Cardiac Resynchronisation Therapy for all Patients Requiring Ventricular Pacing

Transcription

1 Cardiac Resynchronisation Therapy for all Patients Requiring Ventricular Pacing Philippe Mabo University Hospital, Rennes, France ESC Congress 2010, Stockholm 29 Aug 2010

2 Which Patients? Candidate for class I CRT indication are excluded from the present discussion

3 Which Patients? Candidate for class I CRT indication excluded from the present discussion Candidate for class I PM indication: symptomatic SND symptomatic AVB

4 Which Patients? Candidate for class I CRT indication excluded from the present discussion Candidate for class I PM indication: symptomatic SND symptomatic AVB Requiring ventricular pacing: SND excluded

5 Sinus node disease Pacing mode selection ESC Guidelines No V pacing

6 Which Patients? Candidate for class I CRT indication excluded from the present discussion Candidate for class I PM indication: symptomatic SND symptomatic AVB Requiring ventricular pacing: SND excluded symptomatic AVB

7 Which Patients? Candidate for class I CRT indication excluded from the present discussion Candidate for class I PM indication: symptomatic SND symptomatic AVB Requiring ventricular pacing: SND excluded symptomatic AVB Requiring frequent ventricular pacing: paroxysmal AVB excluded permanent AVB

8 ESC Guidelines AV block Pacing mode selection

9 Potential benefit of CRT? To prevent the deleterious effects of apical RV pacing Molecular consequences Histopathologic consequences Myocardial consequences LV functional consequences Clinical consequences

10 Left Ventricular Electrical Activation Normal activation RV apical pacing Cassidy DM, Circ 1984;70:37-42 Vassallo JA, JACC 1986;7:

11 Relative Units Contractile Discoordination Generates Marked Regional Disparities in Expression of Stress Kinases and Ca Handling Proteins in Region of Late Activation (high stress) Phospho-P38 MAP kinase Phospholamban ] ] ] ] se epi se endo lat epi lat endo Std ] ] ] Std se epi se endo lat epi ] lat endo se epi se endo lat epi lat endo 0 se epi se endo lat epi lat endo Adapted from Spragg, Leclercq, Kass et al, Circulation 2003

12 Histopathologic consequences Karpawich. PACE 2004;27: 844-9

13 Myocardial consequences 8 mongrel dogs paced at LV free wall for 6 months (5 controls) before pacing after pacing early activated regions 17% thinner late activated septum 23% thicker myocyte diameter 18% larger in septum than free wall septum free wall Van Oosterhout et al., Circulation months

14 LVEF 70 % LV functional consequences 61±8 58±6 52±8 p<0.01 p< ±6 60±4 56±7 p<0.01 p<0.01 Rest Exercise 70 Septal LVEF % Leclercq. Am Heart J. 1995; 129: ±11 P< ±1 Rest ns 51±8 71±14 P< ±12 55±15 Exercise ns AAIR DDDR VVIR

15 Recovery of LV function after RVA pacing Nahlavi. J Am Coll Cardiol 2004;44:1883-8

16 LV remodeling 33 CCAVB vs 30 healthy subjects FU : years Thambo. Circulation 2004;110:

17 Clinical consequences DAVID Trial. JAMA 2002;288:

18 Steinberg. J Cardiol Electrophysiol 2005; 16: Clinical consequences Sub-study of the MADIT II trial % of V pacing ( 76% of the 742 ICD patients) 2 groups: Cum VP 0-50% Cum VP %

19 Clinical consequences (MADIT II trial) Steinberg. J Cardiol Electrophysiol 2005; 16:

20 Clinical consequences (MADIT II trial) Steinberg. J Cardiol Electrophysiol 2005; 16:

21 Alternative options Alternative RV pacing sites - RVOT pacing - Septal pacing - His-bundle pacing - Dual RV pacing Biventricular pacing

22 RVOT vs RVA pacing ROVA study Cross-over trial: RVOT vs apex vs RVdual site End-points: QOL, NYHA class, 6 WT, LVEF 103 patients with CHF, LVEF < 40%, permanent AF Age: years NYHA class II / III : 53% / 47% LVEF: % AV node ablation: 64%, slow ventricular response: 28% Stambler. J Cardiovasc Electrophysiol 2003;14:1180-6

23 ROVA study No significant difference between RVA and RVOT for: QoL NYHA class 6 WT LVEF better with RVA : % vs % (p=0.04) No additional benefit when dual pacing sites RVOT + RVA vs RVA or RVOT Stambler. J Cardiovasc Electrophysiol 2003;14:1180-6

24 Septal pacing Cross-over study : Septal versus Apical pacing (n = 28) AF patient + complete AVB - LVEF > 45% : n = 16 (52 + 3%) - LVEF < 45% : n = 12 (38 + 5%) LVEF * NS * Septal Apical Global LVEF> 45% LVEF <45% *: p< 0.01 Victor. J Cardiovascul Electrophysiol 2006;177:

25 Septal pacing Tse. J Am Coll Cardiol 2002;40:

26 Permanent Direct His-Bundle Pacing Deshmukh. Circulation 2000;101: pts with permanent AF, DCM and QRS< 120 ms 12 permanently His paced V pacing threshold V

27 Permanent Direct His-Bundle Pacing Deshmukh. Circulation 2000;101:

28 His-bundle pacing Occhetta. J Am Coll Cardiol 2006;47:

29 Alternative RV pacing sites Small populations Short FU Reproducibility of lead positionning The most attractive: septal implant

30 Biventricular pacing versus RVA The HOBIPACE study 30 patients, 21 SR - 9 AF Kindermann. J Am Coll Cardiol 2006;47:

31 Biventricular pacing versus RVA The HOBIPACE study Kindermann. J Am Coll Cardiol 2006;47:

32 Biventricular pacing versus RVA The HOBIPACE study Kindermann. J Am Coll Cardiol 2006;47:

33 CRT vs DDD Normal LVEF (> 45%) Indication for permanent pacing N = 177 patients PACE trial Adapted from NEJM 2009

34 PACE: study limitations Sinus node disease: 38 % in RV pacing arm 45 % in BiV pacing arm 2007 guidelines: preserve natural AV conduction in SND Ventricular pacing was «forced» in patients without need for ventricular capture Results may be driven by an unacceptable pacing modality in SND patients SND is not an indication for BiV pacing

35 CRT Ongoing Trials BLOCK-HF: morbi-mortality trial BioPace: mortality trial

36 BLOCK-HF trial Randomized, multicentric, prospective, double-blind, parallel-group-design (Sponsor Medtronic) BiV vs RV Enrollment: n=1636 Primary endpoint: all cause mortality/hf related urgent care/ significant increase in LVESVI Inclusion criteria: pacing indication for AVB, NYHA I-III, LVEF < 50%

37 BioPace Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization Randomized, multicentric, prospective, single-blind, parallelgroup-design (Sponsor: SJM) Enrollment Goal: 1800 patients in 93 centers Primary endpoint: all cause mortality Patients with conventional indication for pacemaker implantation with the aim of permanent ventricular stimulation: any standard-indication for permanent (>2/3 of the time) ventricular pacing LVEF without any limitation any QRS-width

38 BioPace: Study Timelines Hardware Randomization, Implant & Pre- Hospital Discharge Balanced Randomization: LVEF AF QRS width LBBB (unpaced QRS) ICD Center Short FU: Survival Status Can be done by phone M1 M3* M6 M12 M18 M24 M30 M36 Pre-Implant RV Group 1 - Control BiV M1 M3* M6 M12 M18 M24 M30 M36 Group 2 Therapy Pre-Implant: M1 & M3 FU: M12 & M24 FU: Post M24 FU: PIC Echo ECG M1 visit can be performed anywhere between 1-3 Months post-implant Echo/QoL/6MWT Device FU AV/PV Optimization Device FU AV/PV Optimization NYHA /Medication NYHA /Medication M3 visit is optional NYHA /Medication

39 Limitations to extend CRT indications Complexity of implant procedure restricted to experienced centers Increase of adverse event rate Overcost: LV lead, CRT device Device longevity

40 «Present» ESC Guidelines CRT-P indication

41 My proposals Patients with preserve LV function: no indication for CRT (optimize RV lead position) Patients with severe LV dysfunction (LVEF < 35%): consider CRT according to co-morbidity and lifeexpectancy Patients with moderate LV dysfunction: try to not enlarge QRS by optimization of the RV lead Consider up-grading to CRT in patients in NYHA class III-IV with LVEF < 35% and permanent RV pacing

42 But Please, follow the new 2010 ESC guidelines (Presentation by K Dickstein, room Stockholm) And wait for results of on-going trials to support larger indications of CRT in AVB population

43 New 2010 ESC Guidelines Coordination: PE Vardas et K Dickstein In patients in NYHA function class III/IV and a concomitant class I pacemaker indication, LVEF 35%, QRS width 120 ms, optimal medical therapy CRT-P/CRT-D is recommended to reduce morbidity. Class of recommendation I, level of evidence B. In patients in NYHA function class III/IV and a concomitant class I pacemaker indication, LVEF 35%, QRS width <120 ms, optimal medical therapy CRT-P/CRT-D should be considered to reduce morbidity. Class of recommendation IIa, level of evidence C.

44 New 2010 ESC Guidelines Coordination: PE Vardas et K Dickstein In patients in NYHA function class II and a concomitant class I pacemaker indication, LVEF 35%, QRS width <120 ms, optimal medical therapy, CRT-P/CRT-D might be considered to reduce morbidity. Class of recommendation IIb, level of evidence C.