Fourteen asymptomatic first-degree relatives of ARVD/C probands (the ARVD/C-r group; mean age, 38.0 ¡À 13.2 years) with a pathogenic plakophilin-2 mutation and a group of age-matched controls (n?= 56; mean age, 38.2 ¡À 12.7 years) were included at a 1:4 ratio. A complete echocardiographic evaluation (dimensions, global systolic parameters, and visual assessment and deformation imaging of the RV free wall including Doppler tissue imaging and two-dimensional strain echocardiography) was obtained. Peak systolic strain less negative than ?18 % and/or postsystolic shortening (postsystolic index > 15 % ) in any RV segment was considered abnormal.
RV dimensions in the ARVD/C-r group were similar to those in controls (RV outflow tract, 15.4 ¡À 2.9 vs 14.4 ¡À 1.9 mm/m2, P?= NS; RV inflow tract, 18.6 ¡À 2.6 vs 19.1 ¡À 2.6 mm/m2, P?= NS), and global systolic parameters were moderately reduced (tricuspid annular plane systolic excursion, 20.0 ¡À 3.2 vs 23.9 ¡À 2.8 mm, P?= .001; RV fractional area change, 40.3 ¡À 8.4 vs 40.6 ¡À 7.1, P?= NS). According to task force criteria, 57 % of the ARVD/C-r group and 29 % of controls were classified as abnormal when applying the 1994 criteria and 29 % and 4 % when applying the 2010 criteria, respectively. Doppler tissue imaging and two-dimensional strain deformation (and strain rate) values were reduced in the ARVD/C-r group in the basal and mid RV segments compared with controls (P < .001). In the ARVD/C-r group, peak systolic strain less negative than ?18 % was seen in six patients (43 % ), postsystolic strain in nine (64 % ), and either abnormality in 10 (71 % ), almost exclusively in the basal segment; these findings were observed in none of the controls.
The 2010 criteria for ARVD/C improve specificity, whereas sensitivity is significantly reduced in this asymptomatic population. In contrast, echocardiographic deformation imaging detects functional abnormalities in the subtricuspid region in 71 % of asymptomatic carriers of a pathogenic plakophilin-2 mutation, while regional deformation was normal in all control subjects, indicating superiority of both sensitivity and specificity with these new modalities.