Paul Dorian, MD Hôpital St Michel, Toronto Défibrillateurs Implantables pour Prévenir la Mort Subite- Pour Qui et Comment? Paul Dorian, MD Hôpital St Michel, Toronto

Patient ER (FV spontanée)

The Inventor of the AICD History of the AICD 1966- Dr. M. Mirowski conceives the idea of an implantable defibrillator after his friend, colleague and mentor Dr. Harry Heller dies of sudden cardiac death Guidant logo in upper right corner/ Dr. Michel Mirowski (1924-1990) The Inventor of the AICD

History of ICD Therapy 1975 - The first device is implanted and tested in an animal 1980 - The first patient is implanted with an AICD device

ICD’s Today ( 2004) Small devices – Pectoral site Transvenous, single incision Local anesthesia; conscious sedation hospital stay usually 0-1 days Few complications ( similar to pacemakers_) Perioperative mortality < 0.5% Programmable therapy options Single- or dual-chamber therapy Battery longevity up to 9 years Recognizes VT and VF – 99% Terminates VT and VF – 99% Pacemaker Today’s devices are implanted pectorally, either subcutaneously or submuscularly in most patients. 1998 actual implants (estimates): 45,000 in U.S. 10,000 outside of U.S. 55,000 Worldwide Battery longevity projections for Medtronic devices: GEM 5.0 years – 100% pacing, monthly shocks 6.9 years – 100% pacing, quarterly shocks 9.1 years – 100% sensing, 0% pacing, quarterly shocks GEM DR 5.5 years – 100% pacing, monthly shocks 6.6 years – 100% pacing, quarterly shocks 7.8 years – 0% pacing, monthly shocks 9.6 years – 0% pacing, quarterly shocks Micro Jewel II 4.9 years – 100% pacing, monthly shocks 7.8 years – 100% sensing, 0% pacing, quarterly shocks Jewel AF 5.1 years – 100% pacing, monthly shocks 8.9 years – 0% pacing, quarterly shocks

Anti-tachycardia pacing therapy Antitachycardia Pacing (ATP) Shock (cardioversion)

Qui a besoin d’un Defibrillateur Implantable ? Tous qui sont a haut risque de TV soutenue ou FV: Dysfonction du VG Maladie Coronarienne ou cardiomyopathie Surtout histoire antecedante de tachycadie ventriculaire ou arret cardiaque ( FV)

The Penalty for Failure is Death Fu Manchu

Relation between triggers and substrate in SCD Big Trigger Trigger Small trigger lightning NSVT VPB, EAD Ischemia Tachycardia Adrenergic drive Good EF Substrate Poor EF The substrate is DYNAMIC

Categories of ICD indications “Secondary prophylaxis” : Patients with a prior history of sustained VT or VF No reversible factors ( eg acute MI) “Primary prophylaxis” : Patients with no history of sustained VT or VF Risk factors for sudden death - severe LV dysfunction - Heart failure symptoms - Non sustained VT ? - inducible VT at EP study?

Meta-Analysis of ICD Secondary Prevention Trials: AVID, CASH, CIDS Pts with prior sustained VT or VF Death Arrhythmic Death Amio Amio ICD ICD Years Years Number at risk: ICD: 934 715 467 273 159 104 934 715 467 273 159 104 Amio: 932 664 427 248 128 82 932 664 427 248 128 82 Connolly et al. Eur Heart J 2000;21:2071-8

Long term follow up of Patients Treated with Amiodarone in CIDS (SMH, n=60) Mortality 100 Mortality or Recurrence of Arrhythmia 80 Mortality, Recurrence of Arrhythmia or Discontinuation of Amiodarone Due to Side Effects Freedom From Event (%) 60 40 20 2 4 6 8 10 12 Time (Years) Bokhari et al Circ. 2004

Vaccin pour prevenir la Mort Subite? Facteurs de risque – Fraction d’éjection < 30% Cicatrise du VG surtout ancien infarctus Tachycardie non soutenue sur Holter ( ?) symptômes d’insuffisance cardiaque

Time after Enrollment (Years) MUSTT Study: CAD, EF < 40% , NSVT ( > 4d post MI), inducible VT/VF (17% < 1mo, 22% 1mo-1 yr post MI) 0.6 No EP-Guided AA Rx EP-Guided Rx, No ICD 0.5 Not randomized EP-Guided Rx, ICD 0.4 Mortality Rate 0.3 p < 0.001 0.2 0.1 1 2 3 4 5 Time after Enrollment (Years) Buxton AE. N Engl J Med. 1999;341:1882-90. 20

Probability of Survival MADIT-II : ICD’s for patients with prior MI and EF < 30%, no prior arrhythmias 1.0 0.9 Defibrillator 0.8 Probability of Survival 0.7 Conventional P = 0.007 0.6 0.0 1 2 3 4 Year No. at Risk Defibrillator 742 502 (0.91) 274 (0.94) 110 (0.78) 9 Conventional 490 329 (0.90) 170 (0.78) 65 (0.69) 3 Moss AJ. NEJM 2002;346:877-83.

QRS Prolongation: A Strong Independent Risk Factor for Mortality in Patients with Severe Ischemic Heart disease QRS Duration, ms Mortality, % <100 (n=58) 13.8 100-119 (n=86) 17.6 120-139 (n=65) 23.6 140-159 (n=44) 45.5  140 (n=60) 43.3 Kalahasti V et al, PACE 2002;24:528

Noninvasive ECG Parameters in Multivariate Cox Model for Predicting Total Mortality in MADITT II Patients Randomized to Conventional Therapy Variable Age ≥ 65 years NYHA ≥ II BUN > 25 No BB use AFib QRS > 0.12 sec HR 1.47 2.00 1.94 1.57 2.36 1.90 (95% CI) (0.86-2.52) (1.20-3.34) (1.17-3.21) (0.94-2.66) (1.14-4.89) (1.14-3.14) P value 0.164 0.008 0.010 0.089 0.021 0.013 Zareba et al, NASPE 2002

HR = 0.37 (p=0.004) 63% reduction in mortality Survival in Defibrillator Group and Conventional Treatment Group in 364 MADITT II Patients with QRS > 0.12 sec (excluding paced patients) MORTALITY 2-yr 36% 14% 3-yr 53% 21% Conv ICD HR = 0.37 (p=0.004) 63% reduction in mortality Zareba et al NASPE 2002

SCD HeFT-Enrollment Scheme DCM ± CAD and CHF EF ≤ 35% NYHA Class II or III 6 minute walk, Holter R Placebo Amiodarone ICD n=847 n=845 n=829

Mortality by Intention to Treat 28.9% 35.8% 34.1% Amiodarone vs. Placebo ICD Therapy vs. Placebo HR 1.06 0.77 97.5% CI 0.86, 1.30 0.62, 0.96 P-Value 0.529 0.007 ICD pts – 5%/yr risk of appropriate shock

No Technology is perfect Inappropriate shocks Lead fracture. Dislodgement Infection Short battery life ( 5-7 years) Complex programming and follow-up Doesn’t prevent all sudden death

ICDs in SCD-HeFT 2.2% not implanted 4.0% removed, not replaced 4.6% serious complications at implant, no deaths 9.4% serious complications in follow-up 5.0% appropriate shocks / pt / yr total: 7.4% shocks / pt / yr

Aucune technologie n’est parfaite choc non appropriée ( pour tachycardie non dangereuse) Infection Durée courte de vie des batteries ( env. 5 ans) programmation compliquée Et…. Prolonge pas la vie de tous

CABG Patch : ICD immediately after CABG EF <35%, +ve SAECG 30 27% 24% 20 Cumulative Mortality (%) Defibrillator Group 10 Control Group p = 0.64 12 24 36 48 Month Defibrillator Gr. 446 384 313 213 61 Control Group 454 399 308 199 57 Bigger JT. NEJM 1997;337(22):1569-1575.

Early post MI ICD vs control: All-Cause Mortality DINA IT Early post MI ICD vs control: All-Cause Mortality Months Day 6-40 post MI, EF < 35%, depressed HRV

Why Don’t ICDs Save Everyone From Dying a Sudden Death?  Some patients die from CHF or MI or Asystole / PEA  Some VT / VF is a precursor to non-arrhythmic death  Some VT / VF presents as electrical storm - electrical success, but poor outcome

ICD Implant Rates continue to diverge between Europe and USA MUSTT MADIT II ??? Annual ICD implants per million inhabitants MADIT & AVID USA * ICD implant rates/million population for all of Europe (red), compared to the U.S. (yellow), during the 1990s. Superimposed are the important studies – MADIT, AVID, and MUSTT (see later slides for details) – the first two published in 1996, and MUSTT in 1999, all of which had an important impact on ICD therapy acceptance in the U.S., but apparently little or no impact in Europe. Although the European implant rates are also steadily increasing, It is apparent that the curves are in fact diverging, with the U.S. over 200 implants/million, roughly 5-fold the European rate. The next major study, MADIT II, finished end 2001, and we will be interested to see the impact both in Europe and the U.S. of MADIT II. CANADA Europe Updated from Nisam S, 2000

The Real Questions in Deciding on ICD Recommendation What is the annual risk of sudden arrhythmic death? (or the risk / device lifetime, ~ 5 years) What is the annual risk of death from other causes? All ICDs are Prophylactic

MERCI

Meta-analysis of All Primary Trials of ICD for Primary Prophylaxis

Recommendations for ICD Class I: Patients with ischemic heart disease and LV ejection fraction ≤ 30%, measured at least one month post myocardial infarction and three months post coronary revascularization procedure*. (Level of Evidence: A) Add risk stratification during the presentation * Coronary bypass surgery or percutaneous coronary intervention

ACC/AHA format of classification of recommendations Class IIa Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. IIa: Weight of evidence/opinion is in favour of usefulness/efficacy. IIb: Usefulness/efficacy is less well established by evidence/opinion.

Recommendations for ICD Class IIa: Patients with ischemic heart disease and LV dysfunction (LVEF = 31 - 35%), measured at least one month post myocardial infarction (MI) and three months post coronary revascularization procedure* with inducible VF/sustained VT at electrophysiology study. (Level of Evidence: B)

Recommendations for ICD Class IIa: Patients with non-ischemic cardiomyopathy present for greater than or equal to 9 months, LV dysfunction (LVEF ≤ 30 %), and heart failure NYHA functional class II-III. (Level of Evidence: B) Patients with familial or inherited conditions such as but not limited to long QT syndrome, hypertrophic cardiomyopathy, Brugada syndrome or arrhythmogenic right ventricular cardiomyopathy, and at a high risk for life-threatening ventricular tachyarrhythmias. (Level of Evidence: B)

Recommendations for ICD Class IIb: Patients with ischemic heart disease, prior myocardial infarction (MI), LV dysfunction (LVEF = 31-35%) with either no inducible VF/sustained VT at electrophysiology study, or without an electrophysiology study. (Level of Evidence: C) Patients with non-ischemic cardiomyopathy present for at least nine months, LV dysfunction (LVEF = 31–35%) and NYHA functional class II-III heart failure. (Level of Evidence: C) Severe symptoms (e.g. syncope) attributable to sustained ventricular tachyarrythmias while awaiting cardiac transplantation. (Level of Evidence: C)