CLINICAL RESEARCH: HEART FAILURE
Apparently normal mitral valves in patients with heart failure demonstrate biochemical and structural derangements
An extracellular matrix and echocardiographic study
K. Jane Grande-Allen, PhD*,*,
Allen G. Borowski, RDCS ,
Richard W. Troughton, MB ChB, PhD, FRACP,
Penny L. Houghtaling, MS ,
Nicholas R. DiPaola, PhD, ,
Christine S. Moravec, PhD,,
Ivan Vesely, PhD|| and
Brian P. Griffin, MD, FACC
* 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."
|
Abbreviations and Acronyms
| | CHF = congestive heart failure | | DCM = dilated cardiomyopathy | | DNA = deoxyribonucleic acid | | ECM = extracellular matrix | | GAG = glycosaminoglycan | | ICM = ischemic cardiomyopathy | | LV = left ventricular | | MR = mitral regurgitation | | TEE = transesophageal echocardiography | | TTE = transthoracic echocardiography |
|
This article has been cited by other articles:
|
|
|
|
 
E. H. Stephens, T. A. Timek, G. T. Daughters, J. J. Kuo, A. M. Patton, L. S. Baggett, N. B. Ingels, D. C. Miller, and K. J. Grande-Allen
Significant Changes in Mitral Valve Leaflet Matrix Composition and Turnover With Tachycardia-Induced Cardiomyopathy
Circulation,
September 15, 2009;
120(11_suppl_1):
S112 - S119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Dal-Bianco, E. Aikawa, J. Bischoff, J. L. Guerrero, M. D. Handschumacher, S. Sullivan, B. Johnson, J. S. Titus, Y. Iwamoto, J. Wylie-Sears, et al.
Active Adaptation of the Tethered Mitral Valve: Insights Into a Compensatory Mechanism for Functional Mitral Regurgitation
Circulation,
July 28, 2009;
120(4):
334 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Maurer
Mitral Leaflet in Functional Regurgitation: Passive Bystander or Active Player?
Circulation,
July 28, 2009;
120(4):
275 - 277.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. H. Stephens, T. C. Nguyen, A. Itoh, N. B. Ingels Jr, D. C. Miller, and K. J. Grande-Allen
The Effects of Mitral Regurgitation Alone Are Sufficient for Leaflet Remodeling
Circulation,
September 30, 2008;
118(14_suppl_1):
S243 - S249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. D. Gillam
Is It Time to Update the Definition of Functional Mitral Regurgitation?: Structural Changes in the Mitral Leaflets With Left Ventricular Dysfunction
Circulation,
August 19, 2008;
118(8):
797 - 799.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chaput, M. D. Handschumacher, F. Tournoux, L. Hua, J. L. Guerrero, G. J. Vlahakes, and R. A. Levine
Mitral Leaflet Adaptation to Ventricular Remodeling: Occurrence and Adequacy in Patients With Functional Mitral Regurgitation
Circulation,
August 19, 2008;
118(8):
845 - 852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. W.M. Fedak, P. M. McCarthy, and R. O. Bonow
Evolving Concepts and Technologies in Mitral Valve Repair
Circulation,
February 19, 2008;
117(7):
963 - 974.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Fann, N. B. Ingels Jr., and D. C. Miller
Pathophysiology of Mitral Valve Disease
Card. Surg. Adult,
January 1, 2008;
3(2008):
973 - 1012.
[Full Text]
|
|
|
|
|
|
|
S. H. Rahimtoola
The Year in Valvular Heart Disease
J. Am. Coll. Cardiol.,
January 23, 2007;
49(3):
361 - 374.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. A. Timek, D. T. Lai, P. Dagum, D. Liang, G. T. Daughters, N. B. Ingels Jr, and D. C. Miller
Mitral Leaflet Remodeling in Dilated Cardiomyopathy
Circulation,
July 4, 2006;
114(1_suppl):
I-518 - I-523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. C. Caira, S. R. Stock, T. G. Gleason, E. C. McGee, J. Huang, R. O. Bonow, T. C. Spelsberg, P. M. McCarthy, S. H. Rahimtoola, and N. M. Rajamannan
Human Degenerative Valve Disease Is Associated With Up-Regulation of Low-Density Lipoprotein Receptor-Related Protein 5 Receptor-Mediated Bone Formation
J. Am. Coll. Cardiol.,
April 18, 2006;
47(8):
1707 - 1712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, D. Berman, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, W. Y.W. Lew, D. Sahn, and S. Tsimikas
Highlights of the Year in JACC 2005
J. Am. Coll. Cardiol.,
January 3, 2006;
47(1):
184 - 202.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Grande-Allen, J. E. Barber, K. M. Klatka, P. L. Houghtaling, I. Vesely, C. S. Moravec, and P. M. McCarthy
Mitral valve stiffening in end-stage heart failure: Evidence of an organic contribution to functional mitral regurgitation
J. Thorac. Cardiovasc. Surg.,
September 1, 2005;
130(3):
783 - 790.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. O'Brien and D. P. Fishbein
Mitral valve abnormalities in congestive heart failure: An interplay between form and function?
J. Am. Coll. Cardiol.,
January 4, 2005;
45(1):
62 - 64.
[Full Text]
[PDF]
|
|
|
|
