Ventricular remodelling following ischaemic events: A biochemical, neurohormonal & functional study

Abstract Not Provided

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

Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy

© 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-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 (January 2019) in accordance with the publisher’s archiving policyBackground Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. Methods Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. Results Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). Conclusions The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up

Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery.

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.RNA-sequencing was undertaken at the CRUK Cambridge Institute Genomics Core. Cell sorting was performed at the NIHR Cambridge BRC Cell Phenotyping Hub. PL received a Society for Endocrinology Early Career Grant. GR received an Addenbrooke’s Charitable Trust / Evelyn Trust Cambridge Clinical Research Fellowship [16-69] and a Royal College of Surgeons Research Fellowship. The work was partially funded by a project grant from the EFSD/Novo Nordisk Programme for Diabetes Research in Europe

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

Information Theory and Atrial Fibrillation (AF): A Review

Atrial Fibrillation (AF) is the most common cardiac rhythm disorder seen in hospitals and in general practice, accounting for up to a third of arrhythmia related hospitalizations. Unfortunately, AF treatment is in practice complicated by the lack of understanding of the fundamental mechanisms underlying the arrhythmia, which makes detection of effective ablation targets particularly difficult. Various approaches to AF mapping have been explored in the hopes of better pinpointing these effective targets, such as Dominant Frequency (DF) analysis, complex fractionated electrograms (CFAE) and unipolar reconstruction (FIRM), but many of these methods have produced conflicting results or require further investigation. Exploration of AF using information theoretic-based approaches may have the potential to provide new insights into the complex system dynamics of AF, whilst also providing the benefit of being less reliant on empirically derived definitions in comparison to alternate mapping approaches. This work provides an overview of information theory and reviews its applications in AF analysis, with particular focus on AF mapping. The works discussed in this review demonstrate how understanding AF from a signal property perspective can provide new insights into the arrhythmic phenomena, which may have valuable clinical implications for AF mapping and ablation in the future

Institutional variation in quality of cardiovascular implantable electronic device implantation

IN RESPONSE: Dr. Emami and colleagues suggest that our use of administrative data overestimated the risk for CIED complications. However, their conclusion is not supported by our findings or the broader literature. Clinical studies have consistently shown a high rate of CIED complications despite not using administrative data. In Australia and New Zealand, multicenter clinical audits report a 3.9% to 4.6% rate of in-hospital complications. This rate increases to 11.9% (with 7.9% requiring reoperation) when early postdischarge complications are included