• Mario Kasner, Dirk Westermann, Begoña Lopez, Regina Gaub, Felicitas Escher, Uwe Kühl, Heinz-Peter Schultheiss, and Carsten Tschöpe.
• Department of Cardiology and Pneumology, Campus Benjamin Franklin, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
• J. Am. Coll. Cardiol. 2011 Feb 22; 57 (8): 977-85.

ObjectivesWe attempted to correlate echocardiographic analysis of diastolic function with changes of myocardial collagen in middle-aged patients with heart failure (HF) despite normal ejection fraction (EF).BackgroundIncreased collagen deposition may contribute to the deterioration of the left ventricular compliance and diastolic dysfunction in HF.MethodsWe investigated 41 patients (median age 50 years [interquartile range: 41 to 57 years]) with normal EF (median 62% [interquartile range: 56% to 70%]) whose endomyocardial biopsies were taken previously. Assessment of diastolic function was performed by mitral-flow and tissue Doppler measurements. Sirius red and immunohistologic staining was performed to determine collagen volume fraction (CVF) and cross-linking, collagen types I and III expression, and lysyl-oxidase (LOX) expression. Expression of collagen messenger ribonucleic acid was determined by real-time polymerase chain reaction.ResultsTwenty-six patients with HFNEF with diastolic dysfunction showed a significant increase in total collagen and collagen I expression compared with that of 15 controls. This was accompanied with enhanced collagen cross-linking and LOX overexpression in HFNEF. Among all flow Doppler, only deceleration time of E was associated with CVF (R = 0.43), whereas tissue Doppler parameters correlated with CVF, collagen I at the protein and mRNA levels (E' [R = -0.58, -0.60, -0.45]; E'/A' [R = -0.32, -0.36, -0.31]), and left ventricular filling index (E/E' [R = 0.72, 0.68, 0.63]), respectively. No correlation with collagen III was found. The degree of collagen cross-linking and LOX expression was related to E' (R = -0.55 and -0.60) and E/E' (R = 0.72 and 0.71), respectively, but not to flow Doppler. Collagen overexpression correlated with reduced exercise capacity.ConclusionsPatients with HFNEF showed increased content of myocardial collagen type I, enhanced collagen cross-linking, and LOX expression, which were associated with impaired diastolic tissue Doppler parameters.Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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