Download CRT in Patients with Permanent AF vs. Sinus Rhythm: Symptomatic

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