Reciprocal organ interactions during heart failure-a position paper from the ESC working group on myocardial function

Michele Ciccarelli, Dana Dawson, Inês Falcao-Pires, Mauro Giacca, Nazha Hamdani, Stéphane Heymans, Astrid Hooghiemstra, Annebet Leeuwis, Dorien Hermkens, Carlo Gabriele Tocchetti, Jolanda van der Velden, Serena Zacchigna, Thomas Thum

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Abstract

Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.

Original languageEnglish
Article numbercvab009
Pages (from-to)2416–2433
Number of pages18
JournalCardiovascular Research
Volume117
Issue number12
Early online date22 Jan 2021
DOIs
Publication statusPublished - 1 Nov 2021

Bibliographical note

Acknowledgements
We thank Sabine Kafert-Kasting, Hannover Medical School, who participated in the writing and technical editing of the manuscript.

Conflict of interest: C.G.T. holds patents in the field of cardiovascular disease. M.G. and T.T. hold patents in the field of non-coding RNAs and therapeutic applications thereof. T.T. is the founder and shareholder of Cardior Pharmaceuticals GmbH. T.T. reports fees/support from Novo Nordisk, Takeda, Amicus Therapeutics, Böhringer Ingelheim, and Sanofi-Genzyme (outside the scope of this position paper). S.H. reports personal fees from Astra Zeneca as a consultant preclinical development, personal fees from Cellprothera, as well as grants from Pfizer outside the submitted work. All other authors have nothing to disclose.

Funding
This work was supported by the British Heart Foundation, in particular, BHF Project Grant No. PG/17/64/33205 (to D.D.); European Union Commission’s Seventh Framework program (GA 305507 [HOMAGE] to S.H.) and EU Horizon 2020 project CARDIOREGENIX (GA 825670 to T.T.); ERA-Net-CVD project MacroERA (01KL1706 to S.H.); IMI2-CARDIATEAM (No. 821508 to S.H.); Netherlands Cardiovascular Research Initiative—an initiative with support of the Dutch Heart Foundation (CVON2016-Early HFPEF, 2015-10; CVON She-PREDICTS, 2017-21; and CVON Arena-PRIME, 2017-18 to S.H.; CVON 2018-28 & 2012-06 Heart Brain Connection; and CVON-Dosis 2014-20 to J.v.d.V., A.H., A.L., and D.H.); Research Foundation Flanders FWO (G091018N and G0B5930N to S.H.); Deutsche Forschungsgemeinschaft (KFO311/TH903/20 to T.T.); AIRC (IG 2016 19032 to S.Z.); Dutch Federation of University Medical Centres, the Netherlands Organisation for Health Research and Development and the Royal Netherlands Academy of Sciences, and the Netherlands Organization for Sciences-ZonMW (VICI 91818602 to J.v.d.V.) as well as Project NETDIAMOND (POCI-01-0145-FEDER-016385), supported by European Structural and Investment Funds, Lisbon's Regional Operational Program 2020 and national funds from the Portuguese Foundation for Science and Technology (to I. F.-P.).

Keywords

  • Heart failure
  • Multi-organ clinical syndrome
  • Lung
  • Intestine
  • Kidney
  • Brain
  • Adipose tissue
  • Liver
  • Non-coding RNAs

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