Abstract 4367211: Impact of Histologic Fibrosis Patterns and Myocardial Involvement on Diastolic Dysfunction in Non-Dilated Cardiomyopathy

Background: Myocardial fibrosis is a key determinant of diastolic dysfunction in non-dilated left ventricular cardiomyopathy (ND-LVCM). However, the extent to which fibrosis burden and histological distribution patterns influence diastolic function—particularly across specific etiologies such as amyloidosis—remains incompletely understood. Hypothesis: We hypothesized that the extent and pattern of myocardial fibrosis correlate with diastolic function indices, including global longitudinal strain (GLS) and deceleration time (DcT), and that in cardiac amyloidosis, the deposition pattern may be a more relevant determinant of diastolic impairment than overall fibrosis burden. Methods: We retrospectively analyzed 201 patients with ND-LVCM (left ventricular end-diastolic diameter <55 mm) who underwent endomyocardial biopsy, echocardiography, and cardiac MRI. Fibrosis burden was quantified via Masson trichrome staining and expressed as percentage of tissue area. In patients with cardiac amyloidosis (n=56), Congo red–positive deposits were semi-quantitatively classified as diffuse, scattered, or perivascular using image analysis software. Diastolic function was assessed by GLS and DcT. Subgroups included sarcoidosis (n=14), Fabry disease (n=12), hypertensive cardiomyopathy (n=49), hypertrophic cardiomyopathy (n=38), and unclassified ND-LVCM (n=32). Linear regression and subgroup analyses were performed. Results: Across the entire cohort, GLS showed a significant inverse correlation with myocardial fibrosis extent (GLS = −23.98 + 0.47 × fibrosis%, R 2 = 0.29, p < 0.0001). However, this correlation was attenuated in patients with cardiac amyloidosis. In the amyloidosis subgroup, GLS and DcT were more strongly influenced by the pattern of amyloid deposition: diffuse deposition was associated with markedly reduced GLS and shortened DcT, while perivascular or scattered patterns showed milder impairment. Fibrosis percentage alone was not a significant predictor of GLS in this subgroup. Across the full cohort, fibrosis extent also showed a weak but significant correlation with DcT (p < 0.05). Conclusions: In ND-LVCM, myocardial fibrosis burden correlates with diastolic dysfunction. However, in cardiac amyloidosis, the spatial pattern of amyloid deposition may more accurately reflect functional impairment than overall fibrosis extent. These findings highlight the clinical importance of detailed histological evaluation in understanding restrictive physiology.