Device therapy in heartfailure Update of the ESC guidelines. Karl Swedberg

Transcription

1 Device therapy in heartfailure Update of the ESC guidelines Karl Swedberg Professor of Medicine Department of emergency and cardiovascular medicine Sahlgrenska Academy University of Gothenburg, Sweden

2 Disclosure No conflicts in relation to this presentation

3 2010 Focused Update of ESC Guidelines on Device Therapy in Heart Failure An Update of the 2008 ESC guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and the 2007 ESC guidelines for Cardiac and Resynchronization Therapy, developed in collaboration with the HFA and EHRA Authors/Task Force Members: Kenneth Dickstein* (Chairperson) (Norway), Panos E. Vardas** (Chairperson) (Greece), Angelo Auricchio (Switzerland), Jean-Claude Daubert (France), Cecilia Linde (Sweden), John McMurray (UK), Piotr Ponikowski (Poland), Silvia Giuliana Priori (Italy), Richard Sutton (UK), Dirk van Veldhuisen (Netherlands) ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland), Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK), Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos Vardas (Greece), Petr Widimsky (Czech Republic) Document Reviewers, Michal Tendera (CPG Review Coordinator) (Poland), Stefan D. Anker (Germany), Jean-Jacques Blanc (France), Maurizio Gasparini (Italy), Arno W. Hoes (Netherlands), Carsten W. Israel (Germany), Zbigniew Kalarus (Poland), Bela Merkely (Hungary), Karl Swedberg (Sweden), A. John Camm (UK) European Heart Journal doi: /eurheartj/ehq337

4 Classes of Recommendations Class I Class II Class IIa Class IIb Class III Definition Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure. Suggested wording to use Is recommended/is indicated Weight of evidence/opinion is Should be considered in favour of usefulness/efficacy. Usefulness/efficacy is less well established by evidence/opinion. Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful. May be considered Is not recommended European Heart Journal doi: /eurheartj/ehq337

5 LEVELS OF EVIDENCE European Heart Journal doi: /eurheartj/ehq337

6 Evidence table 1: Inclusion criteria in RCTs evaluating CRT in heart failure Trial Patients NYHA class LVEF(%) LVEDD (mm) SR/AF QRS (ms) ICD MUSTIC-SR (16) 58 III 35% 60 SR 150 No MIRACLE (5) 453 III,IV 35% 55 SR 130 No MUSTIC AF (35) 43 III 35% 60 AF 200 No PATH CHF (6) 41 III,IV 35% NA SR 120 No MIRACLE ICD (8) 369 III,IV 35% 55 SR 130 Yes CONTAK CD (55) 227 II,IV 35% NA SR 120 Yes MIRACLE ICD II (9) 186 II 35% 55 SR 130 Yes PATH CHF II (56) 89 III,IV 35% NA SR 120 Yes/No COMPANION (10) 1520 III,IV 35% NA SR 120 Yes/No CARE HF (11) 814 III,IV 35% 30 SR 120 No CARE HF (17) 813 III,IV 35% 30 SR 120 No REVERSE (21, 22) 610 I,II <40% 55 SR >120 Yes/No MADIT CRT (20) 1800 I,II <30% NA SR >130 ms Yes European Heart Journal doi: /eurheartj/ehq337

7 CARE-HF Mortality or CV hospitalisation RRR=52% Cleland et al. N Engl J Med 2005;352:

8 Recommendation in patients with heart failure in NYHA function class III/IV Recommendation Patient Population Class LoE CRT-P/CRT-D* is recommended to reduce morbidity and mortality NYHA function class III/IV LVEF 35%, QRS 120 ms, SR Optimal medical therapy Class IV patients should be ambulatory** I A *Reasonable expectation of survival with good functional status for >1 year for CRT-D. Patients with a secondary prevention indication for an ICD should receive a CRT-D. ** No admissions for HF during the last month and a reasonable expectation of survival >6 months. European Heart Journal doi: /eurheartj/ehq337

9 CRT-P/CRT-D in patients with heart failure in NYHA function class III/IV Key points: New: LV dilatation no longer required New: Class IV patients should be ambulatory New: Reasonable expectation of survival with good functional status for >1 year for CRT-D Evidence is strongest for patients with typical LBBB Similar level of evidence for CRT-P and CRT-D European Heart Journal doi: /eurheartj/ehq337

10 Percentage Hospitalised for HF or Died REVERSE 24-months analysis: Reductions in risk of first HF hospitalisation or death 30% 25% 20% Hazard Ratio: %CI: P= % 15% RRR=62% CRT OFF 11.7% 10% 5% 0% CRT ON Months Since Randomisation Number at Risk CRT OFF CRT ON Daubert et al. JACC 2009;54:

11 Probability of Survival Free of Heart Failure MADIT-CRT RRR=34% N Engl J Med 2009;361

12 MADIT-CRT: Risk of death or heart failure Moss et al. N Engl J Med 2009;361:

13 Recommendation in patients with heart failure in NYHA function class II Recommendation Patient Population Class Level CRT preferentially by CRT-D is recommended to reduce morbidity or to prevent disease progression* NYHA function class II LVEF 35%, QRS 150 ms, SR Optimal medical therapy I A * The guideline indication has been restricted to patients with HF in NYHA function class II with a QRS width 150 ms, a population with a high likelihood of a favourable response. European Heart Journal doi: /eurheartj/ehq337

14 CRT-D in patients with heart failure in NYHA function class I/II Key points: 2 recent, randomised, prospective, multicentre trials in mild HF (MADIT-CRT and REVERSE) demonstrate reduced morbidity 18% of patients in REVERSE and 15% of patients in MADIT-CRT were in NYHA I class at baseline Improvement primarily seen in patients with QRS 150 ms and/or typical LBBB Women with LBBB showed a particularly favourable response Survival advantage not established In MADIT-CRT the extent of reverse remodelling was concordant with and predictive of improvement in clinical outcomes European Heart Journal doi: /eurheartj/ehq337

15 RAFT

16 RAFT CRT/ICD in mild-moderate symptoms Tang et al NEJM 2010

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18 Atrial Fibrillation HF hospitalisation / 1 year AV ablation vs. AF drugs Ferreira et al. Europace 2008;10:

19 Comparison of CRT in sinusrythm (n=1042), AF with AV ablation (n=118) vs. AF drug (n=125) therapy Adjusted hazard ratios for death Atrial Fibrillation Gasparini et al. Eur Heart J 2008;29:

20 Recommendations in patients with heart failure and permanent atrial fibrillation Recommendations Patient Population Class Level CRT-P/CRT-D* should be considered to reduce morbidity NYHA function class III/IV LVEF 35%, QRS 130 ms Pacemaker dependency induced by AV nodal ablation IIa B CRT-P/CRT-D* should be considered to reduce morbidity NYHA function class III/IV LVEF 35%, QRS 130 ms Slow ventricular rate and frequent pacing** IIa C *Reasonable expectation of survival with good functional status for >1 year for CRT-D. Patients with a secondary prevention indication for an ICD should receive a CRT-D. ** Frequent pacing is defined as 95% pacemaker dependency European Heart Journal doi: /eurheartj/ehq337

21 CRT-P/CRT-D in patients with heart failure and permanent atrial fibrillation Key points: Approximately 1/5 of CRT implantations in Europe are in patients with permanent AF NYHA class III/IV symptoms and an LVEF 35% are well-established indications for ICD Frequent pacing is defined as 95% pacemaker dependency AV nodal ablation may be required to assure adequate pacing Evidence strongest for patients with an LBBB pattern Insufficient evidence for mortality recommendation European Heart Journal doi: /eurheartj/ehq337

22 Recommendations in patients with heart failure and a concomitant class I pacemaker indication Recommendations Patient Population Class Level CRT-P/CRT-D* is recommended to reduce morbidity CRT-P/CRT-D* should be considered to reduce morbidity CRT-P/CRT-D* may be considered to reduce morbidity NYHA function class III/IV LVEF 35%, QRS 120 ms NYHA function class III/IV LVEF 35%, QRS<120 ms NYHA function class II LVEF 35%, QRS<120 ms I IIa IIb B C C * Reasonable expectation of survival with good functional status for >1 year for CRT-D. Patients with a secondary prevention indication for an ICD should receive a CRT-D. European Heart Journal doi: /eurheartj/ehq337

23 Key points: CRT-P/CRT-D in patients with heart failure and a conventional pacemaker indication In patients with a conventional indication for pacing, NYHA III/IV symptoms, LVEF 35%, QRS width 120 ms, a CRT-P/CRT-D is indicated RV pacing will induce dyssynchrony Chronic RV pacing in patients with LV dysfunction should be avoided CRT may permit adequate uptitration of beta-blocker treatment European Heart Journal doi: /eurheartj/ehq337

24 HEARTMATE Survival n=192 Slaughter et al. N Engl J Med 2009;361:

25 Recommendation in patients with severe heart failure ineligible for transplant Recommendations Patient Population Class Level LVAD may be considered as destination treatment to reduce mortality NYHA function class IIIB/IV LVEF 25% peak VO2<14 ml/kg/min* IIb B *If obtainable European Heart Journal doi: /eurheartj/ehq337

26 Left Ventricular Assist Device as destination therapy for patients with severe HF ineligible for cardiac transplantation Key points: The NIH INTERMACS registry indicates that ~10% of patients in clinical practice receive an LVAD as destination therapy Patient population mainly consists of patients on inotropic (and/or mechanical) support prior to LVAD implantation Patient selection is crucial and candidates should not have significant renal, pulmonary or hepatic dysfunction or infection The available evidence suggests that a continuous flow device is superior to a pulsatile flow device No controlled data available as bridge to heart transplantation European Heart Journal doi: /eurheartj/ehq337

27 Gaps in evidence CRT in Patients with Heart Failure Selection criteria CRT Implantation Issues Chronological/biological age? Major Comorbidities? QRS between ms? RBBB? LVEF >35%? Role of imaging to detect volumes/ mechanical dyssynchrony/viable myocardium Mitral insufficiency? NYHA function class I? CRT-P or CRT-D? Importance of operator experience? Role of imaging to determine optimal lead placement? Skills in optimal AV, VV programming? Which factors in patient selection, lead placement or follow-up predict a poor response? Health resource utilisation and cost/benefit ratio?

28 Summary of indications for CRT in patients with heart failure Patient population Recommendations CoR LoE CRT-P/CRT-D* is recommended to reduce morbidity and mortality NYHA class III/IV symptoms LVEF 35%, QRS 120 ms, SR Optimal medical therapy Class IV patients should be ambulatory** I A CRT preferentially by CRT-D* is recommended to reduce morbidity or to prevent disease progression NYHA class II symptoms LVEF 35%, QRS 150 ms, SR I A CRT-P/CRT-D* should be considered to reduce morbidity Permanent Atrial Fibrillation NYHA class III/IV LVEF 35%, QRS 130 ms Pacemaker dependency induced by AV nodal ablation IIa B CRT-P/CRT-D* should be considered to reduce morbidity Permanent Atrial Fibrillation NYHA class III/IV LVEF 35%, QRS 130 ms Slow ventricular rate and frequent pacing*** IIa C CRT-P/CRT-D* is recommended to reduce morbidity Class I indication for pacemaker NYHA class III/IV LVEF 35%, QRS 120 ms I B CRT-P/CRT-D* should be considered to reduce morbidity Class I indication for pacemaker NYHA class III/IV LVEF 35%, QRS<120 ms IIa C CRT-P/CRT-D* may be considered to reduce morbidity Class I indication for pacemaker NYHA class II LVEF 35%, QRS<120 ms IIb C LVAD may be considered as destination treatment to reduce mortality NYHA IIIB/IV symptoms Ineligible for cardiac transplantation LVEF 25% IIb B

29 BACKUP

30 Evidence table 1: Inclusion criteria in RCTs evaluating CRT in heart failure Trial Patients NYHA class LVEF(%) LVEDD (mm) SR/AF QRS (ms) ICD MUSTIC-SR (16) 58 III 35% 60 SR 150 No MIRACLE (5) 453 III,IV 35% 55 SR 130 No MUSTIC AF (35) 43 III 35% 60 AF 200 No PATH CHF (6) 41 III,IV 35% NA SR 120 No MIRACLE ICD (8) 369 III,IV 35% 55 SR 130 Yes CONTAK CD (55) 227 II,IV 35% NA SR 120 Yes MIRACLE ICD II (9) 186 II 35% 55 SR 130 Yes PATH CHF II (56) 89 III,IV 35% NA SR 120 Yes/No COMPANION (10) 1520 III,IV 35% NA SR 120 Yes/No CARE HF (11) 814 III,IV 35% 30 SR 120 No CARE HF (17) 813 III,IV 35% 30 SR 120 No REVERSE (21, 22) 610 I,II <40% 55 SR >120 Yes/No MADIT CRT (20) 1800 I,II <30% NA SR >130 ms Yes RAFT (57) 1800 Canada II,III <30% >60 SR/AF > * Yes European Heart Journal doi: /eurheartj/ehq337

31 Evidence table 2: Endpoints, design and main findings of the RCTs evaluating CRT in heart failure Trial Endpoints Design Main findings MUSTIC-SR (16) 6MWT, QoL, pvo 2, Hosp Single-blinded, controlled, crossover, 6 months CRT-P improved: 6MWT, QOL, pvo 2 ; reduced Hosp MIRACLE (8) NYHA class, QoL, pvo 2 Double-blinded, controlled, 6 months CRT-P improved: NYHA, pvo 2, 6MWT MUSTIC AF (35) 6MWT, QoL, pvo 2, Hosp Single-blinded, controlled, crossover, 6 months CRT-P improved all; reduction of Hosp PATH CHF (6) 6MWT, pvo 2 Single-blinded, controlled, crossover, 12 months CRT-P improved: 6MWT; pvo 2 MIRACLE ICD (8) 6MWT, QoL, Hosp Double-blinded, ICD vs. CRT-D 6 months CRT-D improved all from baseline (not ICD) CONTAK CD (54) All-cause death + HF Hosp, pvo 2, 6MWT, NYHA class, QoL, LVEDD, LVEF Double-blinded, ICD vs. CRT-D 6 months CRT-D improved: pvo 2, 6MWT; reduced LVEDD and increased LVEF MIRACLE ICD II (9) VE/CO 2, pvo 2, NYHA, QoL, 6MWT, LV volumes, LVEF Double-blinded, ICD vs. CRT-D 6 months CRT-D improved: NYHA, VE/CO 2 ; volumes, LVEF COMPANION (10) (1) All-cause death or Hosp Double-blinded, controlled, OPT, CRT-D, CRT-P, about 15 months CRT-P/CRT-D: reduced (1) CARE-HF (11) (1) All-cause death or CV event (2) All-cause death Double-blinded, controlled, OPT, CRT-P, 29 months CRT-P reduced (1) and (2) REVERSE (21) (1) % worsened by clinical composite endpoint, (2) LVESVi, (3) HF hosp, (4) all-cause death Double-blinded, controlled, OPT, CRT-P +ICD, 12months Primary endpoint NS CRT-P/CRT-D reduced (2) and (3) hosp but not (4) MADIT CRT (20) (1) HFevent or death (2) All-cause death (3) LVESV Controlled, CRTP, CRT-D, 2.4 years CRT-D reduced (1) and (3c) but not (2) European Heart Journal doi: /eurheartj/ehq337

32 Primary Event Rate after 1 year (per 100-person years) Concordance with Outcomes ICD Quartiles CRT-D Quartiles Percent Change in LV End Diastolic Volume, Baseline to 12-months Solomon et al Circ /CIRCULATIONAHA

33 Traditionally, guideline recommendations are based on the outcomes in the cohort of patients described by the inclusion criteria in the protocols of Randomised Clinical Trials. In contrast to previous guidelines, this focused update considers the characteristics of the patients included in the trials and contains several examples. The text accompanying these recommendations explains and justifies the decisions to diverge from a traditional recommendation based strictly on the protocol inclusion criteria. The task force hopes that the users of the Guidelines will appreciate that this adjustment provides a more realistic application of the trial evidence to daily clinical practice.

34 Monitoring of MADIT CRT by the DSMB N Engl J Med 2009;361

35 In MADIT-CRT, although the protocol permitted inclusion of patients in both NYHA I and II function class, only 15% of the patients included in this trial were classified as NYHA I, many of whom had been previously symptomatic. Similarly, although the inclusion criteria permitted randomisation of patients with a QRS width 130 m, the favourable effect on the primary endpoint was limited to patients with a QRS width 150 ms, a prospective, prespecified cut-off.

36 In patients with mild symptoms and a QRS width of ms, clinicians may wish to assess other criteria associated with a favourable outcome such as: dyssynchrony by echocardiography LV dilatation LBBB non-ischaemic cardiomyopathy recent NYHA class III symptoms

37 ESC CRT SURVEY Age 75 (%) 31% NYHA I 2% NYHA II 20% Atrial fibrillation 23% QRS duration < 120 ms 9% QRS duration ms 10% Eur Heart J 2009;30:

38 Parachutes appear to reduce the risk of injury, but their effectiveness has not been proved with randomised controlled trials