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ICDs for Heart Failure

ICDs for Heart Failure. Derek T. Connelly President - Heart Rhythm UK Consultant Cardiologist - Glasgow Royal Infirmary September 2005. ICD Technology. ICD Technology. ICD Trials: “Secondary prevention”. Randomised Trials of ICD Therapy.

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ICDs for Heart Failure

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  1. ICDs for Heart Failure Derek T. Connelly President - Heart Rhythm UK Consultant Cardiologist - Glasgow Royal Infirmary September 2005

  2. ICD Technology

  3. ICD Technology

  4. ICD Trials:“Secondary prevention”

  5. Randomised Trials of ICD Therapy “Secondary prevention” - patients who have had sustained VT or VF • Antiarrhythmics versus Implantable Defibrillator (AVID) - 1997 • Cardiac Arrest Study Hamburg (CASH) - 2000 • Canadian Implantable Defibrillator Study (CIDS) - 2000

  6. Antiarrhythmics Versus Implantable Defibrillator (AVID) • 6000 patients screened, 1016 randomised • Mean age 65, 79% male, mean LVEF 31% • Inclusion arrhythmia: • Ventricular fibrillation 45% • Ventricular tachycardia with syncope 21% • Symptomatic VT with LVEF <40% 34% • ICD in 507, Antiarrhythmic drugs in 509 N Engl J Med 1997; 337: 1576-83

  7. N Engl J Med 1997; 337: 1576-83

  8. AVID subgroups N Engl J Med 1997; 337: 1576-83

  9. Meta-analysis - ICD v Amiodarone S J Connolly, Eur Heart J 2000; 21:2071-8

  10. Meta-analysis - ICD v Amiodarone S J Connolly, Eur Heart J 2000; 21:2071-8

  11. ICD Trials:“Primary prevention”

  12. Randomised Trials of ICD Therapy “Primary prevention” - patients who have not yet had VT or VF, but are thought to be at high risk • Multicenter Automatic Defibrillator Implantation Trial (MADIT) -1996 • Multicenter UnSustained Tachycardia Trial (MUSTT) - 1999 • MADIT 2 – 2002 • COMPANION – 2004 • SCD-HeFT - 2004

  13. Studies of Non-Sustained VTin pts with CAD, poor LV, inducible sustained VT • Multicenter Automatic Defibrillator Implantation Trial (MADIT) • Hypothesis that survival with ICD is better than with antiarrhythmic drugs when VT cannot be suppressed by IV procainamide • Multicenter UnSustained Tachycardia Trial (MUSTT) • Hypothesis that survival with EP guided Rx (with ICD for drug failures) is better than controls

  14. Multicenter Automatic Defibrillator Implantation Trial (MADIT) • Post - MI patients with asymptomatic non-sustained VT and LVEF < 35%; age 25 - 80 • Sustained VT reproducibly inducible at EPS and not suppressible with IV procainamide • Randomised to antiarrhythmic drugs or ICD Moss et al N Engl J Med 1996; 335: 2933-40

  15. MADIT - Results Moss et al N Engl J Med 1996; 335: 2933-40

  16. MUSTT Protocol

  17. MUSTT Results • 2202 pts with NSVT studied, 767 inducible, 704 pts randomised • 351 EP guided Rx, 353 no antiarrhythmic Rx • 40% on b-blockers, 75% on ACE inhibitors • 158 pts (45%) on antiarrhythmic drugs • Class I 26%, amio 10%, sotlol 9% • 161 pts (46%) had ICD Buxton et al N Engl J Med 1999; 341: 1882-90

  18. MUSTT Results • 5 year mortality 24% in pts with ICD, 55% in those without (p<0.001) • antiarrhythmic drugs had no effect on mortality • Relative risk of total mortality in ICD treated patients was 0.40 (95% CI 0.27-0.59) Buxton et al N Engl J Med 1999; 341: 1882-90

  19. MUSTT - Results Buxton et al. N Engl J Med 1999 ;341:1882-90

  20. UK ICD Guidelines • ‘Secondary Prevention’: • Cardiac arrest due to VT or VF • Spontaneous sustained VT with syncope or significant haemodynamic compromise • Sustained VT with poor ejection fraction (<35%), NYHA Class > 3 www.nice.org.uk September 2000

  21. UK ICD Guidelines • ‘Primary Prevention’: • Previous MI and all of the following: • Non-sustained VT on 24 hour ECG monitoring • Inducible VT on electrophysiological testing • LV ejection fraction < 35%, NYHA Class > 3 • A familial condition with a high risk of sudden death, e.g. Long QT, HOCM, Brugada syndrome, ARVD, repaired tetralogy of Fallot www.nice.org.uk September 2000

  22. NICE ICD GuidelinesAdditional Recommendations • Protocols for the implantation of ICDs should be developed, to include: • early referral of appropriate patients • rapid decision making and implantation • conscious sedation rather than GA • rehabilitative approach to after-care, including psychological preparation for living with ICD • early discharge • efficient and comprehensive follow-up

  23. ICD Trials: Why is the benefit greater in “Primary Prevention” studies? • In AVID, CASH and CIDS, the main entry criterion was ventricular arrhythmia • Some patients had preserved LV function • Mortality reduction with ICD 28% overall • Mortality reduction 34% in patients with LVEF < 35% • In MADIT and MUSTT, the main entry criterion was poor LV function • LVEF <35% in MADIT, <40% in MUSTT • Mortality reduction with ICD 54 - 60% • Heterogeneity in antiarrhythmic drug use

  24. 1990’s Patients at highest risk of sudden death are those with ventricular arrhythmias (spontaneous or induced) The ICD is a treatment for ventricular arrhythmias 2000’s Patients at highest risk of sudden death are those with heart failure due to poor LV systolic function The ICD is a treatment for heart failure Who benefits most from ICDs?

  25. MADIT-2 • Post MI, LVEF < 30% • ICD or control • Post - randomisation: non-invasive markers, EP study • Primary end-point total mortality; secondary: QOL, cost • Target enrolment 1200 patients Klein et al Am J Cardiol 1999; 83: 91D-97D

  26. MADIT-2 • Study terminated November 20, 2001 • 1232 patients randomised • 742 defibrillator, 490 conventional • Mean follow-up 20 months (range 6 days - 53 months • 105 deaths in ICD group (14.2%) • 97 deaths in conventional group (19.8%) • 31% reduction in risk of death with ICD Moss et al New Engl J Med 2002; 346: 877-883

  27. MADIT-2Concomitant therapies • ACE inhibitors used in 70% •  blockers used in 70% • Statins used in 68% • 57% had previously had CABG • 44% had previously had PTCA • MADIT-2 targeted patients who were considered suitable for CABG / PTCA • Benefit of ICD is over & above benefit from revascularisation

  28. MADIT II Results Moss et al New Engl J Med 2002; 346: 877-883

  29. MADIT-2Subgroup analyses and additional tests • Heart rate variability (several parameters), signal averaged ECG - not useful • EP study performed in those with ICD • If EP +ve, more likely to get VT • If EP -ve, more likely to get VF ! • Overall limited usefulness • QRS width - powerful predictor of benefit from ICD

  30. MADIT II - Subgroup analysis Moss et al New Engl J Med 2002; 346: 877-883

  31. COMPANION Results Bristow et al New Engl J Med 2004; 350: 2140

  32. COMPANION Results Bristow et al New Engl J Med 2004; 350: 2140

  33. COMPANION Subgroups Bristow et al New Engl J Med 2004; 350: 2140

  34. Companion Study • Biventricular pacing (+ ICD) • Improves quality of life • Improves 6-minute walk time • Reduces need for hospitalisation for heart failure • Improves NYHA functional class

  35. MIRACLE ICD Study Efficacy of antitachycardia pacing • 88% from RV (336 episodes) • 95% from LV (658 episodes)

  36. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) • 2500 patients with symptomatic heart failure (NYHA 2-3) and LV ejection fraction < 35% • 50% ischaemic, 50% idiopathic DCM • Randomised to • No antiarrhythmic therapy • Amiodarone • ICD • 5 year follow-up • Results presented March 2004

  37. Hypothesis and Primary Endpoint • To determine, by intention-to-treat analysis, if amiodarone or a conservatively programmed shock-only ICD reduces all-cause mortality compared to placebo* in patients with either ischemic or non-ischemic NYHA Class II and III CHF and EF < 35%. * Double-blind for drug therapy

  38. Baseline Enrollment Characteristics • Age 60.1 yrs (51.7, 68.5) median (25th, 75th percentiles) • Female 23% • Minorities 23% • Heart rate 73 bpm (63, 84) • Blood pressure • Systolic 118 mmHg (106, 130) • Diastolic 70 mmHg (62, 80) • Weight 190 lbs (164, 219)

  39. Baseline Enrollment Characteristics • CHF duration 24.5 mo (8.1, 59.4) • LV EF 25.0 (20.0, 30.0 • NYHA II, III 70%, 30% • Ischemic, non-ischemic 52%, 48% • 6 minute walk 1130 ft (840, 1360) • Diabetes 30% • CABG and/or Perc. Revasc. 37% • H/O Hypertension 56% • H/O Hyperlipidemia 53% • H/O AF 15% • H/O NSVT 23% • ECG QRS duration ms 112 ms (96, 140), 41% > 120

  40. Background Medications BaselineLast follow-up ACE Inhibitor 85% 72% ACE Inhibitor or ARB 96% 87% Beta-blocker 69% 78% Spironolactone 19% 31% Loop diuretics 82% 80% Aspirin 56% 55% Statin 38% 47% Median follow-up 45.5 months

  41. Mortality by Intention-to-Treat 0.4 • Median follow-up: 45.5 mo (34.8, 55.2) • Vital status known on 100% of 2,521 patients 36.1% 7.2%/year 0.3 0.2 Mortality Amiodarone 0.1 ICD Therapy Placebo 0 0 6 12 18 24 30 36 42 48 54 60 Months of follow-up

  42. Mortality by Intention-to-Treat 0.4 HR 97.5% Cl P-Value Amiodarone vs. Placebo 1.06 0.86, 1.30 0.529 0.3 0.2 Mortality Amiodarone 0.1 ICD Therapy Placebo 0 0 6 12 18 24 30 36 42 48 54 60 Months of follow-up

  43. Amiodarone vs. PlaceboHazard Ratios Patient Group N HR 97.5% Cl All Patients 1692 1.06 0.86, 1.30 NYHA Class Class II 1195 0.85 0.65, 1.11 Class III 497 1.44 1.05, 1.97 CHF Etiology Ischemic 879 1.05 0.81, 1.36 Non-Ischemic 813 1.07 0.76, 1.51 0.5 1 2 4

  44. Additional Subgroups: Amiodarone vs. Placebo Patient Group N HR 97.5% Cl Gender Female 398 1.17 0.72, 1.90 Male 1294 1.04 0.83, 1.30 LVEF <30% 1407 1.04 0.84, 1.29 > 30% 285 1.24 0.66, 2.31 Age < 65 1119 1.00 0.76, 1.32> 65 573 1.13 0.83, 1.52 QRS Duration < 120 ms 999 1.06 0.80, 1.41> 120 ms 692 1.05 0.78, 1.41 Race White 1292 1.06 0.84, 1.34 Non-White 400 1.08 0.71, 1.62 Enrolling Country U.S. 1534 1.07 0.86, 1.32 Non-U.S. 158 0.98 0.52, 1.84 Beta Blocker Yes 1162 1.10 0.85, 1.42 No 530 0.98 0.69, 1.38 Diabetes Yes 514 1.20 0.87, 1.65 No 1178 1.00 0.77, 1.30 0.5 1 2 4

  45. Mortality by Intention-to-Treat 0.4 HR 97.5% Cl P-Value Amiodarone vs. Placebo 1.06 0.86, 1.30 0.529 ICD Therapy vs. Placebo 0.77 0.62, 0.96 0.007 0.3 0.2 Mortality Amiodarone 0.1 ICD Therapy Placebo 0 0 6 12 18 24 30 36 42 48 54 60 Months of follow-up

  46. ICD vs. PlaceboHazard Ratios Patient Group N HR 97.5% Cl All Patients 1676 0.77 0.62, 0.96 NYHA Class Class II 1160 0.54 0.40, 0.74 Class III 516 1.16 0.84, 1.61 CHF Etiology Ischemic 884 0.79 0.60, 1.04 Non-Ischemic 792 0.73 0.50, 1.04 0.25 0.5 1 2

  47. Additional Subgroups: ICD vs. Placebo Patient Group N HR 97.5% Cl Gender Female 382 0.96 0.58, 1.61 Male 1294 0.73 0.57, 0.93 LVEF <30% 1390 0.73 0.57, 0.92 > 30% 285 1.08 0.57, 2.07 Age < 65 1098 0.68 0.50, 0.93> 65 578 0.86 0.62, 1.18 QRS Duration < 120 ms 977 0.84 0.62, 1.14> 120 ms 699 0.67 0.49, 0.93 Race White 1283 0.78 0.61, 1.00 Non-White 393 0.75 0.48, 1.17 Enrolling Country U.S. 1512 0.82 0.65, 1.04 Non-U.S. 164 0.37 0.17, 0.82 Beta Blocker Yes 1157 0.68 0.51, 0.91 No 519 0.92 0.65, 1.30 Diabetes Yes 524 0.95 0.68, 1.33 No 1152 0.67 0.50, 0.90 0.125 0.25 0.5 1 2 4

  48. SCD-HeFT: Conclusions • In class II or III CHF patients with EF < 35% on good background drug therapy, the mortality rate for placebo-controlled patients is 7.2% per year over 5 years • Simple, shock-only ICDs decrease mortality by 23% • Amiodarone, when used as a primary preventive agent, does not improve survival

  49. SCD-HeFT – Cost-benefit analysis • Cost per life-year saved (US$) • LVEF < 30% $33,509 • LVEF > 30% $29,275 • Age > 65 $39,469 • Age < 65 $29,164 • QRS > 120 ms $31,244 • QRS < 120 ms $34,821 • Ischaemic $33,603 • Non-ischaemic $32,170 DB Mark, AHA November 2004

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