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)

Rudolf A. de Boer, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Jean-Sébastien Hulot, Université de Paris, PARCC, INSERM, Paris, France.
Carlo Gabriele Tocchetti, Department of Translational Medical Sciences and Interdepartmental Center of Clinical and Translational Research, Federico II University, Naples, Italy.
Joseph Pierre Aboumsallem, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
Pietro Ameri, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, Genoa, Italy.
Stefan D. Anker, Department of Cardiology & Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Charité-Universitätsmedizin Berlin (Campus CVK), Berlin, Germany.
Johann Bauersachs, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Edoardo Bertero, Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg, Germany.
Andrew J. Coats, San Raffaele Pisana Scientific Institute, Rome, Italy.
Jelena Čelutkienė, Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Ovidiu Chioncel, Emergency Institute for Cardiovascular Diseases 'Prof. C.C. Iliescu', University of Medicine Carol Davila, Bucharest, Romania.
Pierre Dodion, Innate Pharma, Marseille, France.
Thomas Eschenhagen, Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Dimitrios Farmakis, University of Cyprus Medical School, Nicosia, Cyprus.
Antoni Bayes-Genis, Heart Failure Unit and Cardiology Department, Hospital Universitari Germans Trias i Pujol, CIBERCV, Badalona, Spain.
Dirk Jäger, Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany.
Ewa A. Jankowska, Department of Heart Diseases, Wroclaw Medical University, and Centre for Heart Diseases, University Hospital, Wroclaw, Poland.
Richard N. Kitsis, Departments of Medicine (Cardiology) and Cell Biology, Wilf Family Cardiovascular Research Institute, Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, NY, USA.
Suma H. Konety, Cardiovascular Division, Cardio-Oncology Program, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
James Larkin, Royal Marsden NHS Foundation Trust, London, UK.
Lorenz Lehmann, Cardio-Oncology Unit, Department of Cardiology, University of Heidelberg, Heidelberg, Germany.
Daniel J. Lenihan, Cardio-Oncology Center of Excellence, Cardiovascular Division, Washington University in St. Louis, St. Louis, MO, USA.
Christoph Maack, Comprehensive Heart Failure Center, University Clinic Würzburg, Würzburg, Germany.
Javid J. Moslehi, Division of Cardiovascular Medicine and Oncology, Cardio-Oncology Program, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Oliver J. Müller, Department of Internal Medicine III, University of Kiel, Kiel, Germany.
Patrycja Nowak-Sliwinska, School of Pharmaceutical Sciences, University of Geneva, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland.
Massimo Francesco Piepoli, Heart Failure Unit, Cardiology, G. da Saliceto Hospital, Piacenza, University of Parma, Parma, Italy.
Piotr Ponikowski, Department of Heart Diseases, Wroclaw Medical University, and Centre for Heart Diseases, University Hospital, Wroclaw, Poland.
Radek Pudil, 1st Department Medicine-Cardioangiology, University Hospital and Medical Faculty, Hradec Kralove, Czech Republic.
Peter P. Rainer, Medical University of Graz, University Heart Center - Division of Cardiology, Graz, Austria.
Frank Ruschitzka, Department of Cardiology, University Hospital Zurich, University Heart Center, Zurich, Switzerland.
Douglas Sawyer, Center for Molecular Medicine, Maine Medical Center Research Institute, Maine Medical Center, Scarborough, ME, USA.

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.