MRI in HCM Left ventricular (LV) Mass: Accurate measurement of LV mass (LV wall thickness) is essential to diagnosis of HCM. LV mass is difficult to estimate by echocardiography due to distortions of LV shape. We have demonstrated that MRI provides an accurate and reproducible estimation of maximum LV wall thickness and LV mass in HCM. This finding has allowed us to develop protocols to study the phenotype of novel genetic causes of HCM, and to evaluate potential ability of several genes and drugs to modify the cardiac phenotype. Stress MRI studies also provided valuable information about LV function and myocardial perfusion. Spiral HCM: Cine fast gradient echo cardiac MRI in about a hundred HCM patients has identified a new variant of HCM: ?spiral HCM' is characterized by rotation of the maximum LV wall thickness by 90 degrees around the short axis from base to apex. Spiral HCM is associated with generation of LV outflow obstruction and a more complete systolic ejection during exercise. Stress Perfusion MRI: Identification of myocardial ischemia has important prognostic and therapeutic implications in HCM patients. We performed dipyramidole stress gadpentetate dimeglumine perfusion MRI in 16 patients with non-obstructive HCM and normal coronary arteries. MRI detected perfusion defect in 12 patients with an average of 6+/- segments per patient. All defects involved the subendocardium. Most of the defects were in regions of LV hypertrophy. The remaining defects were in areas with normal LV wall thickness. Exercise thallium scintigraphy in 7 patients. The findings suggest that apparent cavity dilatation observed during nuclear studies is the result of subendocardial ischemia involving hypertrophic regions. Modifying Factors HCM may be caused by mutations in sarcomeric genes, and the associated cardiac hypertrophy may be a maladaptive response to impaired function of contractile proteins. However, the molecular mechanisms whereby the sarcomeric mutations lead to the increased cardiac mass are unknown. Notably, the associated cardiac hypertrophy varies significantly in HCM, even in affected individuals with the identical mutation. To explain the phenotypic variability we are assessing the potential role of several genes that may modify clinical expression of HCM caused by sarcomeric gene mutations. Our studies include assessing therapeutic strategies that may cause reversal of the disease phenotype. Renin-Angiotensin System: The severity of LV hypertrophy may be related to inheritance of a deletion (D) polymorphism of the ACE gene and plasma ACE levels. We are conducting a double-blind placebo-controlled study of enalapril (ACE inhibitor) and losartan (AT1 receptor inhibitor) either singly or in combination to cause regression of LV hypertrophy and to improve myocardial perfusion and LV diastolic function in non-obstructive HCM. The study also evaluates the electrophysiologic properties of these drugs and their ability to attenuate cardiac pain sensation.
