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Influences of Ivabradine treatment on serum levels of cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in patients with chronic heart failure

	author = {Peter JIRAK and Dzeneta FEJZIC and Vera PAAR and Bernhard WERNLY and Rudin PISTULLI and Ilonka ROHM and Christian JUNG and Uta C HOPPE and P Christian SCHULZE and Michael LICHTENAUER and Atilla YILMAZ and Daniel KRETZSCHMAR},
	title = {Influences of Ivabradine treatment on serum levels  of cardiac biomarkers sST2, GDF-15, suPAR and  H-FABP in patients with chronic heart failure},
	journal = {Acta Pharmacologica Sinica},
	volume = {39},
	number = {7},
	year = {2018},
	keywords = {},
	abstract = {Chronic heart failure (CHF) represents a major cause of hospitalization and death.  Recent evidence shows that novel biomarkers such as soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) are correlated with inflammatory and ischemic responses in CHF patients.  In this study we examined the effects of Ivabradine that inhibited the hyperpolarization-activated cyclic nucleotide-gated channel (HCN channel, also called funny current If), thereby leading to selective heart rate reduction and improved myocardial oxygen supply on the cardiac biomarkers sST2, GDF-15, suPAR and H-FABP in 50 CHF patients at the University Hospital of Jena.  Patients were divided into three groups based on the etiology of CHF: dilated cardiomyopathy (DCM, n=20), ischemic cardiomyopathy (ICM, n=20) and hypertensive cardiomyopathy (HCM, n=10).  The patients were administered Ivabradine (5 mg, bid for 3 months, and 7.5 mg bid for further 3 months).  Analyses of cardiovascular biomarkers were performed at baseline as well as at 3- and 6-month follow-ups. At 6-month follow-up, GDF-15 levels were significantly reduced compared to baseline levels (P=0.0215), indicating a reduction in the progress of cardiac remodeling.  H-FABP concentration was significantly lower in DCM patients compared to ICM (1.89 vs 3.24 µg/mL) and HCM patients (1.89 vs 3.80 µg/mL), and decreased over the 6-month follow-up (P=0.0151).  suPAR median levels remained elevated, implying major ongoing inflammatory processes.  As shown by significant decreases in GDF-15 and H-FABP levels, a reduction in ventricular remodeling and sub-clinical ischemia could be assumed.  However, markers of hemodynamic stress (sST2) and inflammation (suPAR) showed no change or progression after 6 months of Ivabradine treatment in CHF patients.  Further studies are necessary to validate the clinical applicability of these novel cardiovascular biomarkers.},
	issn = {1745-7254},	url = {}