Effect of Aldosterone on Energy Starvation in Heart Failure

Phase 4

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Results with spironolactone	spironolactone	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.

Primary Outcome Measures

Name	Time	Method
Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 6 Months	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.
Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging	baseline and 6 months	T1=left ventricular relaxation rate on magnetic resonance imaging, which is correlated with interstitial fibrosis.
Left Ventricular Work-metabolic Index (WMI) at Baseline	baseline	WMI=\[left ventricular stroke work/decay rate of 11C-acetate\]
Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at Baseline	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.
Left Ventricular Work-metabolic Index (WMI) at 6 Months	6 months	WMI=\[left ventricular stroke work/decay rate of 11C-acetate\]

Secondary Outcome Measures

Name	Time	Method
Minnesota Living With Heart Failure Questionnaire,at Baseline	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.
6 Minute Walk Test (6MWT) at Baseline	baseline	6MWT assesses distance walked over 6 minutes
6 Minute Walk Test (6MWT) at 6 Months	6 months	6MWT assesses distance walked over 6 minutes
Minnesota Living With Heart Failure Questionnaire.at 6 Months	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.