Provocative Cases: Issues in the Expanding Use of CRT in Treating CHF Patients

Transcription

1 Provocative Cases: Issues in the Expanding Use of CRT in Treating CHF Patients David E. Krummen, MD Associate Professor of Medicine University of California San Diego and VA San Diego Healthcare System May 18, 2012

2 Disclosures - Funding NIH Grant studying Computational Modeling of CRT Co-Investigator AHA Beginning Grant-In-Aid studying Ventricular Fibrillation - Principle Investigator NIH Grant studying Atrial Fibrillation Co- Investigator Fellowship Program receives funding from Boston Scientific, Medtronic, St. Jude, Biotronic, and Biosense-Webster

3 Brief Review?

4 Lecture Outline and Definitions Brief Review Discuss several cases to define the expanded population who are candidates for cardiac resynchronization therapy (CRT, CRT-D) with biventricular defibrillators (BiV ICDs) Questions

5 Dual Chamber ICD Configuration Pulse generator Atrial lead Ventricular lead RV coil

6 ICD Function (A, top) ICD interrogation showing initiation of VT. (B, bottom) interrogation shows VF which is appropriately detected and shocked to sinus rhythm.

7 Biventricular ICD Configuration

8 Biventricular ICD Radiography

9 Cases

10 Current Guidelines: It is known that CRT is an effective therapy in patients with HF and IVCD: CRT can improve exercise tolerance and NYHA functional class and reduce both mortality and the need for hospitalization (ref 1). Established criteria (ref 2) Patients who are in sinus rhythm, with an LVEF 35 percent, and a QRS >120 msec, who have moderate to severe symptoms (NYHA class III or IV HF) despite optimal medical therapy, CRT-D is recommended (Grade 1A). (1) McAlister et al. JAMA 2007 (2) Epstein et al. Heart Rhythm 2008

11 Patient 1 Patient 1 is a 61 year old male s/p anterioseptal myocardial infarction, hypothyroidism, and hyperlipidemia with a LV EF initially 16% but improved to 26% with medical management over the past year. Patient 1 reports that he generally feels well, but is winded after climbing up several flights of stairs (NYHA Class II).

12 QRS duration 152 msec ECG 1

13 Questions Is this patient a candidate for ICD therapy? What type of ICD should be discussed with him? What benefits might this have for this patient? What are the data for mortality reduction?

14 RAFT Trial (ref 3) 1798 patients with an LV EF < 30% QRS > 120 msec, NYHA Class II or III Randomly assigned to CRT-D versus ICD alone At 40 months, CRT-D group had fewer deaths and hospitalizations for CHF -Higher rate of procedural complications (infections, lead dislodgement) in CRT group (3) Tang et al. NEJM 2010

15 RAFT Trial Results Addition of CRT to ICD significantly decreased death in patients with mild CHF (NYHA Class II).

16 Conclusions Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. The relative risk of death was reduced by 25%, resulting in an absolute mortality reduction of 6 percentage points at 5 years.

17 Discussion Patient 1 Is this patient a candidate for ICD therapy? What type of ICD should be discussed with him? What benefits might this have for this patient? What are the data for mortality reduction? Questions

18 Next patient

19 Patient 2 Patient 2 is a 57 year old male s/p kidney transplant, persistent AF and atrial tachycardia s/p failed antiarrhythmic therapy and failed cardioversion x 3, suboptimal rate control despite 2 AV nodal agents (not a candidate for calcium channel blocker), EF 28% on good medical therapy, NYHA Class III.

20 AF with RVR, LBBB, QRS duration 138 ECG 2

21 Questions Although clearly an ICD candidate, should CRT be considered in this patient with AF? What else should be recommended to the patient?

22 Evidence in AF Data on CRT in AF are limited Patients with atrial arrhythmias were excluded from the major CRT trials, including CARE-HF and COMPANION

23 AF and CRT Meta-analysis by Upadhyay (ref 4) et al on 4 prospective cohort studies and the MUSTIC randomized trial. Compared responses in 797 patients with sinus rhythm and 367 patients in AF AV node ablation in AF was 56% (4) Upadhyay et al. JACC 2008

24 Benefit of CRT in AF Patients in AF treated by CRT benefit substantially and significantly from CRT Relative to patients in sinus rhythm, these benefits are greater in regard to echocardiographic improvement and smaller in regard to functional outcomes There was no statistically significant difference in mortality between the 2 groups at 1 year

25 Change of Ejection Fraction for Patients in SR Versus AF Patients with AF had better echocardiographic response to CRT than patients with sinus rhythm.

26 Conclusions Patients in AF show significant improvement after CRT, with potentially greater improvement in EF as NSR patients, but smaller benefits in regard to functional outcomes.

27 Importance of AV Node Ablation Gasparini et al (ref 5) evaluated patients with CHF and AF. They compared 48 patients with AF on rate control medications versus 114 patients after AVJ ablation and compared to 511 sinus rhythm controls Within the AF group, only patients s/p AVJ showed improvements in LV EF. Gasparini et al. JACC 2006

28 Importance of AV Node Ablation Gasparini et al, JACC 2006;48:7343

29 Conclusions CHF patients treated with CRT showed improvements in LVEF and functional capacity only if AVJ ablation performed.

30 Discussion Patient 2 Although clearly an ICD candidate, should CRT be considered? What else should be recommended to the patient?

31 Let s Continue

32 Patient 3 Patient 3 is a 57 year old male with nonischemic cardiomyopathy, EF 30%, on good medical management with NYHA Class I symptoms. Referred for consideration of BiV ICD

33 QRS duration 155 ECG 3

34 Questions Patient 3 Is this patient a candidate for an ICD? For CRT? What are the data?

35 MADIT-CRT Trial Moss et al (ref 6) studied 1820 patients with ischemic or nonischemic cardiomyopathy EF 30% or less QRS duration of 130 msec or more NYHA class I or II symptoms The primary end point was death from any cause or a nonfatal heart-failure event (6) Moss et al. NEJM 2009

36 Kaplan-Meier Estimates of the Probability of Survival Free of Heart Failure Moss A et al. N Engl J Med 2009; /NEJMoa

37 Changes in Mean Echocardiographic Left Ventricular Volumes and Ejection Fraction between Baseline and 1-Year Follow-up Moss A et al. N Engl J Med 2009; /NEJMoa

38 Results: MADIT-CRT The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events in these patients with asymptomatic or mildly symptomatic CHF. A substudy by Zareba et al (ref 7) showed that the benefits were seen primarily in a prespecified subgroup of patients with LBBB. (7) Zareba et al. Circ 2011

39

40 Recommendations FDA expanded indication for CRT-D (Sept 16, 2010): Asymptomatic or mildly symptomatic CHF (NYHA Class I or II) EF 30% or less QRS duration of 130 msec or more LBBB

41 Discussion Patient 3 Is this patient a candidate for an ICD? For CRT? What are the data?

42 Final Case

43 Patient 4 Patient 4 is a 72 year old female with Mobitz II heart block s/p pacemaker, ischemic cardiomyopathy, EF 32%, native QRS duration 96 msec (no BBB), NYHA class II.

44 Questions Patient 4 Is this patient a candidate for an ICD? For CRT? What additional data are required?

45 Pacemaker interrogation High percentage of pacing (95%)

46 CRT Guidelines (ref 2) CRT may be considered for patients with LVEF < 35% with NYHA Class I or II symptoms who are receiving optimal medical therapy and who are undergoing implantation of an ICD with anticipated frequent ventricular pacing (Grade 2B). (2) Epstein et al. Heart Rhythm 2008

47 Discussion Patient 4 Is this patient a candidate for an ICD? For CRT? What additional data are required?

48 Summary and Recommendations CRT is an effective therapy in patients with HF and IVCD. CRT can improve exercise tolerance and NYHA functional class and reduce both mortality and the need for hospitalization in patients in sinus rhythm. For patients who are in sinus rhythm, with an LVEF 35 percent, and as QRS >120 msec, who have moderate to severe symptoms (NYHA class III or IV HF) despite optimal medical therapy, CRT-D is recommended (Grade 1A). *For patients who are in sinus rhythm, with an LVEF 30 percent, and a QRS 130* msec, who have mild symptoms (NYHA class II HF) despite optimal medical therapy, CRT-D is recommended (Grade 1A). *FDA expanded indications, Sept 16, 2010

49 Summary and Recommendations *For patients who are in sinus rhythm, with an LVEF 30 percent, and a QRS 130* msec and left bundle branch block, who have NYHA Class I symptoms, CRT-D is recommended (Grade 2B). *For patients with LVEF 35 percent with NYHA functional class III or ambulatory class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT-D is recommended (Grade 2B). For patients whose functional status and life expectancy are limited predominantly by chronic noncardiac conditions, CRT is not indicated. *FDA expanded indications, Sept 16, 2010

50 Summary and Recommendations CRT-D recommendations are similar for patients with atrial fibrillation (Grade 2B). *(Already included in European guidelines) AV node ablation is suggested following CRT-D (Grade 2B). In patients with AF undergoing AV node ablation with an EF of 35%, CRT-D is recommended (Grade 2B).

51 Additional Issues Efficacy in NYHA Class IV Lindenfeld et al (ref 8) appears effective Age - CARE-HF and COMPANION Trials - Equivalent benefit above and below 65 RBBB Unclear benefit - Exclusion from CRT for NYHA Class I Cost effectiveness Feldman et al (ref 9) - $43,000 per QALY for CRT-D Echocardiography ASE Consensus statement, Gorcsan et al (ref 10) CRT should not be withheld by echo findings, and echo should not routinely recommend CRT

52 The End

53 Thank You Clinical Acknowledgements: UCSD: Greg Feld, MD Sanjiv Narayan, MD, PhD Ulrika Green, MD Vincent Chen, MD Nav Sawhney, MD Subha Varahan, MD Ravi Kilaru, MD Kishlay Anand, MD Siva Mulpuru, MD Huy Phan, MD Joycelle Martinez, NP Vivika Wax, NP EP Lab and Office Staff Clinical Acknowledgements: VA: Sanjiv Narayan, MD, PhD Marian Holland, MD Stephanie Yoakum, NP Liz Greer, RN Donna Cooper, RN Tony Moyeda, CVT Ken Hopper, CVT Research: Andrew McCulloch, PhD Wouter-Jan Rappel, PhD Kathleen Mills, BS Paul Clopton, MS Carey Briggs, BS

54 References 1. McAlister FA, Ezekowitz J, Hooton N, et al. Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA : the journal of the American Medical Association 2007;297: Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: executive summary. Heart Rhythm 2008;5: Tang AS, Wells GA, Talajic M, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. The New England journal of medicine 2010;363: Upadhyay GA, Choudhry NK, Auricchio A, Ruskin J, Singh JP. Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. Journal of the American College of Cardiology 2008;52: Gasparini M, Auricchio A, Regoli F, et al. Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. Journal of the American College of Cardiology 2006;48: Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. The New England journal of medicine 2009;361: Zareba W, Klein H, Cygankiewicz I, et al. Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 2011;123: Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association class IV heart failure. Circulation 2007;115: Feldman AM, de Lissovoy G, Bristow MR, et al. Cost effectiveness of cardiac resynchronization therapy in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial. Journal of the American College of Cardiology 2005;46: Gorcsan J, 3rd, Abraham T, Agler DA, et al. Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting--a report from the American Society