The genetically determined role of the compact myocardial layer in excessively trabeculated left ventricular noncompaction

Abstract Background: Left ventricular excessive trabeculation (LVET) ranges from preserved ejection fraction (EF) morphology to reduced EF Noncompaction cardiomyopathy. Emerging evidence indicates that EF reduction is more strongly associated with thinning of the Compact myocardial layer (CL) than with trabeculation alone, although the precise role of the CL in LVET has yet to be determined. Aim: We aimed to evaluate Trabeculated layer (TL) and CL thickness in LVET subjects with preserved EF across genotypes, establish genotype-specific CL thickness cut-offs, and analyse their association with LV parameters. Methods: We enrolled 54 LVET subjects with matched healthy Controls. In CMR, functional, volumetric and myocardial-mass parameters were measured using threshold-based analysis. TL thicknesses were assessed using calliper tools and CL thickness was measured using OptiLayer software. For genetic testing, cardiac NGS panels were used; LVET subjects were classidied into Benign (B), VUS, and Pathogenic (P) subgroups according to ACMG databases. Results: LVET subjects showed thicker TL and thinner CL compared to Controls. CL thickness differed among genetic subgroups: P variants were associated with significantly thinner apical segments, with a cut-off of 5 mm (93% of P <5 mm, 41% of VUS < 5 mm, 8% of B<5 mm, p < 0.05). TL thickness showed no association with genotype. CL thickness correlated with global circumferential strain ( r = 0.461, p < 0.01), indicating subclinical dysfunction. Conclusion: CL thinning in LVET with preserved EF was associated with P genetic background and may represent early morphological alterations. These findings suggest potential roles in diagnosis, risk stratification, and follow-up, which should be further evaluated in longitudinal studies.