Relation of functional and morphological changes in mitochondria to myocardial contractile and relaxation reserves in asymptomatic to mildly symptomatic patients with hypertrophic cardiomyopathy

Aims To examine the relation between mitochondrial dysfunction and myocardial contractile and relaxation reserves in hypertrophic cardiomyopathy (HCM). Methods and results Thirty HCM patients (LVEF ≥60%) underwent biventricular cardiac catheterization analysis both at rest and during atrial pacing as well as myocardial 99mTc-sestamibi scintigraphy at rest to calculate washout rate. Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The HCM patients were divided into two groups—group A: normal force–frequency relation and a pressure half-time ( T 1/2) of <30 ms ( n = 15); group B: abnormal force–frequency relation or T 1/2 of ≥30 ms ( n = 15). The 99mTc-sestamibi washout rate was significantly correlated with T 1/2 for all patients ( r = 0.74, P < 0.01) and was also significantly greater in group B (29.2 ± 6.3%) than in group A (19.3 ± 3.1%). The abundance of mRNAs for mitochondrial electron transport-related enzymes was significantly higher in group A than in group B. Mitochondria showed a greater variation in size and were more disorganized in group B than in group A. Conclusion Mitochondria showed functional impairment and morphological disorganization in the left ventricle of HCM patients without baseline systolic dysfunction. These mitochondrial changes were associated with impaired myocardial contractile and relaxation reserves.