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      Levosimendan in pulmonary hypertension and right heart failure

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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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          2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure.

          Piotr Ponikowski, Adriaan A. Voors, Stefan D. Anker … (2016)
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            Guidelines for the diagnosis and treatment of pulmonary hypertension.

            N Galie, M Hoeper, M. Humbert … (2009)
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              Left ventricular heart failure and pulmonary hypertension†

              Stephan Rosenkranz, J. Gibbs, Rolf Wachter … (2015)
              In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65–80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a ‘left ventricular phenotype’ to a ‘right ventricular phenotype’ across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pulm Circ
                Journal ID (iso-abbrev): Pulm Circ
                Journal ID (publisher-id): PUL
                Journal ID (hwp): sppul
                Title: Pulmonary Circulation
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Print): 2045-8932
                ISSN (Electronic): 2045-8940
                Publication date (Electronic): 06 July 2018
                Publication date Collection: Jul-Sep 2018
                Volume: 8
                Issue: 3
                Electronic Location Identifier: 2045894018790905
                Affiliations
                [1-2045894018790905]Department of Cardiology, Institute of Clinical Medicine, Aarhus University Hospital, Denmark
                Author notes
                [*]Mona Sahlholdt Hansen, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. Email: monasahlholdt@ 123456gmail.com
                Article
                Publisher ID: 10.1177_2045894018790905
                DOI: 10.1177/2045894018790905
                PMC ID: 6058424
                PubMed ID: 29979110
                SO-VID: 8311a988-1f5c-4602-8869-31b377bbefa6
                Copyright © © The Author(s) 2018
                License:

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 9 November 2017
                Date accepted : 29 June 2018
                Funding
                Funded by: Novo Nordisk Foundation, FundRef ;
                Award ID: NNF17OC0024868
                Categories
                Subject: Review Article
                Custom metadata
                cover-date July-September 2018

                ScienceOpen disciplines: Respiratory medicine
                Keywords: right heart failure,levosimendan,calcium sensitizer,pulmonary hypertension,pulmonary arterial hypertension,congenital heart disease
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: right heart failure, levosimendan, calcium sensitizer, pulmonary hypertension, pulmonary arterial hypertension, congenital heart disease

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