Disopyramide Effects on Exercise Tolerance in Obstructive Hypertrophic Cardiomyopathy

Overview

Disopyramide treatment in obstructive hypertrophic cardiomyopathy (oHCM) patients reduces left ventricular outflow tract obstruction (LVOTO) and improves symptoms but leads to decreased peak oxygen consumption (pVO2) and exercise capacity. Despite these changes, quality of life shows a non-significant trend toward improvement.

Background

Hypertrophic cardiomyopathy is a genetic disorder characterized by left ventricular thickening, often causing LVOTO in two-thirds of patients. This obstruction results in symptoms such as syncope, dyspnea, and exercise intolerance. First-line treatments include beta-blockers and calcium channel blockers, with disopyramide used after these agents fail but before invasive septal reduction. Recent therapies like mavacamten have shown improvements in LVOTO and exercise capacity, but the impact of disopyramide on cardiopulmonary exercise testing (CPET) parameters remains unclear.

Data Highlights

Key Findings

• Disopyramide significantly reduced peak exercise LVOT gradient from 63 to 41 mmHg (P = 0.014).
• Resting LVOT gradient decreased from 40 to 29 mmHg, though not statistically significant (P = 0.08).
• Resting and peak heart rates were significantly reduced after treatment (P = 0.02 and P = 0.001, respectively), indicating chronotropic insufficiency.
• Peak oxygen consumption (pVO2) decreased significantly from 20 to 17 mL/kg/min (P = 0.02), reflecting reduced exercise capacity.
• No significant changes were observed in ejection fraction, diastolic function, VE/VCO2 slope, or oxygen pulse.
• Quality of life showed a non-significant trend toward improvement (MLHFQ score reduction from 28.9 to 27; P = 0.19) alongside NYHA class improvement.

Clinical Implications

Disopyramide effectively reduces LVOTO and improves symptoms in oHCM patients but may impair exercise capacity due to chronotropic insufficiency. Clinicians should weigh the benefits of symptom relief and LVOTO reduction against potential decreases in peak exercise tolerance when considering disopyramide. Alternative therapies like mavacamten may offer improved exercise capacity without chronotropic compromise.

Conclusion

Disopyramide improves hemodynamic obstruction and symptoms in obstructive hypertrophic cardiomyopathy but is associated with reduced exercise capacity. These findings highlight the need to balance symptomatic benefits with functional limitations in treatment decisions.

References

1. San Camillo Forlanini Hospital Study 2024 -- Effects of Disopyramide on Exercise Tolerance in Patients with Obstructive Hypertrophic Cardiomyopathy