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Heart Failure and Atrial Fibrillation Stephen Wilton ACC Rockies Banff March 15, 2016 Disclosures • Research funding: – St. Jude Medical • Consulting / Honoraria – Boehringer Ingelheim – Arca Biopharma Key Points • HF and AF are linked, and together are bad news • AF interferes with HF therapy • Rate or Rhythm Control for AF in patients with HF? The Heart Failure Epidemic Annual Canadian Heart Failure Deaths Heart and Stroke Foundation, 2016 The AF Epidemic Framingham Lloyd-Jones, Circulation, 2004 The AF Epidemic Miyasaka, Circulation, 2006 AF - Heart Failure Interaction New York Heart Association Class II II -IIIII III-IV III Maisel, Am J Cardiol, 2003 IV HTN DM Valvular HD ↑filling pressures Intracellular Ca++ dysregulation Neurohumoral activation HF OSA Atrial remodeling Structural Electrophysiologic AF Fibrosis Rapid rate Ventricular remodeling (response to↓CO) CAD Irregular rhythm No atrial systole ↑MR, TR ↑filling pressures Intracellular Ca++ dysregulation Neurohumoral activation HF Atrial remodeling Structural Electrophysiologic AF Fibrosis Rapid rate Ventricular remodeling (response to↓CO) Irregular rhythm No atrial systole ↑MR, TR Adapted from Anter, Circulation, 2009 AF - Heart Failure Interaction Framingham HF → AF AF → HF Santhanakrishnan, Circulation, 2016 We have a crisis March 14, 2016 Key Points • HF and AF are linked, and together are bad news • AF interferes with HF therapy • Rate or Rhythm Control for AF in patients with HF? SR AF Kotecha, Lancet, 2014 Beta-blockers for AF in HF Role of dose HFrEF HFpEF Miller, Canadian Cardiovascular Congress, 2014 Beta-blockers for AF in HF Role of achieved heart rate HFrEF HFpEF Miller, Canadian Cardiovascular Congress, 2014 Role of genotype-directed β-blockade BEST Genetic substudy Aleong, JACC HF, 2013 AF interferes with HF therapy ICDs Daubert, JACC, 2008; Poole, NEJM, 2008 AF interferes with HF Therapy CRT CRT works by: – Optimizing atrioventricular timing – Biventricular pacing to resynchronize contraction AF interferes with HF therapy Cardiac Resynchronization Therapy 12-lead Holter analysis in 19 patients with AF, 9 responders Only 9 had effective pacing (>90% paced) Kamath, JACC, 2009 AF and CRT - Evidence Gap COMPANION n % AF 1212 CARE HF 412 0 0 REVERSE MADIT CRT 419 1820 0 0 RAFT Euro CRT Survey* 1798 2438 13 23 *Dickstein, EHJ, 2009 CRT in AF vs. Sinus Rhythm Death from any cause Mortality N = 7,495 25.5% with AF F/U 33 months Wilton, Heart Rhythm, 2011 CRT in AF Role of AV node ablation Wilton, Heart Rhythm, 2011 Does CRT increase risk of AF? Evidence from RAFT Competing Risk HR: 1.20 (1.0-1.42; p = 0.045) Wilton et al, unpublished Impact of new AF on CRT outcomes Evidence from RAFT Wilton et al, unpublished What about Digoxin? Bavishi, Int J Card, 2015 Digoxin - Power of Confounding Ziff, BMJ, 2015 Digoxin - Power of Confounding Ziff, BMJ, 2015 Key Points • HF and AF are linked, and together are bad news • AF interferes with HF therapy • Rate or Rhythm Control for AF in patients with HF? Pharmacologic Rhythm Control • AF-CHF trial Roy, NEJM, 2008 Why don’t antiarrhythmic drugs work? Statistical arguments Sinus Rhythm in follow-up (%) 80% Rhythm Control 70% 73% Rate Control Cross-over 10%,66% 21% Cross-over 12.2%, 29.2% 62.6% 60% 56% 28% 50% 47% 39% 40% 34.6% 34% 30% 26% 20% 10% 10% 10% 8% 0% 0% PIAF Mean f/u 1 yr RACE 1 yr 2.3 yrs AFFIRM STAF 3.5 yrs 1.2 yrs AF-CHF CAFÉ II 3.1 yrs Why don’t antiarrhythmic drugs work? Clinical arguments Amiodarone in SCD-HeFT: NYHA 3 group Bardy, NEJM, 2005 Why don’t antiarrhythmic drugs work? Clinical arguments Dronedarone in PALLAS (Permanent AF) Connolly, NEJM, 2011 What about AF ablation? • Eliminate AF triggers, modify substrate • Most studies include patients without heart failure • Avoid long term drug toxicity • Long term benefit unproven • Superior to drugs for AF control Change in LVEF 6 to 12 months post Wilton, Am J Cardiol, 2010 Ablation vs. Amiodarone for Treatment of Atrial Fibrillation in Patients with Congestive Heart Failure and an Implanted ICD/CRTD (AATAC-AF in Heart Failure) ClinicalTrials.gov Identifier: NCT00729911/ P.I. Andrea Natale Luigi Di Biase, Prasant Mohanty, Sanghamitra Mohanty, Pasquale Santangeli, Chintan Trivedi, Dhanunjaya Lakkireddy, Madhu Reddy,Pierre Jais, Sakis Themistoclakis, Antonio Dello Russo, Michela Casella, Gemma Pelargonio, Maria Lucia Narducci, Robert Schweikert, Petr Neuzil, Javier Sanchez, Rodney Horton, Salwa Beheiry, Richard Hongo, Steven Hao, Antonio Rossillo, Giovanni Forleo, Claudio Tondo, J. David Burkhardt, Michel Haissaguerre, Andrea Natale Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, Texas, USA;; Late-breaking trials, ACC 2015, San Diego California Pacific Medical Center, San Francisco, California, USA; University of Kansas, Kansas City, USA; University of Sacred Heart, Rome, Italy; AF Ablation for Heart Failure Kaplan–Meier curves success rate AATAC AF –comparing Primary Endpoint 70% in group 1, 34% patients in group 2 were recurrence-free with around 10% of Amio discontinuation due to side effect DiBiase, ACC 2015. AF Ablation for Heart Failure AATAC AF – Secondary Endpoints • Over 2 years of follow-up, AF ablation group had: – Fewer hospitalizations: 32% vs. 57%, p<0.0001 • Lower mortality: – 8 vs. 18, p = 0.037 DiBiase, ACC 2015. Ongoing Canadian Trials RAFT-AF • International, Canadian-led RCT (A. Tang, G. Wells, PIs) • CIHR funding for 5 years • Primary hypothesis: • Catheter ablation-based atrial fibrillation rhythm control as compared with rate control in patients with heart failure of either impaired LV function (LVEF ≤ 45%) or preserved LV function (LVEF > 45%) will reduce all cause mortality or heart failure hospitalization. Ongoing Canadian Trials RAFT- Permanent AF • Primary objective: • To determine whether CRT will reduce allcause mortality or hospitalization for heart failure in patients with permanent AF, mild to moderate heart failure, left ventricular systolic dysfunction, and prolonged QRS duration, when compared to implantable cardioverter defibrillator (ICD) therapy alone Key Points • HF and AF are linked, and both together is bad • AF interferes with HF therapy • Best management of AF in patients with HF is unknown • Ongoing clinical studies may provide clarity