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in category cardiovascular medicine

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1: The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin
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Posted 03 Apr 2020

The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin
27,179 downloads medRxiv cardiovascular medicine

Ehud Chorin, Matthew Dai, Eric Shulman, Lalit Wadhwani, Roi-Bar-Cohen, Chirag Barbhaiya, Anthony Aizer, Douglas Holmes, Scott Bernstein, Michael Spinelli, David S Park, Larry A. Chinitz, Lior Jankelson

We report the change in the QT interval in 84 adult patients with SARS-CoV-2 infection treated with Hydroxychloroquine/Azithromycin combination. QTc prolonged maximally from baseline between days 3 and 4. in 30% of patients QTc increased by greater than 40ms. In 11% of patients QTc increased to >500 ms, representing high risk group for arrhythmia. The development of acute renal failure but not baseline QTc was a strong predictor of extreme QTc prolongation.

2: mRNA COVID-19 Vaccination and Development of CMR-confirmed Myopericarditis
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Posted 16 Sep 2021

mRNA COVID-19 Vaccination and Development of CMR-confirmed Myopericarditis
22,413 downloads medRxiv cardiovascular medicine

Tahir Kafil, Mariana M Lamacie, Sophie Chenier, Heather Taggart, Nina Ghosh, Alexander Dick, Gary Small, Peter Liu, Rob S Beanlands, Lisa Mielniczuk, David Birnie, Andrew M Crean

IntroductionSeveral case reports or small series have suggested a possible link between mRNA COVID vaccines and the subsequent development of myocarditis and pericarditis. This study is a prospective collection and review of all cases with a myocarditis/pericarditis diagnosis over a 2-month period at an academic medical center. MethodsProspective case series from 1st June 2021 until 31st July 2021. Patients were identified by admission and discharge diagnoses which included myocarditis or pericarditis. Inclusion criteria: in receipt of mRNA vaccine within one month prior to presentation; The CMR protocol included cine imaging, native T1 and T2 mapping, late gadolinium enhancement and post contrast T1 mapping. All CMR studies were read in consensus by two experienced readers. Diagnosis was based on clinical presentation, ECG/echo findings and serial troponins and was confirmed in each case by CMR. Incidence was estimated from total doses of mRNA vaccine administered in the Ottawa region for the matching time-period. This data was obtained from the Public Health Agency of Ottawa. Results32 patients were identified over the period of interest. Eighteen patients were diagnosed with myocarditis; 12 with myopericarditis; and 2 with pericarditis alone. The median age was 33 years (18-65 years). The sex ratio was 2 females to 29 males. In 5 cases, symptoms developed after only a single dose of mRNA vaccine. In 27 patients, symptoms developed after their second dose of. Median time between vaccine dose and symptoms was 1.5 days (1-26 days). Chest pain was the commonest symptom, but many others were reported. Non-syncopal non-sustained ventricular tachycardia was seen in only a single case. Median LV ejection fraction (EF) was 57% (44-66%). Nine patients had an LVEF below the normal threshold of 55%. Incidence of myopericarditis overall was approximately 10 cases for every 10,000 inoculations. Summary and ConclusionsThis is the largest series in the literature to clearly relate the temporal relationship between mRNA COVID vaccination, symptoms and CMR findings. In most patients, symptom onset began within the first few days after vaccination with corresponding abnormalities in biomarkers and on ECG. Cardiac MRI confirmed acute myocardial and pericardial changes with the presence of edema demonstrated with both tissue mapping and late gadolinium enhancement. Symptoms settled quickly with standard therapy and patients were discharged within a few days. No major adverse cardiac events and no significant arrythmias were noted during inpatient stay. Further follow up will be required to ascertain the longer-term outcomes of this patient group.

3: Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers
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Posted 14 Jul 2020

Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers
16,210 downloads medRxiv cardiovascular medicine

Rocio Eiros, Manuel Barreiro-Perez, Ana Martin-Garcia, Julia Almeida, Eduardo Villacorta, Alba Perez-Pons, Soraya Merchan, Alba Torres-Valle, Clara Sanchez-Pablo, David Gonzalez-Calle, Oihane Perez-Escurza, Ines Toranzo, Elena Diaz-Pelaez, Blanca Fuentes-Herrero, Laura Macias-Alvarez, Guillermo Oliva-Ariza, Quentin Lecrevisse, Rafael Fluxa, Jose L Bravo-Grandez, Alberto Orfao, Pedro L Sanchez

Background: Cardiac sequelae of past SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in health-care workers to report evidence of pericarditis and myocarditis after SARS-CoV-2 infection. Methods We studied 139 health-care workers with confirmed past SARS-CoV-2 infection (103 diagnosed by RT-PCR and 36 by serology). Participants underwent clinical assessment, electrocardiography, laboratory tests including immune cell profiling and cardiac magnetic resonance (CMR) imaging. Pericarditis was diagnosed when classical criteria were present, and the diagnosis of myocarditis was based on the updated CMR Lake-Louise-Criteria. Results: Median age was 52 years (IQR 41-57), 100 (72%) were women, and 23 (16%) were previously hospitalized for Covid-19 pneumonia. At examination (10.4 [9.3-11.0] weeks after infection-like symptoms), all participants presented hemodynamic stability. Chest pain, dyspnoea or palpitations were observed in 58 (42%) participants; electrocardiographic abnormalities in 69 (50%); NT-pro-BNP was elevated in 11 (8%); troponin in 1 (1%); and CMR abnormalities in 104 (75%). Isolated pericarditis was diagnosed in 4 (3%) participants, myopericarditis in 15 (11%) and isolated myocarditis in 36 (26%). Participants diagnosed by RT-PCR were more likely to still present symptoms than participants diagnosed by serology (73 [71%] vs 18 [50%]; p=0.027); nonetheless, the prevalence of pericarditis or myocarditis was high in both groups (44 [43%] vs 11 [31%]; p=0.238). Most participants (101 [73%]) showed altered immune cell counts in blood, particularly decreased eosinophil (37 [27%]; p<0.001) and increased CD4-CD8-/loT alpha beta-cell numbers (24 [17%]; p<0.001). Pericarditis was associated with elevated CD4-CD8-/loT alpha beta-cell numbers (p=0.011), while participants diagnosed with myopericarditis or myocarditis had lower (p<0.05) plasmacytoid dendritic cell, NK-cell and plasma cell counts and lower anti-SARS-CoV-2-IgG antibody levels (p=0.027). Conclusions: Pericarditis and myocarditis with clinical stability are frequent long after SARS-CoV-2 infection, even in presently asymptomatic subjects. These observations will probably apply to the general population infected and may indicate that cardiac sequelae might occur late in association with an altered (delayed) innate and adaptative immune response.

4: How to differentiate COVID-19 pneumonia from heart failure with computed tomography at initial medical contact during epidemic period
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Posted 06 Mar 2020

How to differentiate COVID-19 pneumonia from heart failure with computed tomography at initial medical contact during epidemic period
8,847 downloads medRxiv cardiovascular medicine

Zhaowei Zhu, Jianjun Tang, Xiangping Chai, Zhenfei Fang, Qiming Liu, Xinqun Hu, Danyan Xu, Jia He, Liang Tang, Shi Tai, Yuzhi Wu, Shenghua Zhou

OBJECTIVESTo compare chest CT findings in heart failure with those of Corona Virus Disease 2019 (COVID-19) pneumonia. BACKGROUNDDuring epidemic period, chest computed tomography (CT) has been highly recommended for screening patients with suspected COVID-19. However, the comparison of CT imaging between heart failure and COVID-19 pneumonia has not been fully elucidated. METHODSPatients with heart failure (n=12), COVID-19 pneumonia (n=12) and one patient with both diseases were retrospectively enrolled. Clinical information and imaging of chest CT were collected and analyzed. RESULTSThere was no difference of ground glass opacity (GGO), consolidation, crazy paving pattern, lobes affected and septal thickening between heart failure and COVID-19 pneumonia. However, less rounded morphology (8.3% vs. 67%, p=0.003), more peribronchovascular thickening (75% vs. 33%, p=0.041) and fissural thickening (33% vs. 0%, p=0.028), less peripheral distribution (33% vs. 92%, p=0.003) were found in heart failure group than that in COVID-19 group. Importantly, there were also more patients with upper pulmonary vein enlargement (75% vs. 8.3%, p=0.001), subpleural effusion and cardiac enlargement in heart failure group than that in COVID-19 group (50% vs. 0%, p=0.005, separately). Besides, more fibrous lesions were found in COVID-19 group although there was no statistical difference (25% vs. 0%, P=0.064) CONCLUSIONSAlthough there are some overlaps of CT imaging between heart failure and COVID-19, CT is still a useful tool in differentiating COVID-19 pneumonia.

5: Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 patients without clinical signs of cardiac involvement
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Posted 26 Aug 2020

Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 patients without clinical signs of cardiac involvement
7,428 downloads medRxiv cardiovascular medicine

Gaetano Pietro Bulfamante, Gianluca Lorenzo Perrucci, Monica Falleni, Elena Sommariva, Delfina Tosi, Carla Martinelli, Paola Songia, Paolo Poggio, Stefano Carugo, Giulio Pompilio

Background - Cardiovascular complication in patients affected by novel Coronavirus respiratory disease (COVID-19) are increasingly recognized. However, although a cardiac tropism of SARS-CoV-2 for inflammatory cells in autopsy heart samples of COVID-19 patients has been reported, the presence of the virus in cardiomyocytes has not been documented yet. Methods - We investigated for SARS-CoV-2 presence in heart tissue autopsies of 6 consecutive COVID-19 patients deceased for respiratory failure showing no signs of cardiac involvement and with no history of heart disease. Cardiac autopsy samples were analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays. Results - The presence of SARS-CoV-2 into cardiomyocytes was invariably detected. A variable pattern of cardiomyocytes injury was observed, spanning from the absence of cell death and subcellular alterations hallmarks to the intracellular oedema and sarcomere ruptures. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike RNA. Conclusions - In this analysis of autopsy cases, the presence of SARS-CoV-2 into cardiomyocytes, determining variable patterns of intracellular involvement, has been documented. All these findings suggest the need of a cardiologic surveillance even in survived COVID-19 patients not displaying a cardiac phenotype, in order to monitor potential long-term cardiac sequelae.

6: Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in COVID-19
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Posted 26 Jul 2020

Clinical Outcomes With the Use of Prophylactic Versus Therapeutic Anticoagulation in COVID-19
4,986 downloads medRxiv cardiovascular medicine

Jishu K Motta, Rahila O Ogunnaike, Rutvik Shah, Stephanie Stroever, Harold V Cedeno, Shyam K Thapa, John J Chronakos, Eric J Jimenez, Joann Petrini, Abhijith Hegde

Background: This study is the first of its kind to assess the impact of preemptive therapeutic dose anticoagulation on mortality compared to prophylactic anticoagulation among COVID-19 patients. Its findings provide insight to clinicians regarding the management of COVID-19, particularly with the known prothrombotic state. Research Question: To determine the impact of anticoagulation on in-hospital mortality among COVID-19 positive patients with the a priori hypothesis that there would be a lower risk of in-hospital mortality with use of preemptive therapeutic over prophylactic dose enoxaparin or heparin. Study Design and Methods: Study Design: Retrospective cohort study from April 1 - April 25, 2020. The date of final follow-up was June 12, 2020. Setting: Two large, acute care hospitals in Western Connecticut. Participants: Five hundred and one inpatients were identified after discharge as 18 years or older and positive for SARS-CoV-2. The final sample size included 374 patients after applying exclusion criteria. Demographic variables were collected via hospital billing inquiries, while the clinical variables were abstracted from patients medical records. Exposure: Preemptive enoxaparin or heparin at a therapeutic or prophylactic dose. Main Outcome: In-hospital mortality. Results: When comparing preemptive therapeutic to prophylactic anticoagulation through multi-variable analysis, risk of in-hospital mortality was 2.3 times greater in patients receiving preemptive therapeutic anticoagulation (95% CI = 1.0, 4.9; p = 0.04). Interpretation: An increase in in-hospital mortality was observed with preemptive therapeutic anticoagulation. Thus, in the management of COVID-19 and its complications, we recommend further research and cautious use of preemptive therapeutic over prophylactic anticoagulation.

7: Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection
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Posted 24 Apr 2020

Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection
4,781 downloads medRxiv cardiovascular medicine

Anuradha Lala, Kipp W Johnson, Adam J Russak, Ishan Paranjpe, Shan Zhao, Sulaiman Solani, Akhil Vaid, Fayzan Chaudhry, Jessica K De Freitas, Zahi A. Fayad, Sean P Pinney, Matthew Levin, Alexander Charney, Emilia Bagiella, Jagat Narula, Benjamin S Glicksberg, Girish Nadkarni, James Januzzi, Donna M Mancini, Valentin Fuster

Background: The degree of myocardial injury, reflected by troponin elevation, and associated outcomes among hospitalized patients with Coronavirus Disease (COVID-19) in the US are unknown. Objectives: To describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19. Methods: Patients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value <0.03ng/mL) measured within 24 hours of admission were included (n=2,736). Demographics, medical history, admission labs, and outcomes were captured from the hospital EHR. Results: 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. Even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were associated with death (adjusted HR: 1.77, 95% CI 1.39-2.26; P<0.001) while greater amounts (e.g. troponin I>0.09 ng/dL, n=530, 19.4%) were associated with more pronounced risk (adjusted HR 3.23, 95% CI 2.59-4.02). Conclusions: Myocardial injury is prevalent among patients hospitalized with COVID-19, and is associated with higher risk of mortality. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation likely reflects non-ischemic or secondary myocardial injury.

8: Antithrombotic Therapy in COVID-19: Systematic Summary of Ongoing or Completed Randomized Trials
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Posted 06 Jan 2021

Antithrombotic Therapy in COVID-19: Systematic Summary of Ongoing or Completed Randomized Trials
4,363 downloads medRxiv cardiovascular medicine

Azita H. Talasaz, Parham Sadeghipour, Hessam Kakavand, Maryam Aghakouchakzadeh, Elaheh Kordzadeh-Kermani, Benjamin W Van Tassell, Azin Gheymati, Hamid Ariannejad, Seyed Hossein Hosseini, Sepehr Jamalkhani, Michelle Sholzberg, Manuel Monreal, David Jimenez, Gregory Piazza, Sahil A. Parikh, Ajay Kirtane, John W. Eikelboom, Jean M. Connors, Beverley J. Hunt, Stavros V. Konstantinides, Mary Cushman, Jeffrey I. Weitz, Gregg W. Stone, Harlan Krumholz, Gregory YH Lip, Samuel Z. Goldhaber, Behnood Bikdeli

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiologic features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and critically-ill patients with COVID-19. This manuscript provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.

9: Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children
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Posted 07 Oct 2021

Comparison of MIS-C Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine related Myocarditis in Children
4,202 downloads medRxiv cardiovascular medicine

Trisha Patel, Michael Kelleman, Zachary West, Andrew Peter, Matthew Dove, Arene Butto, Matthew Oster

Background: Although rare, myocarditis in the pediatric population is a disease process that carries significant morbidity and mortality. Prior to the SARS-CoV-2 related (COVID-19) pandemic, enteroviruses were the most common cause of classic myocarditis. However, since 2020, myocarditis linked to multisystem inflammatory syndrome in children (MIS-C) is now common. In recent months, myocarditis related to COVID-19 vaccines has also been described. This study aims to compare these three different types of myocarditis with regards to clinical presentation, course, and outcomes. Methods: In this retrospective cohort study, we included all patients <21 years of age hospitalized at our institution with classic viral myocarditis from 2015-2019, MIS-C myocarditis from 3/2020-2/2021 and COVID-19 vaccine-related myocarditis from 5/2021-6/2021. We compared demographics, initial symptomatology, treatment, laboratory data, and echocardiogram findings. Results: Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had COVID-19 vaccine-related myocarditis. Peak troponin was highest in the classic myocarditis group, whereas the MIS-C myocarditis group had the highest recorded brain natriuretic peptide (BNP). There were significant differences in time to recovery of normal left ventricular ejection fraction (LVEF) for the three groups: nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with COVID-19 vaccine-related myocarditis (n=9, 100%) had normal LVEF at the time of discharge, but a lower proportion of the classic myocarditis group (n=30, 70%) had a normal LVEF at discharge (p<0.001). Three months post-discharge, 18 of 40 children (45%) in the classic myocarditis group still required heart failure treatment, whereas only one of the MIS-C myocarditis patients and none of the COVID-19 vaccine-associated myocarditis patients did. Conclusions: Compared to those with classic myocarditis, those with MIS-C myocarditis had more significant hematologic derangements and worse inflammation at presentation, but had better clinical outcomes, including rapid recovery of cardiac function. Patients with COVID-19 vaccine-related myocarditis had similar clinical presentation to patients with classic myocarditis, but their pattern of recovery was similar to those with MIS-C, with prompt resolution of symptoms and improvement of cardiac function. Long-term follow-up should focus on cardiac and non-cardiac consequences of myocarditis associated with COVID-19 illness and vaccination. Key Words: MIS-C, myocarditis, COVID-19, mRNA vaccine

10: Risk of Cardiovascular Events after Covid-19: a double-cohort study
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Posted 29 Dec 2021

Risk of Cardiovascular Events after Covid-19: a double-cohort study
3,735 downloads medRxiv cardiovascular medicine

Larisa G Tereshchenko, Adam Bishop, Nora Fisher-Campbell, Jacqueline Levene, Craig Morris, Hetal Patel, Erynn Beeson, Jessica Blank, J.G. Bradner, Michelle Coblens, Jacob Corpron, Jenna Davison, Kathleen Denny, Mary Earp, Simeon Florea, Howard Freeman, Olivia Fuson, Florian Guillot, Kazi Haq, Jessica Hyde, Ayesha Khader, Clinton Kolseth, Morris Kim, Olivia Krol, Lisa Lin, Liat Litwin, Aneeq Malik, Evan Mitchell, Aman Mohapatra, Cassandra Mullen, Chad Nix, Ayodele Oyeyemi, Christine Rutlen, Lisa Corley-Stampke, Ashley Tam, Inga Van Buren, Jessica Wallace, Akram Khan

Objective: To determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular events and all-cause mortality. Methods: We conducted a retrospective double-cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection [COVID-19(+) cohort] and its documented absence [COVID-19(-) cohort]. The study investigators drew a simple random sample of records from all Oregon Health & Science University (OHSU) Healthcare patients (N=65,585) with available COVID-19 test results, performed 03.01.2020 - 09.13.2020. Exclusion criteria were age < 18y and no established OHSU care. The primary outcome was a composite of cardiovascular morbidity and mortality. All-cause mortality was the secondary outcome. Results: The study population included 1355 patients (mean age 48.7 {+/-} 20.5 y; 770(57%) female, 977(72%) white non-Hispanic; 1072(79%) insured; 563(42%) with cardiovascular disease (CVD) history). During a median 6 months at risk, the primary composite outcome was observed in 38/319 (12%) COVID-19(+) and 65/1036 (6%) COVID-19(-) patients (p=0.001). In Cox regression adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk of the primary composite outcome (HR 1.71; 95%CI 1.06-2.78; p=0.029). Inverse-probability-weighted estimation, conditioned for 31 covariates, showed that for every COVID-19(+) patient, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19(-): average treatment effect on the treated -65.5 (95%CI -125.4 to -5.61) days; p=0.032. Conclusions: Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.

11: The association of cardiovascular disease and other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis
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Posted 14 May 2020

The association of cardiovascular disease and other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis
3,684 downloads medRxiv cardiovascular medicine

Paddy Ssentongo, Anna E Ssentongo, Emily S. Heilbrunn, Djibril M Ba, Vernon M. Chinchilli

Background Exploring the association of coronavirus-2019 disease (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic to optimize survival. The objective of this systematic review and meta-analysis is to explore the association of pre-existing conditions with COVID-19 mortality. Methods We searched MEDLINE, OVID databases, SCOPUS, and medrxiv.org for the period December 1, 2019, to May 1, 2020. The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions. Comorbidities explored were cardiovascular diseases (coronary artery disease, hypertension, cardiac arrhythmias, and congestive heart failure), chronic obstructive pulmonary disease, type 2 diabetes, cancer, chronic kidney disease, chronic liver disease, and stroke. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Results Ten chronic conditions from 19 studies were included in the meta-analysis (n = 61,455 patients with COVID-19; mean age, 61 years; 57% male). Overall the between-study study heterogeneity was medium and studies had low publication bias and high quality. Coronary heart disease, hypertension, congestive heart failure, and cancer significantly increased the risk of mortality from COVID-19. The risk of mortality from COVID-19 in patients with coronary heart disease was 2.4 times as high as those without coronary heart disease (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension as high as that compared to those without hypertension (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure were at 2.5 times the risk of mortality compared to those without congestive heart failure (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions COVID-19 patients with all any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer have an increased risk of mortality. Tailored infection prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.

12: Interpretable AI for beat-to-beat cardiac function assessment
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Posted 25 Nov 2019

Interpretable AI for beat-to-beat cardiac function assessment
3,559 downloads medRxiv cardiovascular medicine

David Ouyang, Bryan He, Amirata Ghorbani, Curt P. Langlotz, Paul A. Heidenreich, Robert A. Harrington, David H. Liang, Euan A. Ashley, James Y. Zou

Accurate assessment of cardiac function is crucial for diagnosing cardiovascular disease1, screening for cardiotoxicity2,3, and deciding clinical management in patients with critical illness4. However human assessment of cardiac function focuses on a limited sampling of cardiac cycles and has significant interobserver variability despite years of training2,5,6. To overcome this challenge, we present the first beat-to-beat deep learning algorithm that surpasses human expert performance in the critical tasks of segmenting the left ventricle, estimating ejection fraction, and assessing cardiomyopathy. Trained on echocardiogram videos, our model accurately segments the left ventricle with a Dice Similarity Coefficient of 0.92, predicts ejection fraction with mean absolute error of 4.1%, and reliably classifies heart failure with reduced ejection fraction (AUC of 0.97). Prospective evaluation with repeated human measurements confirms that our model has less variance than experts. By leveraging information across multiple cardiac cycles, our model can identify subtle changes in ejection fraction, is more reproducible than human evaluation, and lays the foundation for precise diagnosis of cardiovascular disease. As a new resource to promote further innovation, we also make publicly available one of the largest medical video dataset of over 10,000 annotated echocardiograms. Key PointsO_LIVideo based deep learning evaluation of cardiac ultrasound accurately identifies cardiomyopathy and predict ejection fraction, the most common metric of cardiac function. C_LIO_LIUsing human tracings obtained during standard clinical workflow, deep learning semantic segmentation accurately labels the left ventricle frame-by-frame, including in frames without prior human annotation. C_LIO_LIComputational cardiac function analysis allows for beat-by-beat assessment of ejection fraction, which more accurately assesses cardiac function in patients with atrial fibrillation, arrhythmias, and heart rate variability. C_LI

13: Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia
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Posted 27 Feb 2020

Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia
3,459 downloads medRxiv cardiovascular medicine

Hui Hui, Yingqian Zhang, Xin Yang, Xi Wang, Bingxi He, Li Li, Hongjun Li, Jie Tian, Yundai Chen

ObjectiveTo investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia. MethodsIn this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients. ConclusionOur results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.

14: Classification of 12-lead ECGs: the PhysioNet/Computing in Cardiology Challenge 2020
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Posted 14 Aug 2020

Classification of 12-lead ECGs: the PhysioNet/Computing in Cardiology Challenge 2020
3,352 downloads medRxiv cardiovascular medicine

Erick A. Perez Alday, Annie Gu, Amit Shah, Chad Robichaux, An-Kwok Ian Wong, Chengyu Liu, Feifei Liu, Ali Bahrami Rad, Andoni Elola, Salman Seyedi, Qiao Li, Ashish Sharma, Gari D Clifford, Matthew A Reyna

The subject of the PhysioNet/Computing in Cardiology Challenge 2020 was the identification of cardiac abnormalities in 12-lead electrocardiogram (ECG) recordings. A total of 66,405 recordings were sourced from hospital systems from four distinct countries and annotated with clinical diagnoses, including 43,101 annotated recordings that were posted publicly. For this Challenge, we asked participants to design working, open-source algorithms for identifying cardiac abnormalities in 12-lead ECG recordings. This Challenge provided several innovations. First, we sourced data from multiple institutions from around the world with different demographics, allowing us to assess the generalizability of the algorithms. Second, we required participants to submit both their trained models and the code for reproducing their trained models from the training data, which aids the generalizability and reproducibility of the algorithms. Third, we proposed a novel evaluation metric that considers different misclassification errors for different cardiac abnormalities, reflecting the clinical reality that some diagnoses have similar outcomes and varying risks. Over 200 teams submitted 850 algorithms (432 of which successfully ran) during the unofficial and official phases of the Challenge, representing a diversity of approaches from both academia and industry for identifying cardiac abnormalities. The official phase of the Challenge is ongoing.

15: Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 mediated myocarditis
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Posted 14 Apr 2020

Myocyte Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2 mediated myocarditis
2,669 downloads medRxiv cardiovascular medicine

Nathan R Tucker, Mark D. Chaffin, Kenneth C Bedi, Irinna Papangeli, Amer-Denis Akkad, Alessandro Arduini, Sikander Hayat, Gokcen Eraslan, Christoph Muus, Roby Paul Bhattacharyya, Christian M Stegmann, Human Cell Atlas Lung Biological Network, Kenneth Margulies, Patrick T. Ellinor

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 infection of host cells occurs predominantly via binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. Hypertension and pre-existing cardiovascular disease are risk factors for morbidity from COVID-19, and it remains uncertain whether the use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) impacts infection and disease. Here, we aim to shed light on this question by assessing ACE2 expression in normal and diseased human myocardial samples profiled by bulk and single nucleus RNA-seq.

16: Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection
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Posted 04 Apr 2022

Cardiac impairment in Long Covid 1-year post-SARS-CoV-2 infection
2,623 downloads medRxiv cardiovascular medicine

Adriana Roca-Fernandez, Malgorzata Wamil, Alison Telford, Valentina Carapella, Alessandra Borlotti, David Monteiro, Helena Thomaides-Brears, Matthew D Kelly, Andrea Dennis, Rajarshi Banerjee, Matthew Robson, Michael Brady, Gregory Lip, Sacha Bull, Melissa J Heightman, Ntobeko Ntusi, Amitava Banerjee

Background Long Covid is associated with multiple symptoms and impairment in multiple organs. Cardiac impairment has been reported to varying degrees by varying methodologies in cross-sectional studies. Using cardiac magnetic resonance (CMR), we investigated the 12-month trajectory of cardiac impairment in individuals with Long Covid. Methods 534 individuals with Long Covid underwent baseline CMR (T1 and T2 mapping, cardiac mass, volumes, function, and strain) and multi-organ MRI at 6 months (IQR 4.3,7.3) since first post-COVID-19 symptoms and 330 were rescanned at 12.6 (IQR 11.4, 14.2) months if abnormal findings were reported at baseline. Symptoms, standardised questionnaires, and blood samples were collected at both timepoints. Cardiac impairment was defined as one or more of: low left or right ventricular ejection fraction (LVEF and RVEF), high left or right ventricular end diastolic volume (LVEDV and RVEDV), low 3D left ventricular global longitudinal strain (GLS), or elevated native T1 in [&ge;]3 cardiac segments. A significant change over time was reported by comparison with 92 healthy controls. Results The technical success of this multiorgan assessment in non-acute settings was 99.1% at baseline, and 98.3% at follow up, with 99.6% and 98.8% for CMR respectively. Of individuals with Long Covid, 102/534 [19%] had cardiac impairment at baseline; 71/102 had complete paired data at 12 months. Of those, 58% presented with ongoing cardiac impairment at 12 months. High sensitivity cardiac troponin I and B-type natriuretic peptide were not predictive of CMR findings, symptoms, or clinical outcomes. At baseline, low LVEF, high RVEDV and low GLS were associated with cardiac impairment. Low LVEF at baseline was associated with persistent cardiac impairment at 12 months. Conclusion Cardiac impairment, other than myocarditis, is present in 1 in 5 individuals with Long Covid at 6 months, persisting in over half of those at 12 months. Cardiac-related blood biomarkers are unable to identify cardiac impairment in Long COVID. Subtypes of disease (based on symptoms, examination, and investigations) and predictive biomarkers are yet to be established. Interventional trials with pre-specified subgroup analyses are required to inform therapeutic options.

17: Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study
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Posted 24 Mar 2020

Myocardial injury is associated with in-hospital mortality of confirmed or suspected COVID-19 in Wuhan, China: A single center retrospective cohort study
2,443 downloads medRxiv cardiovascular medicine

Fan Zhang, Deyan Yang, Jing Li, Peng Gao, Taibo Chen, Zhongwei Cheng, Kangan Cheng, Quan Fang, Wan Pan, Chunfeng Yi, Hongru Fan, Yonghong Wu, Liwei Li, Yong Fang, Juan Liu, Guowei Tian, Liqun He

BackgroundSince December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce. ObjectivesTo investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19. MethodsDemographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25th December, 2019 to 15th February, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death. ResultsA total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58{+/-}13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was elevated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality. ConclusionsCardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2 could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.

18: Self-reported Morisky 8 item medication adherence scale to statins concords with pill count method and correlates with serum lipid profile parameters and Serum HMGCoA Reductase levels
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Posted 23 Sep 2019

Self-reported Morisky 8 item medication adherence scale to statins concords with pill count method and correlates with serum lipid profile parameters and Serum HMGCoA Reductase levels
2,274 downloads medRxiv cardiovascular medicine

Abhinav Grover, Mansi Oberoi, Harmeet Rehan, Lalit Gupta, Madhur Yadav

BackgroundIt is imperative that non-compliance to statins be identified and addressed to optimize the clinical benefit of statins. Patient self-reporting methods are convenient to apply in clinical practice but need to be validated. ObjectiveWe studied the concordance of a patient self-report method, MMAS (Morisky eight item medication adherence scale) with pill count method in measuring adherence to statins and their correlation with extended lipid profile parameters and serum HMGCoA-R (hydroxymethylglutaryl coenzyme A reductase) enzyme levels. MethodsMMAS and pill count method were used to measure the adherence to statins in patients on statins for any duration. Patients were subjected to estimation of extended lipid profile and serum HMGCoA-R levels at the end of 3 months follow-up. ResultsOut of a total of 200 patients included in the study, 117 patients had low adherence (score less than 6 on MMAS) whereas 65 and 18 patients had medium (score 6 to less than 8) and high adherence (score of 8) respectively. Majority of patients who had low adherence to statins by MMAS were nonadherent by pill count method yielding concordance of 96.5%. Medium or high adherence to statins by MMAS method had concordance of 89.1% with pill count method. The levels of total cholesterol, low density lipoprotein-cholesterol, apolipoprotein B and HMGCoA-R were significantly negatively correlated with compliance measured by pill count and MMAS with similar correlation coefficients. HMGCoA-R levels demonstrated a plateau phenomenon with levels being 9-10 ng/ml when compliance to statin therapy was greater than 60% by pill count and greater than 6 on Morisky scale. ConclusionIn conclusion, MMAS and pill count methods showed concordance in measuring adherence to statins. These methods need to be explored further for their interchangeability as surrogates for biomarker levels.

19: A novel art of continuous non-invasive blood pressure measurement
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Posted 14 Dec 2019

A novel art of continuous non-invasive blood pressure measurement
2,048 downloads medRxiv cardiovascular medicine

J├╝rgen Fortin, Dorothea Rogge, Christian Fellner, Doris Flotzinger, Julian Grond, Katja Lerche, Bernd Saugel

AO_SCPLOWBSTRACTC_SCPLOWWearable sensors to continuously measure blood pressure (BP) and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct BP measurement are too bulky. Here we present a new art of continuous non-invasive arterial blood pressure monitoring (CNAP2GO). It directly measures BP by using a new "volume control technique" and could be used for small wearable sensors integrated in a finger ring. As a software prototype, CNAP2GO showed excellent BP measurement performance in comparison with invasive BP in 46 patients having surgery. The resulting pulsatile BP signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.

20: Investigation of an estimate of daily resting heart rate using a consumer wearable device
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Posted 18 Oct 2019

Investigation of an estimate of daily resting heart rate using a consumer wearable device
2,009 downloads medRxiv cardiovascular medicine

Allison Russell, Conor Heneghan, Subbu Venkatraman

Resting heart rate is accepted as a valid overall indicator of cardiovascular risk and is a low-cost easy-to-measure metric that can be collected in both home and clinical settings. Wearable devices such as smartwatches and trackers can measure heart rate continuously using optical technology. This study reports initially on the agreement between the resting heart rate reported by a wearable device (Fitbit Charge HR and Fitbit Blaze) and a chest-based consumer electrocardiogram (Polar H7). In 45 subjects, the reported resting heart rates agreed within 0.89 bpm over a resting period of 5 mins. The same device and algorithm was then used in a population of 168 subjects (45.9{+/-} 15.6 yrs) who were asked to collect their resting heart rate for four days under seven different conditions and times (at wake sitting/lying down, pre-breakfast, pre-lunch, pre-dinner, and before bed sitting/lying down). The reported values were compared with the Daily Resting Heart Rate (DRHR) reported by the wearable device. The measurement lying down before wake were closest to the DRHR (mean error of 0.0 bpm with a 25-75th percentile spread of {+/-}3.5bpm. There was a significant circadian variation in the reported resting heart rate across subjects, with the highest values reported in the middle of the day. Within individual subjects, the median standard deviation of heart rate at rest was 3-5bpm even measured under nominally similar conditions over four days.

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