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1.
A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus.
Farmakis, D, Agostoni, P, Baholli, L, Bautin, A, Comin-Colet, J, Crespo-Leiro, MG, Fedele, F, García-Pinilla, JM, Giannakoulas, G, Grigioni, F, et al
International journal of cardiology. 2019;:83-90
Abstract
Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.
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Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial.
Quirós-Fernández, R, López-Plaza, B, Bermejo, LM, Palma-Milla, S, Gómez-Candela, C
Nutrients. 2019;(3)
Abstract
Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by -28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (-28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (-15.75 ± 9.9 mmHg; p < 0.001) and diastolic (-6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (-15.75 ± 9.9 vs. -2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.
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3.
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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4.
The perioperative effect of magnesium sulfate in patients with concentric left ventricular hypertrophy undergoing cardiac surgery: A double-blinded randomized study.
Soliman, R, Abukhudair, W
Annals of cardiac anaesthesia. 2019;(3):246-253
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Abstract
OBJECTIVE The objective of this study was to assess the cardioprotective effect of magnesium sulfate in patients with left ventricular concentric hypertrophy undergoing cardiac surgery. DESIGN The study was a double-blinded randomized study. SETTING This study was conducted at a cardiac center. PATIENTS The study included 250 patients. INTERVENTION The study included two groups (each = 125): Group M - the patients who received magnesium sulfate infusion (15 mg/kg/h). The infusion was started 20 min before induction, during surgery, and the first postoperative 24 h. Group C - the patients who received an equal amount of normal saline. MEASUREMENTS The variables included troponin I level, creatinine kinase-MB (CK-MB) level, electrocardiograph (ECG) with automatic ST-segment analysis (leads II and V), E/A peak ratio, end-diastolic volume, cardiac index (CI), heart rate, mean arterial blood pressure (MAP), mean arterial pulmonary pressure (mPAP), pulmonary and systemic vascular resistances, and pharmacological and mechanical support. MAIN RESULTS The troponin I level, CK-MB, and ECG changes were lower in Group M than Group C (P < 0.05). The E/A peak ratio and end-diastolic volume increased in Group M than Group C (P < 0.05). There was a significant increase in the CI and a decrease in the heart rate, mPAP, pulmonary vascular resistances, and pharmacological and mechanical support in Group M compared to Group C (P < 0.05). There were minimal changes in the MAP and systemic vascular resistance in Group M compared to Group C (P < 0.05). CONCLUSION The magnesium sulfate provides a cardioprotective effect in patients with concentric ventricular hypertrophy undergoing cardiac surgery. It decreases the incidence of perioperative myocardial infarction and arrhythmia. Furthermore, it decreases the requirement of pharmacological and mechanical support.
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Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial.
Kamenshchikov, NO, Mandel, IA, Podoksenov, YK, Svirko, YS, Lomivorotov, VV, Mikheev, SL, Kozlov, BN, Shipulin, VM, Nenakhova, AA, Anfinogenova, YJ
The Journal of thoracic and cardiovascular surgery. 2019;(6):2328-2336.e1
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Abstract
OBJECTIVES The aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS A total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS). RESULTS NO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 ± 0.39 ng/mL versus 2.41 ± 0.55 ng/mL, respectively (P = .001). The CK-MB value was significantly lower in NO-treated group compared with the control group 24 hours after surgery: 47.69 ± 8.08 U/L versus 62.25 ± 9.78 U/L, respectively (P = .001); and the VIS was significantly lower in the NO-treated group 6 hours after the intervention. CONCLUSIONS NO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with lower levels of VIS and cardiospecific blood markers cTnI and CK-MB.
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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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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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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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Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.
Edwards, MR, Forbes, G, MacDonald, N, Berdunov, V, Mihaylova, B, Dias, P, Thomson, A, Grocott, MP, Mythen, MG, Gillies, MA, et al
BMJ open. 2019;(1):e023455
Abstract
INTRODUCTION Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice. METHODS The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide. ETHICS/DISSEMINATION The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER ISRCTN39653756.
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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.