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 Tc-99m-MIBI washout is reportedly caused by mitochondrial dysfunction. Methods Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial Tc-99m-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 mu g/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 Tc-99m-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients. (C) 2013 by the American College of Cardiology Foundation