Managing Atrial Fibrillation in the Heart Failure Patient

Transcription

1 Managing Atrial Fibrillation in the Heart Failure Patient Jonathan S. Steinberg, MD Professor of Medicine (adj) University of Rochester School of Medicine & Dentistry Director, Arrhythmia Institute Valley Health System New York, NY

2 Disclosures Consultant: Medtronic, Boston Scientific, Biosense Webster, AliveCor, Janssen, Pfizer, Allergan Speaker s Bureau: Bristol-Myers Squibb, Pfizer Research Grant: Medtronic, Biosense Webster

3 Prevalence of AF in Systolic Heart Failure Annual Incidence ~ 5% From Maisel and Stevenson, AJC 2003

4 Incidence of AF in Diastolic Dysfunction Stroke risk increased similarly in HFrEF and HFpEF T s

5 Prognosis is Negatively Influenced by Presence of AF Dries et al, JACC 1998; Santhankrishnan et al, Circulation 2016

6 Prognosis is Negatively Influenced by Presence of AF Framingham Study 2016 AF HFrEF/HFpEF Dries et al, JACC 1998; Santhankrishnan et al, Circulation 2016

7 Therapeutic Objectives for AF Management are Universal Symptom relief Stroke prevention Rhythm control Antiarrhythmic drug Catheter ablation Rate control Medical therapy with AVN blockers AVJ ablation and pacemaker ( Ablate + Pace )

8 Annual Stroke Rate (%) Refinement of Stroke Risk Stratification in AF: CHA 2 DS 2 -VASc CHADS 2 Risk Factor Score Annual Risk of Stroke (%) Cardiac failure 1 HTN 1 Age 75 y 1 Diabetes 1 Stroke 2 CHA 2 DS 2 -VASc Risk Factor Score Cardiac failure 1 HTN 1 Age 75 y 2 Diabetes 1 Stroke 2 Vasc dz (MI, PAD, aortic ath) 1 Age y 1 Sex category (female) CHADS 2 CHA 2 DS 2 -VASc Total Score Gage BF, et al. JAMA. 2001:285(22); ; Lip GY, Halperin JL. Am J Med. 2010;123(6):

9 Annual Stroke Rate (%) Refinement of Stroke Risk Stratification in AF: CHA 2 DS 2 -VASc CHADS 2 Risk Factor Score Annual Risk of Stroke (%) Cardiac failure 1 HTN 1 16 CHA 2 DS 2 -VASc C in CHA 2 DS 2 -VASc refers to documented 14 moderate-to-severe systolic dysfunction [i.e. 12 heart CHA 2 DS failure 2 -VASc with reduced ejection fraction (HF- 10 REF)] or patients Score with recent decompensated 8 heart failure requiring hospitalization, 6 irrespective of ejection fraction [i.e. both HF-REF 4 Age 75 y 1 Diabetes 1 Stroke 2 Risk Factor Cardiac failure 1 HTN 1 Age 75 y 2 Diabetes 1 Stroke 2 Vasc dz (MI, PAD, aortic ath) 1 Age y 1 Sex category (female) CHADS 2 and heart failure with preserved ejection fraction 2 (HF-PEF)] Total Score Gage BF, et al. JAMA. 2001:285(22); ; Lip GY, Halperin JL. Am J Med. 2010;123(6):

10 Risk of Stroke in Patients with HF Framingham Heart Study Adj. RR 4.1 Adj. RR 2.8 Lee et al, Circ Heart Fail 2013

11 Pivotal Warfarin-Controlled Trials Stroke Prevention in AF Warfarin vs. Placebo 2,900 Patients 6 Trials of Warfarin vs. Placebo ROCKET AF (Rivaroxaban) 2010 NOACs vs. Warfarin 71,683 Patients ENGAGE AF-TIMI 48 (Edoxaban) 2013 RE-LY (Dabigatran) 2009 ARISTOTLE (Apixaban) 2011

12 The Novel Oral Anticoagulants X TF/VIIa IX VIIIa IXa Va Xa II Rivaroxaban Apixaban Edoxaban Dabigatran IIa Fibrinogen Fibrin Adapted from: Weitz JI, Bates SM. J Thromb Haemost 2005

13 Properties of an Ideal Anticoagulant Properties Oral, once-daily dosing Rapid onset of action Minimal food or drug interactions Predictable/consistent anticoagulant effect Nonrenal clearance Rapid offset in action Antidote/reversal agent Benefit Ease of administration No need for bridging Simplified dosing No coagulation monitoring Safe in patients with renal insufficiency Simplifies management if bleeding or intervention For emergencies

14 NOACs vs Warfarin: Stroke/SEE RE-LY [150 mg] ROCKET AF Risk Ratio (95% CI) 0.66 ( ) 0.88 ( ) ARISTOTLE 0.80 ( ) ENGAGE AF-TIMI 48 [60 mg] 0.88 ( ) Combined 0.81 ( ) Favors NOAC N=58,541 Favors Warfarin p=< Ruff et al, Lancet. 2013

15 NOACs vs Warfarin: Major Bleeding RE-LY [150 mg] ROCKET AF Risk Ratio (95% CI) 0.94 ( ) 1.03 ( ) ARISTOTLE 0.71 ( ) ENGAGE AF-TIMI 48 [60 mg] 0.80 ( ) Combined 0.86 ( ) Favors NOAC N=58,498 Favors Warfarin p=0.06 Ruff et al, Lancet. 2013

16 ESC 2012 AF Guidelines

17 Prevention of Stroke: Challenges of Warfarin in Heart Failure Witt et al; J Thromb Haemost 2010

18 Prevention of Stroke: Challenges of Warfarin in Heart Failure TTR HF Witt et al; J Thromb Haemost 2010

19 NOAC Efficacy in Heart Failure D 110 D 150 Apixaban Rivaroxaban Edox 60 Edox 30

20 ROCKET AF Heart Failure Analysis N = 9033 (64%) EF < 40% in 1/3 Stroke and bleeding rates similar in HF and non-hf cohorts Riva rx effect similar in both cohorts Riva effect similar LVEF NYHA class HFrEF/HFpEF Van Diepen et al; Circ HF 2013

21 Network Meta-Analysis Tereshchenko and Steinberg, JAHA (in press)

22 Network Meta-Analysis Tereshchenko and Steinberg, JAHA (in press)

23 Therapeutic Objectives for AF Management are Universal Symptom relief Stroke prevention Rhythm control Catheter ablation Rate control AVJ ablation and pacemaker

24 Pivotal Trials With Adequate Power and Hard Cardiovascular Outcomes Ongoing CASTLE-AF (2008) RAFT-AF (2011)

25 Therapeutic Objectives for AF Management are Universal Symptom relief Stroke prevention Rhythm control Catheter ablation Rate control AVJ ablation and pacemaker

26 CARE-HF

27 CARE-HF

28 Atrial Fibrillation in CRT-D Recipients New CRT device volume in US approximated 100,000 in 2011 Annual costs of $1.8 billion 2012 NCDR ICD US Registry data: 31% of 326,000 patients had AF NCDR ICD US Registry data: 36% of 87,692 CRT-D patients had AF 2 Rhythm in CRT Patients at Implant Sinus AF 1 Auricchio et al, AJC 2007; Dickstein et al, Eur Heart J 2009; Medtronic, Inc. (internal data); 2 NCDR ICD Registry Data 28

29 Official Guideline Recommendations ESC 2012 IIA Recommendation - AHA/ACC/HRS Updated 2012 McMurray et al, Eur Heart J 2012; Tracey et al, Circulation 2012

30 RAFT Findings in AF Substudy ( 60 bpm at rest, 90 bpm during 6MHW test) CRT-D (n =114) ICD (n=115) 30 Healey et al, Circulation HF 2012

31 RAFT Findings in AF Substudy ( 60 bpm at rest, 90 bpm during 6MHW test) Patients with permanent AF who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared to standard ICD. CRT-D (n =114) ICD (n=115) 31 Healey et al, Circulation HF 2012

32 The Challenge of AF in the CRT Patient With Heart Failure CRT depends upon synchronizing ventricular activation via biventricular pacing with atrial activity (ie AV synchrony) In the absence of organized atrial activity (eg AF), there can be no coordinated AV synchrony and conducted atrial impulses inevitably compete with pacing impulses to capture the ventricles. To overcome this, one must: Sufficiently control conducted ventricular rate Boriani, Eur J HF 2011 Steinberg JS, JACC 2006

33 The Challenge of AF in the CRT Patient With Heart Failure CRT depends upon synchronizing ventricular activation via biventricular pacing with atrial activity (ie AV synchrony) In the absence of organized atrial activity (eg AF), there can be no coordinated AV synchrony and conducted atrial impulses inevitably compete with pacing impulses to capture the ventricles. To overcome this, one must: Sufficiently control conducted ventricular rate Boriani, Eur J HF 2011 Steinberg JS, JACC 2006

34 Suggestion That AVJ Ablation is the Solution 34

35 Physicians Have Concerns of Pacemaker Dependency After AVJ Ablation Is fear of PM dependency unfounded? Redundancy of pacing leads (RV and LV) Bipolar or quadripolar leads Intense remote surveillance now routine

36 Randomized Clinical Trials of Atrial Fibrillation in Patients Undergoing Cardiac Resynchronization Therapy AVJ ablation in patients with permanent AF who undergo CRT results in improved outcome Greater reduction in LVESV Reduced risk of heart failure event or death AF ablation vs rate control (medication and AVJ) Early vs deferred AVJ ablation

37 Lip et al, EHJ 2016

38 Thank you!