190 | Chapter 9 researchers with divergent backgrounds became engaged in investigating the disease, profiting from each other’s insights and expertise. New insights in the value of echocardiographic deformation imaging in ARVC could be integrated with the work of other clinical researchers investigating the value of new cardiac magnetic resonance (CMR) techniques16 or novel electrocardiographic techniques17. Furthermore, preclinical studies from colleagues from the medical physiology lab provided us with new insights into the role of calcium transients13 and colleagues from the Hubrecht lab elucidated disease pathways which are responsible for the decreased contractility which we observe in PKP2 variant carriers18. An ongoing question in the field of ARVC is whether electrical abnormalities precede structural abnormalities. We do see regional deformation abnormalities in a very early stage, even in the absence of electrical abnormalities according to the 2010 TFC (the “subclinical stage” in Chapter 3). However, it could be that these deformation abnormalities actually rely on delayed electrical activation rather than a structural substrate. Impairment of the cardiac desmosome can lead to both structural abnormalities and electrical conduction abnormalities.18 Another question is whether it matters for a patient’s prognosis whether electrical delay or a local substrate of decreased contractility causes deformation abnormalities. One method we have applied to try to answer these questions is the use of model estimations of the CircAdapt model. In Chapter 6 we presented two cases of ARVC patients with early deformation abnormalities. In the Digital Twin of the first patient, abnormal regional myocardial function was estimated to result from reduced contractility with little contribution of mechanical activation delay. The second patient showed heterogeneous mechanical activation in an early stage and experienced a lifethreatening arrhythmia shortly after. While hypotheses on the arrhythmogenicity of different substrates have to be tested in cohorts with more events, it shows the potential clinical value of unraveling the electro-mechanical coupling. Another approach to distinguish electrical from structural disease substrates would be the integration of multimodality data. Colleagues from the department of electrophysiology in the University Medical Center Utrecht have developed a non-invasive ECG imaging method using 67 electrode body surface potential mapping (BSM). While it is difficult to derive information on electrical conduction of the RV on a regular 12-lead surface ECG, this new method allows more detailed evaluation of RV electrical disease. Figure 2 shows an example of a patient in an early stage of ARVC disease in whom CMR imaging, ECG imaging and echocardiography were performed on the same day. Estimations of tissue properties in the patient’s Digital Twin showed only little electrical delay, while regional contractility of the subtricuspid segment was clearly diminished. While the presented case represents only one time point in one patient, it shows the potential of integrating data from different diagnostics in a way that makes sense from a clinical perspective. Besides, it fits nicely into the strategy of the 2023 cardiomyopathy guideline3, which proposes to start with a clinical scenario by combining incidental findings from different diagnostic modalities.
RkJQdWJsaXNoZXIy MTk4NDMw