Ischemic mitral regurgitation (IMR) is a disease where the normal mitral valve (MV) structure is dysfunctional due to left ventricular (LV) remodeling after a myocardial infarction (MI). IMR affects nearly 3 million Americans and the magnitude of this problem is expected to grow as the population ages. IMR has a substantial mortality rate that is associated with even mild MR severity. Mitral valve repair with undersized ring annuloplasty has been the preferred treatment strategy for IMR; however, the recurrence of moderate or severe IMR within 12 months of surgery is common. Recent high profile results from the Cardiothoracic Surgical Trials Network (CTSN) mul- ticenter randomized trials on IMR have confirmed a high incidence of early recurrent IMR. More importantly, these studies highlighted the adverse impact of recurrent IMR on LV remodeling and clinical outcomes. The CTSN trials demonstrated no significant difference in LV volume reduction or survival at 12 and 24 months between repair and replacement groups; however, subgroup analysis demonstrated that repair patients that developed recurrent IMR had no reduction in LV volume while repair patients without recurrence experienced LV volume reduction that was superior to patients having valve replacement. The results of the CTSN IMR trials indicate an unmet need for a pre-operative risk stratification tool that reliably predicts MV repair failure. Such a tool would significantly reduce the problem of recurrent IMR by performing valve repair only in patients likely to experience a durable result and performing valve replacement in patients with high risk of recurrence. The long term goal is to improve quality of surgical therapy in IMR by improving risk-stratification pre-operatively using image analysis tools. The overall objective of this proposal is to improve the prediction IMR recurrence by ex- panding this model to include the left ventricle (LV). The rationale is that while IMR manifests as MV malcoapta- tion, the root cause of the disease is LV remodeling. The central hypothesis is that features extracted from the integrated left ventricular and mitral valve (LVMV) model will predict recurrence more accurately than the current MV-only model. To fulfill this objective and test the central hypothesis by pursuing the following specific aims: 1) Develop the 4D integrated LVMV model and compare the accuracy of fitting this model to intraoperative 3DTE images to that of the existing MV-only model. 2) Assess the ability of biomarkers derived from the integrated LVMV model to predict IMR recurrence, and compare to the predictive value of the MV-only model. The project is significant because, if successful, the integrated LVMV model will be incorporated into the Gorman lab ongoing effort translating this technology to the operating room, thus improving survival rates, reducing the impending clinical burden and the number of repeated procedures.

Public Health Relevance

The proposed project tackles the high impact problem of ischemic mitral regurgitation (IMR) recurrence after surgical repair by developing a reliable real-time pre-operative risk stratification tool using image analysis of 3D transesophageal echocardiography. This will enable surgeons to optimize mitral surgical treatment in IMR on a case-by-case basis. If successful, the proposed research has the potential to virtually eliminate the problem of IMR recurrence, maximize long-term outcomes for millions of IMR patients and significantly decrease the im- pending clinical burden expected with an aging population.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30HL142138-02
Application #
9754718
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Meadows, Tawanna
Project Start
2018-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104