heart failure and atrial fibrillation - acc rockies · 2020-03-10 · u niv ers ity of sac red h...
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Heart Failure and Atrial
Fibrillation
Stephen Wilton
ACC Rockies
Banff
March 15, 2016
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Disclosures
• Research funding:
– St. Jude Medical
• Consulting / Honoraria
– Boehringer Ingelheim
– Arca Biopharma
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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?
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The Heart Failure Epidemic
Annual Canadian Heart Failure Deaths
Heart and Stroke Foundation, 2016
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The AF EpidemicFramingham
Lloyd-Jones, Circulation, 2004
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The AF Epidemic
Miyasaka, Circulation, 2006
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AF - Heart Failure Interaction
Maisel, Am J Cardiol, 2003
New York Heart Association Class
I II - III III-IV IVIIIIII
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HF AFFibrosis
Rapid rate
Irregular rhythm
No atrial systole
↑MR, TR
↑filling pressures
Intracellular Ca++
dysregulation
Neurohumoral
activation
Structural
Electrophysiologic
Ventricular
remodeling(response to↓CO)
Atrial
remodeling
HTN DM Valvular HD OSA CAD
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HF AFFibrosis
Rapid rate
Irregular rhythm
No atrial systole
↑MR, TR
↑filling pressures
Intracellular Ca++
dysregulation
Neurohumoral
activation
Structural
Electrophysiologic
Ventricular
remodeling(response to↓CO)
Atrial
remodeling
Adapted from Anter, Circulation, 2009
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AF - Heart Failure Interaction
HF → AF AF → HF
Framingham
Santhanakrishnan, Circulation, 2016
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We have a crisis March 14, 2016
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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?
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SR AF
Kotecha, Lancet, 2014
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Beta-blockers for AF in HF
Miller, Canadian Cardiovascular Congress, 2014
Role of dose
HFrEF HFpEF
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Beta-blockers for AF in HF
Miller, Canadian Cardiovascular Congress, 2014
Role of achieved heart rate
HFrEF HFpEF
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Role of genotype-directed β-blockade
BEST Genetic substudy
Aleong, JACC HF, 2013
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AF interferes with HF therapy
Daubert, JACC, 2008; Poole, NEJM, 2008
ICDs
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AF interferes with HF TherapyCRT
CRT works by:
– Optimizing atrioventricular timing
– Biventricular pacing to resynchronize contraction
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AF interferes with HF therapyCardiac Resynchronization Therapy
12-lead Holter analysis in 19 patients with AF, 9 responders
Only 9 had effective pacing (>90% paced)
Kamath, JACC, 2009
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AF and CRT - Evidence Gap
COMPANION CARE HF
REVERSE MADITCRT
RAFT Euro CRT Survey*
n 1212 412 419 1820 1798 2438
% AF 0 0 0 0 13 23
*Dickstein, EHJ, 2009
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CRT in AF vs. Sinus RhythmDeath from any cause
Wilton, Heart Rhythm, 2011
N = 7,495
25.5% with
AF
F/U 33
months
Mortality
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CRT in AF
Role of AV node ablation
Wilton, Heart Rhythm, 2011
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Does CRT increase risk of AF?Evidence from RAFT
Wilton et al, unpublished
Competing Risk HR: 1.20 (1.0-1.42; p = 0.045)
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Impact of new AF on CRT outcomesEvidence from RAFT
Wilton et al, unpublished
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What about Digoxin?
Bavishi, Int J Card, 2015
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Digoxin - Power of Confounding
Ziff, BMJ, 2015
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Digoxin - Power of Confounding
Ziff, BMJ, 2015
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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?
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Pharmacologic Rhythm Control
• AF-CHF trial
Roy, NEJM, 2008
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Why don’t antiarrhythmic drugs work?
56%
39%
62.6%
34%
73%
66%
10% 10%
34.6%
8%
26%
0%0%
10%
20%
30%
40%
50%
60%
70%
80%
PIAF RACE AFFIRM STAF AF-CHF CAFÉ II
Rhythm Control
Rate Control
28% 47%
Mean f/u 1 yr 2.3 yrs 3.5 yrs 1.2 yrs 3.1 yrs
1 yr
Cross-over12.2%, 29.2%
Cross-over10%, 21%
Statistical argumentsS
inu
s R
hyth
m in
fo
llow
-up
(%
)
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Why don’t antiarrhythmic drugs work?
Clinical arguments
Amiodarone in SCD-HeFT: NYHA 3 groupBardy, NEJM, 2005
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Why don’t antiarrhythmic drugs work?
Clinical arguments
Dronedarone in PALLAS (Permanent AF)Connolly, NEJM, 2011
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What about AF ablation?
• Eliminate AF
triggers, modify
substrate
• Avoid long term
drug toxicity
• Superior to drugs
for AF control
• Most studies
include patients
without heart failure
• Long term benefit
unproven
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Change in LVEF6 to 12 months post
Wilton, Am J Cardiol, 2010
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Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, Texas, USA;;
California Pacific Medical Center, San Francisco, California, USA;
University of Kansas, Kansas City, USA;
University of Sacred Heart, Rome, Italy;
University of Tor Vergata, Rome, Italy;
Cardiac Arrhythmia Research Centre, Centro Cardiologico Monzino IRCCS, Milan, Italy;
Ospedale dell’ Angelo, Mestre, Venice, Italy;;
Hôpital Cardiologique du Haut Lévêque, Université Victor-Segalen Bordeaux, France;
Akron General Hospital, Akron, Ohio, USA;
Department of Cardiology, Na Homolce Hospital, Roentgenova 2, Prague, Czech Republic
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
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AF Ablation for Heart Failure
DiBiase, ACC 2015.
AATAC AF – Primary EndpointKaplan–Meier curves comparing success rate
70% in group 1, 34% patients in group 2 were
recurrence-free with around 10% of Amio
discontinuation due to side effect
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AF Ablation for Heart Failure
• 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.
AATAC AF – Secondary Endpoints
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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.
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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
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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