Examining the Relationship and Prognostic Implication of Diabetic Status and Extracellular Matrix Expansion by Cardiac Magnetic Resonance

Background: Although not fully understood, diabetes mellitus is thought to be associated with cardiac fibrosis and stiffness due to alteration of myocardial extracellular matrix. Newer cardiac magnetic resonance techniques may be able to identify extracellular matrix expansion by measuring extracellular volume fraction (ECV). We used cardiac magnetic resonance to evaluate the association of alteration in the extracellular matrix with diabetic status and its implications on incident heart failure events and all-cause mortality. Methods: We studied 442 patients who underwent comprehensive contrast cardiac magnetic resonance to assess cardiac morphology and function, left ventricular replacement fibrosis, and pre-post contrast T1 mapping to quantify ECV. The cohort did not have coexisting pathologies associated with ECV alteration. We categorized our final cohort based on diabetic status using criteria from the American Diabetic Association. Subsequent heart failure hospitalization and all-cause death were ascertained. Results: Our patients were predominantly white with a median age of 57 with 48% being men. Compared with nondiabetes mellitus, diabetes mellitus was significantly associated with elevated ECV after adjusting for clinical and imaging covariates: β coefficient 1.33 (95% CI, 0.22-2.44); P=0.02. Over a median follow-up of 24.5 (interquartile range, 14.8-33.4) months, 52 deaths and 24 heart failure events occurred. Patients with diabetes mellitus and elevated ECV had the worst outcomes compared with patients with diabetes mellitus and normal ECV or nondiabetics. Elevated ECV remained an independent predictor of outcomes (hazard ratio, 3.31 [95% CI, 1.93-5.67]; P<0.001) after adjusting for covariates. Conclusions: Elevated ECV is an independent predictor of mortality among patients with diabetes mellitus and may have an additive effect with diabetes mellitus on outcomes. ECV may represent a novel noninvasive biomarker to evaluate severity of diabetic heart disease.