Mariarosaria De Luca, Giorgio Bosso, Antonio Valvano, Vincenzo Guardasole, Amodio Botta, Vincenzo Carbone, Giovanni Carella, Andrea Del Buono, Giuseppe Di Giovanni, Biagio Fimiani, Franco Guarnaccia, Emanuela Lapice, Emilia Martedì, Giuseppe Memoli, Domenica Oliva, Geremia Romano, Antonio Cittadini, Giovanni Battista Zito, Ugo Oliviero
SCODIAC was a pilot study which revealed an increasing use of SGLT2i in 123 outpatients affected with Heart Failure (HF) and Type 2 Diabetes Mellitus. SCODIAC-II study, the second phase of the program, has been carried out to determine diagnostic and therapeutic pathways in a larger group of patients and to verify whether the use of innovative antidiabetic therapies could modify echocardiographic parameters and cardiovascular therapies. 406 HF-diabetic patients, referred to Cardiologists and Diabetologists of pertaining healthcare districts in Campania, were enrolled in this retrospective study and divided in Group A, composed of 136 patients with preserved Ejection Fraction (HF-pEF)(> 45%) and Group B, formed of 270 patients with reduced EF (HF-rEF)(≤ 45%)...
October 17, 2020: Internal and Emergency Medicine
Jason Galo, Diego Celli, Rosario Colombo
Sacubitril/valsartan is a new medication approved for the treatment of heart failure with reduced ejection fraction. While the drug failed to meet the primary endpoint in patients with heart failure with preserved ejection fraction in the PARAGON-HF trial, improvements were noted in several secondary endpoints. Valsartan is an angiotensin receptor blocker and sacubitril is a neprilysin inhibitor. Neprilysin is postulated to have a role in the degradation of beta-amyloid in the brain; therefore, sacubitril could theoretically increase beta-amyloid plaque deposition in the brain and potentially increase the risk of Alzheimer's disease...
October 16, 2020: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Bee Ling Kelly Chng, Jin Shing Hon, Hong Chan, Yiliang Zheng, Fei Gao, Loon Yee Louis Teo, Kheng Leng David Sim
BACKGROUND: The Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION) and PIONEER-HF trials have shown that sacubitril/valsartan can be initiated early and safely in patients with heart failure with reduced ejection fraction (HFrEF) shortly after an acute heart failure episode during hospitalisation. However, it is unclear whether the results can be translated to Asian populations. Hence, this real-world study was designed with the aim of comparing the safety and tolerability of sacubitril/valsartan initiation in an inpatient versus outpatient setting...
October 5, 2020: Heart, Lung & Circulation
Michele Emdin, Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Georgios Georgiopoulos, Luigi Francesco Saccaro, Carlo Mario Lombardi, Claudio Passino, Elisabetta Cerbai, Marco Metra, Michele Senni
The significant morbidity and mortality associated with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. Reduced cyclic guanosine monophosphate levels contribute to HF progression. Among molecules modulating the nitric oxide (NO)-GMP-phosphodiesterase (PDE) pathway, the evaluation of nitrates, synthetic natriuretic peptides (NP), and NP analogs has yielded mixed results. Conversely, sacubitril/valsartan, combining NP degradation inhibition through neprilysin and angiotensin receptor blockade, has led to groundbreaking findings in HFrEF...
October 13, 2020: Journal of the American College of Cardiology
Jingwen Hu, Yucheng Wu, Xiujuan Zhou, Xiaozhi Wang, Wanying Jiang, Junyu Huo, Qijun Shan
This study aimed at analyzing the clinical profile of real-world patients with heart failure with reduced ejection fraction (HFrEF) and evaluating the safety and efficacy of sacubitril/valsartan among Asian patients in daily practice. We conducted a single-center prospective observational cohort study of HFrEF patients treated with sacubitril/valsartan from September 2017 to September 2018 with a follow-up of 6 months. The mean (SD) age of the 110 patients enrolled was 59.7 ± 13.3, 85 (77.3%) were men and 41 (37...
October 2020: Journal of Cardiovascular Pharmacology
Michael Boettcher, Stephanie Loewen, Mireille Gerrits, Corina Becker
BACKGROUND: Vericiguat, a direct stimulator of soluble guanylate cyclase, has been developed as a first-in-class therapy for symptomatic chronic heart failure (HF) and ejection fraction < 45%. METHODS: Safety, pharmacodynamic (PD), and pharmacokinetic (PK) interactions between vericiguat and drugs used in HF (sacubitril/valsartan [SV] and aspirin [acetylsalicylic acid]) or with a narrow therapeutic index (warfarin) were evaluated in three phase I studies...
October 8, 2020: Clinical Pharmacokinetics
Małgorzata Lelonek
Heart failure with preserved ejection fraction (HFpEF) is an increasingly common condition, particularly with the aging of the population. HFpEF is associated with high morbidity and mortality, with poor quality of life and high rate of heart failure rehospitalization. In HFpEF previous studies failed to reach a positive outcome. There is currently no approved treatment for HFpEF. The overall the PARAGON-HF trial population showed a 13% reduction in the primary endpoint (cardiovascular death and total heart failure hospitalizations) with sacubitril/valsartan treatment vs valsartan, which was of borderline statistical significance...
October 6, 2020: Kardiologia Polska
Sashiananthan Ganesananthan, Nisar Shah, Parin Shah, Hossam Elsayed, Julie Phillips, Ann Parkes, Angharad Morgan, Zaheer Yousef
BACKGROUND: Sacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables. METHODS AND RESULTS: From June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration...
October 2020: Open Heart
Nasrien E Ibrahim, Ileana L Piña, Alexander Camacho, Devavrat Bapat, G Michael Felker, Alan S Maisel, Javed Butler, Margaret F Prescott, Cheryl A Abbas, Scott D Solomon, James L Januzzi
Background : Among patients with heart failure and reduced ejection fraction (HFrEF, left ventricular [LV] EF ≤40%) sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardiac remodeling. Data regarding racial and ethnic differences in response to S/V are lacking. Methods : This was an analysis from the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure Study. Longitudinal changes in N-terminal pro B-type natriuretic peptide (NT-proBNP), cardiac reverse remodeling, and health status scores were compared between groups using multivariate latent growth curve modeling...
October 3, 2020: Circulation. Heart Failure
Dominique Croteau, Fuzhong Qin, Jordan M Chambers, Ethan Kallick, Ivan Luptak, Marcello Panagia, David R Pimentel, Deborah A Siwik, Wilson S Colucci
Mice with obesity and metabolic heart disease (MHD) due to a high-fat, high-sucrose diet were treated with placebo, a clinically relevant dose of sacubitril (SAC)/valsartan (VAL), or an equivalent dose of VAL for 4 months. There were striking differences between SAC/VAL and VAL with regard to: 1) diastolic dysfunction; 2) interstitial fibrosis; and to a lesser degree; 3) oxidative stress-all of which were more favorably affected by SAC/VAL. SAC/VAL and VAL similarly attenuated myocardial hypertrophy and improved myocardial energetics...
September 2020: JACC. Basic to Translational Science
Kieran F Docherty, Muthiah Vaduganathan, Scott D Solomon, John J V McMurray
Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms among patients with chronic heart failure with reduced ejection fraction compared to enalapril, the gold standard angiotensin-converting enzyme inhibitor. In the 5 years since the publication of the results of PARADIGM-HF, further insight has been gained into integrating a neprilysin inhibitor into a comprehensive multidrug regimen, including a renin-angiotensin aldosterone system (RAS) blocker...
October 2020: JACC. Heart Failure
Daniele Masarone, Vittoria Errigo, Enrico Melillo, Fabio Valente, Rita Gravino, Marina Verrengia, Ernesto Ammendola, Rossella Vastarella, Giuseppe Pacileo
BACKGROUND: right ventricle-pulmonary artery (RV-PA) coupling assessed by measuring the tricuspid anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio has been recently proposed as an early marker of right ventricular dysfunction in patients with heart failure with a reduced ejection fraction (HFrEF). METHODS: As the effects of sacubitril/valsartan therapy on RV-PA coupling remain unknown, this study aimed to analyse the effect of this drug on TAPSE/PASP in patients with HFrEF...
September 29, 2020: Journal of Clinical Medicine
Philip Houck, Hari Dandapantula, Donna Wilkinson
Objective The purpose of this paper is to assign a dollar value to life-saving medication, surgical procedures, and medical devices. The knowledge of the wide variation in the cost of drugs, surgery, and devices allows providers and patients to choose higher-valued therapies. Cost is a significant barrier to health. The current reimbursement system is complicated, representing a significant barrier to saving lives by promoting health disparity. Background The cost analysis of heart failure therapies is an important tool in the education of physicians, patients, and vendors of the intervention...
August 27, 2020: Curēus
N N Nalivaeva, I A Zhuravin, A J Turner
Neprilysin (NEP) is an integral membrane-bound metallopeptidase with a wide spectrum of substrates and physiological functions. It plays an important role in proteolytic processes in the kidney, cardiovascular regulation, immune response, cell proliferation, foetal development etc. It is an important neuropeptidase and amyloid-degrading enzyme which makes NEP a therapeutic target in Alzheimer's disease (AD). Moreover, it plays a preventive role in development of cancer, obesity and type-2 diabetes. Recently a role of NEP in COVID-19 pathogenesis has also been suggested...
September 25, 2020: Mechanisms of Ageing and Development
John R Teerlink, Rafael Diaz, G Michael Felker, John J V McMurray, Marco Metra, Scott D Solomon, Kirkwood F Adams, Inder Anand, Alexandra Arias-Mendoza, Tor Biering-Sørensen, Michael Böhm, Diana Bonderman, John G F Cleland, Ramon Corbalan, Maria G Crespo-Leiro, Ulf Dahlström, Rafael Diaz, Luis E Echeverria Correa, James C Fang, Gerasimos Filippatos, Cândida Fonseca, Eva Goncalvesova, Assen R Goudev, Jonathan G Howlett, David E Lanfear, Mayanna Lund, Peter Macdonald, Vyacheslav Mareev, Shin-Ichi Momomura, Eileen O'Meara, Alexander Parkhomenko, Piotr Ponikowski, Felix J A Ramires, Pranas Serpytis, Karen Sliwa, Jindrich Spinar, Thomas M Suter, Janos Tomcsanyi, Hans Vandekerckhove, Dragos Vinereanu, Adriaan A Voors, Mehmet B Yilmaz, Faiez Zannad, Lucie Sharpsten, Jason C Legg, Siddique A Abbasi, Claire Varin, Fady I Malik, Christopher E Kurtz
AIMS: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. METHODS AND RESULTS: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37...
September 27, 2020: European Journal of Heart Failure
Robert J Mentz, Haolin Xu, Emily C O'Brien, Laine Thomas, Tamas Alexy, Bhanu Gupta, Juan Vilaro, Anuradha Lala, Adam D DeVore, Ravi Dhingra, Alexandros Briasoulis, Marc A Simon, Josef Stehlik, Jo E Rodgers, Shannon M Dunlay, Martha Abshire, Quinn S Wells, Kurt G Barringhaus, Peter M Eckman, Brian D Lowes, Johana Espinoza, Rosalia Blanco, Xian Shen, Carol I Duffy, Adrian F Hernandez
BACKGROUND: In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) vs. enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice. METHODS: PROVIDE-HF was a prospective study within a national research network (PCORnet) of HFrEF outpatients recently initiated on sacubitril/valsartan vs. controls with recent ACE-I/ARB initiation/dose change...
September 24, 2020: American Heart Journal
Raj M Khandwalla, Daniel Grant, Kade Birkeland, J Thomas Heywood, Emmanuel Fombu, Robert L Owens, Steven R Steinhubl
BACKGROUND: AWAKE-HF evaluated the effect of the initiation of sacubitril/valsartan versus enalapril on activity and sleep using actigraphy in patients who have heart failure with reduced ejection fraction (HFrEF). METHODS: In this randomized, double-blind study, patients with HFrEF (n = 140) were randomly assigned to sacubitril/valsartan or enalapril for 8 weeks, followed by an 8-week open-label phase with sacubitril/valsartan. Primary endpoint was change from baseline in mean activity counts during the most active 30 min/day at week 8...
September 26, 2020: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Hongzhou Zhang, Tieqiu Huang, Wen Shen, Xiuxiu Xu, Pingping Yang, Dan Zhu, Haiyang Fang, Hongbing Wan, Tao Wu, Yanqing Wu, Qinghua Wu
AIMS: Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril-valsartan in patients with HF are controversial. We performed a meta-analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril-valsartan, valsartan, and enalapril in patients with HF. METHODS AND RESULTS: We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials...
September 25, 2020: ESC Heart Failure
Santiago Jiménez-Marrero, Cristina Enjuanes, Sergi Yun, Josep Comín-Colet
Background: Chronic heart failure (CHF) is a growing epidemic. The cornerstone of pharmacological therapy in CHF patients with reduced ejection fraction (HFrEF) is the inhibition of the renin-angiotensin-aldosterone system (RAAS). One of the adverse effects of RAAS blockade is the development of hyperkalaemia, which often limits the optimization of recommended, Class I treatments. In this context, potassium binders patiromer or sodium zirconium cyclosilicate (ZS-9) provide an opportunity to optimize the pharmacological management of these patients...
August 2020: European Heart Journal. Case Reports
Renato De Vecchis, Andrea Paccone
Anthracyclines are the cornerstone of treatment for many solid and hematological cancers such as breast cancer or lymphoma for the past 50 years. Nevertheless, in a non-negligible proportion of patients, they elicit dilated cardiomyopathy as a side effect, which causes in turn cardiac decompensation. Conversely, for some years, sacubitril/valsartan has been proposed as a new therapeutic paradigm for all varieties of heart failure with reduced left ventricular ejection fraction, due to its balanced enhancement of natriuretic peptides' properties coupled with a blocking effect on the AT1 angiotensin receptors...
2020: SAGE Open Medical Case Reports
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