Institute for Clinical and Experimental Medicine
Published January 1, 2024 | Version v1
Journal article Open

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function

Authors/Creators

  • 1. Department of Internal Medicine, University of Genova, Genoa, Italy
  • 2. Department of Translational Medical Sciences, Interdepartmental Center for Clinical and Translational Research (CIRCET), and Interdepartmental Hypertension ResearchCenter (CIRIAPA), Federico II University, Naples, Italy
  • 3. Content and Communication, Branded Products, Orion Pharma, Espoo, Finland
  • 4. Deutsches Herzzentrum der Charité,Klinik für Kardiologie, Angiologie und Intensivmedizin (Campus CBF), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Berlin Institute of Health Centerfor Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany
  • 5. Institute of Experimental Cardiology, University Hospital Heidelberg, University ofHeidelberg and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany
  • 6. Heart Institute, Hospital Universitari GermansTrias i Pujol, CIBERCV, Universitat Autònoma de Barcelona, Barcelona, Spain
  • 7. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
  • 8. CardiovascularResearch Foundation, New York, NY, USA
  • 9. Department of Management, Information and Production Engineering, University of Bergamo, Dalmine (BG), Italy
  • 10. Department ofCardiology, Istituto Auxologico Italiano IRCCS Ospedale San Luca, Milan, Italy
  • 11. Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Division of Cardiology,Department of Medicine, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA, USA
  • 12. PHEniX laboratory, Department of Pulmonary Medicine, AmsterdamUMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands;
  • 13. msterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, TheNetherlands
  • 14. First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;
  • 15. Program of Cardiovascular Diseases,CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain
  • 16. CIBERCV, Madrid, Spain
  • 17. University of Milan, Milan, Italy
  • 18. Cardiology Division, San Paolo University Hospital,Milan, Italy
  • 19. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
  • 20. Division of Allergy, Pulmonary andCritical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 21. Comprehensive Heart Failure Center (CHFC) and Medical Clinic I, University ClinicWürzburg, Würzburg, Germany
  • 22. St.Georges Hospital, London, UK
  • 23. Institut klinicke a experimentalni mediciny
  • 24. Department of Internal Medicine V, University Hospital Schleswig-Holstein, and German Centre for Cardiovascular Research (DZHK), Partner siteHamburg/Kiel/Lübeck, Kiel, Germany
  • 25. Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
  • 26. Department of Internal Medicine and Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus-Liebig University, Giessen, Germany
  • 27. Division of Cardiology, MedicalUniversity of Graz, Graz, Austria
  • 28. BioTechMed Graz, Graz, Austria
  • 29. Department of Medicine, St. Johann in Tirol General Hospital, St. Johann in Tirol, Austria
  • 30. Division ofCardiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  • 31. Max-Rubner Center (CMR), Department of Cardiology, Charité-UniversitätsmedizinBerlin, Berlin, Germany
  • 32. Pulmonary Hypertension Association Europe, Vienna, Austria
  • 33. Department of Cardiovascular Research,European Center for Angioscience (ECAS), Heidelberg University, Mannheim, Germany;
  • 34. Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle uponTyne, UK
  • 35. Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
  • 36. Institute of Molecular and Translational TherapeuticStrategies (IMTTS), Hannover Medical School, Hannover, Germany

Description

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.

Notes

B.A.B. was supported by the National Institutes of Health (grants R01HL128526, R01 HL162828 and U01 HL160226) and by the United StatesDepartment of Defense (grant W81XWH2210245). SC was supportedby the Italian Ministry of Health (5 × 1000). S.Y.C. was supported byNational Institutes of Health (grants R01 HL124021 and HL 122596)and by the American Heart Association (grant 18EIA33900027). F.d.M.was supported by the Netherlands CardioVascular Research Initiative, theDutch Heart Foundation, Dutch Federation of University Medical Cen-tres, the Netherlands Organisation for Health Research and Develop-ment, and the Royal Netherlands Academy of Sciences (CVON-2012-08PHAEDRA, CVON-2018-29 PHAEDRA-IMPACT, and CVON-2017-10Dolphin-Genesis). F.d.M. was further supported by The NetherlandsOrganization for Scientific Research (NWO-VIDI: 917.18.338) and theDutch Heart Foundation Dekker senior post-doc grant (2018T059).V.M. was supported by the Ministry of Health of the Czech Republic(grant NU22-02-00161) and by the National Institute for Research ofMetabolic and Cardiovascular Diseases (Programme EXCELES, ID ProjectNo. LX22NPO5104 – funded by the European Union – Next Genera-tion EU). G.G.S. was supported by DZHK (German Centre for Cardio-vascular Research) with JRG, SE and DHZK/BHF/DHF joint Partnershipgrants; and by Deutsche Forschungsgemeinschaft (DFG, German ResearchFoundation – SFB-1470 – A02). K.S. was supported by the EuropeanResearch Council under the European Union’s Horizon 2020 research andinnovation programme (grant number 759248) and the German ResearchFoundation DFG (CRC1366 C07, project number 394046768). P.v.d.M.was supported by a grant from the HORIZON Europe ERC (ERC CoG101045236, DISSECT-HF). G.R. was supported by the Italian Ministry ofHealth (Ricerca Corrente 2023). C.G.T. is supported by the Italian Ministryof Health (PNRR-MAD-2022-12376632 and RF-2016-02362988).

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Has metadata
38639017 (PMID)
Is part of
1388-9842 (ISSN)
1879-0844 (ISSN)
References
10.1002/ejhf.3236 (DOI)