Abstract 16873: Circulating Multimarker Profile of Patients with Symptomatic Heart Failure Demonstrates Enhanced Fibrotic Degradation and Reduced Extracellular Matrix Remodeling
Introduction: Maladaptive cardiac remodeling involves dysregulated angiogenesis and progressive myocardial fibrosis. Recent evidence suggests potential crosstalk between angiogenic and fibrotic signaling pathways in heart failure. Few studies have simultaneously examined circulating markers of angiogenesis and fibrosis in patients with cardiomyopathy.
Hypothesis: Our hypothesis was that biomarkers of angiogenesis and fibrosis correlate with heart failure severity.
Methods: Blood samples were collected prospectively from 52 consecutive patients with cardiomyopathy (CM); 17 ischemic (iCM) and 35 non-ischemic (niCM); referred for diagnostic cardiac catheterization. 19 patients without cardiovascular risk factors served as controls. We measured serum levels of markers of collagen synthesis [procollagen type I C-peptide (PIP), procollagen type III C-peptide (P3NP)], collagen degradation [carboxyterminal telopeptide of type I collagen (ICTP)], pro-angiogenesis [placental growth factor (PIGF), vascular endothelial growth factor (VEGF)], anti-angiogenesis [soluble Fms-Like Tyrosine Kinase 1 (sFlt1)], extracellular matrix remodeling [matrix metalloprotease-2 (MMP2), matrix metalloprotease-9 (MMP9), tissue inhibitor of matrix metalloprotease-1 (TIMP-1)], aldosterone and transforming growth factor beta 1 (TGFB). Group means were compared by unpaired student’s T test and correlations between markers were assessed by unweighted Spearman coefficients.
Results: Among all 52 CM patients compared to controls, P3NP, ICTP, MMP2, TIMP-1, PIGF and sFlt1 were elevated. The PIP/ICTP, PIGF/sFlt1, and VEGF/sFlt1 ratios were reduced among all CM patients consistent with fibrotic degradation and anti-angiogenesis. Compared to iCM, patients with niCM had lower levels of ICTP, MMP2, MMP9, and PIGF. The PIP/ICTP, MMP-9/TIMP-1 and VEGF/sFlt1 ratios were lower in patients with NYHA class III/IV HF compared to class I/II HF.
Conclusions: In patients with symptomatic heart failure, the circulating biomarker profile is consistent with fibrotic degradation and minimal angiogenesis. Further validation of a multimarker approach in a larger patient cohort may guide patient selection for therapies targeted at fibrosis and angiogenesis.
Author Disclosures: K.J. Morine: None. V. Paruchuri: None. X. Qiao: None. N.N. Mohammad: None. A. McGraw: None. A. Yunis: None. I.Z. Jaffe: None. N.K. Kapur: Speakers Bureau; Modest; Maquet; Abiomed; Heartware. Consultant/Advisory Board; Modest; Thoratec; Abiomed; Cardiac Assist; Maquet. Research Grant; Significant; Cardiac Assist; Abiomed; Maquet.
- © 2014 by American Heart Association, Inc.