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 EpidemicFramingham

Lloyd-Jones, Circulation, 2004

The AF Epidemic

Miyasaka, Circulation, 2006

AF - Heart Failure Interaction

Maisel, Am J Cardiol, 2003

New York Heart Association Class

I II - III III-IV IVIIIIII

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

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

AF - Heart Failure Interaction

HF → AF AF → HF

Framingham

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

Miller, Canadian Cardiovascular Congress, 2014

Role of dose

HFrEF HFpEF

Beta-blockers for AF in HF

Miller, Canadian Cardiovascular Congress, 2014

Role of achieved heart rate

HFrEF HFpEF

Role of genotype-directed β-blockade

BEST Genetic substudy

Aleong, JACC HF, 2013

AF interferes with HF therapy

Daubert, JACC, 2008; Poole, NEJM, 2008

ICDs

AF interferes with HF TherapyCRT

CRT works by:

– Optimizing atrioventricular timing

– Biventricular pacing to resynchronize contraction

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

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

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

CRT in AF

Role of AV node ablation

Wilton, Heart Rhythm, 2011

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)

Impact of new AF on CRT outcomesEvidence 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?

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

(%

)

Why don’t antiarrhythmic drugs work?

Clinical arguments

Amiodarone in SCD-HeFT: NYHA 3 groupBardy, 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

• Avoid long term

drug toxicity

• Superior to drugs

for AF control

• Most studies

include patients

without heart failure

• Long term benefit

unproven

Change in LVEF6 to 12 months post

Wilton, Am J Cardiol, 2010

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

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

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

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