Real-World Use and Predictors of Response to Disopyramide in Patients with Obstructive Hypertrophic Cardiomyopathy

Niccolò Maurizi; Chiara Chiriatti; Carlo Fumagalli; Mattia Targetti; Silvia Passantino; Panagiotis Antiochos; Ioannis Skalidis; Chiara Chiti; Giulia Biagioni; Alessia Tomberli; Sara Giovani; Raffaele Coppini; Franco Cecchi; Iacopo Olivotto

doi:10.3390/jcm12072725

Real-World Use and Predictors of Response to Disopyramide in Patients with Obstructive Hypertrophic Cardiomyopathy

J Clin Med. 2023 Apr 6;12(7):2725. doi: 10.3390/jcm12072725.

Authors

Affiliations

¹ Department of Clinical and Experimental Medicine, University of Florence, 50121 Florence, Italy.
² Service of Cardiology, University Hospital of Lausanne, 1009 Lausanne, Switzerland.
³ Cardiomyopathy Unit, Careggi University Hospital, 50134 Florence, Italy.
⁴ Department NeuroFarBa, University of Florence, 50121 Florence, Italy.
⁵ Fondazione AICARM, 50100 Florence, Italy.
⁶ Service of Cardiology, Meyer Children's Hospital IRCCS, 50139 Florence, Italy.

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.

Keywords: disopyramide; hypertrophic cardiomyopathy; obstructive HCM management.

Grants and funding

I.O. was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement no. 777204: “SILICOFCM-In Silico trials for drug tracing the effects of sarcomeric protein mutations leading to familial cardiomyopathy”.