General Discussion and Future Perspectives | 193 imposes high wall stress causing cardiomyocyte detachment and gap junction remodeling, triggering apoptosis and fibroadiposis. Afterload and hence systolic wall stress increases to a disproportionately greater extent in the RV compared to the LV.30 Moreover, even without a known genetic cause of desmosomal dysfunction, excessive wall stress on the thin-walled RV may cause an ARVC phenotype with malignant arrhythmias originating from the RV, the so-called exercise-induced ARVC.31 These effects of exercise in patient with ARVC or a genetic predisposition to develop the disease may not only be important in advising exercise restriction; the detrimental effect of exercise may also have consequences for diagnostic testing. Early disease manifestation might already be detectable during excercise, while the functional abnormalities are too subtle to be detected in rest. Another hypothesis, in line with the findings by La Gerche et al. in exerciseinduced ARVC31, is that significant progression of RV dysfunction during exercise is associated with worse outcome. Preliminary computer simulations with the CircAdapt model seem to support these hypotheses: when introducing a mild disease substrate in the basal segment of the RV free wall, stepwise increasing cardiac output from 5L to 15L per minute results in increasingly abnormal regional deformation. During peak exercise, the simulated deformation shows a clearly abnormal type III with systolic stretching, while the disease substrate on tissue level did not change. Figure 4. Simulated regional RV deformation in early ARVC during exercise A mild disease substrate is introduced in the basal segment of the RV free wall. In rest, deformation in the basal segment is slightly abnormal with delayed onset of shortening (type II). By increasing the cardiac output and keeping other factors constant, a highly pathologic RV deformation pattern develops with predominantly systolic stretching (type III). CO = cardiac output. Electrocardiography is already routinely performed during exercise in order to detect arrhythmia in ARVC patients and family members at risk. Concurrently, ultrasound machines deployed in clinical settings are well-suited for exercise imaging of the RV. Given the infrastructure already being present in most hospitals, an intriguing avenue for research arises—namely, the exploration of the additional diagnostic and prognostic insights offered by RV deformation imaging during exercise for ARVC patients and family members at risk. Towards clinical implementation After more than two decades of research on echocardiographic deformation imaging, the technique is now starting to be integrated into clinical practice. An important contributing factor to wider implementation is the increasing availability of speckle tracking deformation imaging in standard clinical ultrasound machines. Another factor is that semi-automated analyses make it less time-consuming. On this aspect, there is still more to gain with the introduction of fully automated analyses which will be both time-saving and less observer dependent. Deeplearning based automated analysis will probably enter the clinical arena soon, since great 9
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