Calcific aortic stenosis (AS) is the most common valvular heart disease, characterized by a chronic increase in the hemodynamic load to the left ventricle (LV) [1]. LV adaptation in this setting plays an important role for the occurrence of symptoms, heart failure development and definition of prognosis [2]. Myocardial fibrosis (MF) is an important component of LV remodeling, driving the transition from hypertrophy to heart failure [3] However, the mechanisms behind this transition are not completely enlighten.

Myocardial ischemia and ensue angina pectoris had been long time recognized as classical phenomena in patients with AS, independent from the presence of concomitant coronary artery disease [4]. Several mechanisms have been proposed to explain the disproportion between myocardial oxygen demand and supply. However, the greatest compromise of subendocardial coronary flow reserve was mostly deduced from old studies focused on the assessment of structural myocardial changes and MF at endomyocardial biopsies (EMB) [5]. More recently, the existence of a decreasing collagen gradient from the endocardium to the mid-myocardium has been confirmed in patient with severe AS [6], and this gradient is assumed to be related to low endocardial perfusion, reflecting a reparative response to ischemia and subsequent cardiomyocyte cell loss [7].

We hypothesize that the combination of histopathology with the specific assessment of ultrastructural changes at endomyocardial tissue sampling of patients with severe AS, may provide additional information towards the mechanisms underlying myocardial remodeling in this context.

Our aim was therefore to describe morphological and ultrastructural myocardial changes at endomyocardial sampling, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy.