LV and LA mechanics in pediatric HCM : a CMR study of phenotype-genotype correlation

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Background Paediatric hypertrophic cardiomyopathy (HCM) is a leading cause of sudden death. The relationship between the genotype variation and phenotype expression has not been fully elucidated, with some studies showing association with an increased hypertrophy and MYH7 or multiple genetic variations. In HCM fibrosis and hypertrophy contribute to left ventricular (LV) mechanics’ alteration resulting in subendocardial dysfunction. The latter is associated with a decreased global longitudinal and radial strains (GLS, GRS), whereas epicardial thickening leads to preserved global circumferential strain (GCS) and LV twist. Children with HCM have reduced LA function, measurable by both volumetric and strain analysis and reduced LA mechanics are associated with poor exercise capacity. Feature tracking –cardiac magnetic resonance (FT-CMR) has enhanced the non-invasive assessment of myocardial deformation in HCM. The main aim of our study was to assess differences of LV and LA mechanics features on CMR between patients harbouring multiple pathogenic or likely pathogenic variants (MGv, n=16) or single genetic variations (SGv, n=35). Methods Our retrospective CMR study included 51 patients (1.7–18.8 years ago). CMR data were: LV and LA’s morphological values, late gadolinium enhancement (LGE) of LA and LV walls, LV feature tracking (FT) derived strain and LV twist (LVT). LV twist was calculated as the difference between basal and apical rotation. The LA feature FT derived strain, LA conduit function, reservoir function and pump function were computed. Results In MGv group, the indexed LV mass 108.8 +/-53.0 vs 74.3+/- 22.2 in SGv (p = 0.03). LGE was present in 51% patients of the whole cohort, with LGE in 64 % of MGv group. LV FT derived strain values and LA function were not statistically significant different between groups (MGv vs SGv: GLS −15.8+/−5.3 vs −18.7+/−4.8, GCS −27.8+/8 vs −31.1+/−8.6, GRS 44.7+/−24.6 vs 62.3+/−32). LVT was reduced in MGv group (0.04+/−7.6) vs (7.4+/−7.4) in SGv (p = 0.003). LA contractile function did not differ between the groups (MGv vs SGv: GLS LA 25.1+/−14.2 vs 27.6+/−13.5). LA reservoir, conduction and pump function did not differ between the groups. LVT was significantly correlated with the LA contractile function. An increased of LVT was associated with an increased LA GLS and EF (p = 0.011; p = 0.004). Conclusions Patients with multiple genetic variants have a greater LV mass and altered LV mechanics with reduced LV twist. This study gives insights in phenotype- genotype correlation in paediatric HCM and warrants larger longitudinal studies to assess its clinical significance.