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Updated: Jul 23, 2025
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Body surface potential mapping detects early disease onset in plakophilin-2-pathogenic variant carriers
Manon Kloosterman1, Machteld J Boonstra1, Rob W Roudijk1
1Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Body surface potential mapping (BSPM) detects subtle electrical abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC) variant carriers, even when standard ECGs appear normal. This suggests electrical changes may precede structural heart disease.
Area of Science:
- Cardiology
- Medical Imaging
- Genetics
Background:
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited heart disease.
- Early detection and risk stratification are challenging due to varied symptoms.
- Standard 12-lead ECGs may miss subtle abnormalities.
Purpose of the Study:
- To investigate if body surface potential mapping (BSPM) is more sensitive than standard ECG for detecting early signs of ARVC.
- To identify electrical abnormalities in carriers of plakophilin-2 (PKP2) pathogenic variants.
Main Methods:
- Obtained 67-electrode BSPM in 42 PKP2 variant carriers and 25 controls.
- Created subject-specific heart/torso models from CT/MRI for precise mapping.
- Analyzed QRS and STT isopotential maps, correlating patterns with cardiac anatomy.
- Acquired right ventricular (RV) echocardiographic deformation imaging for functional assessment.
Main Results:
- Identified abnormal QRS and STT patterns in 31/42 PKP2 variant carriers using BSPM.
- 17 of these carriers showed normal 12-lead ECGs.
- In pre-clinical carriers, BSPM detected abnormalities in 7/12 with normal RV deformation.
Conclusions:
- BSPM can detect depolarization and repolarization abnormalities in ARVC variant carriers missed by standard ECG.
- Electrical abnormalities identified by BSPM may precede functional or structural changes in ARVC.
- BSPM shows promise for early disease detection and risk stratification in ARVC.
Aims:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited cardiac disease. Early detection of disease and risk stratification remain challenging due to heterogeneous phenotypic expression. The standard configuration of the 12 lead electrocardiogram (ECG) might be insensitive to identify subtle ECG abnormalities. We hypothesized that body surface potential mapping (BSPM) may be more sensitive to detect subtle ECG abnormalities.
Methods And Results:
We obtained 67 electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carriers and control subjects. Subject-specific computed tomography/magnetic resonance imaging based models of the heart/torso and electrode positions were created. Cardiac activation and recovery patterns were visualized with QRS- and STT-isopotential map series on subject-specific geometries to relate QRS-/STT-patterns to cardiac anatomy and electrode positions. To detect early signs of functional/structural heart disease, we also obtained right ventricular (RV) echocardiographic deformation imaging. Body surface potential mapping was obtained in 25 controls and 42 PKP2-pathogenic variant carriers. We identified five distinct abnormal QRS-patterns and four distinct abnormal STT-patterns in the isopotential map series of 31/42 variant carriers. Of these 31 variant carriers, 17 showed no depolarization or repolarization abnormalities in the 12 lead ECG. Of the 19 pre-clinical variant carriers, 12 had normal RV-deformation patterns, while 7/12 showed abnormal QRS- and/or STT-patterns.
Conclusion:
Assessing depolarization and repolarization by BSPM may help in the quest for early detection of disease in variant carriers since abnormal QRS- and/or STT-patterns were found in variant carriers with a normal 12 lead ECG. Because electrical abnormalities were observed in subjects with normal RV-deformation patterns, we hypothesize that electrical abnormalities develop prior to functional/structural abnormalities in ARVC.
