title: Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission.
abstract: OBJECTIVE
  Diabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.
  
  
  RESULTS
  We enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models.
  
  
  CONCLUSIONS
  Diabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wong
authors.forename: Kayla M
authors.initials: KM
authors.lastname: Piehler
authors.forename: Ian A
authors.initials: IA
authors.lastname: Kang
authors.forename: Ajay
authors.initials: A
authors.lastname: Kadakkal
authors.forename: Peter
authors.initials: P
authors.lastname: Kellman
authors.forename: David S
authors.initials: DS
authors.lastname: Schwartzman
authors.forename: Suresh R
authors.initials: SR
authors.lastname: Mulukutla
authors.forename: Marc A
authors.initials: MA
authors.lastname: Simon
authors.forename: Sanjeev G
authors.initials: SG
authors.lastname: Shroff
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schelbert
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality / Q000473:pathology*; D058065:Diabetic Cardiomyopathies / Q000401:mortality / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000473:pathology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects
keywords: MRI; collagen; diabetes; extracellular matrix; extracellular volume fraction; fibrosis