Antifailure therapy including spironolactone improves left ventricular energy supply-demand relations in nonischemic dilated cardiomyopathy.

Abstract

BACKGROUND:

Left ventricular (LV) energy supply-demand imbalance is postulated to cause "energy starvation" and contribute to heart failure (HF) in nonischemic dilated cardiomyopathy (NIDCM). Using cardiac magnetic resonance (CMR) and [(11)C] acetate positron emission tomography (PET), we evaluated LV perfusion and oxidative metabolism in NIDCM and the effects of spironolactone on LV supply-demand relations.

METHODS AND RESULTS:

Twelve patients with NIDCM underwent CMR and PET at baseline and after ≥6 months of spironolactone therapy added to a standard HF regimen. The myocardial perfusion reserve index (MPRI) was calculated after gadolinium injection during adenosine, as compared to rest. The monoexponential clearance rate of [(11)C] acetate (kmono) was used to calculate the work metabolic index (WMI), an index of LV mechanical efficiency, and kmono/RPP (rate-pressure product), an index of energy supply/demand. At baseline, the subendocardium was hypoperfused versus the subepicardium (median MPRI, 1.63 vs. 1.80; P<0.001), but improved to 1.80 (P<0.001) after spironolactone. The WMI increased (P=0.001), as did kmono/RPP (P=0.003). These improvements were associated with reverse remodeling, increased LV ejection fraction, and decreases in LV mass and systolic wall stress (all P<0.002).

CONCLUSIONS:

NIDCM is associated with subendocardial hypoperfusion and impaired myocardial oxidative metabolism, consistent with energy starvation. Antifailure therapy improves parameters of energy starvation and is associated with augmented LV performance.

CLINICAL TRIAL REGISTRATION URL:

http://www.clinicaltrials.gov/ Unique identifier: ID NCT00574119.

• Authors: Susan P Bell, Douglas W Adkisson, Mark A Lawson, Li Wang, Henry Ooi, Douglas B Sawyer, Marvin W Kronenberg
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 3 Issue 4 (Aug 27 2014) ISSN: 2047-9980 [Electronic] England
• PMID: 25164945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Chemical References

• Mineralocorticoid Receptor Antagonists
• Spironolactone

Topics

• Cardiomyopathy, Dilated (complications, diagnostic imaging, drug therapy)
• Energy Metabolism
• Female
• Heart Failure (diagnostic imaging, drug therapy, etiology)
• Heart Ventricles (diagnostic imaging, metabolism)
• Humans
• Magnetic Resonance Imaging
• Magnetic Resonance Imaging, Cine
• Male
• Middle Aged
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Myocardial Perfusion Imaging
• Myocardium (metabolism)
• Positron-Emission Tomography
• Spironolactone (therapeutic use)
• Ventricular Function, Left