Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a CMR correlation study

Abstract Background Myocardial fibrosis (MF) takes part in left ventricular (LV) remodeling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural events that occur in this transition are not fully enlightened. Aim To describe histopathology changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR); to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). Methods One-hundred-fifty-eight patients (73[68-77]years, 50%women) 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). Results Non-ischemic LGE was present in 106 patients (67.1%) (median fraction: 5.0% [2.0-9.7]). Native T1 was above normal: 1053ms[1024-1071] and T2 within normal range (39.3ms[37.3-42.0]). Median MF was 11.9%[6.54-19.97], with predominant type I collagen perivascular distribution (95.3%). Subendocardial cardiomyocyte ischemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodeling expression. MF quantification at EMB was correlated with LGE mass and indexed ECV (p=0.008; p=0.017, respectively). Conclusion Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischemic insult. ECM remodeling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR involving LGE, T1 mapping derived indexes and their combination with LV morphofunctional characterization.