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J Am Coll Cardiol, 2005; 45:54-61, doi:10.1016/j.jacc.2004.06.079 © 2005 by the American College of Cardiology Foundation |
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* Bioengineering, Rice University, Houston, Texas
Cardiovascular Medicine
Biostatistics
Kaufman Center for Heart Failure
|| Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio
Manuscript received January 30, 2004; revised manuscript received May 10, 2004, accepted May 11, 2004.
* Reprint requests and correspondence: Dr. K. Jane Grande-Allen, Department of Bioengineering, MS 142, Rice University, PO Box 1892, Houston, Texas 77251-1892 (Email: grande{at}rice.edu).
OBJECTIVES: This study assessed apparently normal mitral valves from patients with congestive heart failure (CHF) using biochemical and echocardiographic measures of extracellular matrix (ECM) and anatomy.
BACKGROUND: Mitral regurgitation (MR) is frequently found in patients with CHF. This MR is considered purely functional, yet animal studies suggest that altered left ventricular (LV) function leads to increased cellularity and fibrosis of the mitral valve. Therefore, we hypothesized that patients with CHF might have partly organic MR, via dysfunctional valvular remodeling.
METHODS: Mitral valves from transplant recipient hearts of patients with CHF (23 dilated, 14 ischemic) were analyzed for deoxyribonucleic acid (DNA), collagen, glycosaminoglycan (GAG), and water concentrations and compared with autopsy controls. Cardiac dimensions and functional parameters (measured from recent echocardiograms) were compared with biochemical parameters using a repeated measures generalized linear model.
RESULTS: The mitral valves in CHF had up to 78% more DNA (p < 0.03), 59% more GAGs (p < 0.02), and 15% more collagen (p < 0.007), but 7% less water (p < 0.05) than normal. The absence of anterior leaflet redundancy was associated with these deranged biochemical measures (p < 0.03). Associations were found between leaflet thickness and DNA concentration (+, p = 0.003), annular diameter and chordal collagen (+, p = 0.03), and water concentration and both left atrial diameter (–, p = 0.008) and LV collagen concentration (–, p = 0.04).
CONCLUSIONS: Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."
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