Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte Stiffness

Ines Falcao-Pires, Nazha Hamdani, Attila Borbely, Cristina Gavina, Casper G. Schalkwijk, Jolanda van der Velden, Loek van Heerebeek, Ger J. M. Stienen, Hans W. M. Niessen, Adelino F. Leite-Moreira, Walter J. Paulus*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

137 Citations (Web of Science)

Abstract

Background-Aortic stenosis (AS) and diabetes mellitus (DM) are frequent comorbidities in aging populations. In heart failure, DM worsens diastolic left ventricular (LV) dysfunction, thereby adversely affecting symptoms and prognosis. Effects of DM on diastolic LV function were therefore assessed in aortic stenosis, and underlying myocardial mechanisms were identified. Methods and Results-Patients referred for aortic valve replacement were subdivided into patients with AS and no DM (AS; n = 46) and patients with AS and DM (AS-DM; n = 16). Preoperative Doppler echocardiography and hemodynamics were implemented with perioperative LV biopsies. Histomorphometry and immunohistochemistry quantified myocardial collagen volume fraction and myocardial advanced glycation end product deposition. Isolated cardiomyocytes were stretched to 2.2-mu m sarcomere length to measure resting tension (F(passive)). Expression and phosphorylation of titin isoforms were analyzed with gel electrophoresis with ProQ Diamond and SYPRO Ruby stains. Reduced LV end-diastolic distensibility in AS-DM was evident from higher LV end-diastolic pressure (21 +/- 1 mm Hg for AS versus 28 +/- 4 mm Hg for AS-DM; P = 0.04) at comparable LV end-diastolic volume index and attributed to higher myocardial collagen volume fraction (AS, 12.9 +/- 1.1% versus AS-DM, 18.2 +/- 2.6%; P
Original languageEnglish
Pages (from-to)1151-1159
JournalCirculation
Volume124
Issue number10
DOIs
Publication statusPublished - 6 Sep 2011

Keywords

  • aortic valve stenosis
  • myocytes, cardiac
  • diabetes mellitus
  • diastole
  • fibrosis
  • titin
  • myofilamentary proteins

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