The Clinical Utility of Deformation Imaging in Early Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiomyopathy which is characterized by progressive fibro-fatty replacement of the myocardium. Clinically, this disease may lead to life-threatening arrhythmias and heart failure. Since ACM is an inherited cardiomyopathy, the relatives of ACM patients are also at a certain risk of developing this disease. However, most of the relatives who are screened are found to be in a preclinical phase, which implies that symptoms and other clinical signs of disease are absent. The management of these relatives is a major challenge, because disease expressivity is variable and penetrance is incomplete, the latter implying that not all relatives with a genetic predisposition will develop the disease. However, the ones who will develop the disease are at risk of life-threatening arrhythmias and sudden cardiac death in an early stage of disease. Timely identification of the relatives who are at higher risk of developing the disease would provide opportunities to prevent life-threatening ventricular arrhythmias, for example by intensifying follow-up protocols or by offering early therapeutic intervention. To enable the early identification of high-risk relatives, there is an ongoing quest for the earliest detectable signs of disease expression. Echocardiographic deformation imaging has been proposed as a tool that might reveal the earliest functional changes in ACM. This advanced imaging technique enables quantification of global and regional mechanical myocardial function by tracking acoustic markers in the myocardium ("speckles") during contraction and relaxation. Although this technique seems very promising to unmask early (subclinical) signs of disease in relatives, the clinical role of this technique in this population remains unclear. In this thesis, the clinical utility of deformation imaging in relatives of ACM patients is investigated. Moreover, genotype-specific studies are conducted to investigate whether deformation phenotypes differ among relatives with different genetic variants.