# Novel therapeutic approaches to Mitral valve repair in ischemic heart disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $638,920

## Abstract

ABSTRACT:
The overarching goal of this R01 application from a collaborative new and early stage investigator, is to define
the mechanistic basis for recurrent functional mitral regurgitation (FMR) after undersizing mitral
annuloplasty(UMA) in heart failure patients, and translate the mechanistic insights into the development of a
new surgical technique that eliminates this problem. 2-3 million Americans suffer from FMR developing from
ischemic cardiomyopathy. Volume overload imposed by FMR not only elevates pulmonary pressures and
causes dyspnea, but imposes a unique low pressure hemodynamic stress on the already cardiomyopathic
ventricle. This stress elevates sympathetic drive and causes breakdown of cardiac extracellular matrix and
leads to rapid ventricular dysfunction. Timely repair of FMR is now considered necessary and patients are
promptly referred for surgical repair, but poor repair durability and post-repair recurrence of FMR continue to
haunt these patients and their cardiologists. A recent randomized controlled trial reported that in patients
receiving FMR repair with an undersizing annuloplasty ring (current gold standard), FMR was fully repaired at
the time of surgery, but at 1 year 34% of the patients developed recurrent moderate or greater FMR, and at 2
years 64% had repair failure. This situation needs to be improved, but mechanistic insights into recurrent FMR
after annuloplasty are scarce and thus techniques for improvement are lacking. We developed and validated a
novel patient imaging (3D echo+MRI) derived biomechanical modeling platform to investigate the mechanism
causing recurrent FMR in patients receiving annuloplasty. A retrospective study was performed using this
model on a select set of FMR patient images at our institution, which resulted in a hypothesis that poor inter-
papillary muscle lateral shortening governs the risk of developing FMR, and that surgically approximating the
papillary muscles can eliminate recurrent FMR. We validated our hypothesis in an ex-vivo mitral valve model
and in a chronic swine model, and recently published these results. In this R01 application, we propose to
conduct a prospective trial to confirm that patients with poor inter-papillary muscle lateral shortening develop
recurrent FMR after mitral annuloplasty (Aim 1); that poor-inter papillary muscle lateral shortening leads to
elevated tethering forces on the anterior and posterior mitral leaflet edges that reduces their systolic
parallelization that is essential to achieve adequate coaptation (Aim 2); and finally propose papillary muscle
approximation as a new technique to reduce recurrent FMR after annuloplasty, and enable reverse ventricular
remodeling(Aim 3). A multi-disciplinary team has been assembled with expertise in heart valve biomechanics,
cardiac surgery, cardiac imaging and clinical trials, in a high volume cardiac surgery center that provides an
excellent environment to conduct this work. Ultimately, this work would provid...

## Key facts

- **NIH application ID:** 10241943
- **Project number:** 5R01HL133667-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Robert Allan Guyton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $638,920
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241943

## Citation

> US National Institutes of Health, RePORTER application 10241943, Novel therapeutic approaches to Mitral valve repair in ischemic heart disease (5R01HL133667-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241943. Licensed CC0.

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