Thinning of the compact myocardial layer in excessive trabeculated individuals with genetic involvement

Introduction Compact layer thickness (CLT) below 5 mm has been identified as a prognostic parameter in noncompaction with heart failure. However, the relationship between CLT and genetic involvement, as well as the significance of CLT in left ventricular excessive trabeculation (LVET) with preserved ejection fraction (LVEF), remains unclear. Purpose We aimed to investigate CLT and noncompact layer thickness (NCLT) in symptomatic LVET individuals with preserved LVEF; to compare these parameters to a control population (C); and to analyse their associations with genetic mutations and clinical manifestation. Methods Our retrospective study included 54 symptomatic LVET individuals with preserved LVEF (40±14 years, 21 female) and 54 C subjects (39±15 years, 21 female). The threshold-based post-processing method was used to determine left ventricular volumetric parameters, LVEF, total, compact and trabeculated muscle mass on cardiac MRI (CMR) images. The CLT and NCLT parameters were measured at the basal (bas), mid-ventricular (mid) and apical (apic) segments according to the AHA-17 segment model. Personal and family history was assessed during cardiogenetic counselling. All LVET subjects underwent genetic testing using a 174-gene next-generation sequencing panel and they were classified into three subgroups: individuals with pathogenic mutations (P, n=15), those with variant of unknown significance (VUS, n=27) and those without genetic involvement (benign - B, n=12). Additionally, LVET subjects were also divided based on CLT into CLT<5 mm and CLT>5 mm subgroups. Results The LVET population showed significantly higher volumetric, total and trabeculated myocardial mass, bas, mid and apic NCLT and lower EF and apic CLT (LVNC: 4.8 mm; C: 5.4 mm; p<0.001) parameters compared to the C group. When comparing the CMR parameters among the genetic LVET subgroups, significant differences were only observed in the values of mid and apic CLT, being lower in P subjects compared to the VUS and B subgroups. Furthermore, mid and apic CLT below 5 mm gave a significant association with genetic involvement as B subjects showed CLT>5 mm; the VUS subgroup was approximately equally divided between CLT>5 mm and CLT<5 mm; while CLT<5 mm was significantly more common among P individuals (Figure 1 and 2). Additionally, apic CLT<5 mm was found to be specific for LVET individuals with a positive family history of cardiomyopathy or sudden cardiac death. Conclusion Our results suggest that thinning of the apical CLT is present in symptomatic LVET subjects with preserved cardiac function, particularly in individuals carrying pathogenic mutations rather than in sporadic LVET cases. Therefore, determining CLT in hypertrabeculated phenotypes may be useful for risk stratification and follow-up in LVET individuals.