Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy

Background: The class Ia antiarrhythmic drug disopyramide relieves the outflow tract obstruction of hypertrophic obstructive cardiomyopathy (HOCM). Disopyramide, however, has several adverse effects, such as dysuria and thirst, resulting from its anticholinergic activity. A new class Ia antiarrhythmic drug, cibenzoline, has little anticholinergic activity. The aim of this study is to elucidate whether cibenzoline attenuates left ventricular pressure gradient (LVPG) in patients with HOCM.

Methods and results: Ten patients with HOCM (mean age, 59+/-12 years) participated in this study. LVPG and left ventricular functions were measured before and 2 hours after administration of a single oral dose of 150 or 200 mg cibenzoline. LVPG decreased from 123+/-60 to 39+/-33 mm Hg (P=.0026). The E/A ratio in transmitral Doppler flow increased from 1.20+/-0.84 to 2.00+/-1.72 (P=.029). Isovolumic relaxation time increased from 73+/-16 to 101+/-23 ms (P=.0026). Left ventricular diastolic dimension remained unchanged, but left ventricular systolic dimension enlarged significantly, from 21.6+/-2.4 to 26.2+/-3.3 mm (P=.0004). Fractional shortening decreased from 47.6+/-6.1% to 34.6+/-8.8% (P=.0007). Left ventricular ejection time index decreased significantly, and preejection period index increased in all the patients. Decreased LVPG remained maintained even in the long-term treatment with cibenzoline. Conclusions These results indicate that cibenzoline can markedly attenuate LVPG in patients with HOCM. A decrease in myocardial contractility seems to be closely related to a marked decrease in LVPG.