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

Peter JIRAK1, Dzeneta FEJZIC1, Vera PAAR1, Bernhard WERNLY1, Rudin PISTULLI2, Ilonka ROHM2, Christian JUNG3, Uta C HOPPE1, P Christian SCHULZE2, Michael LICHTENAUER1, Atilla YILMAZ4, Daniel KRETZSCHMAR2
1 Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Austria
2 Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, University Hospital Jena, Friedrich Schiller University Jena, Germany
3 Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Duesseldorf, Germany
4 Clinic of Internal Medicine II, Elisabeth-Hospital Schmalkalden, Germany
Correspondence to: Daniel KRETZSCHMAR:,
DOI: 10.1038/aps.2017.167
Received: 9 August 2017
Accepted: 29 September 2017
Advance online: 14 December 2017


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.
Keywords: heart failure; cardiomyopathy; Ivabradine; heart rate; biomarker; sST2; GDF-15; suPAR; H-FABP

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