Exercise Diego Medvedofsky 2/2012

1. Exercise Diego Medvedofsky 2/2012

3. Background • ~50% of pts with symptomatic HF experience HFpEF • Morbi-mortality is high and comparable to HF with reduced LVEF (HFrEF) • In HFpEF no effective therapeutic strategies shown to be effective in large clinical trials

4. Background • In HFrEF exercise training (ET) improves exercise capacity and reduces morbidity (Van Tol, Eur J Heart Fail 2006) • HF-ACTION also demonstrated a benefit with ET in HFrEF (Piepoli, BMJ 2004, O’Connor, JAMA 2009) • Conditions associated with HFpEF (endothelial dysfunction, systemic inflammation, metabolic sme) are improved by ET (Adamopoulos, Eur Heart J 2001, Boulé, JAMA 2001, Linke, JACC 2001)

5. Objectives To determine whether structured exercise training (ET) improves • Exercise performnce • LV diastolic FC • Quality of life (QoL) in pts with HF with preserved ejection fraction (HFpEF)

6. Methods • Prospective, multicenter, blind, RCT in HFpEF • NYHA II/III • LVEF≥50% • Sinus • At least 1 of: overweight, DM, HTN, hyperlipidemia, smoking

7. Methods: Exclusion criteria • Significant valvular disorders, pulmonary disease, angina, untreated CAD>50%, S/P MI, anemia, BP>150/100 mmHg, relevant arrhythmia, change in CV cardiovascular medication in previous 4 weeks

9. Methods • 64 pts (age 65±7, 56% female) with HFpEF were prospectively randomized (2:1) to • From 1/2007-8/2007 • Supervised endurance/resistance training in addition to usual care (ET, n=44) • Usual care alone (UC) (n=20)

12. Intervention • Supervised, facility based training program • Endurance and resistance (32 sessions) • Weeks 1-4: aerobic endurance (cycling) • Target HR of 50-60% of peak oxygen uptake (peak VO2) baseline

13. Intervention • From week 5: • ↑ training freq and workload • Added resistance training (bench press, leg press, leg curl, rowing machine, triceps dip, latissimus pull down)

14. Methods • Primary endpoint • Change in peak VO2 after 3 months

15. Methods • Secondary endpoints • Systolic and diastolic function • Effects on cardiac structure [LV mass index (LVMI) and LA volume index (LAVI)] • QoL [Health Survey (SF-36) and Minnesota Questionnaire (MLWHFQ)] • Serum biomarkers: • NT-proBNP • PINP (serum procollagen type I-NP)

18. Results • Peak VO2 • The mean benefit of ET was 3.3 ml/min/kg (95% CI: 1.8 to 4.8, p<0.001), NNT 3.5 • Increase in 6 min walk of 24 m (<0.001)

21. Results • E/e' and LA volume index • ↓ with ET, unchanged with UC • The physical functioning score (36-Item Short-Form Health Survey) • ↑ with ET, unchanged with UC

22. Safety • Brief episodes of palpitations (2) • Dyspnea (3) • Mild musculoskeletal discomfort (9)

23. Compliance • Training group - exercise sessions • N=15 (34%) participated in >90% • N=23 (52%) in 70% to 90% • N=6 (14%) in <70%

24. Conclusions • 1ST multicenter, prospective RCT • Effects of supervised, structured ET on HFpEF pts • exercise capacity • diastolic function (atrial reverse remodeling and improved LV diastolic function) • QoL • Endurance/resistance ET over 3 months was a feasible, safe, and effective intervention

25. Limitations • Nature of ET interventions prohibits pure blinding • Small number of younger and middle aged pts in short-term follow-up

27. Background • Adults with congenital heart disease (CHD) are at increased risk of mortality and morbidity • Parameters of cardiopulmonary exercise testing (CPX) identified as strong predictors of mortality in adults with CHD • guide clinicians in assessing prognosis and planning interventions

28. Investigation • Relation between CPX parameters and their combination • may provide optimal prognostic info on midterm survival in this population

29. Methods • 1375 pts w/adult (>14y) CHD (33±13 y) • Retrospectively • CPX • Single center, 10 years (1999-2008) • All cause mortality • Measured: • Peak oxygen consumption (peak VO2) • Ventilation/CO2 (VE/VCO2 slope) • HR reserve (peak - resting HR)

30. Cardiopulmonary Exercise Testing • On a treadmill - modified Bruce protocol • All patients were encouraged to exercise to exhaustion • Respiratory mass spectrometer: ventilation, VO2, VCO2 • ECG: HR • Manually sphygmomanometry: BP • Pulse oximetry: O2 saturation

31. SO2<90% 16% I 51% II 39% Simple: ASD VSD PDA AO coartat

32. BB, CCB, AMIODAR

34. Results • Follow-up of 5.8 years • 117 patients died: • HF 41 • SCD 34 • Perioperative 12 • Inf 5 • PE 1 • Hemoptysis 1 • Brain hemorrhage 1 • Out of Hospital 21

35. Results

36. Results • Risk of death ↑ with: • ↓ peak VO2 • ↓ HR reserve • ↑ VE/VCO2 slope in noncyanotic pts • Not predictive in cyanotic pts • Combination of peak VO2+HR reserve • greatest predictive info • ↓ in pts with peak respiratory exchange ratio <1.0

37. (Neg chronotropic agents)

39. Conclusions • Peak VO2 and HR reserve data can be used to generate estimates of 5-year survival across a wide spectrum of adults with CHD

40. Conclusions • CPX: strong prognostic info in adult pts w/CHD • Data useful for comparing the exercise capacity of a particular patient vs pts in the same diagnostic group

41. Limitations • Retrospective • Part of routine evaluation • Tertiary center • Ed: patients terminated exercise before reaching their cardiovascular limit

42. THANKS THANKS