Prof L DE ROY Université de Louvain Université de Louvain CLINIQUES UNIVERSITAIRES UCL DE MONT-GODINNEBelgique QUAND PROPOSER UN TRAITEMENT ELECTRIQUE ?

J Am Coll Cardiol 2002;40:1703–19

Recommendations for ICD Therapy Class I (A) J Am Coll Cardiol 2002;40:1703–19 P=0.009 Moss AJ, N Engl J Med 1996;335: Buxton AE,, N Engl J Med 1999 MADIT I MADIT II Moss AJ, N Engl J Med 2002;346: P=0.007 LVEF35% LVEF30% MUSTT Class II a (B)

J Am Coll Cardiol 2002;40:1703–19 N Engl J Med 2001;344: N Engl J Med 2002;346: Pacing Recommendations for Dilated Cardiomiopathy P=0.03 P<0.001 MIRACLE MUSTIC

Swedberg et al., EHJ 2005;26:

CRT Pacemakers

N Engl J Med 2004;350: CRTP -CRTD

Cleland JG, N Engl J Med 2005;352: Class I B CRTP

CARE-HF trial : extension phase Cleland et al Eur Heart J 2006;27: All cause mortality Worsening heart failure Sudden cardiac death

Swedberg et al., EHJ 2005;26: ICD – ICD +CRT (COMPANION) (AVID) (MADIT II/SCD HeFT) Class II a (B) Class I (A) ICD +CRT ICD

Class II a (B)

Hunt SA,Circulation 2005;20: e154-e685

Cardiac Resynchronization (CRTP / CRTD) Stage C Therapy:Reduced LVEF with Symptoms Hunt SA,Circulation 2005;20: e154-e685 The use of an ICD in combination with CRT should be based on the indications for ICD therapy. CARE-HF

Stage D Therapy Patients with refractory end-stage HF and implantable defibrillators should receive information about the option to inactivate defibrillation. Inform on option to inactivate defibrillation

Boriani G., J Interv Card Electrophysiol 2007 Characteristics of patients enrolled and QRS eligibility criteria of the major RCTs on CRT

Results of cardiac resynchronization in CHF from CRT* *with estimated extent of effect Boriani G., J Interv Card Electrophysiol 2007, feb 24

Indication to CRT according to recent ACC/AHA guidelines CL I (A) Boriani G., J Interv Card Electrophysiol 2007

Quen est-il de lasynchronisme et QRS fins

Bleeker GB, J Am Coll Cardiol 2006;48:2243–50 Magnitude of Improvement in Clinical and Echocardiographic Parameters After CRT* n =33

Changes in LVESV, LVEDV, and EF in HF pts with narrow QRS complexes with/without significant systolic asynchrony according to asynchrony index Left ventricular end-systolic vol. Left ventricular end-diastolic vol. Left ventricular ejection fraction Yu CM.,J Am Coll Cardiol 2006;48:2251–7 N=102

Quen est-il de la classe IV

Time to mode of death by treatment arm for NYHA class IV in COMPANION trial A. Time to sudden death Lindenfeld JA, Circulation. 2007;115: B. Time to HF death N=217 CRTD CRT

FAUT-IL ADJOINDRE SYSTEMATIQUEMENT UN DAI A LA CRT ?

Residual risk of sudden cardiac death in heart failure beta-blocker trials Field M, J Interv Card Electrophysiol, 2007

Survival for biventricular ICD and biventricular PM Ermis C, J Cardiovasc Electrophysiol 2004(15):

CRTD VS CRT META-ANALYSIS OF COMPANION + ERMIS: ALL CAUSE MORTALITY: OR = 0.69 (0.53,0.91) P= ABDULLA 2006

Estimated annualized sudden cardiac death rates in patients with nonischemic dilated cardiomyopathy receiving medical therapy Field M, J Interv Card Electrophysiol, 2007

NNT Resynchronisation 1 an3 ans1 an3.5 ans1 an CRT-DCRT-PCarvedilolCaptoprilSuccinate de metoprolol Aurrichio et al, Circulation 2004, 109;

Number of patients with NYHA class IV heart failure enrolled in primary prevention ICD trials Field M, J Interv Card Electrophysiol, 2007

Delnoy PP., J Cardiovasc Electrophysiol, 2007(18): Percentage of patients after 2 years survival with sustained LV remodeling or an increase in absolute LVEF of 5% after CRT N=89 sustained LV remodeling means LV end systolic volume (LVESV) reduction of 10%

Lindenfeld JA, Circulation. 2007;115: NYHA class IV endpoints by treatment arm in COMPANION trial Primary time to all-cause death or hospitalization Secondary time to all-cause death Time to all-cause death or HF hospitalization N=217

Death among patients with AF randomized to CRT vs RV pacing Bradley DJ.,Heart Rhythm 2007;4:224 –232 MUSTIC–AF: Multisite Stimulation in Cardiomyopathy Study–Atrial Fibrillation PAVE: Post AV Nodal Ablation Evaluation OPSITE: Optimal Pacing SITE Study CRT: 49% reduction in the relative risk of all-cause mortality p=0.547

Results of cardiac resynchronization in CHF from CRT* *with estimated extent of effect Boriani G., J Interv Card Electrophysiol, 2007

Abdulla J.,Cardiology 2006;106:249–255 Effect of CRT on all-cause mortality

Identification des patients: les études en resynchronisation MIRACLE MIRACLE NYHA III-IV NYHA III-IV FE< 35% FE< 35% QRS > 130 ms QRS > 130 ms Φ LVED > 55mm Φ LVED > 55mm Rythme sinusal Rythme sinusal CARE-HF NYHA III-IV (+ de 6 sem) NYHA III-IV (+ de 6 sem) Ischémique ou non Ischémique ou non DTDS > 30 mm/m² DTDS > 30 mm/m² FE <35% FE <35% QRS > 120 ms QRS > 120 ms Si ms 2 des critères suivants sont requis: Retard pré-éjection Ao > 140 msRetard pré-éjection Ao > 140 ms Délai inter-vent mécan.> 40 msDélai inter-vent mécan.> 40 ms Retard activation postéro-lat. paroi vent. gaucheRetard activation postéro-lat. paroi vent. gauche Rythme sinusal Rythme sinusal CRT - P CRT COMPANION NYHA III-IV NYHA III-IV CHF isch ou non CHF isch ou non Hospit dans lannée écoulée Hospit dans lannée écoulée FE<35% FE<35% Φ LVED > 60 mm Φ LVED > 60 mm QRS >120ms QRS >120ms PR >150ms PR >150ms Rythme sinusal Rythme sinusal CRT - D 1.Amélioration NYHA, périmètre de marche, QoL. 2.Réduit les hospitalisations pour IC et toutes causes 1.Réd. Mortalité tt causes - 36% 2.Réd. Hospitalisations - 52% 3.Amélioration des symptômes 4.Amélioration des capacités deffort 1.Réduction de la mortalité -36% 2.Réduc. Hospitalisations -37% Bénéfices Devices Patients

CARE-HF 813 patients (82 centres en Europe) TMO [404 patients] TMO + CRT-P [409 patients] Critères dinclusion : - NYHA III-IV, -QRS > 120ms, - LVEDD > 30 mm -FE < 35%. Objectifs primaires : - mortalité - hospitalisation pour cause cardiovasculaire Etiologie HF38% ischémique Fraction déjection26% NYHA [%]0 – 0 – 94 – 6 Durée du suivi29.4 mois Arythmies auriculaires21% Historique de diabète21% Durée du QRS165 ms QRS > 120 ms100% Test de marche 6 min- ACE I 80% Bétabloquant72% Diurétique99% Spironolactone56% Statine39% La réduction du risque absolu (RA) est de 9.4% (p = 0.002) après 29.4 mois. Elle (RA) grimpe à 13.4% ( p< ) après 36.4 mois (Care HF extension) Cleland JN Engl J Med. April 14, 2005;352: % p = 0.002

COMPANION patients (128 centres au Etats-Unis) TMO [308 patients] TMO + CRT-P [617 patients] Critères dinclusion : -NYHA III-IV, -QRS > 120 ms, - PR interval > 150ms, -LVEDD > 60mm - EF < 35%. Objectifs primaires : mortalité ou hospitalisation Etiologie HF59% ischémique Fraction déjection22% NYHA [%]0 – 0 – 86 – 14 Durée du suivi12 mois Arythmies auriculaires- Historique de diabète41% Durée du QRS160 ms QRS > 120 ms100% Test de marche 6 min258 m ACE I 69% Bétabloquant68% Diurétique97% Spironolactone55% Statine- Le défibrillateur associé à la resynchronisation diminue la mortalité de 36% (p = 0.003) par rapport au groupe contrôle. Bardy GH. N Engl J Med. January 20, 2005;352: TMO + CRT-D [595 patients] - 36% p = 0.003

Mort subite TV soutenue Patient IC symptomat. FE Basse < 30 – 35% Post MI > 40 j NYHA III-IV QRS Long > 120 ms FE altérée NYHA III IV FE Basse < 35% QRS Long > 120 ms Critères dinclusion ESC Remboursements MADIT II CARE HF COMPANION Pt NYHA I-III FE <30% Post infar asympt LVD Pt NYHA III-IV FE <35 DTDS >30 mm/m QRS > 150 NYHA III-IV CHF isch ou non Hospit dans lannée écoulée FE<35% Φ LVED > 60 mm QRS >120ms PR >150ms Mort subite TV soutenue CRT-D DAI CRT SymptômesSyncope Périodes de vertige BradycardieProphylaxieHF Dysfonction cérébrale Ethiologie Fibrose tissu de conduct. Post MI Congénital Chirurgical /complic. chir. Ablation Syndrome sinus carotid. Cardiomyop – Myocardite Maladie valvulaire ECG AV Block Block Faisceau de Hiss Block de branche Syndrome sinusal Tachy atriale Tachy ventriculaire AVID Pt survivants de FV FV avec syncope FV avec FE < 40% + sympt Pt NYHA I-III FE <35% Post infar asympt Tachy vent MADIT I Pt CHF FE<35% NYHA II-III SCD- HeFT Remboursements

Saluke TV,Circulation, 2004;109: Life-Years Gained per Device Implanted

Cleland JGF,The European Journal of Heart Failure 6 (2004) 501–508 Meta-analysis of trials comparing ICD with control on mortality in patients with heart failure and/or left ventricular systolic dysfunction

All-cause mortality among patients with NICM randomised to ICD vs medical therapy in secondary prevention NICM=nonischemic cardiomyopathy Desai AS, JAMA 2004;292/

Total annual costs of New York Heart Association class III–IV heart failure patients Field M, J Interv Card Electrophysiol, 2007

LV ejection fraction after CRT at 2 years survival Delnoy PP., J Cardiovasc Electrophysiol, 2007(18): P<0.001

Number of patients with NYHA class IV heart failure enrolled in primary prevention ICD trials Field M, J Interv Card Electrophysiol, 2007

Abdulla J.,Cardiology 2006;106:249–255 Effect of ICD on cardiac death in randomized controlled trials

Patients With Cardiac Structural Abnormalities or Remodeling Who Have Not Developed HF Symptoms Class I 1.All Class I recommendations for Stage A should apply to patients with cardiac structural abnormalities who have not developed HF. (Levels of Evidence: A, B, and C as appropriate) 2. Beta-blockers and ACEIs should be used in all patients with a recent or remote history of MI regardless of EF or presence of HF. (Level of Evidence: A) 3. Beta-blockers are indicated in all patients without a history of MI who have a reduced LVEF with no HF symptoms (see Table 3 and text). (Level of Evidence: C) 4. Angiotensin converting enzyme inhibitors should be used in patients with a reduced EF and no symptoms of HF, even if they have not experienced MI. (Level of Evidence: A) Hunt SA,Circulation 2005;20: e154-e685

Patients With Cardiac Structural Abnormalities or Remodeling Who Have Not Developed HF Symptoms Class I 5. An ARB should be administered to post-MI patients without HF who are intolerant of ACEIs and have a low LVEF. (Level of Evidence: B) 6. Patients who have not developed HF symptoms should be treated according to contemporary guidelines after an acute MI. (Level of Evidence: C) 7. Coronary revascularization should be recommended in appropriate patients without symptoms of HF in accordance with contemporary guidelines (Level of Evidence: A) 8. Valve replacement or repair should be recommended for patients with hemodynamically significant valvular stenosis or regurgitation and no symptoms of HF in accordance with contemporary guidelines. (Level ofEvidence: B) Hunt SA,Circulation 2005;20: e154-e685

Patients With Cardiac Structural Abnormalities or Remodeling Who Have Not Developed HF Symptoms Class IIa Placement of an ICD is reasonable in patients with ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are NYHA functional class I on chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: B) Class IIb Placement of an ICD might be considered in patients without HF who have nonischemic cardiomyopathy and an LVEF less than or equal to 30% who are in NYHA functional class I with chronic optimal medical therapy and have a reasonable expectation of survival with good functional status for more than 1 year. (Level of Evidence: C) Hunt SA,Circulation 2005;20: e154-e685

Applying Classification of Recommendations and level of evidence Hunt SA,Circulation 2005;20: e154-e685

Major implantable ICD trials Zipes DP,Europace 2006(8):

Swedberg et al., EHJ 2005;26:

N Engl J Med 2004;350:

Zipes DP, Europace 2006(8):

Ventricular arrhythmia and sudden cardiac death related to specific pathology Left ventricular dysfunction due to prior myocardial infarction Recommendations for ICD implantation Class I Zipes DP, Europace 2006(8):

Placement of an ICD is reasonable in patients with ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are NYHA functional class I on chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. Hunt SA,Circulation 2005;20: e154-e685 SCD-HeFT Bardy GH, N Engl J Med 2005;352:225-37

Patients With Current or Prior Symptoms of HF, With Reduced LVEF Hunt SA,Circulation 2005;20: e154-e685 SCD-HeFT Bardy GH, N Engl J Med 2005;352:225-37

Stage D Therapy Recommended Therapies Include: Control of fluid retention Referral to a HF program for appropriate pts Discussion of options for end-of-life care Informing re: option to inactivate defibrillator Device use in appropriate patients Surgical therapy – Cardiac transplantation Mitral valve repair or replacement Other Drug Therapy – Positive inotrope infusion as palliation in appropriate patients

(MADIT II

Swedberg et al., EHJ 2005;26: N Engl J Med 1997;337: AVID P<0.02

LES RECOMMENDATIONS

Stage B Therapy: Asymptomatic LV dysfunction Placement of an ICD is reasonable in patients with ischemic cardiomyopathy who are at least 40 days post-MI, have an LVEF of 30% or less, are NYHA functional class I on chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (MADIT II) Placement of an ICD might be considered in patients without HF who have nonischemic cardiomyopathy and an LVEF less than or equal to 30% who are in NYHA functional class I with chronic optimal medical therapy and have a reasonable expectation of survival with good functional status for more than 1 year. (DEFINITE, SCD-HeFT) ICD Hunt SA,Circulation 2005;20: e154-e685

Desai AS, JAMA 2004;292/ All-cause mortality among patients with NICM randomised to ICD or CRT-D vs medical therapy in primary prevention NICM=nonischemic cardiomyopathy P=0.02

Placement of an ICD might be considered in patients without HF who have nonischemic cardiomyopathy and an LVEF less than or equal to 30% who are in NYHA functional class I with chronic optimal medical therapy and have a reasonable expectation of survival with good functional status for more than 1 year. Hunt SA,Circulation 2005;20: e154-e685 SCD-HeFT Bardy GH, N Engl J Med 2005;352:225-37

Stages of Heart Failure At Risk for Heart Failure: STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction Heart Failure: STAGE C Past or current symptoms of HF STAGE D End-stage HF

Recommended Therapies: General measures as advised for Stages A and B Drug therapy for all patients Diuretics for fluid retention ACEI Beta-blockers Drug therapy for selected patients Aldosterone Antagonists ARBs Digitalis Hydralazine/nitrates ICDs in appropriate patients Cardiac resynchronization in appropriate patients Exercise Testing and Training Stage C Therapy:Reduced LVEF with Symptoms

An ICD is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia. (AVID) ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with ischemic heart disease who are at least 40 days post-MI, have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and have reasonable expectation of survival with a good functional status for more than 1 year. (MADIT II) Stage C Therapy:Reduced LVEF with Symptoms Hunt SA,Circulation 2005;20: e154-e685 ICD

Patients With Current or Prior Symptoms of HF, With Reduced LVEF Hunt SA,Circulation 2005;20: e154-e685 N Engl J Med 1997;337: P<0.02

ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in sudden cardiac death in patients with nonischemic cardiomyopathy who have an LVEF less than or equal to 30%, with NYHA functional class II or III symptoms while undergoing chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. (DEFINITE; SCD-HeFT) Placement of an ICD is reasonable in patients with LVEF of 30% to 35% of any origin with NYHA functional class II or III symptoms who are taking chronic optimal medical therapy and who have reasonable expectation of survival with good functional status of more than 1 year. Stage C Therapy:Reduced LVEF with Symptoms ICD Hunt SA,Circulation 2005;20: e154-e685

Patients With Current or Prior Symptoms of HF, With Reduced LVEF Hunt SA,Circulation 2005;20: e154-e685 SCD-HeFT Bardy GH, N Engl J Med 2005;352:225-37

Patients With Current or Prior Symptoms of HF, With Reduced LVEF Hunt SA,Circulation 2005;20: e154-e685 MADIT II Moss AJ, N Engl J Med 2002;346: Bardy GH, N Engl J Med 2005;352: SCD-HeFT

Trials overview Etudes # patients AgeCoronariensFE Suivi (mois) Mortalité groupe contrôle RRR MADIT MUSTT MADIT II COMPANION DEFINITE SCD-HeFT DINAMIT neg Arch maladies du coeur et des vaisseaux 99,

NNT Défibrillateurs NNT Défibrillateurs 1 ans2 ans1 an3.5 ans1 an DAI CarvedilolCaptoprilSuccinate de metoprolol Aurrichio et al, Circulation 2004, 109; NNT 3.3 ans DAI

Le NNT des def. diminue avec le temps Le NNT des def. diminue avec le temps

Saluke TV,Circulation, 2004;109: Lifeyears gained from ICD implantation

Brugada syndrome Recommendations for ICD implantation Class I Class IIa Zipes DP, Europace 2006(8):

Long QT syndrome Recommendations for ICD implantation Zipes DP, Europace 2006(8): Class I Class IIb Class IIa

The CRT trials Behan MW,Int J Clin Pract, 2006, 60, 9, 1107–1114

Indications majeures de Défibrillateurs Arrêt cardiaque Arrêt cardiaque VF ou TVVF ou TV sans causes aiguë ou réversiblesans causes aiguë ou réversible TV soutenue spontanée I TV soutenue spontanée I sur cardiopathie symptomatiquesur cardiopathie symptomatique TV soutenue spontanée II TV soutenue spontanée II mal toléréemal tolérée TR ou ablation ayant échouéTR ou ablation ayant échoué sans anomalie cardiaquesans anomalie cardiaque Syncope Syncope sans cause connuesans cause connue avec TV soutenue ou FV déclenchableavec TV soutenue ou FV déclenchable avec anomalie cardiaqueavec anomalie cardiaque Patient avec maladie génétique Patient avec maladie génétique à haut risque de mort subite par FVà haut risque de mort subite par FV sans TRx connusans TRx connu Coronariens I Coronariens I 1 mois après IM et 3 mois après revascularisation1 mois après IM et 3 mois après revascularisation FE 35%FE 35% arythmie ventriculaire déclenchablearythmie ventriculaire déclenchable Coronariens II Coronariens II 1 mois post IM et 3 mois après revascularisation1 mois post IM et 3 mois après revascularisation FE30%FE30% NYHA II ou IIINYHA II ou III Insuffisance cardiaque Insuffisance cardiaque NYHA III ou IVNYHA III ou IV FE 35%FE 35% QRS 120 msQRS 120 ms TMOTMO Cardiomyopathie dilatée Cardiomyopathie dilatée FE 35%FE 35% NYHA II ou IIINYHA II ou III ClassePreuve IAIA IBIB IBIB IBIB IIaB IBIB IBIB Trouble du rythme ventriculaire documenté Remboursement Cardiopathies

Class III J Am Coll Cardiol 2002;40:1703–19

J Am Coll Cardiol 2002;40:111– 8 Symptoms HOSPITALISATION Class I A

N Engl J Med 2002;346: MIRACLE Class I A

P=0.007 MADIT II Moss AJ, N Engl J Med 2002;346:

Swedberg et al., EHJ 2005;26: SCD-HeFT DEFINITE MADIT II Bardy GH, N Engl J Med 2005;352: Kadish A, N Engl J Med 2004;350: Moss AJ, N Engl J Med 2002;346: Class I (A)

Bardy GH, N Engl J Med 2005;352: SCD-HeFT trial DEFINITE P=0.006 Kadish A, N Engl J Med 2004;350: DEFINITE