Biomarkers to Predict the Response to Cardiac Resynchronization Therapy

Ward Heggermont; Angelo Auricchio; Marc Vanderheyden


Europace. 2019;21(11):1609-1620. 

In This Article

Adrenergic Signalling

Intermedin (adrenomedullin-2) is a member of the calcitonin gene-related peptide (CGRP) family of hormones, which play a role in the regulation of cardiovascular homeostasis, anti-diuresis, anti-natriuresis, and prolactin release.[30] Strikingly, also auto-antibodies for β1-adrenergic and muscarinic receptors are found in HF patients throughout. In a retrospective analysis of 73 HF patients[31] (NYHA II–III–IV, LVEF <35%), who all received CRT-D therapy, those auto-antibodies were measured in CRT responders and non-responders. A significantly higher percentage of patients with β1-positivity was observed in the non-responders (57% vs. 27%; P = 0.004), whereas antimuscarinic antibodies were not differentially regulated. The adrenergic signalling cascade is of great importance in HF: the blunted myocardial contractile reserve is partially caused by a down-regulation of β1-adrenoreceptors in the myocardium. In a preliminary study involving a limited number of patients, the proof-of-concept was shown that successful CRT pacing resulted in a significant up-regulation of β1-adrenoreceptor gene expression in the myocardium.[32] Pezzali et al. showed that gene polymorphisms in beta-adrenergic receptors may influence the LV reverse remodelling after CRT, and possibly also the incidence of malignant ventricular tachyarrhythmias.[33]