Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation

Jonathan D. Kochav, Jiwon Kim, Robert Judd, Han W. Kim, Igor Klem, John Heitner, Dipan Shah, Chetan Shenoy, Afshin Farzaneh-Far, Venkateshwar Polsani, Ramsey Kalil, Pablo Villar-Calle, Lakshmi Nambiar, Razia Sultana, Michele Parker, Preston Cargile, Omar K. Khalique, Martin B. Leon, Dimitrios Karmpaliotis, Mark RatcliffeRobert Levine, William A. Zoghbi, Richard B. Devereux, Chaya S. Moskowitz, Raymond Kim, Jonathan W. Weinsaft

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


OBJECTIVES: The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.

BACKGROUND: FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.

METHODS: Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.

RESULTS: A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.

CONCLUSIONS: Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Original languageEnglish (US)
Pages (from-to)826-839
Number of pages14
JournalJACC: Cardiovascular Imaging
Issue number4
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health grants R01 HL128278 (Drs. Weinsaft, Ratcliffe, Levine, and J. Kim), R01 HL128099 and R01 HL141917 (Dr. Levine), R01-HL63348 (Dr. Ratcliffe), K23 HL140092 (Dr. J. Kim), K23 HL132011 (Dr. Shenoy), and T32 HL7854-23 (Dr. Kochav). It was also funded by the Glorney-Raisbeck Fellowship/NY Academy of Medicine (Dr. Kochav). Dr. Judd has an equity interest. Dr. R. Kim serves on the Board of Directors. Mr. Cargile is an employee of Heart Imaging Technologies. Dr. Klem is a consultant for and receives speaker honorarium from Bayer; and receives funding from Medtronic. Dr. Karmpaliotis receives funding from Abbott Vascular, Boston Scientific, and Abiomed; and has equity in Saranas, Soundbite, and Traverse Vascular. Dr. Leon receives funding from Abbott Vascular, Boston Scientific, and Medtronic. Dr. Weinsaft has received speaker honoraria from GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation


  • cardiac magnetic resonance
  • ischemia
  • mitral regurgitation
  • Mitral Valve Insufficiency/diagnostic imaging
  • Predictive Value of Tests
  • Ventricular Function, Left
  • Humans
  • Middle Aged
  • Papillary Muscles/diagnostic imaging
  • Male
  • Stroke Volume
  • Ischemia
  • Female
  • Aged

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation'. Together they form a unique fingerprint.

Cite this