Published online before print February 5, 2007, doi: 10.1161/CIRCULATIONAHA.106.638569
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(Circulation. 2007;115:888-895.)
© 2007 American Heart Association, Inc.
Heart Failure |
Diastolic Heart Failure
Evidence of Increased Myocardial Collagen Turnover Linked to Diastolic Dysfunction
From the Heart Failure Unit (R.M., M.L., C.O., C.C., A.P., K.M.), St Vincent’s University Hospital, Dublin, Ireland, and School of Medicine & Medical Science, St Vincent’s University Hospital and the Conway Institute of Biomolecular and Biomedical Research, University College Dublin (J.B., S.C.D.), Dublin, Ireland.
Correspondence to Dr Kenneth McDonald, Heart Failure Unit, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. E-mail kenneth.mcdonald{at}ucd.ie
Received May 16, 2005; accepted November 27, 2006.
Background— The pathophysiology of diastolic heart failure (DHF) is poorly understood. One potential explanation is an active fibrotic process that produces increased ventricular stiffness, which compromises filling. The present study investigates collagen metabolism in hypertensive patients in different phases of diastolic function with and without proven DHF.
Methods and Results— We studied 86 hypertensive patients divided into groups according to the presence of DHF (32 with, 54 without) and phase of diastolic function (20 with normal function, 38 with impaired relaxation, 10 with pseudonormalization, and 16 with restrictive-like filling). Serum carboxy-terminal, amino-terminal, and carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, matrix metalloproteinases (MMPs; total MMP-1, active MMP-2, and MMP-9), and tissue inhibitor of MMPs levels were assayed by radioimmunoassay and ELISA. Doppler-echocardiographic assessment of diastolic filling was made with measurements of E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Serum carboxy-terminal telopeptide of procollagen type I, carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 levels (P<0.001 for all, controlled for age and gender) were greater in patients with DHF than in those without. When we controlled for age and gender, levels of serum carboxy-terminal telopeptide of procollagen type I, tissue inhibitor of MMP-1, amino-terminal propeptide of procollagen type III (all P<0.001), carboxy-terminal telopeptide of procollagen type I(P=0.008), and MMP-2 (P=0.03) were greater in more severe phases of diastolic dysfunction. Within phases of diastolic dysfunction, serum carboxy-terminal telopeptide of procollagen type I, amino-terminal propeptide of procollagen type III, MMP-2, and MMP-9 were elevated in those with DHF compared with those without DHF (all P<0.001).
Conclusions— These data demonstrate serological evidence of an active fibrotic process in DHF, which is more marked in more severe diastolic dysfunction. This observation may help explain the pathophysiology of DHF and may suggest new avenues for diagnostic and therapeutic intervention.
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