), and aging (Ma and He, 2012; Ramsey et al., 2017; Salminen et al., 2012; Sandberg et al., 2014; Sarlette et al., 2008; Tanji et al., 2013) [1-6].,Cells offset oxidative stress by the action of housekeeping antioxidative enzymes (such as superoxide dismutase, catalase, glutathione peroxidase) as well direct and indirect antioxidants (Dinkova-Kostova and Talalay, 2010) [7].,The DNA sequence responsible for modulating the antioxidative and cytoprotective responses of the cells has been identified as the antioxidant response element (ARE), while the nuclear factor erythroid 2-related factor (NRF2) is the major regulator of the xenobiotic-activated receptor (XAR) responsible for activating the ARE-pathway, thus defined as the NRF2-ARE system (Ma and He, 2012) [1].,In addition, the interplay between the NRF2-ARE system and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB, a protein complex that controls cytokine production and cell survival), has been further investigated in relation to neurodegenerative and neuroinflammatory disorders.,On these premises, we provide a review analysis of current understanding of the NRF2-NF-ĸB interplay, their specific role in major CNS disorders, and consequent therapeutic implication for the treatment of neurodegenerative and cerebrovascular diseases.,fx1,•ROS overproduction promotes cerebrovascular and neurodegenerative disorders.,•NRF2 activity is critical to maintain the redox balance against oxidative stress.,•NF-κB modulates inflammatory/immune responses, apoptosis and cell growth.,•NRF2 and NF-κB pathways interfere with one another at the transcription level.,•NRF2 enhancing/NF-κB inhibitory substances could relieve CNS disorders.,ROS overproduction promotes cerebrovascular and neurodegenerative disorders.,NRF2 activity is critical to maintain the redox balance against oxidative stress.,NF-κB modulates inflammatory/immune responses, apoptosis and cell growth.,NRF2 and NF-κB pathways interfere with one another at the transcription level.,NRF2 enhancing/NF-κB inhibitory substances could relieve CNS disorders. | 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. | 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 |
Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality.,A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease.,The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy.,Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis.,Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury.,Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum.,Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists.,Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective.,This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment.,From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes. | Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention. | 1 |
The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world.,Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined.,In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2.,To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum.,We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB.,These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease.,Our findings suggest potential therapeutic targets for COVID-19.,Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines.,Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades. | 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. | 1 |
Acute rheumatic fever (ARF) and rheumatic heart disease cause substantial burdens worldwide.,Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited.,Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and ARF recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality.,Factors associated with adherence (percent of doses administered) were analyzed using logistic regression.,Nested case-control and case-crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (OR) with 95% CIs Adherence estimates (7728) were analyzed.,Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence.,Alcohol misuse was associated with lower adherence.,The risk of ARF recurrence did not decrease until ≈40% of doses had been administered.,Receiving <80% was associated with a 4‐fold increase in the odds of ARF recurrence (case-control OR: 4.00 [95% CI: 1.7-9.29], case-crossover OR: 3.31 [95% CI: 1.09-10.07]) and appeared to be associated with increased all‐cause mortality (case-control OR: 1.90 [95% CI: 0.89-4.06]; case-crossover OR 1.91 [95% CI: 0.51-7.12]).,We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced ARF recurrence, and a likely reduction in mortality, in our setting.,These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes. | Rheumatic heart disease (RHD) poses a major disease burden among disadvantaged populations globally.,It results from acute rheumatic fever (ARF), a complication of Group A Streptococcal (GAS) infection.,These conditions are acknowledged as diseases of poverty, however the role of specific social and environmental factors in GAS infection and progression to ARF/RHD is not well understood.,The aim of this systematic review was to determine the association between social determinants of health and GAS infection, ARF and RHD, and the effect of interventions targeting these.,We conducted a systematic literature review using PubMed, the Cochrane Library and Embase.,Observational and experimental studies that measured: crowding, dwelling characteristics, education, employment, income, nutrition, or socioeconomic status and the relationship with GAS infection, ARF or RHD were included.,Findings for each factor were assessed against the Bradford Hill criteria for evidence of causation.,Study quality was assessed using a standardised tool.,1,164 publications were identified. 90 met inclusion criteria, comprising 91 individual studies.,49 (50.5%) were poor quality in relation to the specific study question.,The proportion of studies reporting significant associations between socioeconomic determinants and risk of GAS infection was 57.1%, and with ARF/RHD was 50%.,Crowding was the most assessed factor (14 studies with GAS infection, 36 studies with ARF/RHD) followed by socioeconomic status (6 and 36 respectively).,The majority of studies assessing crowding, dwelling characteristics, education and employment status of parents or cases, and nutrition, reported a positive association with risk of GAS infection, ARF or RHD.,Crowding and socioeconomic status satisfactorily met the criteria of a causal association.,There was substantial heterogeneity across all key study aspects.,The extensive literature examining the role of social determinants in GAS infection, ARF and RHD risk lacks quality.,Most were observational, not interventional.,Crowding as a cause of GAS infection and ARF/RHD presents a practical target for prevention actions. | 1 |
With the recent approval and widespread administration of the Pfizer-BioNTech, Moderna, and Janssen vaccines worldwide, incidence of severe Coronavirus Disease 2019 (COVID-19) infection has significantly decreased.,In spite of their undisputed role in reducing the severity of the disease and reduction of the disease burden in the community, there have been case reports of serious side effects with these vaccines.,We aim to describe a case report of myocarditis following administration of the Janssen vaccine in a healthy, young male and review the available literature on COVID-19 vaccine related myocarditis and its possible pathogenesis.,This case and literature review notes a temporal association between COVID-19 vaccination and myocarditis.,Despite these observations, the benefits of the vaccines far outweigh the risks of possible myocarditis. | Reports have emerged of myocarditis and pericarditis predominantly after the second dose of the coronavirus disease messenger ribonucleic acid vaccine.,We describe 13 patients aged 12-17 years who presented with chest pain within 1 week after their second dose of the Pfizer vaccine and were found to have elevated serum troponin levels and evidence of myopericarditis. | 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) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2.,ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain.,ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form.,An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7.,Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis.,The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors.,Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane.,Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis.,Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency.,We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions.,The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis.,In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7.,In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection. | 1 |
Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes.,However, there are not many published articles on the pathological findings in the liver of patients with COVID-19.,We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment.,We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy.,We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases.,Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection.,With the exception of three cases that had not been tested for D-dimer, all 14 patients’ D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment.,Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage.,Rare megakaryocytes were found in sinusoids.,COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract.,Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus.,The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract.,Possible mechanisms are also discussed. | Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course.,Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths.,In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany.,Our evaluation provides a systematic overview of the first 80 consecutive full autopsies.,A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19).,In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab.,In the other 74 cases, SARS-CoV-2 infection had already been known antemortem.,The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years).,In the study cohort, 34 deceased were female (38%) and 46 male (62%).,Overall, 38% of the deceased were overweight or obese.,All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus.,A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3.,Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death.,In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism.,Peripheral pulmonary artery embolisms were found in nine other cases.,Overall, deep vein thrombosis has been found in 40% of the cases.,This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far. | 1 |
To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown.,Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020.,The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously.,We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)].,There was a 47% drop in total numbers (562 vs.,1053).,Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent.,During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively.,The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12).,Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed.,In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.,Graphical Abstract | It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).,This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital.,The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China.,Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection.,Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension.,After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs.,1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013].,Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs.,3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041).,The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs.,3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774).,However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20).,While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19.,However, the results should be considered as exploratory and interpreted cautiously. | 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. | This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit in France with severe coronavirus disease 2019 (COVID-19). | 1 |
Graphical abstractImpact of the COVID-19 pandemic on patients with cardiovascular disease worldwide.ACS, acute coronary syndrome; CV, cardiovascular; HF, heart failure; ICD, implantable cardioverter-defibrillator.,Impact of the COVID-19 pandemic on patients with cardiovascular disease worldwide.,ACS, acute coronary syndrome; CV, cardiovascular; HF, heart failure; ICD, implantable cardioverter-defibrillator. | Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures.,We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.,We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database.,Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina).,We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery).,We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.,Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43).,This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline.,During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46).,In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45).,The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.,Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020.,The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease.,The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.,UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre. | 1 |
Supplemental Digital Content is available in the text.,Ca2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca2+-ATPase 2a).,Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI).,To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI.,ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia.,Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA partially abrogated the ischemia-induced contractile dysfunction.,Overexpression of ZFAS1 in otherwise normal mice created similar impairment of cardiac function as that observed in MI mice.,Moreover, at the cellular level, ZFAS1 overexpression weakened the contractility of cardiac muscles.,At the subcellular level, ZFAS1 deleteriously altered the Ca2+ transient leading to intracellular Ca2+ overload in cardiomyocytes.,At the molecular level, ZFAS1 was found to directly bind SERCA2a protein and to limit its activity, as well as to repress its expression.,The effects of ZFAS1 were readily reversible on knockdown of this lncRNA.,Notably, a sequence domain of ZFAS1 gene that is conserved across species mimicked the effects of the full-length ZFAS1.,Mutation of this domain or application of an antisense fragment to this conserved region efficiently canceled out the deleterious actions of ZFAS1.,ZFAS1 had no significant effects on other Ca2+-handling regulatory proteins.,ZFAS1 is an endogenous SERCA2a inhibitor, acting by binding to SERCA2a protein to limit its intracellular level and inhibit its activity, and a contributor to the impairment of cardiac contractile function in MI.,Therefore, anti-ZFAS1 might be considered as a new therapeutic strategy for preserving SERCA2a activity and cardiac function under pathological conditions of the heart. | Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell-type specificity of nuclear receptors remain poorly understood.,Here we outline a role for a non-coding RNA in modulating the cell type-specific actions of LXRs, sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis.,We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the critical cholesterol efflux gene Abca1.,Mice lacking the MeXis gene show reduced Abca1 expression in a tissue-selective manner.,Furthermore, loss of MeXis in mouse bone marrow cells alters chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis.,Mechanistic studies reveal that MeXis interacts with and guides promoter binding of the transcriptional coactivator DDX17.,The identification of MeXis as a lncRNA modulator of LXR-dependent gene expression expands our understanding of the mechanisms underlying cell-type selective actions of nuclear receptors in physiology and disease. | 1 |
Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).,To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.,We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network.,The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715).,The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism.,Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White.,Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common.,Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting.,Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all).,Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis. | 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 |
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. | A potential link between mortality, D-dimer values and a prothrombotic syndrome has been reported in patients with COVID-19 infection.,The National Institute for Public Health of the Netherlands asked a group of Radiology and Vascular Medicine experts to provide guidance for the imaging workup and treatment of these important complications.,This report summarizes evidence for thromboembolic disease, potential diagnostic and preventive actions as well as recommendations for patients with COVID-19 infection. | 1 |
High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID‐19 patients, but the characteristics of symptomatic VTE in general COVID‐19 patients have not been described.,To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID‐19 patients.,This retrospective study enrolled all COVID‐19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020.,A total of 2779 patients were confirmed with COVID‐19.,In comparison to 23,434 non‐COVID‐19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non‐severe hospitalized COVID‐19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively.,When 104 VTE cases and 208 non‐VTE cases were compared, pulmonary embolism cases had a higher rate for in‐hospital death (OR 6.74, 95% CI 2.18-20.81).,VTE developed at a median of 21 days (interquartile range 13.25-31) since onset.,Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D‐dimer on admission, and D‐dimer increment (DI) ≥1.5‐fold; of these, DI ≥1.5‐fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10−10).,A novel model consisting of three simple coagulation variables (fibrinogen and D‐dimer levels on admission, and DI ≥1.5‐fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710).,There is an excess risk of VTE in hospitalized COVID‐19 patients.,This novel model can aid early identification of patients who are at high risk for VTE. | Severe coronavirus disease 2019 (COVID‐19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients.,To investigate the mechanism of microthrombosis in COVID‐19 progression.,We assessed von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin‐cofactor (VWF:RCo), VWF multimers, VWF propeptide (VWFpp), and ADAMTS13 activity in a cross‐sectional study of 50 patients stratified according to their admission to three different intensity of care units: low (requiring high‐flow nasal cannula oxygenation, n = 14), intermediate (requiring continuous positive airway pressure devices, n = 17), and high (requiring mechanical ventilation, n = 19).,Median VWF:Ag, VWF:RCo, and VWFpp levels were markedly elevated in COVID‐19 patients and increased with intensity of care, with VWF:Ag being 268, 386, and 476 IU/dL; VWF:RCo 216, 334, and 388 IU/dL; and VWFpp 156, 172, and 192 IU/dL in patients at low, intermediate, and high intensity of care, respectively.,Conversely, the high‐to‐low molecular‐weight VWF multimers ratios progressively decreased with increasing intensity of care, as well as median ADAMTS13 activity levels, which ranged from 82 IU/dL for patients at low intensity of care to 62 and 55 IU/dL for those at intermediate and high intensity of care.,We found a significant alteration of the VWF‐ADAMTS13 axis in COVID‐19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio that was strongly associated with disease severity.,Such an imbalance enhances the hypercoagulable state of COVID‐19 patients and their risk of microthrombosis. | 1 |
The cause-and-effect relationship of QTc prolongation in Coronavirus disease 2019 (COVID-19) patients has not been studied well.,We attempt to better understand the relationship of QTc prolongation in COVID-19 patients in this study.,This is a retrospective, hospital-based, observational study.,All patients with normal baseline QTc interval who were hospitalized with the diagnosis of COVID-19 infection at two hospitals in Ohio, USA were included in this study.,Sixty-nine patients had QTc prolongation, and 210 patients continued to have normal QTc during hospitalization.,The baseline QTc intervals were comparable in the two groups.,Patients with QTc prolongation were older (mean age 67 vs.,60, P 0.003), more likely to have underlying cardiovascular disease (48% versus 26%, P 0.001), ischemic heart disease (29% versus 17%, P 0.026), congestive heart failure with preserved ejection fraction (16% versus 8%, P 0.042), chronic kidney disease (23% versus 10%, P 0.005), and end-stage renal disease (12% versus 1%, P < 0.001).,Patients with QTc prolongation were more likely to have received hydroxychloroquine (75% versus 59%, P 0.018), azithromycin (18% vs.,14%, P 0.034), a combination of hydroxychloroquine and azithromycin (29% vs 7%, P < 0.001), more than 1 QT prolonging agents (59% vs.,32%, P < 0.001).,Patients who were on angiotensin-converting enzyme inhibitors (ACEi) were less likely to develop QTc prolongation (11% versus 26%, P 0.014).,QTc prolongation was not associated with increased ventricular arrhythmias or mortality.,Older age, ESRD, underlying cardiovascular disease, potential virus mediated cardiac injury, and drugs like hydroxychloroquine/azithromycin, contribute to QTc prolongation in COVID-19 patients.,The role of ACEi in preventing QTc prolongation in COVID-19 patients needs to be studied further. | To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication.,This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020.,Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists.,The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis.,The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs.,At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days.,Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation.,In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours.,In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities.,The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage. | 1 |
Increasing evidence suggests that features of the gut microbiota correlate with ischemic stroke.,However, the specific characteristics of the gut microbiota in patients suffering different types of ischemic stroke, or recovering from such strokes, have rarely been studied, and potential microbiotic predictors of different types of stroke have seldom been analyzed.,We subjected fecal specimens from patients with lacunar or non-lacunar acute ischemic infarctions, and those recovering from such strokes, to bacterial 16S rRNA sequencing and compared the results to those of healthy volunteers.,We identified microbial markers of different types of ischemic stroke and verified that these were of diagnostic utility.,Patients with two types of ischemic stroke, and those recovering from ischemic stroke, exhibited significant shifts in microbiotic diversities compared to healthy subjects.,Cluster of Orthologous Groups of Proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed reduced metabolic and transport-related pathway activities in ischemic stroke patients.,We performed fivefold cross-validation using a Random Forest model to identify two optimal bacterial species (operational taxonomic units; OTUs) serving as markers of lacunar infarction; these were Lachnospiraceae (OTU_45) and Bacteroides (OTU_4), and the areas under the receiver operating characteristic curves (AUCs under the ROCs) were 0.881 and 0.872 respectively.,In terms of non-lacunar acute ischemic infarction detection, the two optimal species were Bilophila (OTU_330) and Lachnospiraceae (OTU_338); the AUCs under the ROCs were 0.985 and 0.929 respectively.,In post-ischemic stroke patients, the three optimal species were Pseudomonas (OTU_35), Sphingomonadaceae (OTU_303), and Akkermansia (OTU_9); the AUCs under the ROCs were 1, 0.897, and 0.846 respectively.,Notably, the gut microbial markers were of considerable value for utility when diagnosing lacunar infarction, non-lacunar acute ischemic infarction, and post-ischemic stroke.,This study is the first to characterize the gut microbiotic profiles of patients with lacunar or non-lacunar, acute ischemic strokes, and those recovering from stroke, and to identify microbiotic predictors of such strokes. | Chronic systemic inflammation contributes to the pathogenesis of many age‐related diseases.,Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age‐related inflammation.,Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke.,Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke.,Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG).,Mice were subjected to ischemic stroke (middle cerebral artery occlusion; MCAO) or sham surgery.,During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S ribosomal RNA analysis of bacterial content.,We found that the microbiota is altered after experimental stroke in young mice and resembles the biome of uninjured aged mice.,In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9‐fold (p < 0.001) compared to young.,This increased F:B ratio in aged mice is indicative of dysbiosis.,Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6‐fold increase in F:B ratio, p < 0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels.,Conversely, altering the microbiota in aged to resemble that of young (∼9‐fold decrease in F:B ratio, p < 0.001) increased survival and improved recovery following MCAO.,Aged biome increased the levels of systemic proinflammatory cytokines.,We conclude that the gut microbiota can be modified to positively impact outcomes from age‐related diseases.,Ann Neurol 2018;83:23-36 | 1 |
To describe the place and causes of acute cardiovascular death during the COVID-19 pandemic.,Retrospective cohort of adult (age ≥18 years) acute cardiovascular deaths (n=5 87 225) in England and Wales, from 1 January 2014 to 30 June 2020.,The exposure was the COVID-19 pandemic (from onset of the first COVID-19 death in England, 2 March 2020).,The main outcome was acute cardiovascular events directly contributing to death.,After 2 March 2020, there were 28 969 acute cardiovascular deaths of which 5.1% related to COVID-19, and an excess acute cardiovascular mortality of 2085 (+8%).,Deaths in the community accounted for nearly half of all deaths during this period.,Death at home had the greatest excess acute cardiovascular deaths (2279, +35%), followed by deaths at care homes and hospices (1095, +32%) and in hospital (50, +0%).,The most frequent cause of acute cardiovascular death during this period was stroke (10 318, 35.6%), followed by acute coronary syndrome (ACS) (7 098, 24.5%), heart failure (6 770, 23.4%), pulmonary embolism (2 689, 9.3%) and cardiac arrest (1 328, 4.6%).,The greatest cause of excess cardiovascular death in care homes and hospices was stroke (715, +39%), compared with ACS (768, +41%) at home and cardiogenic shock (55, +15%) in hospital.,The COVID-19 pandemic has resulted in an inflation in acute cardiovascular deaths, nearly half of which occurred in the community and most did not relate to COVID-19 infection suggesting there were delays to seeking help or likely the result of undiagnosed COVID-19. | Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence. | 1 |
We sought to study the impact of COVID‐19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST‐elevation myocardial infarction (STEMI) in a non‐hot‐spot region.,COVID‐19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain.,From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18‐hospital system.,Pre‐ and post‐COVID‐19 cohorts were based on March 23rd, 2020, whenstay‐at‐home orders were initiated in Ohio.,We used presenting heart rate, blood pressure, troponin, new Q‐wave, and left ventricle ejection fraction (LVEF) to assess severity.,Duration of intensive care unit stay, total length of stay, door‐to‐balloon (D2B) time, and radial versus femoral access were used to assess patterns of care.,Post‐COVID‐19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q‐wave, and higher initial troponin; however, these did not reach statistical significance.,Among post‐COVID‐19 patients, those with >12‐hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs.,8.5 ng/ml, p = .03).,Of these, 27% avoided the hospital due to fear of COVID‐19, 18% believed symptoms were COVID‐19 related, and 9% did not want to burden the hospital during the pandemic.,COVID‐19 has remarkably affected STEMI presentation and care.,Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis. | The coronavirus SARS-CoV-2 outbreak led to the most recent pandemic of the twenty-first century.,To contain spread of the virus, many nations introduced a public lockdown.,How the pandemic itself and measures of social restriction affect hospital admissions due to acute cardiac events has rarely been evaluated yet.,German public authorities announced measures of social restriction between March 21st and April 20th, 2020.,During this period, all patients suffering from an acute cardiac event admitted to our hospital (N = 94) were assessed and incidence rate ratios (IRR) of admissions for acute cardiac events estimated, and compared with those during the same period in the previous three years (2017-2019, N = 361).,Admissions due to cardiac events were reduced by 22% as compared to the previous years (n = 94 vs. an average of n = 120 per year for 2017-2019).,Whereas IRR for STEMI 1.20 (95% CI 0.67-2.14) and out-of-hospital cardiac arrest IRR 0.82 (95% CI 0.33-2.02) remained similar, overall admissions with an IRR of 0.78 (95% CI 0.62-0.98) and IRR for NSTEMI with 0.46 (95% CI 0.27-0.78) were significantly lower.,In STEMI patients, plasma concentrations of high-sensitivity troponin T at admission were significantly higher (644 ng/l, IQR 372-2388) compared to 2017-2019 (195 ng/l, IQR 84-1134; p = 0.02).,The SARS-CoV-2 pandemic and concomitant social restrictions are associated with reduced cardiac events admissions to our tertiary care center.,From a public health perspective, strategies have to be developed to assure patients are seeking and getting medical care and treatment in time during SARS-CoV-2 pandemic.,The online version of this article (10.1007/s00392-020-01681-2) contains supplementary material, which is available to authorized users. | 1 |
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. | 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 |
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. | 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. | 1 |
•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. | Supplemental Digital Content is available in the text.,The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function.,Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD.,In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function.,The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging.,Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample.,Among 3254 patients, RD was present in 487 patients (15%).,The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001).,Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function.,Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function.,In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased.,Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm.,URL: https://www.clinicaltrials.gov.,Unique identifier: NCT00470587. | 1 |
Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021.,After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.,We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition.,We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons.,Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis.,Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable.,The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal.,The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46).,As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20).,The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637.,The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients.,The clinical presentation of myocarditis after vaccination was usually mild. | 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. | 1 |
Supplemental Digital Content is available in the text.,Coronavirus disease 2019 (COVID-19) evolved quickly into a global pandemic with myriad systemic complications, including stroke.,We report the largest case series to date of cerebrovascular complications of COVID-19 and compare with stroke patients without infection.,Retrospective case series of COVID-19 patients with imaging-confirmed stroke, treated at 11 hospitals in New York, between March 14 and April 26, 2020.,Demographic, clinical, laboratory, imaging, and outcome data were collected, and cases were compared with date-matched controls without COVID-19 from 1 year prior.,Eighty-six COVID-19-positive stroke cases were identified (mean age, 67.4 years; 44.2% women).,Ischemic stroke (83.7%) and nonfocal neurological presentations (67.4%) predominated, commonly involving multivascular distributions (45.8%) with associated hemorrhage (20.8%).,Compared with controls (n=499), COVID-19 was associated with in-hospital stroke onset (47.7% versus 5.0%; P<0.001), mortality (29.1% versus 9.0%; P<0.001), and Black/multiracial race (58.1% versus 36.9%; P=0.001).,COVID-19 was the strongest independent risk factor for in-hospital stroke (odds ratio, 20.9 [95% CI, 10.4-42.2]; P<0.001), whereas COVID-19, older age, and intracranial hemorrhage independently predicted mortality.,COVID-19 is an independent risk factor for stroke in hospitalized patients and mortality, and stroke presentations are frequently atypical. | Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition. | 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. | 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 |
Neovascularization and vascular remodeling are functionally important for brain repair after stroke.,We show that neutrophils accumulate in the peri-infarct cortex during all stages of ischemic stroke.,Neutrophils producing intravascular and intraparenchymal neutrophil extracellular traps (NETs) peak at 3-5 days.,Neutrophil depletion reduces blood-brain barrier (BBB) breakdown and enhances neovascularization at 14 days.,Peptidylarginine deiminase 4 (PAD4), an enzyme essential for NET formation, is upregulated in peri-ischemic brains.,Overexpression of PAD4 induces an increase in NET formation that is accompanied by reduced neovascularization and increased BBB damage.,Disruption of NETs by DNase 1 and inhibition of NET formation by genetic ablation or pharmacologic inhibition of PAD increases neovascularization and vascular repair and improves functional recovery.,Furthermore, PAD inhibition reduces stroke-induced STING-mediated production of IFN-β, and STING knockdown and IFN receptor-neutralizing antibody treatment reduces BBB breakdown and increases vascular plasticity.,Collectively, our results indicate that NET release impairs vascular remodeling during stroke recovery.,Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage.,Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury. | Regulation of neural inflammation is considered as a vital therapeutic target in ischemic stroke.,All-trans retinoic acid (atRA), a potent immune modulator, has raised interest in the field of stroke therapy.,However, the immunological mechanisms for atRA-mediated neuroprotection remain elusive.,The current study evaluated the impact of atRA on post-stroke neural inflammation and elucidated the mechanisms involved in the regulation of related neutrophil functions.,atRA was prophylactically administered to mice 1 day before transient middle cerebral artery occlusion (tMCAO, 1 h) and repeated daily immediately after reperfusion for 3 days.,Stroke outcomes, neutrophil polarization, and formation of neutrophil extracellular traps (NETs) in the stroke lesion were assessed.,Neutrophil depletion was induced with anti-Ly6G antibodies.,Primary neutrophil cultures were used to explore the mechanisms of atRA treatment.,Prophylactic atRA treatment reduced infarct volumes and neurological deficits at 1 day after tMCAO.,Post-stroke neural inflammation was attenuated and neutrophil accumulation in lesion was downregulated. atRA treatment skewed neutrophil toward N2 phenotype which facilitated its clearance by macrophage and inhibited NETs formation.,The functions of neutrophil were indispensable in the protective effects of atRA and were associated with suppression to STAT1 signaling by atRA.,Administration of atRA after stroke still provided efficient protection to cerebral ischemia.,atRA displays potent therapeutic efficacy in ischemic stroke by attenuating neural inflammation.,Treatment of atRA impeded neutrophil accumulation, favored N2 polarization, and forbade NETs formation in ischemic lesion.,STAT1 signaling played a decisive role in the mechanisms of atRA-afforded regulation to neutrophil.,The online version of this article (10.1186/s12974-019-1557-6) contains supplementary material, which is available to authorized users. | 1 |
Amiodarone, one of the most widely prescribed antiarrhythmic drugs to treat both ventricular and supraventricular arrhythmias, has been identified as a candidate drug for use against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,We present the rationale of using amiodarone in the COVID-19 scenario, as well as whether or not amiodarone administration represents a potential strategy to prevent SARS-CoV-2 infection, rather than simply used to treat patients already symptomatic and/or with severe coronavirus disease 2019 (COVID-19), based on current evidence. | High incidence of thrombosis in COVID‐19 patients indicates a hypercoagulable state.,Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest.,To illustrate the incidence of criteria (lupus anticoagulant [LAC], anticardiolipin [aCL] immunoglobulin G [IgG]/IgM, antibeta2‐glycoprotein I antibodies [aβ2GPI] IgG/IgM) and noncriteria (anti‐phosphatidyl serine/prothrombin [aPS/PT], aCL, and aβ2GPI IgA) aPL in a consecutive cohort of critically ill SARS‐CoV‐2 patients, their association with thrombosis, antibody profile and titers of aPL.,Thirty‐one consecutive confirmed COVID‐19 patients admitted to the intensive care unit were included. aPL were measured at one time point, with part of the aPL‐positive patients retested after 1 month.,Sixteen patients were single LAC‐positive, two triple‐positive, one double‐positive, one single aCL, and three aCL IgG and LAC positive.,Seven of nine thrombotic patients had at least one aPL.,Sixteen of 22 patients without thrombosis were aPL positive, amongst them two triple positives.,Nine of 10 retested LAC‐positive patients were negative on a second occasion, as well as the double‐positive patient.,Seven patients were aPS/PT‐positive associated to LAC.,Three patients were aCL and aβ2GPI IgA‐positive.,Our observations support the frequent single LAC positivity during (acute phase) observed in COVID‐19 infection; however, not clearly related to thrombotic complications.,Triple aPL positivity and high aCL/aβ2GPI titers are rare.,Repeat testing suggests aPL to be mostly transient.,Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID‐19 patients. | 1 |
To assess the relationship between preoperative vitamin D (vitD) supplementation and the development of postoperative atrial fibrillation (POAF).,The study group consisted of 328 consecutive patients.,The ınfluence of preoperative vitD supplementation on POAF was reviewed in 136 patients who underwent coronary artery bypass graft surgery with vitD insufficiency (n=80) and vitD deficiency (n=56).,Patients were assigned to receive either oral vitD (50.000 U) (treatment group, n=68) or not (control group, n=68) 48 hours before surgery.,Patients were followed up during hospitalisation process with respect to POAF.,There was no significant difference between treatment and control groups with regards to age, gender, diabetes mellitus, smoking history, chronic obstructive pulmonary disease, left atrial diameter, and biochemical parameters.,Also, there was no significant difference between these groups with regards to mean vitD level on both insufficiency and deficiency patients (24.6±3.7 vs.,24.9±3.9 ng/ml P=0.837, 11.4±4.9 vs.,10.9±5.2 ng/ml P=0.681, respectively).,Although the occurrence of POAF was not significantly different among treatment and control groups in patients with vitD insufficiency (31% vs.,33% P=0.538), there was a significant difference between the two groups regarding to POAF in patients with vitD deficiency (18% vs.,29% P=0.02).,Although preoperative vitD supplementation was not found to be associated with prevention of POAF in patients with vitD insufficiency, it was found to be strongly associated with prevention of POAF in those with vitD deficiency. | Postoperative atrial fibrillation (PoAF) is a common complication after coronary artery bypass grafting (CABG).,The aim of the present study was to evaluate the association between development of PoAF and vitamin D levels in patients undergoing isolated CABG.,This prospective randomized clinical trial was conducted on the patients with isolated CABG.,The study was terminated when 50 patients in both PoAF(+) group and PoAF(-) group were reached.,Development of AF until discharge period was assessed.,Vitamin D level was measured immediately after AF; it was measured on the discharge day for the patients without PoAF.,Predictive values of the independent variables were measured for the development of PoAF.,The groups were separated as PoAF(-) group (66% male, mean age 58.18±10.98 years) and PoAF(+) group (74% male, mean age 61.94±10.88 years).,25(OH) vitamin D level (OR=0.855, 95% CI: 0.780-0.938, P=0.001) and > 65 years (OR=3.525, 95% CI: 1.310-9.483, P=0.013) were identified as an independent predictor of postoperative AF after CABG surgery in multivariate analysis.,The cut-off level for 25(OH) vitamin D level in receiver-operating characteristic curve analysis was determined as 7.65 with sensitivity of 60% and specificity of 64% for predicting PoAF (area under the curve: 0.679, P=0.002).,Vitamin D level is considered an independent predictor for development of PoAF.,Lower vitamin D levels may be one of the reasons for PoAF. | 1 |
Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series.,Larger studies have been limited by both geography and specialty.,Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies.,The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.,During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care.,Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations).,Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available.,Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.,The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020.,Data lock for this report was on April 26, 2020.,During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies.,Median patient age was 71 years (range 23-94; IQR 58-79).,Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis.,The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses.,Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.,To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19.,Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.,This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.,None. | 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 |
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. | Despite growing evidence of cardiovascular complications associated with coronavirus disease 2019 (COVID-19), there are few data regarding the performance of transthoracic echocardiography (TTE) and the spectrum of echocardiographic findings in this disease.,A retrospective analysis was performed among adult patients admitted to a quaternary care center in New York City between March 1 and April 3, 2020.,Patients were included if they underwent TTE during the hospitalization after a known positive diagnosis for COVID-19.,Demographic and clinical data were obtained using chart abstraction from the electronic medical record.,Of 749 patients, 72 (9.6%) underwent TTE following positive results on severe acute respiratory syndrome coronavirus-2 polymerase chain reaction testing.,The most common clinical indications for TTE were concern for a major acute cardiovascular event (45.8%) and hemodynamic instability (29.2%).,Although most patients had preserved biventricular function, 34.7% were found to have left ventricular ejection fractions ≤ 50%, and 13.9% had at least moderately reduced right ventricular function.,Four patients had wall motion abnormalities suggestive of stress-induced cardiomyopathy.,Using Spearman rank correlation, there was an inverse relationship between high-sensitivity troponin T and left ventricular ejection fraction (ρ = −0.34, P = .006).,Among 20 patients with prior echocardiograms, only two (10%) had new reductions in LVEF of >10%.,Clinical management was changed in eight individuals (24.2%) in whom TTE was ordered for concern for acute major cardiovascular events and three (14.3%) in whom TTE was ordered for hemodynamic evaluation.,This study describes the clinical indications for use and diagnostic performance of TTE, as well as findings seen on TTE, in hospitalized patients with COVID-19.,In appropriately selected patients, TTE can be an invaluable tool for guiding COVID-19 clinical management. | 1 |
Coronavirus disease 2019 (COVID‐19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders.,Based on that, several anticoagulation guidelines have been proposed.,We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID‐19.,Patients with COVID‐19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020.,We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in‐hospital mortality).,The study enrolled 2878 patients with COVID‐19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization.,After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88).,Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death.,In contrast, therapeutic or prophylactic low‐ or high‐dose anticoagulation started during hospitalization were not associated with any of the outcomes.,Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization.,Anticoagulation therapy introduced in early disease could better prevent COVID‐19-associated coagulopathy and endotheliopathy, and lead to a better prognosis. | 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 |
Controversy has arisen in the scientific community on whether the use of renin‐angiotensin system (RAS) inhibitors in the context of COVID‐19 would be beneficial or harmful.,A meta‐analysis of eligible studies comparing the occurrence of severe and fatal COVID‐19 in infected hypertensive patients who were under treatment with angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted.,PubMed, Google Scholar, the Cochrane Library, medRxiv and bioRxiv were searched for relevant studies.,Fixed‐effects models or random‐effects models were used depending on the heterogeneity between estimates.,A total of eighteen studies with 17 311 patients were included.,The use of RAS inhibitors was associated with a significant 16% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR: 0.84 (95% CI: 0.73‐0.95), P = .007, I2 = 65%.,The results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis of COVID‐19, and could even be protective in hypertensive subjects.,Hypertensive patients should continue these drugs even if they become infected with SARS‐CoV‐2.,Controversy exists on whether RAS inhibitors are beneficial or harmful in COVID‐19.,In this meta‐analysis, the use of RAS inhibitors was not associated with a worse COVID‐19 prognosis and was even protective in hypertensive patients.,Patients should continue these drugs during their COVID‐19 illness. | It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).,This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital.,The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China.,Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection.,Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension.,After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs.,1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013].,Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs.,3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041).,The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs.,3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774).,However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20).,While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19.,However, the results should be considered as exploratory and interpreted cautiously. | 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. | An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients. | 1 |
We are witnessing an unparalleled pandemic caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated with coronavirus disease 2019 (COVID-19).,Current data show that SARS-CoV-2 results in mild flu-like symptoms in the majority of healthy and young patients affected.,Nevertheless, the severity of COVID-19 respiratory syndrome and the risk of adverse or catastrophic outcomes are increased in patients with pre-existing cardiovascular disease.,Patients with adult congenital heart disease (ACHD)-by definition-have underlying cardiovascular disease.,Many patients with ACHD are also afflicted with residual haemodynamic lesions such as valve dysfunction, diminished ventricular function, arrhythmias or cyanosis, have extracardiac comorbidities, and face additional challenges regarding pregnancy.,Currently, there are emerging data of the effect of COVID-19 on ACHD patients, but many aspects, especially risk stratification and treatment considerations, remain unclear.,In this article, we aim to discuss the broad impact of COVID-19 on ACHD patients, focusing specifically on pathophysiology, risk stratification for work, self-isolation, hospitalization, impact on pregnancy, psychosocial health, and longer-term implications for the provision of ACHD care. | We sought to assess the impact and predictors of coronavirus disease 2019 (COVID‐19) infection and severity in a cohort of patients with congenital heart disease (CHD) at a large CHD center in New York City.,We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID‐19 between March 1, 2020 and July 1, 2020.,The primary end point was moderate/severe response to COVID‐19 infection defined as (1) death during COVID‐19 infection; or (2) need for hospitalization and/or respiratory support secondary to COVID‐19 infection.,Among 53 COVID‐19‐positive patients with CHD, 10 (19%) were <18 years of age (median age 34 years of age).,Thirty‐one (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair.,Eight (15%) had a genetic syndrome, 6 (11%) had pulmonary hypertension, and 9 (17%) were obese.,Among adults, 18 (41%) were physiologic class C or D.,For the entire cohort, 9 (17%) had a moderate/severe infection, including 3 deaths (6%).,After correcting for multiple comparisons, the presence of a genetic syndrome (odds ratio [OR], 35.82; P=0.0002), and in adults, physiological Stage C or D (OR, 19.38; P=0.002) were significantly associated with moderate/severe infection.,At our CHD center, the number of symptomatic patients with COVID‐19 was relatively low.,Patients with CHD with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection. | 1 |
Tetrahydrobiopterin is a cofactor of endothelial NO synthase (eNOS), which is critical to embryonic heart development.,We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects (CHDs) induced by pregestational diabetes mellitus in mice.,Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring.,Pregnant mice were treated with sapropterin or vehicle during gestation.,CHDs were identified by histological analysis.,Cell proliferation, eNOS dimerization, and reactive oxygen species production were assessed in the fetal heart.,Pregestational diabetes mellitus results in a spectrum of CHDs in their offspring.,Oral treatment with sapropterin in the diabetic dams significantly decreased the incidence of CHDs from 59% to 27%, and major abnormalities, such as atrioventricular septal defect and double‐outlet right ventricle, were absent in the sapropterin‐treated group.,Lineage tracing reveals that pregestational diabetes mellitus results in decreased commitment of second heart field progenitors to the outflow tract, endocardial cushions, and ventricular myocardium of the fetal heart.,Notably, decreased cell proliferation and cardiac transcription factor expression induced by maternal diabetes mellitus were normalized with sapropterin treatment.,Furthermore, sapropterin administration in the diabetic dams increased eNOS dimerization and lowered reactive oxygen species levels in the fetal heart.,Sapropterin treatment in the diabetic mothers improves eNOS coupling, increases cell proliferation, and prevents the development of CHDs in the offspring.,Thus, sapropterin may have therapeutic potential in preventing CHDs in pregestational diabetes mellitus. | The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort.,This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome).,Cases with CHDs were recruited through ten sites, 2010-2014.,Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction.,Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes.,Eleven percent of cases had a genetic diagnosis.,Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%).,Across CHD types, there were significant differences (p<0.05) in the distribution of all four case characteristics (e.g., sex), four parental characteristics (e.g., maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g., learning disabilities).,Several characteristics (e.g., sex) were also significantly different across CHD subtypes.,The PCGC cohort is one of the largest CHD cohorts available for the study of genetic determinants of risk and outcomes.,The majority of cases do not have a genetic diagnosis.,This description of the PCGC cohort, including differences across CHD types and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC. | 1 |
At the end of last year, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an acute respiratory illness epidemic in Wuhan, China [1, 2].,The World Health Organization (WHO) termed this illness coronavirus disease 2019 (COVID-19).,The coronavirus family have been shown to enter cells through binding angiotensin-converting enzyme 2 (ACE-2), found mainly on alveolar epithelium and endothelium.,Activation of endothelial cells is thought to be the primary driver for the increasingly recognised complication of thrombosis.,Pulmonary thrombosis appears to be common in COVID-19 pneumonia and takes two forms, proximal pulmonary emboli and/or distal thrombosis.,The possible mechanisms and clinical implications are discussed.https://bit.ly/372Xdhw | 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 Pipeline Embolisation Device with Shield technology (PED-Shield) is suggested to have reduced thrombogenicity.,This reduced thrombogenicity may make it possible to use safely in the acute treatment of aneurysmal subarachnoid haemorrhage (aSAH) on single antiplatelet therapy (SAPT).,To evaluate the safety and efficacy of the off-label use of PED-Shield with SAPT for the acute treatment of aSAH.,Patients who underwent acute treatment of ruptured intracranial aneurysms with the PED-Shield with SAPT were retrospectively identified from prospectively maintained databases at three Australian neurointerventional centres.,Patient demographics, aneurysm characteristics, clinical and imaging outcomes were reviewed.,Fourteen patients were identified (12 women), median age 64 (IQR 21.5) years.,Aneurysm morphology was saccular in seven, fusiform in five, and blister in two.,Aneurysms arose from the anterior circulation in eight patients (57.1%).,Six (42.9%) patients were poor grade (World Federation of Neurological Societies grade ≥IV) SAH.,Median time to treatment was 1 (IQR 0.5) day.,Complete or near complete aneurysm occlusion (Raymond-Roy <3) was achieved in 12 (85.7%) patients at the end of early-acute follow-up (median day 7 after SAH).,Permanent, treatment-related morbidity occurred in one (7.1%) patient and one (7.1%) treatment-related death occurred.,The use of a postoperative heparin infusion (n=5) was associated with a higher rate of all complications (80.0% vs 11.1%, p=0.023) and symptomatic complications (60% vs 0.0%, p=0.028).,No symptomatic ischaemic or haemorrhagic complications were observed in the patients who did not receive a post-operative heparin infusion.,Nine (64.3%) patients were functionally independent on discharge from the treatment centre.,The PED-Shield may be safe to use in the acute treatment of ruptured intracranial aneurysms with SAPT.,Further investigation with a formal treatment registry is needed. | Endovascular stents and flow diverter stents (FDS) have revolutionized the treatment of intradural aneurysms; however, the need for dual anti-platelet treatment (DAPT) limits their use and can cause additional issues.,Therefore, there is a need to develop stent coatings that negate the need for DAPT.,Two different hydrophilic polymer coatings (HPC-I and HPC-II) were used to coat small nickel titanium plates to initially test the hydrophilic properties of these coatings when applied to nickel titanium.,The plates were subsequently incubated with non-medicated whole blood from healthy volunteers for 10 min and stained with a CD61 immunofluorescent antibody that allows detection of adherent platelets.,The coatings were applied to FDS wires and were again incubated with non-medicated whole blood from the same volunteers.,Scanning electron microscopy was used to detect adherent platelets on the wire surface.,The HPC-II coating (1.12 ± 0.4%) showed a significantly lower CD61 +ve cell count (p ≤ 0.001) compared to both uncoated NiTi plates (48.61 ± 7.3%) and those with the HPC-I coating (mean 40.19 ± 8.9%).,Minimal adherent platelets were seen on the FDS nickel titanium wires coated with the HPC-II compared to uncoated FDS under electron microscopy.,There is a significant decrease in the number of adherent CD61 +ve platelets on nickel titanium surfaces coated with the HPC-II coating compared to uncoated surfaces.,The coating can be successfully applied to the wires of flow diverters.,The results of this study are promising with regard to the development of new anti-thrombogenic endovascular devices. | 1 |
Supplemental Digital Content is available in the text.,A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide.,Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein.,Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences.,This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection. | Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles. | 1 |
A patient with coronavirus disease 19 (COVID‐19) developed acute myocardial infarction (AMI) complicated by extensive coronary thrombosis and cardiogenic shock.,She underwent percutaneous coronary intervention and placement of a mechanical circulatory support device but subsequently died from shock.,This report illustrates the challenges in managing patients with COVID‐19, AMI, and cardiogenic shock. | 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. | 1 |
COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19. | A Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has become a pandemic disease named Coronavirus Disease-19 (COVID-19) of epochal dimension.,The clinical spectrum of COVID-19 is wide, ranging from asymptomatic forms to severe pneumonia, sepsis and multiple organ dysfunction syndromes resulting in poor outcomes.,Among the various consequences of severe COVID-19, cardiovascular (CV) collapse appears the most serious and potentially lethal.,On the other hand, pre-existent CV comorbidities are also associated with higher mortality.,The most reliable hypothetical pathogenetic mechanism for CV complications and cardiac injury in severe COVID-19 patients appears to be a sustained endothelial dysfunction, caused by the interplay of inflammation and coagulation.,In this review, we survey papers addressing issues related to severe COVID-19, characterized by enhanced lung microvascular loss, hypercytokinemia, hypoxemia and thrombosis.,We discuss about how the virus-induced downregulation of the angiotensin converting enzyme-2 (ACE2) receptor, used to enter the host cell, could affect the renin-angiotensin system, attempting to clarify the doubts about the use of ACE inhibitors and Angiotensin-II receptor blockers in COVID-19 patients.,Finally, we point out how the delicate and physiological homeostatic function of the endothelium, which turns into a disastrous battlefield of the complex interaction between “cytokine and coagulative storms”, can be irreparably compromised and result in systemic inflammatory complications.,•Cardiovascular (CV) collapse appears the most serious consequence of severe COVID-19.,•Endothelial dysfunction as pathogenetic mechanism for (CV) complications in COVID-19 patients•Hyperinflammation, immune dysregulation, hypoxia may drive vascular damage in COVID-19 patients.,•Hypercoagulability state characterizes patients with severe COVID-19.,Cardiovascular (CV) collapse appears the most serious consequence of severe COVID-19.,Endothelial dysfunction as pathogenetic mechanism for (CV) complications in COVID-19 patients,Hyperinflammation, immune dysregulation, hypoxia may drive vascular damage in COVID-19 patients.,Hypercoagulability state characterizes patients with severe COVID-19. | 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. | 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 |
To evaluate the impact of COVID‐19 pandemic migitation measures on of ST‐elevation myocardial infarction (STEMI) care.,We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID‐19 pandemic mitigation measures.,This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data.,Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times.,Two periods, January 2019-February 2020 and March-April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively.,A generalized estimating equations approach was used to estimate the change in response variables at AC from BC.,Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18-38, p < .001), number of activations leading to angiography (34%, 95% CI: 12-50, p = .005) and number of activations leading to PPCI (20%, 95% CI: 11-27, p < .001).,A decline in STEMI activations drove the reductions in angiography and PPCI volumes.,Relative to BC, the D2B times in the AC period increased on average by 20%, 95%CI (−0.2 to 44, p = .05).,The COVID‐19 Pandemic has adversely affected many aspects of STEMI care, including timely access to the cardiac catheterization laboratory for PPCI. | The coronavirus SARS-CoV-2 outbreak led to the most recent pandemic of the twenty-first century.,To contain spread of the virus, many nations introduced a public lockdown.,How the pandemic itself and measures of social restriction affect hospital admissions due to acute cardiac events has rarely been evaluated yet.,German public authorities announced measures of social restriction between March 21st and April 20th, 2020.,During this period, all patients suffering from an acute cardiac event admitted to our hospital (N = 94) were assessed and incidence rate ratios (IRR) of admissions for acute cardiac events estimated, and compared with those during the same period in the previous three years (2017-2019, N = 361).,Admissions due to cardiac events were reduced by 22% as compared to the previous years (n = 94 vs. an average of n = 120 per year for 2017-2019).,Whereas IRR for STEMI 1.20 (95% CI 0.67-2.14) and out-of-hospital cardiac arrest IRR 0.82 (95% CI 0.33-2.02) remained similar, overall admissions with an IRR of 0.78 (95% CI 0.62-0.98) and IRR for NSTEMI with 0.46 (95% CI 0.27-0.78) were significantly lower.,In STEMI patients, plasma concentrations of high-sensitivity troponin T at admission were significantly higher (644 ng/l, IQR 372-2388) compared to 2017-2019 (195 ng/l, IQR 84-1134; p = 0.02).,The SARS-CoV-2 pandemic and concomitant social restrictions are associated with reduced cardiac events admissions to our tertiary care center.,From a public health perspective, strategies have to be developed to assure patients are seeking and getting medical care and treatment in time during SARS-CoV-2 pandemic.,The online version of this article (10.1007/s00392-020-01681-2) contains supplementary material, which is available to authorized users. | 1 |
The COVID-19 pandemic has disrupted healthcare services around the world, which may have serious implications for the prognosis of patients with acute cardiovascular disease.,We conducted a systematic review to assess the extent to which health services related to the care and management of acute cardiovascular events have been impacted during the COVID-19 pandemic.,PubMed, MedRxiv and Google Scholar were searched for observational studies published up to August 12, 2020 for studies that assessed the impact of the pandemic on the care and management of people with acute CVD.,In total, 27 articles were included.,Of these, 16 examined the impact on acute coronary syndromes (ACS), eight on strokes, one on ACS and strokes, and 2 on other types of CVD.,When comparing the COVID-19 period to non-COVID-19 periods, eleven studies observed a decrease in ACS admissions ranging between 40 and 50% and five studies showed a decrease in stroke admissions of between 12 and 40%.,Four studies showed a larger reduction in non-ST-segment elevation myocardial infarctions (NSTEMI) compared to ST-segment elevation myocardial infarctions (STEMI).,A decrease in the number of reperfusion procedures, a shortening in the lengths of stay at the hospital, and longer symptom-to-door times were also observed.,The COVID-19 pandemic has led to a substantial decrease in the rate of admissions for acute CVD, reductions in the number of procedures, shortened lengths of stay at the hospital and longer delays between the onset of the symptoms and hospital treatment.,The impact on patient’s prognosis needs to be quantified in future studies. | Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures.,We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.,We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database.,Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina).,We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery).,We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.,Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43).,This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline.,During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46).,In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45).,The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.,Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020.,The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease.,The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.,UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre. | 1 |
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. | While the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads all over the world, the healthcare systems are facing the dramatic challenge of simultaneously fight against the outbreak and life-threating emergencies.,In this biological setting, emergency departments and neurovascular teams are exposed to high risk of infection and should therefore be prepared to deal with neurological emergencies safely.,The purpose of this article is to analyze the current evidence on COVID-19 in the context of acute ischemic stroke and to describe the model of behavior we are putting into action to maintain the stroke pathway both rapid for the patient and safe for the healthcare professionals.,We reserve a specific focus on personal protection equipment, dress code and healthcare professional behavior. | 1 |
Supplemental Digital Content is available in the text.,In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring.,However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle.,Here, we used chronic hypoxia in the chicken embryo-an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother or the placenta.,Fertilized chicken eggs were exposed to normoxia (N; 21% O2) or hypoxia (H; 13.5%-14% O2) from the start of incubation (day 0) until day 19 (hatching, ≈day 21).,Following hatching, all birds were maintained under normoxic conditions until ≈6 months of adulthood.,Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetrical growth restriction (body weight, −8.6%; biparietal diameter/body weight ratio, +7.5%) in the hatchlings (all P<0.05).,At adulthood (181±4 days), chickens from hypoxic incubations remained smaller (body weight, −7.5%) and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to NG-nitro-L-arginine methyl ester, −43%; phenylephrine pressor response during NO blockade, −61%) with significant hypertension (mean arterial blood pressure, +18%), increased cardiac work (ejection fraction, +12%; fractional shortening, +25%; enhanced baroreflex gain, +456%), and left ventricular wall thickening (left ventricular wall volume, +36%; all P<0.05).,Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction, and cardiac wall remodeling in adulthood in the absence of any maternal or placental effects. | Evidence derived from human clinical studies and experimental animal models shows a causal relationship between adverse pregnancy and increased cardiovascular disease in the adult offspring.,However, translational studies isolating mechanisms to design intervention are lacking.,Sheep and humans share similar precocial developmental milestones in cardiovascular anatomy and physiology.,We tested the hypothesis in sheep that maternal treatment with antioxidants protects against fetal growth restriction and programmed hypertension in adulthood in gestation complicated by chronic fetal hypoxia, the most common adverse consequence in human pregnancy.,Using bespoke isobaric chambers, chronically catheterized sheep carrying singletons underwent normoxia or hypoxia (10% oxygen [O2]) ± vitamin C treatment (maternal 200 mg.kg−1 IV daily) for the last third of gestation.,In one cohort, the maternal arterial blood gas status, the value at which 50% of the maternal hemoglobin is saturated with oxygen (P50), nitric oxide (NO) bioavailability, oxidative stress, and antioxidant capacity were determined.,In another, naturally delivered offspring were raised under normoxia until early adulthood (9 months).,Lambs were chronically instrumented and cardiovascular function tested in vivo.,Following euthanasia, femoral arterial segments were isolated and endothelial function determined by wire myography.,Hypoxic pregnancy induced fetal growth restriction and fetal oxidative stress.,At adulthood, it programmed hypertension by enhancing vasoconstrictor reactivity and impairing NO-independent endothelial function.,Maternal vitamin C in hypoxic pregnancy improved transplacental oxygenation and enhanced fetal antioxidant capacity while increasing NO bioavailability, offsetting constrictor hyper-reactivity and replenishing endothelial function in the adult offspring.,These discoveries provide novel insight into mechanisms and interventions against fetal growth restriction and adult-onset programmed hypertension in an animal model of complicated pregnancy in a species of similar temporal developmental milestones to humans. | 1 |
Supplemental Digital Content is available in the text.,Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia.,Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism.,Overall, 37 patients and 28 healthy subjects were studied.,Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry.,The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay.,The contribution of platelets to coagulation factor activity was selectively measured.,Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001) were detected in patients.,Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P=nonsignificant).,The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001 versus controls).,Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets.,Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients.,Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation.,Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy.,Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response.,The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.,This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands.,With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020.,In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course.,Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78).,Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days).,In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course.,Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract.,In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain.,In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata.,Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]).,Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets..,In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs.,However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19.,This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19.,Amsterdam UMC Corona Research Fund. | 1 |
The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection.,The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart.,Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection.,In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used).,The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.,Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification.,In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction.,Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment.,Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits.,Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies.,Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury. | 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 |
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many countries have introduced strict hygiene measures of social distancing to prevent further spreading of the disease.,This may have led to a decreased presentation to hospital of patients with acute medical conditions and time-dependent management, such as stroke.,We conducted a nationwide cohort study using administrative database of all hospitalized patients with main diagnosis of acute ischemic stroke (AIS), transient ischemic attack, or intracerebral hemorrhage.,Data from a total of 1463 hospitals in Germany were included.,We compared case numbers and treatment characteristics of pandemic (March 16 to May 15, 2020) and prepandemic (January 16 to March 15, 2020) cases and also with corresponding time period in 2019.,We identified a strong decline for hospitalization of AIS (−17.4%), transient ischemic attack (−22.9%), and intracerebral hemorrhage (−15.8%) patients during the pandemic compared with prepandemic period.,IVT rate in patients with AIS was comparable (prepandemic versus pandemic: 16.4% versus 16.6%, P=0.448), whereas mechanical thrombectomy rate was significantly higher during the pandemic (8.1% versus 7.7%, P=0.044).,In-hospital mortality was significantly increased in patients with AIS during the pandemic period (8.1% versus 7.6%, P=0.006).,Besides a massive decrease in absolute case numbers, our data suggest that patients with AIS who did seek acute care during the pandemic, continued to receive acute recanalization treatment in Germany. | 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. | 1 |
The gut microbiota has been linked to cardiovascular diseases.,However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined.,Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls.,The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health.,Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort.,We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis.,Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.,The gut microbiota may play a role in cardiovascular diseases.,Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease. | 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 |
High incidence of thrombosis in COVID‐19 patients indicates a hypercoagulable state.,Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest.,To illustrate the incidence of criteria (lupus anticoagulant [LAC], anticardiolipin [aCL] immunoglobulin G [IgG]/IgM, antibeta2‐glycoprotein I antibodies [aβ2GPI] IgG/IgM) and noncriteria (anti‐phosphatidyl serine/prothrombin [aPS/PT], aCL, and aβ2GPI IgA) aPL in a consecutive cohort of critically ill SARS‐CoV‐2 patients, their association with thrombosis, antibody profile and titers of aPL.,Thirty‐one consecutive confirmed COVID‐19 patients admitted to the intensive care unit were included. aPL were measured at one time point, with part of the aPL‐positive patients retested after 1 month.,Sixteen patients were single LAC‐positive, two triple‐positive, one double‐positive, one single aCL, and three aCL IgG and LAC positive.,Seven of nine thrombotic patients had at least one aPL.,Sixteen of 22 patients without thrombosis were aPL positive, amongst them two triple positives.,Nine of 10 retested LAC‐positive patients were negative on a second occasion, as well as the double‐positive patient.,Seven patients were aPS/PT‐positive associated to LAC.,Three patients were aCL and aβ2GPI IgA‐positive.,Our observations support the frequent single LAC positivity during (acute phase) observed in COVID‐19 infection; however, not clearly related to thrombotic complications.,Triple aPL positivity and high aCL/aβ2GPI titers are rare.,Repeat testing suggests aPL to be mostly transient.,Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID‐19 patients. | 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. | 1 |
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. | La sobrecarga asistencial y los cambios organizativos frente a la pandemia de COVID-19 podrían estar repercutiendo en la atención al ictus agudo en la Comunidad de Madrid.,Encuesta estructurada en bloques: características del hospital, cambios en infraestructura y recursos, circuitos de código ictus, pruebas diagnósticas, rehabilitación y atención ambulatoria.,Análisis descriptivo según el nivel de complejidad en la atención del ictus (disponibilidad o no de unidad de ictus y de trombectomía mecánica).,De los 26 hospitales del SERMAS que atienden urgencias en adultos, 22 cumplimentaron la encuesta entre el 16 y 27 de abril.,El 95% han cedido neurólogos para atender a pacientes afectados por la COVID-19.,Se han reducido camas de neurología en el 89,4%, modificado los circuitos en urgencias para ictus en el 81%, con circuitos específicos para sospecha de infección por SARS-CoV2 en el 50%, y en el 42% de los hospitales los pacientes con ictus agudo positivos para SARS-CoV2 no ingresan en camas de neurología.,Ha mejorado el acceso al tratamiento, con trombectomía mecánica las 24 h en el propio hospital en 10 hospitales, y se han reducido los traslados interhospitalarios secundarios.,Se ha evitado el ingreso de pacientes con ataque isquémico transitorio o ictus leve (45%) y se han incorporado consultas telefónicas para seguimiento en el 100%.,Los cambios organizativos de los hospitales de la Comunidad de Madrid frente a la pandemia por SARS-Co2 han modificado la dedicación de recursos humanos e infraestructuras de las unidades de neurología y los circuitos de atención del ictus, realización de pruebas diagnósticas, ingreso de los pacientes y seguimiento. | 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 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. | 1 |
A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID‐19 assisted in the intensive care unit (ICU).,However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown.,To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis.,We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independent of the presence of signs or symptoms of DVT.,All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux.,The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6.,Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden.,In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98‐18.82).,Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87‐5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23‐5.77).,Significant differences between subjects with and without DVT were D‐dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P < .01).,DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis. | 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 | 1 |
Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).,To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.,We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network.,The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715).,The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism.,Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White.,Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common.,Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting.,Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all).,Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis. | 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 |
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. | Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China.,The clinical data in other centers is limited.,This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19).,Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group.,Clinical information was collected and analyzed for the following objectives: 1.,Comparisons of basic characteristics between two groups; 2.,Risk factors for death on admission using logistic regression; 3.,Dynamic changes of radiographic and laboratory parameters between two groups in the course.,Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89).,Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression.,Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×109/L, CRP>77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04).,In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group.,Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients.,Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome. | 1 |
Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces blood glucose, as well as blood pressure, body weight, and albuminuria in patients with type 2 diabetes mellitus (T2DM).,In the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, patients with T2DM and high cardiovascular risk treated with canagliflozin had a significantly lower risk of the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; hospitalization for heart failure; and renal outcomes, but also a greater risk of lower-limb amputation.,Cardiovascular outcomes trials of some other T2DM agents (i.e., empagliflozin, dapagliflozin, liraglutide, semaglutide, albiglutide) have also shown potential cardiovascular and renal benefits.,As a result, diabetes treatment guidelines have begun to incorporate consideration of cardiovascular and renal benefits into their treatment recommendations.,Antihyperglycemic agents with proven beneficial cardiovascular effects represent a new opportunity for the diabetologist and cardiologist, in the setting of a multidisciplinary approach, to concomitantly improve glycemic control and reduce the risk of cardiovascular events in patients with T2DM.,This review briefly discusses the pharmacology of canagliflozin, including clinical and preclinical data; it also describes the effects of canagliflozin on cardiovascular outcomes and side-effects, and compares these effects with other glucose-lowering agents with proven cardiovascular benefits. | Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy.,Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner.,The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice.,Thirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks.,After 8 weeks, heart structure and function were evaluated by echocardiography.,Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson’s trichrome stain and Western blot.,Results showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis.,Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling.,Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice.,Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy. | 1 |
Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects.,To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes.,It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine.,As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.,•Cardiac arrhythmias are more common in critically ill COVID-19 patients.,•Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,•Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,•More data are required to better understand the pathophysiology and to validate management strategies.,Cardiac arrhythmias are more common in critically ill COVID-19 patients.,Arrhythmias occur not only as a result of direct viral effect, but also due to systemic illness and drug interactions.,Management strategies to minimize the impact on arrhythmias and exposure to COVID-19 infection are imperative.,More data are required to better understand the pathophysiology and to validate management strategies. | 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. | 1 |
Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner.,NcRNAs include microRNAs, long non-coding RNAs and circular RNAs.,They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity.,Stroke is one of the leading causes of death and physical disability worldwide.,Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain.,In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers.,We also review ncRNAs acting as possible therapeutic targets in future precision medicine.,Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS. | Activation of the NOD-like receptor protein (NLRP3)-inflammasome has been postulated to mediate inflammatory responses to brain damage during ischemic/reperfusion (I/R) injury.,We therefore hypothesized that MCC950, a selective NLRP3-inflammasome inhibitor provides protection in mouse model of transient middle cerebral artery occlusion (tMCAO).,Focal cerebral ischemia was induced by 60 min tMCAO followed by intraperitoneal administration of MCC950 (50 mg/kg) or saline at 1 h and 3 h post-occlusion.,After 24 h of I/R, mice were tested for neurological outcome and were sacrificed for the analysis of infarct size and estimating NLRP3-inflammasome and apoptotic markers as well.,Spectrophotometric method was used to determine hemoglobin (Hb) content as a marker of intracerebral hemorrhage.,MCC950-treated mice showed a substantial reduction in infarction, edema and Hb content compared to saline controls in parallel with improved neurological deficits.,MCC950 reduced expression of NLRP3-inflammasome cleavage products Caspase-1 and interlukin-1β (IL-1β) in penumbral region.,These protective effects of MCC950 were associated with decreased TNF-α levels as well as poly (ADP-ribose) polymerase (PARP) and Caspase-3 cleavage and paralleled less phosphrylated NFκBp65 and IκBα levels.,Taken together, these data indicate that inhibition of NLRP3-inflammasome with MCC950 has therapeutic potential in ischemic stroke models.,Further investigations into the therapeutic efficacy and protocols are needed to confirm whether MCC950 treatment could be a promising candidate for clinical trials. | 1 |
Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD).,CVD is the leading cause of mortality worldwide.,In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide.,These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD.,A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.,The online version of this article (10.1007/s13238-018-0549-0) contains supplementary material, which is available to authorized users. | Trimethylamine‐N‐oxide (TMAO) has recently been identified as a novel and independent risk factor for promoting atherosclerosis through inducing vascular inflammation.,However, the exact mechanism is currently unclear.,Studies have established a central role of nucleotide‐binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in the pathogenesis of vascular inflammation.,Here, we examined the potential role of the NLRP3 inflammasome in TMAO‐induced vascular inflammation in vitro and in vivo and the underlying mechanisms.,Experiments using liquid chromatography‐tandem mass spectrometry, Western blot, and fluorescent probes showed that TMAO‐induced inflammation in human umbilical vein endothelial cells (HUVECs) and aortas from ApoE−/− mice.,Moreover, TMAO promoted NLRP3 and activated caspase‐1 p20 expression and caspase‐1 activity in vitro and in vivo.,Notably, a caspase‐1 inhibitor (YVAD), an NLRP3 inhibitor (MCC950), as well as NLRP3 short interfering RNA attenuated TMAO‐induced activation of the NLRP3 inflammasome, subsequently leading to suppression of inflammation in HUVECs.,TMAO additionally stimulated reactive oxygen species (ROS) generation, in particular, mitochondrial ROS, while inhibiting manganese superoxide dismutase 2 (SOD2) activation and sirtuin 3 (SIRT3) expression in HUVECs and aortas from ApoE−/− mice.,TMAO‐induced endothelial NLRP3 inflammasome activation was ameliorated by the mitochondrial ROS scavenger Mito‐TEMPO, or SIRT3 overexpression in HUVECs.,Conversely, TMAO failed to further inhibit magnesium SOD2 and activate the NLRP3 inflammasome or induce inflammation in SIRT3 short interfering RNA-treated HUVECs and aortas from SIRT3−/− mice.,TMAO promoted vascular inflammation by activating the NLRP3 inflammasome, and the NLRP3 inflammasome activation in part was mediated through inhibition of the SIRT3‐SOD2-mitochondrial ROS signaling pathway. | 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. | Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias.,However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality.,We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death.,Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block.,Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88).,The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%.,Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%.,Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias.,Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event.,Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge.,However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029. | 1 |
•Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,•Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,•Left ventricular dysfunction and hypokinesis was common and should be managed.,•Steroids were often used but implications on viral clearance should be considered.,Myocarditis in COVID-19 was relatively rare but can be severe and lead to mortality.,Cardiac MRI showing cardiac oedema and injury was valuable in diagnosing myocarditis.,Left ventricular dysfunction and hypokinesis was common and should be managed.,Steroids were often used but implications on viral clearance should be considered.,Myocarditis caused by SARS-CoV-2 infection was proposed to account for a proportion of cardiac injury in patients with COVID-19.,However, reports of coronavirus-induced myocarditis were scarce.,The aim of this review was to summarise the published cases of myocarditis and describe their presentations, diagnostic processes, clinical characteristics and outcomes.,A literature search of MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL and OpenGrey on was performed on 3 June 2020.,Studies of myocarditis in patients with COVID-19 were included, and those only reporting cardiac injury or heart failure were excluded.,Cases were “confirmed” myocarditis if diagnosed on cardiac magnetic resonance imaging (CMR) or histopathology.,Those without were grouped as “possible” myocarditis.,A total of 31 studies on 51 patients were included; 12 cases were confirmed myocarditis while 39 had possible myocarditis.,The median age was 55 and 69% were male.,The most common presenting symptoms were fever, shortness of breath, cough and chest pain.,Electrocardiogram changes included non-specific ST-segment and T-wave changes and ventricular tachycardia.,Most patients had elevated cardiac and inflammatory biomarkers.,Left ventricular dysfunction and hypokinesis was common.,CMR established the diagnosis in 10 patients, with features of cardiac oedema and cardiac injury.,Five patients had histopathological examination.,Some cases required mechanical ventilation and extracoporeal membrane oxygenation, and 30% of patients recovered but 27% died.,COVID-19 myocarditis was associated with ECG, cardiac biomarker and echocardiographic changes, and the manifestation could be severe leading to mortality.,Endomyocardial biopsy was not available in most cases but CMR was valuable. | A 78-year-old patient with acute respiratory distress was transferred to our hospital with ST segment elevation on electrocardiography.,Coronary angiography revealed normal coronary arteries.,Thorax computerized tomography showed ground glass opacification with consolidation in the lungs and mild pericardial effusion demonstrating myopericarditis associated with COVID-19. | 1 |
COVID-19-associated coagulopathy (CAC) characterized by the elevated D-dimer without remarkable changes of other global coagulation markers is associated with various thrombotic complications and disease severity.,The purpose of this review is to elucidate the pathophysiology of this unique coagulopathy.,The authors performed online search of published medical literature through PubMed using the MeSH (Medical Subject Headings) term "COVID-19," "SARS-CoV-2," "coronavirus," "coagulopathy," and "thrombus.",Then, selected 51 articles that closely relevant to coagulopathy in COVID-19.,The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the pneumocytes, immune cells, and vascular endothelial cells.,The alveolar damage and the pulmonary microvascular thrombosis are the major causes of acute lung injury in COVID-19.,The endotheliopathy that occurs is due to direct SARS-CoV-2 infection and activation of other pathways that include the immune system and thromboinflammatory responses leading to what is termed CAC.,As a result, both microvascular and macrovascular thrombotic events occur in arterial, capillary, venule, and large vein vascular beds to produce multiorgan dysfunction and thrombotic complications.,In addition to the endothelial damage, SARS-CoV-2 also can cause vasculitis and presents as a systemic inflammatory vascular disease.,Clinical management of COVID-19 includes anticoagulation but novel therapies for endotheliopathy, hypercoagulability, and vasculitis are needed.,The endotheliopathy due to direct endothelial infection with SARS-COV-2 and the indirect damage caused by inflammation play the predominant role in the development of CAC.,The intensive control of thromboinflammation is necessary to improve the outcome of this highly detrimental contagious disease. | The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis.,This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure.,While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host.,SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic.,It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature.,This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease.,Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode.,The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms.,The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic. | 1 |
As severe acute respiratory syndrome coronavirus 2 continues to spread worldwide, there have been increasing reports from Europe, North America, Asia, and Latin America describing children and adolescents with COVID-19-associated multisystem inflammatory conditions.,However, the association between multisystem inflammatory syndrome in children and COVID-19 is still unknown.,We review the epidemiology, causes, clinical features, and current treatment protocols for multisystem inflammatory syndrome in children and adolescents associated with COVID-19.,We also discuss the possible underlying pathophysiological mechanisms for COVID-19-induced inflammatory processes, which can lead to organ damage in paediatric patients who are severely ill.,These insights provide evidence for the need to develop a clear case definition and treatment protocol for this new condition and also shed light on future therapeutic interventions and the potential for vaccine development.,For the French, Chinese, Arabic, Spanish and Russian translations of the abstract see Supplementary Materials section. | Children were relatively spared during COVID-19 pandemic.,However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome-“Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2” (PIMS-TS) has caused concern.,We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children’s hospital.,Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020.,Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters.,Fifteen children with median age of 8.8 (IQR 6.4-11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups.,All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP).,Transient valve regurgitation was present in 10 patients (67%).,Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2.,Fourteen (93%) had coronary artery abnormalities, with normalization in 6.,ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge.,Ten (67%) needed inotropes and/or vasopressors.,None needed extracorporeal life support.,Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram.,All patients were discharged alive and twelve (80%) have been reviewed since.,Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review.,We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes. | 1 |
This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors.,PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020.,Forty-five chronic (≥ 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included.,Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10).,Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI − 6.79 to − 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI − 2.87 to − 0.18, P = 0.04).,In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI − 2.97 to − 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI − 3.43 to − 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI − 4.06 to − 2.15; P = 0.02]).,Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02).,These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure.,No other significant improvements were observed for other specified fruits.,More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.,The online version of this article (10.1007/s00394-020-02299-w) contains supplementary material, which is available to authorized users. | Cardiovascular disease is a leading cause of death and reduced quality of life, proven by the latest data of the Global Burden of Disease Study, and is only gaining in prevalence worldwide.,Clinical trials have identified chronic inflammatory disorders as cardiovascular risks, and recent research has revealed a contribution by various inflammatory cells to vascular oxidative stress.,Atherosclerosis and cardiovascular disease are closely associated with inflammation, probably due to the close interaction of inflammation with oxidative stress.,Classical therapies for inflammatory disorders have demonstrated protective effects in various models of cardiovascular disease; especially established drugs with pleiotropic immunomodulatory properties have proven beneficial cardiovascular effects; normalization of oxidative stress seems to be a common feature of these therapies.,The close link between inflammation and redox balance was also supported by reports on aggravated inflammatory phenotype in the absence of antioxidant defense proteins (e.g., superoxide dismutases, heme oxygenase-1, and glutathione peroxidases) or overexpression of reactive oxygen species producing enzymes (e.g., NADPH oxidases).,The value of immunomodulation for the treatment of cardiovascular disease was recently supported by large-scale clinical trials demonstrating reduced cardiovascular mortality in patients with established atherosclerotic disease when treated by highly specific anti-inflammatory therapies (e.g., using monoclonal antibodies against cytokines).,Modern antidiabetic cardiovascular drugs (e.g., SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 analogs) seem to share these immunomodulatory properties and display potent antioxidant effects, all of which may explain their successful lowering of cardiovascular risk. | 1 |
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