70 | Chapter 4 Right ventricular mechanical dispersion Increased RVMD in pathogenic desmosomal mutation carriers was only related to increased heterogeneity in contractility (20.0±14.7%) compared to the group with normal RVMD (7.70±4.99%) (p<0.001). Regional heterogeneities of both compliance and activation delay were not significantly different between subjects with low and high RVMD (compliance: 16.0±10.5% vs 13.8±10.2%, p=0.054; activation delay: 20.6±26.0ms vs 11.1±15.6ms, p=0.195). Parameter estimation The estimated RV tissue properties were highly reproducible, with a minimum inter- and intra-observer ICC of 0.91 and 0.86, respectively. Reproducibility of the simulations was sufficient, with a minimum ICC of 0.76. In all simulations of the same subject, the trend in local RVfw heterogeneity was similar. Supplemental Table 2 shows the ICC of the estimated model parameters and Supplemental Table 3 shows the ICC of the individual estimated tissue properties. The simulations ran on average in 25 ± 10 hours per patient. The duration of the simulations depended on the heart rate, the quality of the initial subset, and the number of beats needed to find a hemodynamic stable simulation for each random state. The average dimensional error between modelled and measured strain was 0.84 ± 0.35. DISCUSSION In this study, patient-specific simulations were successfully used to estimate regional RVfw tissue properties from echocardiographic deformation imaging data in 68 subjects with a pathogenic AC mutation and 20 control subjects. Regional heterogeneities of contractility and compliance in the RV free wall were largest in subjects in the structural disease stage. Our patient-specific simulations suggested that structural abnormalities according to the 2010 TFC were associated with an increased heterogeneity in RVfw myocardial tissue contractility and compliance. The most advanced disease substrates were found predominantly in the RVfw basal segment. To our knowledge, this is the first time that regional ventricular tissue properties are quantified using patient-specific simulations based on non-invasively measured longitudinal strain patterns. This method reveals potentially important information about myocardial disease substrates and thereby paves the way for personalized medicine. In a previous study, we showed that desmosomal mutation carriers with more advanced AC disease stages have the most abnormal RV basal deformation pattern.4 In the same study, using computer simulations it was concluded that this abnormal mechanical behaviour of the RV cannot be explained by an electromechanical activation delay alone. Non-personalized simulations representing subgroups of AC mutation carriers showed that at least some degree of local mechanical dysfunction was needed to reproduce the measured RV deformation abnormalities. A recently published sensitivity analysis confirmed that model parameters related to both activation delay and mechanical dysfunction are essential to reproduce myocardial deformation using the CircAdapt model.8 The current study extends this previous work by estimating patient-specific myocardial substrates in all three RVfw segments and by including the LV mechanics for a more realistic approach of the patient’s hemodynamics. These patient-specific simulations confirmed hypothesis that abnormal deformation patterns
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