904-52 Verapamil Therapy in Infants with Hypertrophic Cardiomyopathy

Abstract

The safety and efficacy of verapamil therapy in infants with hypertrophic cardiomyopathy (HCM) was prospectively evaluated in 17 children presenting at age 2 days to 1 year (median 3.5 months) with primary HCM (asymmetric or regional hypertrophy excluding infants of diabetic mothers, and metabolic disorders). Acute response to intravenous verapamil infusion was assessed during cardiac catheterization. Effects of chronic therapy were assessed by clinical, echocardiographic, and Holter monitor evaluation. At presentation, 10 of 17 were symptomatic (7 congestive heart failure, 4 cyanosis, 1 arrhythmia, 1 apnea). Three cases were diagnosed on prenatal ultrasound. There was a positive family history in 7/15,16/17 had murmurs, all had abnormal ECGs, 6 had weight > 5%ile, and 2 had Noonan's syndrome. Acute verapamil infusion was well tolerated by all, without adverse electrophysiologic effects. Hemodynamic effects of verapamil were consistent with a negative inotropic effect with a significant fall in cardiac index (4.6 ± 1.2 to 4.0 ± 0.7 l/min/m 2 ), no change in end-diastolic pressure (15 ± 8 mmHg before to 15 ± 6 mmHg after), and a small fall in systolic blood pressure (mean -7 mmHg). In the 8 patients with LV outflow obstruction, the LV to aortic gradient decreased by -18 mmHg mean (range +1 to -45). Followup is not available in 1 of 17 patients. Two patients underwent surgery for subaortic stenosis. During 1 to 116 months (mean 32 months) of oral verapamil therapy, two patients died (one sudden, one after cardiac transplant). The sudden death occurred during Holter monitoring and appeared unrelated to verapamil. Complete heart block was seen transiently in one but other significant electrophysiologic side effects were not observed. Among the 14 survivors with followup, 6 are clinically and echocardiographically improved, 8 are stable, and none have had clinical deterioration or worsening disease on echocardiography. Echocardiographically, LV outflow obstruction decreased in 8/10 patients, remained unchanged in 1, and increased in the patient who subsequently underwent cardiac transplantation. Two patients have had complete resolution of hypertrophy on echocardiogram. We found that verapamil was well tolerated in infants with HCM without evidence of adverse effects and outcome was considerably better in these patients compared with prior reports. Resolution of hypertrophy in some patients suggests that either reversal of the phenotypic expression of this disorder is possible or else clinical and echocardiographic criteria may result in misdiagnosis.