Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

R.A. de Boer; J.S. Hulot; C.G. Tocchetti; J.P. Aboumsallem; P. Ameri; S.D. Anker; J. Bauersachs; E. Bertero; A.J.S. Coats; J. Celutkiene; O. Chioncel; P. Dodion; T. Eschenhagen; D. Farmakis; A. Bayes-Genis; D. Jager; E.A. Jankowska; R.N. Kitsis; S.H. Konety; J. Larkin; L. Lehmann; D.J. Lenihan; C. Maack; J.J. Moslehi; O.J. Muller; P. Nowak-Sliwinska; M.F. Piepoli; P. Ponikowski; R. Pudil; P.P. Rainer; F. Ruschitzka; D. Sawyer; P.M. Seferovic; T. Suter; T. Thum; P. van der Meer; L.W. Van Laake; S. von Haehling; S. Heymans; A.R. Lyon; J. Backs

doi:10.1002/ejhf.2029

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

R.A. de Boer^*, J.S. Hulot, C.G. Tocchetti, J.P. Aboumsallem, P. Ameri, S.D. Anker, J. Bauersachs, E. Bertero, A.J.S. Coats, J. Celutkiene, O. Chioncel, P. Dodion, T. Eschenhagen, D. Farmakis, A. Bayes-Genis, D. Jager, E.A. Jankowska, R.N. Kitsis, S.H. Konety, J. LarkinL. Lehmann, D.J. Lenihan, C. Maack, J.J. Moslehi, O.J. Muller, P. Nowak-Sliwinska, M.F. Piepoli, P. Ponikowski, R. Pudil, P.P. Rainer, F. Ruschitzka, D. Sawyer, P.M. Seferovic, T. Suter, T. Thum, P. van der Meer, L.W. Van Laake, S. von Haehling, S. Heymans, A.R. Lyon, J. Backs

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

Original language	English
Pages (from-to)	2272-2289
Number of pages	18
Journal	European journal of heart failure
Volume	22
Issue number	12
DOIs	https://doi.org/10.1002/ejhf.2029
Publication status	Published - 1 Dec 2020

Keywords

ANTHRACYCLINE CARDIOTOXICITY
Angiogenesis
CACHEXIA
CARDIAC DYSFUNCTION
CLONAL HEMATOPOIESIS
Cancer
Cardio&#8208
Cardiotoxicity
Clonal haematopoiesis
DISEASE
DOXORUBICIN
Extracellular matrix
Heart failure
INCREASED RISK
Inflammation
Metabolism
RADIATION-EXPOSURE
SYMPATHETIC-NERVOUS-SYSTEM
TUMOR-GROWTH
angiogenesis
anthracycline cardiotoxicity
cachexia
cancer
cardiac dysfunction
cardio&#8208
cardiotoxicity
clonal haematopoiesis
clonal hematopoiesis
disease
doxorubicin
extracellular matrix
heart failure
increased risk
inflammation
metabolism
oncology
radiation-exposure
sympathetic-nervous-system
tumor-growth
Cardio-oncology

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de Boer, R. A., Hulot, J. S., Tocchetti, C. G., Aboumsallem, J. P., Ameri, P., Anker, S. D., Bauersachs, J., Bertero, E., Coats, A. J. S., Celutkiene, J., Chioncel, O., Dodion, P., Eschenhagen, T., Farmakis, D., Bayes-Genis, A., Jager, D., Jankowska, E. A., Kitsis, R. N., Konety, S. H., ... Backs, J. (2020). Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). European journal of heart failure, 22(12), 2272-2289. https://doi.org/10.1002/ejhf.2029

@article{1e2febd4b96044388ebfc834c9c6b191,

title = "Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)",

abstract = "The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.",

keywords = "ANTHRACYCLINE CARDIOTOXICITY, Angiogenesis, CACHEXIA, CARDIAC DYSFUNCTION, CLONAL HEMATOPOIESIS, Cancer, Cardio&#8208, Cardiotoxicity, Clonal haematopoiesis, DISEASE, DOXORUBICIN, Extracellular matrix, Heart failure, INCREASED RISK, Inflammation, Metabolism, RADIATION-EXPOSURE, SYMPATHETIC-NERVOUS-SYSTEM, TUMOR-GROWTH, angiogenesis, anthracycline cardiotoxicity, cachexia, cancer, cardiac dysfunction, cardio&#8208, cardiotoxicity, clonal haematopoiesis, clonal hematopoiesis, disease, doxorubicin, extracellular matrix, heart failure, increased risk, inflammation, metabolism, oncology, radiation-exposure, sympathetic-nervous-system, tumor-growth, Cardio-oncology",

author = "{de Boer}, R.A. and J.S. Hulot and C.G. Tocchetti and J.P. Aboumsallem and P. Ameri and S.D. Anker and J. Bauersachs and E. Bertero and A.J.S. Coats and J. Celutkiene and O. Chioncel and P. Dodion and T. Eschenhagen and D. Farmakis and A. Bayes-Genis and D. Jager and E.A. Jankowska and R.N. Kitsis and S.H. Konety and J. Larkin and L. Lehmann and D.J. Lenihan and C. Maack and J.J. Moslehi and O.J. Muller and P. Nowak-Sliwinska and M.F. Piepoli and P. Ponikowski and R. Pudil and P.P. Rainer and F. Ruschitzka and D. Sawyer and P.M. Seferovic and T. Suter and T. Thum and {van der Meer}, P. and {Van Laake}, L.W. and {von Haehling}, S. and S. Heymans and A.R. Lyon and J. Backs",

note = "Funding Information: R.A.d.B. reports grants from European Research Council, AstraZeneca, Abbott, Bristol‐Myers Squibb, Novartis, Novo Nordisk, Roche, during the conduct of the study; personal fees from Abbott, AstraZeneca, Novartis, Roche, outside the submitted work. S.v.H. reports personal fees from Bayer, Boehringer Ingelheim, BRAHMS, Chugai, Novartis, Pharmacosmos, Roche, Vifor, outside the submitted work; and owns shares in Actimed. J.B. reports personal fees from Bayer, outside the submitted work; has a patent EP2954322B1 ( method for cardiovascular risk stratification) issued. C.M. reports personal fees from AstraZeneca, Bristol‐Myers Squibb, Berlin Chemie, Novartis, Amgen, Boehringer Ingelheim, Sevier, outside the submitted work. J.M. reports personal fees from Pfizer, Novartis, Takeda, Bristol‐Myers Squibb, GSK, Nektar, AstraZeneca, Audentes, Myovant, Regeneron, during the conduct of the study. D.F. reports personal fees from Abbott Laboratories, Bayer, Boehringer‐Ingelheim, Menarini, Novartis, Orion Pharma, Roche Diagnostics, outside the submitted work. A.R.L. reports grants and personal fees from Servier, Pfizer, personal fees from Novartis, Roche, Takeda, Boehringer Ingelheim, Amgen, Clinigen Group, Ferring Pharmaceuticals, Eli Lily, Bristol‐Myers Squibb, Eisai Ltd, Myocardial Solutions, Heartfelt Technologies, outside the submitted work. P.A. reports personal fees from Novartis, Servier, Daiichi‐Sankyo, Bayer, Pfizer, AstraZeneca, Jansenn, Merck Sharp & Dohme, GlaxoSmithKline, grants and personal fees from Boehringer Ingelheim, outside the submitted work. T.E. reports a speaker honorarium for Novartis, related to sacubitril/valsartan, not relevant for this work. O.J.M. reports personal fees from Bayer, Bristol‐Myers Squibb, Daiichi‐Sankyo, Pfizer, Servier, outside the submitted work. J.S.H. reports grants from Leducq Foundation, Fondation pour la Recherche M{\'e}dicale, Sanofi, Servier, Bioserenity, personal fees from Amgen, Bayer, AstraZeneca, Bristol‐Myers Squibb, personal fees and non‐financial support from Novartis, outside the submitted work. P.v.d.M. reports grants and personal fees from Vifor Pharma, AstraZeneca, Pfizer, grants from Ionis, Corvidia, personal fees from Servier, outside the submitted work. R.N.K. reports he is Co‐Founder and President, ASPIDA Therapeutics Inc. P.P.R. reports personal fees and non‐financial support from Novartis, non‐financial support from Sanofi, Abbott, Daiichi‐Sankyo, Bayer, outside the submitted work. J.{\v C}. reports personal fees from Roche Diagnostics, AstraZeneca, Servier, Berlin‐Chemie, Novartis, outside the submitted work. E.A.J. reports personal fees from Boehringer Ingelheim, Vifor Pharma, Servier, Bayer, Berlin‐Chemie, Novartis, Abbott, AstraZeneca, outside the submitted work. T.T. reports personal fees from Cardior Pharmaceuticals, other from Novo Nordisk, outside the submitted work. J.B. reports personal fees from Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi‐Sankyo, Medtronic, MSD, Novartis, Pfizer, Servier, grants and personal fees from Abiomed, CvRX, Vifor, Zoll, outside the submitted work. A.A.J.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimensions, CVRx, Enopace, Faraday, Gore, Impulse Dynamics, Respicardia, Stealth Peptides, Corvia, Arena, ESN Cleer, outside the submitted work. P.P. reports personal fees from Boehringer Ingelheim, Amgen, Vifor, Servier, Bayer, BMS, Respicardia, Berlin‐Chemie, Novartis, Abbott Vascular, AstraZeneca, outside the submitted work. C.G.T. reports grants from Federico II University/Ricerca di Ateneo, during the conduct of the study; personal fees from Alere, outside the submitted work; has a Canadian Patent No. 2613477, issued on Dec 3, 2013 Inventors: Nazareno Paolocci, David A. Kass, Carlo G. Tocchetti. Owner: Johns Hopkins University Entitled: THIOL‐SENSITIVE POSITIVE INOTROPES JHU Ref.: C04755‐P04755‐05 with royalties paid. D.J.L. reports personal fees from Acorda, Inc, Bristol‐Myers Squibb, Lilly, Roche, Inc, grants from Myocardial Solutions, outside the submitted work. F.R.: since 1st January 2018: no personal payments, all payments directly to the University of Zurich. Before 2018: F.R. reports grants and personal fees from SJM/Abbott, Servier, Bayer, personal fees from Zoll, Novartis, AstraZeneca, Sanofi, Amgen, BMS, Pfizer, Fresenius, Vifor, Roche, Cardiorentis, Boehringer Ingelheim, other from Heartware, grants from Mars, outside the submitted work. L.L. reports personal fees from MSD, Daiichi‐Sankyo, Novartis, Servier, outside the submitted work. M.S.P. reports grants from Novartis, Servier, Vifor. O.C. reports grants from Servier, Vifor, Novartis, grants and other from Boehringer Ingelheim, outside the submitted work. P.D. reports other from Innate Pharma, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, Abbott Vascular, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, Cardiac Dimensions, Actimed Therapeutics, outside the submitted work. P.M.S. reports honorarium for lecture from Medtronic, Abbott, Servier, AstraZeneca, Respicardia, consultancy agreement and honorarium for lecture from Boehringer Ingelheim, Novartis, consultancy agreement from Vifor Pharma. D.J. reports other from Amgen Inc, Bayer Pharma AG, BMS GmbH & Co KGaA, CureVac AG, Definiens AG; Genmab A‐S, F. Hoffmann‐La Roche Ltd, Vaximm AG; Zelluna Immunotherapy AS, Life Science Inkubator GmbH, outside the submitted work. J.L. reports grants and personal fees from Achilles Therapeutics, BMS, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, personal fees from AstraZeneca, Boston Biomedical, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Sorono, Pierre Fabre, Secarna, Vitaccess, Covance, grants Aveo, Pharmacyclics, outside the submitted work. All other authors have nothing to disclose. Conflict of interest: in vitro Funding Information: R.A.d.B. is supported by the European Research Council [ERC CoG 818 715, SECRETE-HF], and furthermore by the Netherlands Heart Foundation (CVON DOSIS, grant [2014-40], CVON SHE-PREDICTS-HF, grant [2017-21]; CVON RED-CVD, grant [2017-11]; and CVON PREDICT2, grant [2018-30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant [917.13.350]), and by a grant from the Leducq Foundation (Cure PhosphoLambaN induced Cardiomyopathy, Cure-PLaN). S.H. gets support of the ERA-Net-CVD project MacroERA, [01KL1706], and IMI2-CARDIATEAM [N. 821 508], from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant [2017-21], CVON Arena-PRIME, 2017-18, support of FWO [G091018N] (2017) and [G0B5920N] (2019). J.B. is supported by the Collaborative Research Center (SFB) 1118 of the German Research Foundation (DFG), by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium f?r Bildung und Forschung (BMBF) and by the Ministerium f?r Wissenschaft, Forschung und Kunst (MWK) Baden W?rttemberg. C.M. is funded by the German Research Foundation [DFG; Ma 2528/7-1; SFB 894; TRR 219] and the Federal Ministry of Education and Research [BMBF; BMBF; 01EO1504]. A.R.L. is supported by a grant from the Leducq Foundation (Cardio-Oncology Network). A.B.G. is supported by TerCel [RD16/0011/0006, RD16/0011/0028], CIBER Cardiovascular - [CB16/11/00403, the CERCA Programme/Generalitat de Catalunya, and ?la Caixa? Banking Foundation. C.G.T. is supported by a ?Federico II University/Ricerca di Ateneo? grant. Funding Information: R.A.d.B. is supported by the European Research Council [ERC CoG 818 715, SECRETE‐HF], and furthermore by the Netherlands Heart Foundation (CVON DOSIS, grant [2014‐40], CVON SHE‐PREDICTS‐HF, grant [2017‐21]; CVON RED‐CVD, grant [2017‐11]; and CVON PREDICT2, grant [2018‐30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant [917.13.350]), and by a grant from the Leducq Foundation (Cure PhosphoLambaN induced Cardiomyopathy, Cure‐PLaN). S.H. gets support of the ERA‐Net‐CVD project MacroERA, [01KL1706], and IMI2‐CARDIATEAM [N. 821 508], from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016‐Early HFPEF, 2015‐10, CVON She‐PREDICTS, grant [2017‐21], CVON Arena‐PRIME, 2017‐18, support of FWO [G091018N] (2017) and [G0B5920N] (2019). J.B. is supported by the Collaborative Research Center (SFB) 1118 of the German Research Foundation (DFG), by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium f{\"u}r Bildung und Forschung (BMBF) and by the Ministerium f{\"u}r Wissenschaft, Forschung und Kunst (MWK) Baden W{\"u}rttemberg. C.M. is funded by the German Research Foundation [DFG; Ma 2528/7‐1; SFB 894; TRR 219] and the Federal Ministry of Education and Research [BMBF; BMBF; 01EO1504]. A.R.L. is supported by a grant from the Leducq Foundation (Cardio‐Oncology Network). A.B.G. is supported by TerCel [RD16/0011/0006, RD16/0011/0028], CIBER Cardiovascular ‐ [CB16/11/00403, the CERCA Programme/Generalitat de Catalunya, and {\textquoteleft}la Caixa{\textquoteright} Banking Foundation. C.G.T. is supported by a {\textquoteleft}Federico II University/Ricerca di Ateneo{\textquoteright} grant. P.A. is supported by the Italian Ministry of Health ([GR‐2018‐12 365 661], CHANGE Study). L.L. is supported by the German Centre for Cardiovascular Research (DZHK). T.E. is supported by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium f{\"u}r Bildung und Forschung (BMBF) and the European Horizon 2020 Programme (REANIMA), ERA‐CVD Variation, and ITN TRAIN‐HEART. O.J.M. is supported by the German Research Foundation (DFG) [DFG MU_1654/11–1], the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium f{\"u}r Bildung und Forschung (BMBF) [81Z0700201] as well as the European Horizon 2020 programme [CardioReGenix]. J.S.H. is supported by INSERM, the French National Research Agency [NADHeart ANR‐17‐CE17‐0015‐02, PACIFIC ANR‐18‐CE14‐0032‐01, CORRECT_LMNA ANR‐19‐CE17‐0013‐02], BPIFrance [2018‐PSPC‐07], the ERA‐Net‐CVD [ANR‐16‐ECVD‐0011‐03] (Clarify project), F{\'e}d{\'e}ration Fran{\c c}aise de Cardiologie, the Fondation pour la Recherche M{\'e}dicale, and by a grant from the Leducq Foundation [18CVD05]. P.v.d.M. is supported by the European Research Council [ERC StG STOP‐HF 715732], Dutch Heart Foundation (DHF) grant eSCAPE‐HF and the Human Frontier Science Program (HFSP) grant [RGY0071/2014]. R.P. is supported by Research project of Charles University Prague, Progress Q40/03. R.N.K. is supported by National Institutes of Health grants [R01HL130861 and R01HL138475]; Department of Defense grants [PR151134P1 and PR191593]; AHA grant [18SRG34280018]; and Foundation Leducq grant [RA15CVD04]. P.P.R. is supported by the ERA‐NET CVD project AIR‐MI and the Austrian Society of Cardiology. J.B. got support from the Erich und Emmy Hoselmann‐Stiftung. J.M. is supported by grants from National Institutes of Health (NIH) [R56 HL141466] and [R01 HL141466]. L.V.L. is supported by the Netherlands Heart Foundation (Dekker Senior Clinical Scientist (2019 T056). P.N.S. is supported by the European Research Council (ERC StG 680 209, OPTIM) and Swiss Innovation Agency ‐ InnoSwiss (28747). P.D. is an employee of Innate Pharma and owns shares of the company. T.T. is supported by an ERC Consolidator grant Longheart and Deutsche Forschungsgemeinschaft [KFO311]. Publisher Copyright: {\textcopyright} 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2020",

month = dec,

day = "1",

doi = "10.1002/ejhf.2029",

language = "English",

volume = "22",

pages = "2272--2289",

journal = "European journal of heart failure",

issn = "1388-9842",

publisher = "Wiley",

number = "12",

}

de Boer, RA, Hulot, JS, Tocchetti, CG, Aboumsallem, JP, Ameri, P, Anker, SD, Bauersachs, J, Bertero, E, Coats, AJS, Celutkiene, J, Chioncel, O, Dodion, P, Eschenhagen, T, Farmakis, D, Bayes-Genis, A, Jager, D, Jankowska, EA, Kitsis, RN, Konety, SH, Larkin, J, Lehmann, L, Lenihan, DJ, Maack, C, Moslehi, JJ, Muller, OJ, Nowak-Sliwinska, P, Piepoli, MF, Ponikowski, P, Pudil, R, Rainer, PP, Ruschitzka, F, Sawyer, D, Seferovic, PM, Suter, T, Thum, T, van der Meer, P, Van Laake, LW, von Haehling, S, Heymans, S, Lyon, AR & Backs, J 2020, 'Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)', European journal of heart failure, vol. 22, no. 12, pp. 2272-2289. https://doi.org/10.1002/ejhf.2029

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). / de Boer, R.A.; Hulot, J.S.; Tocchetti, C.G. et al.
In: European journal of heart failure, Vol. 22, No. 12, 01.12.2020, p. 2272-2289.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

AU - de Boer, R.A.

AU - Hulot, J.S.

AU - Tocchetti, C.G.

AU - Aboumsallem, J.P.

AU - Ameri, P.

AU - Anker, S.D.

AU - Bauersachs, J.

AU - Bertero, E.

AU - Coats, A.J.S.

AU - Celutkiene, J.

AU - Chioncel, O.

AU - Dodion, P.

AU - Eschenhagen, T.

AU - Farmakis, D.

AU - Bayes-Genis, A.

AU - Jager, D.

AU - Jankowska, E.A.

AU - Kitsis, R.N.

AU - Konety, S.H.

AU - Larkin, J.

AU - Lehmann, L.

AU - Lenihan, D.J.

AU - Maack, C.

AU - Moslehi, J.J.

AU - Muller, O.J.

AU - Nowak-Sliwinska, P.

AU - Piepoli, M.F.

AU - Ponikowski, P.

AU - Pudil, R.

AU - Rainer, P.P.

AU - Ruschitzka, F.

AU - Sawyer, D.

AU - Seferovic, P.M.

AU - Suter, T.

AU - Thum, T.

AU - van der Meer, P.

AU - Van Laake, L.W.

AU - von Haehling, S.

AU - Heymans, S.

AU - Lyon, A.R.

AU - Backs, J.

N1 - Funding Information: R.A.d.B. reports grants from European Research Council, AstraZeneca, Abbott, Bristol‐Myers Squibb, Novartis, Novo Nordisk, Roche, during the conduct of the study; personal fees from Abbott, AstraZeneca, Novartis, Roche, outside the submitted work. S.v.H. reports personal fees from Bayer, Boehringer Ingelheim, BRAHMS, Chugai, Novartis, Pharmacosmos, Roche, Vifor, outside the submitted work; and owns shares in Actimed. J.B. reports personal fees from Bayer, outside the submitted work; has a patent EP2954322B1 ( method for cardiovascular risk stratification) issued. C.M. reports personal fees from AstraZeneca, Bristol‐Myers Squibb, Berlin Chemie, Novartis, Amgen, Boehringer Ingelheim, Sevier, outside the submitted work. J.M. reports personal fees from Pfizer, Novartis, Takeda, Bristol‐Myers Squibb, GSK, Nektar, AstraZeneca, Audentes, Myovant, Regeneron, during the conduct of the study. D.F. reports personal fees from Abbott Laboratories, Bayer, Boehringer‐Ingelheim, Menarini, Novartis, Orion Pharma, Roche Diagnostics, outside the submitted work. A.R.L. reports grants and personal fees from Servier, Pfizer, personal fees from Novartis, Roche, Takeda, Boehringer Ingelheim, Amgen, Clinigen Group, Ferring Pharmaceuticals, Eli Lily, Bristol‐Myers Squibb, Eisai Ltd, Myocardial Solutions, Heartfelt Technologies, outside the submitted work. P.A. reports personal fees from Novartis, Servier, Daiichi‐Sankyo, Bayer, Pfizer, AstraZeneca, Jansenn, Merck Sharp & Dohme, GlaxoSmithKline, grants and personal fees from Boehringer Ingelheim, outside the submitted work. T.E. reports a speaker honorarium for Novartis, related to sacubitril/valsartan, not relevant for this work. O.J.M. reports personal fees from Bayer, Bristol‐Myers Squibb, Daiichi‐Sankyo, Pfizer, Servier, outside the submitted work. J.S.H. reports grants from Leducq Foundation, Fondation pour la Recherche Médicale, Sanofi, Servier, Bioserenity, personal fees from Amgen, Bayer, AstraZeneca, Bristol‐Myers Squibb, personal fees and non‐financial support from Novartis, outside the submitted work. P.v.d.M. reports grants and personal fees from Vifor Pharma, AstraZeneca, Pfizer, grants from Ionis, Corvidia, personal fees from Servier, outside the submitted work. R.N.K. reports he is Co‐Founder and President, ASPIDA Therapeutics Inc. P.P.R. reports personal fees and non‐financial support from Novartis, non‐financial support from Sanofi, Abbott, Daiichi‐Sankyo, Bayer, outside the submitted work. J.Č. reports personal fees from Roche Diagnostics, AstraZeneca, Servier, Berlin‐Chemie, Novartis, outside the submitted work. E.A.J. reports personal fees from Boehringer Ingelheim, Vifor Pharma, Servier, Bayer, Berlin‐Chemie, Novartis, Abbott, AstraZeneca, outside the submitted work. T.T. reports personal fees from Cardior Pharmaceuticals, other from Novo Nordisk, outside the submitted work. J.B. reports personal fees from Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi‐Sankyo, Medtronic, MSD, Novartis, Pfizer, Servier, grants and personal fees from Abiomed, CvRX, Vifor, Zoll, outside the submitted work. A.A.J.C. reports personal fees from AstraZeneca, Bayer, Menarini, Novartis, Nutricia, Servier, Vifor, Actimed, Cardiac Dimensions, CVRx, Enopace, Faraday, Gore, Impulse Dynamics, Respicardia, Stealth Peptides, Corvia, Arena, ESN Cleer, outside the submitted work. P.P. reports personal fees from Boehringer Ingelheim, Amgen, Vifor, Servier, Bayer, BMS, Respicardia, Berlin‐Chemie, Novartis, Abbott Vascular, AstraZeneca, outside the submitted work. C.G.T. reports grants from Federico II University/Ricerca di Ateneo, during the conduct of the study; personal fees from Alere, outside the submitted work; has a Canadian Patent No. 2613477, issued on Dec 3, 2013 Inventors: Nazareno Paolocci, David A. Kass, Carlo G. Tocchetti. Owner: Johns Hopkins University Entitled: THIOL‐SENSITIVE POSITIVE INOTROPES JHU Ref.: C04755‐P04755‐05 with royalties paid. D.J.L. reports personal fees from Acorda, Inc, Bristol‐Myers Squibb, Lilly, Roche, Inc, grants from Myocardial Solutions, outside the submitted work. F.R.: since 1st January 2018: no personal payments, all payments directly to the University of Zurich. Before 2018: F.R. reports grants and personal fees from SJM/Abbott, Servier, Bayer, personal fees from Zoll, Novartis, AstraZeneca, Sanofi, Amgen, BMS, Pfizer, Fresenius, Vifor, Roche, Cardiorentis, Boehringer Ingelheim, other from Heartware, grants from Mars, outside the submitted work. L.L. reports personal fees from MSD, Daiichi‐Sankyo, Novartis, Servier, outside the submitted work. M.S.P. reports grants from Novartis, Servier, Vifor. O.C. reports grants from Servier, Vifor, Novartis, grants and other from Boehringer Ingelheim, outside the submitted work. P.D. reports other from Innate Pharma, outside the submitted work. S.D.A. reports grants and personal fees from Vifor Int, Abbott Vascular, personal fees from Bayer, Boehringer Ingelheim, Novartis, Servier, Impulse Dynamics, Cardiac Dimensions, Actimed Therapeutics, outside the submitted work. P.M.S. reports honorarium for lecture from Medtronic, Abbott, Servier, AstraZeneca, Respicardia, consultancy agreement and honorarium for lecture from Boehringer Ingelheim, Novartis, consultancy agreement from Vifor Pharma. D.J. reports other from Amgen Inc, Bayer Pharma AG, BMS GmbH & Co KGaA, CureVac AG, Definiens AG; Genmab A‐S, F. Hoffmann‐La Roche Ltd, Vaximm AG; Zelluna Immunotherapy AS, Life Science Inkubator GmbH, outside the submitted work. J.L. reports grants and personal fees from Achilles Therapeutics, BMS, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, personal fees from AstraZeneca, Boston Biomedical, Eisai, EUSA Pharma, GSK, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Sorono, Pierre Fabre, Secarna, Vitaccess, Covance, grants Aveo, Pharmacyclics, outside the submitted work. All other authors have nothing to disclose. Conflict of interest: in vitro Funding Information: R.A.d.B. is supported by the European Research Council [ERC CoG 818 715, SECRETE-HF], and furthermore by the Netherlands Heart Foundation (CVON DOSIS, grant [2014-40], CVON SHE-PREDICTS-HF, grant [2017-21]; CVON RED-CVD, grant [2017-11]; and CVON PREDICT2, grant [2018-30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant [917.13.350]), and by a grant from the Leducq Foundation (Cure PhosphoLambaN induced Cardiomyopathy, Cure-PLaN). S.H. gets support of the ERA-Net-CVD project MacroERA, [01KL1706], and IMI2-CARDIATEAM [N. 821 508], from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant [2017-21], CVON Arena-PRIME, 2017-18, support of FWO [G091018N] (2017) and [G0B5920N] (2019). J.B. is supported by the Collaborative Research Center (SFB) 1118 of the German Research Foundation (DFG), by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium f?r Bildung und Forschung (BMBF) and by the Ministerium f?r Wissenschaft, Forschung und Kunst (MWK) Baden W?rttemberg. C.M. is funded by the German Research Foundation [DFG; Ma 2528/7-1; SFB 894; TRR 219] and the Federal Ministry of Education and Research [BMBF; BMBF; 01EO1504]. A.R.L. is supported by a grant from the Leducq Foundation (Cardio-Oncology Network). A.B.G. is supported by TerCel [RD16/0011/0006, RD16/0011/0028], CIBER Cardiovascular - [CB16/11/00403, the CERCA Programme/Generalitat de Catalunya, and ?la Caixa? Banking Foundation. C.G.T. is supported by a ?Federico II University/Ricerca di Ateneo? grant. Funding Information: R.A.d.B. is supported by the European Research Council [ERC CoG 818 715, SECRETE‐HF], and furthermore by the Netherlands Heart Foundation (CVON DOSIS, grant [2014‐40], CVON SHE‐PREDICTS‐HF, grant [2017‐21]; CVON RED‐CVD, grant [2017‐11]; and CVON PREDICT2, grant [2018‐30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant [917.13.350]), and by a grant from the Leducq Foundation (Cure PhosphoLambaN induced Cardiomyopathy, Cure‐PLaN). S.H. gets support of the ERA‐Net‐CVD project MacroERA, [01KL1706], and IMI2‐CARDIATEAM [N. 821 508], from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016‐Early HFPEF, 2015‐10, CVON She‐PREDICTS, grant [2017‐21], CVON Arena‐PRIME, 2017‐18, support of FWO [G091018N] (2017) and [G0B5920N] (2019). J.B. is supported by the Collaborative Research Center (SFB) 1118 of the German Research Foundation (DFG), by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium für Bildung und Forschung (BMBF) and by the Ministerium für Wissenschaft, Forschung und Kunst (MWK) Baden Württemberg. C.M. is funded by the German Research Foundation [DFG; Ma 2528/7‐1; SFB 894; TRR 219] and the Federal Ministry of Education and Research [BMBF; BMBF; 01EO1504]. A.R.L. is supported by a grant from the Leducq Foundation (Cardio‐Oncology Network). A.B.G. is supported by TerCel [RD16/0011/0006, RD16/0011/0028], CIBER Cardiovascular ‐ [CB16/11/00403, the CERCA Programme/Generalitat de Catalunya, and ‘la Caixa’ Banking Foundation. C.G.T. is supported by a ‘Federico II University/Ricerca di Ateneo’ grant. P.A. is supported by the Italian Ministry of Health ([GR‐2018‐12 365 661], CHANGE Study). L.L. is supported by the German Centre for Cardiovascular Research (DZHK). T.E. is supported by the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium für Bildung und Forschung (BMBF) and the European Horizon 2020 Programme (REANIMA), ERA‐CVD Variation, and ITN TRAIN‐HEART. O.J.M. is supported by the German Research Foundation (DFG) [DFG MU_1654/11–1], the German Centre for Cardiovascular Research (DZHK) and the Bundesministerium für Bildung und Forschung (BMBF) [81Z0700201] as well as the European Horizon 2020 programme [CardioReGenix]. J.S.H. is supported by INSERM, the French National Research Agency [NADHeart ANR‐17‐CE17‐0015‐02, PACIFIC ANR‐18‐CE14‐0032‐01, CORRECT_LMNA ANR‐19‐CE17‐0013‐02], BPIFrance [2018‐PSPC‐07], the ERA‐Net‐CVD [ANR‐16‐ECVD‐0011‐03] (Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation [18CVD05]. P.v.d.M. is supported by the European Research Council [ERC StG STOP‐HF 715732], Dutch Heart Foundation (DHF) grant eSCAPE‐HF and the Human Frontier Science Program (HFSP) grant [RGY0071/2014]. R.P. is supported by Research project of Charles University Prague, Progress Q40/03. R.N.K. is supported by National Institutes of Health grants [R01HL130861 and R01HL138475]; Department of Defense grants [PR151134P1 and PR191593]; AHA grant [18SRG34280018]; and Foundation Leducq grant [RA15CVD04]. P.P.R. is supported by the ERA‐NET CVD project AIR‐MI and the Austrian Society of Cardiology. J.B. got support from the Erich und Emmy Hoselmann‐Stiftung. J.M. is supported by grants from National Institutes of Health (NIH) [R56 HL141466] and [R01 HL141466]. L.V.L. is supported by the Netherlands Heart Foundation (Dekker Senior Clinical Scientist (2019 T056). P.N.S. is supported by the European Research Council (ERC StG 680 209, OPTIM) and Swiss Innovation Agency ‐ InnoSwiss (28747). P.D. is an employee of Innate Pharma and owns shares of the company. T.T. is supported by an ERC Consolidator grant Longheart and Deutsche Forschungsgemeinschaft [KFO311]. Publisher Copyright: © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

AB - The co-occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre-clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time.

KW - ANTHRACYCLINE CARDIOTOXICITY

KW - Angiogenesis

KW - CACHEXIA

KW - CARDIAC DYSFUNCTION

KW - CLONAL HEMATOPOIESIS

KW - Cancer

KW - Cardio&#8208

KW - Cardiotoxicity

KW - Clonal haematopoiesis

KW - DISEASE

KW - DOXORUBICIN

KW - Extracellular matrix

KW - Heart failure

KW - INCREASED RISK

KW - Inflammation

KW - Metabolism

KW - RADIATION-EXPOSURE

KW - SYMPATHETIC-NERVOUS-SYSTEM

KW - TUMOR-GROWTH

KW - angiogenesis

KW - anthracycline cardiotoxicity

KW - cachexia

KW - cancer

KW - cardiac dysfunction

KW - cardio&#8208

KW - cardiotoxicity

KW - clonal haematopoiesis

KW - clonal hematopoiesis

KW - disease

KW - doxorubicin

KW - extracellular matrix

KW - heart failure

KW - increased risk

KW - inflammation

KW - metabolism

KW - oncology

KW - radiation-exposure

KW - sympathetic-nervous-system

KW - tumor-growth

KW - Cardio-oncology

U2 - 10.1002/ejhf.2029

DO - 10.1002/ejhf.2029

M3 - Article

C2 - 33094495

SN - 1388-9842

VL - 22

SP - 2272

EP - 2289

JO - European journal of heart failure

JF - European journal of heart failure

IS - 12

ER -

de Boer RA, Hulot JS, Tocchetti CG, Aboumsallem JP, Ameri P, Anker SD et al. Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). European journal of heart failure. 2020 Dec 1;22(12):2272-2289. doi: 10.1002/ejhf.2029