Background Sacubitril/Valsartan has been shown to improve symptoms and outcomes in patients with heart failure (HF) reduced ejection fraction in a single large randomised controlled trial. However, real-world data on its effect is limited. Purpose Our centre operates a dedicated HF clinic for the initiation and titration of Sacubitril/Valsartan in suitable patients. We report on patient tolerability and incidence of adverse effects. We also assessed change in New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) post-treatment, as well as HF hospitalisation and mortality at 6 months. Methods We conducted a retrospective review of all patients seen in the clinic between January 2016 to January 2019. Patient demographics and pre-initiation treatments were recorded. We compared NYHA class and LVEF category as measured by echocardiography, at initiation and post-titration to the maximum tolerated dose. Data on HF admissions were obtained from electronic hospital records and mortality from a national database. Results A total of 179 patients were initiated on Sacubitril/Valsartan and included in the study. Mean age was 71 years (41–90), and 138 (77%) were male. Half of the patient cohort (89) had an ischaemic aetiology. Prior to initiation, all patients were established on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Almost all were on a beta-blocker (99%) and mineralocorticoid receptor antagonist (98%). 56 patients (31%) had a Cardiac Resynchronisation Therapy (CRT) device and 31 (17%) had an Implantable Cardioverter-Defibrillator (ICD). Only 4 patients (2%) had to discontinue treatment completely due to an adverse reaction. Among them, 3 patients sustained an acute kidney injury (AKI) while 1 patient had increased breathlessness. 40 patients (22%) reported symptomatic hypotension which required dose reduction. 7 patients (4%) sustained an AKI. 2 patients reported a rash and 1 patient reported nausea. Figure 1 shows the change in NYHA class after establishment on Sacubitril/Valsartan. Data on change in LVEF post establishment of Sacubitril/Valsartan was available in 124 patients and is shown in figure 2. A total of 133 patients had completed titration of treatment by July 2018 and included in the analysis of 6-month outcome. 13 patients had one HF hospitalisation and all-cause mortality was 4.5% (6 patients). Only 1 patient had heart failure documented as the primary cause of death. Change in NYHA class and LVEF Conclusion In our cohort of well treated HF patients with reduced ejection fraction, 40% of patients experienced an improvement in NYHA class after establishment on Sacubitril/Valsartan while 35% of patients also experienced a significant improvement in LVEF. Treatment was well tolerated and the discontinuation rate was low when managed in a dedicated HF clinic focused on initiation of Sacubitril/Valsartan.
P38-mitogen activated protein kinases (of which there are 4 isoforms; α, β, γ and δ) are serine/threonine kinases that are activated in response to stress stimuli. Classically studies have only examined the role of p38α in the myocardium. However, p38γ is also highly and preferentially expressed in the myocardium. The aim of this study is to investigate the role of p38γ in the progression of pathological hypertrophy following abdominal aortic banding. Comparisons of cardiac function and structure of wild type (WT) and p38γ knock out (KO) mice in response to abdominal aortic banding found that KO mice develop less ventricular hypertrophy than their corresponding WT controls, and have preserved cardiac function. We observed that basal p38γ myocardial staining is primarily localised at the membranes and throughout the cytoplasm. Following aortic constriction nuclear staining of p38γ incre ases but no accumulation of p38α is observed. This suggests that the two isoforms play distinct roles in the heart.To elucidate its signaling pathway and identify endogenous substrates of p38γ we have generated an analogue sensitive p38γ, which is mutated at a gatekeeper residue, to specifically track endogenous substrates in the myocardium. The mutation allows only the mutant kinase, but not WT kinases, to utilise analogues of ATP that are expanded at the N-6 position and contain a visible tag on the γ-phosphate. Transfer of this tag to substrates allows subsequent isolation and identification. Using this technique we have been able to identify, amongst other substrates, Cypher and Calpastatin as novel targets of p38γ.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.