Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study.

ABSTRACT

AIMS: Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). METHODS AND RESULTS: One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125). CONCLUSION: Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.