Real-World Use and Predictors of Response to Disopyramide in Patients with Obstructive Hypertrophic Cardiomyopathy
Niccolò Maurizi1,2, Chiara Chiriatti3, Carlo Fumagalli3
1Department of Clinical and Experimental Medicine, University of Florence, 50121 Florence, Italy.
Insights
Disopyramide effectively reduces left ventricular outflow obstruction in obstructive hypertrophic cardiomyopathy, particularly in patients with milder symptoms. The drug demonstrated a safe profile, with side effects mainly being anticholinergic.
Area of Science:
- Cardiology
- Pharmacology
- Genetics and disease
Background:
- Obstructive hypertrophic cardiomyopathy (oHCM) is a significant condition.
- Disopyramide is used to manage left ventricular outflow obstruction (LVOTO) and symptoms in oHCM.
- Real-world data on disopyramide's effectiveness and patient characteristics predicting response are limited.
Purpose of the Study:
- To evaluate the real-world efficacy and safety of disopyramide in patients with oHCM.
- To identify patient characteristics associated with a positive response to disopyramide therapy.
Main Methods:
- Retrospective analysis of 1527 HCM patients from 1980-2021; 372 had LVOTO.
- Disopyramide efficacy and safety assessed over 12 months in 118 patients.
- Response defined by NYHA class and LVOT gradient reduction; safety assessed via QTc interval and adverse events.
Main Results:
- Disopyramide therapy was initiated in 118 patients (32%), with 24% showing a complete response.
- Patients in NYHA class I/II at baseline were more likely to respond (86%) compared to those in NYHA III/IV.
- Prolonged QTc interval occurred in 69% of patients; 26% experienced side effects, primarily anticholinergic.
Conclusions:
- Disopyramide is underutilized in oHCM but effective in reducing LVOTO and symptoms.
- Treatment response is associated with less severe disease phenotypes (NYHA class I/II).
- Disopyramide exhibits a safe pro-arrhythmic profile in this patient cohort.
Abstract:
Background: Although disopyramide has been widely used to reduce left ventricular outflow obstruction (LVOTO) and to improve symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM), its use in real world as well as patient characteristics associated with a positive treatment response are still unclear. Methods: From 1980 to 2021, 1527 patients with HCM were evaluated and 372 (23%) had a LVOTO with active follow-up. The efficacy and safety of disopyramide were assessed systematically during 12 months (2-, 6-, and 12-month visits). Responders were patients with a final NYHA = I and a LVOTO < 30 mmHg; incomplete responders were those patients with NYHA > I and a LVOTO < 30 mmHg; and non-responders were symptomatic patients with no change in functional class NYHA and a LVOT gradient > 30 mmHg. Results: Two-hundred-fifty-four (66%) patients were in functional class NYHA I/II and 118 (34%) in NYHA III/IV. A total of 118/372 (32%, 55 ± 16 years) underwent disopyramide therapy. Twenty-eight (24%) patients responded to therapy, 39 (33%) were incomplete responders, and 51 (43%) did not respond. Responder were mainly patients in functional NYHA class I/II (24/28, 86%), whereas incomplete responders and non-responders were more often in functional NYHA class III/IV (50/54 (93%)). An independent predictor of response to disopyramide treatment was the presence of NYHA I/II at the initiation of therapy (HR 1.5 (95% CI 1.1-4.5), p = 0.03). No major life-threatening arrhythmic events or syncope occurred, despite 19 (16%) patients showing reduced QTc from baseline, 19 (16%) having no difference, while 80 (69%) patients had prolonged QTc interval. Thirty-one (26%) patients experienced side effects, in particular, 29 of the anticholinergic type. Conclusions: Disopyramide was underused in oHCM but effective in reducing LVOTO gradients and symptoms in slightly symptomatic patients with less severe disease phenotype with a safe pro-arrhythmic profile.
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