Microstructural disease and hypoperfusion in dilated cardiomyopathy underpin midwall septal fibrosis

The presence of midwall septal fibrosis (MSF) in dilated cardiomyopathy (DCM) has been shown to be associated with adverse clinical outcomes, but the underlying pathophysiological mechanisms are incompletely understood. We investigated whether MSF associates with a distinct pattern of myocardial microstructural and microvascular abnormalities using advanced cardiovascular magnetic resonance (CMR).

This was a prospective, multi-referral, single-center study comparing the hearts of patients with a current or prior diagnosis of DCM with and without MSF ("MSF+"/"MSF-"), to a control cohort of a similar age and sex distribution. All underwent single-magnet 3 Tesla CMR, including cardiac diffusion tensor imaging (cDTI), quantitative rest perfusion, and multiparametric tissue characterization. Prespecified analyses compared DCM with controls, and MSF+ with MSF-; secondary analyses included regional septal and within-subject segmental comparisons.

About 121 participants were studied: 34 MSF+ (51±14years; 74% male), 27 MSF- (48±15 years; 63% male), and 60 controls (45±13 years; 58% male). Compared with controls, the DCM cohort demonstrated increased mean diffusivity (MD) (1.49 v 1.43 ×10^-3mm²/s, p<0.001) and reduced second eigenvector angle (E2A) (34.7 vs. 40.2°, p=0.001), consistent with microstructural abnormality, along with reduced resting myocardial blood flow (rMBF) (0.66 vs. 0.70 mL/g/min, p=0.045). Within the DCM cohort, MSF+ patients exhibited increased MD (1.51 vs. 1.46 ×10^-3mm²/s, p=0.006) and decreased rMBF (0.64 vs. 0.71 mL/g/min, p=0.013) compared to MSF-. Septal analyses demonstrated increased MD, decreased E2A, decreased FA, and reduced rMBF in DCM. Within-patient comparisons showed decreased perfusion in fibrotic segments compared with non-fibrotic myocardium. In exploratory analyses, decreased rMBF was associated with greater ventricular ectopic burden.

Midwall septal fibrosis in DCM identifies a distinct myocardial phenotype characterized by microstructural remodeling and impaired myocardial perfusion, with regional and segmental specificity. These findings provide mechanistic insight into the adverse prognostic associations of MSF and highlight a potential imaging-guided pathway for risk stratification and therapies.