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 I II - III III-IV I II III IV Maisel, Am J Cardiol, 2003
HTN DM Valvular HD OSA CAD ↑filling pressures Atrial remodeling Intracellular Ca ++ Structural dysregulation Electrophysiologic Neurohumoral activation HF AF Fibrosis Rapid rate Ventricular Irregular rhythm remodeling No atrial systole (response to↓CO) ↑MR, TR
↑filling pressures Atrial remodeling Intracellular Ca ++ Structural dysregulation Electrophysiologic Neurohumoral activation HF AF Fibrosis Rapid rate Ventricular Irregular rhythm remodeling No atrial systole (response to↓CO) ↑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 CARE REVERSE MADIT RAFT Euro CRT HF CRT Survey* n 1212 412 419 1820 1798 2438 % AF 0 0 0 0 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 80% Rhythm Control Sinus Rhythm in follow-up (%) 73% Cross-over 10%, 21% 70% Rate Control Cross-over 66% 62.6% 12.2%, 29.2% 60% 56% 28% 47% 50% 39% 40% 34.6% 34% 30% 26% 20% 10% 10% 10% 8% 0% 0% PIAF RACE AFFIRM STAF AF-CHF CAFÉ II Mean f/u 1 yr 2.3 yrs 3.5 yrs 1.2 yrs 3.1 yrs 1 yr
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 • Most studies triggers, modify include patients substrate without heart failure • Avoid long term • Long term benefit drug toxicity 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 ’ ; Late-breaking trials, ACC 2015, San Diego ’ ; ôpit Lévêque é
AF Ablation for Heart Failure – AATAC AF – 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 all- cause 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
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