Circulation: Arrhythmia and Electrophysiology
Paroxysmal atrial fibrillation was associated with lower stroke and mortality than persistent and permanent atrial fibrillation in this substudy examining atrial fibrillation patterns from the large, multicenter ENGAGE AF TIMI 48 randomized trial of edoxaban compared with warfarin. Similar to the primary trial results, edoxaban was noninferior to warfarin across each of the patterns of atrial fibrillation.
Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation
Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48)
Mark S. Link, MD, Robert P. Giugliano, MD, SM, Christian T. Ruff, MD, MPH, Benjamin M. Scirica, MD, MPH, Heikke Huikuri, MD, Ali Oto, MD, Andrea E.Crompton, RN, BSN, Sabina A. Murphy, MPH, Hans Lanz, MD, Michele F. Mercuri, MD, Elliott M. Antman, MD, Eugene Braunwald, MD on behalf of the ENGAGE AF-TIMI 48 Investigators
Correspondence to: Mark S. Link, MD, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390. E-mail
BACKGROUND: Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported.
METHODS AND RESULTS: The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (≥7 days but <1 year), or permanent (≥1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj=0.015) and permanent AF (1.95%/year; P-adj=0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/yr; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment.
CONCLUSIONS: In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF.
Circ Arrhythm Electrophysiol. 2017;10:e004267. DOI: 10.1161/CIRCEP.116.004267
Circulation: Cardiovascular Genetics
This large, multiethnic exome-wide study aimed to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis, a strong heritable risk factor for coronary heart disease. Coronary artery calcification and carotid intima-media thickness were measured in thousands of participants of European and African ancestry who were genotyped for 247 870 DNA sequence variants across the genome. The authors found the APOE ε2 allele was inversely associated with CAC independent of LDL-cholesterol, for the first time across multiple ethnicities.
Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis
Pradeep Natarajan, MD, MMSc; Joshua C. Bis, PhD; Lawrence F. Bielak, DDS, MPH; Amanda J. Cox, PhD; Marcus Dörr, MD; Mary F. Feitosa, PhD; Nora Franceschini, MD; MPH, Xiuqing Guo, PhD; Shih-Jen Hwang, PhD; Aaron Isaacs, PhD; Min A Jhun, PhD; Maryam Kavousi, MD, PhD; Ruifang Li-Gao, MSc, Leo-Pekka Lyytikäinen, MD; Riccardo E. Marioni, PhD; Ulf Schminke, MD; Nathan O. Stitziel, MD, PhD; Hayato Tada, MD; Jessica van Setten, PhD; Albert V. Smith, PhD; Dina Vojinovic, MD, MSc; Lisa R. Yanek, MPH; Jie Yao, MD, MS; Laura M. Yerges-Armstrong, PhD; Najaf Amin, PhD; Usman Baber, MD; Ingrid B. Borecki, PhD; J. Jeffrey Carr, MD, MSc; Yii-Der Ida Chen, PhD; L. Adrienne Cupples, PhD; Pim A. de Jong, MD, PhD; Harry de Koning, PhD; Bob D. de Vos, MSc; Ayse Demirkan, PhD; Valentin Fuster, MD, PhD; Oscar H. Franco, MD, PhD; Mark O. Goodarzi, MD, PhD; Tamara B. Harris, MD; Susan R. Heckbert, MD, PhD; Gerardo Heiss, MD, PhD; Udo Hoffmann, MD, PhD; Albert Hofman, MD, PhD; Ivana Išgum, PhD; J. Wouter Jukema, MD, PhD; Mika Kähönen, MD, PhD; Sharon L. R. Kardia, PhD; Brian G. Kral, MD, MPH; Lenore J. Launer, PhD; Joe Massaro, PhD; Roxana Mehran, MD; Braxton D. Mitchell, PhD, MPH; Thomas H. Mosley Jr, PhD; Renée de Mutsert, PhD; Anne B. Newman, MD; Khanh-Dung Nguyen, PhD; Kari E. North, PhD; Jeffrey R. O’Connell, PhD; Matthijs Oudkerk, MD; James S. Pankow, PhD, MPH; Gina M. Peloso, PhD; Wendy Post, MD, MS; Michael A. Province, PhD; Laura M. Raffield, PhD; Olli T. Raitakari, MD, PhD; Dermot F. Reilly, PhD; Fernando Rivadeneira, MD, PhD; Frits Rosendaal, MD, PhD; Samantha Sartori, PhD; Kent D. Taylor, PhD; Alexander Teumer, PhD; Stella Trompet, PhD; Stephen T. Turner, MD; Andre G. Uitterlinden, PhD; Dhananjay Vaidya, PhD, MPH, MBBS; Aad van der Lugt, MD, PhD; Uwe Völker, PhD; Joanna M. Wardlaw, MD; Christina L. Wassel, PhD, MS; Stefan Weiss, PhD; Mary K. Wojczynski, PhD; Diane M. Becker, ScD, PhD; Lewis C. Becker, MD; Eric Boerwinkle, PhD; Donald W. Bowden, PhD; Ian J. Deary, PhD; Abbas Dehghan, MD, PhD; Stephan B. Felix, MD; Vilmundur Gudnason, MD, PhD; Terho Lehtimäki, MD, PhD; Rasika Mathias, ScD; Dennis O. Mook-Kanamori, MD, PhD; Bruce M. Psaty, MD; Daniel J. Rader, MD; Jerome I. Rotter, MD; James G. Wilson, MD; Cornelia M. van Duijn, PhD; Henry Völzke, MD; Sekar Kathiresan, MD; Patricia A. Peyser, PhD; Christopher J. O’Donnell, MD, MPH; CHARGE Consortium
Correspondence to: Christopher J. O’Donnell, MD, MPH, Harvard Medical School, Boston Veterans Affairs Healthcare System, 1400 Veterans of Foreign Wars Parkway, Bldg 1 5B-113, Boston, MA 02132. E-mail; or Pradeep Natarajan, MD, MMSc, Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. E-mail email@example.com
BACKGROUND: The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.
METHODS AND RESULTS: We studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima–media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima–media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10−10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10−12) and 1.4% reduced carotid intima–media thickness (P=4×10−14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10−11).
CONCLUSIONS: Exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.
Circ Cardiovascular Genetics. 2016;9:511–520. DOI: 10.1161/CIRCGENETICS.116.001572
Circulation: Cardiovascular Imaging
Though common, it is difficult to predict ventricular tachyarrhythmias in patients with heart failure with reduced ejection fraction. This study assessed patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) with speckle-tracking data available. These hypothesis-generating results suggest that inferior wall strain may provide modest incremental predictive value when added to biomarkers and echocardiographic markers to predict ventricular tachyarrhythmias.
Regional Longitudinal Deformation Improves Prediction of Ventricular Tachyarrhythmias in Patients With Heart Failure With Reduced Ejection Fraction
A MADIT-CRT Substudy (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy)
Tor Biering-Sørensen, MD, PhD, Dorit Knappe, MD, Anne-Catherine Pouleur, MD, Brian Claggett, PhD, Paul J. Wang, MD, Arthur J. Moss, MD, Scott D. Solomon, MD, Valentina Kutyifa, MD, PhD
Correspondence to: Scott D. Solomon, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail
BACKGROUND: Left ventricular dysfunction is a known predictor of ventricular arrhythmias. We hypothesized that measures of regional longitudinal deformation by speckle-tracking echocardiography predict ventricular tachyarrhythmias and provide incremental prognostic information over clinical and conventional echocardiographic characteristics.
METHODS AND RESULTS: We studied 1064 patients enrolled in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy) with speckle-tracking data available. Peak longitudinal strain was obtained for the septal, lateral, anterior, and inferior myocardial walls at baseline. The end point was the first event of ventricular tachycardia (VT) or fibrillation (VF). During the median follow-up of 2.9 years, 254 (24%) patients developed VT/VF. Patients with VT/VF had significantly lower left ventricular ejection fraction (28.3% versus 29.5%; P<0.001) and longitudinal strain in all myocardial walls compared with patients without VT/VF (anterior-strain, −7.7% versus −8.8%; P<0.001; lateral-strain, −7.3% versus −7.9%; P=0.022; inferior-strain, −8.3% versus −9.9%; P<0.001; septal-strain, −9.1% versus −10.0%; P<0.001). After multivariate adjustment, only anterior and inferior longitudinal strain remained independent predictors of VT/VF (anterior: hazard ratio, 1.08 [1.03–1.13]; P=0.001; inferior: hazard ratio, 1.08 [1.04–1.12]; P<0.001; per 1% absolute decrease for both). When including B-type natriuretic peptide in the model, only a decreasing myocardial function in the inferior myocardial wall predicted VT/VF (hazard ratio, 1.05 [1.00–1.11]; P=0.039). Only strain obtained from the inferior myocardial wall provided incremental prognostic information for VT/VF over clinical and echocardiographic parameters (C statistic 0.71 versus 0.69; P=0.005).
CONCLUSIONS: Assessment of regional longitudinal myocardial deformation in the inferior region provided incremental prognostic information over clinical and echocardiographic risk factors in predicting ventricular tachyarrhythmias.
Circ Cardiovasc Imaging. 2017;10:e005096. DOI: 10.1161/CIRCIMAGING.116.005096
Circulation: Cardiovascular Interventions
There are limited data available on 30-day readmissions after transcatheter aortic valve replacement (TAVR). This study analyzed more than 12 000 patients undergoing TAVR from the Nationwide Readmissions Database and showed that 17.9% of TAVR cases are readmitted with the greatest risk related to baseline comorbidities, TAVR access site, and postprocedure complications. An awareness of these predictors will help to identify high-risk patients. The study highlights the important need for strategies to reduce readmissions, thus improving the effectiveness of TAVR.
Thirty-Day Readmissions After Transcatheter Aortic Valve Replacement in the United States
Insights From the Nationwide Readmissions Database
Dhaval Kolte, MD, PhD, Sahil Khera, MD, M. Rizwan Sardar, MD, Neil Gheewala, MD, MPH, Tanush Gupta, MD, Saurav Chatterjee, MD, Andrew Goldsweig, MD, Wilbert S. Aronow, MD, Gregg C. Fonarow, MD, Deepak L. Bhatt, MD, MPH, Adam B. Greenbaum, MD, Paul C. Gordon, MD, Barry Sharaf, MD, J. Dawn Abbott, MD
Correspondence to: J. Dawn Abbott, MD, Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, 593 Eddy Street, RIH APC814, Providence, RI 02903. E-mail
BACKGROUND: Readmissions after cardiac procedures are common and contribute to increased healthcare utilization and costs. Data on 30-day readmissions after transcatheter aortic valve replacement (TAVR) are limited.
METHODS AND RESULTS: Patients undergoing TAVR (International Classification of Diseases-Ninth Revision-CM codes 35.05 and 35.06) between January and November 2013 who survived the index hospitalization were identified in the Nationwide Readmissions Database. Incidence, predictors, causes, and costs of 30-day readmissions were analyzed. Of 12 221 TAVR patients, 2188 (17.9%) were readmitted within 30 days. Length of stay >5 days during index hospitalization (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.24–1.73), acute kidney injury (HR, 1.23; 95% CI, 1.05–1.44), >4 Elixhauser comorbidities (HR, 1.22; 95% CI, 1.03–1.46), transapical TAVR (HR, 1.21; 95% CI, 1.05–1.39), chronic kidney disease (HR, 1.20; 95% CI, 1.04–1.39), chronic lung disease (HR, 1.16; 95% CI, 1.01–1.34), and discharge to skilled nursing facility (HR, 1.16; 95% CI, 1.01–1.34) were independent predictors of 30-day readmission. Readmissions were because of noncardiac causes in 61.8% of cases and because of cardiac causes in 38.2% of cases. Respiratory (14.7%), infections (12.8%), bleeding (7.6%), and peripheral vascular disease (4.3%) were the most common noncardiac causes, whereas heart failure (22.5%) and arrhythmias (6.6%) were the most common cardiac causes of readmission. Median length of stay and cost of readmissions were 4 days (interquartile range, 2–7 days) and $8302 (interquartile range, $5229–16 021), respectively.
CONCLUSIONS: Thirty-day readmissions after TAVR are frequent and are related to baseline comorbidities, TAVR access site, and postprocedure complications. Awareness of these predictors can help identify and target high-risk patients for interventions to reduce readmissions and costs.
Circ Cardiovasc Interv. 2017;10:e004472. DOI: 10.1161/CIRCINTERVENTIONS.116.004472
Circulation: Cardiovascular Quality and Outcomes
This cross-sectional analysis from 2003 to 2007 of the prevalence of hypertension, diabetes mellitus, and smoking and regional coordinates for the participants of the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) provides a geographical variation description of the prevalence of these major cardiovascular risk factors across the continental United States. The results show the regional and racial variation of these risk factors. The study highlights the importance of an awareness of geographic heterogeneity for efforts to prevent cardiovascular disease.
Heat Maps of Hypertension, Diabetes Mellitus, and Smoking in the Continental United States
Matthew Shane Loop, PhD, George Howard, DrPH, Gustavo de los Campos, PhD, Mohammad Z. Al-Hamdan, PhD, Monika M. Safford, MD, Emily B. Levitan, ScD, Leslie A. McClure, PhD
Correspondence to: Matthew Shane Loop, PhD, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 137 E Franklin Street, Ste 203, Chapel Hill, NC 27599. E-mail
BACKGROUND: Geographic variations in cardiovascular mortality are substantial, but descriptions of geographic variations in major cardiovascular risk factors have relied on data aggregated to counties. Herein, we provide the first description of geographic variation in the prevalence of hypertension, diabetes mellitus, and smoking within and across US counties.
METHODS AND RESULTS: We conducted a cross-sectional analysis of baseline risk factor measurements and latitude/longitude of participant residence collected from 2003 to 2007 in the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Of the 30 239 participants, all risk factor measurements and location data were available for 28 887 (96%). The mean (±SD) age of these participants was 64.8 (±9.4) years; 41% were black; 55% were female; 59% were hypertensive; 22% were diabetic; and 15% were current smokers. In logistic regression models stratified by race, the median(range) predicted prevalence of the risk factors were as follows: for hypertension, 49% (45%–58%) among whites and 72% (68%–78%) among blacks; for diabetes mellitus, 14% (10%–20%) among whites and 31% (28%–41%) among blacks; and for current smoking, 12% (7%–16%) among whites and 18% (11%–22%) among blacks. Hypertension was most prevalent in the central Southeast among whites, but in the west Southeast among blacks. Diabetes mellitus was most prevalent in the west and central Southeast among whites but in south Florida among blacks. Current smoking was most prevalent in the west Southeast and Midwest among whites and in the north among blacks.
Conclusions: Geographic disparities in prevalent hypertension, diabetes mellitus, and smoking exist within states and within counties in the continental United States, and the patterns differ by race.
Circ Cardiovasc Qual Outcomes. 2017;10:e003350. DOI: 10.1161/CIRCOUTCOMES.116.003350
Circulation: Heart Failure
This meta-analysis compares revascularization with medical treatment in patients with coronary artery disease and reduced left ventricular ejection fraction (<40%). Compared with medical treatment, both coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) were associated with improved mortality. Compared with PCI, CABG provided greater reductions in mortality. The results suggest that revascularization is superior to medical treatment in improving survival in patients with ischemic heart disease with reduced ejection fraction.
Survival Benefits of Invasive Versus Conservative Strategies in Heart Failure in Patients With Reduced Ejection Fraction and Coronary Artery Disease
Georg Wolff, MD, Dimitrios Dimitroulis, MD, Felicita Andreotti, MD, PhD, Michalina Kołodziejczak, MD, Christian Jung, MD, PhD, Pietro Scicchitano, MD, Fiorella Devito, MD, Annapaola Zito, MD, Michele Occhipinti, MD, Battistina Castiglioni, MD, Giuseppe Calveri, MD, Francesco Maisano, MD, Marco M. Ciccone, MD, Stefano De Servi, MD, Eliano P. Navarese, MD, PhD
Correspondence to: Eliano P. Navarese, MD, PhD, Department of Cardiology, Multimedica IRCCS Via Milanese 300, 20099 Milan, Italy. E-mail
BACKGROUND: Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment.
METHODS AND RESULTS: We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61–0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62–0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75–0.90; P<0.001).
CONCLUSIONS: The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting.
Circ Heart Failure. 2017;10:e003255. DOI: 10.1161/CIRCHEARTFAILURE.116.003255
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- © 2017 American Heart Association, Inc.