42 | Chapter 3 DISCUSSION This study provides an external validation of the use of RV deformation pattern recognition and RV mechanical dispersion in AC patients and mutation positive family members. Both abnormal deformation patterns and prolonged RV mechanical dispersion were independent markers of patients with a history of VA, highlighting the role of deformation analyses in the echocardiographic assessment of AC patients. Combining the two parameters increased the association to VA, indicating an independent and incremental value of these techniques which may help risk stratification of AC patients. RV deformation patterns This study, for the first time, links abnormal RV deformation patterns to arrhythmic events. Previous studies have focused on the use of RV deformation patterns for early detection of AC disease manifestation and the correlation with clinical disease stages, based on the presence of 2010 TFC.6,19 Subsequently, prognostic value of the patterns was shown for prediction of disease progression, defined as development of new 2010 TFC during follow-up7, and structural progression on echocardiography25. The distribution of deformation patterns over disease stages of increasing severity was similar in both cohorts and in line with previous results6, and it was therefore considered a successful external validation. (Figure 2) We found clearly abnormal deformation patterns in the RV subtricuspid segment in a significant number of subjects without any electrical or structural 2010 TFC, indicating presence of mechanical dysfunction already in an early stage of the disease.6 Importantly, abnormal RV deformation patterns had an excellent sensitivity for detection of patients with VA, with a negative predictive value of 0.98. Specificity was suboptimal when taking only past events into account. A prospective setting is however needed, since abnormalities now classified as false-positive might be indicators of a risk of future lifethreatening arrhythmic events. RV mechanical dispersion We observed a marked increase in RV mechanical dispersion for patients with VA in both cohorts with no difference by ROC comparison, suggesting mechanical dispersion as an externally valid marker of VA. Mean RV mechanical dispersion was higher in the Utrecht cohort, partly caused by several outliers. (Figure 2, panel B) The association between RV mechanical dispersion and arrhythmia was in line with previous reports on patients with early AC disease12 and exercise induced arrhythmias.26 Previous studies and a consensus document on multi-modality imaging in AC have suggested cut-offs for RV mechanical dispersion.8,9,15 We observed that dichotomizing at the optimal threshold resulted in a significant loss of information, indicating better abilities of mechanical dispersion used as a continuous parameter. Combining the two RV deformation methods Previously, it was not clear whether the two RV deformation methods assess the same underlying pathology, and comparative data were not available. By applying both methods on the total cohort and associating them to the same definition of arrhythmic outcome, this
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