HCM is myocardial disease with an autosomal dominant pattern of inheritance characterized by LV hypertrophy. Our efforts are directed at developing therapeutic strategies to improve symptoms and prognosis and elucidate the genetic/molecular abnormalities in HCM and related myopathies. Following the demonstration that DDD pacemakers relieve drug-refractory symptoms in adult patients with obstructive HCM, we have initiated a prospective study to examine the ability of DDD pacing to relieve this condition in HCM children between the ages of 5-15 years. To date, 38 children have been recruited and one-year follow-up cardiac evaluation in about 20 of these patients indicates that pacing is effective in improving both left and right-sided outflow obstruction and causes striking cardiac remodelling in an age group associated with most rapid cardiac thickening and hemodynamic deterioration. Atrial fibrillation (AF) is a serious rhythm abnormality that occurs in 10% of HCM. We have demonstrated the ability of radiofrequency AV node ablation and implantation of pacemakers to improve symptoms and cardiac hemodynamics in 40 HCM patients with AF. A prospective study is underway to investigate the ability of ACE inhibitor and angiotensin blockade to improve diastolic function, improve myocardial perfusion and cause regression of cardiac hypertrophy in nonobstructive HCM. To date, we have identified about 30 mutations in the beta-myosin heavy chain (beta-MHC) gene that cause HCM in 57 unrelated kindreds. The clinical correlates of these mutations are being investigated. Some of the mutations have been demonstrated to result in abnormal skeletal fiber mechanics and energy utilization. About 30% of HCM patients with beta- MHC gene mutation do not develop cardiac hypertrophy as shown by echocardiography. We propose to study the relation between ACE levels and severity of LV hypertrophy in HCM patients with distinct beta-MHC gene mutations.
