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inotropics in heart failure

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https://www.readbyqxmd.com/read/28514771/istaroxime-a-potential-anticancer-drug-in-prostate-cancer-exerts-beneficial-functional-effects-in-healthy-and-diseased-human-myocardium
#1
Markus Wallner, Mounir Khafaga, Ewald Kolesnik, Aris Vafiadis, Gerold Schwantzer, Deborah M Eaton, Pero Curcic, Martin Köstenberger, Igor Knez, Peter P Rainer, Martin Pichler, Burkert Pieske, Dirk Von Lewinski
The current gold standard for prostate cancer treatment is androgen deprivation therapy and antiandrogenic agents. However, adverse cardiovascular events including heart failure can limit therapeutic use. Istaroxime, which combines Na+-K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in prostate cancer (PC) models and may also improve cardiac function. Considering the promising anticancer effects of istaroxime, we aimed to assess its functional effects on human myocardium...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28506910/omecamtiv-mecarbil-activates-ryanodine-receptors-from-canine-cardiac-but-not-skeletal-muscle
#2
Péter Nánási, Marta Gaburjakova, Jana Gaburjakova, János Almássy
Due to the limited results achieved in the clinical treatment of heart failure, a new inotropic strategy of myosin motor activation has been developed. The lead molecule of myosin activator agents is omecamtiv mecarbil, which binds directly to the heavy chain of the cardiac β-myosin and enhances cardiac contractility by lengthening the lifetime of the acto-myosin complex and increasing the number of the active force-generating cross-bridges. In the absence of relevant data, the effect of omecamtiv mecarbil on canine cardiac ryanodine receptors (RyR 2) has been investigated in the present study by measuring the electrical activity of single RyR 2 channels incorporated into planar lipid bilayer...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28501522/long-term-effects-of-flosequinan-on-the-morbidity-and-mortality-of-patients-with-severe-chronic-heart-failure-primary-results-of-the-profile-trial-after-24-years
#3
Milton Packer, Bertram Pitt, Jean-Lucien Rouleau, Karl Swedberg, David L DeMets, Lloyd Fisher
OBJECTIVES: The objective of this clinical trial was to evaluate the long-term effects of flosequinan on the morbidity and mortality of patients with severe chronic heart failure. BACKGROUND: Flosequinan was the first oral vasodilator to be used in the clinic to augment the effects of digitalis, diuretics, and angiotensin-converting enzyme inhibitors in heart failure. However, the drug activated neurohormonal systems and exerted both positive inotropic and chronotropic effects, raising concerns about its safety during long-term use...
May 2, 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28496024/a-survival-case-of-fulminant-right-side-dominant-eosinophilic-myocarditis
#4
Keishi Moriwaki, Kaoru Dohi, Taku Omori, Muneyoshi Tanimura, Emiyo Sugiura, Shiro Nakamori, Toshiki Sawai, Kyoko Imanaka-Yoshida, Norikazu Yamada, Masaaki Ito
A 59-year-old Japanese woman was admitted to a nearby hospital with dyspnea and general malaise. Transthoracic echocardiography revealed right ventricular (RV) dilatation with severely reduced systolic function and leftward shift of the intraventricular septum. She was initially diagnosed with acute right heart failure, and fell into cardiogenic shock requiring an intra-aortic balloon pump and inotropic agents. An endomyocardial biopsy (EMB) demonstrated extensive interstitial edema, infiltration of inflammatory cells including numerous eosinophils, and myocytolysis with eosinophil degranulation...
May 12, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28486910/clinical-significance-of-the-sympathetic-nervous-system-in-the-development-and-progression-of-pulmonary-arterial-hypertension
#5
Ru-Xia Liu, Qian Luo, Hui Qiao, Juan Yu, Qian-Long Zhang, Peng Wang, Yong-Gang Cao, Chang-Lin Jiang, Li-Hui Qu
Pulmonary arterial hypertension (PAH) is defined as a complex disease of clinically characterized by elevated pulmonary pressure eventually resulting in right heart failure and premature death. To date, PAH still remains a life-threatening disease. Published evidence suggests that patients with PAH present profound sympathetic nervous system abnormalities and sympathetic activity has been shown to be increased. The mechanism of PAH is still complex and poorly understood. <p> Results: Some data have showed that adrenoceptors are involved in the process of the pathology and have different functions in the progression of PAH followed by heart failure...
January 12, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28476660/%C3%AE-adrenergic-induced-sr-ca-2-leak-is-mediated-by-an-epac-nos-pathway
#6
Laëtitia Pereira, Dan J Bare, Samuel Galice, Thomas R Shannon, Donald M Bers
Cardiac β-adrenergic receptors (β-AR) and Ca(2+)-Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca(2+) signaling. Elevated diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca(2+) leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1)...
May 2, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28465311/accuracy-of-seattle-heart-failure-model-and-heartmate-ii-risk-score-in-non-inotrope-dependent-advanced-heart-failure-patients-insights-from-the-roadmap-study-risk-assessment-and-comparative-effectiveness-of-left-ventricular-assist-device-and-medical-management
#7
REVIEW
David E Lanfear, Wayne C Levy, Josef Stehlik, Jerry D Estep, Joseph G Rogers, Keyur B Shah, Andrew J Boyle, Joyce Chuang, David J Farrar, Randall C Starling
BACKGROUND: Timing of left ventricular assist device (LVAD) implantation in advanced heart failure patients not on inotropes is unclear. Relevant prediction models exist (SHFM [Seattle Heart Failure Model] and HMRS [HeartMate II Risk Score]), but use in this group is not established. METHODS AND RESULTS: ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) is a prospective, multicenter, nonrandomized study of 200 advanced heart failure patients not on inotropes who met indications for LVAD implantation, comparing the effectiveness of HeartMate II support versus optimal medical management...
May 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28451448/quality-of-life-and-long-term-mortality-in-patients-with-advanced-chronic-heart-failure-treated-with-intermittent-low-dose-intravenous-inotropes-in-an-outpatient-setting
#8
Fernando Chernomordik, Dov Freimark, Michael Arad, Michael Shechter, Shlomi Matetzky, Yulia Savir, Nir Shlomo, Amir Peled, Ilan Goldenberg, Yael Peled
AIMS: There are limited data on the effect of low-dose, intermittent inotropic therapy in an outpatient setting on the quality of life (QOL) in patients with advanced refractory heart failure (HF) symptoms. We aimed to analyse the effect of this treatment modality on QOL and subsequent survival. METHODS AND RESULTS: The study population comprised 287 consecutive patients with advanced refractory HF symptoms who were treated with low-dose, intravenous intermittent inotropic therapy in the HF Day Care Service at Sheba Medical Centre between September 2000 and September 2012...
May 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28449477/continuous-administration-of-recombinant-human-b-type-natriuretic-peptide-can-improve-heart-and-renal-function-in-patients-after-cardiopulmonary-bypass-surgery
#9
Shiguan Le, Jian Xiao, Wei Li, Jing Wang, Qing Wang, Wang Xi, Jibin Xu, Zhinong Wang
BACKGROUND: Any cardiac surgery under cardiopulmonary bypass (CPB) will induce ischemia-reperfusion injury and systematic inflammatory response, which may lead to exacerbation. Conventional therapy strategy is to use inotropes, diuretics and vasodilator drugs, yet, the therapeutic effects of which need to be improved. Recombinant human B-type natriuretic peptide (rhBNP) has been shown to be efficacious in the treatment of acute decompensated heart failure and acute myocardial infarction...
March 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28376837/heartmate-3-fully-magnetically-levitated-left-ventricular-assist-device-for-the-treatment-of-advanced-heart-failure-1%C3%A2-year-results-from-the-ce-mark-trial
#10
Thomas Krabatsch, Ivan Netuka, Jan D Schmitto, Daniel Zimpfer, Jens Garbade, Vivek Rao, Michiel Morshuis, Friedhelm Beyersdorf, Silvana Marasco, Laura Damme, Yuriy Pya
BACKGROUND: The HeartMate 3 Left Ventricular Assist System (LVAS) (St. Jude Medical Inc., St Paul, MN) with full magnetic levitation allows for wide and consistent blood flow paths and an artificial pulse designed for enhanced hemocompatibility. The HeartMate 3 received market approval in the European Union in 2015 following completion of a multicenter study. After reaching the 6-month study endpoint, patients continue to be followed for 2 years with the 1-year results presented herein...
April 4, 2017: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/28371822/elabela-apj-axis-protects-from-pressure-overload-heart-failure-and-angiotensin-ii-induced-cardiac-damage
#11
Teruki Sato, Chitose Sato, Ayumi Kadowaki, Hiroyuki Watanabe, Lena Ho, Junji Ishida, Tomokazu Yamaguchi, Akinori Kimura, Akiyoshi Fukamizu, Josef M Penninger, Bruno Reversade, Hiroshi Ito, Yumiko Imai, Keiji Kuba
Aims: Elabela/Toddler/Apela (ELA) has been identified as a novel endogenous peptide ligand for APJ/Apelin receptor/Aplnr. ELA plays a crucial role in early cardiac development of zebrafish as well as in maintenance of self-renewal of human embryonic stem cells. Apelin was the first identified APJ ligand, and exerts positive inotropic heart effects and regulates the renin-angiotensin system. The aim of this study was to investigate the biological effects of ELA in the cardiovascular system...
June 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28371247/ivabradine-current-and-future-treatment-of-heart-failure
#12
REVIEW
Lene Thorup, Ulf Simonsen, Daniela Grimm, Elise R Hedegaard
In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm...
April 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28348102/acute-peritoneal-dialysis-in-patients-with-acute-kidney-injury
#13
Seong Cho, Sung-Rok Kim, Yu-Ji Lee
♦ Background: The purpose of this study was to evaluate the efficacy, complications, and mortality rate associated with acute peritoneal dialysis (PD) in patients with acute kidney injury (AKI). ♦ Methods: A total of 75 patients who were treated at Samsung Changwon Hospital between February 2005 and March 2016 were included in the study sample. The outcomes included in-hospital survival, renal recovery, metabolic and fluid control rates, and technical success rates. ♦ Results: Refractory heart failure was the most frequent cause of acute PD (49...
March 27, 2017: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
https://www.readbyqxmd.com/read/28341544/echocardiographic-assessment-of-right-ventricular-function-in-routine-practice-which-parameters-are-useful-to-predict-one-year-outcome-in-advanced-heart-failure-patients-with-dilated-cardiomyopathy
#14
Takayuki Kawata, Masao Daimon, Koichi Kimura, Tomoko Nakao, Seitetsu L Lee, Megumi Hirokawa, Tomoko S Kato, Masafumi Watanabe, Yutaka Yatomi, Issei Komuro
BACKGROUND: Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM)...
March 21, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28336302/-vasopressors-and-inotropes-use-in-pediatrics
#15
Adrián García-Canales, Rocío Alejandra Peña-Juárez, Luz de María Sandoval-Franco
The cardiovascular system is a dynamic system whose function is to ensure adequate delivery of oxygen, nutrients and hormones to the tissues, necessary for cell metabolism, also synthesizes and modifies vasoactive components to regulate vascular tone and myocardial function. These components have become critical in the management of pediatric patients in critical condition with heart failure and shock which has proven its beneficial effects, however its use and abuse brings harmful effects, increase mortality, associated with arrhythmias and increase myocardial oxygen consumption favoring the presence of ischemia, therefore is necessary to know the mechanism of action and indications of these drugs to minimize the harmful effects...
March 20, 2017: Archivos de Cardiología de México
https://www.readbyqxmd.com/read/28325140/vitamins-in-heart-failure-friend-or-enemy
#16
George Georgiopoulos, Christina Chrysohoou, Georgia Vogiatzi, Nikolaos Magkas, Ippokratis Bournelis, Sofia Bampali, Damien Gruson, Dimitris Tousoulis
BACKGROUND: The failing heart is characterized by a depleted metabolic energy reserve and the up-regulation of several molecular mechanisms leading to cardiac hypertrophy, inflammation, fibrosis, angiogenesis, and apoptosis. Dietary or non-dietary supplementation of vitamins could potentially benefit energy balance. OBJECTIVE: The objective of the present study was to evaluate all available information on vitamins supplementation in patients with chronic HF for possible beneficial effect on metabolic, inotropic, chronotropic and hemodynamic indices...
March 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28315072/direct-myosin-activation-by-omecamtiv-mecarbil-for-heart-failure-with-reduced-ejection-fraction
#17
Mitchell A Psotka, John R Teerlink
Myosin is the indispensable molecular motor that utilizes chemical energy to produce force for contraction within the cardiac myocyte. Myosin activity is gated by intracellular calcium levels which are regulated by multiple upstream signaling cascades that can be altered for clinical utility using inotropic medications. In contrast to clinically available cardiac inotropes, omecamtiv mecarbil is a novel direct myosin activator developed to augment left ventricular systolic function without the undesirable secondary effects of altered calcium homeostasis...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28295363/angiotensin-ii-activates-cav-1-2-ca-2-channels-through-%C3%AE-arrestin2-and-casein-kinase-2-in-mouse-immature-cardiomyocytes
#18
Toshihide Kashihara, Tsutomu Nakada, Katsuhiko Kojima, Toshikazu Takeshita, Mitsuhiko Yamada
KEY POINTS: Angiotensin II (AngII) is crucial in cardiovascular regulation in perinatal mammalians. Here we show that AngII increases twitch Ca(2+) transients of mouse immature but not mature cardiomyocytes by robustly activating CaV 1.2 L-type Ca(2+) channels through a novel signalling pathway involving angiotensin type 1 (AT1 ) receptors, β-arrestin2 and casein kinase 2. A β-arrestin-biased AT1 receptor agonist, TRV027, was as effective as AngII in activating L-type Ca(2+) channels...
March 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28276970/advances-in-chemical-pharmacotherapy-for-managing-acute-decompensated-heart-failure
#19
REVIEW
Srikanth Yandrapalli, Sohaib Tariq, Wilbert S Aronow
Acute decompensated heart failure (ADHF) contributes largely to the burden of heart failure and is associated with a poorer prognosis. Although numerous clinical trials evaluated the benefit of newer medications for ADHF, most of them were not successful. Areas covered: This review focusses on the updates on recent developments in chemical pharmacotherapy for the management of ADHF. A MEDLINE search for relevant review articles and original investigations on newer drugs for ADHF provided us with necessary literature...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28274560/antithrombin-iii-is-associated-with-acute-liver-failure-in-patients-with-end-stage-heart-failure-undergoing-mechanical-circulatory-support
#20
Judith Hoefer, Hanno Ulmer, Juliane Kilo, Raimund Margreiter, Michael Grimm, Peter Mair, Elfriede Ruttmann
OBJECTIVE: There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. METHODS: A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria...
February 9, 2017: Journal of Thoracic and Cardiovascular Surgery
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