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1.
Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.
Psotka, MA, Gottlieb, SS, Francis, GS, Allen, LA, Teerlink, JR, Adams, KF, Rosano, GMC, Lancellotti, P
Journal of the American College of Cardiology. 2019;(18):2345-2353
Abstract
The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.
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2.
Inotropes and vasopressors use in cardiogenic shock: when, which and how much?
Levy, B, Buzon, J, Kimmoun, A
Current opinion in critical care. 2019;(4):384-390
Abstract
PURPOSE OF REVIEW Data and interventional trials regarding vasopressor and inotrope use during cardiogenic shock are scarce. Their use is limited by their side-effects and the lack of solid evidence regarding their effectiveness in improving outcomes. In this article, we review the current use of vasopressor and inotrope agents during cardiogenic shock. RECENT FINDINGS Two recent Cochrane analyses concluded that there was not sufficient evidence to prove that any one vasopressor or inotrope was superior to another in terms of mortality. A recent RCT and a meta-analysis on individual data suggested that norepinephrine may be preferred over epinephrine in patients with cardiogenic shock . For inotrope agents, when norepinephrine fails to restore perfusion, dobutamine represents the first-line agent. Levosimendan is a calcium sensitizer agent, which improves acute hemodynamics, albeit with uncertain effects on mortality. SUMMARY When blood pressure needs to be restored, norepinephrine is a reasonable first-line agent. Dobutamine is the first-line inotrope agent wheraes levosimendan can be used as a second-line agent or preferentially in patients previously treated with beta-blockers. Current information regarding comparative effective outcomes is nonetheless sparse and their use should be limited as a temporary bridge to recovery, mechanical circulatory support or heart transplantation.
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3.
New Applications of Oleanolic Acid and its Derivatives as Cardioprotective Agents: A Review of their Therapeutic Perspectives.
Sun, N, Li, D, Chen, X, Wu, P, Lu, YJ, Hou, N, Chen, WH, Wong, WL
Current pharmaceutical design. 2019;(35):3740-3750
Abstract
Oleanolic acid is an analogue of pentacyclic triterpenoids. It has been used as a hepatic drug for over 20 years in China. Currently, there are only five approved drugs derived from pentacyclic triterpenoids, including oleanolic acid (liver diseases), asiaticoside (wound healing), glycyrrhizinate (liver diseases), isoglycyrrhizinate (liver disease) and sodium aescinate (hydrocephalus). To understand more about the bioactivity and functional mechanisms of oleanolic acid, it can be developed as a potent therapeutic agent, in particular, for the prevention and treatment of heart diseases that are the leading cause of death for people worldwide. The primary aim of this mini-review is to summarize the new applications of oleanolic acid and its derivatives as cardioprotective agents reported in recent years and to highlight their therapeutic perspectives in cardiovascular diseases.
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4.
Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond.
Tschöpe, C, Kherad, B, Klein, O, Lipp, A, Blaschke, F, Gutterman, D, Burkhoff, D, Hamdani, N, Spillmann, F, Van Linthout, S
European journal of heart failure. 2019;(1):14-22
Abstract
Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.
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5.
Novel Pharmacotherapy for Hypertrophic Cardiomyopathy.
Wong, TC, Martinez, M
Cardiology clinics. 2019;(1):113-117
Abstract
Medical therapy for hypertrophic cardiomyopathy (HCM) has focused on minimizing the impact of symptoms due to left ventricular outflow tract obstruction and diastolic dysfunction. This article briefly discusses currently available therapy and focuses on both clinically available medications with novel applications for HCM as well as novel medications under development with specific indication for HCM. Finally, a brief summary of the current gaps and potential targets for pharmacotherapy is discussed.
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6.
NICORANDIL EFFICACY IN THE TREATMENT OF ISCHEMIC HEART DISEASE (REVIEW).
Gvishiani, M, Gabunia, L, Makharadze, T, Gongadze, N
Georgian medical news. 2018;(280-281):152-155
Abstract
Nicorandil is an antianginal agent with a dual mechanism of action. It belongs to ATP-senitive potassium channel openers which has the beneficial effect in angina pectoris, playing an significant role in the dilation of arteries, veins and coronary artery. It leads to the relaxation of vascular smooth muscle and causes vasodilatation of major epicardial vessels. This effect is crucial for reducing risks of further damage in cases when percutaneous coronary intervention (PCI) is necessary. Relevant new studies concluded that Nicorandil has antiarrhythmic and cardioprotective effects by improving reperfusion, ultimately leading to a reduction in microvascular damage caused by PCI. Furthermore, Nicorandil addition to the standard therapy of paitents with ischemic heart disease has demonstrated improved quality of life.
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7.
Innovative Strategies in Heart Failure: Present and Future.
Rodríguez-Mañero, M, Grigorian-Shamagian, L, Rábago, G, Abou-Jokh, C, Álvarez, B, Brion, M, González-Juanatey, JR
Archives of medical research. 2018;(8):558-567
Abstract
Heart failure (HF) is a progressively debilitating disease that considerably decreases the life expectancy and quality of life. It has become an important area of focus since it remains one of the most common reasons for admission in patients over the age of 65. Importantly, the incidence of HF has not declined within the past 20 years, but the survival after onset has increased in younger patients and men. This has been in part due to the growing interest in therapies that may decrease morbidity, mortality, along with the substantial health care expenditures associated with the disease. It can be said that over the past 50 years, there have been three distinct eras relating to HF management; a) the non-pharmacologic era, focused its treatments on fluid restriction; b) the pharmacologic era, marked by the increased use of inotropes and diuretics and the discovery of vasodilators, and the posterior discovery of medications relating to neurohormonal pathways; c) the device era, with the discovery, acceptance, and increased use of implantable cardioverter defibrillators, cardiac resynchronization therapy (CRT), and left ventricular assist devices (LVADs) among others. A new forth era could be about to arrive, with the advent of regenerative therapies. In this review article will discuss new therapeutic discoveries as well as provide insight into future therapies.
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8.
Impact of chocolate on the cardiovascular health.
Gammone, MA, Efthymakis, K, Pluchinotta, FR, Bergante, S, Tettamanti, G, Riccioni, G, D'Orazio, N
Frontiers in bioscience (Landmark edition). 2018;(5):852-864
Abstract
The antioxidants such as polyphenols, especially flavonols, present in large quantitites in cocoa, cause vasodilation, modulate inflammatory markers and cardiovascular health, and possess a range of protective cardiovascular effects. On the other hand, overconsumption of chocolate can lead to tachyarrhythmias, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and ventricular fibrillation due to its caffeine content. This review describes both the cardioprotective and adverse effects of chocolate and its constituents.
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9.
Phosphocreatine in Cardiac Surgery Patients: A Meta-Analysis of Randomized Controlled Trials.
Mingxing, F, Landoni, G, Zangrillo, A, Monaco, F, Lomivorotov, VV, Hui, C, Novikov, M, Nepomniashchikh, V, Fominskiy, E
Journal of cardiothoracic and vascular anesthesia. 2018;(2):762-770
Abstract
OBJECTIVE There is experimental evidence that phosphocreatine (PCr) can decrease ischemia/reperfusion injury of the heart. The authors investigated if PCr would improve heart performance as compared with standard treatment in cardiac surgery. DESIGN Meta-analysis of randomized controlled trials. SETTING Hospitals. PARTICIPANTS Adult and pediatric patients undergoing cardiac surgery. INTERVENTIONS The ability of PCr to improve cardiac outcomes as compared with standard treatment was investigated. MEASUREMENTS AND MAIN RESULTS PubMed/Medline, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, WANGFANG DATA, and VIP Paper Check System were searched to March 1 2017. The authors included 26 randomized controlled trials comprising 1,948 patients. Random and fixed-effects models were used to estimate odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI). PCr use was associated with reduced rates of intraoperative inotropic support (27% v 44%; OR 0.47, 95% CI 0.35-0.61; p < 0.001), major arrhythmias (16% v 28%; OR 0.44, 95% CI 0.27-0.69; p < 0.001), as well as increased spontaneous recovery of the cardiac rhythm immediately after aortic declamping (50% v 34%; OR 2.45, 95% CI 1.82-3.30; p < 0.001) as compared with standard treatment. The use of PCr decreased myocardial damage and augmented left ventricular ejection fraction in the postoperative period; however, MD for these outcomes were small and do not seem to be clinically significant. CONCLUSIONS In randomized trials, PCr administration was associated with reduced rates of intraoperative inotropic support and major arrhythmias, and increased spontaneous recovery of the cardiac rhythm after aortic declamping. Large multicenter evidence is needed to validate these findings.
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10.
[Vasopressors and inotropes: use in paediatrics].
García-Canales, A, Peña-Juárez, RA, Sandoval-Franco, LM
Archivos de cardiologia de Mexico. 2018;(1):39-50
Abstract
The cardiovascular system is a dynamic system, which is required to ensure adequate delivery of oxygen, nutrients, and hormones to the tissues that are necessary for cell metabolism. It also synthesises and modifies the vasoactive components that regulate vascular tone and myocardial function. These vasoactive components have demonstrated their beneficial effects in the management of paediatric patients in a critical condition with heart failure and shock. However, their use and abuse brings harmful effects, increases mortality, and is associated with arrhythmias. An increase in myocardial oxygen consumption favours the presence of ischaemia, therefore it is necessary to know the mechanism of action and indications of these drugs to minimise their harmful effects. The purpose of this review is to describe the pharmacology and clinical applications of inotropic and vasopressor agents in the paediatric patient in acritical condition.