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

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.

Prognostic Value of Vasodilator Stress Cardiac Magnetic Resonance Imaging: A Multicenter Study With 48 000 Patient-Years of Follow-up.

Importance: Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. Objective: To determine whether stress CMR is associated with patient mortality. Design, Setting, and Participants: Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. Main Outcomes and Measures: All-cause patient mortality. Results: Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (HR, 1.883; 95% CI, 1.680-2.112; P < .001), patients with (HR, 1.955; 95% CI, 1.712-2.233; P < .001) and without (HR, 1.578; 95% CI, 1.235-2.2018; P < .001) a history of CAD, and patients with normal (HR, 1.385; 95% CI, 1.194-1.606; P < .001) and abnormal left ventricular ejection fraction (HR, 1.836; 95% CI, 1.299-2.594; P < .001). Conclusions and Relevance: Clinical vasodilator stress CMR is associated with patient mortality in a large, diverse population of patients with known or suspected CAD as well as in multiple subpopulations defined by history of CAD and left ventricular ejection fraction. These findings provide a foundational motivation to study the comparative effectiveness of stress CMR against other modalities.