Cardiovascular response to exercise and Rehabilitation in the Heart Failure patient

1. Cardiovascular response to exercise and Rehabilitation in the Heart Failure patient Alain COHEN SOLAL Hôpital Lariboisière, Paris Bruxelles, 14.10.06

2. Rest is the first treatment of chronic heart failure ….. E Braunwald, Textbook of Internal Medicine, WB Saunders Ed, 1986

3. Vicious circle of CHF Peripheral abnormalities Cardiac dysfunction Fatigue Physical deconditioning

4. No relationship between LVEF and exercise capacity VO2max (ml/min/kg) Cohen Solal A et al. Heart 1996

5. The O2/CO2 transport chain in CHF Training

6. Vascular abnormalities :Major endothelial dysfunction in CHF % change in arterial diameter before 20 p<0.05 L-NMMA after L-NMMA 15 - 50% 10 * * 5 0 CHF Normals B Hornig et al, Circulation, 1995;1996:210

7. Morphologic abnormalities of peripheral muscles in CHF CHF Normals H Drexler et al

8. Mitochondrial density and exercise capacity in CHF 50 p< 0.0001 r = 0. 57 n = 60 45 40 35 30 Peak VO2 ml/kg/mn 25 20 15 CHF 10 Controls 5 0 0 2 4 6 8 Mitochondrial density H Drexler et al, Circulation 1992 ; 85 : 1751

9. Comparison ACE-I/physical training in CHF T Meyer et al Int J Cardiol

10. Physical rehabilitation

11. Princeps study in London • 20 patients • LVEF < 35% • NYHA III • 3 months of home training (cycle) vs 3 months of inactivity (cross over)

13. Overall effects of rehabilitation on peak VO2(10 controlled studies) 50 Gain in peak VO2 (%) 40 30 20 10 0 Control Trained

14. Exercise training and peak VO2 Circulation 2003; 107: 1210-25

15. Peak VO2: OKbut what about Quality of Life ? from R Belardinelli et al

16. Is it dangerous to train CHF patients ? • No, • If contra-indications related to the cause of HF are respected • (major hypotension, invalidating angina, uncontrolled ventricular arrhythmias, PHT? cardiac thrombus ?) • Far from an episode of decompensation • On optimal treatment(at least ACE-I/diu + BB ++ ..)

18. Mechanisms of action of cardiac rehabilitations ? • Heart • Vessels • Muscle • Autonomic nervous system • Lung

19. Effects on the heart • Improvement in myocardia perfusion (1) • Decrease in myocardial ischemia (2) • Improvement in ED vasodilatation (5) • Increase in exercise CO (3) • No deleterious effect on cardiac remodeling (4) • (1) V. Froelicher et al, JAMA 1984; 10: 1291 • (2) AA. Ehsani et al, Am J Cardiol 1982; 50: 246 • (3) AJS. Coats et al,Circulation 1992; 85: 2119 • P. Dubach et al, JACC 1997; 29: 1591 • (4) P. Giannuzzi et al (Etude EAMI), JACC 1993; 22: 1821 • (5) R. Hambrecht et al, JACC 1993; 22: 468

20. The PET Study 100 CAD pts, PTCA-stent based therapy vs exercise training 6 months follow up Exercise PTCA/Stent Hambrecht R et al. Circulation 2004

21. Benefits of training in HF 4 - 6 months Exercise * Anaerobic treshold ** Sullivan MJ - Circulation 1988; 78: 506-15 * e 1989; 79: 324-9 **

22. ELVD - CHF LV Function and Remodeling Control Group (n=44) Exercise Training Group (n=45) Baseline 142  26 107  24 25  4 6 Months 135  2* 97  24* 29  4* Baseline 147  41 110  34 25  4 6 Months 156  42*† 118  34‡ 25  5‡ EDV ml/m2 EVS ml/m2 EF % * p<0.01 time effect within group; † p<0.001 interaction; ‡ p<0.01 interaction

23. LV remodeling & exercise training JACC, 1993 Am Heart J, 1996 Circulation, 1997 JACC, 1997 Afzal A - Progress Cardiov Dis 1998: 41: 175-90

24. Effects on the vessels • Rest and exercise vasodilatation improved (1) • Improvement in endothelium-dependent vasodilatation (2) • (1) AJS. Coats et al, Circulation 1996; 85: 2119 • (2) B. Hornig et al, Circulation 1996; 93: 210 • R. Hambrecht et al, Circulation 1998;98: 2709

25. Effects of training on endothelial function in CHF pts Change in diameter (%) 20 p<0.05 p<0.05 15 10 5 0 Trained CHF Controls CHF B Hornig et al, Circulation, 1995;1996:210

26. Mechanisms of the effects of training on peripheral vasodilatation • Increased eNOS ? • Increased VEGF ? • Decrease in oxydative stress ?

27. Effects on the muscle CHF trained CHF R Hambrecht et al

28. Effects on the autonomic nervous system • Decrease in sympathetic tone and increase in parasympathetic tone (1) • Decrease in plasma norepinephrine, improvement in MIBG uptake (2) • Increases HR variability (3) • (1) AJS. Coats et al, Circulation 1992; 85: 2119 • (2) R. Hambrecht et, JACC 1995; 25: 1239, Agostini D, 2000 • (3) AJS. Coats et al, Circulation 1992; 85: 2119

29. Effects on HRV AJS. Coats et al, Circulation 1992; 85: 2119

31. Electric myocardial stability and exercise training (*p<0.05, ** p<0.01) Male rats, treadmill, 8 weeks H Dor-Haim, Israel Heart Society 06

32. Exercise ventilation and training Ventilation (l/min) 50 • Lactate • PWP? • + diaphragm • ergoreflex Before 17 patients Trained 40 * 30 * 20 10 0 Repos 25 W 50 W Max * p < 0.05 AJS Coats et al, Circulation 1992; 85: 2119

33. Training and BNP in CHF Passino et al. JACC 06

34. Other possibles mechanisms of action potentially beneficial • Increase in cardiac NO synthase • Reduction in oxidative stress • Anti-inflammatory action (TNF alpha, interleukins) • ……

35. Which patients ? • Patients in NYHA class II-III • Class IV ? • Patients on a transplant list ? • Class I patients ? • Women ? • Which peak VO2?

36. Which protocol ? • High (usually, 60-70% peak VO2) vs low (40% peak VO2) level exercise training • Low level : periphery +++, autonomic tone • High level : heart • Anaerobic threshold based • Interval training vs usual training • Segmental training vs dynamic training • Home-based or hospital-based training • 3 or 5 days per weeks ? 2, 3 or 6 months

37. % increase in exercise tolerance 70 60 r = 0.74, p< 0.01 50 40 30 20 10 0 -10 -20 -30 -40 0 20 40 60 80 100 120 Observance (%) Compliance and training response AJS. Coats et al, Circulation 1990;85:2119-31

38. Duration of the effect • Most of the studies have used 3-6 month periods of training • Improvement seems to level off after the 1st-3rd month • Acceptability of a long-term training program ? Phase III remains a major problem

39. Other questions • Do betablockers limit benefit ? • Should we systematically propose a rehab programme to a patient on a transplant list? • Can we remove from the transplant list a patient significantly improved by training? • Effects on outcome ?

40. Durée (min.) p<0.01 vs placebo Effects of betablockers on exercise tolerance nTA 70% VO2 max Van Bortel L.M.A.B. 1992 Cardiovascular Drugs and Therapy 6:239-247

41. Effects of traing in CRT patients VO2peak (ml/kg/min) Conraads V et al. WCC 06

42. Am J Cardiol 2005;95:734–741 • 227 advanced HF adults referred for initial HxT evaluation • 52 ± 10 years old • 2nd evaluation: > 60 days after initial evaluation (352±238 days) Conclusions 3. Patients who improved to low risk for peak VO2 had a 1-year survival, but patients who improved to low risk and were treated with blockers had a 1-year survival rate (83%) comparable to that after transplant (84%).

43. Effects on outcome

44. EXTRAMATCH NNT during 2 years to save 1 life: 17

45. ExtraMATCH : mortality ExTraMATCH coll BMJ 16.01.2004

46. Unsustained effects of Exercise on mortality (EXERT Study, Montreal) • N=181 McKelvie RS et al. Am Heart J. 2002;144:23-30

47. Heart Failure -AControlled Trial Investigating Outcomes of exercise TraiNing HF – ActionNHLBIinitiative and funding • Randomized trial, 3 000 pts NYHA class II–IV, EF<35% • ET + usual carevsusual care - 2 years intervention • 52 centres in US (44 centres), Canada (8 centres), 5 in France • Expecting to find a 20 % reduction in death and hospitalization rates

48. Subject Demographics

49. Prior Cardiac Procedures

50. Cost-effectiveness • Data lacking in CHF