Exercise Intolerance in Elderly Patients With Diastolic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of weight loss via hypocaloric diet, aerobic exercise training, combined hypocaloric diet and exercise training, and attention control in patients with heart failure and a normal ejection fraction (HFNEF) and body mass index greater than or equal to 30.

Detailed Description
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Heart failure with a normal ejection fraction (HFNEF, previously termed diastolic heart failure), accounts for the majority of heart failure cases in the population > 65 years old and has been recognized as a true geriatric syndrome. Exercise intolerance is the primary chronic symptom of HFNEF and a major determinant of these patients' severely reduced quality of life; however little is known regarding its pathophysiology and treatment. Therefore, our work has focused on understanding the pathophysiology of exercise intolerance in HFNEF and developing and testing interventions that may improve this pivotal outcome in this highly prevalent disorder of older persons. The aims of the proposed study are to conduct a randomized, controlled, single-blinded, 2x2 design trial to examine the effects of weight loss via hypocaloric diet, aerobic exercise training, combined hypocaloric diet and exercise training, and attention control in patients with HFNEF and body mass index >30 in order to test the following hypotheses: 1) Both weight loss and exercise training will improve exercise intolerance and quality of life in older, obese patients with HFNEF; 2) The combination of weight loss and exercise training will produce complementary effects on body and thigh muscle composition and additive improvements in exercise intolerance in HFNEF; 3) Improvements in exercise intolerance will correlate with improvements in lean body mass, reversal of adverse thigh muscle remodeling, and increased thigh muscle capillarity. The study has the potential to significantly advance our understanding of exercise intolerance and its treatment in the large population of older persons with HFNEF.

Official Title
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Study of the Effect of Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction.(SECRET)

Conditions
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Heart Failure, Diastolic, Obesity

Intervention / Treatment
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* Behavioral: Exercise
* Dietary Supplement: Dietary Intervention
* Behavioral: Diet and exercise
* Other: Attention Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart failure clinical score greater than or equal to 3 Age 60 and over Normal ejection fraction greater than or equal to 50% BMI greater than or equal to 30 Exclusion Criteria: Valvular heart disease Significant change in cardiac medication <4 weeks Uncontrolled hypertension Recent or debilitating stroke Cancer or other noncardiovascular conditions with life expectancy less than 2 years Significant Anemia Renal insufficiency (creatinine >2.5mg/dl) Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder Plans to leave area within 6 months Refuses informed consent Failure to pass screening test:pulmonary function, echocardiogram,or exercise

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Exercise Training<br>Exercise participants will undergo a 1-hour supervised exercise program 3 times per week for 20 weeks consisting primarily of walking exercise using an individualized exercise prescription based on the initial exercise stress testing results. | Behavioral: Exercise<br>* walking, treadmill and bicycle exercise<br>|
| Active Comparator: Dietary Intervention<br>A hypocaloric diet will be developed to achieve a 2800 kcal/week deficit, which should produce about 0.4 kg (1 lb) weight loss per week. | Dietary Supplement: Dietary Intervention<br>* Subjects will be provided meals and instructions for individual food selections.<br>|
| Active Comparator: Attention control<br>Attention control participants will be provided a counseling session regarding general health education at baseline and will be contacted by staff via telephone every 2 weeks to discuss general health status. | Other: Attention Control<br>* control group- continue their previously randomized life style<br>|
| Active Comparator: Diet and Exercise<br>A hypocaloric diet will be developed to achieve a 2450 kcal/week deficit in addition to undergoing a 1-hour supervised exercise program 3 times per week for 20 weeks consisting primarily of walking exercise using an individualized exercise prescription based on the initial exercise stress testing results. | Behavioral: Exercise<br>* walking, treadmill and bicycle exercise<br>Behavioral: Diet and exercise<br>* Subjects will be provided meals and instructions for individual food selections and will undergo walking, treadmill and bicycle exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise Capacity | Exercise capacity assessed as Peak VO2 (ml/kg/min) via treadmill cardiopulmonary exercise testing using the modified Naughton protocol to the end point of exhaustion. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | Heart failure-specific quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ) on a range 0-100; higher scores indicate better quality of life. | 20 weeks | 
| Body Composition | Total Body Fat Mass and Total Non-bone Lean Mass via DEXA | 20 weeks | 
| Thigh Muscle Composition | Thigh Skeletal Muscle and Subcutaneous Fat via MRI | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diastolic heart failure, Heart Failure, Elderly, Obesity