Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)

Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction

The purpose of this study is to examine the effects of weight loss via hypocaloric diet (CR)and aerobic exercise (AT) compared to the effects of weight loss via hypocaloric diet (CR), aerobic training (AT)and resistance training (RT).

Heart failure with preserved ejection fraction (HFPEF) is the most common form of HF, is nearly unique to the older population, particularly older women, and is increasing in prevalence. Exercise intolerance, with severe exertional dyspnea and fatigue, is the primary manifestation of chronic HFPEF and is a major determinant of these patients' severely reduced quality of life (QOL). However, its pathophysiology is poorly understood and its optimal treatment remains undefined.

Our recent data and others' indicate that in older HFPEF patients, both increased adiposity and abnormalities in skeletal muscle are major contributors to exercise intolerance and potential therapeutic targets. Obesity is one of the strongest risk factors for HFPEF, and is a robust predictor of physical disability in older persons. The investigator recently reported that in HFPEF compared to age-matched controls, percent total and leg lean mass are significantly reduced and independently predict exercise capacity.

Using MRI and needle biopsy of the thigh muscle, the investigators found increased fat infiltration, reduced capillary density and percent type I oxidative fibers, and trends for reduced muscle mitochondrial mass and function. Reduced exercise capacity was related to each of these muscle abnormalities, supporting their important role in HFPEF.

Diet, with or without aerobic exercise, can increase exercise capacity and quality of life in older obese persons with a variety of disorders, but usually results in significant loss of skeletal muscle mass, which could potentially have adverse long term consequences. The purpose of this trial is to determine if addition of resistance training to diet plus aerobic exercise training can improve skeletal muscle mass and function in HFPEF.

Multiple lines of evidence and our preliminary data indicate that resistance training (RT) may be an ideal addition to CR+AT for HFPEF, since RT reliably increases muscle mass, quality, strength, and function, significantly more than AT, and can prevent nearly 50% of the muscle mass loss during CR.

Therefore, the primary aim of the proposed study is to conduct a randomized, single-blinded 20-week intervention trial of RT added to CR+AT in 84 overweight / obese (BMI greater than 28 kg/m2), older (age greater than 60 years) HFPEF patients to test the following primary hypothesis:

The addition of resistance training to CR+AT will improve exercise capacity.

Inclusion Criteria:

1. Age 60 years or older
2. Ejection fraction ≥ 50%
3. Left Ventricular Diastolic Dysfunction ≥ grade 1
4. BMI ≥ 28 kg/m2
5. HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score >/= 3 or Rich et al. criteria for HF

Exclusion Criteria:

1. Valvular heart disease as the primary etiology of CHF (congestive heart failure)
2. Significant change in cardiac medication or Heart Failure symptoms <6 weeks
3. Hospitalization or urgent care visit <6 weeks
4. Uncontrolled hypertension
5. Uncontrolled diabetes
6. Evidence of significant Chronic Obstructive Pulmonary Disease (COPD)
7. Recent or debilitating stroke
8. Cancer or other noncardiovascular conditions with life expectancy less than 2 years
9. Significant anemia (<10 g/dL Hgb)
10. Significant renal insufficiency (eGFR <30 mL/min/1.73m2)
11. Pregnant or of child-bearing potential
12. Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder
13. Plans to leave area within the study period
14. Refuses informed consent -