Electrophysiological Methods for Early Detection and Risk Stratification in Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease which is characterized by fibrofatty replacement of the myocardial tissue and pre-dominantly, but not exclusively, affects the epicardial side of the right ventricle. In clinical practice, heart failure, ventricular tachycardia and sudden cardiac death are observed. This thesis focused on early detection of disease and risk stratification in (young) patients and family members with pathogenic variants in PKP2 and PLN, genes which are associated with the majority of ACM cases in the Netherlands. Next, we also studied families with a specific founder variant in SCN5A to provide insights in the phenomenon of variable expression of this specific variant. Using the standard electrocardiogram (ECG), the significance of fragmented QRS complexes and right bundle branch block morphology during sustained ventricular tachycardia were studied for both diagnostic value as for risk stratification. Furthermore, efforts were made to reduce the variation during serial ECG registrations. The last two chapters describe the methodological aspects and clinical validation of inverse ECG, a non-invasive diagnostic tool to estimate local activation timings and activation patterns of the myocardium based on data derived from ECG and cardiac imaging using cardiac MRI or CT.