Circulation: Arrhythmia and Electrophysiology
Although VT ablation can be challenging in nonischemic cardiomyopathy, this large series shows that ablation, which requires epicardial ablation in about a third of patients, can usually reduce recurrent ventricular tachycardia.
Long-Term Outcome After Catheter Ablation of Ventricular Tachycardia in Patients With Nonischemic Dilated Cardiomyopathy
Daniele Muser, MD, Pasquale Santangeli, MD, PhD, Simon A. Castro, MD, Rajeev K. Pathak, MBBS, PhD, Jackson J. Liang, DO, Tatsuya Hayashi, MD, Silvia Magnani, MD, Fermin C. Garcia, MD, Mathew D. Hutchinson, MD, Gregory G. Supple, MD, David S. Frankel, MD, Michael P. Riley, MD, PhD, David Lin, MD, Robert D. Schaller, DO, Sanjay Dixit, MD, Erica S. Zado, PA-C, David J. Callans, MD, Francis E. Marchlinski, MD
Correspondence to: Francis Marchlinski, MD, Hospital of the University of Pennsylvania, 9 Founders Pavilion–Cardiology, 3400 Spruce St, Philadelphia, PA 19104. E-mail
BACKGROUND: Catheter ablation (CA) of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy can be challenging because of the complexity of underlying substrates. We sought to determine the long-term outcomes of endocardial and adjuvant epicardial CA in nonischemic dilated cardiomyopathy.
METHODS AND RESULTS: We examined 282 consecutive patients (aged 59±15 years, 80% males) with nonischemic dilated cardiomyopathy who underwent CA. Ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal electrograms for unmappable VT. Adjuvant epicardial ablation was performed for recurrent VT or persistent inducibility after endocardial–only ablation. Epicardial ablation was performed in 90 (32%) patients. Before ablation, patients failed a median of 2 antiarrhythmic drugs), including amiodarone, in 166 (59%) patients. The median follow-up after the last procedure was 48 (19–67) months. Overall, VT-free survival was 69% at 60-month follow-up. Transplant-free survival was 76% and 68% at 60- and 120-month follow-up, respectively. Among the 58 (21%) patients with VT recurrence, CA still resulted in a significant reduction of VT burden, with 31 (53%) patients having only isolated (1–3) VT episodes in 12 (4–35) months after the procedure. At the last follow-up, 128 (45%) patients were only on β-blockers or no treatment, 41 (15%) were on sotalol or class I antiarrhythmic drugs, and 62 (22%) were on amiodarone.
CONCLUSIONS: In patients with nonischemic dilated cardiomyopathy and VT, endocardial and adjuvant epicardial CA is effective in achieving long-term VT freedom in 69% of cases, with a substantial improvement in VT burden in many of the remaining patients.
Circ Arrhythm Electrophysiol.2016;9:e004328. DOI: 10.1161/CIRCEP.116.004328.
Circulation: Cardiovascular Genetics
This large-scale meta-analysis examines the impact cigarette smoking has on DNA methylation and its persistence many years after smoking cessation. The findings suggest new insights into the long-term impact tobacco exposure has on DNA methylation signals and its effects on human health and disease.
Epigenetic Signatures of Cigarette Smoking
Roby Joehanes, PhD; Allan C. Just, PhD; Riccardo E. Marioni, PhD; Luke C. Pilling, PhD; Lindsay M. Reynolds, PhD; Pooja R. Mandaviya, MSc; Weihua Guan, PhD; Tao Xu, PhD; Cathy E. Elks, PhD; Stella Aslibekyan, PhD; Hortensia Moreno-Macias, ScD; Jennifer A. Smith, PhD, MPH; Jennifer A. Brody, BA; Radhika Dhingra, PhD; Paul Yousefi, MPH; James S. Pankow, PhD; Sonja Kunze, PhD; Sonia H. Shah, PhD; Allan F. McRae, PhD; Kurt Lohman, Mstat; Jin Sha, MS; Devin M. Absher, PhD; Luigi Ferrucci, MD, PhD; Wei Zhao, PhD; Ellen W. Demerath, PhD; Jan Bressler, PhD; Megan L. Grove, MS; Tianxiao Huan, PhD; Chunyu Liu, PhD; Michael M. Mendelson, MD; Chen Yao, PhD; Douglas P. Kiel, MD, MPH; Annette Peters, PhD; Rui Wang-Sattler, PhD; Peter M. Visscher, PhD; Naomi R. Wray, PhD; John M. Starr, PhD; Jingzhong Ding, PhD; Carlos J. Rodriguez, MD, MPH; Nicholas J. Wareham, PhD; Marguerite R. Irvin, PhD; Degui Zhi, PhD; Myrto Barrdahl, PhD; Paolo Vineis, MD; Srikant Ambatipudi, PhD; André G. Uitterlinden, PhD; Albert Hofman, MD, PhD; Joel Schwartz, PhD; Elena Colicino, PhD; Lifang Hou, MD, PhD; Pantel S. Vokonas, MD; Dena G. Hernandez, PhD; Andrew B. Singleton, PhD; Stefania Bandinelli, MD; Stephen T. Turner, MD; Erin B. Ware, PhD, MPH; Alicia K. Smith, PhD; Torsten Klengel, MD; Elisabeth B. Binder, MD, PhD; Bruce M. Psaty, MD, PhD; Kent D. Taylor, PhD; Sina A. Gharib, MD; Brenton R. Swenson, MPP; Liming Liang, PhD; Dawn L. DeMeo, MD, MPH; George T. O’Connor, MD, MS; Zdenko Herceg, DVM, MSc, PhD; Kerry J. Ressler, MD, PhD; Karen N. Conneely, PhD; Nona Sotoodehnia, MD, MPH; Sharon L. R. Kardia, PhD; David Melzer, MBBCh, PhD; Andrea A. Baccarelli, MD, PhD; Joyce B. J. van Meurs, PhD; Isabelle Romieu, MD, ScD; Donna K. Arnett, PhD; Ken K. Ong, MB BChir, PhD; Yongmei Liu, MD, PhD; Melanie Waldenberger, PhD; Ian J. Deary, PhD; Myriam Fornage, PhD; Daniel Levy, MD; Stephanie J. London, MD, DrPH
Correspondence to: Stephanie J. London, MD, DrPH, Epidemiology Branch, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Room A306, Research Triangle Park, NC 27709. E-mail
BACKGROUND: DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders.
METHODS AND RESULTS: To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine–phosphate–guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1×10−7 (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1×10−7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs.
CONCLUSIONS: Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.
Circ Cardiovasc Genet. 2016;9:436-447. DOI: 10.1161/CIRCGENETICS.116.001506.
Circulation: Cardiovascular Imaging
This study evaluates invasive hemodynamics at rest and during supine exercise in patients with severe asymptomatic aortic stenosis. The results show that left atrial dilatation and diastolic E/e′ by echocardiography correlated well with invasive measurements of pulmonary capillary wedge pressure and mean pulmonary artery pressure during exercise. They provide hemodynamic information in asymptomatic aortic stenosis and may be useful for risk stratification of severe asymptomatic aortic stenosis.
Association Between Left Atrial Dilatation and Invasive Hemodynamics at Rest and During Exercise in Asymptomatic Aortic Stenosis
Nicolaj Lyhne Christensen, MD, Jordi Sanchez Dahl, MD, PhD, Rasmus Carter-Storch, MD, Rine Bakkestrøm, MD, Kurt Jensen, MSc, Flemming Hald Steffensen, MD, PhD, Eva Vad Søndergaard, MD, PhD, Lars Videbæk, MD, PhD, Jacob Eifer Møller, MD, PhD, DMSc
Correspondence to: Nicolaj Lyhne Christensen, MD, Department of Cardiology Odense University Hospital, Sdr. Blvd 29, DK-5000 Odense C, Denmark. E-mail
BACKGROUND: Transition from an asymptomatic to symptomatic state in severe aortic stenosis is often difficult to assess. Identification of a morphological sign of increased hemodynamic load may be important in asymptomatic aortic stenosis to identify patients at risk.
METHODS AND RESULTS: Thirty-nine patients with asymptomatic severe aortic stenosis (aortic valve area <1 cm2, peak jet velocity >3.5 m/s) underwent exercise testing with simultaneous invasive hemodynamic monitoring and Doppler echocardiography. Cardiac index, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were recorded. Patients were followed up for the composite end point of death, unplanned hospitalization, or aortic valve replacement. Patients were stratified into 2 groups according to left atrial (LA) volume index ≥35 mL/m2. In 25 patients (64%) LA volume index was ≥35 mL/m2. Aortic valve area was similar between groups (0.81±0.15 versus 0.84±0.18 cm2; P=0.58). PCWP was higher at rest and during exercise in patients with LA volume index ≥35 mL/m2 (P<0.01), despite similar cardiac index. At rest, PCWP was <12 mm Hg in 11 patients (44%) with LA dilatation, whereas PCWP was <25 mm Hg in 1 patient (4%) with exercise. LA volume index and E/e′ predicted exercise PCWP>30 mm Hg with areas under the receiver operating curve of 0.75 and 0.84, respectively. During follow-up, 14 cardiac events were recorded. LA volume was associated with a hazard ratio of 1.90 (95% confidence interval, 0.92–4.15).
CONCLUSIONS: LA size reflects hemodynamic burden in patients with asymptomatic severe aortic stenosis. Quantitative measurements of LA and diastolic function are associated with left ventricular filling pressures with exercise and could be used to identify asymptomatic patients with increased hemodynamic burden.
Circ Cardiovasc Imaging.2016;9 e005156. DOI: 10.1161/CIRCIMAGING.116.005156.
Circulation: Cardiovascular Interventions
Previous studies provide conflicting results regarding cognitive function after transcatheter aortic valve implantation (TAVI). This study confirms that either deterioration or improvement of cognitive function may occur after TAVI. Preinterventional aortic valve area was significantly lower among patients with versus without improvement in cognitive function after TAVI, suggesting that hemodynamic improvement after TAVI may improve cognitive function in some individuals.
Evolution of Cognitive Function After Transcatheter Aortic Valve Implantation
Andreas W. Schoenenberger, MD, Chantal Zuber, André Moser, PhD, Marcel Zwahlen, PhD, Peter Wenaweser, MD, Stephan Windecker, MD, Thierry Carrel, MD, Andreas E. Stuck, MD, Stefan Stortecky, MD
Correspondence to: Andreas W. Schoenenberger, MD, Division of Geriatrics, Inselspital, Bern University Hospital, Freiburgstrasse, CH-3010 Bern, Switzerland. E-mail
BACKGROUND: This study aimed to assess the evolution of cognitive function after transcatheter aortic valve implantation (TAVI). Previous smaller studies reported conflicting results on the evolution of cognitive function after TAVI.
METHODS AND RESULTS: In this prospective cohort, cognitive function was measured in 229 patients ≥70 years using the Mini Mental State Examination before and 6 months after TAVI. Cognitive deterioration or improvement was defined as change of ≥3 points decrease or increase in the Mini Mental State Examination score between baseline and follow-up. Cognitive deterioration was found in 29 patients (12.7%). Predictive analysis using logistic regression did not identify any statistically significant predictor of cognitive deterioration. A review of individual medical records in 8 patients with a major Mini Mental State Examination score decrease of ≥5 points revealed specific causes in 6 cases (postinterventional delirium in 2; postinterventional stroke, progressive renal failure, progressive heart failure, or combination of preexisting cerebrovascular disease and mild cognitive impairment in 1 each). Among 48 patients with impaired baseline cognition (Mini Mental State Examination score <26 points), 18 patients (37.5%) cognitively improved. The preinterventional aortic valve area was lower in patients who cognitively improved (median aortic valve area 0.60 cm2) as compared with patients who did not improve (median aortic valve area 0.70 cm2; P=0.01).
CONCLUSIONS: This is the first study providing evidence that TAVI results in cognitive improvement among patients who had impaired preprocedural cognitive function, possibly related to hemodynamic improvement in patients with severe aortic stenosis. Our results confirm that some patients experience cognitive deterioration after TAVI.
Circ Cardiovasc Interv.2016;9:e003590. DOI: 10.1161/CIRCINTERVENTIONS.116.003590.
Circulation: Cardiovascular Quality and Outcomes
This study considers the concordance between evidence and practice guidelines regarding the value of tight glycemic control as a strategy to prevent chronic complications in patients with type 2 diabetes. Published statements and guidelines continue to endorse tight glycemic control to prevent microvascular complications despite accumulating research evidence from the last two decades that does not support such a strong recommendation.
Glycemic Control for Patients with Type 2 Diabetes Mellitus
Our Evolving Faith in the Face of Evidence
René Rodríguez-Gutiérrez, MD, MSc, Victor M. Montori, MD, MSc
Correspondence to: Victor M. Montori, MD, MSc, Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, 200 1st St SW, Rochester, MN 55905. E-mail
BACKGROUND: We sought to determine the concordance between the accumulating evidence about the impact of tight versus less tight glycemic control in patients with type 2 diabetes mellitus since the publication of UKPDS (UK Prospective Diabetes Study) in 1998 until 2015 with the views about that evidence published in journal articles and practice guidelines.
METHODS AND RESULTS: We searched in top general medicine and specialty journals for articles referring to glycemic control appearing between 2006 and 2015 and identified the latest practice guidelines. To summarize the evidence, we included all published systematic reviews and meta-analyses of contemporary randomized trials of glycemic control measuring patient-important microvascular and macrovascular outcomes, and completed a meta-analysis of their follow-up extensions. We identified 16 guidelines and 328 statements. The body of evidence produced estimates warranting moderate confidence. This evidence reported no significant impact of tight glycemic control on the risk of dialysis/transplantation/renal death, blindness, or neuropathy. In the past decade, however, most published statements (77% to 100%) and guidelines (95%) unequivocally endorsed benefit. There is also no significant effect on all-cause mortality, cardiovascular mortality, or stroke; however, there is a consistent 15% relative-risk reduction of nonfatal myocardial infarction. Between 2006 and 2008, most statements (47% to 83%) endorsed the benefit; after 2008 (ACCORD), only a minority (21% to 36%) did.
CONCLUSIONS: Discordance exists between the research evidence and academic and clinical policy statements about the value of tight glycemic control to reduce micro- and macrovascular complications. This discordance may distort priorities in the research and practice agendas designed to improve the lives of patients with type 2 diabetes mellitus.
Circ Cardiovasc Qual Outcomes.2016;9:504-512. DOI: 10.1161/CIRCOUTCOMES.116.002901.
Circulation: Heart Failure
In this multiracial cohort, the authors compared risk factors for incident heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Anemia, multiple medical comorbidity, and atrial fibrillation associated with HFpEF, whereas prior MI was specifically associated with HFrEF. The results further highlight obesity as an important risk factor of HFpEF, particularly among African American women.
Risk Factors for Incident Hospitalized Heart Failure with Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women
Charles B. Eaton, MD, MS, Mary Pettinger, MS, Jacques Rossouw, MB, ChB, Lisa Warsinger Martin, MD, Randi Foraker, PhD, MA, Abdullah Quddus, MD, Simin Liu, MD, ScD, Nina S. Wampler, DSc, MPH, Wen-Chih Hank Wu, MD, JoAnn E. Manson, MD, DrPH, Karen Margolis, MD, MPH, Karen C. Johnson, MD, MPH, Matthew Allison, MD, MPH, Giselle Corbie-Smith, MD, Msc, Wayne Rosamond, PhD, Khadijah Breathett, MD, Liviu Klein, MD
Correspondence to: Charles B. Eaton, MD, MS, Memorial Hospital of Rhode Island, 111 Brewster St, Pawtucket, RI. E-mail
BACKGROUND: Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized.
METHODS AND RESULTS: We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors.
CONCLUSIONS: In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women.
Circulation: Heart Failure.2016;9:e002883. DOI: 10.1161/CIRCHEARTFAILURE.115.002883.
- © 2016 American Heart Association, Inc.