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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
26,549 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
16,387 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
15,031 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
7,718 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
7,069 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
4,799 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
4,480 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
3,807 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: 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
3,277 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.

10: 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
2,831 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

11: 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
2,534 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 P 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.

12: 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
2,395 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.

13: 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
2,276 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.

14: 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
1,900 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.

15: 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
1,771 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.

16: Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring
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Posted 25 Apr 2020

Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring
1,642 downloads medRxiv cardiovascular medicine

Archana Ramireddy, Harpriya S. Chugh, Kyndaron Reinier, Joseph Ebinger, Eunice Park, Michael Thompson, Eugenio Cingolani, Susan Cheng, Eduardo Marban, Christine Albert, Sumeet S. Chugh

Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc [&ge;]500 ms (if QRS <120 ms) or QTc [&ge;]550 (if QRS [&ge;]120 ms) and b) increased QTc of [&ge;]60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62{+/-}17 yrs, 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448{+/-}29 ms and increased to 459{+/-}36ms (p=0.005) with medications. Significant prolongation was observed only in men (18{+/-}43 ms vs -0.2{+/-}28 ms in women, p=0.02). 12% of patients reached critical QTc prolongation. In a multivariable logistic regression, age, sex, Tisdale score, Elixhauser score, and baseline QTc were not associated with critical QTc prolongation (p>0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17{+/-}39 vs. 0.5{+/-}40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.

17: The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study
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Posted 01 Jun 2020

The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study
1,620 downloads medRxiv cardiovascular medicine

Kyle Johnson, Maedeh Khayyat-Kholghi, Blake Johnson, Larisa G Tereshchenko

Background: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of Covid-19 confirmed cases and deaths. Methods: We conducted a geospatial study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population. Findings: After adjustment for confounders, the ACEI use rate did not associate with Covid-19 confirmed case rate (direct county-own effect +0.11 %; 95%CI -0.31 to 0.53; P=0.600, and indirect spillover effect -0.53 %; 95%CI -3.89 to 2.84; P=0.760). The ARB use rate was associated with increased Covid-19 confirmed case rate (direct county-owned effect +0.12 %; 95%CI 0.05-0.19; P=0.002, and indirect spillover effect -0.33 %; 95%CI -2.11 to 1.44; P=0.714). Sensitivity analysis indicated an absence of significant reverse causality bias for analyses with Covid-19 confirmed case rate, but not death rate outcome. Interpretation: Our results highlight the safety of ACEI use for patients with clinical indications for ACEI use. However, an increase in ARB use by 1% was associated with a 0.12 % increase in Covid-19 confirmed cases. The use of ARB, due to known ACE2 upregulation, may facilitate SARS-CoV-2 entry into target cells and increase infectivity. Cluster-randomized controlled trial is warranted to answer the question of whether the replacement of ARB by ACEI may reduce the Covid-19 confirmed case rate.

18: Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study
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Posted 12 Jun 2020

Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study
1,592 downloads medRxiv cardiovascular medicine

Daniel R. Morales, Mitchell M Conover, Seng Chan You, Nicole Pratt, Kristin Kostka, Talita Duarte Salles, Sergio Fernandez Bertolin, Maria Aragon, Scott Duvall, Kristine Lynch, Thomas Falconer, Kees van Bochove, Cynthia Sung, Michael E Matheny, Christophe G. Lambert, Fredrik Nyberg, Thamir M AlShammari, Andrew E Williams, Rae Woong Park, James Weaver, Anthony G. Sena, Martijn J Schuemie, Peter R. Rijnbeek, Ross D. Williams, Jennifer C. E. Lane, Albert Prats Uribe, Lin Zhang, Carlos Areia, Harlan Krumholz, Daniel Prieto Alhambra, Patrick B. Ryan, George M Hripcsak, Marc A Suchard

Introduction: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. Methods: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) use to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. Results: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 - 1.05) and marginally significant for mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between drug- classes for COVID-19 hospitalization or pneumonia risk across all comparisons. Conclusion: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.

19: COVID-19 Myocardial Pathology Evaluated Through scrEening Cardiac Magnetic Resonance (COMPETE CMR)
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Posted 02 Sep 2020

COVID-19 Myocardial Pathology Evaluated Through scrEening Cardiac Magnetic Resonance (COMPETE CMR)
1,557 downloads medRxiv cardiovascular medicine

Daniel Eugene Clark, Amar Parikh, Jeffrey M Dendy, Alex B Diamond, Kristen George-Durrett, Frank A Fish, Warne Fitch, Sean G Hughes, Jonathan H Soslow

Background Myocarditis is a leading cause of sudden cardiac death among competitive athletes and may occur without antecedent symptoms. COVID-19-associated myocarditis has been well-described, but the prevalence of myocardial inflammation and fibrosis in young athletes after COVID-19 infection is unknown. Objectives This study sought to evaluate the prevalence and extent of cardiovascular involvement in collegiate athletes that had recently recovered from COVID-19. Methods We conducted a retrospective cohort analysis of collegiate varsity athletes with prior COVID-19 infection, all of whom underwent cardiac magnetic resonance (CMR) prior to resumption of competitive sports in August 2020. Results Twenty-two collegiate athletes with prior COVID-19 infection underwent CMR. The median time from SARS-CoV-2 infection to CMR was 52 days. The mean age was 20.2 years. Athletes represented 8 different varsity sports. This cohort was compared to 22 healthy controls and 22 tactical athlete controls. Most athletes experienced mild illness (N=17, 77%), while the remainder (23%) were asymptomatic. No athletes had abnormal troponin I, electrocardiograms, or LVEF < 50% on echocardiography. Late gadolinium enhancement was found in 9% of collegiate athletes and one athlete (5%) met formal criteria for myocarditis. Conclusions Our study suggests that the prevalence of myocardial inflammation or fibrosis after an asymptomatic or mild course of ambulatory COVID-19 among competitive athletes is modest (9%), but would be missed by ECG, Ti, and strain echocardiography. Future investigation is necessary to further phenotype cardiovascular manifestations of COVID-19 in order to better counsel athletes on return to sports participation.

20: ACE2 levels are altered in comorbidities linked to severe outcome in COVID-19
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Posted 05 Jun 2020

ACE2 levels are altered in comorbidities linked to severe outcome in COVID-19
1,557 downloads medRxiv cardiovascular medicine

Valur Emilsson, Elias F Gudmundsson, Thor Aspelund, Brynjolfur G Jonsson, Alexander Gudjonsson, Lenore J Launer, John R Lamb, Valborg Gudmundsdottir, Lori L Jennings, Vilmundur Gudnason

Aims: Severity of outcome in COVID-19 is disproportionately higher among the obese, males, smokers, those suffering from hypertension, kidney disease, coronary heart disease (CHD) and/or type 2 diabetes (T2D). We examined if serum levels of ACE2, the cellular entry point for the coronavirus SARS-CoV-2, were altered in these high-risk groups. Methods: Associations of serum ACE2 levels to hypertension, T2D, obesity, CHD, smokers and males in a single center population-based study of 5457 Icelanders from the Age, Gene/Environment Susceptibility Reykjavik Study (AGES-RS) of the elderly (mean age 75+/-6 years). Results: Smokers, males, and individuals with T2D or obesity have altered serum levels of ACE2 that may influence productive infection of SARS-CoV-2 in these high-risk groups. Conclusion: ACE2 levels are upregulated in some patient groups with comorbidities linked to COVID-19 and as such may have an emerging role as a circulating biomarker for severity of outcome in COVID-19.

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