Verapamil was shown to lower gradients in an acute study after intravenous infusion (15). It too has been shown to increase exercise tolerance (16). However, verapamil has been associated with as high as a 25% cardiac complication rate, including pulmonary edema and sudden death (17). This may occur because, in an individual patient, the vaso-dilating effects of verapamil may overshadow the negative inotropic effects. The high incidence of side effects was seen in a series of referral patients; side effects may not be as high in a less sick group of patients. Nevertheless, rather than verapamil we have used disopyramide for our obstructed patients who do not respond to beta blockade. The class Ia antiarrhythmic cibenzoline has been reported by Japanese investigators to be efficacious in reducing systolic outflow gradients in 10 patients (18). LV fractional shortening decreased by 27%, similar in magnitude to that reduction observed with disopyramide. This agent is not available in the United States. This antiarrhythmic does not have the vagolytic side effects of disopyramide. Most asymptomatic patients are not candidates for medical therapy because no medical treatment has been shown in a randomized trial to improve the natural history or decrease mortality Twenty percent are receiving no medication because they are asymptomatic. Of the 40 treated patients, 43% are currently on more than one medication for their HCM. Rapid Relief of Obstruction. It is important to note that gradients can vary spontaneously from day to day. A variety of circumstances of daily life have been shown to increase the gradient, including the post-prandial state, ethanol ingestion, erect posture and exercise. Echocardiograms performed after the patient has eaten studies the patient physiologically "at their worst"; this is useful when correlating symptoms of daily life with the echocardiogram. The process of finding the right drug to reduce outflow obstruction can be time consuming and frustrating for the symptomatic patient and the doctor alike. The physician seeks to give the smallest dose of drug(s) that works. So, drugs are generally introduced with gradually increasing dosage with echos performed after each dose change or with addition of a new drug. This strategy can not only result in prolonged hospital stays, repeated office visits and multiple echocardiograms, but it is also expensive. To facilitate rapid elimination of outflow obstruction we have evolved a system of acute drug testing with repeat echocardiograms on the same visit. Patients are treated using a clinical protocol of acute drug testing with the goal of rapid gradient elimination on sequential Doppler echocardiography (19). Intravenous metoprolol, to a dose of 15 mg is used first, unless contraindicated. If the Doppler gradient is reduced within 30 minutes to less than 30 mm Hg, oral beta-blockers are continued as sole therapy. If a > 30 mm Hg gradient persists, oral disopyramide is administered on the same day. We give disopyramide 250 mg as an oral loading dose and then repeat the echocardiogram 2 1/2 hours later (10). In patients with a contraindication to disopyramide, oral verapamil is begun 240-360 mg/day in divided doses. Treatment failures (defined as persistent gradient > 30 mm Hg) are identified by Doppler within 48 hours and combination regimens are begun.   PREVIOUS PAGE     NEXT PAGE