Abstract & Commentary
With Comments by John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is on the Editorial Board of Clinical Cardiology Alert.
Synopsis: Disopyramide has a useful role in the therapeutic armamentarium for obstructive cardiomyopathy.
Source: Sherrid MV, et.al. J Am Coll Cardiol. 2005;45: 1251-1258.
This paper describes a 4-center study on the use of disopyramide in patients with hypertrophic cardiomyopathy. Four centers, 2 US, 1 UK and 1 Polish, with specialized clinics for patients with obstructive hypertrophic cardiomyopathy reviewed their patient records for the period between 1990 and 1999. They identified 491 patients with hypertrophic cardiomyopathy who had outflow obstruction at rest (gradient greater than or equal to 30 mm/Hg). Of these, 118 patients (24%) were treated with disopyramide. They then did a retrospective comparison between the disopyramide patients and the other patients. The data form the basis for this report.
Drug treatment was not randomized and was at the individual clinician’s discretion. Disopyramide was titrated up to a maximum dose of 600 mg per day. It was started either in an inpatient or an outpatient setting. At regular follow-up visits, patients had electrocardiograms, assessment of New York Heart Association functional class, and echocardiograms.
At the time of their initial evaluation, the 118 patients in the disopyramide group were 47 ± 20 years of age and 51% were male. They had a mean left ventricular outflow gradient at rest of 74 ± 35 mm/Hg and a mean New York Heart Association functional class of 2.3 ± 0.7. In the disopyramide group, therapy with the drug was begun 8 ± 17 months after their initial evaluation except in 10 patients who had been started on the drug prior to initial evaluation. Beta blockers were used in 98% of the disopyramide patients, amiodarone in 10%, and calcium channel blockers in 32%. In the disopyramide group, 78% (66 patients) were successfully managed medically and did not require a major intervention (eg, surgical septal myomectomy, alcohol septal ablation, or dual chamber pacing) during follow-up.
Among these patients, the average peak outflow gradient decreased substantially from 75 ± 33 to 40 ± 32 mm/Hg. Associated with this improvement in gradient, the mean NYHA functional class score decreased from 2.3 ± 0.7 to 1.7 ± 0.6.
Forty disopyramide patients required interventions 2.0 ± 2.1 years after beginning drug therapy. Baseline characteristics in the disopyramide group were not effective in identifying those who would require intervention. Disopyramide was discontinued because of adverse effects in 8 patients. Five of these had persistent dry mouth and 3 had symptomatic prostatism. Patients who went on to surgical myectomy, alcohol or septal ablation, or dual chamber pacing had higher gradients while taking disopyramide than those who did not require intervention. During the follow-up period, there were 4 sudden deaths in patients taking disopyramide at the time. One other patient died after discontinuing disopyramide. The annual sudden death rate for the entire group was 1% per year. In comparison to the patients not treated with disopyramide, there was a trend that did not achieve significance in the annualized all cause cardiac death rate, 1.4% for the disopyramide patients vs 2.6% for the other patients. Trends that were not significant were also noted for annualized sudden death rate (1% per year vs 1.8% per year) and total mortality (2.8% per year vs 3.8% per year). The hazard ratio for all cause cardiac death while taking disopyramide was 0.55 (confidence interval = 0.24 to 1.20; P = 0.13).
After a multivariate analysis that included variables such as treatment with surgical septal myectomy, beta blockers, calcium channel blockers, or amiodarone, maximum LV wall thickness and age, the hazard ratio for all cause cardiac death on disopyramide, still showed no significant difference between the disopyramide and the nondisopyramide comparison group, with a hazard ratio of 0.72 (confidence interval 0.32 to 1.64; P = 0.43).
Sherrid and colleagues conclude that disopyramide has a useful role in the therapeutic armamentarium for obstructive cardiomyopathy. In patients who responded, they observed a reduction in left ventricular outflow tract gradients and symptom improvement. In this series, no proarrhythmic effects were noted. Although we usually worry about proarrhythmia with antiarrhythmic drugs in patients with significant LVH, at least in this series, this did not seem to be a problem.
Comments
Hypertrophic cardiomyopathy remains a difficult clinical problem. This retrospective analysis from 4 specialized centers for hypertrophic obstructive cardiomyopathy shows that disopyramide has potential benefit in this population. Although this was a retrospective, nonrandomized comparison, the data are strong enough to suggest that a trial of disopyramide is certainly warranted, particularly if disopyramide and a beta blocker can be used together. It appears that the need for a nonpharmacologic intervention is decreased and the progression of the disease can be stabilized.
Disopyramide has a useful role in the therapeutic armamentarium for obstructive cardiomyopathy.
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