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

Susan P Bell, Douglas W Adkisson, Mark A Lawson, Li Wang, Henry Ooi, Douglas B Sawyer, Marvin W Kronenberg, Susan P Bell, Douglas W Adkisson, Mark A Lawson, Li Wang, Henry Ooi, Douglas B Sawyer, Marvin W Kronenberg

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.

Keywords: Energy metabolism; heart failure; magnetic resonance imaging; myocardial perfusion imaging; positron emission tomography.

© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1.
Figure 1.
Selected mid‐ventricular short‐axis images during the first‐pass transit of contrast through the heart. A, Before contrast arrival. B, Contrast arrival within the right ventricle. C, Contrast arrival within the left ventricle. D, Delayed endocardial contrast arrival (arrows).
Figure 2.
Figure 2.
Mid‐ventricular short‐axis images of NIDCM patient. A, Peak arrival of Gd‐DTPA within myocardium during adenosine infusion. B, LV segmented by software and anterior segment of mid‐ventricular short‐axis image selected for comparison, divided into endocardium (green) and epicardium (red). C, Signal intensity‐time curves for LV (black), subendocardium, and supepicardium, as above. The LV curve shows earlier arrival and greater peak signal intensity than the myocardial segments. Gd‐DTPA indicates gadolinium‐diethylenetriamine pentaacetic acid; LV, left ventricular; NIDCM, nonischemic dilated cardiomyopathy.
Figure 3.
Figure 3.
Comparison of myocardial perfusion index (MPI) in NIDCM at rest and during adenosine infusion for each subject at baseline and after ≥6 months of spironolactone therapy. NIDCM indicates nonischemic dilated cardiomyopathy.
Figure 4.
Figure 4.
Comparison of subendocardial MPRI (A) and WMI (B) for each subject at baseline and after spironolactone therapy. The MPRI and WMI increased in 11 of 12 patients and decreased in none. MPRI indicates myocardial perfusion reserve index; WMI, work metabolic index.

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