Myocardial Fibrosis Quantified by Extracellular Volume Is Associated With Subsequent Hospitalization for Heart Failure, Death, or Both Across the Spectrum of Ejection Fraction and Heart Failure Stage

• Published in: Journal of the American Heart Association 2015-12, Vol.4 (12), p.n/a
• Main Authors: Schelbert, Erik B, Piehler, Kayla M, Zareba, Karolina M, Moon, James C, Ugander, Martin, Messroghli, Daniel R, Valeti, Uma S, Chang, Chung-Chou H, Shroff, Sanjeev G, Diez, Javier, Miller, Christopher A, Schmitt, Matthias, Kellman, Peter, Butler, Javed, Gheorghiade, Mihai, Wong, Timothy C
• Format: Article
• Language: English
• Subjects: Adult; cardiovascular magnetic resonance; extracellular matrix; extracellular volume fraction; Female; Fibrosis; heart failure; Heart Failure - epidemiology; Heart Failure - mortality; Heart Failure - pathology; Heart Failure - physiopathology; Hospitalization - statistics & numerical data; Humans; Male; Medicin och hälsovetenskap; Middle Aged; myocardial fibrosis; Myocardium - pathology; Original Research; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Stroke Volume; T1 mapping
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.115.002613

Myocardial fibrosis (MF) in noninfarcted myocardium may be an interstitial disease pathway that confers vulnerability to hospitalization for heart failure, death, or both across the spectrum of heart failure and ejection fraction. Hospitalization for heart failure is an epidemic that is difficult to predict and prevent and requires potential therapeutic targets associated with outcomes. We quantified MF with cardiovascular magnetic resonance extracellular volume fraction (ECV) measures in 1172 consecutive patients without amyloidosis or hypertrophic or stress cardiomyopathy and assessed associations with outcomes using Cox regression. ECV ranged from 16.6% to 47.8%. Over a median of 1.7 years, 111 patients experienced events after cardiovascular magnetic resonance, 55 had hospitalization for heart failure events, and there were 74 deaths. ECV was more strongly associated with outcomes than "nonischemic" MF observed with late gadolinium enhancement, thus ECV quantified MF in multivariable models. Adjusting for age, sex, renal function, myocardial infarction size, ejection fraction, hospitalization status, and heart failure stage, higher ECV was associated with hospitalization for heart failure (hazard ratio 1.77; 95% CI 1.32 to 2.36 for every 5% increase in ECV), death (hazard ratio 1.87 95% CI 1.45 to 2.40) or both (hazard ratio 1.85, 95% CI 1.50 to 2.27). ECV improved classification of persons at risk and improved model discrimination for outcomes (eg, hospitalization for heart failure: continuous net reclassification improvement 0.33, 95% CI 0.05 to 0.66; P=0.02; 0.16, 95% CI 0.01 to 0.33; P=0.02; integrated discrimination improvement 0.037, 95% CI 0.008 to 0.073; P