Cardiac devices beyond pacemaker and ICD Prof. Dr. Martin Borggrefe

Transcription

1 Cardiac devices beyond pacemaker and ICD Prof. Dr. Martin Borggrefe Mannheim

2 CRT studies

3 Patient selection CRT: NYHA III-IV, EF 35%, SR, QRS 120ms, LVEDD>55mm (25-45)% Non-Responder

4 The Concept: Cardiac Contractility Modulation (CCM) Delay Duration Amplitude P<0.05 vs. HF Apply CCM Signal P<0.05 vs. NL NL HF HF+CCM Normalize Gene expression Detect local activation Muscle Force CCM Enhance contractility

5 Echocardiography in HF Dogs: Increase in Contractile Strength Baseline CCM Treatment LVED: 4.19 cm 4.00 cm LVES: 3.57 cm 3.16 cm FS: 15% 21%

6 CCM in CHF dogs: Ejection fraction Chronic CCM (3 months) Therapy in Heart Failure Dogs LV Ejection Fraction (%) CHF- Sham (n=7) CHF- CCM (n=7) Sabbah HN et al., P53, Heart Failure 2007; Imai M et al., J Am Coll Cardiol 2007; 49:

7 LV EF % CCM signals Provide Additional Effect on Top of β-blocker Chronic CCM Therapy in Dogs With Heart Failure 55 CONTROL 55 MET-CR/XL 55 MET + CCM p< p< p< PRE POST 25 PRE POST 25 PRE POST

8 Cardiac Contractility Modulation Signals Rapidly Drive Local Gene Expression to Normal CCM signals have a rapid impact, local impact to normalize gene expression Normalization of gene expression was demonstrated in animal studies and in a randomized controlled study in patients Densitometric units P<0.05 vs. HF P<0.05 vs. NL 0 NL HF HF+CCM mrna mrna Expression of of SERCA-2A Key protein in the handling of cellular calcium Key protein in the handling of cellular calcium

9 CCM Rapidly Normalized Expression of BNP mrna Near CCM Electrode Site 8000 P<0.05 vs. NL P<0.05 vs. HF 0 NL HF HF+CCM NL HF HF + CCM NL HF HF + CCM

10 Cardiac Contractility Modulation Clinical Application of CCM Therapy Goal: Reduction of CHF Symptoms Improvement in Quality of Life of CHF Patients Potential Candidates for CCM Therapy: CHF - NYHA II-III by systolic LV-dysfunction Despite of optimal medical therapy

11 Optimizer Implant IPG Atrial Lead Millar (dp/dt max ) CCM Leads ICD Lead

12 Borggrefe et al. Eur Heart J 2008; 29: FIX-CHF-4 Study Inclusion Criteria EF 35% Class II or III Optimal, stable medical therapy Exclusion Criteria Peak VO2 < 10 Active ischemia Persistent atrial fibrillation Eligible for CRT

13 FIX-CHF-4 Study Sequence Baseline Testing Device Implantation Testing 2 Week Stabilization Randomization Acute Hemodynamic Phase I Phase II PHASE 1 3 w/d PHASE 2 1 Death 2 w/d Group 1 (80) 12 Weeks Device On 12 Weeks Device Off Informed Consent (181) Baseline Testing Device Implant Procedure (178) dp/dt max >5% 2 week Run-In (166) Randomization (164) NO Group 2 (84) 12 Weeks Device Off 12 Weeks Device On 12 (w/d) 2 Death 1 Death 3 w/d 2 Death 1 w/d 74 Completers 77 Completers Borggrefe et al. Eur Heart J 2008; 29: Open Label Treatment

14 Baseline Characteristics Group I Group II NR (n=80) (n=84) (n=17) Age (years) 58.9± ± ±11.4 Gender 71 (88.8%) M 68 (81%) M 15 (88.2%) M 9 (11.2%) F 16 (19%) F 2 (11.8%) F CHF Etiology: Ischemic 51 (63.8%) 47 (56%) 13 (76.5%) Idiopathic 28 (35%) 32 (38%) 4 (23.5%) Other 1 (1.2%) 5 (6%) Resting HR (bpm) 71± ± ±12.2 Systolic BP (mmhg) 114.7± ± ±19.6 QRS Duration (ms) 119.9± ± ±33.5 NYHA II 22 (27.5%) 17 (20%) 4 (23.5%) III 58 (72.5%) 67 (80%) 13 (76.5%) MLWHFQ 38.9± ± ±26 6 minute walk (M) 386± ± ±88 Peak VO2 (ml O2/min/kg) 14.1±3 13.6± ±2 EF (%) 29.3± ± ±11.7 LV EDD (mm) 69.3± ± ±10.2 Borggrefe et al. Eur Heart J 2008; 29:

15 Significant Improvement in Exercise Tolerance ( Peak VO 2 ) Borggrefe et al. Eur Heart J 2008; 29: VO (ml/kg/min) ON P=0.03 P= OFF

16 Significant Improvement in Quality of Life Measured using MLWHFQ Borggrefe et al. Eur Heart J 2008; 29: ON OFF MLWHFQ P =0.03

17 Exercise Tolerance (6MW) Borggrefe et al. Eur Heart J 2008; 29: P=0.05 6MW (m) OFF ON

18 CCM vs. CRT: 6min WT meters MWT after Treatment (Active - Control) n=369 0 n=164 6 Mo n=444 6 Mo n=46 6 Mo n=34 3 Mo 6 Mo 2,5 n=435 6 Mo Pieske; HF 2007, Hamburg

19 US IDE Study (FIX-HF-5) Multi-center, unblinded, pivotal study 50 participating centers (all US) 1:1 randomization to the Optimizer III System or Optimal Medical Management 6-month efficacy endpoint 1-year safety endpoint First US randomization occurred on April 8, 2005 and the last on June 12, subjects randomized Pivotal US Study 213 Control, 215 Active therapy

20 Key Inclusion/Exclusion Criteria EF 35% NYHA Class III or IV symptoms Narrow QRS Duration Required optimal medical treatment including ACE-I and/or ARB and β-blockers for at least 3 months No permanent or persistent atrial fibrillation Patients were required to have an ICD.

21 Efficacy Measurements Cardiopulmonary Stress Test Anaerobic Threshold Peak VO2 Minnesota Living with Heart Failure Questionnaire NYHA 6 Minute Hall Walk Test Changes from BASELINE to 24 Weeks

22 Overall Summary (Differences between Treatment and Control) Peak VO2 (ml/kg/min) p=0.024 Anaerobic Threshold (ml/kg/min) p=ns p= MLWHFQ -6-9 NYHA p< Six Minute Walk (M) p=0.108 Significant effects on peak VO2, MLWHFQ and NYHA Positive trend in 6MW

23 Subgroup Analysis NYHA III EF 25%

24 Overall Subgroup Summary (Difference between Treatment and Control) Peak VO2 (ml/kg/min) p=0.001 Anaerobic Threshold (ml/kg/min) p= p= MLWHFQ -6-9 NYHA p= Six Minute Walk (M) p=0.044

25 Peak VO2 over Time Subgroup EF 25% and NYHA III 2 (ml/kg/min) Effect maintained through 50 weeks Treatment Peak VO Follow Up (Weeks) Control

26 Anaerobic Threshold over Time Subgroup EF 25% and NYHA III VAT (ml/kg/min) Effect maintained through 50 weeks Follow Up (Weeks) Treatment Control

27 Patients Population Current patient population eligible for CCM are patients with symptomatic Heart failure and normal QRS duration despite otimal medical therapy Recent finding Show that CCM is more Effective in Patients in Class III Heart failure and EF > 25% Recent findings suggest that CCM is less effective in Patients with sever HF that are in NYHA class IV and very low EF

28 Chronic Vagus Nerve Stimulation: A New Treatment Modality for Congestive Heart Failure

29 Background I Increased sympathetic activity and reduced vagal activity are associated with increased mortality both after myocardial infarction and in heart failure; further vagal withdrawal has been documented to precede acute decompensation. Experimental studies indicate that increased parasympathetic activity by means of vagal stimulation may reduce mortality in animal models of post-infarction sudden cardiac death and of chronic heart failure.

30 Background II: Effects of Vagal Stimulation Reduction of heart rate (Bilgutay 1968) Antiarrhythmic effects (Schwartz 1991) Dilatation of coronary arteries (Feigl 1998) Antiinflammatory action (Tracey 2002) Reduction of SCD in HF model (rat) (Sunagawa 2004)

31 CardioFit System

32 Blocking Stimulation Selectivity Multi-contact electrode allows unidirectional selective stimulation by fiber type Stimulation of cardiac parasympathetic fibers Minimal activation of non-cardiac fibers

33 Main stimulation train parameters and characteristics Stimulation Paradigm 30 min ON / 10 min OFF 20s ON / 40s OFF Up to 25% stimulation duty cycle

34 Vagal stimulation for CHF Steering Committee Peter J. Schwartz (Chairman), Gaetano M. De Ferrari, Helmut Klein, Karl Swedberg, Rami Biran. Investigators Italy: Peter J. Schwartz, Gaetano M. De Ferrari, Antonio Sanzo; Pavia. Antonello Gavazzi, Attilio Iacovoni; Bergamo. Germany: Martin Borggrefe; Jürgen Kuschyk; Mannheim. Markus Zabel; Göttingen. Helmut Klein, Jan Smid, R.C. Braun-Dullaeus; Magdeburg. Serbia: Goran Milasinovic, Srdjan Raspopovic; Belgrade. The Netherlands: Harry J.G.M. Crijns, Robert Dennert; Maastricht. De Ferrari et al. Eur Heart J 2011; 32:

35 De Ferrari et al. Eur Heart J 2011; 32: Inclusion Criteria Chronic heart failure, NYHA II-III; Age years; Sinus rhythm; Average 24-hour heart rate b/min; Optimal medical treatment with no change in the previous 3 months with the exception of diuretic dose; Left ventricular ejection fraction 35%.

36 Population of the Study (n=32) Male/Female 30/2 Age (years) Duration of HF (years) Ischemic/Non ischemic 20/12 ICD 19 (59%) Diabetes Mellitus 5 (16%) Beta-blockers 31 (97%) ACE-I/ARB 31 (97%) Diuretics 29 (91%) Anti-aldosterone 19 (59%) Nitrates 14 (44%) De Ferrari et al. Eur Heart J 2011; 32:

37 Rx a.p. und lateral

38 De Ferrari et al. Eur Heart J 2011; 32: Results: Responder 17% 31% 52% Full responder ( 3 points) Partial responder (1-2 points) Non responder ( 0 points) Composite Score: EF, WD, QoL, NYHA, LVESVI

39 b/min De Ferrari et al. Eur Heart J 2011; 32: Results: Resting Heart Rate p=0.014 p= Baseline 3 Months 6 Months

40 Results: HR Stimulation Response

41 Results: NYHA Class IV n=2 n=2 Died III n=15 n=15 Died Died n=4 n=5 II n=15 n=15 n=19 n=13 I n=6 n=11 n=11 Baseline 3 Months 6 Months De Ferrari et al. Eur Heart J 2011; 32:

42 De Ferrari et al. Eur Heart J 2011; 32: Results: Quality of Life (MLwHF ) P< P< Baseline 3 Months 6 Months

43 meters De Ferrari et al. Eur Heart J 2011; 32: Results: Six-Minute Walk Test p= P< Baseline 3 Months 6 Months

44 Left Ventricular Volumes Indices P= P>0.05 P>0.05 P>0.05 LVEDVi LVESVi 120 ml/m Baseline 3 Months 6 Months De Ferrari et al. Eur Heart J 2011; 32:

45 % De Ferrari et al. Eur Heart J 2011; 32: Left Ventricular Ejection Fraction p= p= Baseline 3 Months 6 Months

46 Conclusions Chronic VS in patients with advanced CHF is feasible and appears to be well tolerated and safe. Initial data suggest subjective and objective improvement. A larger controlled study is warranted.

47 Electric Therapy 2010.??

48 Can we save a patient s life with a single device? Yes we can!!!