Clavel's laboratory

Dr Marie-Annick Clavel obtained a doctorate in veterinary medicine (DVM) at Claude Bernard University in Lyon (France) and a doctorate in science clinics and biomedicals at Laval University in Quebec City (QC, Canada). She has continued her training with a three-year postdoctoral fellowship at the Mayo Clinic in Rochester (MN, United States of America). She is an associate professor at the Department of Medicine at Laval University (Quebec) and a researcher at the University Institute of Cardiology and Pneumology of Quebec since 2014. Her research program objectives are to elucidate the differences gender in pathophysiology, clinical presentation, diagnosis and fate in patients with heart valve disease and especially aortic stenosis. She is more interested in patients with heart failure, poor blood flow and markers of discordant severity of aortic stenosis. She has published over 200 articles scientific and more than 400 abstracts in national congresses and international.

In aortic valve stenosis, she showed for the first time that women have less aortic valve calcifications than men for the same hemodynamic severity of aortic stenosis. Then, her team has shown that women have more valve fibrosis than men, localized in denser connective tissue. In mitral insufficiency isolated, it has shown that the patient is undergoing significant treatment. In addition, women are treated even less often than men and the surgery for primary mitral insufficiency is delayed, due to non-sex-specific disease severity marker underestimating severity of the disease and its consequences in women. This processing time for women with mitral insufficiency leads to further insufficiency heart after surgery.

In patients with aortic stenosis with markers of discordant severity on echocardiography, Dr. Clavel provided several new clues to assess the true severity of aortic stenosis, such as the projected aortic valve surface at normal flow and the calcium score aortic valve. In addition, it has shown that at least 50% of these patients with echocardiographic discordance presented with severe stenosis without regard the state of flow and the benefit of an intervention on the aortic valve.

Dr Clavel introduced the concept of natriuretic peptide ratio of type B, by dividing the measured level of the peptide by the maximum normal value expected for the patient's age and sex. This new setting was a powerful predictor of the outcome of patients with aortic stenosis and that in asymptomatic patients, the elevation of the BNP ratio was a predictor of poor prognosis under medical treatment and thus, these patients may benefit from early surgery (i.e. before the onset symptoms). It also demonstrated that the BNP ratio is useful in mitral regurgitation and may also aid in the surgical decision.

Dr. Clavel holds the Canada Research Chair in women's heart valve health and has received several awards of excellence from Canadian Institutes of Health Research, The Stroke Foundation heart, the Canadian Cardiology Society, the Jacques de Champlain and the Quebec Clinical Research Club. Her works of research is or has been funded by health research institutes of Canada, Heart and Stroke Foundation, University Foundation Laval and the founding of the IUCPQ.

Mission and projects

The aim of her research program is to elucidate the differences between the sexes in the pathophysiology, diagnosis and treatment of patients with heart valve disease and in particular aortic stenosis.

Aortic stenosis is the third most important cardiovascular disease in high income countries. This damage to the aortic valve is characterized by calcification and significant fibrosis of the valve tissues which will lead to obstruction of the blood flow between the left ventricle and the aorta. For years, aortic stenosis has been studied in all-male animal models with the aim of minimizing heterogeneity and in cohorts predominantly made up of men because male gender has been presented as a risk factor for the disease. Thus, our understanding of the role of sex in the pathophysiology, presentation and fate of patients with aortic stenosis limits our ability to personalize patient management and optimize their treatment for a better outcome. In recent work, Dr. Clavel and her team have shown that for the same hemodynamic severity of the disease, women have a lower valvular calcium load than men. This difference is explained by a greater fibrosis of the aortic valve in women and greater calcification in men.

Mitral regurgitation is the second most prevalent valve disease (after aortic stenosis). Women seem to be more affected by this disease, however men are more often referred for surgery. Interestingly, we have shown that the application of the severity thresholds proposed in the practice guides, without indexation in relation to the body surface or the size of the patient's heart, tended to underestimate the disease in women. This will lead to a delay in treatment or even an absence of treatment marked in women and therefore a darker outcome.

The overall goal of Dr. Clavel’s research program is to characterize the differences between men and women in the pathophysiology, diagnosis and treatment of valve disease. Studies leading to this overall goal will be performed on available data from human cohorts, explanted human valves, valve interstitial cells, mouse models of aortic stenosis, and prospective interventional studies in patients. The first objective of this program is to document the prevalence, presentation at diagnosis and clinical outcome of patients with valve disease according to sex. The second objective is to study the modulation of the renin-angiotensin system (RAS) and sex hormones in the sex-related differences in the pathophysiology of aortic stenosis. The third objective is to evaluate an existing mouse model of aortic stenosis that mimics sex-related differences in the pathophysiology of aortic stenosis and to explore the mechanisms behind these differences. Finally, the fourth objective is to use this mouse model to assess the effect of various therapies on the rate of disease progression and to determine whether the magnitude of this effect differs between females and males. Dr. Clavel's program aims to bring new knowledge and raise awareness of gender specificity in the pathophysiology and epidemiology of valve diseases and the need for gender-specific management in order to improve patient outcomes. . Thus, the results of his research program could have an important impact on the guidelines for the management of patients with valvular disease, by establishing specific guidelines for women and men.