Dr. Imai explained that although various drugs with negative inotropic effects have been used in hypertrophic obstructive cardiomyopathy (HOCM) to reduce the left ventricular pressure gradient (LVPG), few data exist to help physicians choose an agent for the individual patient.

The purpose of the current clinical trial was to compare pilsicainide, a pure Na channel-blocker, with 4 drugs that have some degree of proven efficacy in reduction of LVPG: propranolol (a beta-blocker), verapamil (a Ca channel-blocker), disopyramide (a class 1a antiarrhythmic), and cibenzoline (another class 1a antiarrhythmic). The patient population was to consist of adults with proven HOCM and LVPG without provocation of greater than 40 mm Hg.

All 24 participants had baseline left ventricular (LV) function and LVPG assessments, and then they were divided into 2 groups of 12 patients each. The first group (Group A, mean LVPG 84.5±28.5 mmHg) was used to evaluate the effects of propranolol, verapamil, and disopyramide. The other group (Group B, mean LVPG 92.5±40.3 mmHg) was used to evaluate the effects of pilsicainide, disopyramide, and cibenzoline.

Patients received before-treatment and after-treatment evaluations for each of the 3 drugs they tested. Echocardiography was used to assess LVPG, percent fractional shortening (%FS), peak E/A wave ratio (E/A ratio), isovolumic relaxation time (IRT), and deceleration time (DcT). Each drug was given intravenously as follows: disopyramide (1.2mg/kg), cibenzoline (1.4mg/kg), pilsicainide (1.0mg/kg), verapamil (0.1mg/kg), and propranolol (0.2mg/kg).

In testing with the first group of patients (Group A), disopyramide was clearly superior to verapamil and propranolol in reduction of LVPG. In testing with the second group of patients (Group B), disopyramide, cibenzoline, and pilsicainide had roughly equivalent effects on LVPG (-55.5±28.0% with disopyramide [from 92.5 to 40.3 mm Hg], -58.5±21.3% with cibenzoline [from 103.1 to 44.4 mmHg], -54.5±15.5% with pilsicainide [from 107 to 47.5 mmHg]).

The other parameters that were measured were percent fractional shortening (%FS), peak E/A wave ratio (E/A ratio), isovolumic relaxation time (IRT), and deceleration time (DcT). In contrast to the effects of propranolol and verapamil, the effects of the three class 1 antiarrhythmic agents (pilsicainide, disopyramide, cibenzoline) were similar and without statistical significance: Percent fractional shortening was significantly decreased, E/A ratio was significantly increased, and DcT was significantly prolonged.

Dr. Imai concluded that the efficacy for reduction of LVPG by pilsicainide (the pure Na channel-blocker) is comparable with that of the other class 1 antiarrhythmic agents, disopyramide and cibenzoline. In contrast, the sample beta-blocker and Ca channel-blocker (propranolol and verapamil) have a variety of effects other than reduction in LVPG in this population of patients with HOCM.