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

14 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


  • cardiac magnetic resonance
  • ischemia
  • mitral regurgitation

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine


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