Increased ^99mTc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients

Objectives: This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM). Background: Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial ^99mTc-MIBI washout is reportedly caused by mitochondrial dysfunction. Methods: Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial ^99mTc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dt_max) (an index of myocardial contractility) and LV pressure half-time (T_1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 μg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%. Results: WR was significantly correlated with the percentage changes in LV dP/dt_max (%LV dP/dt_max) (r: -0.59; p = 0.01) and T_1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dt_max was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044). Conclusions: Increased ^99mTc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients.