Effect of Aldosterone on Energy Starvation in Heart Failure

Study Overview
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Brief Summary
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We plan to study the concept of energy starvation in heart failure by evaluation of patients with nonischemic dilated cardiomyopathy (NIDCM) (heart failure with reduced heart pump function due to causes other than heart attack). We will use a combination of positron emission tomography and magnetic resonance imaging to study metabolism, anatomy, function, blood flow and efficiency, before and after 6 months' treatment with the drug spironolactone which blocks the deleterious effects of the hormone aldosterone on the myocardium (heart muscle).

Detailed Description
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Preliminary results showed reduced subendocardial myocardial perfusion reserve in NIDCM compared to normal subjects, and that the degree of impaired perfusion reserve was related to the oxidative metabolic rate as measured by positron emission tomography.

Official Title
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Effect of Aldosterone on Energy Starvation in Heart Failure

Conditions
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Heart Failure, Nonischemic Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: spironolactone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Nonischemic dilated cardiomyopathy Left ventricular ejection fraction 35% or less Stable heart failure symptoms Able to undergo both positron emission tomography and magnetic resonance imaging with gadolinium Able to tolerate treatment with spironolactone Exclusion Criteria: Serum potassium >5.0 Serum creatinine >2.5 Contraindications to magnetic resonance imaging such as internal cardioverter-defibrillator.

Ages Eligible for Study
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Minimum Age: 18 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Results with spironolactone<br>patients with heart failure due to nonischemic dilated cardiomyopathy will be studied by 11C acetate positron emission tomography and magnetic resonance imaging using vasodilator and gadolinium to judge myocardial blood flow, before and after 6 months' treatment with spironolactone. | Drug: spironolactone<br>* spironolactone 50 mg daily for 6 months<br>* Other names: Aldactone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Work-metabolic Index (WMI) at Baseline | WMI=[left ventricular stroke work/decay rate of 11C-acetate] | baseline | 
| Left Ventricular Work-metabolic Index (WMI) at 6 Months | WMI=[left ventricular stroke work/decay rate of 11C-acetate] | 6 months | 
| Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at Baseline | MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope. | baseline | 
| Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 6 Months | MPRI =calculated myocardial perfusion reserve index based on Gadolinium accretion into myocardium. MPRI was calculated as the ratio of stress/rest relative perfusion upslope, corrected for LV cavity upslope. | 6 months | 
| Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging | T1=left ventricular relaxation rate on magnetic resonance imaging, which is correlated with interstitial fibrosis. | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Test (6MWT) at Baseline | 6MWT assesses distance walked over 6 minutes | baseline | 
| 6 Minute Walk Test (6MWT) at 6 Months | 6MWT assesses distance walked over 6 minutes | 6 months | 
| Minnesota Living With Heart Failure Questionnaire,at Baseline | The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure. | baseline | 
| Minnesota Living With Heart Failure Questionnaire.at 6 Months | The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. Each question is scored from 0 (none or not applicable) to 5 (very much). Total scores range from 0-105. Low scores indicate less adverse impact, while higher scores reflect more adverse impact of heart failure. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, positron emission tomography, magnetic resonance imaging, myocardial energetics, myocardial perfusion