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Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2017;70:832-40 - Vol. 70 Num.10 DOI: 10.1016/j.rec.2016.12.038

Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure

Kattalin Echegaray a, Ion Andreu b, Ane Lazkano c, Iñaki Villanueva a, Alberto Sáenz d, María Reyes Elizalde b, Tomás Echeverría a, Begoña López e,f,g, Asier Garro c, Arantxa González e,f,g, Elena Zubillaga h, Itziar Solla a, Iñaki Sanz a, Jesús González a, Alberto Elósegui-Artola i, Pere Roca-Cusachs i,j, Javier Díez e,f,g,k, Susana Ravassa e,f,g, Ramón Querejeta a,c,

a Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain
b Departamento de Materiales, CEIT y TECNUN, Universidad de Navarra, San Sebastián, Guipúzcoa, Spain
c Área de Enfermedades Sistémicas, Instituto de Investigación Biodonostia, San Sebastián, Guipúzcoa, Spain
d Servicio de Cirugía Cardiaca, Policlínica Guipúzcoa, San Sebastián, Guipúzcoa, Spain
e Programa de Enfermedades Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Navarra, Spain
f Área de Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain
g CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
h Servicio de Medicina Interna, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain
i Área de Mecanobiología Celular y Molecular, Instituto de Bioingeniería de Cataluña, Barcelona, Spain
j Unidad de Biofísica y Bioingeniería, Universidad de Barcelona, Barcelona, Spain
k Servicio de Cardiología y de Cirugía Cardiaca, Clínica Universidad de Navarra, Pamplona, Navarra, Spain


Aortic stenosis. Myocardial fibrosis. Stiffness. Heart failure. Diastolic dysfunction. Mysial and nonmysial collagen.


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.


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.


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.


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.


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1885-5857/© 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved