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Published on: April 11, 2025
Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive
Christopher M Andrews1, Neil T Srinivasan2, Stefania Rosmini2
1From the Department of Biomedical Engineering (C.M.A., Y.R.) and Cardiac Bioelectricity and Arrhythmia Center (C.M.A., Y.R.), Washington University, St. Louis, MO; Department of Medicine, Cardiovascular Division, Washington University in St. Louis, MO (Y.R.); Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom (N.T.S., M.O., S.J., A.P., W.J.M., P.D.L.); and Institute of Cardiovascular Science, University College London, United Kingdom (N.T.S., S.R., H.B., M.O., S.J., A.P., W.J.M., J.C.M., P.D.L.). rudy@wustl.edu.
Insights
Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients show distinct electrical abnormalities and repolarization issues. Electrocardiographic imaging and MRI can aid in early ARVC diagnosis and monitoring.
Area of Science:
- Cardiology
- Electrophysiology
- Medical Imaging
Background:
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a key cause of sudden cardiac death in young individuals.
- Noninvasive assessment and understanding of ARVC disease substrate are crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the electrophysiological substrate properties in ARVC patients using electrocardiographic imaging (ECGI) and cardiac magnetic resonance (CMR).
- To explore the relationship between electrical abnormalities, scar burden, and ventricular ectopy in ARVC.
Main Methods:
- Studied 20 genotyped ARVC patients and 20 healthy controls.
- Utilized electrocardiographic imaging for noninvasive cardiac electrophysiology mapping.
- Employed advanced late gadolinium enhancement (LGE) CMR for scar imaging.
Main Results:
- ARVC patients exhibited prolonged ventricular activation duration and epicardial activation-recovery intervals compared to controls.
- Observed abnormal epicardial activation breakthrough, nonuniform conduction, and fractionated electrograms in ARVC patients, even in early disease stages.
- Electrophysiological abnormalities colocalized with LGE scar, and premature ventricular contractions correlated with repolarization abnormalities and scar markers.
Conclusions:
- Electrocardiographic imaging effectively reveals distinct electrophysiological substrate properties in ARVC patients.
- Repolarization abnormalities in regions of ventricular ectopy origin represent a novel mechanistic finding in ARVC.
- ECGI and LGE-CMR show potential for early diagnosis and noninvasive follow-up of ARVC.
Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in the young. Improved noninvasive assessment of ARVC and better understanding of the disease substrate are important for improving patient outcomes.
Methods And Results:
We studied 20 genotyped ARVC patients with a broad spectrum of disease using electrocardiographic imaging (a method for noninvasive cardiac electrophysiology mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration (median, 52 versus 42 ms; P=0.007) and prolonged mean epicardial activation-recovery intervals (a surrogate for local action potential duration; median, 275 versus 241 ms; P=0.014). In these patients, we observed abnormal and varied epicardial activation breakthrough locations and regions of nonuniform conduction and fractionated electrograms. Nonuniform conduction and fractionated electrograms were present in the early concealed phase of ARVC. Electrophysiological abnormalities colocalized with late gadolinium enhancement scar, indicating a relationship with structural disease. Premature ventricular contractions were common in ARVC patients with variable initiation sites in both ventricles. Premature ventricular contraction rate increased with exercise, and within anatomic segments, it correlated with prolonged repolarization, electric markers of scar, and late gadolinium enhancement (all P<0.001).
Conclusions:
Electrocardiographic imaging reveals electrophysiological substrate properties that differ in ARVC patients compared with healthy controls. A novel mechanistic finding is the presence of repolarization abnormalities in regions where ventricular ectopy originates. The results suggest a potential role for electrocardiographic imaging and late gadolinium enhancement in early diagnosis and noninvasive follow-up of ARVC patients.
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