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https://www.readbyqxmd.com/read/28520449/-novelties-in-the-treatment-of-heart-failure
#1
Filip Souček, Jan Novak
Heart failure (HF) is a complex clinical syndrome which is manifested by characteristic symptoms and objective signs of cardiac insufficiency. The incidence of HF, particularly its chronic form, is estimated 0.4-2 % in the central and western Europe, with an increase in higher age groups, affecting 10-20 % of the population aged over 80. With respect to its growing incidence and prevalence, novel modalities of pharmacological and non-pharmacological treatment are being developed in order to improve quality of life and survival of the affected patients...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28482627/improvement-of-pulmonary-arterial-compliance-and-further-pulmonary-hemodynamic-effects-of-serelaxin-in%C3%A2-a%C3%A2-sheep-model
#2
René Schiffner, Juliane Reiche, Martin Schmidt, Christian Jung, Sebastian Walther, Andrey Irintchev, Sabine J Bischoff
BACKGROUND: The influence of the recombinant form of human relaxin-2 (serelaxin) on pulmonary hemodynamics under physiologic conditions have not been the subject of studies in an animal model up until now. METHODS: We therefore utilised the large animal model sheep, convenient in its similar cardiovascular physiology, to investigate said influence. All animals underwent right heart catheterization, a safe and reliable invasive procedure for the assessment of pulmonary hemodynamics, and then received either 30μg/kg serelaxin (n = 11) or saline (n = 13)...
May 2, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28454809/day-vs-night-does-time-of-presentation-matter-in-acute-heart-failure-a-secondary-analysis-from-the-relax-ahf-trial
#3
Peter S Pang, John R Teerlink, Leandro Boer-Martins, Claudio Gimpelewicz, Beth A Davison, Yi Wang, Adriaan A Voors, Thomas Severin, Piotr Ponikowski, Tsushung A Hua, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Gad Cotter, Marco Metra
BACKGROUND: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial. METHODS: This is a post hoc analysis of the RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo, both in addition to usual AHF therapy...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28453725/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#4
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
Aims: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. Methods and results: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28452195/serelaxin-in-addition-to-standard-therapy-in-acute-heart-failure-rationale-and-design-of-the-relax-ahf-2-study
#5
John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Peter S Pang, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A Hua, Thomas Severin, Marco Metra
Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180...
June 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28398333/top-heart-failure-contender-serelaxin-flops
#6
(no author information available yet)
No abstract text is available yet for this article.
April 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28377719/serelaxin-treatment-reduces-oxidative-stress-and-increases-aldehyde-dehydrogenase-2-to-attenuate-nitrate-tolerance
#7
Chen Huei Leo, Dhanushke T Fernando, Lillie Tran, Hooi Hooi Ng, Sarah A Marshall, Laura J Parry
Background: Glyceryl trinitrate (GTN) is a commonly prescribed treatment for acute heart failure patients. However, prolonged GTN treatment induces tolerance, largely due to increased oxidative stress and reduced aldehyde dehydrogenase-2 (ALDH-2) expression. Serelaxin has several vasoprotective properties, which include reducing oxidative stress and augmenting endothelial function. We therefore tested the hypothesis in rodents that serelaxin treatment could attenuate low-dose GTN-induced tolerance. Methods and Results: Co-incubation of mouse aortic rings ex vivo with GTN (10 μM) and serelaxin (10 nM) for 1 h, restored GTN responses, suggesting that serelaxin prevented the development of GTN tolerance...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28370794/short-term-48-hours-intravenous-serelaxin-infusion-has-no-effect-on-myogenic-tone-or-vascular-remodeling-in-rat-mesenteric-arteries
#8
Maria Jelinic, Chen Huei Leo, Sarah A Marshall, Sevvandi N Senadheera, Laura J Parry, Marianne Tare
BACKGROUND: Short-term intravenous serelaxin (recombinant human relaxin-2) infusion enhances endothelium-dependent relaxation in mesenteric arteries. This is initially underpinned by increased nitric oxide (NO) followed by a transition to prostacyclin. The effects of short-term intravenous serelaxin treatment on pressure-induced myogenic tone and vascular remodeling in these arteries are unknown. Therefore, we investigated the effects of serelaxin infusion on pressure-induced myogenic tone and passive mechanical wall properties in mesenteric arteries...
March 31, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/28245243/serelaxin-as-a-potential-treatment-for-renal-dysfunction-in-cirrhosis-preclinical-evaluation-and-results-of-a-randomized-phase-2-trial
#9
Victoria K Snowdon, Neil J Lachlan, Anna M Hoy, Patrick W F Hadoke, Scott I Semple, Dilip Patel, Will Mungall, Timothy J Kendall, Adrian Thomson, Ross J Lennen, Maurits A Jansen, Carmel M Moran, Antonella Pellicoro, Prakash Ramachandran, Isaac Shaw, Rebecca L Aucott, Thomas Severin, Rajnish Saini, Judy Pak, Denise Yates, Neelesh Dongre, Jeremy S Duffield, David J Webb, John P Iredale, Peter C Hayes, Jonathan A Fallowfield
BACKGROUND: Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28217307/worse-prognosis-of-real-world-patients-with-acute-heart-failure-from-the-czech-ahead-registry-in-comparison-to-patients-from-the-relax-ahf-trial
#10
Jindrich Spinar, Jiri Jarkovsky, Lenka Spinarova, Jiri Vitovec, Ales Linhart, Petr Widimsky, Roman Miklik, Kamil Zeman, Jan Belohlavek, Filip Malek, Cestmir Cihalik, Jiri Spac, Marian Felsoci, Petr Ostadal, Ladislav Dusek, Jiri Kettner, Jan Vaclavik, Simona Littnerova, Zdeněk Monhart, Josef Malek, Jiri Parenica
AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial...
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28150186/serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#11
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
BACKGROUND: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib. METHODS: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram. RESULTS: AFib was present in 41.3% of patients...
February 1, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28108636/serelaxin-treatment-promotes-adaptive-hypertrophy-but-does-not-prevent-heart-failure-in-experimental-peripartum-cardiomyopathy
#12
Justus Nonhoff, Melanie Ricke-Hoch, Mirco Mueller, Britta Stapel, Tobias Pfeffer, Martina Kasten, Michaela Scherr, Constantin von Kaisenberg, Johann Bauersachs, Arash Haghikia, Denise Hilfiker-Kleiner
AIMS: Peripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM. METHODS AND RESULTS: In healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter...
January 20, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28073832/reperfusion-therapy-with-recombinant-human-relaxin-2-serelaxin-attenuates-myocardial-infarct-size-and-nlrp3-inflammasome-following-ischemia-reperfusion-injury-via-enos-dependent-mechanism
#13
Juan Valle Raleigh, Adolfo G Mauro, Teja Devarakonda, Carlo Marchetti, Jun He, Erica Kim, Scott Filippone, Anindita Das, Stefano Toldo, Antonio Abbate, Fadi N Salloum
Aims: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. Methods and results: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28067255/serelaxin-treatment-reverses-vascular-dysfunction-and-left-ventricular-hypertrophy-in-a-mouse-model-of-type-1-diabetes
#14
Hooi Hooi Ng, Chen Huei Leo, Darnel Prakoso, Chengxue Qin, Rebecca H Ritchie, Laura J Parry
Serelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28009437/serelaxin-in-clinical-development-past-present-and-future
#15
REVIEW
Elaine Unemori
The availability of highly purified recombinant human relaxin, serelaxin, has allowed clinical trials to be conducted in several indications and the elucidation of its pharmacology in human subjects. These studies have demonstrated that serelaxin has unique haemodynamic properties that are likely to contribute to organ protection and long-term outcome benefits in acute heart failure. Clinical observations support its consideration for therapeutic use in other patient populations, including those with chronic heart failure, coronary artery disease, portal hypertension and acute renal failure...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27972086/budget-impact-analysis-of-standard-care-with-serelaxin-in-treatment-of-patients-with-acute-decompensated-heart-failure
#16
G Tolordava, E Arinina, R Yagudina, A Kulikov
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972082/cost-effectiveness-analysis-of-serelaxin-in-treatment-of-patients-with-acute-decompensated-heart-failure
#17
G Tolordava, E Arinina, R Yagudina, A Kulikov
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27833558/serelaxin-elicits-bronchodilation-and-enhances-%C3%AE-adrenoceptor-mediated-airway-relaxation
#18
Maggie Lam, Simon G Royce, Chantal Donovan, Maria Jelinic, Laura J Parry, Chrishan S Samuel, Jane E Bourke
Treatment with β-adrenoceptor agonists does not fully overcome the symptoms associated with severe asthma. Serelaxin elicits potent uterine and vascular relaxation via its cognate receptor, RXFP1, and nitric oxide (NO) signaling, and is being clinically evaluated for the treatment of acute heart failure. However, its direct bronchodilator efficacy has yet to be explored. Tracheal rings were prepared from male Sprague-Dawley rats (250-350 g) and tricolor guinea pigs, and precision cut lung slices (PCLSs) containing intrapulmonary airways were prepared from rats only...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27825893/evaluating-the-efficacy-safety-and-tolerability-of-serelaxin-when-added-to-standard-therapy-in-asian-patients-with-acute-heart-failure-design-and-rationale-of-relax-ahf-asia-trial
#19
Naoki Sato, Carolyn S P Lam, John R Teerlink, Barry H Greenberg, Hiroyuki Tsutsui, Byung-Hee Oh, Jian Zhang, Martin Lefkowitz, Tsushung A Hua, Thomas Holbro, Miriam Marshood, Xing Li Wang, Junbo Ge
BACKGROUND: Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments...
January 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/27769970/evolving-therapies-for-the-management-of-chronic-and-acute-decompensated-heart-failure
#20
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
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