Electrical remodelling post cardiac resynchronization therapy in patients with ischemic and non-ischemic heart failure

Crown Copyright © 2018 Published by Elsevier Inc. This manuscript version is made available under the CC-BYNC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (December 2018) in accordance with the publisher’s archiving policyBackground The beneficial effects of cardiac resynchronization therapy (CRT) in heart failure are largely considered to be due to improved mechanical contractility. The contributory role of electrical remodelling is less clear. We sought to evaluate the impact of electrical remodelling in these patients. Methods 33 patients with conventional indications for CRT and with ischemic (ICM) (n = 17) and non-ischemic (NICM) (n = 16) aetiologies for heart failure were prospectively recruited. Functional parameters of peak exercise oxygen consumption (VO2max) and Minnesota quality of life (QOL) score, echocardiographic measures of LV functions and parameters of electrical remodelling, e.g. intrinsic QRS duration (iQRSD), intracardiac conduction times of LV pacing to RV electrocardiogram (LVp-RVegm), were measured at CRT implant and after 6 months. Results Only two electrical parameters predicted functional or symptomatic improvement. LVp-RVegm reduction significantly correlated with improvement in VO2max (r = −0.42, p = 0.03 while reduction in iQRSD significantly correlated with improvement in QOL score (r = 0.39, p = 0.04). The extent of changes in LVp-RVegm and iQRSD was significantly greater in NICM than in ICM patients (p = 0.017 and p = 0.042 for heterogeneity). There was also significant differential impact on QOL score in the NICM relative to the ICM group (p = 0.003) but none with VO2max. On multivariate analysis, only non-ischemic aetiology was a significant determinant of reduction in iQRSD. Conclusion CRT induces potentially beneficial reduction in LVp-RVegm and iQRSD, which are seen selectively in NICM rather than ICM patients. The extent of improvement in these markers is associated with some functional and symptomatic measures of CRT efficacy

Endothelial dysfunction and glycocalyx shedding in heart failure:insights from patients receiving cardiac resynchronisation therapy

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process