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

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 I), 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.

Dilated cardiomyopathy

“…In a small study, sST2 was significantly higher in patients with DCM than in controls 197 . sST2 has been found to predict the risk of developing heart failure in patients with DCM in several recent studies 193,[198][199][200] . When combined with NT-proBNP, which is released under conditions of pressure overload and, therefore, is a marker for heart failure, serum sST2 levels provide additive value in predicting sudden death in patients with heart failure and an LVEF ≤45% 201 .…”

Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

“…In the last years, novel cardiac biomarkers have emerged as promising diagnostic tools for the assessment of different cardiovascular disease entities [10,11]. As a result to the complex pathophysiological background of most cardiovascular diseases, a multi-marker approach was reported as most effective for diagnosis, therapy monitoring and risk prediction due to the incorporation of different pathophysiologic processes covered by each respective marker [10,12].…”

Carcinoid heart disease involving the left heart: a case report and biomarker analysis

“…The novel biomarkers sST2, GDF-15, soluble urokinase-type plasminogen activator receptor (suPAR), and H-FABP showed a response in patients with chronic heart failure. 17 In patients with acute myocardial infarction, the biomarkers (sST2, GDF-15, H-FABP, and suPAR) were significantly elevated than in the control groups without coronary heart disease. 14…”

“…13 Recent studies showed significantly elevated biomarkers (sST2, GDF-15, and H-FABP) in patients with acute myocardial infarction or heart failure than in patients without coronary artery disease and good systolic left ventricular function. [13][14][15] An association of these biomarkers and cardiac diseases was recently found, but additional clinical trials are warranted to investigate the clinical significance of these findings. In our patient, we wanted to investigate the concentrations of the biomarkers mentioned earlier, because they portray various pathophysiological pathways of the heart.…”