Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin

Abstract

Background: Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF. Methods and results: Fourteen patients (9 men, 5 women, mean age 68 ± 13 years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48 h and 9 ± 2 months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age-and sex-matched subjects served as controls.In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47 ± 0.2 vs. 0.97 ± 0.3 ng/mL, p < 0.001; NT-proBNP: 2007 ± 114 vs. 229 ± 72 pmol/L, p < 0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9 ± 2 months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99 ± 0.1 vs. 0.47 ± 0.2 ng/mL, p < 0.001) and decrease in NT-proBNP (938 ± 591 vs. 2007 ± 114 pmol/L, p < 0.05). Conclusions: Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.

Apelin

“…Plasma apelin levels increase in interventions, such as cardiac resynchronization therapy and LV-assisted device implantation, which could improve LV function. [30][31][32] These data suggest that apelin has a cardioprotective function, which is consistent with our observation that plasma apelin is reduced compared with healthy controls in the postinfarct period. Therefore, apelin may have a potential therapeutic function for apelin upregulation following AMI.…”

International Union of Basic and Clinical Pharmacology. LXXIV. Apelin Receptor Nomenclature, Distribution, Pharmacology, and Function

“…Overall, plasma apelin seems to rise in early heart failure (Chen et al, 2003) but to normalize or decrease in later stages (Chen et al, 2003;Chong et al, 2006;Miettinen et al, 2007). Treatments such as chronic resynchronization therapy and placement of a left ventricular assist device increase apelin peptide levels (Chen et al, 2003;Francia et al, 2007). Apelin receptor mRNA was found to be decreased in left ventricle from patients with idiopathic dilated cardiomyopathy (Földes et al, 2003).…”

Role of adipokines in cardiovascular disease

“…Decreased plasma levels of apelin have been observed in patients with lone atrial fibrillation (Ellinor et al 2006) and chronic heart failure (Chong et al 2006) in which cardiac resynchronisation therapy helps to improve them (Francia et al 2007). Hypoxia up-regulates apelin synthesis in cardiovascular tissues (Ronkainen et al 2007) as does ischaemic cardiomyopathy in rats (Atluri et al 2007).…”