title: Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure.
abstract: OBJECTIVE
  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.
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Kattalin
authors.initials: K
authors.lastname: Echegaray
authors.affiliation: Departamento de Materiales, CEIT y TECNUN, Universidad de Navarra, San Sebastián, Guipúzcoa, Spain.
authors.forename: Ion
authors.initials: I
authors.lastname: Andreu
authors.affiliation: Área de Enfermedades Sistémicas, Instituto de Investigación Biodonostia, San Sebastián, Guipúzcoa, Spain.
authors.forename: Ane
authors.initials: A
authors.lastname: Lazkano
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Villanueva
authors.affiliation: Servicio de Cirugía Cardiaca, Policlínica Guipúzcoa, San Sebastián, Guipúzcoa, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sáenz
authors.affiliation: Departamento de Materiales, CEIT y TECNUN, Universidad de Navarra, San Sebastián, Guipúzcoa, Spain.
authors.forename: María Reyes
authors.initials: MR
authors.lastname: Elizalde
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Echeverría
authors.affiliation: Programa de Enfermedades Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Navarra, Spain; Área de Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: López
authors.affiliation: Área de Enfermedades Sistémicas, Instituto de Investigación Biodonostia, San Sebastián, Guipúzcoa, Spain.
authors.forename: Asier
authors.initials: A
authors.lastname: Garro
authors.affiliation: Programa de Enfermedades Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Navarra, Spain; Área de Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: González
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Zubillaga
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Solla
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Sanz
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: González
authors.affiliation: Área de Mecanobiología Celular y Molecular, Instituto de Bioingeniería de Cataluña, Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Elósegui-Artola
authors.affiliation: Área de Mecanobiología Celular y Molecular, Instituto de Bioingeniería de Cataluña, Barcelona, Spain; Unidad de Biofísica y Bioingeniería, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Roca-Cusachs
authors.affiliation: Programa de Enfermedades Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Navarra, Spain; Área de Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Servicio de Cardiología y de Cirugía Cardiaca, Clínica Universidad de Navarra, Pamplona, Navarra, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.affiliation: Programa de Enfermedades Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Navarra, Spain; Área de Enfermedades Cardiovasculares, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Ravassa
authors.affiliation: Servicio de Cardiología, Hospital Universitario Donostia, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain; Área de Enfermedades Sistémicas, Instituto de Investigación Biodonostia, San Sebastián, Guipúzcoa, Spain. Electronic address: sravassa@unav.es.
authors.forename: Ramón
authors.initials: R
authors.lastname: Querejeta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D001783:Blood Flow Velocity; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D003971:Diastole; D055119:Elastic Modulus / Q000502:physiology; D005109:Extracellular Matrix; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D012720:Severity of Illness Index; D013318:Stroke Volume
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Aortic stenosis; Colágeno misial y no misial; Diastolic dysfunction; Disfunción diastólica; Estenosis aórtica; Fibrosis miocárdica; Heart failure; Insuficiencia cardiaca; Myocardial fibrosis; Mysial and nonmysial collagen; Rigidez; Stiffness