34 | Chapter 3 were referred between 1997 and 2016.13 Due to inadequate image quality for RV deformation analyses, 4 subjects were replaced by other matched subjects from the Oslo cohort during the matching process. For the purpose of external validation, the two cohorts were kept separated first. The association between RV deformation patterns and disease stage was determined in the Oslo cohort and compared to the Utrecht cohort, where the method was initially developed. The external validity of the association between RV mechanical dispersion and arrhythmic events was tested in the Utrecht cohort and compared to the Oslo cohort. Subsequently, the two cohorts were merged to compare both RV deformation techniques and to explore added value of combining them in the total cohort. The study was approved by both local institutional ethics review boards and complies with the declaration of Helsinki. Collection of data Clinical characteristics We recorded clinical characteristics at inclusion, including demographics, anti-arrhythmic or beta blocker medication, presence of an ICD, and history of cardiac syncope (sudden loss of consciousness followed by spontaneous sudden awakening). By applying the 2010 TFC5, we determined fulfilment of a definite AC diagnosis. Date of inclusion was defined as the date of first complete echocardiographic examination suitable for performing deformation imaging. Electrocardiography We performed standard 12-lead ECG recording and 24-hour Holter monitoring at inclusion. The extent of T-wave inversions (TWI), presence of epsilon waves and increased terminal activation duration (TAD) were recorded according to the 2010 TFC. Arrhythmias were recorded on either 12-lead ECG, Holter or ICD monitoring.5 The amount of premature ventricular complexes per 24 hours on Holter monitoring was documented and non-sustained ventricular tachycardia was defined as consecutive runs of ≥3 ventricular beats >100 beats/min for <30s.14 Echocardiography We performed echocardiography, using a GE Vivid 7, E9 or E95 scanner (GE Healthcare, Horten, Norway). Cineloops were stored for post-processing with EchoPac version 202 (GE Healthcare). We assessed structural and functional abnormalities defined in the 2010 TFC5 and parameters from the EACVI consensus paper.15 Details on acquisition of the RV focused 4-chamber view and post-processing in echocardiographic speckle tracking deformation imaging were previously described more extensively.16-18 We assessed the subtricuspid deformation pattern in a single wall tracing of the RV lateral free wall, which was automatically divided into a basal, mid, and apical segment. Timing of the pulmonary valve closure was assessed by Doppler traces in the RV outflow tract, obtained in the parasternal short-axis view. The following deformation parameters were measured in the basal segment: time to onset of shortening (or electro-mechanical interval (EMI))19, systolic peak strain20 and the amount post-systolic shortening21 (definitions in supplementary material). Based on these parameters, a distinction into three different deformation patterns has previously been observed in AC and simulated using a computer model.6 (Figure 1, panel A) For RV mechanical dispersion, we used a 6-segment RV model, including both the lateral wall and the interventricular septum. It was calculated as the standard deviation (SD) of the segmental time intervals from onset Q/R on the surface ECG to maximum shortening, represented by the automatically detected peak negative strain.8,9 (Figure 1, panel
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