TY - JOUR
T1 - 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
AU - Schelbert, Erik B.
AU - Piehler, Kayla M.
AU - Zareba, Karolina M.
AU - Moon, James C.
AU - Ugander, Martin
AU - Messroghli, Daniel R.
AU - Valeti, Uma S.
AU - Chang, Chung Chou H.
AU - Shroff, Sanjeev G.
AU - Diez, Javier
AU - Miller, Christopher A.
AU - Schmitt, Matthias
AU - Kellman, Peter
AU - Butler, Javed
AU - Gheorghiade, Mihai
AU - Wong, Timothy C.
N1 - Funding Information:
This work was supported by a grant from The Pittsburgh Foundation (PA), Grant M2009-0068; and an American Heart Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and the American Heart Association (Dallas, TX). This work was also supported by Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
Funding Information:
Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and the American Heart Association (Dallas, TX). This work was also supported by Grant Number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
Funding Information:
This work was supported by a grant from The Pittsburgh Foundation (PA), Grant M2009-0068; and an American Heart
Funding Information:
Dr Schelbert has accepted contrast material from Bracco Diagnostics for research purposes beyond the scope of this work. Dr Wong was supported by a grant K12 HS19461-01 from the Agency for Healthcare Research and Quality. Dr Shroff’s research efforts were partially supported by the McGinnis Endowed Chair funds (Pittsburgh, PA). Dr Gheorghi-ade is a consultant for Abbott Laboratories, Astellas, Astra-Zeneca, Bayer Schering Pharma AG, Cardiorentis Ltd, CorThera, Inc, Cytokinetics, Inc, DebioPharm SA, Errekappa Terapeutici (Milan, Italy), GlaxoSmithKline, Ikaria, Intersection Medical, Inc, Johnson & Johnson, Medtronic, Merck, Novartis Pharma AG, Ono Pharmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals Sticares Inter-ACT, Takeda Pharmaceuticals North America, Inc, and Trevena Therapeutics. The remaining authors have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Background-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. Method and Results-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 < 0.01). Conclusion-MF measured by ECV is associated with hospitalization for heart failure, death, or both. MF may represent a principal phenotype of cardiac vulnerability that improves risk stratification. Because MF can be reversible, cells and enzymes regulating collagen could be potential therapeutic targets.
AB - Background-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. Method and Results-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 < 0.01). Conclusion-MF measured by ECV is associated with hospitalization for heart failure, death, or both. MF may represent a principal phenotype of cardiac vulnerability that improves risk stratification. Because MF can be reversible, cells and enzymes regulating collagen could be potential therapeutic targets.
KW - Cardiovascular magnetic resonance
KW - Extracellular matrix
KW - Extracellular volume fraction
KW - Heart failure
KW - Myocardial fibrosis
KW - T1 mapping
UR - http://www.scopus.com/inward/record.url?scp=84991406890&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991406890&partnerID=8YFLogxK
U2 - 10.1161/JAHA.115.002613
DO - 10.1161/JAHA.115.002613
M3 - Article
C2 - 26683218
AN - SCOPUS:84991406890
SN - 2047-9980
VL - 4
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 12
M1 - e002613
ER -