Arrhythmogenic Right Ventricular Cardiomyopathy : Genetic and Electrocardiographic Aspects on Risk of Ventricular Arrhythmia and Diagnosis

Introduction: ARVC (Arrhythmogenic Right Ventricular Cardiomyopathy) is a heritable and relatively rare disease of the heart muscle, primarily affecting the right ventricle, and may cause arrhythmias and heart failure.Diagnosing ARVC is sometimes difficult, navigating diagnostic criteria, but the hardest part is to evaluate the risk of arrhythmia for each patient.Aim: The overall aim of this thesis was to study various aspects of genetic information and electrocardiography (ECG), for their use in diagnosis and risk evaluation in ARVC. Material and methods:Paper I: The genotype-phenotype correlations in four unrelated families with a plakophilin 2 gene variant (PKP2 c.2146-1C>G) were studied, to determine 1) to what extent family members fulfil diagnostic criteria and 2) to assess whether these gene carriers had any specific clinical characteristics in common.Paper II: Patients with definite ARVC but one group with and one without diagnostic ECG criteria were compared to each other and to a healthy control group.The vectorcardiographic parameters 3-dimensional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, and a root mean square of the right sided depolarisation forces (RtRMS-QRS) were assessed, alongside QRS duration, corrected QT interval and an angle measuring the upslope and downslope of the S wave (S-wave angle).Paper III: Combined Annotation Dependent Depletion (CADD, a bioinformatic tool) scores were calculated for all pathogenic and likely pathogenic variants in PKP2 found in patients from two ARVC Registries, and the scores association with arrhythmic events and age at definite ARVC diagnosis were assessed.Paper IV: Digital ECGs (n=6871) from 353 patients with definite ARVC were analysed using Glasgow algorithm to describe the longitudinal development of different ECG characteristics, but also to assess the relationship between the ECG parameters and 1) structural abnormalities and 2) sustained ventricular tachycardia (VT) during a 10-year follow-up.