Heart group - Pr David Montaigne
Presentation of the research topic
As in many areas of patient care, the move away from a ‘one size fits all’ approach to an individualised ‘precision medicine’ approach represents the near and reasonably achievable future of cardiovascular disease treatment. The final goal of personalised cardiac medicine is to deliver optimised medical care and outcomes for each people, providing the best therapy for each patient in terms of efficacy, safety and reduction of associated costs.
Our research activities are therefore dedicated to personalised medicine to prevent and target cardiovascular disease through:
- New imaging biomarkers,
- DNA sequencing of circulating and myocardial leukocytes,
- Phenotyping of myocardial immunometabolism,
- Quantification (using GFET aptamer sensors) of cardiac biomarkers in biological samples (blood, saliva, sweat, exhaled air) from patients, where levels are very low or currently undetectable.
Our translational research, which extends from rodent models to patients, aims to improve understanding of the pathophysiology of cardiac remodelling, to refine cardiovascular risk stratification and the therapeutic strategy associated with benefit/risk, not only in patients with a history of cardiovascular disease, but also in patients with cardiovascular risk factors such as smoking, type 2 diabetes, dyslipidaemia and obesity, even in the absence of any cardiovascular medical history or symptoms.
Our projects focus more specifically on cardiac function, energy metabolism and remodelling in patients with diabetes and/or heart valve disease, and aim to improve patient stratification and develop personalised cardiovascular medicine.
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Key-Words
Cardiac remodelling ; valvulopathies ; arrhythmia ; atrial fibrillation ; energy metabolism ; inter-organ communication ; immuno-metabolism ; cardiac imaging.
MONTAIGNE David
PU-PH – Head of the Cardiovascular Functional Investigation Department (Lille University Hospital) and the Cardiology Department (Armentières Hospital)
david.montaigne[@]chu-lille.fr
ORCID : 0000-0002-2346-863X
COISNE Augustin
PU-PH – Cardiology
augustin.coisne[@]chu-lille.fr
ORCID : 0000-0002-1662-7874
PONTANA François
PU-PH – Radiology and Medical Imaging
francois.pontana[@]chu-lille.fr
ORCID : 0000-0001-5316-7101
LONGERE Benjamin
MCU-PH – Radiology and Medical Imaging
benjamin.longere[@]chu-lille.fr
ORCID : 0000-0002-0340-5404
LEMESLE Gilles
PU-PH – Cardiology
ORCID : 0000-0002-2917-9273
NINNI Sandro
MCU-PH – Cardiology
ORCID : 0000-0001-6179-6098
TAZIBET Amine
Cardiologist - PhD Student
ORCID : 0009-0007-5564-6625
DUBRULLE Henri
Cardiac surgeon - PhD Student
WOITRAIN Eloïse
Engineer - Lille Hospital Center
eloise.woitrain[@]pasteur-lille.fr
ORCID : 0000-0002-9913-9023
BUTRUILLE Laura
Postdoctoral fellow - Lille University
laura.butruille@pasteur-lille.fr
ORCID : 0000-0001-5760-1489
WITOCKX Kimberly
Assistant Engineer - Institut Pasteur de Lille
kimberly.witockx[]univ-lille.fr
ORCID : 0009-0003-9981-8127
We demonstrated in 2018 that time of day affects patients' cardiac outcomes with more severe consequences when surgical aortic valve replacement was performed in the morning compared to the afternoon (Montaigne D, et al., Lancet. 2018).
Through collaboration with members of the Leducq consortium team, we investigated the specificity of clonal haematopoiesis (CHIP) patients undergoing cardiac surgery. We showed that these patients had a significantly higher rate of postoperative atrial fibrillation and an increased risk of major cardiovascular complications (cardiovascular death, stroke, hospitalisation for acute heart failure, etc.) (Ninni S. et al., J Am Coll Cardiol. 2023).
In collaboration with Dr Jérémy Fauconnier of Montpellier, we have identified mitochondrial calcium homeostasis, and more specifically the mitochondrial calcium uniporter complex (MCUC), as a determinant of atrial fibrillation in metabolic syndrome and an attractive therapeutic target (Fossier L. et al., J Am Coll Cardiol 2022).
Our team has developed expertise in the following areas:
- Cardiac imaging (ultrasound, MRI)
- In vivo experiments (models of aortic constriction, telemetry, transoesophageal atrial stimulation, etc.)
- In vitro experiments (cell culture)
- Study of the cardiac phenotype (histology, gene and protein expression, cardiomyocyte energy metabolism, inflammation markers using multiplexing techniques)
- Analysis of mitochondrial function (Oroboros, Sea Horse)
- Immunophenotyping (FACS / single cell RNAseq)
List of mainspublications by the heart group of team 1:
Coisne A, Montaigne D, Aghezzaf S, Ninni S, Lemesle G, Sudre A, Lamblin N, Modine T, Vincentelli A, Juthier F, Leon MB, Granada JF, Bauters C. Clinical Outcomes According to Aortic Stenosis Management: Insights From Real-World Practice. J Am Heart Assoc. 2024 Nov 19;13(22):e036657. doi: 10.1161/JAHA.124.036657. Epub 2024 Nov 15. PMID: 39548024; PMCID: PMC11681392.
Aghezzaf S, Coisne A, Bauters C, Favata F, Delsart P, Coppin A, Seunes C, Schurtz G, Verdier B, Lamblin N, Tazibet A, Le Taillandier de Gabory J, Ninni S, Donal E, Lemesle G, Montaigne D. Feasibility and prognostic significance of ventricular-arterial coupling after myocardial infarction: the RIGID-MI cohort. Eur Heart J Cardiovasc Imaging. 2024 Apr 30;25(5):668-677. doi: 10.1093/ehjci/jead342. PMID: 38133627.
Ninni S, Dombrowicz D, de Winther M, Staels B, Montaigne D, Nattel S. Genetic Factors Altering Immune Responses in Atrial Fibrillation: JACC Review Topic of the Week. J Am Coll Cardiol. 2024 Mar 26;83(12):1163-1176. doi: 10.1016/j.jacc.2023.12.034. PMID: 38508850.
T. Rodrigues, V. Mishyn,Y. R. Leroux, L. Butruille, E. Woitrain, A. Barras, P.Aspermair, H. Happy, C. Kleber, R. Boukherroub, D. Montaigne, W. Knoll, S. Szunerits (2022). Highly performing graphene-based field effect transistor for the differentiation between mild-moderate-severe myocardial injury
. Nano Today, 2022 doi.org/10.1016/j.nantod.2022.101391
Montaigne D, Butruille L, Staels B. PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol. 2021 Dec;18(12):809-823. doi: 10.1038/s41569-021-00569-6. Epub 2021 Jun 14. PMID: 34127848. (Review)
Montaigne D, Marechal X, Modine T, Coisne A, Mouton S, Fayad G, Ninni S, Klein C, Ortmans S, Seunes C, Potelle C, Berthier A, Gheeraert C, Piveteau C, Deprez R, Eeckhoute J, Duez H, Lacroix D, Deprez B, Jegou B, Koussa M, Edme JL, Lefebvre P, Staels B. Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study. Lancet. 2018 Jan 6;391(10115):59-69. doi: 10.1016/S0140-6736(17)32132-3. Epub 2017 Oct 26. PMID: 29107324.
Montaigne D, Marechal X, Coisne A, Debry N, Modine T, Fayad G, Potelle C, El Arid JM, Mouton S, Sebti Y, Duez H, Preau S, Remy-Jouet I, Zerimech F, Koussa M, Richard V, Neviere R, Edme JL, Lefebvre P, Staels B. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation. 2014 Aug 12;130(7):554-64. doi: 10.1161/CIRCULATIONAHA.113.008476. Epub 2014 Jun 13. PMID: 24928681.
Montaigne D, Marechal X, Lefebvre P, Modine T, Fayad G, Dehondt H, Hurt C, Coisne A, Koussa M, Remy-Jouet I, Zerimech F, Boulanger E, Lacroix D, Staels B, Neviere R. Mitochondrial dysfunction as an arrhythmogenic substrate: a translational proof-of-concept study in patients with metabolic syndrome in whom post-operative atrial fibrillation develops. J Am Coll Cardiol. 2013 Oct 15;62(16):1466-73. doi: 10.1016/j.jacc.2013.03.061. Epub 2013 May 1. PMID: 23644086.
List of the different projects and funding of the core group of team 1 :
1- TOMIS and POMI-AF clinical project funded by the “Agence Nationale pour la Recherche” young researcher grant (ANR TOMIS-Leukocyte: ANR-CE14-0003-01) and the Fondation Leducq LEAN 16CVD01 network. The project is dedicated to better understanding post-operative complications (e.g. myocardial infarction, heart failure and atrial fibrillation) after cardiac surgery, with a particular interest in understanding the impact of the time of day of surgery on outcomes.
2- Preci-Diab Heart clinical project: as part of the National Center for Precision Diabetic Medicine www.precidiab.org and funded by the French National Research Agency (ANR-18-IBHU-0001). The project is dedicated to improving patient phenotyping using new biomarkers and cardiac imaging in order to adapt personalized cardiac medicine for type 2 diabetes patients.
3- RIGID-MI project (PI Prof. G Lemesle) This clinical project is dedicated to a better understanding of cardiac remodelling and complications (e.g. myocardial infarction, heart failure and atrial fibrillation) following a myocardial infarction.
4- VALVENORD project (PI Prof. C Bauters) This clinical project aims to gain a better understanding of remodelling and cardiac complications (e.g. myocardial infarction, heart failure and atrial fibrillation) in outpatients with aortic valve stenosis (mild to severe) in the Haut de France region. The project is funded by the “Fédération Française de Cardiologie”.
5- The CALMOS translational project (coll. with J Fauconnier Univ Montpellier) is funded by a grant from the Agence Nationale pour la Recherche (ANR CALMOS: ANR 18-CE17-0003-02). This project is dedicated to better understanding the role of cardiac mitochondria in cardiac arrhythmias.
6- The LivImmCar translational project aims to highlight the interaction of hepatic steatosis associated with metabolic dysfunction (MASH) and its immune alterations with cardiac remodelling in patients suffering from cardiovascular disease. The project is funded by the Fédération Française de Cardiologie and the Fondation pour la Recherche Médicale
Pr MONTAIGNE David
PU-PH de Cardiologie, group leader of "Heart group" in Team 1