Personne : Clisson, Marine
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Université Laval. Département de médecine
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- PublicationRestreintLeft ventricular asymmetric remodeling and subclinical left ventricular dysfunction in patients with calcific aortic valve stenosis : results from a subanalysis of the PROGRESSA study(Elsevier Science Publishers, 2021-03-13) Clisson, Marine; Guzzetti, Ezequiel; Bernard, Jérémy; Larose, Éric; Shen, Mylène; Bédard, Élisabeth; Côté, Nancy; Capoulade, Romain; Pibarot, Philippe; Clavel, Marie-Annick; Tastet, Lionel; Arsenault, MarieBackground: LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS). Methods: Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured. Results: Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionally, these patients had higher baseline Nt-proBNP ratio (median [25–75 percentiles]: 1.04 [0.66–2.41] vs. 0.65 [0.33–1.19], p = 0.02), and significantly reduced LV-GLS (17.9[16.6–19.5] vs. 19.3[17.4–20.7] |%|, p = 0.04). A 1:1 matched analysis showed a significant association of LVAR with reduced LV-GLS (17.9[16.6–19.5] vs. 19.8[18.1–20.7] |%|, p = 0.02) and elevated Nt-proBNP (134[86–348] vs. 83[50–179]pg/ml, p = 0.03). Multivariable analysis also revealed that LVAR remains significantly associated with reduced LV-GLS (p = 0.03) and elevated Nt-proBNP (p = 0.001). LVAR was significantly associated with increased risk of major adverse cardiac events and death (Hazard ratio [95% confidence interval]: 2.32[1.28–4.22], p = 0.006). Conclusions: LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.
- PublicationRestreintSex-differences in echocardiographic assessment of aortic valve in young adult LDLr−/−/ApoB100/100/IGF-II+/− mice(Elsevier, 2020-08-27) Clisson, Marine; Côté, Nancy; Fleury, Marie-Ange; Shen, Mylène; Voisine, Martine; Marette, André; Hervault, Maxime; Annabi, Mohamed Salah; Clavel, Marie-Annick; Boilard, Anne-Julie; Ong, GéraldineBackground LDLr−/−/ApoB100/100/IGF-II+/− mice are used as a calcific aortic valve disease (CAVD) model. However, normal aortic valve hemodynamics i.e. remotely from CAVD onset and the sex-related differences are poorly known. Methods and results Four groups of mice, intact males (IM, n = 49) and females (IF, n = 50), castrated males (CxM, n = 79) and ovariectomized females (OxF: 73), underwent a Doppler-echocardiography at 12 weeks of age. Gonadectomy was performed at 8 weeks. Aortic valve assessment using effective orifice area (EOA, using the continuity equation) and peak aortic transvalvular velocity (VPeak) was feasible in 89% of the mice with good to excellent reliability (intraclass correlation coefficients ranging from 0.90 to 0.98, p < 0.001). Mean VPeak was 104 ± 17 cm/s and mean EOA was 1.18*10−2 ± 0.22*10−2 cm2. EOA indexed to body surface area was 1.5 ± 0.3 cm2/m2. The 95th percentile of Vpeak was 132 cm/s and the 5th percentile of indexed EOA was 1.0 cm2/m2. Interestingly, IM had the highest VPeak (114 ± 14 cm/s) vs each of the other groups (CxM: 106 ± 19 cm/s, OxF: 97 ± 13 cm/s and IF: 96 ± 12 cm/s, ANOVA and corrected p < 0.001). This was mostly explained by a higher stroke volume (ANOVA and corrected p < 0.001) in IM compared to other groups. There were no major sex-differences in ventricular systolic function parameters. Conclusion In LDLr−/−/ApoB100/100/IGF-II CAVD mice model, an aortic EOA <0.8*10−2 cm2 (or indexed EOA <1.0cm2/m2), and a peak aortic valve velocity > 132 cm/s may be proposed as thresholds to define CAVD. Intact male mice appear to have higher velocities.
- PublicationAccès libreOral anticoagulation therapy and progression of calcific aortic valve stenosis(Elsevier Science, 2019-04-08) Clisson, Marine; Shen, Mylène; Bédard, Élisabeth; Côté, Nancy; Capoulade, Romain; Poirier, Paul; Pibarot, Philippe; Clavel, Marie-Annick; Puri, Rishi; Tastet, Lionel; Salaun, Erwan; Arsenault, Marie
- PublicationAccès libreAttenuated mitral leaﬂet enlargement contributes to functional mitral regurgitation after myocardial infarction(Elsevier Biomedical, 2020-01-27) Clisson, Marine; Hadjadj, Sandra; Couët, Jacques; Boulanger, Marie-Chloé; Beaudoin, Jonathan; Handschumacher, Mark D.; Marsit, Ons; Pibarot, Philippe; Drolet, Marie-Claude.; Clavel, Marie-Annick; Kim, Dae-Hee; Côté-Laroche, Claudia; Guerrero, J. Luis; Bouchard, Marc; Bartko, Philipp Emanuel; Mathieu, Patrick; Arsenault, Marie; Aïkawa, Elena; Bischoff, Joyce; Levine, Robert A.Background: Mitral leaflet enlargement has been identified as an adaptive mechanism to prevent mitral regurgitation in dilated left ventricles (LVs) caused by chronic aortic regurgitation (AR). This enlargement is deficient in patients with functional mitral regurgitation, which remains frequent in the population with ischemic cardiomyopathy. Maladaptive fibrotic changes have been identified in post-myocardial infarction (MI) mitral valves. It is unknown if these changes can interfere with valve growth and whether they are present in other valves. Objectives: This study sought to test the hypothesis that MI impairs leaflet growth, seen in AR, and induces fibrotic changes in mitral and tricuspid valves. Methods: Sheep models of AR, AR + MI, and controls were followed for 90 days. Cardiac magnetic resonance, echocardiography, and computed tomography were performed at baseline and 90 days to assess LV volume, LV function, mitral regurgitation and mitral leaflet size. Histopathology and molecular analyses were performed in excised valves. Results: Both experimental groups developed similar LV dilatation and dysfunction. At 90 days, mitral valve leaflet size was smaller in the AR + MI group (12.8 ± 1.3 cm2 vs. 15.1 ± 1.6 cm2, p = 0.03). Mitral regurgitant fraction was 4% ± 7% in the AR group versus 19% ± 10% in the AR + MI group (p = 0.02). AR + MI leaflets were thicker compared with AR and control valves. Increased expression of extracellular matrix remodeling genes was found in both the mitral and tricuspid leaflets in the AR + MI group. Conclusions: In these animal models of AR, the presence of MI was associated with impaired adaptive valve growth and more functional mitral regurgitation, despite similar LV size and function. More pronounced extracellular remodeling was observed in mitral and tricuspid leaflets, suggesting systemic valvular remodeling after MI.
- PublicationAccès libreImpact des résistances vasculaires sur l'évaluation échocardiographique de la sténose aortique(2020) Clisson, Marine; Pibarot, Philippe; Clavel, Marie-AnnickLa sténose aortique calcifiante est la maladie cardiovasculaire la plus commune dans les pays développés après la maladie coronarienne et l’hypertension artérielle systémique. L’évaluation de la sévérité hémodynamique de la sténose aortique est très simple sauf lorsqu’il existe une discordance entre les indices échocardiographiques de sévérité, ce qui est le cas chez 30 à 60% des patients. L’occurrence de cette discordance est bien connue et acceptée dans le cas des patients avec bas débit avec ou sans diminution de la fraction d’éjection. Par contre chez les patients avec un débit cardiaque normal, cette discordance est attribuée à des erreurs de mesure et la sténose est considérée comme non-sévère. Or, nous avons montré récemment qu’au moins 50% des patients dans cette situation pouvaient avoir une sténose aortique sévère et le besoin de subir un remplacement valvulaire aortique afin d’éviter un devenir très sombre. Cette discordance pourrait être fortement liée à la concomitance d’une hypertension artérielle systémique et/ou d’une compliance artérielle diminuée. La présence d’un ou deux de ces facteurs pourrait pseudo-normaliser le gradient transvalvulaire et ainsi masquer la sévérité de la sténose aortique. Notre équipe a d’ailleurs récemment démontré que les patients avec hypertension artérielle systémique ou une compliance artérielle diminuée avaient une sténose aortique moins sévère évaluée par échocardiographie alors que la quantité de calcium, mesuré par tomodensitométrie, sur la valve aortique était identique à celle des patients normotendus et avec une compliance normale. Malheureusement dans cette étude, les mesures de pression artérielle et de compliance étaient faites uniquement au niveau périphérique. Nous avons émis l’hypothèse que le calcul de la compliance centrale expliquerait mieux la discordance entre les marqueurs échocardiographiques de sévérité de la sténose aortique chez des patients normotendus. Nous avons donc réalisé une étude chez 224 patients avec sténose aortique qui ont eu une échocardiographie et une mesure de la compliance artérielle périphérique et centrale à l’aide du SphygmoCor® .
- PublicationRestreintFlexibility of microstructural adaptations in airway smooth muscle(American physiological Society, 2021-05-11) Khadangi, Fatemeh; Clisson, Marine; Henry, Cyndi; Bossé, Ynuk; Dufour-Mailhot, Alexis; Tremblay-Pitre, Sophie; Beaudoin, Jonathan; Clavel, Marie-Annick; Boucher, MagaliThe airway smooth muscle undergoes an elastic transition during a sustained contraction, characterized by a gradual decrease in hysteresivity caused by a relatively greater rate of increase in elastance than resistance. We recently demonstrated that these mechanical changes are more likely to persist after a large strain when they are acquired in dynamic versus static conditions; as if the microstructural adaptations liable for the elastic transition are more flexible when they evolve in dynamic conditions. The extent of this flexibility is undefined. Herein, contracted ovine tracheal smooth muscle strips were kept in dynamic conditions simulating tidal breathing (sinusoidal length oscillations at 5% amplitude) and then subjected to simulated deep inspirations (DI). Each DI was straining the muscle by either 10%, 20%, or 30% and was imposed at either 2, 5, 10, or 30 min after the preceding DI. The goal was to assess whether and the extent by which the time-dependent decrease in hysteresivity is preserved following the DI. The results show that the time-dependent decrease in hysteresivity seen pre-DI was preserved after a strain of 10%, but not after a strain of 20% or 30%. This suggests that the microstructural adaptations liable for the elastic transition withstood a strain at least twofold greater than the oscillating strain that pertained during their evolution (10% vs. 5%). We propose that a muscle adapting in dynamic conditions forges microstructures exhibiting a substantial degree of flexibility.
- PublicationAccès libreAirway smooth muscle adapting in dynamic conditions is refractory to the bronchodilator effect of a deep inspiration(American Physiological Society, 2020-02-01) Clisson, Marine; Khadangi, Fatemeh; Gazzola, Morgan; Bossé, Ynuk; Beaudoin, Jonathan; Clavel, Marie-AnnickAirway smooth muscle (ASM) is continuously strained during breathing at tidal volume. Whether this tidal strain influences the magnitude of the bronchodilator response to a deep inspiration (DI) is not clearly defined. The present in vitro study examines the effect of tidal strain on the bronchodilator effect of DIs. ASM strips from sheep tracheas were mounted in organ baths and then subjected to stretches (30% strain), simulating DIs at varying time intervals. In between simulated DIs, the strips were either held at a fixed length (isometric) or oscillated continuously by 6% (length oscillations) to simulate tidal strain. The contractile state of the strips was also controlled by adding either methacholine or isoproterenol to activate or relax ASM, respectively. Although the time-dependent gain in force caused by methacholine was attenuated by length oscillations, part of the acquired force in the oscillating condition was preserved postsimulated DIs, which was not the case in the isometric condition. Consequently, the bronchodilator effect of simulated DIs (i.e., the decline in force postsimulated versus presimulated DIs) was attenuated in oscillating versus isometric conditions. These findings suggest that an ASM operating in a dynamic environment acquired adaptations that make it refractory to the decline in contractility inflicted by a larger strain simulating a DI.
- PublicationAccès libreVascular burden impact on echocardiographic valvular graft degeneration following a Ross procedure in young adults(Elsevier, 2017-08-14) Bilodeau, Anthony; Clisson, Marine; Shen, Mylène; Mohammadi, Siamak; Perron, Jean; Clavel, Marie-Annick; Tastet, Lionel; Simard, Louis
- PublicationAccès libreShortening of airway smooth muscle is modulated by prolonging the time without simulated deep inspirations in ovine tracheal strips(American Physiological Society, 2019-11-26) Clisson, Marine; Khadangi, Fatemeh; Gazzola, Morgan; Bossé, Ynuk; Beaudoin, Jonathan; Clavel, Marie-AnnickThe shortening of airway smooth muscle (ASM) is greatly affected by time. This is because stimuli affecting ASM shortening, such as bronchoactive molecules or the strain inflicted by breathing maneuvers, not only alter quick biochemical processes regulating contraction but also slower processes that allow ASM to adapt to an ever-changing length. Little attention has been given to the effect of time on ASM shortening. The present study investigates the effect of changing the time interval between simulated deep inspirations (DIs) on ASM shortening and its responsiveness to simulated DIs. Excised tracheal strips from sheep were mounted in organ baths and either activated with methacholine or relaxed with isoproterenol. They were then subjected to simulated DIs by imposing swings in distending stress, emulating a transmural pressure from 5 to 30 cmH2O. The simulated DIs were intercalated by 2, 5, 10, or 30 min. In between simulated DIs, the distending stress was either fixed or oscillating to simulate tidal breathing. The results show that although shortening was increased by prolonging the interval between simulated DIs, the bronchodilator effect of simulated DIs (i.e., the elongation of the strip post- vs. pre-DI) was not affected, and the rate of re-shortening post-simulated DIs was decreased. As the frequency with which DIs are taken increases upon bronchoconstriction, our results may be relevant to typical alterations observed in asthma, such as an increased rate of re-narrowing post-DI.
- PublicationAccès libreProgression of aortic stenosis after an acute myocardial infarction(BMJ, 2022-06-21) Clisson, Marine; Paquin, Amélie; Hadjadj, Sandra; Deschênes, Valérie; Rouabhia, Dounia; Robitaille, Charlotte; Beaudoin, Jonathan; Aikawa, Elena; Marsit, Ons; Levine, Robert A; Pibarot, Philippe; Clavel, Marie-AnnickBackground Myocardial infarction (MI) has been shown to induce fibrotic remodelling of the mitral and tricuspid valves. It is unknown whether MI also induces pathological remodelling of the aortic valve and alters aortic stenosis (AS) progression. We thus compared AS progression after an acute MI and in patients with/without history of MI, and assessed post-MI pathobiological changes within the aortic valve leaflets in a sheep model. Methods Serial echocardiograms in human patients with AS were retrospectively analysed and compared between 3 groups: (1) acute MI at baseline (n=68), (2) prior history of MI (n=45) and (3) controls without MI (n=101). Annualised progression rates of AS severity were compared between these 3 groups. In addition, aortic valves were harvested from 15 sheep: (1) induced inferior MI (n=10) and (2) controls without MI (n=5), for biological and histological analyses. Results In humans, the acute MI, previous MI and control groups had comparable baseline AS severity. Indexed aortic valve area (AVAi) declined faster in the acute MI group compared with controls (−0.07±0.06 vs −0.04±0.04 cm²/m²/year; p=0.004). After adjustment, acute MI status was significantly associated with faster AVAi progression (mean difference: −0.013 (95% CI −0.023 to −0.003) cm²/m²/year, p=0.008). In the post-MI experimental animal model, aortic valve thickness and qualitative/quantitative expression of collagen were significantly increased compared with controls. Conclusions The results of this study suggest that AS progression is accelerated following acute MI, which could be caused by increased collagen production and thickening of the aortic valve after the ischaemic event.