Current Affiliation: Stanford University, Department of Radiology, Stanford, CA, United States.
Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction†
Article first published online: 31 AUG 2007
Published on behalf of the European Society of Cardiology. All rights reserved. © 2007 the Authors
European Journal of Heart Failure
Volume 9, Issue 9, pages 857–864, September 2007
How to Cite
McGinley, J. C., Berretta, R. M., Chaudhary, K., Rossman, E., Bratinov, G. D., Gaughan, J. P., Houser, S. and Margulies, K. B. (2007), Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction. European Journal of Heart Failure, 9: 857–864. doi: 10.1016/j.ejheart.2007.05.013
This project has been supported, in part, through a grant from the Ottawa Heart Institute.
- Issue published online: 31 AUG 2007
- Article first published online: 31 AUG 2007
- Manuscript Accepted: 17 MAY 2007
- Manuscript Revised: 13 APR 2007
- Manuscript Received: 1 MAR 2007
- valvular disease;
- mitral valve regurgitation;
- myocyte physiology;
- left ventricular trabecular physiology;
- calcium transients;
- heart failure
Impaired contractile reserve in chronic MR results from load-independent, myocyte contractile abnormalities.
Investigate the mechanisms of contractile dysfunction in chronic mitral valve regurgitation (MR).
Mild MR was produced in eight dogs followed by pacing induced left ventricular (LV) dilatation over eight months. In-vivo LV dP/dt was measured at several pacing rates. Contractile function was measured in isolated LV trabeculae and myocytes at several stimulation rates and during changes in extracellular [Ca2+]. Identical studies were performed with six control dogs.
Chronic MR resulted in a preserved ejection fraction with decreased dP/dt (p<0.01). LV trabeculae demonstrated significantly lower developed force and a negative force–frequency relation with chronic MR (p<0.05). Myocytes exhibited a negative shortening-frequency relationship in both groups with a greater decline with chronic MR (p<0.001) paralleled by decreases in peak [Ca2+]i transients. Increases in extracellular [Ca2+] abrogated the defects in force generation in trabeculae from animals with chronic MR.
Even with a preserved EF, chronic severe MR results in a significant reduction in intrinsic contractile function and reserve. Functional impairment was load-independent reflecting a predominant defect in calcium cycling rather than impaired peak force generating capacity due to myofibrillar attenuation.