Impairment of subendocardial perfusion reserve and oxidative metabolism in nonischemic dilated cardiomyopathy

Abstract

Background: Cardiac magnetic resonance (CMR) and [(11)C]acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of "energy starvation" in heart failure (HF).

Methods and results: CMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [(11)C]acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P < .001), 0.13 vs 0.17 (P < .001), and 0.13 vs 0.17 (P = .008), respectively]. The subendocardial perfusion reserve was 1.59 ± 0.21 vs 1.86 ± 0.32 for the subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced in proportion to perfusion reserve (P = .02) CONCLUSIONS: Impaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF.

Trial registration: ClinicalTrials.gov NCT00574119.

Keywords: CMR; fibrosis; heart failure; myocardial blood flow; oxidative metabolism.

Figure 1

Mid ventricular short axis images of a control subject (A) and NIDCM patient (B) at peak arrival of gadolinium contrast within myocardium during adenosine infusion.. A circumferential rim of endocardial hypoenhancement is demonstrated in B. (C) Anterior segment of mid ventricular short axis image divided into endocardium (green) and epicardium (red). (D) Signal intensity vs. time plots of first-pass wash-in of contrast into LV (solid black), endocardium (solid green) and epicardium (solid red). The slope of the appearance of contrast is denoted by dashed lines. NIDCM=nonischemic dilated cardiomyopathy, LV=left ventricle

Figure 2

Comparison of transmural, subendocardial and subepicardial myocardial perfusion index (MPI) in NIDCM and control subjects during adenosine infusion.

Figure 3

Comparison of transmural, subendocardial and subepicardial MPRI in NIDCM

Figure 4

A. Serial cardiac images following [11C] acetate injection, with monoexponential decay rate (k_mono). B. Relation of k_mono to systolic rate-pressure product (RPP). There is a linear relation between k_mono and RPP in normal subjects [k_mono(min⁻¹)= 0.034 × 10⁻⁶ + RPP(3.156 × 10⁻⁶), R= 0.81, P= 0.03]. In comparison to normal subjects, nearly all NIDCM patients had reduced k_mono that would be expected for the level of RPP, and the relationship between k_mono and RPP was not significant (P=0.54).

Figure 5

Relation between ratio k_mono/RPP and subendocardial MPRI (myocardial perfusion reserve index) segment shown in Fig. 1, where k_mono (min⁻¹)/RPP (beats per min × mmHg) = 1.44 × 10⁻⁶ + MPRI (2.745 × 10⁻⁶), R= 0.63, P= 0.02]. Please see text for explanation and abbreviations.