Cardio-oncology Program
Cardio-Oncology Program
Board
Pr. Mariana Mirabel
Physician
Pr. Jean-Sébastien Hulot
Physician
Dr. Agnès Lillo-Lelouet
Pharmacologist
Pr. Laure Cabanes
Physician
Steering Committee
Cardio-oncology is as an emerging interdisciplinary field aiming at the improvement of the overall health in cancer patients. The cardio-oncology Unit at Assistance Publique Hôpitaux de Paris – Centre Université de Paris (AP-HP.Centre) is the first of its kind in Paris. Indeed, dedicated healthcare services including outpatients and day-stay clinics were setup on January 1st 2017. The interdisciplinary approach to cardio-oncology involves 11 units working together across the three sites (hôpital européen Georges Pompidou, Cochin and Necker Enfant Malades): the cardio-oncology unit, oncology, gastro-intestinal oncology, thoracic oncology, haematology, general cardiology for specialized procedures, cardiovascular imaging, and pharmacovigilance. We have access to the main biomarkers used for prevention, diagnosis and prognosis of cardiotoxicity (echocardiography and serum biomarkers), as well as more complex biomarkers and procedures including imaging modalities (cardiac magnetic resonance imaging, computed cardiovascular tomography, electrophysiology and coronary angiography). This program provides quaternary invasive diagnostic activities such as endomyocardial biopsy services and pathology accordingly. In addition, all cardiovascular treatment options are available including heart failure clinics, all electrophysiology (pace maker, resynchronization therapies, implanted cardiac defibrillator, portable defibrillators), all percutaneous procedures (coronary angioplasty, trans-aortic valve implantation, mitral valve repair (MitraClip®)) and all cardiovascular surgery (coronary artery bypass, heart valve repair or replacement, temporary or definitive ventricular support, and heart transplantation) treatment options.
From January 2017, over 2,500 patients have been referred to cardio-oncology, including 1,000 patients in 2019 with a 50% relative raise in the number of cases assessed. In order to favor cross fertilization, the cardio-oncology medical team works across sites ((hôpital européen Georges Pompidou, Cochin and Necker Enfant Malades) in close collaboration with the oncology and general cardiology departments. Furthermore, in order to assess challenging cases in a multidisciplinary manner and to develop translational research, a dedicated weekly multidisciplinary concertation meeting (264 patients in 2019) and a monthly research meeting have been setup.
The novelty of the field, the top-level platform for the highest standard of care across this program enable us to have ambition to be the leading center of the Great Paris area in this field.
Clinical research
The physicians, cardiac imaging specialists, pathologists and pharmacists of this program have a track record of research in their fields of expertise, which is a valuable asset for new projects in the emerging area of cardio-oncology.
Clinical research is mainly led by the cardio-oncology unit by means of pilot observational prospective studies to this date. Three observational studies are underway:
- CONFUCIUS: ongoing prospective cardio-oncology cohort including over 1,500 patients to this date.
- MEROPE: prognosis of HER2 monoclonal antibodies in women with breast cancer, recruitment ended October 3rd 2019.
- FABRIC: predictive factors of cardiotoxicity of ibrutinib, recruitment started March 1st 2020.
- ICARE: heart failure due to carfilzomib, recruitment started March 1st 2020.
- An interventional study (AMI) assessing the incidence of cardiovascular events on immune checkpoint inhibitors has been funded by the “Fédération Française de Cardiologie”, using cardiac MRI among other biomarkers, recruitment starting in cardio-oncology through the referral of all consecutive newly treated ICI patients in all oncology departments (CCH and HEGP) scheduled September 1st 2020.
- PRISM: pilot study on the prediction of immune checkpoint inhibitors myocarditis on the expression of Tcells in the tumour, funded by the Cancéropôle Ile de France 2019.
- Other pilot projects are under consideration, with active grant search scheduled in spring-fall 2020.
Translational research
Translational research involves mainly 4 senior researchers from 2 Inserm teams located at PARCC. The main translational research teams are led by Pr. JS Hulot and Pr. B. Tavitian. The field encompasses cell models such as human iPSC in the prediction of ventricular repolarization under diverse oncology drugs to animal cardiac imaging models. Pr. B. Tavitian demonstrated through a mouse model that exposure to sunitinib (an oral antiVEGF tyrosine kinase inhibitor) leads to a metabolic switch by means of bimodal cardiac imaging (echocardiography and nuclear medicine imaging).
The cardio-oncology program includes a wide range of specialties; 2 residents are trained currently within the cardiology and cardio-oncology units; European Fellows attend to clinical wards by means of grants for a varied period of time (from 1 to 6 months rotations).
Dedicated internal seminars are held on a monthly basis.
The cardio-oncology unit has set up the first continuous medical training held on February 4th 2020.
The teams are widely involved in the university teaching of cardiovascular disease within the university of Paris curriculum for medical students (undergraduates and various diplomas).
A newly dedicated diploma led by Paris University (Dr. Mariana Mirabel, Prof. Alain Cohen Solal) and Marseille University (Prof. Franck Thuny) has been launched.
The perspectives in this emerging field are wide, ranging from basic, translational to epidemiology research and interventional research.
The perspectives involve all the expertise already available at AP-HP-Centre: from genetics, cell and animal models, to epidemiology, observational and interventional clinical research.
Our program has recently obtained grants for observational and pilot interventional studies that are to be launched within the coming trimester with the ambition to submit for larger grants in 2020.
| Name Surname | Title/Position | Speciality | Research Unit | Resarch Team |
|---|---|---|---|---|
| Mariana Mirabel | Associate Professor | Cardiologist | UMRS 970-INSERM PARCC | Biology and Pharmacology of Heart Failure |
| Jean-Sébastien Hulot | Full time Professor | Pharmacologist | UMRS 970-INSERM PARCC | Biology and Pharmacology of Heart Failure |
| Agnès Lillo-le-Louet | Full time physician | Pharmacologist | Inserm UMR_S1140 | Haemostasis |
| Laure Cabanes | Full time physician | Cardiologist | – | – |
| Constance Thibault | Full time physician | Oncologist | UMRS 970-INSERM PARCC | Genetics and Metabolics of rare cancers |
| Marguerite Vignon | Full time physician | Haematologist | – | – |
| Elie Mousseaux | Full Prof | Radiologist | UMRS 970-INSERM PARCC | In vivo Imaging Research |
| Geltrude Giura | Full time physician | Cardiologist | – | – |
| Jacques Medioni | Associate Professor | Oncologist | Inserm U987 | – |
| Elizabeth Fabre | Full time physician | Oncologist | UMRS 1138 Centre de Recherche des Cordeliers | Personalized medecine therapeutic optimization |
| Bertrand Tavitian | Full time Professor | Radiologist | UMRS 970-INSERM PARCC | In vivo Imaging Research |
| Laurent Frenzel | Full time Physician | Rheumatologist | U1163 – Imagine – Institut des maladies génétiques | |
| François Goldwasser | Full time Professor | Oncologist Cochin | Institut Cochin | Inserm U1016 – Cnrs UMR8104 |
| Etienne Puymirat | Full time Professor | Cardiologist : interventional | UMRS 970-INSERM PARCC | Biology and Pharmacology of Heart Failure |
| Eloi Marijon | Full time Professor | Cardiologist : Electrophysiology | UMRS 970-INSERM PARCC | Epidemiology of Sudden Cardiac Death |
| Patrick Bruneval | Full time Professor | Pathologist | UMRS 970-INSERM PARCC | Genetics in Arterial Diseases |
The selected following publications highlight the strength of clinical and translational research developed in the cardio-oncology program:
- Almeida Morais L, Cervino C, Thibault C, Oudard S, Vano, Y, Zaanan A, Vignon M, Bouscary, Lillo-Lelouët A, Hulot JS, Mirabel M. A year in cardio-oncology : results of a dedicated clinic in a tertiary centre. Under 2nd revision September 2019.
- Koutkias VG, Lillo-Le Louët A, Jaulent MC. Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies. Expert Opin Drug Saf. 2017 Feb;16(2):113-124. doi: 10.1080/14740338.2017.1257604. Epub 2016 Dec 1. PubMed PMID: 27813420.
- Mirabel M, Damy T, Donal E, Huttin O, Labombarda F, Eicher JC, Cervino C, Laurito M, Offredo L, Tafflet M, Jouven X, Giura G, Desnos M, Jeunemaître X, Empana JP, Charron P, Habib G, Réant P, Hagège A; REMY working group of the French Society of Cardiology. Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy: A study from the French register of hypertrophic cardiomyopathy (REMY). Int J Cardiol. 2019 Jan 15;275:107-113.
- Audeh B, Calvier FE, Bellet F, Beyens MN, Pariente A, Lillo-Le Louet A, Bousquet C. Pharmacology and social media: Potentials and biases of web forums for drug mention analysis-case study of France. Health Informatics J. 2019 Sep 30:1460458219865128. doi: 10.1177/1460458219865128. PubMed PMID: 31566468
- Thibault C, Vano Y, Soulat G, Mirabel M. Immune checkpoint inhibitors myocarditis: not all cases are clinically patent. Eur Heart J 2018 Aug 10. doi: 10.1093/eurheartj/ehy485.
- Huertas A, Thuillot M, Bibault JE, Sharifzadehgan A, Laurans M, Giraud P, Lavergne T, Marijon É, Durdux C. Management of patients with pacemakers or implantable cardioverter defibrillator undergoing radiotherapy. Cancer Radiother. 2018 Oct;22(6-7):515-521.
- Provost J, Garofalakis A, Sourdon J, Bouda D, Berthon B, Viel T, Perez-Liva M, Lussey-Lepoutre C, Favier J, Correia M, Pernot M, Chiche J, Pouysségur J, Tanter M, Tavitian B. Simultaneous positron emission tomography and ultrafast ultrasound for hybrid molecular, anatomical and functional imaging. Nat Biomed Eng. 2018;2:85-94.
- Sourdon J, Lager F, Viel T, Balvay D, Moorhouse R, Bennana E, Renault G, Tharaux PL, Dhaun N, Tavitian B. Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism. 2017 Jul 8;7(11):2757-2774. doi: 10.7150/thno.19551.
