Electrocardiographic Screening of Arrhythmogenic Cardiomyopathy in Genotype-Positive and Phenotype-Negative Relatives

• Published in: Frontiers in cardiovascular medicine 2021-05, Vol.8, p.646391-646391
• Main Authors: Lopez-Ayala, Jose Maria, Gimeno-Blanes, Javier, Lopez-Cuenca, David, Molina, Maria Sabater, Gimeno-Blanes, Juan Ramon
• Format: Article
• Language: English
• Subjects: arrhythmogenic right ventricular cardiomyopathy; Cardiovascular Medicine; early diagnosis; electrocardiogram; familiar screening; genetic carrier
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2021.646391

Background: Arrhythmogenic cardiomyopathy is a hereditary cause of ventricular arrhythmias and sudden death. Identifying the healthy genetic carriers who will develop the disease remains a challenge. A novel approach to the analysis of the digital electrocardiograms of mutation carriers through signal processing may identify early electrocardiographic abnormalities. Methods: A retrospective case–control study included a population of healthy genetics carriers and their wild-type relatives. Genotype-positive/phenotype-negative individuals bore mutations associated with the development of arrhythmogenic cardiomyopathy. The relatives included had a non-pathological 12-lead electrocardiogram, echocardiogram, and a cardiac magnetic resonance. Automatic digital electrocardiographic analyses comprised QRS and terminal activation delay duration, the number of QRS fragmentations, ST slope, and T-wave voltage. Results: Digital 12-lead electrocardiograms from 41 genotype-positive/ phenotype-negative (29 simple carriers and 12 double mutation carriers) and 73 wild-type relatives were analyzed. No differences in the QRS length, the number of QRS fragmentations, and the voltage of the T-wave were observed. After adjusting for potential confounders, double carriers showed an average ST-slope flatter than those of the simple carriers and wild type [5.18° (0.73–8.01), 7.15° (5.14–11.05), and 11.46° (3.94–17.49), respectively, p = 0.005]. There was a significant negative correlation between the ST slope and the age in genotype-positive/phenotype-negative relatives ( r = 0.376, p = 0.021) not observed in their wild-type counterparts ( r = 0.074, p = 0.570). Conclusions: A flattened ST segment may be an early sign of electrical remodeling that precedes T-wave inversion in healthy genetic carriers. A thorough analysis of the digital electrocardiographic signal may help identify and measure early electrical abnormalities.