Effect of Aldosterone on Energy Starvation in Heart Failure

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).

Study Overview

• Status: Completed
• Conditions: Heart Failure; Nonischemic Dilated Cardiomyopathy
• Intervention / Treatment: Drug: spironolactone

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Heart and Vascular Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: spironolactone; spironolactone 50 mg daily for 6 months; Other Names: Aldactone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Marvin W Kronenberg, MD, Vanderbilt University School of Medicine

Publications and helpful links

General Publications

• Lawson MA, Hansen DE, Gupta DK, Bell SP, Adkisson DW, Mallugari RR, Sawyer DB, Ooi H, Kronenberg MW. Modification of ventriculo-arterial coupling by spironolactone in nonischemic dilated cardiomyopathy. ESC Heart Fail. 2021 Apr;8(2):1156-1166. doi: 10.1002/ehf2.13161. Epub 2021 Jan 5.
• Bradham WS, Bell SP, Huang S, Harrell FE Jr, Adkisson DW, Lawson MA, Sawyer DB, Ooi H, Kronenberg MW. Timing of Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy. Am J Med Sci. 2018 Sep;356(3):262-267. doi: 10.1016/j.amjms.2018.06.003. Epub 2018 Jun 8.
• Lawson MA, Bell SP, Adkisson DW, Wang L, Ooi H, Sawyer DB, Kronenberg MW. High reproducibility of adenosine stress cardiac MR myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy. BMJ Open. 2014 Dec 16;4(12):e005984. doi: 10.1136/bmjopen-2014-005984.
• Bell SP, Adkisson DW, Lawson MA, Wang L, Ooi H, Sawyer DB, Kronenberg MW. Antifailure therapy including spironolactone improves left ventricular energy supply-demand relations in nonischemic dilated cardiomyopathy. J Am Heart Assoc. 2014 Aug 27;3(4):e000883. doi: 10.1161/JAHA.114.000883.
• Bell SP, Adkisson DW, Ooi H, Sawyer DB, Lawson MA, Kronenberg MW. Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy. J Card Fail. 2013 Dec;19(12):802-10. doi: 10.1016/j.cardfail.2013.10.010. Epub 2013 Oct 29.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 13, 2007
• First Submitted That Met QC Criteria: December 14, 2007
• First Posted (Estimate): December 17, 2007

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; heart failure; positron emission tomography; myocardial perfusion; myocardial energetics
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Malnutrition; Cardiomegaly; Laminopathies; Heart Failure; Cardiomyopathies; Cardiomyopathy, Dilated; Starvation; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: IRB 070824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO