Association of Myocardial Angiogenesis with Structural and Functional Ventricular Remodeling in Aortic Stenosis Patients with Normal Ejection Fraction

BACKGROUND Although rarefaction of myocardial angiogenesis has been shown to be associated with left ventricular (LV) systolic dysfunction in animal models of ventricular hypertrophy, this relationship has not been investigated in depth nor validated in humans. We aimed to analyze the relationship of myocardial angiogenesis with various functional and structural ventricular remodeling parameters in moderate to severe aortic stenosis (AS) patients with normal LV ejection fraction (LVEF). METHODS A total of 38 moderate or severe AS patients with LVEF > 50% were enrolled for the current study and all patients underwent LV endomyocardial biopsy at the septum during aortic valve replacement. The biopsy specimens were stained for platelet endothelial cell adhesion molecule-1 (CD31) to analyze the density of blood vessels in the myocardium. RESULTS The degree of myocardial angiogenesis tended to increase with worse myocardial systolic function, LV filling pressure and progressed ventricular hypertrophy (Spearman's ρ = -0.388, p = 0.016 for LVEF; Spearman's ρ = 0.442, p = 0.007 for E/e'; Spearman's ρ = 0.424, p = 0.008 for LV mass index). The degree of myocardial angiogenesis was also significantly associated with the degree of aortic valve stenosis (Spearman's ρ = -0.368, p = 0.023). There was significant difference in the degree of myocardial angiogenesis according to the LV geometry (p = 0.016 for mean difference between different LV geometry groups by analysis of variance). Significant predictors of myocardial blood vessel density were LV mass index (β = 0.398, p = 0.010) and LVEF (β = -0.313, p = 0.028). CONCLUSION There is a close relationship between myocardial angiogenesis and LV remodeling in moderate to severe AS patients with normal LVEF, with angiogenesis increasing with LV hypertrophy. Further studies to demonstrate the mechanism underlying this phenomenon is warranted.