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Luk A, Teijeiro-Paradis R, Kochan A, Billia F, Douflé G, Magder S, Mendelson AA, McGuinty C, Granton J. The Etiology and Management of Critical Acute Right Heart Failure. Can J Cardiol 2025:S0828-282X(25)00113-8. [PMID: 39938716 DOI: 10.1016/j.cjca.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 02/03/2025] [Accepted: 02/05/2025] [Indexed: 02/14/2025] Open
Abstract
Right ventricular failure contributes to the morbidity and mortality of acute myocardial function, massive pulmonary embolism, and chronic pulmonary hypertension. Understanding how the normal physiology of the right ventricle (RV) is disrupted is integral to managing patients who present with RV decompensation. Therapeutic advances in mechanical circulatory support, pharmacotherapies to reduce afterload, mechanical and chemical lytic therapies for acute pulmonary embolism have improved outcomes of patients by offloading the RV. In this report we provide an overview of the physiology of the RV, medical management (volume optimization, hemodynamic targets, rhythm management), along with critical care-specific topics (induction with mechanical ventilation, sedation strategies, and mechanical circulatory support) and provide a framework for managing patients who present with leveraging principles of preload, contractility, and afterload. Last, because of the complexity of right ventricular failure management, and the complexity of presentation, we also discuss the role of team-based approach (cardiogenic shock and pulmonary embolism response teams), and highlight its benefits at improving outcomes.
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Affiliation(s)
- Adriana Luk
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
| | | | - Andrew Kochan
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
| | - Filio Billia
- Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada
| | - Ghislaine Douflé
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
| | - Sheldon Magder
- Department of Critical Care, McGill University Health Centre, Montreal, Quebec, Canada
| | - Asher A Mendelson
- Section of Critical Care, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | | | - John Granton
- Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada
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Levitt CV, Williams CA, Ahari J, Pourmand A. Approach to Decompensated Right Heart Failure in the Acute Setting. J Clin Med 2024; 13:869. [PMID: 38337563 PMCID: PMC10856072 DOI: 10.3390/jcm13030869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 01/24/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Acute right heart failure (ARHF) arises when the right ventricle fails to pump blood efficiently to the pulmonary circulation. This inefficiency leads to a decreased blood supply to various organs. ARHF is a significant health concern, often leading to increased hospital admissions and being associated with a higher risk of mortality. This condition underscores the importance of effective cardiac care and timely intervention to manage its complications and improve patient outcomes. Diagnosing ARHF involves a comprehensive approach that includes a physical examination to evaluate the patient's fluid status and heart-lung function, blood tests to identify potential triggers and help forecast patient outcomes and various imaging techniques. These imaging techniques include electrocardiograms, point-of-care ultrasounds, computed tomography, cardiac magnetic resonance imaging, and other advanced monitoring methods. These diagnostic tools collectively aid in a detailed assessment of the patient's cardiac and pulmonary health, essential for effective management of ARHF. The management of ARHF focuses on addressing the underlying causes, regulating fluid balance, and enhancing cardiac function through pharmacological treatments or mechanical support aimed at boosting right heart performance. This management strategy includes the use of medications that modulate preload, afterload, and inotropy; vasopressors; anti-arrhythmic drugs; ensuring proper oxygenation and ventilation; and the utilization of heart and lung assist devices as a bridge to potential transplantation. This review article is dedicated to exploring the pathophysiology of ARHF, examining its associated morbidity and mortality, evaluating the various diagnostic tools available, and discussing the diverse treatment modalities. The article seeks to provide a comprehensive understanding of ARHF, its impact on health, and the current strategies for its management.
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Affiliation(s)
- Catherine V. Levitt
- Department of Emergency Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA (C.A.W.)
| | - Caitlin A. Williams
- Department of Emergency Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA (C.A.W.)
| | - Jalil Ahari
- Pulmonary and Critical Care Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA
| | - Ali Pourmand
- Department of Emergency Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA (C.A.W.)
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Akhtar MS, Hassan MQ, Siddiqui A, Alavudeen SS, Afzal O, Altamimi ASA, Rahman SO, Khurana M, Ahsan MJ, Sharma AK, Tabassum F. Levosimendan: mechanistic insight and its diverse future aspects in cardiac care. Acta Cardiol 2022; 78:170-187. [PMID: 36222590 DOI: 10.1080/00015385.2022.2115761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Inotropic agents are generally recommended to use in patients with acute decompensated heart failure (HF) with reduced ejection fraction (HFrEF) concurrent to end-organ dysfunction. However, due to certain pharmacological limitations like developing life threatening arrhythmia and tolerance, cannot be employed as much as needed. Meanwhile, Calcium ion (Ca2+) sensitisers exhibits their inotropic action by increasing the sensitivity of the cardiomyocyte to intracellular Ca2+ ion and have been reported as emerging therapeutic alternative in HF cases. Levosimendan (LEVO) is an inodilator and with its unique pharmacology justifying its use in a wide range of cardiac alterations in HF particularly in undergoing cardiac surgery. It is also reported to be better than classical inotropes in maintaining cardiac mechanical efficacy and reducing congestion in acute HF with hypotension. This review paper was designed to compile various evidence about basic pharmacology and potential clinical aspects of LEVO in cardiac surgery and other HF associated alterations. This will benefit directly to the researcher in initiating research and to fill the gaps in the area of thrust.
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Affiliation(s)
| | - Md Quamrul Hassan
- Department of Pharmacology, SNS College of Pharmacy, Motihari, India
| | - Aisha Siddiqui
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia
| | | | - Obaid Afzal
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Abdulmalik S A Altamimi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Syed Obaidur Rahman
- Department of Pharmacology, School of Pharmaceutical Education and Research, New Delhi, India
| | - Mallika Khurana
- Department of Pharmacology, School of Pharmaceutical Education and Research, New Delhi, India
| | - Mohamed Jawed Ahsan
- Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur, India
| | - Arun Kumar Sharma
- Department of Pharmacology, Amity Institute of Pharmacy, Noida, India
| | - Fauzia Tabassum
- Department of Pharmacology, College of Dentistry and Pharmacy, Buraydah, Saudi Arabia
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Hu Y, Wei Z, Zhang C, Lu C, Zeng Z. The effect of levosimendan on right ventricular function in patients with heart dysfunction: a systematic review and meta-analysis. Sci Rep 2021; 11:24097. [PMID: 34916560 PMCID: PMC8677770 DOI: 10.1038/s41598-021-03317-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 12/01/2021] [Indexed: 11/11/2022] Open
Abstract
Levosimendan exerts positive inotropic and vasodilatory effects. Currently, its effects on right heart function remain uncertain. This systematic review and meta-analysis is intended to illustrate the impacts of levosimendan on systolic function of the right heart in patients with heart dysfunction. We systematically searched electronic databases (PubMed, the Cochrane Library, Embase and Web of Science) up to November 30, 2020, and filtered eligible studies that reported the impacts of levosimendan on right heart function. Of these, only studies whose patients suffered from heart dysfunction or pulmonary hypertension were included. Additionally, patients were divided into two groups (given levosimendan or not) in the initial research. Then, RevMan5.3 was used to conduct further analysis. A total of 8 studies comprising 390 patients were included. The results showed that after 24 h of levosimendan, patients' right ventricular fractional area change [3.17, 95% CI (2.03, 4.32), P < 0.00001], tricuspid annular plane systolic excursion [1.26, 95% CI (0.35, 2.16), P = 0.007] and tricuspid annular peak systolic velocity [0.86, 95% CI (0.41, 1.32), P = 0.0002] were significantly increased compared to the control group. And there is an increasing trend of cardiac output in levosimendan group [1.06, 95% CI (- 0.16, 2.29), P = 0.09 ] .Furthermore, patients' systolic pulmonary arterial pressure [- 5.57, 95% CI (- 7.60, - 3.54), P < 0.00001] and mean pulmonary arterial pressure [- 1.01, 95% CI (- 1.64, - 0.37), P = 0.002] were both significantly decreased, whereas changes in pulmonary vascular resistance [- 55.88, 95% CI (- 206.57, 94.82), P = 0.47] were not significant. Our study shows that in patients with heart dysfunction, levosimendan improves systolic function of the right heart and decreases the pressure of the pulmonary artery.
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Affiliation(s)
- Yaoshi Hu
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, 530021, Guangxi, China
| | - Zhe Wei
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Chaoyong Zhang
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, 530021, Guangxi, China
| | - Chuanghong Lu
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
- Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, 530021, Guangxi, China
| | - Zhiyu Zeng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
- Guangxi Key Laboratory of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, 530021, Guangxi, China.
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Chen WC, Lin MH, Chen CL, Lai YC, Chen CY, Lin YC, Hung CC. Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials. J Clin Med 2021; 10:4120. [PMID: 34575231 PMCID: PMC8471363 DOI: 10.3390/jcm10184120] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 12/17/2022] Open
Abstract
Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46-0.84), milrinone (OR: 0.50; 95% CI: 0.30-0.84), and dobutamine (OR: 0.75; 95% CI: 0.57-0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17-2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87-2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.
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Affiliation(s)
- Wei-Cheng Chen
- Graduate Institute of Biomedical Sciences, China Medical University, 91 Hsueh-Shih Road, Taichung 404333, Taiwan;
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan; (C.-L.C.); (C.-Y.C.)
- Department of Education, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan
| | - Meng-Hsuan Lin
- Department of Pharmacy, College of Pharmacy, China Medical University, 100 Jingmao Road, Bei-tun Dist., Taichung 406040, Taiwan;
| | - Chieh-Lung Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan; (C.-L.C.); (C.-Y.C.)
| | - Yi-Ching Lai
- Department of Cardiovascular Medicine, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan;
| | - Chih-Yu Chen
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan; (C.-L.C.); (C.-Y.C.)
| | - Yu-Chao Lin
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 2 Yude Road, North Dist., Taichung 404332, Taiwan; (C.-L.C.); (C.-Y.C.)
- School of Medicine, China Medical University, 91 Hsueh-Shih Road, Taichung 404333, Taiwan
| | - Chin-Chuan Hung
- Department of Pharmacy, College of Pharmacy, China Medical University, 100 Jingmao Road, Bei-tun Dist., Taichung 406040, Taiwan;
- Department of Pharmacy, China Medical University Hospital, 2 Yude Road, Taichung 404332, Taiwan
- Department of Healthcare Administration, Asia University, 500 Lioufeng Road, Wufeng, Taichung 41354, Taiwan
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Xiangli S, Lan L, Libiya Z, Jun M, Shubin J. Effect of levosimendan combined with recombinant human brain natriuretic peptide on diuretic resistance. Libyan J Med 2021; 16:1973762. [PMID: 34493175 PMCID: PMC8439246 DOI: 10.1080/19932820.2021.1973762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
Abstract
Levosimendan is a calcium sensitizer used for managing heart failure (HF) because of its inotropic and vasodilatory effects. As many patients do not respond to levosimendan as a monotherapy, it may be necessary to combine it with other diuretic agents such as recombinant human brain natriuretic peptide (rhBNc P). The aim of this study was to investigate efficacy of levosimendan when combined with rhBNP in patients with diuretic resistance and low ejection fraction (EF) rate.The study included HF patients with diuretic resistance and low EF. Before grouping, patients with a 24-hour urine volume of <0.5 mL/kg/h were administered with furosemide injection. Treatment group was administered levosimendan injection based on the original diuretic and rhBNP.One hundred twenty-eight patients were included, with 64 patients each in the control and treatment arms. 24-hour urine volume of the treatment group was significantly higher than that of the control group. Moreover, dyspnea score of the treatment group significantly improved compared with control group. In the treatment group, 12.5% of patients had no significant changes in the urine volume, weight, and dyspnea score before and after the treatment, indicating poor curative effect of the treatment, whereas in the control group, 23.4% of patients had poor curative effect (P < .05). No significant change was observed in the systolic blood pressure, heart rate, and serum creatinine level before and after treatment in both groups.Levosimendan in combination with rhBNP can effectively relieve diuretic resistance, reduce body weight, improve dyspnea, and ensure safety in the treatment process.
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Affiliation(s)
- Shen Xiangli
- Heart Center, Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Li Lan
- Heart Center, Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Zu Libiya
- Heart Center, Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Ma Jun
- Heart Center, Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
| | - Jiang Shubin
- Heart Center, Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, China
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Ong LT. Evidence based review of management of cardiorenal syndrome type 1. World J Methodol 2021; 11:187-198. [PMID: 34322368 PMCID: PMC8299910 DOI: 10.5662/wjm.v11.i4.187] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 05/09/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiorenal syndrome (CRS) type 1 is the development of acute kidney injury in patients with acute decompensated heart failure. CRS often results in prolonged hospitalization, a higher rate of rehospitalization, high morbidity, and high mortality. The pathophysiology of CRS is complex and involves hemodynamic changes, neurohormonal activation, hypothalamic-pituitary stress reaction, inflammation, and infection. However, there is limited evidence or guideline in managing CRS type 1, and the established therapeutic strategies mainly target the symptomatic relief of heart failure. This review will discuss the strategies in the management of CRS type 1. Six clinical studies have been included in this review that include different treatment strategies such as nesiritide, dopamine, levosimendan, tolvaptan, dobutamine, and ultrafiltration. Treatment strategies for CRS type 1 are derived based on the current literature. Early recognition and treatment of CRS can improve the outcomes of the patients significantly.
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Affiliation(s)
- Leong Tung Ong
- Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Wilayah Persekutuan Kuala Lumpur, Malaysia
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Long YX, Cui DY, Kuang X, Hu S, Hu Y, Liu ZZ. Effect of Levosimendan on Ventricular Systolic and Diastolic Functions in Heart Failure Patients: A Meta-Analysis of Randomized Controlled Trials. J Cardiovasc Pharmacol 2021; 77:805-813. [PMID: 34001722 DOI: 10.1097/fjc.0000000000001010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/15/2021] [Indexed: 12/20/2022]
Abstract
ABSTRACT Levosimendan, a calcium sensitizer, exerts inotropic action through improving left ventricular ejection fraction. We noticed that only few clinical studies are published in which the effects of levosimendan on cardiac function are studied by echocardiography. When screening the literature (PubMed, Embase, and CENTRAL, from inception to August 2020), we found 29 randomized controlled trials on levosimendan containing echocardiographic data. We included those studies, describing a total of 574 heart failure patients, in our meta-analysis and extracted 14 ultrasonic parameters, pooling the effect estimates using a random-effect model. Our analysis of the diastolic parameters of the left ventricle shows that levosimendan reduce the early/late transmitral diastolic peak flow velocity ratio [standardized mean difference (SMD) -0.45 to 95% confidence interval (CI) (-0.87 to -0.03), P = 0.037] and E/e' (e': mitral annulus peak early diastolic wave velocity using tissue-doppler imaging) [SMD -0.59, 95% CI (-0.8 to -0.39), P < 0.001]. As it regards the systolic parameters of the right ventricle, levosimendan increased tricuspid annular plane systolic excursion [SMD 0.62, 95% CI (0.28 to 0.95), P < 0.001] and tricuspid annular peak systolic velocity [SMD 0.75, 95% CI (0.35 to 1.16), P < 0.001], and reduced systolic pulmonary artery pressure [SMD -1.02, 95% CI (-1.32, -0.73), P < 0.001]. As it regards the diastolic parameters of the right ventricle, levosimendan was associated with the decrease of Aa (peak late diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD -0.38, 95% CI (-0.76 to 0), P = 0.047] and increase of Ea (peak early diastolic tricuspid annular velocity using tissue-doppler imaging) [SMD 1.03, 95% CI (0.63 to 1.42), P < 0.001] and Ea/Aa [SMD 0.86, 95% CI (0.18 to 1.54), P = 0.013]. We show that levosimendan is associated with an amelioration in the diastolic and systolic functions of both ventricles in heart failure patients.
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Affiliation(s)
- Yu-Xiang Long
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Kumar D, Yadava OP, Ahlawat V, Kundu A, Yadav A, Prakash A. Pre-bypass levosimendan in ventricular dysfunction-effect on right ventricle. Asian Cardiovasc Thorac Ann 2020; 29:260-267. [PMID: 33143432 DOI: 10.1177/0218492320972891] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Levosimendan is an effective calcium sensitizer with complementary mechanisms of action: calcium sensitization and opening of adenosine triphosphate-dependent potassium channels, both on the sarcolemma of the smooth muscle cells in the vasculature and on the mitochondria of cardiomyocytes. Levosimendan has a long-acting metabolite with a half-life of approximately 80 h. There have been a few small studies on this drug regarding right ventricular function. In view of this, we investigated the effect of levosimendan on right ventricular function in patients with coronary artery disease. METHODS This was a prospective, randomized, double-blind study on 50 patients with coronary artery disease and severe left ventricular dysfunction (left ventricular ejection fraction ≤35%) undergoing elective off-pump coronary artery bypass. RESULTS Levosimendan had an inotropic effect on right ventricular myocardium and a vasodilatory effect on blood vessels. It caused a decline in pulmonary vascular resistance (p < 0.018), right ventricular systolic pressure (p < 0.001), and pulmonary artery systolic pressure (p < 0.001), and improved right ventricular diastolic function as shown by the decrease in right ventricular Tei index (p < 0.001), right ventricular end-diastolic pressure, and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity (p < 0.006). However, we found no beneficial effects on intensive care unit or hospital stay (p = 0.164, p = 0.349, respectively) nor a mortality benefit. CONCLUSIONS Levosimendan has salutary effects on right ventricular function in patients with severe left ventricular dysfunction undergoing coronary artery bypass, in terms of improved hemodynamic parameters.
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Affiliation(s)
- Dhanesh Kumar
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
| | - Om Prakash Yadava
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
| | - Vikas Ahlawat
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
| | - Anirban Kundu
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
| | - Amita Yadav
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
| | - Arvind Prakash
- Department of Cardiac Surgery, National Heart Institute, New Delhi, India
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Keller M, Heller T, Lang T, Patzelt J, Schreieck J, Schlensak C, Rosenberger P, Magunia H. Acute changes of global and longitudinal right ventricular function: an exploratory analysis in patients undergoing open-chest mitral valve surgery, percutaneous mitral valve repair and off-pump coronary artery bypass grafting. Cardiovasc Ultrasound 2020; 18:32. [PMID: 32787878 PMCID: PMC7425536 DOI: 10.1186/s12947-020-00218-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 08/07/2020] [Indexed: 11/10/2022] Open
Abstract
Background Right ventricular (RV) function is an important prognostic indicator. The acute effects of cardiac interventions or cardiac surgery on global and longitudinal RV function are not entirely understood. In this study, acute changes of RV function during mitral valve surgery (MVS), percutaneous mitral valve repair (PMVR) and off-pump coronary artery bypass surgery (OPCAB) were investigated employing 3D echocardiography. Methods Twenty patients scheduled for MVS, 23 patients scheduled for PMVR and 25 patients scheduled for OPCAB were included retrospectively if patients had received 3D transesophageal echocardiography before and immediately after MVS, PMVR or OPCAB, respectively. RV global and longitudinal function was assessed using a 3D multiparameter set consisting of global right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), longitudinal contribution to RVEF (RVEFlong) and free wall longitudinal strain (FWLS). Results Longitudinal RV function was significantly depressed immediately after MVS, as reflected by all parameters (RVEFlong: 20 ± 5% vs. 13 ± 6%, p < 0.001, TAPSE: 13.1 ± 5.1 mm vs. 11.0 ± 3.5 mm, p = 0.04 and FWLS: −20.1 ± 7.1% vs. -15.4 ± 5.1%, p < 0.001, respectively). The global RVEF was slightly impaired, but the difference did not reach significance (37 ± 13% vs. 32 ± 9%, p = 0.15). In the PMVR group, both global and longitudinal RV function parameters were unaltered, whereas the OPCAB group showed a slight reduction of RVEFlong only (18 ± 7% vs. 14 ± 5%, p < 0.01). RVEFlong yielded moderate case-to-case but good overall reproducibility. Conclusions TAPSE, FWLS and RVEFlong reflect the depression of longitudinal compared to global RV function initially after MVS. PMVR alone had no impact, while OPCAB had a slight impact on longitudinal RV function. The prognostic implications of these phenomena remain unclear and require further investigation.
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Affiliation(s)
- Marius Keller
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany.
| | - Tim Heller
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany
| | - Tobias Lang
- Chair of Visual Computing, Department of Computer Science, Eberhard-Karls-University, Sand 14, 72076, Tuebingen, Germany
| | - Johannes Patzelt
- Department of Cardiology, Angiology and Intensive Care Medicine, University Hospital, University Heart Center Luebeck, Ratzeburger Allee 160, 23538, Luebeck, Germany
| | - Juergen Schreieck
- Department of Cardiology and Angiology, University Hospital Tuebingen, Eberhard-Karls-University, Otfried-Mueller-Strasse 10, 72076, Tuebingen, Germany
| | - Christian Schlensak
- Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany
| | - Peter Rosenberger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany
| | - Harry Magunia
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tuebingen, Germany
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Papp Z, Agostoni P, Alvarez J, Bettex D, Bouchez S, Brito D, Černý V, Comin-Colet J, Crespo-Leiro MG, Delgado JF, Édes I, Eremenko AA, Farmakis D, Fedele F, Fonseca C, Fruhwald S, Girardis M, Guarracino F, Harjola VP, Heringlake M, Herpain A, Heunks LM, Husebye T, Ivancan V, Karason K, Kaul S, Kivikko M, Kubica J, Masip J, Matskeplishvili S, Mebazaa A, Nieminen MS, Oliva F, Papp JG, Parissis J, Parkhomenko A, Põder P, Pölzl G, Reinecke A, Ricksten SE, Riha H, Rudiger A, Sarapohja T, Schwinger RH, Toller W, Tritapepe L, Tschöpe C, Wikström G, von Lewinski D, Vrtovec B, Pollesello P. Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use. Card Fail Rev 2020; 6:e19. [PMID: 32714567 PMCID: PMC7374352 DOI: 10.15420/cfr.2020.03] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 03/16/2020] [Indexed: 12/12/2022] Open
Abstract
Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.
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Affiliation(s)
- Zoltán Papp
- Department of Cardiology, Faculty of Medicine, University of Debrecen Debrecen, Hungary
| | - Piergiuseppe Agostoni
- Department of Clinical Sciences and Community Health, Centro Cardiologico Monzino, IRCCS Milan, Italy
| | - Julian Alvarez
- Department of Surgery, School of Medicine, University of Santiago de Compostela Santiago de Compostela, Spain
| | - Dominique Bettex
- Institute of Anaesthesiology, University Hospital of Zurich Zurich, Switzerland
| | - Stefan Bouchez
- Department of Anaesthesiology, University Hospital Ghent, Belgium
| | - Dulce Brito
- Cardiology Department, Centro Hospitalar Universitario Lisboa Norte, CCUI, Faculdade de Medicina, Universidade de Lisboa Lisbon, Portugal
| | - Vladimir Černý
- Department of Anaesthesiology, Perioperative Medicine and Intensive Care, Masaryk Hospital, J.E. Purkinje University Usti nad Labem, Czech Republic
| | - Josep Comin-Colet
- Heart Diseases Institute, Hospital Universitari de Bellvitge Barcelona, Spain
| | - Marisa G Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC), CIBERCV, Instituto de Investigacion Biomedica A Coruña (INIBIC), Universidad de a Coruña (UDC) La Coruña, Spain
| | - Juan F Delgado
- Heart Failure and Transplant Program, Cardiology Department, University Hospital 12 Octubre Madrid, Spain
| | - Istvan Édes
- Department of Cardiology, Faculty of Medicine, University of Debrecen Debrecen, Hungary
| | - Alexander A Eremenko
- Department of Cardiac Intensive Care, Petrovskii National Research Centre of Surgery, Sechenov University Moscow, Russia
| | - Dimitrios Farmakis
- Department of Cardiology, Medical School, University of Cyprus Nicosia, Cyprus
| | - Francesco Fedele
- Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology and Geriatric Sciences, La Sapienza University of Rome Rome, Italy
| | - Cândida Fonseca
- Heart Failure Clinic, São Francisco Xavier Hospital, CHLO Lisbon, Portugal
| | - Sonja Fruhwald
- Department of Anaesthesiology and Intensive Care Medicine, Division of Anaesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz Graz, Austria
| | - Massimo Girardis
- Struttura Complessa di Anestesia 1, Policlinico di Modena Modena, Italy
| | - Fabio Guarracino
- Dipartimento di Anestesia e Terapie Intensive, Azienda Ospedaliero-Universitaria Pisana Pisa, Italy
| | - Veli-Pekka Harjola
- Emergency Medicine, Meilahti Central University Hospital, University of Helsinki Helsinki, Finland
| | - Matthias Heringlake
- Department of Anaesthesiology and Intensive Care Medicine, University of Lübeck Lübeck, Germany
| | - Antoine Herpain
- Department of Intensive Care, Hôpital Erasme Brussels, Belgium
| | - Leo Ma Heunks
- Department of Intensive Care Medicine, Amsterdam UMC Amsterdam, the Netherlands
| | - Tryggve Husebye
- Department of Cardiology, Oslo University Hospital Ullevaal Oslo, Norway
| | - Višnja Ivancan
- Department of Anaesthesiology, Reanimatology and Intensive Care, University Hospital Centre Zagreb, Croatia
| | - Kristjan Karason
- Departments of Cardiology and Transplantation, Sahlgrenska University Hospital Gothenburg, Sweden
| | - Sundeep Kaul
- Intensive Care Unit, National Health Service Leeds, UK
| | - Matti Kivikko
- Global Medical Affairs, R&D, Orion Pharma Espoo, Finland
| | - Janek Kubica
- Department of Cardiology and Internal Medicine, Nicolaus Copernicus University Torun, Poland
| | - Josep Masip
- Intensive Care Department, Consorci Sanitari Integral, University of Barcelona Barcelona, Spain
| | | | - Alexandre Mebazaa
- Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals Paris, France
| | | | - Fabrizio Oliva
- Department of Cardiology, Niguarda Ca'Granda Hospital Milan, Italy
| | - Julius-Gyula Papp
- MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, University of Szeged Szeged, Hungary
| | - John Parissis
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Athens, Greece
| | - Alexander Parkhomenko
- Emergency Cardiology Department, National Scientific Centre MD Strazhesko Institute of Cardiology Kiev, Ukraine
| | - Pentti Põder
- Department of Cardiology, North Estonia Medical Centre Tallinn, Estonia
| | - Gerhard Pölzl
- Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck Innsbruck, Austria
| | - Alexander Reinecke
- Klinik für Innere Medizin III, Kardiologie, Universitätsklinikum Schleswig-Holstein Kiel, Germany
| | - Sven-Erik Ricksten
- Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital Gothenburg, Sweden
| | - Hynek Riha
- Cardiothoracic Anaesthesiology and Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine Prague, Czech Republic
| | - Alain Rudiger
- Department of Medicine, Spittal Limmattal Schlieren, Switzerland
| | | | - Robert Hg Schwinger
- Medizinische Klinik II, Klinikum Weiden, Teaching Hospital of University of Regensburg Weiden, Germany
| | - Wolfgang Toller
- Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz Graz, Austria
| | - Luigi Tritapepe
- Anaesthesia and Intensive Care Division, San Camillo-Forlanini Hospital Rome, Italy
| | - Carsten Tschöpe
- Department of Cardiology, Campus Virchow Klinikum, Charité - University Medicine Berlin Berlin, Germany
| | - Gerhard Wikström
- Institute of Medical Sciences, Uppsala University Uppsala, Sweden
| | - Dirk von Lewinski
- Department of Cardiology, Myokardiale Energetik und Metabolismus Research Unit, Medical University of Graz Graz, Austria
| | - Bojan Vrtovec
- Advanced Heart Failure and Transplantation Centre, Department of Cardiology, University Clinical Centre Ljubljana, Slovenia
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12
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Papp Z, Agostoni P, Alvarez J, Bettex D, Bouchez S, Brito D, Černý V, Comin-Colet J, Crespo-Leiro MG, Delgado JF, Édes I, Eremenko AA, Farmakis D, Fedele F, Fonseca C, Fruhwald S, Girardis M, Guarracino F, Harjola VP, Heringlake M, Herpain A, Heunks LMA, Husebye T, Ivancan V, Karason K, Kaul S, Kivikko M, Kubica J, Masip J, Matskeplishvili S, Mebazaa A, Nieminen MS, Oliva F, Papp JG, Parissis J, Parkhomenko A, Põder P, Pölzl G, Reinecke A, Ricksten SE, Riha H, Rudiger A, Sarapohja T, Schwinger RHG, Toller W, Tritapepe L, Tschöpe C, Wikström G, von Lewinski D, Vrtovec B, Pollesello P. Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use. J Cardiovasc Pharmacol 2020; 76:4-22. [PMID: 32639325 PMCID: PMC7340234 DOI: 10.1097/fjc.0000000000000859] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 05/28/2020] [Indexed: 12/12/2022]
Abstract
Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
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Affiliation(s)
- Zoltán Papp
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Piergiuseppe Agostoni
- Department of Clinical Sciences and Community Health, Centro Cardiologico Monzino, IRCCS, Milan, Italy
| | - Julian Alvarez
- Department of Surgery, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Dominique Bettex
- Institute of Anaesthesiology, University Hospital of Zurich, Zurich, Switzerland
| | - Stefan Bouchez
- Department of Anaesthesiology, University Hospital, Ghent, Belgium
| | - Dulce Brito
- Cardiology Department, Centro Hospitalar Universitario Lisboa Norte, CCUI, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Vladimir Černý
- Department of Anaesthesiology, Perioperative Medicine and Intensive Care, Masaryk Hospital, J.E. Purkinje University, Usti nad Labem, Czech Republic
| | - Josep Comin-Colet
- Heart Diseases Institute, Hospital Universitari de Bellvitge, Barcelona, Spain
| | - Marisa G. Crespo-Leiro
- Complexo Hospitalario Universitario A Coruña (CHUAC), CIBERCV, Instituto de Investigacion Biomedica A Coruña (INIBIC), Universidad de a Coruña (UDC), La Coruña, Spain
| | - Juan F. Delgado
- Heart Failure and Transplant Program, Cardiology Department, University Hospital 12 Octubre, Madrid, Spain
| | - István Édes
- Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Alexander A. Eremenko
- Department of Cardiac Intensive Care, Petrovskii National Research Centre of Surgery, Sechenov University, Moscow, Russia
| | - Dimitrios Farmakis
- Department of Cardiology, Medical School, University of Cyprus, Nicosia, Cyprus
| | - Francesco Fedele
- Department of Cardiovascular, Respiratory, Nephrology, Anaesthesiology and Geriatric Sciences, La Sapienza University of Rome, Rome, Italy
| | - Cândida Fonseca
- Heart Failure Clinic, São Francisco Xavier Hospital, CHLO, Lisbon, Portugal
| | - Sonja Fruhwald
- Department of Anaesthesiology and Intensive Care Medicine, Division of Anaesthesiology for Cardiovascular Surgery and Intensive Care Medicine, Medical University of Graz, Graz, Austria
| | - Massimo Girardis
- Struttura Complessa di Anestesia 1, Policlinico di Modena, Modena, Italy
| | - Fabio Guarracino
- Dipartimento di Anestesia e Terapie Intensive, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Veli-Pekka Harjola
- Emergency Medicine, Meilahti Central University Hospital, University of Helsinki, Helsinki, Finland
| | - Matthias Heringlake
- Department of Anaesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck, Germany
| | - Antoine Herpain
- Department of Intensive Care, Hôpital Erasme, Brussels, Belgium
| | - Leo M. A. Heunks
- Department of Intensive Care Medicine, Amsterdam UMC, Amsterdam, the Netherlands
| | - Tryggve Husebye
- Department of Cardiology, Oslo University Hospital Ullevaal, Oslo, Norway
| | - Višnja Ivancan
- Department of Anaesthesiology, Reanimatology and Intensive Care, University Hospital Centre, Zagreb, Croatia
| | - Kristjan Karason
- Departments of Cardiology and Transplantation, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sundeep Kaul
- Intensive Care Unit, National Health Service, Leeds, United Kingdom
| | - Matti Kivikko
- Global Medical Affairs, R&D, Orion Pharma, Espoo, Finland
| | - Janek Kubica
- Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Torun, Poland
| | - Josep Masip
- Intensive Care Department, Consorci Sanitari Integral, University of Barcelona, Barcelona, Spain
| | | | - Alexandre Mebazaa
- Department of Anaesthesiology and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, Paris, France
| | | | - Fabrizio Oliva
- Department of Cardiology, Niguarda Ca'Granda Hospital, Milan, Italy
| | - Julius G. Papp
- MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary
| | - John Parissis
- Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexander Parkhomenko
- Emergency Cardiology Department, National Scientific Centre MD Strazhesko Institute of Cardiology, Kiev, Ukraine
| | - Pentti Põder
- Department of Cardiology, North Estonia Medical Centre, Tallinn, Estonia
| | - Gerhard Pölzl
- Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Alexander Reinecke
- Klinik für Innere Medizin III, Kardiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
| | - Sven-Erik Ricksten
- Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Hynek Riha
- Department of Anaesthesiology and Intensive Care Medicine, Cardiothoracic Anaesthesiology and Intensive Care, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Alain Rudiger
- Department of Medicine, Spittal Limmattal, Schlieren, Switzerland
| | | | - Robert H. G. Schwinger
- Medizinische Klinik II, Klinikum Weiden, Teaching Hospital of University of Regensburg, Weiden, Germany
| | - Wolfgang Toller
- Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria
| | - Luigi Tritapepe
- Anaesthesia and Intensive Care Division, San Camillo-Forlanini Hospital, Rome, Italy
| | - Carsten Tschöpe
- Department of Cardiology, Campus Virchow Klinikum, Charité—University Medicine Berlin, Berlin, Germany
| | - Gerhard Wikström
- Institute of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Dirk von Lewinski
- Department of Cardiology, Myokardiale Energetik und Metabolismus Research Unit, Medical University of Graz, Graz, Austria
| | - Bojan Vrtovec
- Department of Cardiology, Advanced Heart Failure and Transplantation Centre, University Clinical Centre, Ljubljana, Slovenia
| | - Piero Pollesello
- Critical Care Proprietary Products, Orion Pharma, Espoo, Finland.
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Zima E, Farmakis D, Pollesello P, Parissis JT. Differential effects of inotropes and inodilators on renal function in acute cardiac care. Eur Heart J Suppl 2020; 22:D12-D19. [PMID: 32431569 PMCID: PMC7225871 DOI: 10.1093/eurheartj/suaa091] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Pathological interplay between the heart and kidneys is widely encountered in heart failure (HF) and is linked to worse prognosis and quality of life. Inotropes, along with diuretics and vasodilators, are a core medical response to HF but decompensated patients who need inotropic support often present with an acute worsening of renal function. The impact of inotropes on renal function is thus potentially an important influence on the choice of therapy. There is currently relatively little objective data available to guide the selection of inotrope therapy but recent direct observations on the effects of levosimendan and milrinone on glomerular filtration favour levosimendan. Other lines of evidence indicate that in acute decompensated HF levosimendan has an immediate renoprotective effect by increasing renal blood flow through preferential vasodilation of the renal afferent arterioles and increases in glomerular filtration rate: potential for renal medullary ischaemia is avoided by an offsetting increase in renal oxygen delivery. These indications of a putative reno-protective action of levosimendan support the view that this calcium-sensitizing inodilator may be preferable to dobutamine or other adrenergic inotropes in some settings by virtue of its renal effects. Additional large studies will be required, however, to clarify the renal effects of levosimendan in this and other relevant clinical situations, such as cardiac surgery.
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Affiliation(s)
- Endre Zima
- Cardiac Intensive Care, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Dimitrios Farmakis
- Department of Cardiology, University of Cyprus Medical School, Nicosia, Cyprus
| | - Piero Pollesello
- Critical Care Proprietary Products, CO, Orion Pharma, PO Box 65, FIN-02101 Espoo, Finland
| | - John T Parissis
- Second Department of Cardiology, National and Kapodistrian University of Athens, Attikon General Hospital, Athens, Greece
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Guarracino F, Zima E, Pollesello P, Masip J. Short-term treatments for acute cardiac care: inotropes and inodilators. Eur Heart J Suppl 2020; 22:D3-D11. [PMID: 32431568 PMCID: PMC7225903 DOI: 10.1093/eurheartj/suaa090] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Acute heart failure (AHF) continues to be a substantial cause of illness and death, with in-hospital and 3-month mortality rates of 5% and 10%, respectively, and 6-month re-admission rates in excess of 50% in a range of clinical trials and registry studies; the European Society of Cardiology (ESC) Heart Failure Long-Term Registry recorded a 1-year death or rehospitalization rate of 36%. As regards the short-term treatment of AHF patients, evidence was collected in the ESC Heart Failure Long-Term Registry that intravenous (i.v.) treatments are administered heterogeneously in the critical phase, with limited reference to guideline recommendations. Moreover, recent decades have been characterized by a prolonged lack of successful innovation in this field, with a plethora of clinical trials generating neutral or inconclusive findings on long-term mortality effects from a multiplicity of short-term interventions in AHF. One of the few exceptions has been the calcium sensitizer and inodilator levosimendan, introduced 20 years ago for the treatment of acutely decompensated chronic heart failure. In the present review, we will focus on the utility of this agent in the wider context of i.v. inotropic and inodilating therapies for AHF and related pathologies.
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Affiliation(s)
- Fabio Guarracino
- Dipartimento di Anestesia e Terapie Intensive, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Endre Zima
- Cardiac Intensive Care, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Piero Pollesello
- Critical Care Proprietary Products, CO, Orion Pharma, PO Box 65, FIN-02101 Espoo, Finland
| | - Josep Masip
- Intensive Care Department, Consorci Sanitari Integral, University of Barcelona, Barcelona, Spain
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Fredholm M, Jörgensen K, Houltz E, Ricksten S. Levosimendan or milrinone for right ventricular inotropic treatment?-A secondary analysis of a randomized trial. Acta Anaesthesiol Scand 2020; 64:193-201. [PMID: 31556095 DOI: 10.1111/aas.13486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 09/18/2019] [Accepted: 09/18/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND The aim of the present study was to compare the effects of milrinone and levosimendan on right ventricular (RV) inotropy and lusitropy in patients after aortic valve replacement (AVR) for aortic stenosis, a procedure in which an abnormal postoperative RV function may be seen. METHODS In a prospective, blinded trial, 31 patients were randomized to receive either milrinone (0.4 and 0.8 µg/kg/min, n = 16) or levosimendan (0.1 and 0.2 µg/kg/min, n = 15) after AVR for aortic stenosis. RV performance, afterload (pulmonary arterial elastance), RV strain, systolic (SR-S) and early diastolic (SR-E) strain rate were measured by pulmonary artery thermodilution catheterization and transoesophageal two-dimensional speckle tracking echocardiography. To circumvent the indirect effects of inodilator-induced hemodynamic changes on RV systolic and diastolic deformation, pulmonary arterial elastance, central venous pressure and heart rate were maintained constant by atrial pacing, plasma volume expansion with colloids and phenylephrine-induced vasoconstriction during treatment with the inotropes. RESULTS A dose-dependent increase in stroke volume index and cardiac index by approximately 20% were seen with both agents at the highest doses, with no difference between groups (P = .792 and 0.744, respectively). In both groups, RV strain and SR-S dose-dependently increased by 20% and 15%-19%, respectively, at the highest doses (P = .742 and 0.259, respectively) with no difference between groups. SR-E improved by both agents 20%-24% at the highest dose with no difference between groups (P = .714). CONCLUSIONS The direct RV inotropic and lusitropic effects of levosimendan and milrinone were comparable at clinically relevant infusion rates.
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Affiliation(s)
- Martin Fredholm
- Department of Anesthesiology and Intensive Care Medicine at the Sahlgrenska Academy University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden
| | - Kirsten Jörgensen
- Department of Anesthesiology and Intensive Care Medicine at the Sahlgrenska Academy University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden
| | - Erik Houltz
- Department of Anesthesiology and Intensive Care Medicine at the Sahlgrenska Academy University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden
| | - Sven‐Erik Ricksten
- Department of Anesthesiology and Intensive Care Medicine at the Sahlgrenska Academy University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden
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Li H, Duan Y, Chen B, Zhao Y, Su W, Wang S, Wu J, Lu L. New pharmacological treatments for heart failure with reduced ejection fraction (HFrEF): A Bayesian network meta-analysis. Medicine (Baltimore) 2020; 99:e18341. [PMID: 32000355 PMCID: PMC7004768 DOI: 10.1097/md.0000000000018341] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Heart failure with reduced ejection fraction (HFrEF) has contributed to an increasing number of deaths and readmissions over the past few decades. Despite the appearance of standard treatments, including diuretics, β-receptor blockers and angiotensin-converting enzyme inhibitor (ACEI), there are still a large number of patients who have progressive deterioration of heart function and, inevitably, end-stage heart failure. In recent years, new medications for treating chronic heart failure have been clinically applied, but there is controversy surrounding drug selection and whether patients with HFrEF benefit from these medications. Therefore, we aimed to compare and rank different new pharmacological treatments in patients with HFrEF. METHODS We performed a network meta-analysis to identify both direct and indirect evidence from relevant studies. We searched MEDLINE, EMBASE, and PsycINFO through the OVID database and CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating new pharmacological treatments in patients with HFrEF published up to September 30, 2018. We included trials of ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) and angiotensin-neprilysin inhibition (LCZ696). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. Based on these items, more than half of the entries were judged as having an overall low to moderate risk of bias; the remaining studies had a high or unclear risk of bias. The outcomes investigated were left ventricle ejection fraction (LVEF %), heart rate (HR) and serum level of B-type natriuretic peptide (BNP). We performed a random-effects network meta-analysis within a Bayesian framework. RESULTS We deemed 32 trials to be eligible that included 3810 patients and 32 treatments. Overall, 32 (94.1%) trials had a low to moderate risk of bias, while 2 (5.9%) trials had a high risk of bias. The quality of the included studies was rated as low in regard to allocation concealment and blinding and high in regard to other domains according to the Cochrane tools. As for increasing LVEF%, levosimendan was better than placebo (-3.77 (-4.96, -2.43)) and was the best intervention for improving ventricle contraction. As for controlling HR, n3-PUFA was better than placebo (4.01 (-0.44, 8.48)) and was the best choice for regulating HR. As for decreasing BNP, omega-3 was better than placebo (941.99 (-47.48, 1952.89) and was the best therapy for improving ventricle wall tension. CONCLUSIONS Our study confirmed the effectiveness of the included new pharmacological treatments for optimizing the structural performance and improving the cardiac function in the management of patients with HFrEF and recommended several interventions for clinical practice.
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Affiliation(s)
- Heng Li
- Cardiology Department of Tung Wah, Affiliated Hospital of Sun-Yat-Sen University
| | - Yuting Duan
- Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine
| | - Benfa Chen
- Cardiology Department of Tung Wah, Affiliated Hospital of Sun-Yat-Sen University
| | - Yu Zhao
- Cardiology Department of Tung Wah, Affiliated Hospital of Sun-Yat-Sen University
| | - Weiping Su
- Cardiology Department of Tung Wah, Affiliated Hospital of Sun-Yat-Sen University
| | - Shanhua Wang
- Cardiology Department of Tung Wah, Affiliated Hospital of Sun-Yat-Sen University
| | - Jiaming Wu
- Zhongshan Affiliated Hospital, Guangzhou University of Chinese Medicine, China
| | - Liming Lu
- Clinical Research Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine
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Pashkovetsky E, Gupta CA, Aronow WS. Use of levosimendan in acute and advanced heart failure: short review on available real-world data. Ther Clin Risk Manag 2019; 15:765-772. [PMID: 31354283 PMCID: PMC6588712 DOI: 10.2147/tcrm.s188761] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 06/01/2019] [Indexed: 12/18/2022] Open
Abstract
Published data have shown potential advantages of levosimendan in the management of acute decompensated heart failure and advanced heart failure when standard medical therapies threaten hemodynamics and organ perfusion are unable to alleviate clinical symptoms. Levosimendan distinguishes itself from other catecholaminergic inotropes by its three mechanisms of action: positive inotropy, vasodilation, and cardioprotection. In addition, its pharmacokinetics allow for a longer duration of action from the metabolite OR1896 allowing for further cardiovascular therapeutic effects for several days, even after discontinuation of the parent drug.
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Affiliation(s)
- Eugene Pashkovetsky
- Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA
| | - Chhaya Aggarwal Gupta
- Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA
| | - Wilbert S Aronow
- Division of Cardiology, Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA
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18
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Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth 2019; 21:328-332. [PMID: 30052230 PMCID: PMC6078018 DOI: 10.4103/aca.aca_19_18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Context: Inhaled levosimendan may act as selective pulmonary vasodilator and avoid systemic side effects of intravenous levosimendan, which include decrease in systemic vascular resistance (SVR) and systemic hypotension, but with same beneficial effect on pulmonary artery pressure (PAP) and right ventricular (RV) function. Aim: The aim of this study was to compare the effect of inhaled levosimendan with intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Settings and Design: The present prospective randomized comparative study was conducted in a tertiary care hospital. Subjects and Methods: Fifty patients were randomized into two groups (n = 25). Group A: Levosimendan infusion was started immediately after coming-off of cardiopulmonary bypass and continued for 24 h at 0.1 mcg/kg/min. Group B: Total dose of levosimendan which would be given through intravenous route over 24 h was calculated and then divided into four equal parts and administered through inhalational route 6th hourly over 24 h. Hemodynamic profile (pulse rate, mean arterial pressure, pulmonary artery systolic pressure [PASP], SVR) and RV function were assessed immediately after shifting, at 1, 8, 24, and 36 h after shifting to recovery. Statistical Analysis Used: Intragroup analysis was done using paired student t-test, and unpaired student t-test was used for analysis between two groups. Results: PASP and RV-fractional area change (RV-FAC) were comparable in the two groups at different time intervals. There was a significant reduction in PASP and significant improvement in RV-FAC with both intravenous and inhalational levosimendan. SVR was significantly decreased with intravenous levosimendan, but no significant decrease in SVR was observed with inhalational levosimendan. Conclusions: Inhaled levosimendan is a selective pulmonary vasodilator. It causes decrease in PAP and improvement in RV function, without having a significant effect on SVR.
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Affiliation(s)
- Tanveer Singh Kundra
- Department of Cardiac Anaesthesia, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
| | - P S Nagaraja
- Department of Cardiac Anaesthesia, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
| | - K S Bharathi
- Department of Cardiac Anaesthesia, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
| | - Parminder Kaur
- Department of Critical Care, Sir Ganga Ram Hospital, New Delhi, India
| | - N Manjunatha
- Department of Cardiac Anaesthesia, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India
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Lannemyr L, Ricksten S, Rundqvist B, Andersson B, Bartfay S, Ljungman C, Dahlberg P, Bergh N, Hjalmarsson C, Gilljam T, Bollano E, Karason K. Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial. J Am Heart Assoc 2018; 7:e008455. [PMID: 30369310 PMCID: PMC6201411 DOI: 10.1161/jaha.117.008455] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 07/02/2018] [Indexed: 01/07/2023]
Abstract
Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 μg/kg+0.1 μg/kg per minute) or dobutamine (7.5 μg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.
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Affiliation(s)
- Lukas Lannemyr
- Department of Anesthesiology and Intensive Care MedicineUniversity of GothenburgSahlgrenska UniversityGothenburgSweden
| | - Sven‐Erik Ricksten
- Department of Anesthesiology and Intensive Care MedicineUniversity of GothenburgSahlgrenska UniversityGothenburgSweden
| | - Bengt Rundqvist
- Department of TransplantationSahlgrenska University HospitalGothenburgSweden
| | - Bert Andersson
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Sven‐Erik Bartfay
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | | | - Pia Dahlberg
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Niklas Bergh
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Clara Hjalmarsson
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Thomas Gilljam
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Entela Bollano
- Department of CardiologySahlgrenska University HospitalGothenburgSweden
| | - Kristjan Karason
- Department of TransplantationSahlgrenska University HospitalGothenburgSweden
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Abstract
Pulmonary hypertension is a multifactorial disease with a high morbidity and
mortality. Right ventricular function is the most important predictor of
morbidity and mortality in patients suffering from pulmonary hypertension, but
currently there are no approved treatments directly supporting the failing right
ventricle. Levosimendan is a calcium sensitizing agent with inotropic, pulmonary
vasodilatory, and cardioprotective properties. Given its pharmacodynamic
profile, levosimendan could be a potential novel agent for the treatment of
right ventricular failure caused by pulmonary hypertension. The aim of this
review is to provide an overview of the current knowledge on the effects of
levosimendan in pulmonary hypertension and right heart failure.
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Affiliation(s)
- Mona Sahlholdt Hansen
- Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
| | - Asger Andersen
- Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
| | - Jens Erik Nielsen-Kudsk
- Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
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Møller MH, Granholm A, Junttila E, Haney M, Oscarsson-Tibblin A, Haavind A, Laake JH, Wilkman E, Sverrisson KÖ, Perner A. Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure. Acta Anaesthesiol Scand 2018; 62:420-450. [PMID: 29479665 PMCID: PMC5888146 DOI: 10.1111/aas.13089] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 12/28/2017] [Accepted: 01/03/2018] [Indexed: 12/22/2022]
Abstract
Background Adult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient‐important treatment recommendations on this topic. Methods This guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient‐important outcome measures, including mortality and serious adverse reactions. Results For all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions. Conclusions We suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.
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Affiliation(s)
- M. H. Møller
- Department of Intensive Care 4131; Copenhagen University Hospital, Rigshospitalet; Copenhagen Denmark
| | - A. Granholm
- Department of Intensive Care 4131; Copenhagen University Hospital, Rigshospitalet; Copenhagen Denmark
| | - E. Junttila
- Department of Anaesthesiology; Tampere University Hospital; Tampere Finland
| | - M. Haney
- Anaesthesiology and Intensive Care Medicine; Umeå University; Umeå Sweden
| | - A. Oscarsson-Tibblin
- Department of Anaesthesiology and Intensive Care; Department of Medicine and Health; Linköping University; Linköping Sweden
| | - A. Haavind
- Department of Anaesthesiology and Intensive Care; University Hospital Northern Norway; Tromsø Norway
| | - J. H. Laake
- Division of Critical Care; Oslo University Hospital; Oslo Norway
| | - E. Wilkman
- Division of Intensive Care Medicine; Department of Perioperative, Intensive Care and Pain Medicine; Helsinki University Hospital; University of Helsinki; Helsinki Finland
| | - K. Ö. Sverrisson
- Department of Anesthesia & Critical Care; Landspitali University Hospital of Iceland; Reykjavik Iceland
| | - A. Perner
- Department of Intensive Care 4131; Copenhagen University Hospital, Rigshospitalet; Copenhagen Denmark
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Madeira M, Caetano F, Almeida I, Fernandes A, Reis L, Costa M, Gonçalves L. Inotropes and cardiorenal syndrome in acute heart failure – A retrospective comparative analysis. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2017. [DOI: 10.1016/j.repce.2017.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Inotropes and cardiorenal syndrome in acute heart failure - A retrospective comparative analysis. Rev Port Cardiol 2017; 36:619-625. [PMID: 28826934 DOI: 10.1016/j.repc.2017.03.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Revised: 12/12/2016] [Accepted: 03/23/2017] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION Cardiorenal syndrome (CRS) is common in acute heart failure (AHF), and is associated with dire prognosis. Levosimendan, a positive inotrope that also has diuretic effects, may improve patients' renal profile. Published results are conflicting. OBJECTIVES We aimed to assess the incidence of CRS in AHF patients according to the inotrope used and to determine its predictors in order to identify patients who could benefit from the most renoprotective inotrope. METHODS In a retrospective study, 108 consecutive patients with AHF who required inotropes were divided into two groups according to the inotrope used (levosimendan vs. dobutamine). The primary endpoint was CRS incidence. Follow-up for mortality and readmission for AHF was conducted. RESULTS Seventy-one percent of the study population were treated with levosimendan and the remainder with dobutamine. No differences were found in heart failure etiology or chronic kidney disease. At admission, the dobutamine group had lower blood pressure; there were no differences in estimated glomerular filtration rate or cystatin C levels. The levosimendan group had lower left ventricular ejection fraction. CRS incidence was higher in the dobutamine group, and they more often had incomplete recovery of renal function at discharge. In multivariate analysis, cystatin C levels predicted CRS. The dobutamine group had higher in-hospital mortality, of which CRS and the inotrope used were predictors. CONCLUSIONS Levosimendan appears to have some renoprotective effect, as it was associated with a lower incidence of CRS and better recovery of renal function at discharge. Identification of patients at increased risk of renal dysfunction by assessing cystatin C may enable more tailored therapy, minimizing the incidence of CRS and its negative impact on outcome in AHF.
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Abstract
This article seeks to evaluate current practices in heart transplantation. The goals of this article were to review current practices for heart transplantation and its anesthesia management. The article reviews current demographics and discusses the current criteria for candidacy for heart transplantation. The process for donor and receipt selection is reviewed. This is followed by a review of mechanical circulatory support devices as they pertain to heart transplantation. The preanesthesia and intraoperative considerations are also discussed. Finally, management after transplantation is also reviewed.
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Affiliation(s)
- Davinder Ramsingh
- Department of Anesthesiology, Loma Linda Medical Center, 11234 Anderson Street, MC-2532-D, Loma Linda, CA 92354, USA.
| | - Reed Harvey
- Department of Anesthesiology, Ronald Reagan UCLA Medical Center, University of California at Los Angeles, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095-7403, USA
| | - Alec Runyon
- Department of Anesthesiology, Loma Linda Medical Center, 11234 Anderson Street, MC-2532-D, Loma Linda, CA 92354, USA
| | - Michael Benggon
- Department of Anesthesiology, Loma Linda Medical Center, 11234 Anderson Street, MC-2532-D, Loma Linda, CA 92354, USA
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Qiu J, Jia L, Hao Y, Huang S, Ma Y, Li X, Wang M, Mao Y. Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis. Life Sci 2017; 184:30-36. [PMID: 28689804 DOI: 10.1016/j.lfs.2017.07.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 06/22/2017] [Accepted: 07/01/2017] [Indexed: 01/13/2023]
Abstract
AIMS Right heart failure (RHF), which is caused by a variety of heart and lung diseases, has a high morbidity and mortality rate. Levosimendan is a cardiac inotropic drug and vasodilator. The effect of levosimendan on RHF remains unclear. We sought to evaluate the efficacy and safety of levosimendan in patients with acute RHF. MATERIALS AND METHODS We systematically searched PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov to identify studies reporting the efficacy and safety of levosimendan for the treatment of RHF. KEY FINDINGS Ten trials, including 359 participants from 6 RCTs and 4 self-controlled trials, were evaluated. In the 6 RCTs, we found that patients treated with levosimendan for 24h showed a significant increase in tricuspid annular plane systolic excursion [1.53; 95% CI (0.54, 2.53); P=0.002] and ejection fraction [3.59; 95% CI (1.21, 5.98); P=0.003] as well as a significant reduction in systolic pulmonary artery pressure [-6.15; 95% CI (-9.29, -3.02); P=0.0001] and pulmonary vascular resistance [-39.48; 95% CI (-65.59, -13.38); P=0.003], whereas changes in mean pulmonary pressure were nonsignificant. Adverse events did not significantly differ between the two groups. SIGNIFICANCE Our study shows that levosimendan exhibits short-term efficacy for treating RHF in patients with a variety of heart and lung diseases. Additional strict multicentre RCTs with long follow-up times and large sample sizes are required to further validate the efficacy and safety of this treatment.
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Affiliation(s)
- Jiayong Qiu
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Lei Jia
- State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China
| | - Yingying Hao
- Department of Infectious Diseases, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Shenshen Huang
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Yaqing Ma
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Xiaofang Li
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Min Wang
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Yimin Mao
- Department of Respiratory Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
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Cornejo-Avendaño J, Azpiri-López J, Ramírez-Rosales A. Levosimendan in acute decompensated heart failure: Systematic review and meta-analysis. MEDICINA UNIVERSITARIA 2017. [DOI: 10.1016/j.rmu.2017.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Fruhwald S, Pollesello P, Fruhwald F. Advanced heart failure: an appraisal of the potential of levosimendan in this end-stage scenario and some related ethical considerations. Expert Rev Cardiovasc Ther 2016; 14:1335-1347. [PMID: 27778514 DOI: 10.1080/14779072.2016.1247694] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The later stages of heart failure are characterized by a steady decline in quality of life. Clinical priorities should be to maintain functional capacity and quality of life. In the absence of sufficient organs for transplantation, options include left ventricular assist devices and inotropic support. Areas covered: We examined data published in the last two decades on the use of inotropes and inodilators in advanced heart failure. Expert commentary: In the literature, use of conventional inotropes, including adrenergic agonists and phosphodiesterase inhibitors, appears to be suboptimal for achieving the clinical priorities of late-stage heart failure. Evidence suggests instead that the calcium-sensitizing inodilator levosimendan, administered intermittently, delivers improvements in functional capacity and quality of life and does so with no adverse impact on life expectancy. At a terminal or near-terminal stage of heart failure, the therapeutic philosophy should shift towards meeting patients' existential priorities rather than traditional heart failure-centric targets.
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Affiliation(s)
- Sonja Fruhwald
- a Department of Anesthesiology and Intensive Care Medicine, Division of Anesthesiology for Cardiovascular Surgery and Intensive Care Medicine , Medical University of Graz , Graz , Austria
| | - Piero Pollesello
- b Critical Care Proprietary Products , Orion Pharma , Espoo , Finland
| | - Friedrich Fruhwald
- c Department of Internal Medicine, Division of Cardiology , Medical University of Graz , Graz , Austria
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Bozhinovska M, Taleska G, Fabian A, Šoštarič M. The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery. Open Access Maced J Med Sci 2016; 4:510-516. [PMID: 27703584 PMCID: PMC5042644 DOI: 10.3889/oamjms.2016.071] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Revised: 06/21/2016] [Accepted: 06/25/2016] [Indexed: 11/05/2022] Open
Abstract
The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP) channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.
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Affiliation(s)
- Marija Bozhinovska
- Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana, Slovenia
| | - Gordana Taleska
- Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana, Slovenia
| | - Andrej Fabian
- Institute of Physiology, Medical Faculty, University of Ljubljana, Slovenia; Department of Vascular Neurology and Neurological Intensive Therapy, University Clinical Centre Ljubljana, Slovenia
| | - Maja Šoštarič
- Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana, Slovenia
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Mishra A, Kumar B, Dutta V, Arya V, Mishra AK. Comparative Effect of Levosimendan and Milrinone in Cardiac Surgery Patients With Pulmonary Hypertension and Left Ventricular Dysfunction. J Cardiothorac Vasc Anesth 2016; 30:639-46. [DOI: 10.1053/j.jvca.2016.01.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Indexed: 11/11/2022]
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Alvarez Escudero J, Calvo Vecino JM, Veiras S, García R, González A. Clinical Practice Guideline (CPG). Recommendations on strategy for reducing risk of heart failure patients requiring noncardiac surgery: reducing risk of heart failure patients in noncardiac surgery. ACTA ACUST UNITED AC 2015; 62:359-419. [PMID: 26164471 DOI: 10.1016/j.redar.2015.05.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Accepted: 05/04/2015] [Indexed: 12/29/2022]
Affiliation(s)
- J Alvarez Escudero
- Professor and Head of the Department of Anesthesiology, University Hospital, Santiago de Compostela, La Coruña, Spain
| | - J M Calvo Vecino
- Professor and Head of the Department of Anesthesiology, University Hospital, Santiago de Compostela, La Coruña, Spain; Associated Professor and Head of the Department of Anesthesiology, Infanta Leonor University Hospital, Complutense University of Madrid, Madrid, Spain.
| | - S Veiras
- Department of Anesthesiology, University Hospital, Santiago de Compostela, La Coruña, Spain
| | - R García
- Department of Anesthesiology, Puerta del Mar University Hospital. Cadiz, Spain
| | - A González
- Department of Anesthesiology, Puerta de Hierro University Hospital. Madrid, Spain
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Palmerini E, Söderberg S, Mondillo S, Favilli R, Lunghetti S. Effects of levosimendan on heart failure in normotensive patients: does loading dose matter? ACUTE CARDIAC CARE 2015; 17:14-9. [PMID: 25806830 DOI: 10.3109/17482941.2015.1005102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Levosimendan is a calcium sensitizer and K(+)-ATP channel opener with inotropic and vasodilatatory effects irrespective of myocardial oxygen consumption, used for treatment of heart failure (HF). A loading dose is usually given by infusion for 12 h; however, profound lowering of blood pressure often disrupts or prolongs the infusion. The aim of this study was to assess clinical, biochemical and myocardial differences between different regimes of levosimendan therapy, with or without loading dose, and compared to standard therapy in heart failure. METHODS Fifty-seven patients (mean age ± SD: 60.9 ± 9.3 years, 45 males) with HF, New York Heart Association (NYHA) III-IV, reduced left ventricular ejection fraction (LVEF) were included. Twenty patients (NB group) were given levosimendan without loading dose, 14 patients (B group) were given levosimendan with loading dose, and 23 patients (C group) were given standard therapy. Clinical, biochemical and echocardiographic characteristics at baseline and one week after treatment were evaluated. RESULTS Groups were similar at baseline. After one week NHYA class (P < 0.001), NT pro-BNP (P < 0.001), LVEF (P = 0.045), E/A (P = 0.048) E/e' (P < 0.001), and PAPs (P < 0.001) decreased. DT (P = 0.011) and TAPSE (P = 0.035) increased in all groups. CONCLUSIONS Levosimendan, as well as standard therapy, improves myocardial function and symptoms of HF, irrespective of the loading dose administration. Treatment options for patients with end-stage heart failure refractory to conventional medical therapy are limited. Inotropic drugs play an important role in heart failure (HF).
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Affiliation(s)
- Elisabetta Palmerini
- Department of Cardiovascular Diseases, Siena University Hospital , Siena , Italy
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Koster G, Wetterslev J, Gluud C, Zijlstra JG, Scheeren TWL, van der Horst ICC, Keus F. Effects of levosimendan for low cardiac output syndrome in critically ill patients: systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 2014; 41:203-21. [DOI: 10.1007/s00134-014-3604-1] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 12/04/2014] [Indexed: 11/24/2022]
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Moreno N, Tavares-Silva M, Lourenço AP, Oliveira-Pinto J, Henriques-Coelho T, Leite-Moreira AF. Levosimendan: The current situation and new prospects. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2014. [DOI: 10.1016/j.repce.2014.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Balzer F, Treskatsch S, Spies C, Sander M, Kastrup M, Grubitzsch H, Wernecke KD, Braun JP. Early administration of levosimendan is associated with improved kidney function after cardiac surgery - a retrospective analysis. J Cardiothorac Surg 2014; 9:167. [PMID: 25399779 PMCID: PMC4240807 DOI: 10.1186/s13019-014-0167-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Accepted: 09/26/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Several animal studies suggest beneficial effects on kidney function upon administration of levosimendan. As recent data from clinical studies are heterogeneous, we sought to investigate whether levosimendan is associated with improved postoperative kidney function in cardiac surgery patients with respect to timing of its administration. METHODS Retrospective, single centre, observational analysis at a university hospital in Berlin, Germany. All adult patients without preoperative renal dysfunction that underwent coronary artery bypass grafting and/or valve reconstruction/replacement between 01/01/2007 and 31/12/2011 were considered for analyses. RESULTS Out of 1.095 included patients, 46 patients were treated with levosimendan due to a severely reduced left ventricular systolic function preoperatively (LVEF < 35%) and/or clinical signs of a low cardiac output syndrome. Sixty-one percent received the drug whilst in the OR, 39% after postoperative intensive care unit admission. When levosimendan was given immediately after anaesthesia induction, creatinine plasma levels (p = 0.009 for nonparametric analysis of longitudinal data in a two-factorial design) and incidence of postoperative renal dysfunction (67.9% vs. 94.4%; p = 0.033) were significantly reduced in contrast to a later start of treatment. In addition, duration of renal replacement therapy was significantly shorter (79 [35;332] vs. 272 [132;703] minutes; p = 0.046) in that group. CONCLUSIONS Postoperative kidney dysfunction is a common condition in patients under going cardiac surgery. Patients with severely reduced left ventricular function and/or clinical signs of a low cardiac output syndrome who preoperatively presented with a normal kidney function may benefit from an early start of levosimendan administration, i.e. immediately after anaesthesia. TRIAL REGISTRATION Clinicaltrials.gov-ID: NCT01918618 .
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Affiliation(s)
- Felix Balzer
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
| | - Sascha Treskatsch
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
| | - Claudia Spies
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
| | - Michael Sander
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
| | - Mark Kastrup
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
| | - Herko Grubitzsch
- Department of Cardiovascular Surgery, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| | | | - Jan P Braun
- Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Klinikum Hildesheim GmbH, Hildesheim, Germany.
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Moreno N, Tavares-Silva M, Lourenço AP, Oliveira-Pinto J, Henriques-Coelho T, Leite-Moreira AF. Levosimendan: The current situation and new prospects. Rev Port Cardiol 2014; 33:795-800. [PMID: 25459636 DOI: 10.1016/j.repc.2014.05.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Revised: 04/16/2014] [Accepted: 05/04/2014] [Indexed: 12/31/2022] Open
Abstract
Levosimendan is a pyridazinone-dinitrile derivative with positive inotropic and vasodilatory effects that has beneficial effects on myocardial performance. In previous randomized studies levosimendan improved hemodynamics and clinical course, but its effect on prognosis is still unclear. This important issue has limited its use. Although primarily used in the management of acute heart failure syndromes, this new inotropic agent may play a role in other clinical conditions. This review aims to summarize current knowledge on levosimendan and to present future prospects for the use of this drug.
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Affiliation(s)
- Nuno Moreno
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
| | - Marta Tavares-Silva
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - André P Lourenço
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - José Oliveira-Pinto
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Tiago Henriques-Coelho
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
| | - Adelino F Leite-Moreira
- Departamento de Fisiologia e Cirurgia Cardiotorácica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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Pierrakos C, Velissaris D, Franchi F, Muzzi L, Karanikolas M, Scolletta S. Levosimendan in critical illness: a literature review. J Clin Med Res 2014; 6:75-85. [PMID: 24578748 PMCID: PMC3935527 DOI: 10.14740/jocmr1702w] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2013] [Indexed: 01/30/2023] Open
Abstract
Levosimendan, the active enantiomer of simendan, is a calcium sensitizer developed for treatment of decompensated heart failure, exerts its effects independently of the beta adrenergic receptor and seems beneficial in cases of severe, intractable heart failure. Levosimendan is usually administered as 24-h infusion, with or without a loading dose, but dosing needs adjustment in patients with severe liver or renal dysfunction. Despite several promising reports, the role of levosimendan in critical illness has not been thoroughly evaluated. Available evidence suggests that levosimendan is a safe treatment option in critically ill patients and may reduce mortality from cardiac failure. However, data from well-designed randomized controlled trials in critically ill patients are needed to validate or refute these preliminary conclusions. This literature review is an attempt to synthesize available evidence on the role and possible benefits of levosimendan in critically ill patients with severe heart failure.
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Affiliation(s)
- Charalampos Pierrakos
- Department of Intensive Care, Universite Catholique de Louvain, Mont-Godinne University Hospital, Yvoir 5530, Belgium
| | - Dimitrios Velissaris
- Department of Internal Medicine, University of Patras School of Medicine, Patras, Greece
| | - Federico Franchi
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Luigi Muzzi
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Menelaos Karanikolas
- Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 S. Euclid Avenue, St. Louis, MO, USA
| | - Sabino Scolletta
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
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Huang X, Lei S, Zhu MF, Jiang RL, Huang LQ, Xia GL, Zhi YH. Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials. J Zhejiang Univ Sci B 2014; 14:400-15. [PMID: 23645177 DOI: 10.1631/jzus.b1200290] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support. METHODS Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias. RESULTS Data from a total of 3052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1373 [19.6%] in the levosimendan group, versus 328 of 1278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70-0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs. CONCLUSIONS In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.
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Affiliation(s)
- Xuan Huang
- Department of Gastroenterology, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China
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Yilmaz MB, Grossini E, Silva Cardoso JC, Édes I, Fedele F, Pollesello P, Kivikko M, Harjola VP, Hasslacher J, Mebazaa A, Morelli A, le Noble J, Oldner A, Oulego Erroz I, Parissis JT, Parkhomenko A, Poelzl G, Rehberg S, Ricksten SE, Rodríguez Fernández LM, Salmenperä M, Singer M, Treskatsch S, Vrtovec B, Wikström G. Renal effects of levosimendan: a consensus report. Cardiovasc Drugs Ther 2013; 27:581-90. [PMID: 23929366 PMCID: PMC3830192 DOI: 10.1007/s10557-013-6485-6] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).
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Affiliation(s)
- Mehmet B. Yilmaz
- Department of Cardiology, Cumhuriyet University School of Medicine, Sivas, Turkey
| | - Elena Grossini
- Laboratorio di Fisiologia, Dipartimento di Medicina Traslazionale, Università degli Studi del Piemonte Orientale A. Avogadro, Piemonte, Italy
| | - José C. Silva Cardoso
- Faculdade de Medicina, Alameda Prof. Hernâni Monteiro, Universidade do Porto, Porto, Portugal
| | - István Édes
- Institute of Cardiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
| | - Francesco Fedele
- Department of Cardiovascular, Respiratory, Nephrological, and Geriatric Sciences, La Sapienza University of Rome, Rome, Italy
| | | | - Matti Kivikko
- Cardiology and Critical Care, Orion Pharma, Espoo, Finland
| | - Veli-Pekka Harjola
- Departments of Cardiology, Helsinki University Hospital, Helsinki, Finland
| | - Julia Hasslacher
- Internistische Intensiv- und Notfallmedizin, Universitätsklinik für Innere Medizin, Innsbruck, Austria
| | - Alexandre Mebazaa
- Department of Anaesthesia and Intensive Care, INSERM UMR 942, Lariboisière Hospital, University of Paris, Paris, France
| | - Andrea Morelli
- Department of Cardiovascular, Respiratory, Nephrological, and Geriatric Sciences, La Sapienza University of Rome, Rome, Italy
| | - Jos le Noble
- Department of Intensive Care, VieCuri Medical Center, Venlo, The Netherlands
| | - Anders Oldner
- Department of Physiology & Pharmacology, Section of Anaesthesiology & Intensive CareMedicine, Karolinska Institute, Stockholm, Sweden
| | - Ignacio Oulego Erroz
- Department of Pediatrics, Complejo Asistencial Universitario de León, León, Spain
| | | | | | - Gerhard Poelzl
- Department of Cardiology, Medical University Innsbruck, Innsbruck, Austria
| | - Sebastian Rehberg
- Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Muenster, Germany
| | - Sven-Erik Ricksten
- Department of Cardiothoracic Anesthesia and Intensive Care, Sahlgrenska University Hospital, Gothenburg, Sweden
| | | | - Markku Salmenperä
- Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland
| | - Mervyn Singer
- Intensive Care Medicine, University College London, London, UK
| | - Sascha Treskatsch
- Department of Anesthesiology and Intensive Care Medicine, Charité - University Medicine Berlin, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, Germany
| | - Bojan Vrtovec
- Advanced Heart Failure and Transplantation Center, Department of Cardiology, Ljubljana University Medical Center, Ljubljana, Slovenia
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Abstract
The function of the right ventricle (RV) in heart failure (HF) has been mostly ignored until recently. A 2006 report of the National Heart, Lung, and Blood Institute identified a gap between RV research efforts and its clinical importance compared with that of the left ventricle. This recent shift in paradigm is fueled by the prognostic value ascribed to RV failure in HF and morbidity/mortality after myocardial infarction and surgery. In this review, we examine the significance of RV failure in the HF setting, its clinical presentation and pathophysiology, and ways to evaluate RV function using echocardiographic measurements. Furthermore, we discuss the medical management of RV failure including traditional therapies like beta-blockers and newer options like nitric oxide, phosphodiesterase inhibitors, and calcium sensitizers. Mechanical support is also examined. Finally, this review places an emphasis on RV failure in the setting of left ventricular assist devices and heart transplantation.
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Neema PK, Manikandan S, Chandran DA, Rathod RC, Mittnacht AJ, Love BA, Daves SM, Bachman C. Case 5--2011: Acute respiratory distress syndrome in an infant after repair of tetralogy of Fallot. J Cardiothorac Vasc Anesth 2011; 25:867-73. [PMID: 21962301 PMCID: PMC9941529 DOI: 10.1053/j.jvca.2011.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2010] [Indexed: 11/11/2022]
Affiliation(s)
- Praveen Kumar Neema
- Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, India.
| | - Sethuraman Manikandan
- Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, India
| | - Divya Amol Chandran
- Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, India
| | - Ramesh Chandra Rathod
- Department of Anaesthesiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Trivandrum, India
| | | | - Barry A. Love
- Congenital Cardiac Catheterization Laboratory, The Mount Sinai Medical Center, New York, NY
| | - Suanne M. Daves
- Division of Pediatric Cardiac Anesthesia, The Pediatric Heart Institute, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, TN
| | - Catherine Bachman
- Department of Anesthesia and Critical Care, The University of Chicago Medical Center, Chicago, IL
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Fedele F, DʼAmbrosi A, Bruno N, Caira C, Brasolin B, Mancone M. Cost-effectiveness of Levosimendan in Patients With Acute Heart Failure. J Cardiovasc Pharmacol 2011; 58:363-6. [DOI: 10.1097/fjc.0b013e318224e0a2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Mathieu S, Craig G. Levosimendan in the Treatment of Acute Heart Failure, Cardiogenic and Septic Shock: A Critical Review. J Intensive Care Soc 2011. [DOI: 10.1177/175114371101200106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Levosimendan is a drug which increases the sensitivity of the heart to calcium and which opens potassium channels, resulting in inodilation. Clinical trial data from patients suffering from heart failure have demonstrated that it improves haemodynamics without increasing intra-cellular calcium or oxygen consumption. However, there is no consistent evidence of mortality reduction. This narrative review summarises the key trials of its use in acute heart failure, acute coronary syndrome, cardiogenic shock and septic shock.
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Affiliation(s)
- Steve Mathieu
- Steve Mathieu Locum Consultant in Critical Care and Anaesthesia, The Royal Bournemouth Hospital
| | - Gordon Craig
- Gordon Craig Consultant in Critical Care and Anaesthesia, Queen Alexandra Hospital, Portsmouth
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Are pulmonary artery pulsatility indexes able to differentiate chronic pulmonary thromboembolism from pulmonary arterial hypertension? An echocardiographic and catheterization study. Heart Vessels 2010; 26:176-82. [PMID: 20953614 DOI: 10.1007/s00380-010-0044-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Accepted: 03/25/2010] [Indexed: 10/18/2022]
Abstract
The differentiation between chronic pulmonary thromboembolic hypertension (CTEPH) and pulmonary arterial hypertension (PAH) remains a clinical challenge. The aim of our study was to evaluate the usefulness of both echocardiographically and invasively derived pulmonary artery pulsatility indexes in the etiologic differentiation of patients with CTEPH and PAH. We retrospectively analyzed the results of echocardiographic and invasive hemodynamic examinations in 125 patients with either CTEPH (n = 62) or PAH (n = 63). Invasive data were obtained in 52 patients with CTEPH and 43 PAH patients. Using echocardiography, pulmonary artery systolic (PASP), diastolic (PADP) and mean (PAMP) pressures were estimated from velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. Pulse pressure (PP) was calculated as the difference between PASP and PADP. To obtain pulmonary artery pulsatility indexes, we normalized PP by PASP (PP/PASP), by PAMP (PP/PAMP) and by PADP (PP/PADP). Pulsatility indexes assessed by echocardiography did not differ between CTEPH and PAH patients except for PP/PAMP [PP/PAMP (1.82 ± 0.33 vs. 1.40 ± 0.3, p < 0.001)]. Invasively derived pulsatility indexes were significantly higher in subjects with CTEPH (0.60 ± 0.08 vs. 0.53 ± 0.09 for PP/PASP; 0.98 ± 0.21 vs. 0.81 ± 0.21 for PP/PAMP; 1.58 ± 0.52 vs. 1.21 ± 0.41 for PP/PADP; all p < 0.001). The areas under the receiver-operating characteristic curves analysis showed that no cutoff value allowed discriminating between CTEPH and PAH by using echocardiographically or invasively derived pulsatility indices. Invasively derived pulmonary artery pulsatility indexes as well as echocardiographically determined PP/PAMP indexes are higher in CTEPH compared to PAH. However, due to the important overlap no optimal threshold values of these parameters can be given to allow satisfactory discrimination of the two diseases in clinical practice.
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Heart surgery in patients on chronic dialysis: is there still room for improvement in early and long-term outcome? Heart Vessels 2010; 26:46-54. [DOI: 10.1007/s00380-010-0024-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 01/21/2010] [Indexed: 10/19/2022]
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Price LC, Wort SJ, Finney SJ, Marino PS, Brett SJ. Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Crit Care 2010; 14:R169. [PMID: 20858239 PMCID: PMC3219266 DOI: 10.1186/cc9264] [Citation(s) in RCA: 222] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2010] [Revised: 05/30/2010] [Accepted: 09/21/2010] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. METHODS A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. RESULTS Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. CONCLUSIONS This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.
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Affiliation(s)
- Laura C Price
- Department of Critical Care, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
| | - Stephen J Wort
- Department of Critical Care, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
| | - Simon J Finney
- Department of Critical Care, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
| | - Philip S Marino
- Department of Critical Care, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
| | - Stephen J Brett
- Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
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Cavusoglu Y, Beyaztas A, Birdane A, Ata N. Levosimendan and pulmonary hypertension. J Cardiovasc Med (Hagerstown) 2010; 11:478-80. [PMID: 20516805 DOI: 10.2459/jcm.0b013e32833a0a0b] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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48
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Kurt İH, Yavuzer K, Batur MK. Short-term effect of levosimendan on free light chain kappa and lambda levels in patients with decompensated chronic heart failure. Heart Vessels 2010; 25:392-9. [DOI: 10.1007/s00380-009-1216-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2009] [Accepted: 10/23/2009] [Indexed: 10/19/2022]
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49
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Importance of levosimendan on right ventricular function in patients with biventricular heart failure. Crit Care Med 2010. [DOI: 10.1097/ccm.0b013e3181d8c064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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50
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Importance of levosimendan on right ventricular function in patients with biventricular heart failure. Crit Care Med 2010; 38:1389-90; author reply 1390-1. [PMID: 20404640 DOI: 10.1097/ccm.0b013e3181d8a322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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