192 | Chapter 9 In the addendum of this thesis, Chapter 10 addresses mitral annular disjunction. In this condition, the mitral valve hinge points are displaced towards the atrium (Figure 3). While this condition may involve variable parts of the annular circumference, it mainly seems to be associated with severe arrhythmic events when present in the posterolateral wall.23,24 So again, the basal segment of the LV posterolateral seems to be an Achilles heel for cardiac arrhythmias. Recognition of the weak spots of the heart is important in clinical practice to guide focus of early detection of disease in genetic cardiomyopathies. While global diagnostic indices are still preserved, abnormalities in these predilection sites may already introduce an important arrhythmic risk. In Chapter 2 we emphasized that visual assessment of regional abnormalities is difficult and highly dependent on the observer’s experience. Throughout this thesis, echocardiographic deformation imaging repeatedly showed to be a highly sensitive technique for assessment of disease manifestation in the Achilles heels of the heart. Figure 3. Two Achilles heels of the heart: the subtricuspid segment of the RV free wall and the submitral segment of the posterolateral wall in the LV The first is a common predilection site for ARVC disease manifestation in patients with genetic variants impairing desmosomal function. The second is often the first involved LV region in ARVC and can be the source of arrhythmia in case of atrial displacement of the mitral valve annulus (MAD). In both cases, ventricular flow dynamics and a thin wall may lead to high wall stress. This stress can lead to formation of scar tissue in already vulnerable myocardium, which in turn forms a pro-arrhythmic substrate. The influence of exercise While exercise is associated with unequivocal health benefits in the general population, this may not necessarily be the case in patients with genetic cardiomyopathies. If the Achilles heel of the heart is already under stress in rest, the effects of exercise may be an extra trigger for worse outcome. Especially in ARVC, a history of frequent vigorous exercise has been associated with more pronounced phenotypes and worse prognosis.25–27 In preclinical studies in mice expressing a mutated human PKP-2 gene, the abnormal phenotype could be triggered by repeated exercise.28,29 In the presence of dysfunctional cardiac desmosomes, exercise
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