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A proportion of people infected with SARS-CoV-2 develop moderate or severe COVID-19, with an increased risk of thromboembolic complications.,The inflammatory response to SARS-CoV-2 infection can cause an acute-phase response and endothelial dysfunction, which contribute to COVID-19-associated coagulopathy, the clinical and laboratory features of which differ in some respects from those of classic disseminated intravascular coagulation.,Understanding of the pathophysiology of thrombosis in COVID-19 is needed to develop approaches to management and prevention, with implications for short-term and long-term health outcomes.,Evidence is emerging to support treatment decisions in patients with COVID-19, but many questions remain about the optimum approach to management.,In this Viewpoint, we provide a summary of the pathophysiology of thrombosis and associated laboratory and clinical findings, and highlight key considerations in the management of coagulopathy in hospitalised patients with severe COVID-19, including coagulation assessment, identification of thromboembolic complications, and use of antithrombotic prophylaxis and therapeutic anticoagulation.,We await the results of trials that are underway to establish the safety and benefits of prolonged thromboprophylaxis after hospital discharge. | COVID-19 is a complex disease targeting many organs.,Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications.,We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.,This self-controlled case series (SCCS) and matched cohort study was done in Sweden.,The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers.,The controls were matched on age, sex, and county of residence in Sweden.,International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study.,The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period.,The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.,86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study.,When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51-5·55) for the first week, 2·53 (1·29-4·94) for the second week, and 1·60 (0·84-3·04) in weeks 3 and 4 following COVID-19.,When day of exposure was included in the risk period, IRR was 8·44 (5·45-13·08) for the first week, 2·56 (1·31-5·01) for the second week, and 1·62 (0·85-3·09) for weeks 3 and 4 following COVID-19.,The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71-5·15) in the first week, 2·80 (1·60-4·88) in the second week, and 2·10 (1·33-3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06-9·42) for the first week, 2·85 (1·64-4·97) for the second week, and 2·14 (1·36-3·38) for weeks 3 and 4 following COVID-19.,In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58-7·36) and for stroke was 3·63 (1·69-7·80) in the 2 weeks following COVID-19.,When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56-12·20) and for ischaemic stroke was 6·74 (3·71-12·20) in the 2 weeks following COVID-19.,Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke.,This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.,Central ALF-funding and Base Unit ALF-Funding, Region Västerbotten, Sweden; Strategic funding during 2020 from the Department of Clinical Microbiology, Umeå University, Sweden; Stroke Research in Northern Sweden; The Laboratory for Molecular Infection Medicine Sweden. | 1 |
Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events.,Elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have recently been described in patients with COVID-19.,However, their potential role in COVID-19-associated thrombosis remains incompletely understood.,In order to elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis, we conducted a case-control study of patients hospitalized with COVID-19 who developed thrombosis, as compared with gender- and age-matched COVID-19 patients without clinical thrombosis.,We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation.,These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19, as well as novel approaches for thrombosis prevention.,The online version of this article (10.1007/s11239-020-02324-z) 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 |
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. | 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 |
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. | Unlabelled Image,•Venous thromboembolism (VTE) is a frequent complication in COVID-19 patients.,•Single-center study of COVID-19 patients admitted to general ward.,•17.0% of patients with VTE•Lack of thromboprophylaxis and leukocytosis were independent risk factors of VTE.,•VTE is independently associated with worse in-hospital outcomes.,Venous thromboembolism (VTE) is a frequent complication in COVID-19 patients.,Single-center study of COVID-19 patients admitted to general ward.,17.0% of patients with VTE,Lack of thromboprophylaxis and leukocytosis were independent risk factors of VTE.,VTE is independently associated with worse in-hospital outcomes. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
Supplemental Digital Content is available in the text.,The coronavirus disease 2019 (COVID-19) pandemic has potentially caused indirect harm to patients with other conditions via reduced access to health care services.,We aimed to describe the impact of the initial wave of the pandemic on admissions, care quality, and outcomes in patients with acute stroke in the United Kingdom.,Registry-based cohort study of patients with acute stroke admitted to hospital in England, Wales, and Northern Ireland between October 1, 2019, and April 30, 2020, and equivalent periods in the 3 prior years.,One hundred fourteen hospitals provided data for a study cohort of 184 017 patients.,During the lockdown period (March 23 to April 30), there was a 12% reduction (6923 versus 7902) in the number of admissions compared with the same period in the 3 previous years.,Admissions fell more for ischemic than hemorrhagic stroke, for older patients, and for patients with less severe strokes.,Quality of care was preserved for all measures and in some domains improved during lockdown (direct access to stroke unit care, 1-hour brain imaging, and swallow screening).,Although there was no change in the proportion of patients discharged with good outcome (modified Rankin Scale score, ≤2; 48% versus 48%), 7-day inpatient case fatality increased from 6.9% to 9.4% (P<0.001) and was 22.0% in patients with confirmed or suspected COVID-19 (adjusted rate ratio, 1.41 [1.11-1.80]).,Assuming that the true incidence of acute stroke did not change markedly during the pandemic, hospital avoidance may have created a cohort of untreated stroke patients at risk of poorer outcomes or recurrent events.,Unanticipated improvements in stroke care quality should be used as an opportunity for quality improvement and to learn about how to develop resilient health care systems. | 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 |
Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients. | •Unlike venous thromboembolism, no data are available on arterial thrombosis in SARS-CoV2 infected patients.,•We observed severe arterial thrombotic complications despite the use of antiplatelet or anticoagulant therapy.,•We described five irreversible lower limb ischemia and two thoracic aortic free floating thrombi.,•Further studies are needed to evaluate the necessity of therapeutic anticoagulation in COVID-19 patients.,Unlike venous thromboembolism, no data are available on arterial thrombosis in SARS-CoV2 infected patients.,We observed severe arterial thrombotic complications despite the use of antiplatelet or anticoagulant therapy.,We described five irreversible lower limb ischemia and two thoracic aortic free floating thrombi.,Further studies are needed to evaluate the necessity of therapeutic anticoagulation in COVID-19 patients. | 1 |
The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.,The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of “at-risk” patient cohorts for failure to present or delays to treatment.,This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020.,Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality.,A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries.,In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001).,The heterogeneity among centers was not related to the incidence of death due to COVID-19.,A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019.,Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.,The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic.,(Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655). | 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. | 1 |
Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving. | 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 |
A global outbreak of coronavirus disease (COVID‐19), caused by severe acute respiratory coronavirus 2 (SARS‐CoV‐2), has emerged since December 2019, in Wuhan, China.,However, electrocardiograhic (ECG) manifestations of patients with COVID‐19 have not been fully described.,We aim to investigate ECG characteristics in COVID‐19 patients and risk factors of intensive care unit (ICU) admission.,This retrospective observational study included the patients with COVID‐19 at the Wuhan Asia General hospital between February 10, and 26, 2020.,Demographic, clinical, and ECG characteristics were collected, and comparisons were made between the ICU and non‐ICU admission groups.,Logistic regression was used to identify risk factors of ICU admission.,Among 135 included patients (median age: 64 years [interquartile range: 48-72]), ST‐T abnormalities (40%) were the most common ECG feature, followed by arrhythmias (38%).,Cardiovascular disease (CVD) was presented in 48% of the patients.,Six (4.4%) died during hospitalization, and 23 (17.0%) were admitted to the ICU.,Compared with non‐ICU group, the ICU group showed higher heart rate (p = .019) and P‐wave duration (p = .039) and was more frequently associated with CVD (p < .001), ST‐T abnormalities (p = .007), arrhythmias (p = .003), QTc interval prolongation (p = .003), and pathological Q waves (p < .001).,Twenty‐seven patients were re‐examined ECG during admission, and 17 of them presented new findings compared with their initial ECG presentations.,ST‐T abnormalities (p = .040) and history of CVD (p = .0047) were associated with increased risk of ICU hospitalization.,COVID‐19 is frequently related to cardiovascular manifestations including ECG abnormalities and cardiovascular comorbidities.,ST‐T abnormalities and CVD at admission were associated with increased odds of ICU admission. | (Hydroxy)chloroquine ((H)CQ) is being investigated as a treatment for COVID-19, but studies have so far demonstrated either no or a small benefit.,However, these studies have been mostly performed in patients admitted to the hospital and hence likely already (severely) affected.,Another suggested approach uses prophylactic (H)CQ treatment aimed at preventing either severe acute respiratory syndrome coronavirus 2 infection or the development of disease.,A substantial number of clinical trials are planned or underway aimed at assessing the prophylactic benefit of (H)CQ.,However, (H)CQ may lead to QT prolongation and potentially induce life-threatening arrhythmias.,This may be of particular relevance to patients with preexisting cardiovascular disease and those taking other QT-prolonging drugs.,In addition, it is known that a certain percentage of the population carries genetic variant(s) that reduces their repolarization reserve, predisposing them to (H)CQ-induced QT prolongation, and this may be more relevant to female patients who already have a longer QT interval to start with.,This review provides an overview of the current evidence on (H)CQ therapy in patients with COVID-19 and discusses different strategies for prophylactic (H)CQ therapy (ie, preinfection, postexposure, and postinfection).,In particular, the potential cardiac effects, including QT prolongation and arrhythmias, will be addressed.,Based on these insights, recommendations will be presented as to which preventive measures should be taken when giving (H)CQ prophylactically, including electrocardiographic monitoring. | 1 |
Coagulopathy represents one of the most important determinants of morbidity and mortality in coronavirus disease-19 (COVID-19).,Whether standard thromboprophylaxis is sufficient or higher doses are needed, especially in severe patients, is unknown.,To evaluate the safety of intermediate dose regimens of low-weight molecular heparin (LWMH) in COVID-19 patients with pneumonia, particularly in older patients.,We retrospectively evaluated 105 hospitalized patients (61 M, 44 F; mean age 73.7 years) treated with subcutaneous enoxaparin: 80 mg/day in normal weight and mild-to-moderate impair or normal renal function; 40 mg/day in severe chronic renal failure or low bodyweight (< 45 kg); 100 mg/day if bodyweight was higher than 100 kg.,All the patients had radiologically confirmed pneumonia and 63.8% had severe COVID-19.,None of the patients had fatal haemorrhage; two (1.9%) patients had a major bleeding event (one spontaneous hematoma and one gastrointestinal bleeding).,Only 6.7% of patients needed transfusions of red blood cells.,One thrombotic event (pulmonary embolism) was observed.,When compared to younger patients, patients older than 85 years had a higher mortality (40% vs 13.3%), but not an increased risk of bleeding or need for blood transfusion.,The use of an intermediate dose of LWMH appears to be feasible and data suggest safety in COVID-19 patients, although further studies are needed. | 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 |
We present autopsy findings of a 22-year-old man who developed chest pain 5 days after the first dose of the BNT162b2 mRNA vaccine and died 7 hours later.,Histological examination of the heart revealed isolated atrial myocarditis, with neutrophil and histiocyte predominance.,Immunohistochemical C4d staining revealed scattered single-cell necrosis of myocytes which was not accompanied by inflammatory infiltrates.,Extensive contraction band necrosis was observed in the atria and ventricles.,There was no evidence of microthrombosis or infection in the heart and other organs.,The primary cause of death was determined to be myocarditis, causally-associated with the BNT162b2 vaccine. | There have been reports of myocarditis following COVID-19 vaccination.,We surveyed all hospitalized military personnel in the Isareli Defense Forces during the period of the COVID-19 vaccination operation (12/28/2021-3/7/2021) for diagnosed myocarditis.,We identified 7 cases of myocarditis with symptoms starting in the first week after the second dose of COVID-19 Pfizer-BioNTech vaccine.,One case of myocarditis diagnosed 10 days after the second dose of the vaccine was not included.,These 8 cases comprise of all events of myocarditis diagnosed in military personnel during this time period.,All patients were young and generally healthy.,All had mild disease with no sequalae.,The incidence of myocarditis in the week following a second dose of the vaccine was 5.07/100,000 people vaccinated.,Due to the nature of this report no causality could be established.,Clinicians should be aware of the possibility of myocarditis following Pfizer-BioNTech vaccination.,True incidence rates should be further investigated. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
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. | To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020.,Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns.,The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs.,A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care.,He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs.,Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa.,A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough.,Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative.,Autopsy showed acute bronchopneumonia with evidence of aspiration.,Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis.,SARS-CoV-2 testing can be performed at autopsy.,Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes. | 1 |
A prothrombotic state is reported with severe COVID-19 infection, which can manifest in venous and arterial thrombotic events.,Coagulopathy is reflective of more severe disease and anticoagulant thromboprophylaxis is recommended in hospitalized patients.,However, the prevalence of thrombosis on the intensive care unit (ICU) remains unclear, including whether this is sufficiently addressed by conventional anticoagulant thromboprophylaxis.,We aimed to identify the rate of thrombotic complications in ICU-treated patients with COVID-19, to inform recommendations for diagnosis and management.,A systematic review was conducted to assess the incidence of thrombotic complications in ICU-treated patients with COVID-19.,Observational studies and registries reporting thrombotic complications in ICU-treated patients were included.,Information extracted included patient demographics, use of thromboprophylaxis or anticoagulation, method of identifying thrombotic complications, and reported patient outcomes.,In 28 studies including 2928 patients, thrombotic complications occurred in 34% of ICU-managed patients, with deep venous thrombosis reported in 16.1% and pulmonary embolism in 12.6% of patients, despite anticoagulant thromboprophylaxis, and were associated with high mortality.,Studies adopting systematic screening for venous thrombosis with Duplex ultrasound reported a significantly higher incidence of venous thrombosis compared to those relying on clinical suspicion (56.3% vs.,11.0%, p < 0.001).,Despite thromboprophylaxis, there is a very high incidence of thrombotic complications in patients with COVID-19 on the ICU.,Systematic screening identifies many thrombotic complications that would be missed by relying on clinical suspicion and should be employed, with consideration given to increased dose anticoagulant thromboprophylaxis, whilst awaiting results of prospective trials of anticoagulation in this cohort.,The online version contains supplementary material available at 10.1007/s11239-021-02394-7. | The main objective of the study was to determine the prevalence of venous thromboembolism events in patients infected with severe acute respiratory syndrome coronavirus 2 requiring venovenous extracorporeal membrane oxygenation.,The secondary objective was to compare venous thromboembolism events and coagulation variables in patients requiring venovenous extracorporeal membrane oxygenation according to the pathogen.,Retrospective observational analysis at a single center.,Tertiary referral university teaching hospital.,Patients with severe acute respiratory syndrome coronavirus 2-related severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation therapy with an injected CT scan performed after extracorporeal membrane oxygenation retrieval.,None.,We included 13 severe acute respiratory syndrome coronavirus 2 patients requiring venovenous extracorporeal membrane oxygenation.,All of these patients experienced venous thromboembolism: 10 patients (76.9%) had isolated cannula-associated deep vein thrombosis, two patients (15.4%) had isolated pulmonary embolism, and one patient (7.7%) had both cannula-associated deep vein thrombosis and pulmonary embolism.,Eleven patients (84.6%) had cannula-associated deep vein thrombosis.,A jugular associated cannula-associated deep vein thrombosis was identified in seven patients (53.8%), a femoral associated cannula-associated deep vein thrombosis was identified in 10 patients (76.9%), and six patients (46.2%) had both femoral and jugular cannula-associated deep vein thrombosis.,A pulmonary embolism was found in three patients (23.1%).,No patient had central venous catheter-related deep vein thrombosis.,One patient had thrombotic occlusion of the centrifugal pump, and one had oxygenator thrombosis requiring circuit replacement.,Three patients (23.1%) had significant bleeding.,Three patients (23.1%) had laboratory-confirmed heparin-induced thrombocytopenia, and all of them developed cannula-associated deep vein thrombosis.,These three patients had femoral cannula-associated deep vein thrombosis, and two had an oxygenator or pump thrombosis.,The mean activated partial thromboplastin time ratio was higher in the severe acute respiratory syndrome coronavirus 2 group than in the influenza group and the community-acquired pneumonia group (1.91 vs 1.48 vs 1.53; p = 0.001), which was also found in regard to the percentage of patients with an activated partial thromboplastin time ratio greater than 1.8 (47.8% vs 20% vs 20.9%; p = 0.003) and the mean prothrombin ratio (86.3 vs 61.6 vs 67.1; p = 0.003).,There was no difference in baseline characteristics or venous thromboembolism events.,We report a 100% occurrence of venous thromboembolism in critically ill patients supported by venovenous extracorporeal membrane oxygenation for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome using CT scan imaging despite a high target and close monitoring of anticoagulation. | 1 |
The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.,An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020.,Data reported are those available through May 6, 2020.,A multicenter study including three Indianapolis area academic hospitals.,Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals.,One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.,All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.,The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development.,Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019.,Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism.,Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.,One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care.,The mean (± sd) age was 61 ± 16 years and 57% were male.,Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died.,Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital.,Elevated admission d-dimer and peak d-dimer were associated with venous thromboembolism development (p < 0.05). d-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661-0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%.,Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study.,The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.,These data show that coronavirus disease 2019 results in a hypercoagulable state.,Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019. | 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 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. | Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients. | 1 |
To assess the associations between coronavirus disease 2019 (COVID-19) infection and thromboembolism including myocardial infarction (MI), ischemic stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE).,A self-controlled case-series study was conducted covering the whole of Scotland’s general population.,The study population comprised individuals with confirmed (positive test) COVID-19 and at least one thromboembolic event between March 2018 and October 2020.,Their incidence rates during the risk interval (5 days before to 56 days after the positive test) and the control interval (the remaining periods) were compared intrapersonally.,Across Scotland, 1449 individuals tested positive for COVID-19 and experienced a thromboembolic event.,The risk of thromboembolism was significantly elevated over the whole risk period but highest in the 7 days following the positive test (incidence rate ratio, 12.01; 95% CI, 9.91 to 14.56) in all included individuals.,The association was also present in individuals not originally hospitalized for COVID-19 (incidence rate ratio, 4.07; 95% CI, 2.83 to 5.85).,Risk of MI, stroke, PE, and DVT were all significantly higher in the week following a positive test.,The risk of PE and DVT was particularly high and remained significantly elevated even 56 days following the test.,Confirmed COVID-19 infection was associated with early elevations in risk with MI, ischemic stroke, and substantially stronger and prolonged elevations with DVT and PE both in hospital and community settings.,Clinicians should consider thromboembolism, especially PE, among people with COVID-19 in the community. | Many studies confirmed an association between COVID-19 and venous thromboembolism (VTE).,Whether the risk of VTE significantly differed between COVID-19 cohorts and non-COVID-19 cohorts with similar disease severity remains unknown.,The aim of this systematic review with meta-analysis was to compare the rate of VTE between COVID-19 and non-COVID-19 cohorts with similar disease severity.,A systematic literature search (MEDLINE, Embase and Google Scholar) was conducted from January 1, 2020 to March 31, 2021 to identify studies reporting VTE in COVID-19.,Relative risks (RR) were estimated for the effect measure with 95% confidence intervals.,Seven studies (41,768 patients) evaluated VTE in COVID-19 cohorts compared to non-COVID-19 cohorts.,The overall risk of VTE (RR 1.18; 95%CI 0.79-1.77; p = 0.42; I2 = 54%), pulmonary embolism (RR 1.25; 95%CI 0.77-2.03; p = 0.36; I2 = 52%) and deep venous thrombosis (RR 0.92; 95%CI 0.52-1.65; p = 0.78; I2 = 0%) did not significantly differ between COVID-19 and non-COVID-19 cohorts.,However, subgroup analyses suggested an increased risk of VTE amongst CODID-19 versus non COVID-19 cohorts when only patients hospitalized within the intensive care unit (ICU) were considered (RR 3.10; 95%CI 1.54-6.23), which was not observed in cohorts of predominantly non-ICU patients (RR 0.95; 95%CI 0.81-1.11) (Pinteraction = 0.001).,There was no signal for a difference in VTE in COVID-19 cohorts compared to non-COVID-19 cohorts, except for the subgroup of patients hospitalized in the ICU.,These results should be viewed as exploratory and further studies are needed to confirm these results.,Unlabelled Image | 1 |
The emergence of severe acute respiratory syndrome coronavirus 2 virus, which causes coronavirus disease 2019 (COVID-19), led to the declaration of a global pandemic by the World Health Organization on March 11, 2020.,As of February 6, 2021, over 105 million persons have been infected in 223 countries and there have been 2,290,488 deaths.,As a result, emergency medical services and hospital systems have undergone unprecedented healthcare delivery reconfigurations.,Here, we review the effects of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) epidemiology and systems of care.,Areas severely affected by the pandemic have reported increased incidence of OHCA, lower rates of successful resuscitation, and increased mortality.,COVID-19 has significantly impacted patient outcomes through increased disease severity, decreased access to care, and the reshaping of emergency medical response and hospital-based healthcare systems and policies.,The pandemic has negatively influenced attitudes toward resuscitation and challenged providers with novel ethical dilemmas provoked by the scarcity of healthcare resources.,The COVID-19 pandemic has had direct, indirect, psychosocial, and ethical impacts on the cardiac arrest chain of survival. | An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far.,We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve.,We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019.,The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019).,A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001).,The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome.,Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.,Graphical Abstract | 1 |
Since the emergence of the coronavirus disease 19 (COVID-19), a number of studies have reported the presence of cardiovascular diseases in affected patients and linked them with a higher risk of mortality.,We conducted an online search in Medline/PubMed to identify original cohorts comparing data between survivors and non-survivors from COVID-19.,The presence of cardiovascular events and related biomarkers were compared between the 2 groups.,Data on 1,845 hospitalized patients with COVID-19 were pooled from 12 comparative studies.,The overall mortality rate in relation to COVID-19 was 17.6%.,Men aged > 50 years old were more likely to die from COVID-19.,Significant co-morbidities contributing to mortality were hypertension, diabetes mellitus, smoking, a previous history of cardiovascular disease including chronic heart failure, and cerebrovascular accidents.,A significant relationship was observed between mortality and patient presentation with dyspnea, fatigue, tachycardia, and hypoxemia.,Cardiovascular disease-related laboratory biomarkers related to mortality were elevated serum level of lactate dehydrogenase, creatine kinase, brain natriuretic peptide, and cardiac troponin I.,Adverse cardiovascular disease-related clinical events preceding death were shock, arrhythmias, and acute myocardial injury.,In conclusion, severe clinical presentation and elevated biomarkers in COVID-19 patients with established risk factors can predict mortality from cardiovascular causes. | There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications. | 1 |
To evaluate the efficacy of angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) vs calcium channel blockers (CCBs) on the progression of Corona Virus Disease 2019 (COVID‐19) patients with hypertension in Wuhan.,This retrospective single‐center case series analyzed COVID‐19 patients with hypertension, treated with ACEIs/ARBs or CCBs at the Tongji Hospital of Wuhan City, China from 25th January to 15th March 2020.,After propensity score matching analysis, 76 patients were selected into two groups.,Univariate and multivariable analyses were conducted to determine factors related to improvement measures and outcome measures by Cox proportional hazard regression models.,Among 157 patients with confirmed COVID‐19 combined hypertension, including 73 males and 84 females, a median age of 67.28 ± 9.11 vs 65.39 ± 10.85 years.,A univariable analysis indicated that clinical classification, lymphocyte count, and interleukin‐2 receptor were associated with a lengthened negative time of nucleic acid, with a significant difference between two groups (P = .036).,Furthermore, we found no obvious difference in nucleic acid conversion time between ACEIs/ARBs and CCBs groups (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: [0.97, 3.38]; P = .18) in the multivariable analysis as well as chest computed tomography improved time (HR: 0.73; 95% CI [0.45, 1.2]; P = .87), and hospitalization time between ACEIs/ARBs and CCBs groups (HR: 1.06; 95% CI [0.44, 1.1]; P = .83).,Our study provided additional evidence of no obvious difference in progress and prognosis between ACEIs/ACEIs and CCBs group, which may suggest ACEIs/ARBs may have scarcely influence on increasing the clinical severe situations of COVID‐19 patients with hypertension.,1.,Antihypertensive drugs, either ACEIs/ARBs or CCBs had few effects on firstly negative nucleic acid time, firstly chest CT improved time and the hospitalization time of COVID‐19 by a cox Regression analysis.2.,ACEIs/ARBs didn't increase the risk of extended course and poor prognosis of hypertension patients with COVID‐19.,Antihypertensive drugs, either ACEIs/ARBs or CCBs had few effects on firstly negative nucleic acid time, firstly chest CT improved time and the hospitalization time of COVID‐19 by a cox Regression analysis.,ACEIs/ARBs didn't increase the risk of extended course and poor prognosis of hypertension patients with COVID‐19. | In December 2019, COVID-19 outbroke in Wuhan, China.,The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension.,In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020.,All study cases were grouped according to whether they had a history of hypertension.,Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs.,The mean age of 110 patients was 57.7 years (range, 25-86 years), of which 60 (54.5%) were male patients.,The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)].,Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 × 109/L vs 1.26 × 109/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)].,Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)].,In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission.,The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19.,Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension. | 1 |
To assess the effectiveness of acupuncture in patients with post-stroke depression (PSD).,The Cochrane Library, CINAHL, EMBASE, PubMed, SCOPUS, Web of Science, and 4 Chinese databases were electronically searched for articles published between January 1, 2010 and May 31, 2018.,Randomized controlled trials (RCTs) investigating the effects of acupuncture on PSD were included.,The quality of all included trials was assessed according to guidelines published by the Cochrane Collaboration.,Seven trials compared the effectiveness of acupuncture therapy with that of control in alleviating the symptoms of PSD.,Pooled analysis demonstrated that patients in the acupuncture intervention group experienced a significantly higher treatment effect than controls (RR 1.16 [95% CI 1.08-1.24]; P < .0001), with low study heterogeneity (I2 = 4%).,Based on intervention methods, further analysis revealed a statistically significant difference in effectiveness between the acupuncture alone and medicine groups (RR 1.25 [95% CI 1.11 1.41]; Z = 3.78; P = .0002).,There was no statistically significant difference in efficacy between the acupuncture combined with medicine and medicine groups (RR 1.07 [95% CI 0.98-1.17]; P = .11).,This meta-analysis provides evidence supporting the viewpoint that acupuncture is an effective and safe treatment for PSD.,Subgroup analyses further revealed that acupuncture alone resulted in better outcomes than drug therapy in improving depressive symptoms.,Further high-quality RCTs are needed to systematically evaluate the effectiveness of acupuncture for PSD and develop standardized acupuncture protocols. | Poststroke depression is closely related to increased mortality in stroke patients.,Compared with antidepressants, electroacupuncture (EA) treatment for poststroke depression (PSD) has relatively more stable effectiveness and can reduce side effects.,This trial is designed to provide solid evidence for the efficacy and safety of EA treatment for patients with PSD.,This ongoing study is a single-blind, single-center, parallel group, randomized controlled trial.,Sixty-two participants will be recruited from Shanghai Shuguang Hospital and randomized into either the EA group or the sham EA group.,Baihui, Sishencong, Ganshu, Sanyinjiao, and Taichong are selected as the treatment acupoints in both groups.,The EA group will receive the traditional EA treatment with de-qi sensation, and the sham EA group will receive sham EA treatment without needle penetration and electrostimulation.,Participants will receive treatment 3 times per week for a total of 12 sessions over 4 weeks.,The primary outcome is Hamilton Rating Scale for Depression score, and the secondary outcomes are scores on the Zung Self-Rating Depression Scale, National Institutes of Health Stroke Scale, Barthel Index of Activities of Daily Living, and Depression Scale of traditional Chinese medicine.,All of the outcome measures will be assessed at baseline, 2 weeks after EA treatment onset, 4 weeks after treatment onset, and at 8-week follow-up.,Safety assessments will be done at each visit.,The results of this trial will demonstrate the efficacy and safety of EA treatment for PSD with credible and important clinical evidence, thus supporting EA treatment as an ideal choice for PSD treatment.,Chinese Clinical Trial Registry, ChiCTR-IOR-17012610.,Registered on 7 September 2017. http://www.chictr.org.cn/edit.aspx?,pid=21494&htm=4,The online version of this article (10.1186/s13063-018-2548-0) contains supplementary material, which is available to authorized users. | 1 |
Stroke is the second-leading global cause of death behind heart disease in 2013 and is a major cause of permanent disability.,The burden of stroke in terms of mortality, morbidity and disability is increasing across the world.,It is currently observed to be one of the commonest reasons of admission in many health care setups and becoming an alarming serious public health problem in our country Ethiopia.,Despite the high burden of strokes globally, there is insufficient information on the current clinical profile of stroke in low and middle income countries (LMICs) including Ethiopia.,So, this study was aimed to assess risk factors, clinical presentations and predictors of stroke subtypes among adult patients admitted to stroke unit of Jimma university medical center (JUMC).,Prospective observational study design was carried out at stroke unit (SU) of JUMC for 4 consecutive months from March 10-July 10, 2017.,A standardized data extraction checklist and patient interview was used to collect data.,Data was entered into Epi data version 3.1 and analyzed using SPSS version 20.,Multivariable logistic regression was used to identify the predictors of stroke subtypes.,A total of 116 eligible stroke patients were recruited during the study period.,The mean age of the patients was 55.1 ± 14.0 years and males comprised 62.9%.,According to world health organization (WHO) criteria of stroke diagnosis, 51.7% of patients had ischemic while 48.3% had hemorrhagic stroke.,The most common risk factor identified was hypertension (75.9%) followed by family history (33.6%), alcohol intake (22.4%), smoking (17.2%) and heart failure (17.2%).,The most common clinical presentation was headache complained by 75.0% of the patients followed by aphasia 60.3% and hemiparesis 53.4%.,Atrial fibrillation was the independent predictor of hemorrhagic stroke (AOR: 0.08, 95% CI: 0.01-0.68).,The clinical characteristics of stroke in this set up were similar to other low- and middle-resource countries.,As stroke is a high priority chronic disease, large-scale public health campaign should be launched focusing on public education regarding stroke risk factors and necessary interventions.,The online version of this article (10.1186/s12883-019-1412-5) contains supplementary material, which is available to authorized users. | Epidemiological studies aimed at stroke and its risk factors can help identify persons at higher risk and therefore promote stroke prevention strategies.,We aimed to explore the current prevalence of stroke and its associated risk factors in northeast China.,Population based cross sectional study.,Data were collected using a structured precoded questionnaire designed by the Stroke Screening and Prevention Programme of the National Health and Family Planning Commission of China, between January and March 2016.,4100 permanent residents, aged 40 years or older, who had lived in Dehui City of Jilin Province for more than 6 months volunteered to participate in the survey, with a response rate of 92.2%.,For the purpose of the present analysis, 48 subjects were excluded due to missing values, giving a total of 4052 people included in this analysis.,The questionnaire included demographic characteristics, stroke related behavioural factors, personal and family medical history of stroke, physical examination and laboratory testing.,The overall prevalence of stroke in Jilin Province was 7.2% (95% CI 6.3% to 8.2%).,Of all stroke cases, 91.7% (95% CI 87.4% to 94.6%) were ischaemic stroke and 8.3% (95% CI 5.4% to 12.6%) were haemorrhagic stroke.,The prevalence rates of dyslipidaemia, smoking and hypertension were ranked as the top three cerebrovascular risk factors and were 62.1%, 61.8% and 57.3%, respectively.,We found that hypertension, dyslipidaemia and lack of exercise were associated with ischaemic stroke.,However, only hypertension (OR=4.064, 95% CI 1.358 to 12.160) was significantly associated with haemorrhagic stroke.,The prevalence of stroke, especially ischaemic stroke, and associated cerebrovascular risk factors among adults aged 40 years or older in northeast China were high.,A higher regional prevalence of hypertension, dyslipidaemia and lack of exercise may be responsible. | 1 |
•We demonstrate five consecutive cases of predominantly lobar COVID-19-associated intracerebral haemorrhage (ICH).,•Patients were typically relatively young with a severe, prolonged inflammatory prodrome.,•COVID-19-induced endotheliitis/endotheliopathy may underlie associated cerebrovascular events.,•For the clinician, anticoagulation decisions must balance risk of thrombosis with risk of haemorrhage.,We demonstrate five consecutive cases of predominantly lobar COVID-19-associated intracerebral haemorrhage (ICH).,Patients were typically relatively young with a severe, prolonged inflammatory prodrome.,COVID-19-induced endotheliitis/endotheliopathy may underlie associated cerebrovascular events.,For the clinician, anticoagulation decisions must balance risk of thrombosis with risk of haemorrhage. | 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 |
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. | 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 |
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. | The SARS‐CoV‐2 virus binds to the angiotensin‐converting enzyme 2 (ACE2) receptor for cell entry.,It has been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID‐19 infection.,We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID‐19 at two hospitals with a multi‐ethnic catchment population in London (UK).,The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity.,Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset.,A total of 399 patients (33.3%) were taking ACEi or ARB.,Patients on ACEi/ARB were significantly older and had more comorbidities.,The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).,There was no evidence for increased severity of COVID‐19 in hospitalised patients on chronic treatment with ACEi or ARB.,A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials. | 1 |
Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has currently led to a global pandemic with millions of confirmed and increasing cases around the world.,The novel SARS-CoV-2 not only affects the lungs causing severe acute respiratory dysfunction but also leads to significant dysfunction in multiple organs and physiological systems including the cardiovascular system.,A plethora of studies have shown the viral infection triggers an exaggerated immune response, hypercoagulation and oxidative stress, which contribute significantly to poor cardiovascular outcomes observed in COVID-19 patients.,To date, there are no approved vaccines or therapies for COVID-19.,Accordingly, cardiovascular protective and supportive therapies are urgent and necessary to the overall prognosis of COVID-19 patients.,Accumulating literature has demonstrated the beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFA) toward the cardiovascular system, which include ameliorating uncontrolled inflammatory reactions, reduced oxidative stress and mitigating coagulopathy.,Moreover, it has been demonstrated the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors to a group of potent bioactive lipid mediators, generated endogenously, which mediate many of the beneficial effects attributed to their parent compounds.,Considering the favorable safety profile for n-3 PUFAs and their metabolites, it is reasonable to consider n-3 PUFAs as potential adjuvant therapies for the clinical management of COVID-19 patients.,In this article, we provide an overview of the pathogenesis of cardiovascular complications secondary to COVID-19 and focus on the mechanisms that may contribute to the likely benefits of n-3 PUFAs and their metabolites. | 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 |
To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF).,We analyzed for rare loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing study involving 175 adults with TOF from a single site.,We identified nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including an 8-kb deletion, and two predicted damaging.,In ten other probands we found likely disruptive variants in VEGF-related genes: KDR (VEGFR2; two stopgain and two nonsynonymous variants), VEGFA, FGD5, BCAR1, IQGAP1, FOXO1, and PRDM1.,Detection of VEGF-related variants (19/175, 10.9%) was associated with an increased prevalence of absent pulmonary valve (26.3% vs.,3.4%, p < 0.0001) and right aortic arch (52.6% vs.,29.1%, p = 0.029).,Extracardiac anomalies were rare.,In an attempt to replicate findings, we identified three loss-of-function or damaging variants in FLT4, KDR, and IQGAP1 in ten independent families with TOF.,Loss-of-function variants in FLT4 and KDR contribute substantially to the genetic basis of TOF.,The findings support dysregulated VEGF signaling as a novel mechanism contributing to the pathogenesis of TOF. | Congenital heart disease (CHD) is the leading cause of mortality from birth defects.,Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent-offspring trios implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot.,De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies.,Seven genes surpassed thresholds for genome-wide significance and 12 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD.,There was striking overlap between genes with damaging DNMs in probands with CHD and autism. | 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. | 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 |
As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature.,Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis.,However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear.,Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed.,The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit.,First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex.,Moreover, ACE2 expression was upregulated in cases of hypertension and dementia.,ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions.,Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window.,Introduction of spike proteins to invitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties.,Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface.,Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function.,Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients. | With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19. | 1 |
Speculations whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) predisposes to severe coronavirus disease 2019 (COVID-19) or worsens its outcomes.,This study assessed the association of ACE-I/ARB therapy with the development of severe COVID-19.,This multi-center, prospective study enrolled patients hospitalized for COVID-19 and receiving one or more antihypertensive agents to manage either hypertension or cardiovascular disease.,ACE-I/ARB therapy associations with severe COVID-19 on the day of hospitalization, intensive care unit (ICU) admission, mechanical ventilation and in-hospital death on follow-up were tested using a multivariate logistic regression model adjusted for age, obesity, and chronic illnesses.,The composite outcome of mechanical ventilation and death was examined using the adjusted Cox multivariate regression model.,Of 338 enrolled patients, 245 (72.4%) were using ACE-I/ARB on the day of hospital admission, and 197 continued ACE-I/ARB therapy during hospitalization.,Ninety-eight (29%) patients had a severe COVID-19, which was not significantly associated with the use of ACE-I/ARB (OR 1.17, 95% CI 0.66-2.09; P = .57).,Prehospitalization ACE-I/ARB therapy was not associated with ICU admission, mechanical ventilation, or in-hospital death.,Continuing ACE-I/ARB therapy during hospitalization was associated with decreased mortality (OR 0.22, 95% CI 0.073-0.67; P = .008).,ACE-I/ARB use was not associated with developing the composite outcome of mechanical ventilation and in-hospital death (HR 0.95, 95% CI 0.51-1.78; P = .87) versus not using ACE-I/ARB.,Patients with hypertension or cardiovascular diseases receiving ACE-I/ARB therapy are not at increased risk for severe COVID-19 on admission to the hospital.,ICU admission, mechanical ventilation, and mortality are not associated with ACE-I/ARB therapy.,Maintaining ACE-I/ARB therapy during hospitalization for COVID-19 lowers the likelihood of death.,ClinicalTrials.gov, NCT4357535. | Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of coronavirus disease 2019 (COVID-19) infection or affect disease severity.,Prior studies have not examined risks by medication dose.,This retrospective cohort study included people aged ≥18 years enrolled in a US integrated healthcare system for at least 4 months as of 2/29/2020.,Current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications.,COVID-19 infections and hospitalizations were identified through 6/14/2020 from laboratory and hospitalization data.,We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for race/ethnicity, obesity, and other covariates.,Among 322,044 individuals, 826 developed COVID-19 infection.,Among people using ACEI/ARBs, 204/56,105 developed COVID-19 (3.6 per 1,000 individuals) compared with 622/265,939 without ACEI/ARB use (2.3 per 1,000), yielding an adjusted OR of 0.91 (95% CI 0.74-1.12).,For use of <1 defined daily dose (DDD) vs. nonuse, the adjusted OR for infection was 0.92 (95% CI 0.66-1.28); for 1 to <2 DDDs, 0.89 (95% CI 0.66-1.19); and for ≥2 DDDs, 0.92 (95% CI 0.72-1.18).,The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 26% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.98 (95% CI 0.63-1.54), and there was no association with dose.,These findings support current recommendations that individuals on these medications continue their use. | 1 |
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. | Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias.,Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.,The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19.,We also evaluated correlations between the presence of these arrhythmias and mortality.,We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period.,Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality.,We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.,Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs.,All cardiac arrests occurred in patients admitted to the ICU.,In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment.,Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated.,Only cardiac arrests were associated with acute in-hospital mortality.,Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection. | 1 |
The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. | 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 |
An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous.,The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis.,In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included.,A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected.,Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected.,Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis.,D-dimers at baseline were significantly higher in patients with DVT (p < 0.001).,Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE.,The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE.,The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively.,The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer.,Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients.,Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism.,D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. | 1 |
Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N6-methyladenosine (m6A) modifications.,However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR).,In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner.,In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells.,As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knock-down of METTL3 and miR-25-3p had opposite effects.,Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells.,Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis.,Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose.,Collectively, METTL3 rescued cell viability in high-glucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade. | In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body.,This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications.,Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy.,Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy.,In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system.,In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy.,The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network.,Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications. | 1 |
Myocarditis has been reported as a possible clinical presentation or complication in patients with coronavirus disease (COVID)-19 due to SARS-CoV-2.,Despite the alarm that this possibility generated among physicians, there is paucity of information about mechanisms, prevalence, prognosis, diagnosis and therapy of myocarditis in the context of COVID-19.,This brief review has the goal to revise and summarize current knowledge on myocarditis in COVID-19 patients and underline problems especially related to diagnosis and treatment. | 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) 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. | 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 |
Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown.,Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts.,Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients.,Overexpression of circFndc3b in cardiac endothelial cells increases vascular endothelial growth factor-A expression and enhances their angiogenic activity and reduces cardiomyocytes and endothelial cell apoptosis.,Adeno-associated virus 9 -mediated cardiac overexpression of circFndc3b in post-MI hearts reduces cardiomyocyte apoptosis, enhances neovascularization and improves left ventricular functions.,Mechanistically, circFndc3b interacts with the RNA binding protein Fused in Sarcoma to regulate VEGF expression and signaling.,These findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI.,Circular RNAs (circRNAs) are non-coding RNAs generated from pre-mRNAs of coding genes by the splicing machinery whose function in the heart is poorly understood.,Here the authors show that AAV-mediated delivery of the circRNA circFndc3b prevents cardiomyocyte apoptosis, enhances angiogenesis, and attenuates LV dysfunction post-MI in mice by regulating FUS-VEGF-A signalling. | The aim of the present study was to investigate the expression of circular RNAs (circRNAs) in the peripheral blood of coronary artery disease (CAD) patients and the potential use of circRNAs as diagnostic biomarkers of CAD.,We first analysed peripheral blood circRNAs of 12 CAD patients and 12 control individuals by RNA microarray and found that 22 circRNAs were differentially expressed between these two groups: 12 were upregulated, and 10 were downregulated.,Then, we selected 5 circRNAs as candidate biomarkers under stricter screening criteria and verified them in another group of subjects consisting of 30 control individuals and 30 CAD patients with different SYNTAX scores.,These 5 circRNAs were all remarkably increased in the CAD group.,Hsa_circ_0124644 had the largest area under the curve (AUC).,We tested hsa_circ_0124644 in an independent cohort consisting of 115 control individuals and 137 CAD patients.,After we included the risk factors for CAD, the AUC slightly increased from 0.769 (95% confidence interval = [0.710-0.827], P < 0.001) to 0.804 ([0.751-0.857], P < 0.001), and when combined with hsa_circ_0098964, the diagnostic value slightly increased.,Taken together, our results suggest that hsa_circ_0124644 can be used as a diagnostic biomarker of CAD. | 1 |
Current data suggest that COVID-19 is less frequent in children, with a milder course.,However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.,Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’).,A historical cohort of ‘classical’ KD served as a comparator.,Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)).,SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%).,Cardiac involvement included myocarditis in 44% (n=7).,Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L.,Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment.,The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004).,Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children.,Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.,Trial registration number,NCT02377245 | This case series examines cardiac MRI findings in four children and adolescents admitted to intensive care in April 2020 for multisystem inflammatory syndrome and Kawasaki disease-like features related to COVID-19.,Acute myocarditis occurred less than 1 week after onset of fever and gastrointestinal symptoms.,Physical examination showed rash and cheilitis/conjunctivitis.,All patients recovered after intravenous immunoglobulin therapy.,SARS-CoV-2 RT-PCR was negative on nasopharyngeal, stool, and respiratory samples and was positive on serology.,Cardiac MRI showed diffuse myocardial edema on T2-STIR sequences and native-T1 mapping, with no evidence of late gadolinium enhancement suggestive of replacement fibrosis or focal necrosis.,These findings favor post-infectious myocarditis in children and adolescents with COVID-19. | 1 |
The incidence, characteristics, and prognosis of pulmonary embolism (PE) in Coronavirus disease 2019 (COVID-19) have been poorly investigated.,We aimed to investigate the prevalence and the correlates with the occurrence of PE as well as the association between PE and the risk of mortality in COVID-19.,Retrospective multicenter study on consecutive COVID-19 patients hospitalized at 7 Italian Hospitals.,At admission, all patients underwent medical history, laboratory and echocardiographic evaluation.,The study population consisted of 224 patients (mean age 69 ± 14, male sex 62%); PE was diagnosed in 32 cases (14%).,Patients with PE were hospitalized after a longer time since symptoms onset (7 IQR 3-11 days, 3 IQR 1-6 days; p = 0.001) and showed higher D-dimers level (1819 IQR 568-5017 ng/ml vs 555 IQR 13-1530 ng/ml; p < 0.001) and higher prevalence of myocardial injury (47% vs 28%, p = 0.033).,At multivariable analysis, tricuspid annular plane systolic excursion (TAPSE; HR = 0.84; 95% CI 0.66-0.98; p = 0.046) and systolic pulmonary arterial pressure (sPAP; HR = 1.12; 95% CI 1.03-1.23; p = 0.008) resulted the only parameters independently associated with PE occurrence.,Mortality rates (50% vs 27%; p = 0.010) and cardiogenic shock (37% vs 14%; p = 0.001) were significantly higher in PE as compared with non-PE patients.,At multivariate analysis PE was significant associated with mortality.,PE is relatively common complication in COVID-19 and is associated with increased mortality risk.,TAPSE and sPAP resulted the only parameters independently associated with PE occurrence in COVID-19 patients. | 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 |
The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients. | The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. | 1 |
Stroke assistance is facing changes and new challenges since COVID‐19 became pandemic.,A variation on the patient influx might be one of the greater concerns, due to fewer people coming to emergency departments or coming too late.,However, no data quantifying this have been published until now.,The aim was to analyse the impact of the COVID‐19 epidemic outbreak on hospital stroke admissions and their characteristics in our region.,The data of every patient admitted to any hospital of our healthcare system with a diagnosis of ischaemic stroke between 30 December 2019 and 19 April 2020 were reviewed.,Demographic and clinical data were recorded and compared between periods before and after the setting of the state of emergency secondary to the COVID‐19 outbreak.,In total, 354 patients with ischaemic stroke were admitted in our study period.,There was a weekly average of 27.5 cases before the setting of the state of emergency against 12 afterwards (P < 0.001).,This drop in stroke cases occurred progressively from week 11, persisting in time despite the decrease in confirmed cases of COVID‐19.,No differences in the proportion of intravenous thrombolysis (21.1% vs.,21.5%, P = 0.935) or endovascular therapy (12.4% vs.,15.2%, P = 0.510) were found, nor in other demographic or clinical characteristics except for median onset‐to‐door time (102 vs. 183 min, P = 0.015).,This observational study offers the perspective of a whole region in one of the countries more heavily stricken by the SARS‐CoV‐2 epidemic and shows that the decrease of stroke events, since the beginning of the COVID‐19 outbreak, happened globally and without any specific patient distribution. | 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. | 1 |
Little is known about regional differences in volume, treatment, and outcomes of STEMI patients undergoing PCI during the pandemic.,The objectives of this study were to compare COVID-19 pandemic and prepandemic periods with respect to regional volumes, outcomes, and treatment of patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) between January 1, 2019 and March 14, 2020 (pre-COVID period) and between March 15, 2020 and April 4, 2020 (COVID period) in 51 New York State hospitals certified to perform PCI.,The hospitals were classified as being in either high-density or low-density COVID-19 counties on the basis of deaths/10,000 population.,There was a decrease of 43% in procedures/week in high-density COVID-19 counties (p <0.0001) and only 4% in low-density counties (p = 0.64).,There was no difference in the change in risk-adjusted in-hospital mortality rates in either type of county, but STEMI PCI patients in high-density counties had longer times from symptom onset to hospital arrival and lower cardiac arrest rates in the pandemic period.,In conclusion, the decrease in STEMI PCIs during the pandemic was mainly limited to counties with a high density of COVID-19 deaths.,The decrease appears to be primarily related to patients not presenting to hospitals in high-density COVID regions, rather than PCI being avoided in STEMI patients or a reduction in the incidence of STEMI.,Also, high-density COVID-19 counties experienced delayed admissions and less severely ill STEMI PCI patients during the pandemic.,This information can serve to focus efforts on convincing STEMI patients to seek life-saving hospital care during the pandemic. | Although patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment.,This study sought to examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care health system.,Acute cardiovascular hospitalizations were tracked between January 1, 2019, and March 31, 2020.,Daily hospitalization rates were estimated using negative binomial models.,Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference.,From January 1, 2019, to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons.,There were 43.4% (95% confidence interval [CI]: 27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 compared with March 2019 (p < 0.001).,The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [95% CI: -0.04% to +0.02%]; p = 0.50), January 2020 (-0.5% per day [95% CI: -1.6% to +0.5%]; p = 0.31), or February 2020 (+0.7% per day [95% CI: -0.6% to +2.0%]; p = 0.27).,There was significant daily decline in hospitalizations in March 2020 (-5.9% per day [95% CI: -7.6% to -4.3%]; p < 0.001).,Length of stay was shorter (4.8 days [25th to 75th percentiles: 2.4 to 8.3 days] vs.,6.0 days [25th to 75th percentiles: 3.1 to 9.6 days]; p = 0.003) and in-hospital mortality was not significantly different (6.2% vs.,4.4%; p = 0.30) in March 2020 compared with March 2019.,During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations, and patients who were admitted had shorter lengths of stay.,These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic. | 1 |
Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors’ experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection.,Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy.,Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart.,It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis.,Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19. | 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 |
Early studies suggest that acute cerebrovascular events may be common in patients with coronavirus disease 2019 (COVID-19) and may be associated with a high mortality rate.,Most cerebrovascular events described have been ischemic strokes, but both intracerebral hemorrhage and rarely cerebral venous sinus thrombosis (CVST) have also been reported.,The diagnosis of CVST can be elusive, with wide-ranging and nonspecific presenting symptoms that can include headache or altered sensorium alone.,To describe the presentation, barriers to diagnosis, treatment, and outcome of CVST in patients with COVID-19.,We abstracted data on all patients diagnosed with CVST and COVID-19 from March 1 to August 9, 2020 at Boston Medical Center.,Subsequently, we reviewed the literature and extracted all published cases of CVST in patients with COVID-19 from January 1, 2020 through August 9, 2020 and included all studies with case descriptions.,We describe the clinical features and management of CVST in 3 women with COVID-19 who developed CVST days to months after initial COVID-19 symptoms.,Two patients presented with encephalopathy and without focal neurologic deficits, while one presented with visual symptoms.,All patients were treated with intravenous hydration and anticoagulation.,None suffered hemorrhagic complications, and all were discharged home.,We identified 12 other patients with CVST in the setting of COVID-19 via literature search.,There was a female predominance (54.5%), most patients presented with altered sensorium (54.5%), and there was a high mortality rate (36.4%).,During this pandemic, clinicians should maintain a high index of suspicion for CVST in patients with a recent history of COVID-19 presenting with non-specific neurological symptoms such as headache to provide expedient management and prevent complications.,The limited data suggests that CVST in COVID-19 is more prevalent in females and may be associated with high mortality. | Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients.,To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease.,Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020).,The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST).,Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years.,Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000).,The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%.,After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19.,COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke.,The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes. | 1 |
As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of a variety of cancers However, its clinical utility is limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to the formation of reactive oxygen species (ROS).,Accordingly, the prevention of DOX-induced cardiotoxicity is an indispensable goal to optimize therapeutic regimens and reduce morbidity.,Acetylation is an emerging and important epigenetic modification regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs).,Despite extensive studies of the molecular basis and biological functions of acetylation, the application of acetylation as a therapeutic target for cardiotoxicity is in the initial stage, and further studies are required to clarify the complex acetylation network and improve the clinical management of cardiotoxicity.,In this review, we summarize the pivotal functions of HDACs and HATs in DOX-induced oxidative stress, the underlying mechanisms, the contributions of noncoding RNAs (ncRNAs) and exercise-mediated deacetylases to cardiotoxicity.,Furthermore, we describe research progress related to several important SIRT activators and HDAC inhibitors with potential clinical value for chemotherapy and cardiotoxicity.,Collectively, a comprehensive understanding of specific roles and recent developments of acetylation in doxorubicin-induced cardiotoxicity will provide a basis for improved treatment outcomes in cancer and cardiovascular diseases.,Image 1,•Cardiotoxicity caused by DOX is an important problem to be urgently solved in cancer treatment.,•HDACs and HATs mediated-cell death, oxidative stress and inflammation plays a pivotal role in DOX-induced cardiotoxicity.,•Noncoding RNA mediates HDACs to provide novel insights for the development of treatments for DOX-induced cardiotoxicity.,•SIRT activators and HDAC inhibitors are promising drug approaches to attenuate DOX-induced cardiotoxicity.,Cardiotoxicity caused by DOX is an important problem to be urgently solved in cancer treatment.,HDACs and HATs mediated-cell death, oxidative stress and inflammation plays a pivotal role in DOX-induced cardiotoxicity.,Noncoding RNA mediates HDACs to provide novel insights for the development of treatments for DOX-induced cardiotoxicity.,SIRT activators and HDAC inhibitors are promising drug approaches to attenuate DOX-induced cardiotoxicity. | Doxorubicin- (DOX-) induced cardiomyocyte loss results in irreversible heart failure, which limits the clinical applications of DOX.,Currently, there are no drugs that can effectively treat DOX-related cardiotoxicity.,Follistatin-like 1 (FSTL1) has been reported to be a transforming growth factor-beta-inducible gene, and FSTL1 supplementation attenuated ischemic injury and cardiac apoptotic loss in mice.,However, the effect of FSTL1 on DOX-induced cardiomyopathy has not been elucidated.,We aimed to explore whether FSTL1 could prevent DOX-related cardiotoxicity in mice.,Mice were intraperitoneally injected with a single dose of DOX to induce acute cardiotoxicity.,We used an adeno-associated virus system to overexpress FSTL1 in the heart.,DOX administration decreased FSTL1 mRNA and protein expression in the heart and in cells.,FSTL1 prevented DOX-related cardiac injury and inhibited cardiac oxidative stress and apoptosis, thereby improving cardiac function in mice.,FSTL1 also improved cardiomyocyte contractile functions in vitro.,FSTL1 upregulated expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in DOX-treated hearts.,FSTL1 was not capable of protecting against these toxic effects in Nrf2-deficient mice.,In conclusion, FSTL1 protected against DOX-induced cardiotoxicity via upregulation of Nrf2 expression. | 1 |
The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection.,Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019.,What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities.,Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality.,The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body’s innate immune response, and the vascular response to cytokine production.,The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae.,•The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,•Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,•Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress.,The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19).,Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality.,Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply-demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress. | 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 |
During the peak of COVID-19 pandemic, we have noted an increase in positive lower extremity CT angiogram (CTA) exams in patients presenting with leg ischemia.,The goal of this study was to determine whether lower extremity arterial thrombosis was associated with COVID-19 and whether it was characterized by greater severity in these patients.,In this IRB approved retrospective propensity score-matched study, 16 SARS-CoV-2 positive patients who underwent CTA of the lower extremities and 32 SARS-CoV-2 negative patients observed from January to April in 2018-2020 were compared using three scoring system: two systems including all vessels with weighting given in one system to more proximal vessel and in the other to more distal vessels, and a third system where only the common iliac through popliteal arteries were considered.,Correlation with presenting symptoms and outcomes was computed.,Fisher exact tests were used to compare COVID-19 positive to negative patients regarding presence of clots and presenting symptoms.,A Mantel-Haenszel test was used to associate outcome of death/amputation with COVID-19 adjusted by the history of peripheral vascular disease (PVD).,Sixteen patients with confirmed COVID-19 (70 +/- 14 years, 7 women) underwent CTA and 32 propensity-score matched control patients (71 +/- 15 years, 16 women) were included.,All COVID-19 patients (100%, 95%CI: 79-100%) had at least one thrombus while only 69% (95%CI: 50-84%) of controls had thrombi (p=0.02).,94% (95%CI: 70-99.8%) of COVID-19 patients had proximal thrombi compared to 47% (95%CI: 29-65%) of controls (p<0.001).,Mean thrombus score using any of the three scoring systems yielded greater scores in the COVID-19 patients (p<0.001).,Adjusted for history of PVD, death or limb amputation was more common in COVID-19 patients (OR 25, 95%CI 4.3-147, p<0.001).,COVID-19 patients presenting with symptoms of leg ischemia only were more likely to avoid amputation or death than patients presenting also with pulmonary or systemic symptoms (p=0.001).,COVID-19 is associated with lower extremity arterial thrombosis characterized by greater clot burden and a more dire prognosis. | To evaluate the incidence of pulmonary ischaemia in COVID-19 patients on extracorporeal membrane oxygenation (ECMO), and its correlation with pulmonary artery thrombosis.,Computed tomography (CT) thorax of all patients receiving ECMO with proven COVID-19 pneumonitis between March and May 2020 were analysed for the presence and extension of pulmonary thromboembolic disease.,Fifty-one patients were reviewed.,The mean (range) age of 45 (26-66) years; 38/51 (74.5%) were men.,All patients had severe COVID-19 pneumonitis, and 18/51 (35.3%) had macroscopic thrombosis (15 with associated ischaemia); however, 13/51 (25.5%) patients had ischaemia without associated thrombus.,The majority of patients with COVID-19 who received ECMO had areas of ischaemia within consolidated lungs, almost half of these without subtending pulmonary artery thrombosis.,Although the prognostic significance of these findings is unclear, they are highly suggestive of lung ischaemia due to isolated microvascular immune thrombosis.,•High incidence of pulmonary artery thrombosis in COVID-19 ECMO patients.,•Lung ischaemia seen in patients with and without visible pulmonary artery thrombus.,•Ischaemia with no visible thrombus suggest microvascular thrombosis.,High incidence of pulmonary artery thrombosis in COVID-19 ECMO patients.,Lung ischaemia seen in patients with and without visible pulmonary artery thrombus.,Ischaemia with no visible thrombus suggest microvascular thrombosis. | 1 |
There is growing evidence that breastfeeding has short- and long-term cardiovascular health benefits for mothers.,The objectives of this systematic review were to examine the association between breastfeeding and maternal cardiovascular risk factors and outcomes that have not previously been synthesized systematically, including metabolic syndrome, hypertension and cardiovascular disease.,This systematic review meets PRISMA guidelines.,The MEDLINE, EMBASE and CINAHL databases were systematically searched for relevant publications of any study design from the earliest publication date to March 2016.,The reference lists from selected articles were reviewed, and forward and backward referencing were conducted.,The methodological quality of reviewed articles was appraised using validated checklists.,Twenty-one studies meeting the inclusion criteria examined the association between self-reported breastfeeding and one or more of the following outcomes: metabolic syndrome/metabolic risk factors (n = 10), inflammatory markers/adipokines (n = 2), hypertension (n = 7), subclinical cardiovascular disease (n = 2), prevalence/incidence of cardiovascular disease (n = 3) and cardiovascular disease mortality (n = 2).,Overall, 19 studies (10 cross-sectional/retrospective, 9 prospective) reported significant protective effects of breastfeeding, nine studies (3 cross-sectional/retrospective, 5 prospective, 1 cluster randomized controlled trial) reported non-significant findings and none reported detrimental effects of breastfeeding.,In most studies reporting significant associations, breastfeeding remained associated with both short- and long-term maternal cardiovascular health risk factors/outcomes, even after covariate adjustment.,Findings from several studies suggested that the effects of breastfeeding may diminish with age and a dose-response association between breastfeeding and several metabolic risk factors.,However, further longitudinal studies, including studies that measure exclusive breastfeeding, are needed to confirm these findings.,The evidence from this review suggests that breastfeeding is associated with cardiovascular health benefits.,However, results should be interpreted with caution as the evidence gathered for each individual outcome was limited by the small number of observational studies.,Additional prospective studies are needed.,CRD42016047766. | Breastfeeding confers substantial benefits to child health and has also been associated with lower risk of maternal cardiovascular diseases (CVDs) in later life.,However, the evidence on the effects of CVD is still inconsistent, especially in East Asians, in whom the frequency and duration of breastfeeding significantly differ from those in the West.,In 2004-2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30 to 79 years from 10 diverse regions across China.,During 8 years of follow‐up, 16 671 incident cases of coronary heart disease and 23 983 cases of stroke were recorded among 289 573 women without prior CVD at baseline.,Cox regression yielded adjusted hazard ratios (HRs) and 95% CIs for incident CVD by breastfeeding.,Overall, ≈99% of women had given birth, among whom 97% reported a history of breastfeeding, with a median duration of 12 months per child.,Compared with parous women who had never breastfed, ever breastfeeding was associated with a significantly lower risk of CVD, with adjusted HRs of 0.91 (95% CI, 0.84-0.99) for coronary heart disease and 0.92 (95% CI, 0.85-0.99) for stroke.,Women who had breastfed for ≥24 months had an 18% (HR, 0.82; 0.77-0.87) lower risk of coronary heart disease and a 17% (HR, 0.83; 0.79-0.87) lower risk of stroke compared with women who had never breastfed.,Among women who ever breastfed, each additional 6 months of breastfeeding per child was associated with an adjusted HR of 0.96 (95% CI, 0.94-0.98) for coronary heart disease and 0.97 (95% CI, 0.96-0.98) for stroke.,Among Chinese women, a history of breastfeeding was associated with an ≈10% lower risk of CVD in later life and the magnitude of the inverse association was stronger among those with a longer duration of breastfeeding. | 1 |
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. | To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates. | 1 |
Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse.,This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19.,This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020.,Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records.,For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF).,Mean age was 63.5 years, and 45% were women.,Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs.,11.9%; adjusted odds ratio: 3.64; 95% confidence interval: 2.56 to 5.16; p < 0.001), and mortality (40.0% vs.,24.9%; adjusted odds ratio: 1.88; 95% confidence interval: 1.27 to 2.78; p = 0.002).,Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.,History of HF was associated with higher risk of mechanical ventilation and mortality among patients hospitalized for COVID-19, regardless of LVEF. | Admission rates for acute decompensated heart failure (HF) declined during the COVID‐19 pandemic.,However, the impact of this reduction on hospital mortality is unknown.,We describe temporal trends in the presentation of patients with acute HF and their in‐hospital outcomes at two referral centres in London during the COVID‐19 pandemic.,A total of 1372 patients hospitalized for HF in two referral centres in South London between 7 January and 14 June 2020 were included in the study and their outcomes compared with those of equivalent patients of the same time period in 2019.,The primary outcome was all‐cause in‐hospital mortality.,The number of HF hospitalizations was significantly reduced during the COVID‐19 pandemic, compared with 2019 (P < 0.001).,Specifically, we observed a temporary reduction in hospitalizations during the COVID‐19 peak, followed by a return to 2019 levels.,Patients admitted during the COVID‐19 pandemic had demographic characteristics similar to those admitted during the equivalent period in 2019.,However, in‐hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015).,Hospitalization in 2020 was independently associated with worse in‐hospital mortality (hazard ratio 2.23, 95% confidence interval 1.34-3.72; P = 0.002).,During the COVID‐19 pandemic there was a reduction in HF hospitalization and a higher rate of in‐hospital mortality.,Hospitalization for HF in 2020 is independently associated with more adverse outcomes.,Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.,Temporal trends in heart failure admission and adjusted Kaplan-Meier curves for in‐hospital mortality during the COVID‐19 pandemic. | 1 |
The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources.,Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases.,To survey health professionals’ views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents.,3101 responses were received from 141 countries across 6 continents.,88.3% responded that their country was in “total lockdown” and 7.1% in partial lockdown.,78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%.,Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis.,Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service.,The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring.,This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic. | This document is an update to the 2013 publication of the Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Protocols.,Concurrent with this publication, 3 additional task forces will publish documents that should be referred to in conjunction with the present document.,The first is a document on the Clinical Indications for CMR, an update of the 2004 document.,The second task force will be updating the document on Reporting published by that SCMR Task Force in 2010.,The 3rd task force will be updating the 2013 document on Post-Processing.,All protocols relative to congenital heart disease are covered in a separate document.,The section on general principles and techniques has been expanded as more of the techniques common to CMR have been standardized.,A section on imaging in patients with devices has been added as this is increasingly seen in day-to-day clinical practice.,The authors hope that this document continues to standardize and simplify the patient-based approach to clinical CMR.,It will be updated at regular intervals as the field of CMR advances. | 1 |
Although COVID-19 has been reported to be associated with high rates of venous thromboembolism (VTE), the risk of VTE and bleeding after hospitalization for COVID-19 remains unclear, and the optimal hospital VTE prevention strategy is not known.,We collected retrospective observational data on thrombosis and bleeding in 303 consecutive adult patients admitted to the hospital for at least 24 hours for COVID-19.,Patients presenting with VTE on admission were excluded.,Data were collected until 90 days after admission or known death by using medical records and an established national VTE network.,Maximal level of care was ward based in 78% of patients, with 22% requiring higher dependency care (12% noninvasive ventilation, 10% invasive ventilation).,Almost all patients (97.0%) received standard thromboprophylaxis or were already receiving therapeutic anticoagulation (17.5%).,Symptomatic image-confirmed VTE occurred in 5.9% of patients during index hospitalization, and in 7.2% at 90 days after admission (23.9% in patients requiring higher dependency care); half the events were isolated segmental or subsegmental defects on lung imaging.,Bleeding occurred in 13 patients (4.3%) during index hospitalization (1.3% had major bleeding).,The majority of bleeds occurred in patients on the general ward, and 6 patients were receiving treatment-dose anticoagulation, highlighting the need for caution in intensifying standard thromboprophylaxis strategies.,Of 152 patients discharged from the hospital without an indication for anticoagulation, 97% did not receive thromboprophylaxis after discharge, and 3% received 7 days of treatment with low molecular weight heparin after discharge.,The rate of symptomatic VTE in this group at 42 days after discharge was 2.6%, highlighting the need for large prospective randomized controlled trials of extended thromboprophylaxis after discharge in COVID-19.,•The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,•Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19.,The rate of symptomatic VTE in patients after hospitalization for COVID-19 was 2.6% at 42 days after discharge.,Bleeding is a significant cause of morbidity in addition to thrombosis in patients admitted with COVID-19. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world1.,Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%).,The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence.,Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant.,We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes.,In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits.,We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant.,Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants.,Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.,Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. | Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation.,Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci.,As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis.,We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies.,A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population.,Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart.,These results further implicate common genetic polymorphisms in the pathogenesis of DCM.,Structural changes to the left ventricle are characteristic of dilated cardiomyopathy (DCM), a disease for which many rare genetic variants are known.,Here, Pirruccello et al. report GWAS of seven cardiac MRI measurements in the left ventricle and describe shared loci and polygenic association with DCM. | 1 |
Because of the Coronavirus Disease 2019 (COVID-19) pandemic, we were forced to cancel scheduled visits for nearly 150 patients followed in our heart failure (HF) outpatient clinic.,Therefore, we structured a telephone follow-up, developing a standardized 23-item questionnaire from which we obtained the Covid-19-HF score.,The questionnaire was built to reproduce our usual clinical evaluation investigating a patient's social and functional condition, mood, adherence to pharmacological and nonpharmacological recommendations, clinical and hemodynamic status, pharmacological treatment, and need to contact emergency services.,The score was used as a clinical tool to define patients' clinical stability and timing of the following telephone contact on the basis of the assignment to progressively increasing risk score groups: green (0-3), yellow (4-8), and red (≥9).,Here we present our experience applying the score in the first 30 patients who completed the 4-week follow-up, describing baseline clinical characteristics and events that occurred in the period of observation. | In response to the COVID-19 pandemic, US federal and state governments have implemented wide-ranging stay-at-home recommendations as a means to reduce spread of infection.,As a consequence, many US healthcare systems and practices have curtailed ambulatory clinic visits-pillars of care for patients with heart failure (HF).,In this context, synchronous audio/video interactions, also known as virtual visits (VVs), have emerged as an innovative and necessary alternative.,This scientific statement outlines the benefits and challenges of VVs, enumerates changes in policy and reimbursement that have increased the feasibility of VVs during the COVID-19 era, describes platforms and models of care for VVs, and provides a vision for the future of VVs. | 1 |
Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades.,Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge.,Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients.,We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients.,More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus).,The significantly increased product of gut bacterial translocation (LPS and d-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events.,Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury.,Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated.,Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation.,New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.,The online version of this article (10.1186/s40168-018-0441-4) contains supplementary material, which is available to authorized users. | Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases.,Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown.,To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice.,Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations.,Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension.,The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis.,And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately.,Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated.,Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension.,And the significance of early intervention for pre-hypertension was emphasized.,The online version of this article (doi:10.1186/s40168-016-0222-x) contains supplementary material, which is available to authorized users. | 1 |
The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. | The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension. | 1 |
BT200, a pegylated form of the aptamer BT100, inhibits binding of von Willebrand factor (VWF) to platelet glycoprotein GPIb, preventing arterial thrombosis in cynomolgus monkeys.,It is being developed for secondary prevention of arterial thrombosis such as stroke or myocardial infarction.,Inhibition of thrombogenesis by BT200 is expected to provide a therapeutic benefit.,However, there may be unexpected bleeding (eg, incidental trauma) in which a reversal agent is required.,To address this need, BT101, a complementary aptamer, has been developed to specifically inhibit BT100 and BT200 function.,To characterize the effects of BT101 both in vitro and in vivo.,The direct interaction between BT101 and the core aptamer BT100 was evaluated using polyacrylamide gel electrophoresis.,The binding of BT200 to purified human VWF and inhibition of VWF activity was further characterized using enzyme‐linked immunosorbent assay.,VWF‐dependent platelet function was measured by the platelet function analyzer and aggregometry in whole blood.,In addition, both the in vivo pharmacokinetic profile of BT101 as well as its ability to reverse BT200 activity, were evaluated in cynomolgus monkeys.,BT101 bound to the core aptamer BT100 at a 1:1 ratio, inhibited BT200 binding to purified human VWF, and reversed BT200‐induced inhibition of both VWF activity and VWF‐dependent platelet function in vitro.,After intravenous injection to monkeys, BT101 reversed BT200‐induced effects on VWF activity and platelet function within minutes, without causing any adverse effects.,The results of this study demonstrate that BT101 is an effective reversal agent for BT200. | The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific and lay communities about viral infectious disease in the modern era.,Among the many lessons learned for the medical community is the potential for transmissibility and host infectivity of the SARS-CoV-2 virus.,Moreover, it has become clear that the virus can affect any organ including the circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses in the form of innate immunity, leukocyte debris such as cell-free DNA and histones and RNA viral particles.,The following review considers COVID-19-associated vasculitis and vasculopathy as a defining feature of a virus-induced systemic disease with acute, subacute and potential chronic health implications. | 1 |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure.,The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses.,To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19).,Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization.,In the case of out-of-hospital death, patients were included if post-mortem testing was positive.,Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination.,If available, laboratory findings and echocardiograms were reported.,The median age of the decedents was 63.5 years.,The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%).,Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients.,Acute myocardial ischemia was observed in eight (16.0%) patients.,The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%).,The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients.,Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings.,Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes.,A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed. | 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 |
Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population.,We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867).,We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test.,We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273.,This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test.,We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test.,Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273.,Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.,A self-controlled case series using individual-patient-level data from over 38 million people aged 16 years and over, reveals an increased risk of myocarditis within a week of receiving a first dose of ChAdOx1, BNT162b2 and mRNA-1273 vaccines, which was further increased after a second dose of either mRNA vaccine.,SARS-CoV-2 infection was associated with even greater risk of myocarditis, as well as pericarditis and cardiac arrhythmia. | To characterize the clinical course and outcomes of children 12-18 years of age who developed probable myopericarditis after vaccination with the Pfizer-BioNTech (BNT162b2) coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine.,A cross-sectional study of 25 children, aged 12-18 years, diagnosed with probable myopericarditis after COVID-19 mRNA vaccination as per the Centers for Disease Control and Prevention criteria for myopericarditis at 8 US centers between May 10, 2021, and June 20, 2021.,We retrospectively collected the following data: demographics, severe acute respiratory syndrome coronavirus 2 virus detection or serologic testing, clinical manifestations, laboratory test results, imaging study results, treatment, and time to resolutions of symptoms.,Most (88%) cases followed the second dose of vaccine, and chest pain (100%) was the most common presenting symptom.,Patients came to medical attention a median of 2 days (range, <1-20 days) after receipt of Pfizer mRNA COVID-19 vaccination.,All adolescents had an elevated plasma troponin concentration.,Echocardiographic abnormalities were infrequent, and 92% showed normal cardiac function at presentation.,However, cardiac magnetic resonance imaging, obtained in 16 patients (64%), revealed that 15 (94%) had late gadolinium enhancement consistent with myopericarditis.,Most were treated with ibuprofen or an equivalent nonsteroidal anti-inflammatory drug for symptomatic relief.,One patient was given a corticosteroid orally after the initial administration of ibuprofen or an nonsteroidal anti-inflammatory drug; 2 patients also received intravenous immune globulin.,Symptom resolution was observed within 7 days in all patients.,Our data suggest that symptoms owing to myopericarditis after the mRNA COVID-19 vaccination tend to be mild and transient.,Approximately two-thirds of patients underwent cardiac magnetic resonance imaging, which revealed evidence of myocardial inflammation despite a lack of echocardiographic abnormalities. | 1 |
The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component.,While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study.,A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients.,The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities.,Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%).,At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases.,Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting.,In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare. | Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | 1 |
The novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury.,In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection.,COVID-19-associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation.,The complement system represents the first response of the host immune system to SARS-CoV-2 infection, but there is growing evidence that unrestrained activation of complement induced by the virus in the lungs and other organs plays a major role in acute and chronic inflammation, endothelial cell dysfunction, thrombus formation, and intravascular coagulation, and ultimately contributes to multiple organ failure and death.,In this review, we discuss the relative role of the different complement activation products in the pathogenesis of COVID-19-associated tissue inflammation and thrombosis and propose the hypothesis that blockade of the terminal complement pathway may represent a potential therapeutic option for the prevention and treatment of lung and multiorgan damage. | 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 |
We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 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 |
Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19.,However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression.,Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins.,Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58.,The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis.,These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.,•Statin treatment among 13,981 patients with COVID-19 was retrospectively studied•Statin use in this cohort was associated with a lower risk of all-cause mortality•Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort•The benefit of statins among this cohort may be due to immunomodulatory benefits,Statin treatment among 13,981 patients with COVID-19 was retrospectively studied,Statin use in this cohort was associated with a lower risk of all-cause mortality,Adding an ACE inhibitor or an ARB did not affect statin-associated outcome in the cohort,The benefit of statins among this cohort may be due to immunomodulatory benefits,Statins have anti-inflammatory benefits and were suggested as an adjunct therapy for COVID-19.,But statins may increase the expression of ACE2, the receptor for SARS-CoV-2.,Here, Zhang et al. retrospectively analyzed 13,981 COVID-19 cases and found that in-hospital statin use is associated with a lower risk of all-cause mortality. | 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 |
Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19).,However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.,We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing.,We further validated some of the key observations in other human tissues and/or a controlled experimental model.,Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney.,We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs.,We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.,Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney.,Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.,Graphical Abstract | There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications. | 1 |
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. | To analyze the risk factors for pulmonary embolism (PE) in patients infected with COVID-19.,We conducted an observational, retrospective study.,Patients with severe infection with COVID-19 and suspected PE were included.,Patients with higher levels of D-dimer and those requiring intubation were at a higher risk of developing PE.,Higher D-dimer levels were associated with a greater probability of PE 3, 6, 9 and 12 days after determining D-dimer levels with an OR of 1.7, 2.0, 2.4 and 2.4, respectively.,In conclusion, patients infected with COVID-19 requiring OTI with higher levels of D-dimer have an increased risk of developing PE. | 1 |
Mesenchymal stem cells (MSCs) are derived from a wide range of sources and easily isolated and cultured.,MSCs have the capacity for in vitro amplification and self-renewal, low immunogenicity and immunomodulatory properties, and under certain conditions, MSCs can be differentiated into a variety of cells.,In the cardiovascular system, MSCs can protect the myocardium by reducing the level of inflammation, promoting the differentiation of myocardial cells around infarct areas and angiogenesis, increasing apoptosis resistance, and inhibiting fibrosis, which are ideal qualities for cardiovascular repair.,Preclinical studies have shown that MSCs can be transplanted and improve cardiac repair, but challenges, such as their low rate of migration to the ischemic myocardium, low tissue retention, and low survival rate after transplantation, remain.,This article reviews the potential and methods of MSC transplantation in the treatment of cardiovascular diseases (CVDs) and the challenges of the clinical use of MSCs. | Cardiac stem cells (CSCs) are important for improving cardiac function following myocardial infarction, with CSC migration to infarcted or ischemic myocardium important for cardiac regeneration.,Strategies to improve cell migration may improve the efficiency of myocardial regeneration.,Basic fibroblast growth factor (bFGF) is an essential molecule in cell migration, but the endogenous bFGF level is too low to be effective.,The effect of exogenously delivered bFGF on CSC migration was observed in vitro and in vivo in the present study.,The CSC migration index in response to various bFGF concentrations was demonstrated in vitro.,In addition, a murine myocardial infarction model was constructed and bFGF protein expression levels and CSC aggregation following myocardial infarction were observed.,To study cell migration in vivo, CM-Dil-labeled CSCs or bFGF-CSCs were injected into the peri-infarct myocardium following myocardium infarction and cell migration and maintenance in the peri-infarct/infarct area was observed 1 week later.,Protein expression levels of bFGF, CXCR-4 and SDF-1 were assessed, as was myocardium capillary density.,The Akt inhibitor deguelin was used to assess the role of the PI3K/Akt pathway in vitro and in vivo.,The present study demonstrated that bFGF-promoted Sca-1+ CSC migration, with the highest migration rate occurring at a concentration of 45 ng/ml.,The PI3K/Akt pathway inhibitor deguelin attenuated this increase.,The phospho-Akt/Akt ratio was elevated significantly after 30 min of bFGF exposure.,Transplantation of bFGF-treated Sca-1+ CSCs led to improved cell maintenance in the peri-infarct area and increased cell migration to the infarct area, as well as improved angiogenesis.,Protein expression levels of bFGF, CXCR-4 and SDF-1 were upregulated, and this upregulation was partially attenuated by deguelin.,Therefore, bFGF was demonstrated to promote Sca-1+ CSC migration both in vitro and in vivo, partially through activation of the PI3K/Akt pathway.,This may provide a new method for facilitating CSC therapy for myocardium repair after myocardium injury. | 1 |
Supplemental Digital Content is available in the text.,We aimed to investigate the acute stroke presentations during the coronavirus disease 2019 (COVID-19) pandemic.,The data were obtained from a health system with 19 emergency departments in northeast Ohio in the United States.,Baseline period from January 1 to March 8, 2020, was compared with the COVID period from March 9, to April 2, 2020.,The variables included were total daily stroke alerts across the hospital emergency departments, thrombolysis, time to presentation, stroke severity, time from door-to-imaging, time from door-to-needle in thrombolysis, and time from door-to-puncture in thrombectomy.,The 2 time periods were compared using nonparametric statistics and Poisson regression.,Nine hundred two stroke alerts during the period across the emergency departments were analyzed.,Total daily stroke alerts decreased from median, 10 (interquartile range, 8-13) during baseline period to median, 8 (interquartile range, 4-10, P=0.001) during COVID period.,Time to presentation, stroke severity, and time to treatment were unchanged.,COVID period was associated with decrease in stroke alerts with rate ratio of 0.70 (95% CI, 0.60-0.28).,Thrombolysis also decreased with rate ratio, 0.52 (95% CI, 0.28-0.97) but thrombectomy remained unchanged rate ratio, 0.93 (95% CI, 0.52-1.62),We observed a significant decrease in acute stroke presentations by ≈30% across emergency departments at the time of surge of COVID-19 cases.,This observation could be attributed to true decline in stroke incidence or patients not seeking medical attention for emergencies during the pandemic. | 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. | 1 |
Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.,We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States.,The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.,Clinicians abstracted the data onto standardized forms.,We report on 186 patients with MIS-C in 26 states.,The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.,Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).,The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died.,Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease-like features were documented in 74 (40%).,Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation.,The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).,Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.,(Funded by the Centers for Disease Control and Prevention.) | Current data suggest that COVID-19 is less frequent in children, with a milder course.,However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.,Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’).,A historical cohort of ‘classical’ KD served as a comparator.,Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)).,SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%).,Cardiac involvement included myocarditis in 44% (n=7).,Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L.,Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment.,The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004).,Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children.,Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.,Trial registration number,NCT02377245 | 1 |
Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19).,However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.,We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing.,We further validated some of the key observations in other human tissues and/or a controlled experimental model.,Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney.,We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs.,We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.,Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney.,Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.,Graphical Abstract | 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 objectives were to investigate and compare the risks and incidences of venous thromboembolism (VTE) between the 2 groups of patients with coronavirus disease 2019 (COVID-19) pneumonia and community-acquired pneumonia (CAP).,Medical records of 616 pneumonia patients who were admitted to the Yichang Central People’s Hospital in Hubei, China, from January 1 to March 23, 2020, were retrospectively reviewed.,The patients with COVID-19 pneumonia were treated in the dedicated COVID-19 units, and the patients with CAP were admitted to regular hospital campus.,Risks of VTE were assessed using the Padua prediction score.,All the patients received pharmaceutical or mechanical VTE prophylaxis.,VTE was diagnosed using Duplex ultrasound or computed tomography pulmonary angiogram.,Differences between COVID-19 and CAP groups were compared statistically.,All statistical tests were 2 sided, and P<0.05 was considered as statistically significant.,All data managements and analyses were performed by IBM SPSS, version 24, software (SPSS, Inc, Chicago, IL).,Of the 616 patients, 256 had COVID-19 pneumonia and 360 patients had CAP.,The overall rate of VTE was 2% in COVID-19 pneumonia group and 3.6% in CAP group, respectively (P=0.229).,In these two groups, 15.6% of the COVID-19 pneumonia patients and 10% of the CAP patients were categorized as high risk for VTE (Padua score, >4), which were significantly different (P=0.036).,In those high-risk patients, the incidence of VTE was 12.5% in COVID-19 pneumonia group and 16.7% in CAP group (P=0.606).,Subgroup analysis of the critically ill patients showed that VTE rate was 6.7% in COVID-19 group versus 13% in CAP group (P=0.484).,In-hospital mortality of COVID-19 and CAP was 6.3% and 3.9%, respectively (P=0.180).,Our study suggested that COVID-19 pneumonia was associated with hypercoagulable state.,However, the rate of VTE in COVID-19 pneumonia patients was not significantly higher than that in CAP patients. | Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels.,Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited.,This multicenter retrospective study describes the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation.,Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications.,Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death.,The radiographically confirmed VTE rate was 4.8% (95% confidence interval [CI], 2.9-7.3), and the overall thrombotic complication rate was 9.5% (95% CI, 6.8-12.8).,The overall and major bleeding rates were 4.8% (95% CI, 2.9-7.3) and 2.3% (95% CI, 1.0-4.2), respectively.,In the critically ill, radiographically confirmed VTE and major bleeding rates were 7.6% (95% CI, 3.9-13.3) and 5.6% (95% CI, 2.4-10.7), respectively.,Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization (D-dimer >2500 ng/mL, adjusted odds ratio [OR] for thrombosis, 6.79 [95% CI, 2.39-19.30]; adjusted OR for bleeding, 3.56 [95% CI, 1.01-12.66]), critical illness, and death.,Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450 × 109/L (adjusted OR, 3.56 [95% CI, 1.27-9.97]), C-reactive protein (CRP) >100 mg/L (adjusted OR, 2.71 [95% CI, 1.26-5.86]), and erythrocyte sedimentation rate (ESR) >40 mm/h (adjusted OR, 2.64 [95% CI, 1.07-6.51]).,ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than in those without.,DIC, clinically relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations.,Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.,•In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,•D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19.,In addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19.,D-dimer elevation at admission was predictive of bleeding, thrombosis, critical illness, and death in patients with COVID-19. | 1 |
The outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic.,The cellular receptor for SARS-CoV-2 entry is the angiotensin-converting enzyme 2, a membrane-bound homolog of angiotensin-converting enzyme.,Henceforth, this has brought the attention of the scientific community to study the interaction between COVID-19 and the renin-angiotensin system (RAS), as well as RAS inhibitors.,However, these inhibitors are commonly used to treat hypertension, chronic kidney disorder, and diabetes.,Obesity is a known risk factor for heart disease, diabetes, and hypertension, whereas diabetes and hypertension may be indirectly related to each other through the effects of obesity.,Furthermore, people with hypertension, obesity, diabetes, and other related complications like cardiovascular and kidney diseases have a higher risk of severe COVID-19 infection than the general population and usually exhibit poor prognosis.,This severity could be due to systemic inflammation and compromised immune response and RAS associated with these comorbid conditions.,Therefore, there is an urgent need to develop evidence-based treatment methods that do not affect the severity of COVID-19 infection and effectively manage these chronic diseases in people with COVID-19.,The online version of this article (10.1007/s00592-020-01636-z) contains supplementary material, which is available to authorized users. | Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19).,However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.,We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing.,We further validated some of the key observations in other human tissues and/or a controlled experimental model.,Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney.,We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs.,We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.,Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney.,Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.,Graphical Abstract | 1 |
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. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role.,Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies.,Critically however, ethnicity has major effects on thrombotic risk, with a 3-4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans.,In this study, we investigated COVID19 coagulopathy in Caucasian patients.,Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity.,Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC).,In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease.,Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.,Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
Coronavirus disease 2019 (COVID-19) is associated with coagulation activation and high incidence of venous thromboembolism (VTE) in severe patients despite routine thromboprophylaxis.,Conflicting results exist regarding the epidemiology of VTE for unselected anticoagulated COVID-19 patients hospitalized in general wards.,The aim of this study was to evaluate the prevalence of asymptomatic deep venous thrombosis (DVT) in unselected patients with COVID-19 recently hospitalized in general wards.,We performed a systematic complete doppler ultrasound (CDU) at a median 4 days after admission in 42 consecutive COVID-19 patients hospitalized in general wards of our university hospital, irrespective of D-Dimer level, and retrospectively collected clinical, biological and outcome data from electronic charts.,Thromboprophylaxis was systematically applied following a French national proposal.,In our population, the prevalence of asymptomatic DVT was 19% (8/42 patients), with distal thrombosis in 7/8 cases and bilateral DVT in 4/8 cases.,Symptomatic pulmonary embolism was detected in 4 (9.5%) patients, associated to DVT in one case.,Compared to patients without DVT, patients with DVT were older and experienced poorer outcomes.,In conclusion, prevalence of asymptomatic DVT is high in the first days of hospitalization of unselected COVID-19 patients in general wards and may be related to poor prognosis.,Individualized assessment of thromboprophylaxis and early systematic screening for DVT is warranted in this context.,The online version of this article (10.1007/s11239-020-02246-w) contains supplementary material, which is available to authorized users. | Coronavirus Disease 2019 (COVID‐19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality.,The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID‐19 patients.,Information on the benefit/risk ratio of this approach is still lacking.,To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug.,Consecutive COVID‐19 patients admitted between February and April 2020 were included in a retrospective analysis.,Major bleedings (MB) and clinically relevant non‐major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee.,Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants.,The rate of the composite endpoint of MB or CRNMB was 6.9 per 100‐person/months in patients who had been given prophylactic doses, and 26.4 per 100‐person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90‐7.97).,The corresponding rates for overall mortality were 12.2 and 20.1 per 100‐person/months, respectively.,The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants.,In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher.,Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non‐critically ill patients with COVID‐19. | 1 |
Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease.,To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19.,The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients.,This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020.,Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein.,There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration.,Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI.,Higher doses of heparin to achieve therapeutic activated clotting times were also noted.,Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission.,In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes.,This supports the need for establishing COVID-19 status in all STEMI cases.,Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases. | 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 |
Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM).,CVD’s prevalence has been growing over time.,To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published within the last 10 years (2007-March 2017).,We searched Medline, Embase, and proceedings of major scientific meetings for original research documenting the prevalence of CVD in T2DM.,CVD included stroke, myocardial infarction, angina pectoris, heart failure, ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death.,No restrictions were placed on country of origin or publication language.,Two reviewers independently searched for articles and extracted data, adjudicating results through consensus.,Data were summarized descriptively.,Risk of bias was examined by applying the STROBE checklist.,We analyzed data from 57 articles with 4,549,481 persons having T2DM.,Europe produced the most articles (46%), followed by the Western Pacific/China (21%), and North America (13%).,Overall in 4,549,481 persons with T2DM, 52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years.,CVD affected 32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743), 10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505).,CVD was the cause of death in 9.9% of T2DM patients (representing 50.3% of all deaths).,Risk of bias was low; 80 ± 12% of STROBE checklist items were adequately addressed.,Globally, overall CVD affects approximately 32.2% of all persons with T2DM.,CVD is a major cause of mortality among people with T2DM, accounting for approximately half of all deaths over the study period.,Coronary artery disease and stroke were the major contributors. | Supplemental Digital Content is available in the text.,Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk.,The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation.,The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo.,The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event, and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event.,The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.,Secondary outcomes included heart failure hospitalization and a renal composite (40% reduction in estimated glomerular filtration rate, renal replacement therapy, or renal death).,Primary prevention participants (N=3486; 34%) were younger (63 versus 64 years of age), were more often female (45% versus 31%), and had a longer duration of diabetes mellitus (14 versus 13 years) compared with secondary prevention participants (N=6656; 66%).,The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group (36.9 versus 15.7/1000 patient-years, P<0.001).,In the total cohort, the primary end point was reduced with canagliflozin compared with placebo (26.9 versus 31.5/1000 patient-years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.97; P<0.001 for noninferiority, P=0.02 for superiority) with no statistical evidence of heterogeneity (interaction P value=0.18) between the primary (HR, 0.98; 95% CI, 0.74-1.30) and secondary prevention (HR, 0.82; 95% CI, 0.72-0.95) cohorts.,Renal outcomes (HR, 0.59; 95% CI, 0.44-0.79 versus HR, 0.63; 95% CI, 0.39-1.02; interaction P value=0.73) and heart failure hospitalization (HR, 0.68; 95% CI, 0.51-0.90 versus HR, 0.64; 95% CI, 0.35-1.15; interaction P value=0.91) were similarly reduced in the secondary and primary prevention cohorts, respectively.,Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts (HR, 2.07; 95% CI, 1.43-3.00 versus HR, 1.52; 95% CI, 0.70-3.29; interaction P value=0.63).,Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients.,Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups.,Additional studies will provide further insights into the effects of canagliflozin in these patient populations.,URL: https://www.clinicaltrials.gov.,Unique identifiers: NCT01032629 and NCT01989754. | 1 |
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%. | 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 |
Circular RNAs (circRNAs) sequester microRNAs (miRNAs) and repress their endogenous activity.,We hypothesized that artificial circRNA sponges (circmiRs) can be constructed to target miRNAs therapeutically, with a low dosage requirement and extended half-lives compared to current alternatives.,This could present a new treatment approach for critical global pathologies, including cardiovascular disease.,Here, we constructed a circmiR sponge to target known cardiac pro-hypertrophic miR-132 and -212.,Expressed circmiRs competitively inhibited miR-132 and -212 activity in luciferase rescue assays and showed greater stability than linear sponges.,A design containing 12 bulged binding sites with 12 nucleotides spacing was determined to be optimal.,Adeno-associated viruses (AAVs) were used to deliver circmiRs to cardiomyocytes in vivo in a transverse aortic constriction (TAC) mouse model of cardiac disease.,Hypertrophic disease characteristics were attenuated, and cardiac function was preserved in treated mice, demonstrating the potential of circmiRs as novel therapeutic tools.,Subsequently, group I permutated intron-exon sequences were used to directly synthesize exogenous circmiRs, which showed greater in vitro efficacy than the current gold standard antagomiRs in inhibiting miRNA function.,Engineered circRNAs thus offer exciting potential as future therapeutics.,Lavenniah and colleagues detail considerations involved in custom-engineering circular miRNA sponges and demonstrate their greater stability and miRNA antagonism compared to linear miRNA inhibition technology.,In vivo delivery of an engineered circular miRNA sponge improved cardiac function and inhibited hypertrophy in a mouse model of left ventricular pressure overload. | Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown.,Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts.,Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients.,Overexpression of circFndc3b in cardiac endothelial cells increases vascular endothelial growth factor-A expression and enhances their angiogenic activity and reduces cardiomyocytes and endothelial cell apoptosis.,Adeno-associated virus 9 -mediated cardiac overexpression of circFndc3b in post-MI hearts reduces cardiomyocyte apoptosis, enhances neovascularization and improves left ventricular functions.,Mechanistically, circFndc3b interacts with the RNA binding protein Fused in Sarcoma to regulate VEGF expression and signaling.,These findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI.,Circular RNAs (circRNAs) are non-coding RNAs generated from pre-mRNAs of coding genes by the splicing machinery whose function in the heart is poorly understood.,Here the authors show that AAV-mediated delivery of the circRNA circFndc3b prevents cardiomyocyte apoptosis, enhances angiogenesis, and attenuates LV dysfunction post-MI in mice by regulating FUS-VEGF-A signalling. | 1 |
To investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced myocarditis constitutes an important mechanism of cardiac injury, a review was conducted of the published data and the authors’ experience was added from autopsy examination of 16 patients dying of SARS-CoV-2 infection.,Myocarditis is an uncommon pathologic diagnosis occurring in 4.5% of highly selected cases undergoing autopsy or endomyocardial biopsy.,Although polymerase chain reaction-detectable virus could be found in the lungs of most coronavirus disease-2019 (COVID-19)-infected subjects in our own autopsy registry, in only 2 cases was the virus detected in the heart.,It should be appreciated that myocardial inflammation alone by macrophages and T cells can be seen in noninfectious deaths and COVID-19 cases, but the extent of each is different, and in neither case do such findings represent clinically relevant myocarditis.,Given its extremely low frequency and unclear therapeutic implications, the authors do not advocate use of endomyocardial biopsy to diagnose myocarditis in the setting of COVID-19. | The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component.,While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study.,A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients.,The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities.,Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%).,At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases.,Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting.,In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare. | 1 |
Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH).,Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction.,The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation.,Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation.,Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls.,We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH.,The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining.,Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels.,NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed.,RVG/Exos exhibited improved targeting to the brains of SAH mice.,MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65.,Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH.,Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3.,These effects alleviated neurobehavioral impairments and neuroinflammation following SAH. | Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities.,Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury.,This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH.,Two hundred male Sprague-Dawley rats were used.,The endovascular perforation induced SAH.,Bexarotene was administered intraperitoneally at 1 h after SAH induction.,To investigate the underlying mechanism, the selective RXR antagonist UVI3003 and RXR siRNA or SIRT6 inhibitor OSS128167 was administered via intracerebroventricular 1 h before SAH induction.,Post-SAH assessments including SAH grade, neurological score, brain water content, Western blot, and immunofluorescence were performed.,The endogenous RXR and sirtuin 6 (SIRT6) protein levels were increased after SAH.,Bexarotene treatment significantly reduced brain edema and improved the short-/long-term neurological deficit after SAH.,Mechanistically, bexarotene increased the levels of PPARγ and SIRT6; decreased the expression of phosphorylated FoxO3a (p-FoxO3a), IL-6, IL-1β, and TNF-a; and inhibited the microglia activation and neutrophils infiltration at 24 h after SAH.,Either UVI3003, OSS128167, or RXR siRNA abolished the neuroprotective effects of bexarotene and its regulation on protein levels of PPARγ/SIRT6/p-FoxO3a after SAH.,The activation of RXR by bexarotene attenuated neuroinflammation and improved neurological deficits after SAH.,The anti-neuroinflammatory effect was at least partially through regulating PPARγ/SIRT6/FoxO3a pathway.,Bexarotene may be a promising therapeutic strategy in the management of SAH patients.,The online version of this article (10.1186/s12974-019-1432-5) contains supplementary material, which is available to authorized users. | 1 |
We investigated the impact of regionally imposed social and healthcare restrictions due to coronavirus disease 2019 (COVID-19) to the time metrics in the management of acute ischemic stroke patients admitted at the regional stroke referral site for Central South Ontario, Canada.,We compared relevant time metrics between patients with acute ischemic stroke receiving intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy (EVT) before and after the declared restrictions and state of emergency imposed in our region (March 17, 2020).,We identified a significant increase in the median door-to-CT times for patients receiving intravenous tPA (19 min, interquartile range (IQR): 14-27 min vs. 13 min, IQR: 9-17 min, p = 0.008) and/or EVT (20 min, IQR: 15-33 min vs. 11 min, IQR: 5-20 min, p = 0.035) after the start of social and healthcare restrictions in our region compared to the previous 12 months.,For patients receiving intravenous tPA treatment, we also found a significant increase (p = 0.005) in the median door-to-needle time (61 min, IQR: 46-72 min vs. 37 min, IQR: 30-50 min).,No delays in the time from symptom onset to hospital presentation were uncovered for patients receiving tPA and/or endovascular reperfusion treatments in the first 1.5 months after the establishment of regional and institutional restrictions due to the COVID-19 pandemic.,We detected an increase in our institutional time to treatment metrics for acute ischemic stroke patients receiving tPA and/or endovascular reperfusion therapies, related to delays from hospital presentation to the acquisition of cranial CT imaging for both tPA- and EVT-treated patients, and an added delay to treatment with tPA. | When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted.,In this study, we investigated the impact of the COVID-19 outbreak on stroke care across China.,Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy.,We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes.,The survey was distributed to the leaders of stroke centers in these 280 hospitals.,From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% (P<0.0001) and 25.3% (P<0.0001), respectively, in February 2020 as compared with February 2019.,We retrieved 227 valid complete datasets from the 280 stroke centers.,Nearly 50% of these hospitals were designated hospitals for COVID-19.,The capacity for stroke care was reduced in the majority of the hospitals.,Most of the stroke centers stopped or reduced their efforts in stroke education for the public.,Hospital admissions related to stroke dropped ≈40%; thrombolysis and thrombectomy cases dropped ≈25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019.,Many factors contributed to the reduced admissions and prehospital delays; lack of stroke knowledge and proper transportation were significant limiting factors.,Patients not coming to the hospital for fear of virus infection was also a likely key factor.,The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy.,Although many factors contributed, patients not coming to the hospital was probably the major limiting factor.,Recommendations based on the data are provided. | 1 |
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 | 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 |
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 | Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis.,This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China.,All patients underwent compression ultrasonography for identifying DVT.,Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score.,The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55-71) years old and 5 (4-6), respectively.,Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35-56%).,Proximal DVT was recognized in 9% (95% CI 3-15%) of the patients, while 46% (95% CI 35-56%) of patients had distal DVT.,All of the proximal DVT combined with distal DVT.,Risk factors of DVT extension occurred in all distal DVT patients.,As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively.,Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance.,Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06-0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38-3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03-1.84, P = 0.029) were significant DVT risk factors in multivariable analyses.,High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis.,The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT.,More effective VTE prevention and management strategies may need to be addressed. | 1 |
Background: Cardiac damage is frequently referred to in patients with SARS-CoV-2, is usually diagnosed by enzyme elevations, and is generally thought to be due to underlying coronary artery disease.,There are references to cardiomyopathies accompanying coronavirus, but there has been no histologic confirmation.,Case report: A previously healthy 17 year male old presented in full cardiac arrest to the emergency department after a 2 day history of headache, dizziness, nausea and vomiting.,Autopsy demonstrated an enlarged flabby heart with eosinophilic myocarditis.,There was no interstitial pneumonia or diffuse alveolar damage.,Postmortem nasopharyngeal swabs detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known to cause coronavirus disease 2019 (COVID-19).,No other cause for the eosinophilic myocarditis was elucidated.,Conclusion: Like other viruses, SARS-CoV-2 may be associated with fulminant myocarditis. | •COVID-19 is a viral disease caused by SARS-CoV-2.,•Twenty-three autopsy cases demonstrate that COVID-19 is a systemic disease with major pulmonary and cardiac manifestations.,•COVID-19 produces an acute interstitial pneumonia, usually with a prominent diffuse alveolar damage (DAD) component, often coupled with a thrombotic microangiopathy.,•The heart frequently shows acute cardiomyocyte injury and, in some cases, pericarditis and/or myocarditis.,•Patients with fatal COVID-19 frequently are obese and have pre-existing cardiac disease, hypertension and/or diabetes mellitus.,COVID-19 is a viral disease caused by SARS-CoV-2.,Twenty-three autopsy cases demonstrate that COVID-19 is a systemic disease with major pulmonary and cardiac manifestations.,COVID-19 produces an acute interstitial pneumonia, usually with a prominent diffuse alveolar damage (DAD) component, often coupled with a thrombotic microangiopathy.,The heart frequently shows acute cardiomyocyte injury and, in some cases, pericarditis and/or myocarditis.,Patients with fatal COVID-19 frequently are obese and have pre-existing cardiac disease, hypertension and/or diabetes mellitus.,This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas.,Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart.,Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles.,Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients.,Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern.,One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia.,Multifocal acute injury of cardiac myocytes was frequently observed.,Lymphocytic myocarditis was reported in 1 case.,In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis.,Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart).,All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2).,Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy. | 1 |
There is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD).,We examined epidemiological characteristics associated with severe disease, then with death.,We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.,Individuals with suspected iRMD-COVID-19 were included in this French cohort.,Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19.,The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method.,The death rate of hospitalised patients with iRMD-COVID-19 (moderate-severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.,Of 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease.,In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05-1.10), female gender (OR=0.45, 95% CI: 0.25-0.80), body mass index (OR=1.07, 95% CI: 1.02-1.12), hypertension (OR=1.86, 95% CI: 1.01-3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09-3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47-29.62) and rituximab (OR=4.21, 95% CI: 1.61-10.98).,Fifty-eight patients died (8% (total) and 23% (hospitalised)).,Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87-2.42) (n=175 each group).,In the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19.,Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19.,Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.,ClinicalTrials.gov Registry (NCT04353609). | COVID-19 outcomes in people with rheumatic diseases remain poorly understood.,The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.,Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020.,Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation.,Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.,A total of 600 cases from 40 countries were included.,Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died.,In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96).,Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively).,Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06).,Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed.,We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease.,Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation. | 1 |
Exosomes (Exo) secreted from hypoxia-conditioned bone marrow mesenchymal stem cells (BM-MSCs) were found to be protective for ischemic disease.,However, the role of exosomal miRNA in the protective effect of hypoxia-conditioned BM-MSCs-derived Exo (Hypo-Exo) remains largely uncharacterized and the poor specificity of tissue targeting of Exo limits their clinical applications.,Therefore, the objective of this study was to examine the effect of miRNA in Hypo-Exo on the repair of ischemic myocardium and its underlying mechanisms.,We further developed modified Hypo-Exo with high specificity to the myocardium and evaluate its therapeutic effects.,Methods: Murine BM-MSCs were subjected to hypoxia or normoxia culture and Exo were subsequently collected.,Hypo-Exo or normoxia-conditioned BM-MSC-derived Exo (Nor-Exo) were administered to mice with permanent condition of myocardial infarction (MI).,After 28 days, to evaluate the therapeutic effects of Hypo-Exo, infarction area and cardio output in Hypo-Exo and Nor-Exo treated MI mice were compared through Masson's trichrome staining and echocardiography respectively.,We utilized the miRNA array to identify the significantly differentially expressed miRNAs between Nor-Exo and Hypo-Exo.,One of the most enriched miRNA in Hypo-Exo was knockdown by applying antimiR in Hypoxia-conditioned BM-MSCs.,Then we performed intramyocardial injection of candidate miRNA-knockdown-Hypo-Exo in a murine MI model, changes in the candidate miRNA's targets expression of cardiomyocytes and the cardiac function were characterized.,We conjugated Hypo-Exo with an ischemic myocardium-targeted (IMT) peptide by bio-orthogonal chemistry, and tested its targeting specificity and therapeutic efficiency via systemic administration in the MI mice.,Results: The miRNA array revealed significant enrichment of miR-125b-5p in Hypo-Exo compared with Nor-Exo.,Administration of miR-125b knockdown Hypo-Exo significantly increased the infarction area and suppressed cardiomyocyte survival post-MI.,Mechanistically, miR-125b knockdown Hypo-Exo lost the capability to suppress the expression of the proapoptotic genes p53 and BAK1 in cardiomyocytes.,Intravenous administration of IMT-conjugated Hypo-Exo (IMT-Exo) showed specific targeting to the ischemic lesions in the injured heart and exerted a marked cardioprotective function post-MI.,Conclusion: Our results illustrate a new mechanism by which Hypo-Exo-derived miR125b-5p facilitates ischemic cardiac repair by ameliorating cardiomyocyte apoptosis.,Furthermore, our IMT- Exo may serve as a novel drug carrier that enhances the specificity of drug delivery for ischemic disease. | Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI).,After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely.,In humans, EV number correlated closely with the extent of myocardial injury.,We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI.,Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1-positive EV release.,Injected EC-EVs localized to the spleen and interacted with, and mobilized, splenic monocytes in otherwise naive, healthy animals.,Analysis of human plasma EV-associated miRNA showed 12 markedly enriched miRNAs after AMI; functional enrichment analyses identified 1,869 putative mRNA targets, which regulate relevant cellular functions (e.g., proliferation and cell movement).,Furthermore, gene ontology termed positive chemotaxis as the most enriched pathway for the miRNA-mRNA targets.,Among the identified EV miRNAs, EC-associated miRNA-126-3p and -5p were highly regulated after AMI. miRNA-126-3p and -5p regulate cell adhesion- and chemotaxis-associated genes, including the negative regulator of cell motility, plexin-B2.,EC-EV exposure significantly downregulated plexin-B2 mRNA in monocytes and upregulated motility integrin ITGB2.,These findings identify EVs as a possible novel signaling pathway by linking ischemic myocardium with monocyte mobilization and transcriptional activation following AMI.,Acute myocardial infarction elevates circulating endothelial cell-derived extracellular vesicles, which can mobilize monocytes from the spleen and alter transcription. | 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. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
Supplemental Digital Content is available in the text.,Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD).,It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter.,LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue.,We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD.,Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD.,In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls.,Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls.,The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls.,Findings were replicated in a cohort comprising 143 individuals.,This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls.,The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients.,URL: http://www.clinicaltrials.gov.,Unique identifier: NCT02176941. | Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease.,Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type.,The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation.,The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques.,Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR.,Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype.,Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes.,On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture.,Our results substantiate an important role of SMCs in carotid atheroma plaque disruption. | 1 |
To assess the diagnostic and prognosis value of myocardial native T2 measurement in the distinction between Light-chain (AL) and Transthyretin (ATTR) cardiac amyloidosis (CA).,Forty-four patients with CA (24 AL; 20 ATTR) and 40 healthy subjects underwent 1.5 T cardiovascular magnetic resonance (CMR).,They all underwent T1 and T2 mapping (modified Look-Locker inversion recovery), cine and late gadolinium enhancement (LGE) imaging.,The Query Amyloid Late Enhancement (QALE) score, myocardial native T2, T1 and extra cellular volume fraction (ECV) were calculated for all patients.,Of the 44 patients, 36 (82%) exhibited enhancement on LGE images.,Mean QALE score of AL (7.9 ± 6) and ATTR (10.5 ± 5) patients were similar (p = 0.6).,Myocardial native T2 was significantly (p < 0.0001) higher in AL (63.2 ± 4.7 ms) than in ATTR (56.2 ± 3.1 ms) patients, and both higher (p < 0.001) than healthy subjects (51.1 ± 3.1 ms).,Myocardial native T2 was highly correlated with myocardial native T1 (Spearman’s rho = 0.79; p < 0.001) and exhibited higher diagnostic performance than T1 to separate AL and ATTR patients: the area under curve (AUC) of T2 was 0.94 (95% CI: 0.86-1, p < 0.001) and the AUC of T1 was 0.77 (95% CI: 0.62-0.91, p = 0.03).,Myocardial native T2 did not impact overall survival in patients (HR 1.03 (0.94-1.12); p = 0.53) in contrast to ECV that was the best predictor of outcome (HR 1.66 per 0.1 increase in ECV (1.24-2.22); p = 0.0006).,Myocardial native T2 significantly is increased in CA, especially in AL patients in comparison to ATTR patients.,Myocardial native T2 does not impact survival in CA patients in contrast to ECV that was the best predictor of outcome.,Trial Registration and unique number: CNIL cardio 1778041.,Date of registration: 20 December 2012. | While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%.,Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy.,However, prognostic implications of T2 values in this cohort are unknown.,The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC.,We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations.,A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure.,Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation.,A follow-up after 11 ± 7 months was performed in 98% of the patients.,Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time.,During acute disease, elevated global T2 time (odds ratio 6.3, p < 0.02) as well as myocardial fraction with T2 time >80 ms (odds ratio 4.9, p < 0.04) predicted occurrence of the combined endpoint.,Patients with clinical recovery revealed significantly decreased T2 relaxation times at follow-up examinations; however, T2 values were still elevated compared to healthy controls.,Assessment of myocardial T2 relaxation times at initial presentation facilitates CMR-based risk stratification in patients with acute myocarditis.,T2 Mapping may emerge as a new tool to monitor inflammatory myocardial injuries during the course of disease. | 1 |
Background: In May 2021, the U.S.,Food and Drug Administration expanded the Emergency Use Authorization for the Pfizer-BioNTech mRNA Coronavirus disease 2019 (COVID-19) Vaccine (BNT162b2) to include adolescents 12-15 years of age.,As vaccine administration continues to increase, potential adverse outcomes, to include myocarditis, are being reported to the Vaccine Adverse Event Reporting System.,Case Report: This case report describes a 17-year-old male patient who developed focal myocarditis mimicking an ST-segment elevation myocardial infarction (STEMI) 3 days after administration of an mRNA COVID-19 vaccine.,Why Should an Emergency Physician Be Aware of This?,Myocarditis is a rare complication in adolescents receiving mRNA COVID-19 vaccines.,Focal myocarditis may demonstrate localizing electrocardiographic changes consistent with a STEMI.,Overall, complications of the mRNA COVID-19 vaccines are extremely rare.,The vaccine continues to be recommended by public health experts, as the benefits of vaccinations greatly outweigh the rare side effects. | 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 |
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. | 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 |
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. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
To investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls.,SARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination.,The CMR protocol contained sequences to assess structural, functional and tissue-specific data.,One hundred forty-seven athletes (94 male, median 23, IQR 20-28 years) after SARS-CoV-2 infection were included.,Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1).,Only two (1.4%) athletes presented with definite signs of myocarditis.,We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls.,There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups.,Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05).,However, T1 mapping values remained below the cut-off point for most patients.,Among 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%.,Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values. | This cohort study assesses the prevalence of myocarditis in athletes with COVID-19 and compares screening strategies for safe return to play.,What is the prevalence of myocarditis in competitive athletes after COVID-19 infection, and how would different approaches to screening affect detection?,In this cohort study of 1597 US competitive collegiate athletes undergoing comprehensive cardiovascular testing, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.,Screening with cardiovascular magnetic resonance imaging increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4 to 2.3%.,These cardiac magnetic resonance imaging findings provide important data on the prevalence of clinical and subclinical myocarditis in college athletes recovering from symptomatic and asymptomatic COVID-19 infections.,Myocarditis is a leading cause of sudden death in competitive athletes.,Myocardial inflammation is known to occur with SARS-CoV-2.,Different screening approaches for detection of myocarditis have been reported.,The Big Ten Conference requires comprehensive cardiac testing including cardiac magnetic resonance (CMR) imaging for all athletes with COVID-19, allowing comparison of screening approaches.,To determine the prevalence of myocarditis in athletes with COVID-19 and compare screening strategies for safe return to play.,Big Ten COVID-19 Cardiac Registry principal investigators were surveyed for aggregate observational data from March 1, 2020, through December 15, 2020, on athletes with COVID-19.,For athletes with myocarditis, presence of cardiac symptoms and details of cardiac testing were recorded.,Myocarditis was categorized as clinical or subclinical based on the presence of cardiac symptoms and CMR findings.,Subclinical myocarditis classified as probable or possible myocarditis based on other testing abnormalities.,Myocarditis prevalence across universities was determined.,The utility of different screening strategies was evaluated.,SARS-CoV-2 by polymerase chain reaction testing.,Myocarditis via cardiovascular diagnostic testing.,Representing 13 universities, cardiovascular testing was performed in 1597 athletes (964 men [60.4%]).,Thirty-seven (including 27 men) were diagnosed with COVID-19 myocarditis (overall 2.3%; range per program, 0%-7.6%); 9 had clinical myocarditis and 28 had subclinical myocarditis.,If cardiac testing was based on cardiac symptoms alone, only 5 athletes would have been detected (detected prevalence, 0.31%).,Cardiac magnetic resonance imaging for all athletes yielded a 7.4-fold increase in detection of myocarditis (clinical and subclinical).,Follow-up CMR imaging performed in 27 (73.0%) demonstrated resolution of T2 elevation in all (100%) and late gadolinium enhancement in 11 (40.7%).,In this cohort study of 1597 US competitive athletes with CMR screening after COVID-19 infection, 37 athletes (2.3%) were diagnosed with clinical and subclinical myocarditis.,Variability was observed in prevalence across universities, and testing protocols were closely tied to the detection of myocarditis.,Variable ascertainment and unknown implications of CMR findings underscore the need for standardized timing and interpretation of cardiac testing.,These unique CMR imaging data provide a more complete understanding of the prevalence of clinical and subclinical myocarditis in college athletes after COVID-19 infection.,The role of CMR in routine screening for athletes safe return to play should be explored further. | 1 |
In response to the COVID-19 pandemic in Detroit, an earlier termination of resuscitation protocol was initiated in March 2020.,To characterize pre-hospital cardiac arrest careduring COVID-19 in Detroit, we analyzed out-of-hospital cardiac arrest (OHCA) rate of ROSC (return of spontaneous circulation) and patient characteristics before and during the COVID-19 pandemic.,OHCA data was analyzed between March 10th, 2020 - April 30th, 2020 and March 10th, 2019 - April 30th, 2019.,ROSC, patient demographics, arrest location, initial rhythms, bystander CPR and field termination were compared before and during the pandemic.,Descriptive statistics were utilized to compare arrest characteristics between years, and the odds of achieving vs. not achieving ROSC. 2020 vs. 2019 as a predictor for ROSC was assessed with logistic regression.,471 patients were included.,Arrests increased to 291 during the pandemic vs. 180 in 2019 (62% increase).,Age (mean difference + 6; 95% CI: +2.4 to +9.5), arrest location (nursing home OR = 2.42; 95% CI: 1.42-4.31; public place OR = 0.47; 95% CI: 0.25-0.88), BLS response (OR = 0.68; 95% CI: 0.47-0.99), and field termination of resuscitation (OR = 2.36; 95% CI: 1.36-4.07) differed significantly in 2020 compared to 2019.,No significant difference was found in the confounder-adjusted odds of ROSC in 2020 vs 2019 (OR = 0.61; 95% CI: 0.34-1.11).,OHCA increased by 62% during COVID-19 in Detroit, without a significant change in prehospital ROSC.,The rate of ROSC remained similar despite the implementation of an early termination of resuscitation protocol in response to COVID-19. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
Neuroinflammation occurs immediately after stroke onset in the ischemic infarct, but whether neuroinflammation occurs in remote regions supporting plasticity and functional recovery remains unknown.,We used advanced imaging to quantify whole-brain diapedesis of B cells, an immune cell capable of producing neurotrophins.,We identify bilateral B cell diapedesis into remote regions, outside of the injury, that support motor and cognitive recovery in young male mice.,Poststroke depletion of B cells confirms a positive role in neurogenesis, neuronal survival, and recovery of motor coordination, spatial learning, and anxiety.,More than 80% of stroke survivors have long-term disability uniquely affected by age and lifestyle factors.,Thus, identifying beneficial neuroinflammation during long-term recovery increases the opportunity of therapeutic interventions to support functional recovery.,Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury.,B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery.,B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice.,Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation.,Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery.,Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets.,To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo.,These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab.,B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival.,Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery.,Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain. | Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial.,The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments.,Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD −/− mice and Rag1 −/− mice 24 h after adoptive B cell transfer.,Stroke outcome was assessed at days 1 and 3.,Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated.,The local inflammatory response was determined by real-time PCR and immunohistochemistry.,Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot.,Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke.,Additionally, lack of circulating B cells in JHD −/− mice also failed to influence stroke outcome at days 1 and 3.,Furthermore, reconstitution of Rag1 −/− mice with B cells had no influence on infarct volumes.,Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase.,Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke.,The online version of this article (doi:10.1186/s12974-017-0890-x) contains supplementary material, which is available to authorized users. | 1 |
Recent reports have suggested that patients with heart failure (HF) have an altered gut microbiota composition; however, associations with diet remain largely uninvestigated.,We aimed to explore differences in the gut microbiota between patients with HF with reduced ejection fraction and healthy controls, focusing on associations with diet and disease severity.,The microbiota composition of two cross‐sectional cohorts (discovery, n = 40 and validation, n = 44) of patients with systolic HF and healthy controls (n = 266) was characterized by sequencing of the bacterial 16S rRNA gene.,The overall microbial community (beta diversity) differed between patients with HF and healthy controls in both cohorts (P < 0.05).,Patients with HF had shifts in the major bacterial phyla, resulting in a lower Firmicutes/Bacteroidetes (F/B) ratio than controls (P = 0.005).,Patients reaching a clinical endpoint (listing for heart transplant or death) had lower bacterial richness and lower F/B ratio than controls (P < 0.01).,Circulating levels of trimethylamine‐N‐oxide were associated with meat intake (P = 0.016), but not with gut microbiota alterations in HF.,Low bacterial richness and low abundance of several genera in the Firmicutes phylum were associated with low fibre intake.,The gut microbiota in HF was characterized by decreased F/B ratio and reduced bacterial diversity associated with clinical outcome.,The gut microbiota alterations in HF were partly related to low fibre intake, emphasizing the importance of diet as a covariate in future studies.,Our data could provide a rationale for targeting the gut microbiota in HF with high‐fibre diet. | Supplemental Digital Content is available in the text.,Arterial hypertension and its organ sequelae show characteristics of T cell-mediated inflammatory diseases.,Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage.,Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk.,The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health.,Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis.,Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage.,To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout-deficient mice received propionate (200 mmol/L) or control in the drinking water.,To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg-1·d-1 subcutaneous) for 14 days.,To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg-1·d-1 subcutaneous) for 28 days.,Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry.,Blood pressure was measured by radiotelemetry.,Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate.,Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models.,Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II-infused wild-type NMRI mice.,Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout-deficient mice.,Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice.,Cardioprotective effects of propionate were abrogated in regulatory T cell-depleted angiotensin II-infused mice, suggesting the effect is regulatory T cell-dependent.,Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health.,The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease. | 1 |
The COVID-19 pandemic has resulted in excess mortality due to both COVID-19 directly and other conditions, including cardiovascular (CV) disease.,We aimed to explore the excess in-hospital mortality, unrelated to COVID-19 infection, across a range of CV diseases.,A systematic search was performed for studies investigating in-hospital mortality among patients admitted with CV disease without SARS-CoV-2 infection compared with a period outside the COVID-19 pandemic.,Fifteen studies on 27 421 patients with CV disease were included in the analysis.,The average in-hospital mortality rate was 10.4% (n = 974) in the COVID-19 group and 5.7% (n = 1026) in the comparator group.,Compared with periods outside the COVID-19 pandemic, the pooled risk ratio (RR) demonstrated increased in-hospital mortality by 62% during COVID-19 [95% confidence interval (CI) 1.20-2.20, P = 0.002].,Studies with a decline in admission rate >50% during the COVID-19 pandemic observed the greatest increase in mortality compared with those with <50% reduction [RR 2.74 (95% CI 2.43-3.10) vs.,1.21 (95% CI 1.07-1.37), P < 0.001].,The observed increased mortality was consistent across different CV conditions (P = 0.74 for interaction).,In-hospital mortality among patients admitted with CV diseases was increased relative to periods outside the pandemic, independent of co-infection with COVID-19.,This effect was larger in studies with the biggest decline in admission rates, suggesting a sicker cohort of patients in this period.,However, studies were generally poorly conducted, and there is a need for further well-designed studies to establish the full extent of mortality not directly related to COVID-19 infection. | 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. | 1 |
Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection predisposes patients to arterial and venous thrombosis.,This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease‐2019 (COVID‐19).,We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases to identify cases of COVID‐19-associated CVT.,The search period spanned 1 January 2020 to 1 December 2020, and the review protocol (PROSPERO‐CRD42020214327) followed Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines.,Identified studies were evaluated for bias using the Newcastle‐Ottawa scale.,A proportion meta‐analysis was performed to estimate the frequency of CVT among hospitalized COVID‐19 patients.,We identified 57 cases from 28 reports.,Study quality was mostly classified as low.,CVT symptoms developed after respiratory disease in 90%, and the mean interval was 13 days.,CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37%, and parenchymal hemorrhage was found in 42%.,Predisposing factors for CVT beyond SARS‐CoV‐2 infection were present in 31%.,In‐hospital mortality was 40%.,Using data from 34,331 patients, the estimated frequency of CVT among patients hospitalized for SARS‐CoV‐2 infection was 0.08% (95% confidence interval [CI]: 0.01-0.5).,In an inpatient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID‐19 (cohort of 406 patients, 95% CI: 1.47-11.39).,Cerebral venous thrombosis in the context of SARS‐CoV‐2 infection is a rare, although there seems to be an increased relative risk.,High suspicion is necessary, because the diagnosis of this potentially life‐threatening condition in COVID‐19 patients can be challenging.,Evidence is still scarce on the pathophysiology and potential prevention of COVID‐19-associated CVT.,Cerebral venous thrombosis can happen in patients with severe acute respiratory syndrome coronavirus‐2 infection.,Early diagnosis and proper management are paramount, as it is associated with high mortality. | With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19. | 1 |
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