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

Jose Maria Lopez-Ayala,Maria Sabater Molina,Javier Gimeno-Blanes,Juan Ramon Gimeno-Blanes,David Lopez-Cuenca

doi:10.3389/fcvm.2021.646391

Abstract

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.

Highlights

Arrhythmogenic cardiomyopathy is a cause of unexpected sudden death and ventricular arrhythmias in the general population including the youth and competitive athletes [1, 2]
We carried out a retrospective electrocardiographic evaluation in genotype-positive/phenotype-negative relatives of families with a previous diagnosis of arrhythmogenic cardiomyopathy
A total of 41 genotype-positive/phenotype-negative relatives with a digital electrocardiogram were included in the study

Summary

Introduction

Arrhythmogenic cardiomyopathy is a cause of unexpected sudden death and ventricular arrhythmias in the general population including the youth and competitive athletes [1, 2]. This umbrella term encompasses a broad phenotypic spectrum of disease that may predominantly affect one of the ventricles or both [3]. As electrocardiographic changes usually precede the development of subsequent structural abnormalities, it is paramount to identify early electrocardiographic abnormalities that herald an initial electric phase of the disease. 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

Objectives

Methods

Results

Conclusion