Premature ventricular contractions as a target for arrhythmogenic right ventricular cardiomyopathy trials

Area of Science:

• Cardiology
• Clinical Trials
• Electrophysiology

Background:

• Arrhythmogenic right ventricular cardiomyopathy (ARVC) presents challenges for clinical trial outcome definition due to variable arrhythmia occurrence and slow structural changes.
• Novel therapeutics for ARVC are emerging, necessitating robust primary outcome measures for evaluating treatment efficacy.

Purpose of the Study:

• To review the evidence supporting premature ventricular complex (PVC) burden as a primary outcome in ARVC clinical trials.
• To discuss the feasibility and potential limitations of implementing PVC burden as a key clinical metric for ARVC research.

Main Methods:

• Expert review of existing literature on ARVC, ventricular arrhythmias, and clinical trial methodologies.
• Analysis of ambulatory electrocardiogram data and its utility in quantifying PVC burden.
• Evaluation of the proposed use of PVC reduction as a primary endpoint in randomized controlled trials for ARVC.

Main Results:

• Premature ventricular complex (PVC) burden, measured via ambulatory electrocardiogram monitoring, is a proposed metric for ARVC trials.
• Evidence suggests PVC burden can reflect disease activity and treatment response in ARVC patients.
• Implementation requires careful consideration of monitoring protocols and data interpretation.

Conclusions:

• PVC burden represents a promising surrogate endpoint for ARVC clinical trials, potentially offering a more feasible measure than traditional outcomes.
• Further validation and standardization are needed to optimize the use of PVC burden in evaluating novel ARVC therapies.
• Addressing the challenges associated with PVC burden measurement will enhance the design and interpretation of future ARVC research.