Abstract 16609: Histological and Molecular Fingerprints of Low-Gradient Aortic Stenosis
Background: Low-gradient aortic stenosis (LGAS) is associated with a worse prognosis and high operative risk compared to aortic stenosis (AS) with normal left ventricular (LV) ejection fraction (EF). We aimed to investigate histological and molecular correlations of impaired LV function in LGAS.
Methods: Transmural biopsies during aortic valve replacement were obtained from 5 consecutive patients (pt) with LGAS, 7 pt with AS, while 4 donor hearts before transplantation served as controls. Preoperative echocardiography quantified LV global and regional function. The fraction of cardiac interstitial tissue, the intracellular volume fraction of myofibriIs and myofiber diameters were determined by light microscopic morphometry. Expression of sarcoplasmic-endoplasmic reticulum calcium ATPase SERCA-2a and of natrium/calcium exchanger NCX-1 were assessed by immunohistochemical staining.
Results: LGAS was echocardiographically characterized by decreased EF, radial LV strain and -strain rate. Histologically, no differences in myofiber diameters and myofibrillar volume fraction were found, but a significant increase in interstitial volume fraction distinguished LGAS from AS. At protein level, a decrease in SERCA-2a expression and a marked increase in NCX-1 were found in LGAS, compared with both AS and controls (Fig. 1). Correlations were found between SERCA-2a and both myofibrillar volume and radial strain rate, between NCX-1 and EF and between interstitial volume fraction and LV strain (Fig. 2).
Conclusions: LGAS is typically associated with increased interstitial volume, decreased SERCA-2a and strong overexpression of NCX-1, compared to AS with preserved EF.
- © 2013 by American Heart Association, Inc.