Ryanodine Receptor Inhibition with Dantrolene Prevents Ventricular Tachycardia Induction in Patients with Structural...

Area of Science:

• Cardiology
• Pharmacology
• Molecular Medicine

Background:

• No new drugs for ventricular tachycardia (VT) have been developed in over 20 years.
• Leaky intracellular ryanodine receptor-2 (RyR2) calcium release channels in structural heart disease increase VT risk.
• Dantrolene, an RyR2 inhibitor, has shown promise in preventing VT in animal models.

Purpose of the Study:

• To evaluate the efficacy and safety of dantrolene in preventing VT in patients with structural heart disease.
• To assess the effect of dantrolene on cardiac electrophysiologic parameters, hemodynamics, and VT inducibility.

Main Methods:

• A randomized, double-blinded, placebo-controlled clinical trial involving 51 patients undergoing catheter ablation for ventricular arrhythmias.
• Intravenous administration of dantrolene (29 patients) or placebo (22 patients).
• Assessment of VT inducibility, electrophysiologic parameters, and hemodynamics at baseline and after drug administration.

Main Results:

• Dantrolene reduced inducible VT by 66% (OR 0.23, P=0.034), while placebo had no effect.
• Approximately half of the participants were inducible for VT at baseline.
• Dantrolene did not significantly affect conduction velocity, refractory periods, heart rate, ECG intervals, blood pressure, or cardiac function.

Conclusions:

• Dantrolene significantly reduced VT inducibility in high-risk patients with structural heart disease.
• Dantrolene demonstrated a favorable safety profile in this patient population.
• Targeting RyR2 with dantrolene is a safe and effective strategy for arrhythmia prevention in humans.