What is the clinical evidence from this study?

Study design: Observational. Population: Preclinical plakophilin-2 variant carriers. Intervention: CineECG vs. Normal distribution. Primary outcome: Abnormal trajectory of ventricular electrical activity (p=.020).

August 1, 2025Open Access

CineECG detects abnormal electrical activity in the 12-lead ECG of preclinical plakophilin-2 variant carriers

ISIris van der SchaafUtrecht University MKManon KloostermanUniversity Medical Center Utrecht AGAnton P.M. GorgelsElectrophysiology

Key Result

CineECG detected abnormal ventricular electrical activity in preclinical plakophilin-2 variant carriers who had a normal standard ECG (P=0.020).

Study Design

Type

Observational

Structured PICO

Does CineECG detect abnormal electrical activity in preclinical PKP2 variant carriers with a normal standard 12-lead ECG?

Population

104 subjects (median age 24.0 years, 43.3% men), including 37 preclinical plakophilin-2 (likely) pathogenic variant (PKP2-(L)PV) carriers with a normal ECG and no other Task Force Criteria, and 67 age- and sex-matched control subjects.

Intervention

CineECG trajectory analysis of standard 12-lead ECGs to estimate the average location of ventricular electrical activity throughout the cardiac cycle.

Comparator

Age- and sex-matched control subjects (n=67) referred for atrioventricular nodal reentry tachycardia ablation with a normal sinus rhythm ECG, structurally normal heart, and no other history of heart disease.

Outcome

Abnormal depolarization and repolarization trajectories (defined as a trajectory falling less than 95% within the normal distribution of control subjects).surrogate

CineECG can identify subtle, early abnormalities in ventricular depolarization and repolarization in over half of preclinical PKP2 variant carriers whose standard 12-lead ECGs appear normal.

Main Result

p-value: p=.020

Abstract

Background: -(L)PV) are at risk of developing arrhythmogenic cardiomyopathy. Early disease detection is crucial because life-threatening arrhythmias may occur early. CineECG is a novel electrocardiogram (ECG) analysis tool that reconstructs the average trajectory of ventricular electrical activity. Objective: -(L)PV carriers with a normal ECG as per evaluation of 2 cardiologists, who meet no Task Force Criteria other than their PV. Methods: -(L)PV carriers' trajectories were compared with the normal distribution. A trajectory was considered abnormal if it fell less than 95% within the normal distribution. Results: = .020). Conclusion: -(L)PV carriers with a normal ECG. CineECG could be a sensitive tool to unveil early, subtle abnormalities in ventricular electrical activity that would otherwise not be detected.

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