Heart Failure, Nonischemic Dilated Cardiomyopathy
Conditions
Keywords
heart failure, positron emission tomography, magnetic resonance imaging, myocardial energetics, myocardial perfusion
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.
Interventions
DRUGspironolactone
spironolactone 50 mg daily for 6 months
Sponsors
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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=\[left ventricular stroke work/decay rate of 11C-acetate\] |
| Left Ventricular Work-metabolic Index (WMI) at 6 Months | 6 months | 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 Minute Walk Test (6MWT) at 6 Months | 6 months | 6MWT assesses distance walked over 6 minutes |
| 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. |
| 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. |
| 6 Minute Walk Test (6MWT) at Baseline | baseline | 6MWT assesses distance walked over 6 minutes |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Results With 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.
spironolactone: spironolactone 50 mg daily for 6 months | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Results With Spironolactone | — |
|---|---|---|
| Age, Continuous | 52 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 15 participants | — |
| Sex: Female, Male Female | 5 Participants | — |
| Sex: Female, Male Male | 10 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 2 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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.
Time frame: baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Results With Spironolactone | Change in Myocardial Fibrosis (T1 Time) by Magnetic Resonance Imaging | 6 msec | Standard Deviation 37 |
Primary
Left Ventricular Work-metabolic Index (WMI) at 6 Months
WMI=\[left ventricular stroke work/decay rate of 11C-acetate\]
Time frame: 6 months
Population: 12 patients completed study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | Left Ventricular Work-metabolic Index (WMI) at 6 Months | 5.4 (x10^6), mL x mm Hg/m^2 |
Primary
Left Ventricular Work-metabolic Index (WMI) at Baseline
WMI=\[left ventricular stroke work/decay rate of 11C-acetate\]
Time frame: baseline
Population: 12 patients completed study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | Left Ventricular Work-metabolic Index (WMI) at Baseline | 7.4 (x10^6), mL x mm Hg/m^2 |
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Results With Spironolactone | Myocardial Perfusion Index Reserve (MPRI) by Magnetic Resonance Imaging at 6 Months | 1.80 MPRI |
Primary
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.
Time frame: baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Results With Spironolactone | Myocardial Perfusion Reserve Index (MPRI) by Magnetic Resonance Imaging at Baseline | 1.72 MPRI |
Secondary
6 Minute Walk Test (6MWT) at 6 Months
6MWT assesses distance walked over 6 minutes
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | 6 Minute Walk Test (6MWT) at 6 Months | 542 meters |
Secondary
6 Minute Walk Test (6MWT) at Baseline
6MWT assesses distance walked over 6 minutes
Time frame: baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | 6 Minute Walk Test (6MWT) at Baseline | 521 meters |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | Minnesota Living With Heart Failure Questionnaire.at 6 Months | 22 score on a scale |
Secondary
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.
Time frame: baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Results With Spironolactone | Minnesota Living With Heart Failure Questionnaire,at Baseline | 54 score on a scale |