Publications by authors named "Mina K Chung"

192 Publications

Racial Differences and In-Hospital Outcomes Among Hospitalized Patients with COVID-19.

J Racial Ethn Health Disparities 2021 Sep 10. Epub 2021 Sep 10.

Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.

Objective: There is a paucity of data on how race affects the clinical presentation and short-term outcome among hospitalized patients with SARS-CoV-2, the 2019 coronavirus (COVID-19).

Methods: Hospitalized patients ≥ 18 years, testing positive for COVID-19 from March 13, 2020 to May 13, 2020 in a United States (U.S.) integrated healthcare system with multiple facilities in two states were evaluated. We documented racial differences in clinical presentation, disposition, and in-hospital outcomes for hospitalized patients with COIVD-19. Multivariable regression analysis was utilized to evaluate independent predictors of outcomes by race.

Results: During the study period, 3678 patients tested positive for COVID-19, among which 866 were hospitalized (55.4% self-identified as Caucasian, 29.5% as Black, 3.3% as Hispanics, and 4.7% as other racial groups). Hospitalization rates were highest for Black patients (36.6%), followed by other (28.3%), Caucasian patients (24.4%), then Hispanic patients (10.7%) (p < 0.001). Caucasian patients were older, and with more comorbidities. Absolute lymphocyte count was lowest among Caucasian patients. Multivariable regression analysis revealed that compared to Caucasians, there was no significant difference in in-hospital mortality among Black patients (adjusted odds ratio [OR] 0.53; 95% confidence interval [CI] 0.26-1.09; p = 0.08) or other races (adjusted OR 1.62; 95% CI 0.80-3.27; p = 0.18). Black and Hispanic patients were admitted less frequently to the intensive care unit (ICU), and Black patients were less likely to require pressor support or hemodialysis (HD) compared with Caucasians.

Conclusions: This observational analysis of a large integrated healthcare system early in the pandemic revealed that patients with COVID-19 did exhibit some racial variations in clinical presentation, laboratory data, and requirements for advanced monitoring and cardiopulmonary support, but these nuances did not dramatically alter in-hospital outcomes.
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http://dx.doi.org/10.1007/s40615-021-01140-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432274PMC
September 2021

Management of Congenital Long-QT Syndrome: Commentary From the Experts.

Circ Arrhythm Electrophysiol 2021 Jul 9;14(7):e009726. Epub 2021 Jul 9.

Clinical Cardiovascular Research Center, University of Rochester Medical Center, NY (W.Z.).

While published guidelines are useful in the care of patients with long-QT syndrome, it can be difficult to decide how to apply the guidelines to individual patients, particularly those with intermediate risk. We explored the diversity of opinion among 24 clinicians with expertise in long-QT syndrome. Experts from various regions and institutions were presented with 4 challenging clinical scenarios and asked to provide commentary emphasizing why they would make their treatment recommendations. All 24 authors were asked to vote on case-specific questions so as to demonstrate the degree of consensus or divergence of opinion. Of 24 authors, 23 voted and 1 abstained. Details of voting results with commentary are presented. There was consensus on several key points, particularly on the importance of the diagnostic evaluation and of β-blocker use. There was diversity of opinion about the appropriate use of other therapeutic measures in intermediate-risk individuals. Significant gaps in knowledge were identified.
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http://dx.doi.org/10.1161/CIRCEP.120.009726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301722PMC
July 2021

Managing Atrial Fibrillation in Patients With Heart Failure and Reduced Ejection Fraction: A Scientific Statement From the American Heart Association.

Circ Arrhythm Electrophysiol 2021 Jun 15;14(6):HAE0000000000000078. Epub 2021 Jun 15.

Atrial fibrillation and heart failure with reduced ejection fraction are increasing in prevalence worldwide. Atrial fibrillation can precipitate and can be a consequence of heart failure with reduced ejection fraction and cardiomyopathy. Atrial fibrillation and heart failure, when present together, are associated with worse outcomes. Together, these 2 conditions increase the risk of stroke, requiring oral anticoagulation in many or left atrial appendage closure in some. Medical management for rate and rhythm control of atrial fibrillation in heart failure remain hampered by variable success, intolerance, and adverse effects. In multiple randomized clinical trials in recent years, catheter ablation for atrial fibrillation in patients with heart failure and reduced ejection fraction has shown superiority in improving survival, quality of life, and ventricular function and reducing heart failure hospitalizations compared with antiarrhythmic drugs and rate control therapies. This has resulted in a paradigm shift in management toward nonpharmacological rhythm control of atrial fibrillation in heart failure with reduced ejection fraction. The primary objective of this American Heart Association scientific statement is to review the available evidence on the epidemiology and pathophysiology of atrial fibrillation in relation to heart failure and to provide guidance on the latest advances in pharmacological and nonpharmacological management of atrial fibrillation in patients with heart failure and reduced ejection fraction. The writing committee's consensus on the implications for clinical practice, gaps in knowledge, and directions for future research are highlighted.
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http://dx.doi.org/10.1161/HAE.0000000000000078DOI Listing
June 2021

Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19.

Vasc Med 2021 May 19:1358863X211012754. Epub 2021 May 19.

Section of Vascular Medicine, Department of Cardiovascular Medicine; Heart, Vascular & Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.
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http://dx.doi.org/10.1177/1358863X211012754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137864PMC
May 2021

The Essential Vulnerability of Human Cardiac Myocytes to SARS-CoV-2.

JACC Basic Transl Sci 2021 Apr 27;6(4):346-349. Epub 2021 Apr 27.

Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve, University School of Medicine, Cleveland, Ohio, USA.

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http://dx.doi.org/10.1016/j.jacbts.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093578PMC
April 2021

Validating and implementing cardiac telemetry for continuous QTc monitoring: A novel approach to increase healthcare personnel safety during the COVID-19 pandemic.

J Electrocardiol 2021 Jul-Aug;67:1-6. Epub 2021 Apr 27.

Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. Electronic address:

Background: Minimizing direct patient contact among healthcare personnel is crucial for mitigating infectious risk during the coronavirus disease 2019 (COVID-19) pandemic. The use of remote cardiac telemetry as an alternative to 12‑lead electrocardiography (ECG) for continuous QTc monitoring may facilitate this strategy, but its application has not yet been validated or implemented.

Methods: In the validation component of this two-part prospective cohort study, a total of 65 hospitalized patients with simultaneous ECG and telemetry were identified. QTc obtained via remote telemetry as measured by 3 independent, blinded operators were compared with ECG as assessed by 2 board-certified electrophysiologists as the gold-standard. Pearson correlation coefficients were calculated to measure the strength of linear correlation between the two methods. In a separate cohort comprised of 68 COVID-19 patients treated with combined hydroxychloroquine and azithromycin, telemetry-based QTc values were compared at serial time points after medication administration using Friedman rank-sum test of repeated measures.

Results: Telemetry-based QTc measurements highly correlated with QTc values derived from ECG, with correlation coefficients of 0.74, 0.79, 0.85 (individual operators), and 0.84 (mean of all operators). Among the COVID-19 cohort, treatment led to a median QTc increase of 15 milliseconds between baseline and following the 9th dose (p = 0.002), with 8 (12%) patients exhibiting an increase in QTc ≥ 60 milliseconds and 4 (6%) developing QTc ≥ 500 milliseconds.

Conclusions: Cardiac telemetry is a validated clinical tool for QTc monitoring that may serve an expanding role during the COVID-19 pandemic strengthened by its remote and continuous monitoring capability and ubiquitous presence throughout hospitals.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076730PMC
August 2021

COVID-19 and Cardiovascular Disease: From Bench to Bedside.

Circ Res 2021 04 15;128(8):1214-1236. Epub 2021 Apr 15.

Brigham and Women's Hospital, Harvard Medical School, Boston, MA (J.L.).

A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.317997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048382PMC
April 2021

A new machine learning approach for predicting likelihood of recurrence following ablation for atrial fibrillation from CT.

BMC Med Imaging 2021 03 9;21(1):45. Epub 2021 Mar 9.

Center for Computational Imaging and Personalized Diagnostics, Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Drive, Cleveland, OH, 44106-7207, USA.

Objective: To investigate left atrial shape differences on CT scans of atrial fibrillation (AF) patients with (AF+) versus without (AF-) post-ablation recurrence and whether these shape differences predict AF recurrence.

Methods: This retrospective study included 68 AF patients who had pre-catheter ablation cardiac CT scans with contrast. AF recurrence was defined at 1 year, excluding a 3-month post-ablation blanking period. After creating atlases of atrial models from segmented AF+ and AF- CT images, an atlas-based implicit shape differentiation method was used to identify surface of interest (SOI). After registering the SOI to each patient model, statistics of the deformation on the SOI were used to create shape descriptors. The performance in predicting AF recurrence using shape features at and outside the SOI and eight clinical factors (age, sex, left atrial volume, left ventricular ejection fraction, body mass index, sinus rhythm, and AF type [persistent vs paroxysmal], catheter-ablation type [Cryoablation vs Irrigated RF]) were compared using 100 runs of fivefold cross validation.

Results: Differences in atrial shape were found surrounding the pulmonary vein ostia and the base of the left atrial appendage. In the prediction of AF recurrence, the area under the receiver-operating characteristics curve (AUC) was 0.67 for shape features from the SOI, 0.58 for shape features outside the SOI, 0.71 for the clinical parameters, and 0.78 combining shape and clinical features.

Conclusion: Differences in left atrial shape were identified between AF recurrent and non-recurrent patients using pre-procedure CT scans. New radiomic features corresponding to the differences in shape were found to predict post-ablation AF recurrence.
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http://dx.doi.org/10.1186/s12880-021-00578-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941998PMC
March 2021

Management of Arrhythmias After Heart Transplant: Current State and Considerations for Future Research.

Circ Arrhythm Electrophysiol 2021 03 9;14(3):e007954. Epub 2021 Mar 9.

Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, KS (G.M., D.L., R.G.).

Orthotropic heart transplantation remains the most effective therapy for patients with end-stage heart failure, with a median survival of ≈13 years. Yet, a number of complications are observed after orthotropic heart transplantation, including atrial and ventricular arrhythmias. Several factors contribute to arrhythmias, such as autonomic denervation, effect of the surgical technique, acute and chronic rejection, and transplant vasculopathy among others. To minimize risk of future arrhythmias, the bicaval technique and minimizing ischemic time are current surgical standards. Sinus node dysfunction is the most common indication for early (within 30 days) pacemaker implantation, whereas atrioventricular block incidence increases as time from transplant increases. Atrial fibrillation can occur in the first few weeks following transplantation but is uncommon in the long term unless secondary to a precipitant such as acute rejection. The most common atrial arrhythmias are atrial flutters, which are mainly typical, but atypical circuits can be observed such as those that involve the remnant donor atrium in regions immediately adjacent to the atrioatrial anastomosis suture line. Choosing the appropriate pharmacological therapy requires careful consideration due to the potential interaction with immunosuppressive agents. Despite historical concerns, adenosine is effective and safe at reduced doses if administered under cardiac monitoring. Catheter ablation has emerged as an effective treatment strategy for symptomatic supraventricular tachycardias, including ablation of atypical flutter circuits. Cardiac allograft vasculopathy is an important risk factor for sudden cardiac death, yet the role of prophylactic implantable cardioverter-defibrillator implant for sudden death prevention is unclear. Current indications for implantable cardioverter-defibrillator implantation are as in the nontransplant population. A number of questions for future research are posed.
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http://dx.doi.org/10.1161/CIRCEP.120.007954DOI Listing
March 2021

Arrhythmias in Cardiac Sarcoidosis Bench to Bedside: A Case-Based Review.

Circ Arrhythm Electrophysiol 2021 02 16;14(2):e009203. Epub 2021 Feb 16.

University of Washington School of Medicine, Seattle (L.L.V., K.K.P., R.K.C.).

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.
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http://dx.doi.org/10.1161/CIRCEP.120.009203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142901PMC
February 2021

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Nature 2021 02 10;590(7845):290-299. Epub 2021 Feb 10.

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
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http://dx.doi.org/10.1038/s41586-021-03205-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875770PMC
February 2021

Attenuated heart rate recovery is associated with higher arrhythmia recurrence and mortality following atrial fibrillation ablation.

Europace 2021 07;23(7):1063-1071

Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Aims: Heart rate recovery (HRR), the decrease in heart rate occurring immediately after exercise, is caused by the increase in vagal activity and sympathetic withdrawal occurring after exercise and is a powerful predictor of cardiovascular events and mortality. The extent to which it impacts outcomes of atrial fibrillation (AF) ablation has not previously been studied. The aim of this study is to investigate the association between attenuated HRR and outcomes following AF ablation.

Methods And Results: We studied 475 patients who underwent EST within 12 months of AF ablation. Patients were categorized into normal (>12 b.p.m.) and attenuated (≤12 b.p.m.) HRR groups. Our main outcomes of interest included arrhythmia recurrence and all-cause mortality. During a mean follow-up of 33 months, 43% of our study population experienced arrhythmia recurrence, 74% of those with an attenuated HRR, and 30% of those with a normal HRR (P < 0.0001). Death occurred in 9% of patients in the attenuated HRR group compared to 4% in the normal HRR cohort (P = 0.001). On multivariable models adjusting for cardiorespiratory fitness (CRF), medication use, left atrial size, ejection fraction, and renal function, attenuated HRR was predictive of increased arrhythmia recurrence (hazard ratio 2.54, 95% confidence interval 1.86-3.47, P < 0.0001).

Conclusion: Heart rate recovery provides additional valuable prognostic information beyond CRF. An impaired HRR is associated with significantly higher rates of arrhythmia recurrence and death following AF ablation.
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http://dx.doi.org/10.1093/europace/euaa419DOI Listing
July 2021

Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage.

Pflugers Arch 2021 03 16;473(3):461-475. Epub 2021 Jan 16.

Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, 9500 Euclid Avenue, M/S ND50, Cleveland, OH, 44195, USA.

Atrial fibrillation (AF) is strongly associated with risk of stroke and heart failure. AF promotes atrial remodeling that increases risk of stroke due to left atrial thrombogenesis, and increases energy demand to support high rate electrical activity and muscle contraction. While many transcriptomic studies have assessed AF-related changes in mRNA abundance, fewer studies have assessed proteomic changes. We performed a proteomic analysis on left atrial appendage (LAA) tissues from 12 patients with a history of AF undergoing elective surgery; atrial rhythm was documented at time of surgery. Proteomic analysis was performed using liquid chromatography with mass spectrometry (LC/MS-MS). Data-dependent analysis identified 3090 unique proteins, with 408 differentially expressed between sinus rhythm and AF. Ingenuity Pathway Analysis of differentially expressed proteins identified mitochondrial dysfunction, oxidative phosphorylation, and sirtuin signaling among the most affected pathways. Increased abundance of electron transport chain (ETC) proteins in AF was accompanied by decreased expression of ETC complex assembly factors, tricarboxylic acid cycle proteins, and other key metabolic modulators. Discordant changes were also evident in the contractile unit with both up and downregulation of key components. Similar pathways were affected in a comparison of patients with a history of persistent vs. paroxysmal AF, presenting for surgery in sinus rhythm. Together, these data suggest that while the LAA attempts to meet the energetic demands of AF, an uncoordinated response may reduce ATP availability, contribute to tissue contractile and electrophysiologic heterogeneity, and promote a progression of AF from paroxysmal episodes to development of a substrate amenable to persistent arrhythmia.
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http://dx.doi.org/10.1007/s00424-021-02514-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940600PMC
March 2021

Sleep apnea screening instrument evaluation and novel model development and validation in the paroxysmal atrial fibrillation population.

Int J Cardiol Heart Vasc 2020 Dec 4;31:100624. Epub 2020 Sep 4.

Sleep Disorders Center, Neurologic Institute, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States.

Standard sleep apnea (SA) screening instruments perform suboptimally in the atrial fibrillation (AF) population. We evaluated and optimized common OSA screening tools in the AF population. Participants of the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT, NCT02576587) age (±5 years)-, sex-, body mass index (BMI ± 5 kg/m)-matched case control study (n = 150 each group) completed concurrent questionnaires and overnight polysomnography. Models based on STOP, STOP-BANG, Berlin, NoSAS and Epworth Sleepiness Scale and also models with STOP-BANG predictors with resting heart rate or left atrial volume were constructed. "Best subset" analysis was used to select a predictor subset for evaluation. We assessed test performance for two outcome thresholds: apnea-hypopnea index (AHI) ≥ 5 and AHI ≥ 15. Paroxysmal AF participants were: 61.3 ± 12.1 years, BMI = 31.2 ± 6.6 kg/m with median AHI = 11.8(IQR: 3.8, 24.5); 65 (43.3%) with AHI ≥ 15. Only STOP and STOP-BANG did not perform worse in AF relative to controls. For AHI ≥ 15, STOP-BANG (AUC 0.71, 95%CI:0.55-0.85) did not perform as well as NABS - a composite of neck circumference, age, and BMI as continuous variables and snoring (AUC 0.88, 95%CI:0.76-0.96). Optimal model for AHI ≥ 15 was NABS (sensitivity = 45%, specificity = 97%). For AHI ≥ 5, NABS was also the best performing (AUC 0.82, 95%CI:0.68-0.92, sensitivity = 78%, specificity = 67%). We identify a novel, short-item SA screening instrument for use in paroxysmal AF, i.e. NABS, with improved discriminative ability compared to commonly-used instruments. Further validation studies are needed to assess utility in other AF subtypes. : clinicaltrials.gov NCT02576587.
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http://dx.doi.org/10.1016/j.ijcha.2020.100624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752750PMC
December 2020

Machine Learning-Based Risk Assessment for Cancer Therapy-Related Cardiac Dysfunction in 4300 Longitudinal Oncology Patients.

J Am Heart Assoc 2020 12 26;9(23):e019628. Epub 2020 Nov 26.

Genomic Medicine Institute Lerner Research InstituteCleveland Clinic Cleveland OH.

Background The growing awareness of cardiovascular toxicity from cancer therapies has led to the emerging field of cardio-oncology, which centers on preventing, detecting, and treating patients with cardiac dysfunction before, during, or after cancer treatment. Early detection and prevention of cancer therapy-related cardiac dysfunction (CTRCD) play important roles in precision cardio-oncology. Methods and Results This retrospective study included 4309 cancer patients between 1997 and 2018 whose laboratory tests and cardiovascular echocardiographic variables were collected from the Cleveland Clinic institutional electronic medical record database (Epic Systems). Among these patients, 1560 (36%) were diagnosed with at least 1 type of CTRCD, and 838 (19%) developed CTRCD after cancer therapy (de novo). We posited that machine learning algorithms can be implemented to predict CTRCDs in cancer patients according to clinically relevant variables. Classification models were trained and evaluated for 6 types of cardiovascular outcomes, including coronary artery disease (area under the receiver operating characteristic curve [AUROC], 0.821; 95% CI, 0.815-0.826), atrial fibrillation (AUROC, 0.787; 95% CI, 0.782-0.792), heart failure (AUROC, 0.882; 95% CI, 0.878-0.887), stroke (AUROC, 0.660; 95% CI, 0.650-0.670), myocardial infarction (AUROC, 0.807; 95% CI, 0.799-0.816), and de novo CTRCD (AUROC, 0.802; 95% CI, 0.797-0.807). Model generalizability was further confirmed using time-split data. Model inspection revealed several clinically relevant variables significantly associated with CTRCDs, including age, hypertension, glucose levels, left ventricular ejection fraction, creatinine, and aspartate aminotransferase levels. Conclusions This study suggests that machine learning approaches offer powerful tools for cardiac risk stratification in oncology patients by utilizing large-scale, longitudinal patient data from healthcare systems.
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http://dx.doi.org/10.1161/JAHA.120.019628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763760PMC
December 2020

Cardiac Pressure Overload Decreases ETV1 Expression in the Left Atrium, Contributing to Atrial Electrical and Structural Remodeling.

Circulation 2021 Feb 23;143(8):805-820. Epub 2020 Nov 23.

The Leon H. Charney Division of Cardiology (N.Y., J.X., D.N., D.S., X.L., E.O., A.S., D.S.P.), New York University Grossman School of Medicine.

Background: Elevated intracardiac pressure attributable to heart failure induces electrical and structural remodeling in the left atrium (LA) that begets atrial myopathy and arrhythmias. The underlying molecular pathways that drive atrial remodeling during cardiac pressure overload are poorly defined. The purpose of this study is to characterize the response of the ETV1 (ETS translocation variant 1) signaling axis in the LA during cardiac pressure overload in humans and mouse models and explore the role of ETV1 in atrial electrical and structural remodeling.

Methods: We performed gene expression profiling in 265 left atrial samples from patients who underwent cardiac surgery. Comparative gene expression profiling was performed between 2 murine models of cardiac pressure overload, transverse aortic constriction banding and angiotensin II infusion, and a genetic model of cardiomyocyte-selective knockout ().

Results: Using the Cleveland Clinic biobank of human LA specimens, we found that expression is decreased in patients with reduced ejection fraction. Consistent with its role as an important mediator of the NRG1 (Neuregulin 1) signaling pathway and activator of rapid conduction gene programming, we identified a direct correlation between expression level and , , , and levels in human LA samples. In a similar fashion to patients with heart failure, we showed that left atrial ETV1 expression is downregulated at the RNA and protein levels in murine pressure overload models. Comparative analysis of LA RNA sequencing datasets from transverse aortic constriction and angiotensin II-treated mice showed a high Pearson correlation, reflecting a highly ordered process by which the LA undergoes electrical and structural remodeling. Cardiac pressure overload produced a consistent downregulation of , , , and and upregulation of profibrotic gene programming, which includes , and numerous collagen genes. mice displayed atrial conduction disease and arrhythmias. Correspondingly, the LA from mice showed downregulation of rapid conduction genes and upregulation of profibrotic gene programming, whereas analysis of a gain-of-function ETV1 RNA sequencing dataset from neonatal rat ventricular myocytes transduced with showed reciprocal changes.

Conclusions: ETV1 is downregulated in the LA during cardiac pressure overload, contributing to both electrical and structural remodeling.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449308PMC
February 2021

Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies.

Eur Heart J Suppl 2020 Oct 6;22(Suppl J):J34-J48. Epub 2020 Oct 6.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Mineral oil is often used as a clinical trial placebo. Pharmaceutical-grade mineral oil consists of a mixture of saturated hydrocarbons, with a purity and chemical structure that differs substantially from food-grade or technical-/industrial-grade mineral oils. Interest in mineral oil was piqued by suggestions that a portion of the substantially positive results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might be attributable to the theoretical negative effects of mineral oil rather than being due to the clinical benefits of icosapent ethyl. The objective of this review was to explore possible mineral oil safety and efficacy effects and contextualize these findings in light of the REDUCE-IT conclusions. A literature search identified studies employing mineral oil placebos. Eighty studies were identified and relevant data extracted. Adverse events associated with mineral oil were generally gastrointestinal and consistent with use as a lubricant laxative. Changes in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and other biomarkers were inconsistent and generally not statistically significant, or clinically meaningful with mineral oil, as were changes in blood pressure. There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins. These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials.
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http://dx.doi.org/10.1093/eurheartj/suaa117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537802PMC
October 2020

Incidence and Predictors of 30-day Acute Cerebrovascular Accidents Post Atrial Fibrillation Catheter Ablation (From the Nationwide Readmissions Database).

Am J Cardiol 2021 01 13;138:61-65. Epub 2020 Oct 13.

Section of Cardiac Electrophysiology, UW Heart Institute, University of Washington, Seattle, Washington. Electronic address:

Catheter-based ablation is increasingly being used as first-line therapy for atrial fibrillation (AF). Cerebrovascular accidents (CVA) are a known complication. In this study, we investigate the 30-day incidence and predictors of acute CVA postcatheter ablation for AF. The Nationwide Readmissions Database from 2010 to September 2015 was queried for hospitalizations with an ablation procedure and a concurrent AF diagnosis. The primary end point was a composite end point of CVA during index admission or readmission for CVA within 30 days of admission for index hospitalization. The associations between the incidence of end points and the covariates of interest; which included age, gender, hospital characteristics (size, procedural volume, urban/rural status, and teaching status), CHA2DS2-VASc co-morbidity score and its components was assessed using logistic regression. Appropriate survey weighting methodology was applied to generate nationally representative estimates. Of 67,090 weighted hospitalizations for AF ablation, 566 (0.8%) had CVA within 30 days post-ablation. In multivariate regression analysis, factors associated with CVA included hypertension (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.04, 1.85), heart failure (OR 4.97, 95% CI 3.32, 7.44), previous stroke/ transient ischemic attack (OR 3.25, 95% CI 2.39, 4.42) and a lower procedural volume (OR for higher procedural volume: 0.6, 95% CI 0.42, 0.85). CHA2DS2-VASc score (OR 1.27, 95% CI 1.17, 1.39) was associated with CVA in univariate analysis. In conclusion, the CVA incidence within 30-day of catheter-based AF ablation therapy was 0.8%. Higher CHA2DS2-VASc score was associated with higher risk of CVA post-ablation. Hypertension, heart failure, previous stroke/transient ischemic attack, and procedural volume were independently associated with CVA post-ablation.
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http://dx.doi.org/10.1016/j.amjcard.2020.10.020DOI Listing
January 2021

Cross-Center Virtual Education Fellowship Program for Early-Career Researchers in Atrial Fibrillation.

Circ Arrhythm Electrophysiol 2020 11 8;13(11):e008552. Epub 2020 Oct 8.

Department of Medicine, Boston University School of Medicine, MA (T.B.A., C.D.R., E.J.B.).

Background: It is estimated that over 46 million individuals have atrial fibrillation (AF) worldwide, and the incidence and prevalence of AF are increasing globally. There is an urgent need to accelerate the academic development of scientists possessing the skills to conduct innovative, collaborative AF research.

Methods: We designed and implemented a virtual AF Strategically Focused Research Network Cross-Center Fellowship program to enhance the competencies of early-stage AF basic, clinical, and population health researchers through experiential education and mentorship. The pedagogical model involves significant cross-center collaboration to produce a curriculum focused on enhancing AF scientific competencies, fostering career/professional development, and cultivating grant writing skills. Outcomes for success involve clear expectations for fellows to produce manuscripts, presentations, and-for those at the appropriate career stage-grant applications. We evaluated the effectiveness of the fellowship model via mixed methods formative and summative surveys.

Results: In 2 years of the fellowship, fellows generally achieved the productivity metrics sought by our pedagogical model, with outcomes for the 12 fellows including 50 AF-related manuscripts, 7 publications, 28 presentations, and 3 grant awards applications. Participant evaluations reported that the fellowship effectively met its educational objectives. All fellows reported medium to high satisfaction with the overall fellowship, webinar content and facilitation, staff communication and support, and program organization.

Conclusions: The fellowship model represents an innovative educational strategy by providing a virtual AF training and mentoring curriculum for early-career basic, clinical, and population health scientists working across multiple institutions, which is particularly valuable in the pandemic era.
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http://dx.doi.org/10.1161/CIRCEP.120.008552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674267PMC
November 2020

REDUCE-IT INTERIM: accumulation of data across prespecified interim analyses to final results.

Eur Heart J Cardiovasc Pharmacother 2021 May;7(3):e61-e63

Cardiac Pacing and Electrophysiology, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

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http://dx.doi.org/10.1093/ehjcvp/pvaa118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141294PMC
May 2021

Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19).

JAMA Cardiol 2020 09;5(9):1020-1026

Heart, Vascular and Thoracic Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.

Importance: The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use.

Objective: To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation).

Design, Setting, And Participants: Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included.

Exposures: History of taking ACEIs or ARBs at the time of COVID-19 testing.

Main Outcomes And Measures: Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive.

Results: A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15).

Conclusions And Relevance: This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.
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http://dx.doi.org/10.1001/jamacardio.2020.1855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201375PMC
September 2020

Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association.

Circulation 2020 10 15;142(15):e214-e233. Epub 2020 Sep 15.

Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient's arrythmia could be drug-induced is important.
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http://dx.doi.org/10.1161/CIR.0000000000000905DOI Listing
October 2020

Impact of the COVID-19 Pandemic on Healthcare Workers' Risk of Infection and Outcomes in a Large, Integrated Health System.

J Gen Intern Med 2020 11 1;35(11):3293-3301. Epub 2020 Sep 1.

Healthcare Delivery and Implementation Science Center, Cleveland Clinic, Cleveland, OH, USA.

Background: Understanding the impact of the COVID-19 pandemic on healthcare workers (HCW) is crucial.

Objective: Utilizing a health system COVID-19 research registry, we assessed HCW risk for COVID-19 infection, hospitalization, and intensive care unit (ICU) admission.

Design: Retrospective cohort study with overlap propensity score weighting.

Participants: Individuals tested for SARS-CoV-2 infection in a large academic healthcare system (N = 72,909) from March 8-June 9, 2020, stratified by HCW and patient-facing status.

Main Measures: SARS-CoV-2 test result, hospitalization, and ICU admission for COVID-19 infection.

Key Results: Of 72,909 individuals tested, 9.0% (551) of 6145 HCW tested positive for SARS-CoV-2 compared to 6.5% (4353) of 66,764 non-HCW. The HCW were younger than the non-HCW (median age 39.7 vs. 57.5, p < 0.001) with more females (proportion of males 21.5 vs. 44.9%, p < 0.001), higher reporting of COVID-19 exposure (72 vs. 17%, p < 0.001), and fewer comorbidities. However, the overlap propensity score weighted proportions were 8.9 vs. 7.7 for HCW vs. non-HCW having a positive test with weighted odds ratio (OR) 1.17, 95% confidence interval (CI) 0.99-1.38. Among those testing positive, weighted proportions for hospitalization were 7.4 vs. 15.9 for HCW vs. non-HCW with OR of 0.42 (CI 0.26-0.66) and for ICU admission: 2.2 vs. 4.5 for HCW vs. non-HCW with OR of 0.48 (CI 0.20-1.04). Those HCW identified as patient facing compared to not had increased odds of a positive SARS-CoV-2 test (OR 1.60, CI 1.08-2.39, proportions 8.6 vs. 5.5), but no statistically significant increase in hospitalization (OR 0.88, CI 0.20-3.66, proportions 10.2 vs. 11.4) and ICU admission (OR 0.34, CI 0.01-3.97, proportions 1.8 vs. 5.2).

Conclusions: In a large healthcare system, HCW had similar odds for testing SARS-CoV-2 positive, but lower odds of hospitalization compared to non-HCW. Patient-facing HCW had higher odds of a positive test. These results are key to understanding HCW risk mitigation during the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s11606-020-06171-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462108PMC
November 2020

Impact of the COVID-19 pandemic on healthcare workers risk of infection and outcomes in a large, integrated health system.

Res Sq 2020 Aug 19. Epub 2020 Aug 19.

Cleveland Clinic.

Understanding the impact of the COVID-19 pandemic on healthcare workers (HCW) is crucial. Utilizing a health system COVID-19 research registry, we assessed HCW risk for COVID-19 infection, hospitalization and intensive care unit (ICU) admission. Retrospective cohort study with overlap propensity score weighting. Individuals tested for SARS-CoV-2 infection in a large academic healthcare system (N=72,909) from March 8-June 9 2020 stratified by HCW and patient-facing status. SARS-CoV-2 test result, hospitalization, and ICU admission for COVID-19 infection. Of 72,909 individuals tested, 9.0% (551) of 6,145 HCW tested positive for SARS-CoV-2 compared to 6.5% (4353) of 66,764 non-HCW. The HCW were younger than non-HCW (median age 39.7 vs. 57.5, p<0.001) with more females (proportion of males 21.5 vs. 44.9%, p<0.001), higher reporting of COVID-19 exposure (72 vs. 17 %, p<0.001) and fewer comorbidities. However, the overlap propensity score weighted proportions were 8.9 vs. 7.7 for HCW vs. non-HCW having a positive test with weighted odds ratio (OR) 1.17, 95% confidence interval (CI) 0.99-1.38. Among those testing positive, weighted proportions for hospitalization were 7.4 vs.15.9 for HCW vs. non-HCW with OR of 0.42 (CI 0.26-0.66) and for ICU admission: 2.2 vs.4.5 for HCW vs. non-HCW with OR of 0.48 (CI 0.20 -1.04). Those HCW identified as patient-facing compared to not had increased odds of a positive SARS-CoV-2 test (OR 1.60, CI 1.08-2.39, proportions 8.6 vs. 5.5), but no statistically significant increase in hospitalization (OR 0.88, CI 0.20-3.66, proportions 10.2 vs. 11.4) and ICU admission (OR 0.34, CI 0.01-3.97, proportions 1.8 vs. 5.2). In a large healthcare system, HCW had similar odds for testing SARS-CoV-2 positive, but lower odds of hospitalization compared to non-HCW. Patient-facing HCW had higher odds of a positive test. These results are key to understanding HCW risk mitigation during the COVID-19 pandemic.
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http://dx.doi.org/10.21203/rs.3.rs-61235/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444292PMC
August 2020

HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic.

J Arrhythm 2020 Jun 25. Epub 2020 Jun 25.

Society Washington US.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started in the city of Wuhan late in 2019. Within a few months, the disease spread toward all parts of the world and was declared a pandemic on March 11, 2020. The current health care dilemma worldwide is how to sustain the capacity for quality services not only for those suffering from COVID-19 but also for non-COVID-19 patients, all while protecting physicians, nurses, and other allied health care workers.
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http://dx.doi.org/10.1002/joa3.12389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361598PMC
June 2020

Guidance for Rebooting Electrophysiology Through the COVID-19 Pandemic From the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology.

JACC Clin Electrophysiol 2020 08 12;6(8):1053-1066. Epub 2020 Jun 12.

Cooper Medical School of Rowan University, Camden, New Jersey, USA.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.
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http://dx.doi.org/10.1016/j.jacep.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291987PMC
August 2020

SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy.

EBioMedicine 2020 Aug 6;58:102907. Epub 2020 Aug 6.

Heart, Vascular and Thoracic Institute, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.

Background: SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful.

Methods: Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed.

Findings And Interpretation: SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.
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http://dx.doi.org/10.1016/j.ebiom.2020.102907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415847PMC
August 2020
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