Cardiovascular Health Summit 2007Physical Activity as a Treatment of Heart

Failure

Reed Humphrey, PhD, PTProfessor & Chair

School of Physical Therapy & Rehabilitation ScienceCollege of Health Professions and Biomedical Sciences

The University of MontanaMissoula, MT

Management of the Failing Heart

• Medication regimes

• Surgery

• Lifestyle management including exercise

Source: Am J of Cardiology 1994 23; 362

Prognostic significance of peak exercise capacity in patients with coronary artery disease

Source: Circulation 1991 83:783

Survival curves for chronic heart failure patients with LVEF of < 25% by peak exercise oxygen uptake

Factors in Exercise Training Associated with Morbidity & Mortality Benefits for People with

Chronic Heart Failure

Parameter Effect of Exercise Training

Peak VO2 Increase

VO2 at anaerobic threshold Increase

Pulmonary Ventilation Decrease

VE/CO2 Decrease

Mitochodrial density, activity Increase

Blood Lactate Decrease

Type I fiber characteristics Increase

Cardiac Output May increase at peak VO2

Ejection fraction No change

Quality of Life Increased

Smart N, Marwick TH . Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity. Am J Med. 2004 May 15;116(10):693-706.

• PURPOSE: To determine the efficacy of exercise training and its effects on outcomes in patients with heart failure.

• METHODS: MEDLINE, Medscape, and the Cochrane Controlled Trials Registry were searched for trials of exercise training in heart failure patients. Data relating to training protocol, exercise capacity, and outcome measures were extracted and reviewed.

• RESULTS: A total of 81 studies were identified: 30 randomized controlled trials, five nonrandomized controlled trials, nine randomized crossover trials, and 37 longitudinal cohort studies. Exercise training was performed in 2387 patients.

Smart N, Marwick TH . Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity. Am J Med. 2004 May 15;116(10):693-706.

• The average increment in peak oxygen consumption was 17% in 57 studies that measured oxygen consumption directly, 17% in 40 studies of aerobic training, 9% in three studies that only used strength training, 15% in 13 studies of combined aerobic and strength training, and 16% in the one study on inspiratory training.

• There were no reports of deaths that were directly related to exercise during more than 60,000 patient-hours of exercise training. During the training and follow-up periods of the randomized controlled trials, there were 56 combined (deaths or adverse events) events in the exercise groups and 75 combined events in the control groups (P = 0.60). During this same period, 26 exercising and 41 nonexercising subjects died (P = 0.06).

• CONCLUSION: Exercise training is safe and effective in patients with heart failure. The risk of adverse events may be reduced, but further studies are required to determine whether there is any mortality benefit.

ExTraMATCH Collaborative. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) BMJ  2004;328:189

• Objective To determine the effect of exercise training on survival in patients with heart failure due to left ventricular systolic dysfunction.

• Design Collaborative meta-analysis. • Inclusion criteria Randomized parallel group controlled

trials of exercise training for at least eight weeks with individual patient data on survival for at least three months.

• Studies reviewed Nine datasets, totaling 801 patients: 395 received exercise training and 406 were controls.

• Main outcome measure Death from all causes.

ExTraMATCH Collaborative. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) BMJ  2004;328:189

• Results During a mean follow up of 705 days there were 88 (22%) deaths in the exercise arm and 105 (26%) in the control arm. Exercise training significantly reduced mortality (P = 0.015). The secondary end point of death or admission to hospital was also reduced (P = 0.011). No statistically significant subgroup specific treatment effect was observed.

• Conclusion Meta-analysis of randomized trials to date gives no evidence that properly supervised medical training programs for patients with heart failure might be dangerous, and indeed there is clear evidence of an overall reduction in mortality. Further research should focus on optimizing exercise programs and identifying appropriate patient groups to target.

Kaplan-Meier cumulative two year survival (top) and Kaplan-Meier cumulative two year survival or free from admission hospital

(bottom).

Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH) BMJ  2004;328:189

HF-ACTION stands for Heart Failure: A Controlled Trial Investigating Outcomes of

Exercise TraiNing

Why is HF-ACTION important? While many trials conducted over the past decade have shown that exercise can have a positive effect on symptoms suffered by heart failure patients, the 5-year, 3,000-patient randomized trial, to be conducted at more than 50 U.S. and Canadian hospitals, will be the first such large-scale prospective trial designed to determine whether exercise can reduce mortality and hospitalizations for patients with heart failure or any other disease.

Whellan DJ, O’Connor CM, Pina I. Training trials in heart failure: Time to exercise restraint? Am Heart J 2004;147:190-2.

• The Point – No need for small, limited number exercise trials.– Already 14 RCTs– Currently published accompanying article on at-

home exercise was neutral or limited significance for classic outcome measures

• The Paradox – 550,000 new cases annually– Length of HF-Action Trial is 5 years– Who is reading Am Heart J and how does this

position influence referral of patients with HF?

Pre-exercise intervention in patients with LV dysfunction

• Optimal pharmacology • Nutritional support • Dyspnea management (supplemental

oxygen, mobilization of secretions) • Blood chemistry (Hgb and Hct)

Physiological Data Summary

Pina IL, Apstein CS, Balady GJ, Belardinelli R, Chaitman BR, Duscha BD et al. Exercise and heart failure: a statement from the American Heart Association committee on exercise, rehabilitation, and prevention. Circulation 2003; 107(8):1210-1225.

Source: Circulation 1993 87:VI-7

Relationship of LVEF and peak oxygen uptake

Basis for Exercise Prescription

• Usual rules for aerobic exercise prescription– 50-90% HRmax

– Below VT (avoid catecholamine rise; ‘Talk Test’)

– Recruit Type I muscle fibers for endurance adaptation

• What about the alternative use of high intensity or interval training?

• Efficacy of resistance training

• Other considerations

Dubach P et al. Effect of High Intensity Exercise Training on Central Hemodynamic Responses to Exercise in Men with Reduced Left Ventricular Function.J Am Coll Cardiol 1997;29:1591-8

25 males randomized to training or control groups EF 32-33% +/- 6-7% Exercise group: 2 hr daily walking + 4 sessions of cycle

ergometry 40 min at 70-80% peak capacity 1.7L/min increase in cardiac output 23% increase in VO2 at 1 month, 6% additional at 2

months No worsening of hemodynamic or myocardial status

Meyer K et al. Interval Training in Patients with Severe Chronic Heart Failure: Analysis and Recommendations for Exercise Procedures. Med Sci Sports Exerc 1997;29:306-12

18 male patients, mean age 52, 21% EF, 12.2 mlO2/kg Ramp cycle protocols; ordinary (OR) for testing and “steep

ramp” (SR) to determine interval training (IT) loads Interval training 30:60 sec work:rest intervals at 50% of

maximum SR load; SRs repeated weekly for new Rx IT resulted in doubled work rate of 75% OR test with lower

hemodynamic and metabolic stress Significant increase in VO2 w/o complications

LV Function During Steady State & Interval Training

30

40

50

60

70

80

90

0 5 10 15 20

Normals-SSNormals-IntCHD-SSCHD-IntCHF-SSCHF-Int

LVEF (%)

Time (min) K Meyer et al Am J Cardiol 82: 1382, 1998C Foster et al MSSE 31: 1157, 1999

Exercise Dosage & Chronic Heart Failure

Expectations of training: What are the desired outcome(s)?

Improved oxygen transport = improved function Increased volume = weight management Increased fitness = functional range of ability and

cardioprotection

A Continuum of Caloric Expense Independent of Exercise Intensity

600 800 1000 1200 1400 1600 1800 2000

Diabetes Cardioprotection

Fitness Weight loss

Kilocalories/week expended in physical activity

Targeted physiological outcomes

How Important is Exercise Intensity?

• Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002 346(11): 793-801

• Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Exercise type and intensity in relation to coronary heart disease in men. JAMA 2002:288(16):1994-2000

To summarize: Aerobic training and CHF

• Of the studies reviewed, the intensity of training, was ~ 40-90% of peak HR or oxygen consumption (~50% of peak VO2 for most studies), 15-60 minutes duration (30-40 min), 3-7 days per week (3-5 days).

• No major complications• Positive outcome measures in all studies• Cycling most frequently used modality• Low intensity is clearly beneficial, higher

degrees of fitness may be an important secondary outcome

Karlsdottir AE et al. Hemodynamic responses during aerobic and resistance exercise. J Cardiopulm Rehabil. 2002 May-Jun;22(3):170-7.

• PURPOSE: Resistance training has become an accepted part of cardiac rehabilitation programs. Because of the potential for a high afterload to have a negative impact on left ventricular function, there has been concern regarding the safety of resistance training for patients with congestive heart failure.

• METHODS: This study addressed this concern by studying 12 healthy volunteers, 12 patients with stable coronary artery disease, and 12 patients with stable congestive heart failure during upright cycling at 90% of ventilatory threshold, and during one set of 10 repeated leg presses, shoulder presses, and biceps curls at 60% to 70% of 1-repetition maximum. Left ventricular function was measured by echocardiography.

Karlsdottir AE et al. Hemodynamic responses during aerobic and resistance exercise. J Cardiopulm Rehabil. 2002 May-Jun;22(3):170-7.

• RESULTS: The pattern of changes in heart rate, blood pressure, left ventricular ejection fraction, wall thickness, and left ventricular internal diameters was similar across all three groups of subjects, although there were large differences in absolute values. Despite elevations in diastolic and mean arterial pressures during resistance exercise, there was no evidence of significant rest-to-exercise deterioration in left ventricular function during leg press (ejection fraction, 60%-59%, 56%-55%, and 38%-37%), shoulder press (66%-65%, 59%-53%, and 38%-35%), or biceps curls (63%-58%, 53%-54%, and 35%-36%), as compared with cycle ergometry (63%-69%, 51%-57%, and 35%-42%) in the healthy control subjects, the patients with coronary artery disease, and the patients with congestive heart failure, respectively.

• CONCLUSIONS: Left ventricular function remains stable during moderate-intensity resistance exercise, even in patients with congestive heart failure, suggesting that this form of exercise therapy can be used safely in rehabilitation programs.

Werber-Zion G et al. Left ventricular function during strength testing and resistance exercise in patients with left ventricular dysfunction JJ Cardiopul Rehabil 2004;24:100-109

PURPOSE: Deterioration in left ventricular function is a more sensitive marker of myocardial ischemia during exercise than ST segment depression. The current study was designed to evaluate left ventricular function during one-repetition-maximum (1-RM) strength testing and resistance exercise in cardiac patients with moderate left ventricular dysfunction.

METHODS: Using echocardiographic methods, left ventricular function was evaluated in 15 patients with left ventricular dysfunction (age, 65 +/- 6.5 years; ejection fraction, 42.1 +/- 5.8). Measurements were performed during 1-RM testing and resistance exercise (20%, 40%, and 60% of 1-RM using 10 to 15 repetitions) on the one-arm biceps curl (BIC) and bilateral knee extension exercises and compared with measurements of left ventricular function during the symptom-limited graded exercise test (SL-GXT).

Werber-Zion G et al. Left ventricular function during strength testing and resistance exercise in patients with left ventricular dysfunction JJ Cardiopul Rehabil 2004;24:100-109

RESULTS: During the knee extension exercise, there was a slight but significant reduction (P< or =.05) in ejection fraction values at the end of 60% 1-RM, as compared with rest and previous workloads. Significant increases in systolic blood pressure and left ventricular end-systolic volume ratio values (P< or =.05) from rest to exercise were observed across test modes and for all workloads. The prevalence of new wall motion abnormalities during knee extension and BIC 1-RM strength testing was comparable with that observed during SL-GXT. The greatest increase in new wall motion abnormalities was seen during 60% 1-RM of knee extension exercise, as compared with prior workloads, BIC exercises, and SL-GXT.

CONCLUSIONS: Despite an increase in occurrence of ischemic changes during the highest resistance exercise workloads and with larger muscle mass, the findings are small in magnitude and do not suggest reduced cardiac performance.

Selig SE et al. Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow J Card Fail. 2004 Feb;10(1):21-30

BACKGROUND: Resistance exercise training was applied to patients with chronic heart failure (CHF) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance, aerobic power VO2

peak, heart rate variability (HRV), and forearm blood flow (FBF) METHODS AND RESULTS: Thirty-nine CHF patients (New York Heart Association Functional Class=2.3+/-0.5; left ventricular ejection fraction 28%+/-7%; age 65+/-11 years; 33:6 male:female) underwent 2 identical series of tests, 1 week apart, for strength and endurance of the knee and elbow extensors and flexors, VO2 peak, HRV, FBF at rest, and FBF activated by forearm exercise or limb ischemia. Patients were then randomized to 3 months of resistance training (EX, n=19), consisting of mainly isokinetic (hydraulic) ergometry, interspersed with rest intervals, or continuance with usual care (CON, n=20), after which they underwent repeat endpoint testing.

Selig SE et al. Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow. J Card Fail. 2004 Feb;10(1):21-30

• RESULTS: Combining all 4 movement patterns, strength increased for EX by 21+/-30%, P<.01) after training, whereas endurance improved 21+/-21% (P<.01). Corresponding data for CON remained almost unchanged (strength P<.005, endurance P<.003 EX versus CON). VO2 peak improved in EX by 11+/-15% (P<.01), whereas it decreased by 10+/-18% (P<.05) in CON (P<.001 EX versus CON). FBF increased at rest by 20+/-32% (P<.01), and when stimulated by submaximal exercise (24+/-32%, P<.01) or limb ischemia (26+/-45%, P<.01) in EX, but not in CON (P<.01 EX versus CON).

• CONCLUSIONS: Moderate-intensity resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance, VO2 peak, FBF, and HRV.

Delagardelle C et al. Strength/endurance training versus endurance training in congestive heart failure.Med Sci Sports Exerc. 2002 Dec;34(12):1868-72

• PURPOSE: The aim of this study was to compare the effects of endurance training alone (ET) with combined endurance and strength training (CT) on hemodynamic and strength parameters in patients with congestive heart failure (CHF).

• METHODS: Twenty male patients with CHF were randomized into one of two training regimens consisting of endurance training or a combination of endurance and resistance training. Group ET had 40-min interval cycle ergometer endurance training three times per week. Group CT combined endurance and strength training with the same interval endurance training for 20 min, followed by 20 min of strength training. Left ventricular function was assessed at baseline and after 40 training sessions by echocardiography and radionuclide ventriculography. Work capacity was measured with cardiopulmonary exercise test (CPX) and lactate determination. Strength was measured with an isokinetic dynamometer.

Delagardelle C et al. Strength/endurance training versus endurance training in congestive heart failure.Med Sci Sports Exerc. 2002 Dec;34(12):1868-72

• RESULTS: After 40 sessions, the ET group improved functional class, work capacity, peak torque, and muscular endurance. However, peak O2 remained unchanged. Left ventricular ejection fraction (LVEF) and fractional shortening (FS) decreased, whereas left ventricular end-diastolic diameter (LVED) increased. The CT group improved NYHA score, working capacity, peak O2, and peak lactate; peak torque and muscular endurance, LVEF, and FS increased, whereas LVED decreased. Compared with ET, CT was significantly (P < 0.05) better in improving LV function.

• CONCLUSION: Combined endurance/strength training was superior to endurance training alone concerning improvement of LV function, peak VO2, and strength parameters. It appears that for stable CHF patients, a greater benefit can be derived from this training modality.

To summarize: Resistance training and CHF

• No major complications or evidence of associated LV dysfunction

• Of the studies reviewed, the intensity of training, whether circuit or progressive resistance, was ~ 50-80% of repetition maximum or alternately, 10 RM.

• Positive outcome measures in all studies

• Hemodynamic stress no greater than aerobic training

• Consider segmental exercise for decreased hemodynamic effect

Martinez A Selective training of respiratory muscles in patients with chronic heart failure Rev Med Chil. 2001 Feb;129(2):133-9. Representative of 5 reviewed studies, all positive outcomes.

• AIM: To assess the effects of selective training of respiratory muscles in patients with heart failure.

• PATIENTS AND METHODS: Twenty patients with stable chronic heart failure, aged 58.3 +/- 3 years with an ejection fraction of 28 +/- 9%, were subjected to respiratory muscle training with threshold valves. The load was fixed in 30% of PImax in 11 and in 10% of PImax in nine. Two sessions of 15 minutes, 6 days per week, during 6 weeks were done. Degree of dyspnea (Mahler score), maximal oxygen uptake, distance walked in 6 minutes, respiratory muscle function and left ventricular ejection fraction were measured before and after training.

• RESULTS: Both training loads were associated to an improvement in dyspnea, maximal oxygen uptake, PImax, sustained PImax , and maximal sustained load. The distance walked in 6 min only increased in subjects trained at 30% PImax (from 451 +/- 78 to 486 +/- 68 m).

• CONCLUSIONS: Selective training of respiratory muscles results in a functional improvement of patients with chronic heart failure.

To summarize: Ventilatory muscle training and CHF

• Of the studies reviewed, the intensity of training was ~ 15-60% of maximal inspiratory pressure (a threshold of 25% seems likewise important) for duration of 15-30 minutes

• Positive outcome measures in all studies, training duration 8-12 weeks

• Outcome measures included ventilatory muscle strength, dyspnea, QOL and assessments of aerobic endurance

Haykowsky Mj M, Ezekowitz Ja J, Armstrong Pw P.Therapeutic exercise for individuals with heart failure: Special attention to older women with heart failure. J Card Fail. 2004 Apr;10(2):165-73

• BACKGROUND: A cardinal feature of heart failure (HF) is the reduced peak aerobic power (VO(2peak)) secondary to alterations in cardiovascular and musculoskeletal function.

• METHODS AND RESULTS: During the last decade, a number of randomized trials have examined the role that exercise training plays in attenuating the HF-mediated decline in VO(2peak) and muscle strength. The major finding of these investigations was that aerobic or strength training was an effective intervention to increase VO(2peak), muscular strength, distance walked in 6 minutes, and quality of life without negatively altering left ventricular systolic function. Despite these benefits, a limitation of these investigations was the primary focus on males <60 years with impaired left ventricular systolic function. Thus the role that exercise training may play in attenuating the HF-mediated decline in VO(2peak) in women >/=65 years of age remains unknown.

Haykowsky Mj M, Ezekowitz Ja J, Armstrong Pw P.Therapeutic exercise for individuals with heart failure: Special attention to older women with heart failure. J Card Fail. 2004 Apr;10(2):165-73

• CONCLUSION: Older women with HF have a VO(2peak) that is below the minimal threshold level required for independent living. Moreover, older women with HF have greater disability then men and are less likely to be referred to an exercise rehabilitation program. Accordingly, future exercise intervention trials are required to examine the role that exercise training may play in attenuating the HF-mediated decline in cardiorespiratory and musculoskeletal fitness and disability in older women with HF.

Mancini DM et al. Effect of erythropoietin on exercise capacity in patients with moderate to severe chronic heart failure. Circulation. 2003 Jan 21;107(2):294-9

• BACKGROUND: Investigated the effect of erythropoietin (EPO) on exercise performance in anemic patients with CHF.

• METHODS AND RESULTS: Twenty-six anemic patients aged 57+/-11 years were randomized to receive EPO (15 000 to 30 000 IU per week) or placebo for 3 months. Parameters measured at baseline and end therapy included blood parameters (hemoglobin, hematocrit, plasma volume), exercise parameters (peak VO2], exercise duration, 6-minute walk), muscle aerobic metabolism (half-time of VO2 and near infrared recovery), and forearm vasodilatory function. EPO was well tolerated by all patients. Twelve patients in the EPO group felt improvement versus 1 in the placebo group (P<0.05). There were significant increases in hemoglobin (11.0+/-0.5 to 14.3+/-1.0 g/dL, P<0.05), peak VO2 (11.0+/-1.8 to 12.7+/-2.8 mL. min(-1) x kg(-1), P<0.05) and exercise duration (590+/-107 to 657+/-119 s, P<0.004) in the EPO group but no significant changes in the control group.

• CONCLUSION: EPO significantly enhances exercise capacity in patients with CHF. One mechanism of improvement in VO2 is increased oxygen delivery from increased hemoglobin concentration.