A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies

Abstract

Technetium 99m sestamibi (MIBI) is a technetium-labeled myocardial perfusion agent that is taken up by the myocardial cell in proportion to myocardial regional blood flow and remains fixed in the myocardial cell over a long period of time. Previous studies have suggested that MIBI shows very slow myocardial clearance after its initial uptake in an animal model, which is related to mitochondrial function. This study was designed to test the hypothesis that MIBI washout can be used to evaluate the severity of congestive heart failure in comparison to other clinical parameters in patients with cardiomyopathies. After administration of MIBI, 61 patients with nonischemic congestive heart failure (49 with dilated cardiomyopathy and 12 with other cardiomyopathies) and 7 normal control subjects were examined by electrocardiography-gated myocardial perfusion single photon emission computed tomography and planar data acquisition in the early and delayed phases (interval of 3 hours). Myocardial MIBI washout rates were calculated from the early and delayed planar images. Left ventricular function (systolic and diastolic) was analyzed by use of QGS data. Plasma levels of B-type natriuretic peptide and iodine 123 metaiodobenzylguanidine (MIBG) parameters were also measured. Patients were followed up for a mean of 12 months (range, 1-19 months). As the severity of the New York Heart Association (NYHA) functional class advanced, the washout rate of MIBI increased (21.6% +/- 2.4% in those with NYHA class I [n = 23], 28% +/- 4% in those with NYHA class II [n = 27], and 35% +/- 5% in those with NYHA class III [n = 10]; P < .05, analysis of variance). The washout rate of MIBI was positively correlated with the level of B-type natriuretic peptide (r = 0.31, P < .05), end-diastolic volume (r = 0.396, P < .01), and end-systolic volume (r = 0.496, P < .01) and was negatively correlated with left ventricular ejection fraction (r = 0.523, P < .01), peak filling rate (r = 0.444, P < .01), and first-third ejection fraction (r = 0.414, P < .01). The parameters of MIBG scintigraphy were calculated as the heart-mediastinum count ratio (1.9 +/- 3) and washout rate (38% +/- 4%). We found a significant relationship between the washout rate of MIBI and the heart-mediastinum count ratio of MIBG (r = 0.51, P < .01). Patients with a higher washout rate of MIBI had a higher cardiac event rate (> or =28%) than those with a lower washout rate (<28%) (P < .05). The myocardial washout rate of MIBI is thought to be a novel marker for the diagnosis of myocardial damage or dysfunction, providing prognostic information in patients with congestive heart failure.