Chronic ischemic mitral regurgitation (CIMR) remains one of the most vexing, life-threatening clinical problems in cardiac surgery, affects a huge number of patients, leads to congestive heart failure (CHF) which markedly limits life expectancy and functional capacity, and has major adverse implications onU.S. health care costs. Current surgical treatments are not entirely satisfactory, as one-fourth of CIMR repairs may develop severe recurrent mitral regurgitation (MR) within 6 months of operation. Better understanding of mitral function, and the development of more refined procedures based on this enhanced understanding, are clearly needed to improve clinical outcomes. We now have experimental evidence for what appears to be a revolutionary advance in our understanding;direct measurements showing that the mitral valvular-ventricular complex functions as an adaptive control system. In a preliminary experiment, step-function displacements of the posterior mitral leaflet sufficient to cause substantial MR were repeatedly answered within two minutes by geometric alterations of the valvular-ventricular complex to reduce and then eliminate the regurgitation. These findings present a difficult challenge to the traditional view of the mitral valve as a passive system, a view which strongly permeates current medical and surgical practice. The studies outlined in this application employ sophisticated Finite Element modeling and our precise radiopaque marker technology in both acute open-chest and chronic closed-chest ovine experimental models to characterize this newly-discovered control system (itssensors(s), communication network(s), actuator(s), and performance characteristics);to understand the role it plays in CIMR (wherein the valve appears normal, but leaks);and discover which treatments most closely permit continued feedback system control of mitral regurgitation. These studies are made possible by the unique capabilities of our measurement technology to track simultaneously specific transmural LV wall, ventricular, annular, and leaflet anatomical sites with 0.15mm spatial resolution and 17 msec temporal resolution on a beat-to-beat basis over time, from seconds to months. Relevance: Chronic ischemic mitral regurgitation is a serious problem in cardiac surgery. Current treatments are not satisfactory. This research is likely to lead to improved surgical treatments and medical therapies based on rational criteria, not only for chronic ischemic mitral regurgitation, but for other causes of mitral regurgitation, as well.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL067025-09
Application #
7788194
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Buxton, Denis B
Project Start
2001-06-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$484,588
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Biviano, Angelo B; Nazif, Tamim; Dizon, Jose et al. (2016) Atrial Fibrillation Is Associated With Increased Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the Placement of Aortic Transcatheter Valve (PARTNER) Trial. Circ Cardiovasc Interv 9:e002766
Thourani, Vinod H; Kodali, Susheel; Makkar, Raj R et al. (2016) Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis. Lancet 387:2218-25
Kapadia, Samir; Agarwal, Shikhar; Miller, D Craig et al. (2016) Insights Into Timing, Risk Factors, and Outcomes of Stroke and Transient Ischemic Attack After Transcatheter Aortic Valve Replacement in the PARTNER Trial (Placement of Aortic Transcatheter Valves). Circ Cardiovasc Interv 9:
Lindman, Brian R; Maniar, Hersh S; Jaber, Wael A et al. (2015) Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort. Circ Cardiovasc Interv 8:
Kapadia, Samir; Stewart, William J; Anderson, William N et al. (2015) Outcomes of inoperable symptomatic aortic stenosis patients not undergoing aortic valve replacement: insight into the impact of balloon aortic valvuloplasty from the PARTNER trial (Placement of AoRtic TraNscathetER Valve trial). JACC Cardiovasc Interv 8:324-333
Stephens, Elizabeth H; Fahrenholtz, Monica M; Connell, Patrick S et al. (2015) Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular Contraction. Cardiovasc Eng Technol 6:151-9
Stephens, Elizabeth H; Connell, Patrick S; Fahrenholtz, Monica M et al. (2015) Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain. Cardiovasc Eng Technol 6:141-50
Pibarot, Philippe; Weissman, Neil J; Stewart, William J et al. (2014) Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in high-risk patients with severe aortic stenosis: a PARTNER trial cohort--a analysis. J Am Coll Cardiol 64:1323-34
Lindman, Brian R; Stewart, William J; Pibarot, Philippe et al. (2014) Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations. JACC Cardiovasc Interv 7:662-73
Rausch, Manuel K; Famaey, Nele; Shultz, Tyler O'Brien et al. (2013) Mechanics of the mitral valve: a critical review, an in vivo parameter identification, and the effect of prestrain. Biomech Model Mechanobiol 12:1053-71

Showing the most recent 10 out of 106 publications