• Bonnie Ky, Benjamin French, Kosha Ruparel, Nancy K Sweitzer, James C Fang, Wayne C Levy, Douglas B Sawyer, and Thomas P Cappola.
• Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. bonnie.ky@uphs.upenn.edu
• J. Am. Coll. Cardiol. 2011 Jul 19;58(4):386-94.

ObjectivesWe sought to evaluate placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF).BackgroundVascular remodeling is a crucial compensatory mechanism in chronic HF. The angiogenic ligand PlGF and its target receptor fms-like tyrosine kinase 1 modulate vascular growth and function, but their relevance in human HF is undefined.MethodsWe measured plasma PlGF and sFlt-1 in 1,403 patients from the Penn Heart Failure Study, a multicenter cohort of chronic systolic HF. Subjects were followed for death, cardiac transplantation, or ventricular assist device placement over a median follow-up of 2 years.ResultsThe sFlt-1 was independently associated with measures of HF severity, including New York Heart Association functional class (p < 0.01) and B-type natriuretic peptide (p < 0.01). Patients in the 4th quartile of sFlt-1 (>379 pg/ml) had a 6.17-fold increased risk of adverse outcomes (p < 0.01). This association was robust, even after adjustment for the Seattle Failure Model (hazard ratio: 2.54, 95% confidence interval [CI]: 1.76 to 2.27, p < 0.01) and clinical confounders including HF etiology (hazard ratio: 1.67, 95% CI: 1.06 to 2.63, p = 0.03). Combined assessment of sFlt-1 and B-type natriuretic peptide exhibited high predictive accuracy at 1 year (area under the receiver-operator characteristic curve: 0.791, 95% CI: 0.752 to 0.831) that was greater than either marker alone (p < 0.01 and p = 0.03, respectively). In contrast, PlGF was not an independent marker of disease severity or outcomes.ConclusionsOur findings support a role for sFlt-1 in the biology of human HF. With additional study, circulating sFlt-1 might emerge as a clinically useful biomarker to assess the influence of vascular remodeling on clinical outcomes.Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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