Cardiac remodelling – Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

Arantxa González*, A. Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Martin Hülsmann, Inês Falcao-Pires, Javier Díez, Roger S.Y. Foo, Mark Y. Chan, Alberto Aimo, Chukwuemeka G. Anene-Nzelu, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Yuri Belenkov, Tuvia B. Gal, Alain Cohen-Solal, Michael Böhm, Ovidiu ChioncelVictoria Delgado, Michele Emdin, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, James L. Januzzi, Pardeep S. Jhund, Yuri Lopatin, Lars H. Lund, Marco Metra, Davor Milicic, Brenda Moura, Christian Mueller, Wilfried Mullens, Julio Núñez, Massimo F. Piepoli, Amina Rakisheva, Arsen D. Ristić, Patrick Rossignol, Gianluigi Savarese, Carlo G. Tocchetti, Sophie Van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Antoni Bayés-Genís*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

31 Citations (Scopus)

Abstract

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Original languageEnglish
Pages (from-to)927-943
Number of pages17
JournalEuropean Journal of Heart Failure
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities Institute of Health Carlos III (ISCIII) (PI18/01469 and PI21/00946 to A.G.; CB16/11/00403 to A.B.-G and CB16/11/00483 to J.D. projects co-funded by the European Regional Development Funds); the European Commission (H2020 CRUCIAL project 2019–848109-2 to A.G.); the European Research Council (ERC CoG 818715 to R.A.d.B.; ERC-PoC Megfib to T.T.); the National Medical Research Council of Singapore (NMRC; NMRC/STaR/0022/2014 to A.M.R. and MOH-000280 to M.Y.C.); the Health Research Council of New Zealand (02/152, 08/070, 11/1070), National Heart Foundation of New Zealand, New Zealand Lotteries Grant Board, Foundation for Research, Science and Technology and the Christchurch Heart Institute Trust to A.M.R.; the Netherlands Heart Foundation (2017-21; 2017-11; 2018-30; 2020B005) to R.A.d.B.; the leDucq Foundation (Cure-PLaN) to R.A.d.B.; the Deutsche Forschungsgemeinschaft (KFO311 and TRR267 to T.T.; TTR 219 to M.B.; and TRR 1470 to S.V.L.); the Karolinska Institutet, the Swedish Research Council (523–2014-2336), the Swedish Heart Lung Foundation (20150557, 20190310), and the Stockholm County Council (20170112, 20190525) to L.H.L. Conflict of interest: A.M.R. reports research funding from Roche Diagnostics, Novo Nordisk and Bayer Healthcare (outside the submitted work). The UMCG, which employs R.A.d.B. has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche (outside the submitted work). R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). T.T. filed and licensed patents in the field of noncoding RNAs; he is founder and shareholder of Cardior Pharmaceuticals GmbH. He received speaker or other fees from Sanofi, Novo Nordisk. Boehringer Ingelheim, Takeda, Amicus Therapeutics, KSILINK (outside the submitted work). M.H. received consultant and speaker fee from Roche Diagnostics, Boehringer, Astra-Zeneca, Bayer, Biopeutics, Novartis, Vifor, Pfizer, Baxter, Takeda and Sanofi (outside the submitted work). M.Y.C. reports research funding from Astra-Zeneca, Roche Diagnostics, Bayer Healthcare, Boston Scientific and Abbott Technologies (outside the submitted work). S.D.A. reports receiving fees from Abbott, Actimed, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier and Vifor Pharma, and grant support from Abbott and Vifor Pharma (outside the submitted work). M.B. reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier and Vifor (outside the submitted work). V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD and Novartis (outside the submitted work). P.S.J.'s institution has been paid by Novartis, AstraZeneca, NovoNordisk, and Bayer for work on clinical trials. He has received consulting, advisory board, and speakers fees from Novartis, AstraZeneca, and Boehringer Ingelheim, and grants from Boehringer Ingelheim and Analog Devices Inc (outside the submitted work). L.H.L. received grants from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis; consulting fees from Merck, Vifor, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier; speakers honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, Novartis; and he is shareholder in AnaCardio (outside the submitted work). B.M. reports advisory or speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Ely Lilly, Servier, Novartis, Vifor Pharma (outside the submitted work). C.M. received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University of Basel, the University Hospital Basel, the KTI, Abbott, Beckman Coulter, BRAHMS, Idorsia, Ortho Diagnostics, Novartis, Roche, Siemens and Singulex, as well as speaker/consulting honoraria from Amgen, Astra Zeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idorsia, Novartis, Osler, Roche and Sanofi (outside the submitted work). J.N. reports personal fees from AstraZeneca, Novartis, Boehringer-Ingelheim, Eli Lilly, Rovi, NovoNordisk, and Vifor Pharma (outside the submitted work). M.F.P. received consultancy fees from AstraZeneca, CHF Solution, Novartis, and Servier (outside the submitted work). A.D.R. reports research funding from Novartis, Pfizer, GossamerBio, Jansens, and Arena/United Therapeutics as well as speaker fees/consultancies from Actavis, Astra-Zeneca, Berlin Chemie-Menarini, Boehringer Ingelheim, Hemofarm, MSD, Novartis, Pfizer, Sandoz, Servier, and Takeda (outside the submitted work). P.R. reports consulting for Idorsia, G3P, honoraria from AstraZeneca, Bayer, CinCor, CVRx, Fresenius, Grunenthal, Novartis, NovoNordisk, Relypsa, Roche, Servier, Stealth Peptides, and Vifor Fresenius Medical Care Renal Pharma; and travel grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma (outside the submitted work); Cofounder: CardioRenal. G.S. reports grants and personal fees from Vifor, Societá Prodotti Antibiotici, AstraZeneca, Roche, Servier, Novartis, GENESIS, Cytokinetics, Medtronic, Boston Scientific, PHARMACOSMOS, Merck, Bayer, Boehringer Ingelheim (outside the submitted work). C.G.T. has received funding from Amgen and personal fees from Vivalyfe (outside of the submitted work), and is listed as an inventor on two heart failure patents. All other authors have nothing to disclose.

Funding Information:
This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities Institute of Health Carlos III (ISCIII) (PI18/01469 and PI21/00946 to A.G.; CB16/11/00403 to A.B.‐G and CB16/11/00483 to J.D. projects co‐funded by the European Regional Development Funds); the European Commission (H2020 CRUCIAL project 2019–848109‐2 to A.G.); the European Research Council (ERC CoG 818715 to R.A.d.B.; ERC‐PoC Megfib to T.T.); the National Medical Research Council of Singapore (NMRC; NMRC/STaR/0022/2014 to A.M.R. and MOH‐000280 to M.Y.C.); the Health Research Council of New Zealand (02/152, 08/070, 11/1070), National Heart Foundation of New Zealand, New Zealand Lotteries Grant Board, Foundation for Research, Science and Technology and the Christchurch Heart Institute Trust to A.M.R.; the Netherlands Heart Foundation (2017‐21; 2017‐11; 2018‐30; 2020B005) to R.A.d.B.; the leDucq Foundation (Cure‐PLaN) to R.A.d.B.; the Deutsche Forschungsgemeinschaft (KFO311 and TRR267 to T.T.; TTR 219 to M.B.; and TRR 1470 to S.V.L.); the Karolinska Institutet, the Swedish Research Council (523–2014‐2336), the Swedish Heart Lung Foundation (20150557, 20190310), and the Stockholm County Council (20170112, 20190525) to L.H.L.

Funding Information:
A.M.R. reports research funding from Roche Diagnostics, Novo Nordisk and Bayer Healthcare (outside the submitted work). The UMCG, which employs R.A.d.B. has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche (outside the submitted work). R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). T.T. filed and licensed patents in the field of noncoding RNAs; he is founder and shareholder of Cardior Pharmaceuticals GmbH. He received speaker or other fees from Sanofi, Novo Nordisk. Boehringer Ingelheim, Takeda, Amicus Therapeutics, KSILINK (outside the submitted work). M.H. received consultant and speaker fee from Roche Diagnostics, Boehringer, Astra‐Zeneca, Bayer, Biopeutics, Novartis, Vifor, Pfizer, Baxter, Takeda and Sanofi (outside the submitted work). M.Y.C. reports research funding from Astra‐Zeneca, Roche Diagnostics, Bayer Healthcare, Boston Scientific and Abbott Technologies (outside the submitted work). S.D.A. reports receiving fees from Abbott, Actimed, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier and Vifor Pharma, and grant support from Abbott and Vifor Pharma (outside the submitted work). M.B. reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier and Vifor (outside the submitted work). V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, MSD and Novartis (outside the submitted work). P.S.J.'s institution has been paid by Novartis, AstraZeneca, NovoNordisk, and Bayer for work on clinical trials. He has received consulting, advisory board, and speakers fees from Novartis, AstraZeneca, and Boehringer Ingelheim, and grants from Boehringer Ingelheim and Analog Devices Inc (outside the submitted work). L.H.L. received grants from AstraZeneca, Vifor, Boston Scientific, Boehringer Ingelheim, Novartis; consulting fees from Merck, Vifor, AstraZeneca, Bayer, Pharmacosmos, MedScape, Sanofi, Lexicon, Myokardia, Boehringer Ingelheim, Servier; speakers honoraria from Abbott, MedScape, Radcliffe, AstraZeneca, Novartis; and he is shareholder in AnaCardio (outside the submitted work). B.M. reports advisory or speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Ely Lilly, Servier, Novartis, Vifor Pharma (outside the submitted work). C.M. received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University of Basel, the University Hospital Basel, the KTI, Abbott, Beckman Coulter, BRAHMS, Idorsia, Ortho Diagnostics, Novartis, Roche, Siemens and Singulex, as well as speaker/consulting honoraria from Amgen, Astra Zeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idorsia, Novartis, Osler, Roche and Sanofi (outside the submitted work). J.N. reports personal fees from AstraZeneca, Novartis, Boehringer‐Ingelheim, Eli Lilly, Rovi, NovoNordisk, and Vifor Pharma (outside the submitted work). M.F.P. received consultancy fees from AstraZeneca, CHF Solution, Novartis, and Servier (outside the submitted work). A.D.R. reports research funding from Novartis, Pfizer, GossamerBio, Jansens, and Arena/United Therapeutics as well as speaker fees/consultancies from Actavis, Astra‐Zeneca, Berlin Chemie‐Menarini, Boehringer Ingelheim, Hemofarm, MSD, Novartis, Pfizer, Sandoz, Servier, and Takeda (outside the submitted work). P.R. reports consulting for Idorsia, G3P, honoraria from AstraZeneca, Bayer, CinCor, CVRx, Fresenius, Grunenthal, Novartis, NovoNordisk, Relypsa, Roche, Servier, Stealth Peptides, and Vifor Fresenius Medical Care Renal Pharma; and travel grants from AstraZeneca, Bayer, CVRx, Novartis, and Vifor Fresenius Medical Care Renal Pharma (outside the submitted work); Cofounder: CardioRenal. G.S. reports grants and personal fees from Vifor, Societá Prodotti Antibiotici, AstraZeneca, Roche, Servier, Novartis, GENESIS, Cytokinetics, Medtronic, Boston Scientific, PHARMACOSMOS, Merck, Bayer, Boehringer Ingelheim (outside the submitted work). C.G.T. has received funding from Amgen and personal fees from Vivalyfe (outside of the submitted work), and is listed as an inventor on two heart failure patents. All other authors have nothing to disclose. Conflict of interest:

Publisher Copyright:
© 2022 European Society of Cardiology.

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