Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure
Kattalin Echegaray 1 , Ion Andreu 2 , Ane Lazkano 3 , Iñaki Villanueva 1 , Alberto Sáenz 4 , María Reyes Elizalde 2 , Tomás Echeverría 1 , Begoña López 5 , Asier Garro 3 , Arantxa González 5 , Elena Zubillaga 6 , Itziar Solla 1 , Iñaki Sanz 1 , Jesús González 1 , Alberto Elósegui-Artola 7 , Pere Roca-Cusachs 8 , Javier Díez 9 , Susana Ravassa 5 , Ramón Querejeta 10
Introduction and objectives: We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure.
Methods: Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as CIVF and CIIIVF, respectively, by confocal microscopy in areas with YEM evaluation.
Results: Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the CIVF:CIIIVF ratio and YEM were increased (P ≤ .001) in nonmysial regions compared with mysial regions in patients, with a direct correlation (r = 0.895; P < .001) between them.
Conclusions: These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients.
CITATION Rev Esp Cardiol (Engl Ed) . 2017 Oct;70(10):832-840. doi: 10.1016/j.rec.2016.12.038. Epub 2017 Feb 16.