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Clavel, Marie-Annick

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Marie-Annick

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  • PublicationAccès libre
    Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study
    (The Lancet Publishing Group, 2023-11-22) Krasniqi, Lytfi; Schødt Riber, Lars Peter; Nissen, Henrik; Terkelsen, Christian Juhl; Andersen, Niels Holmark; Freeman, Phillip; Povlsen, Jonas A.; Gerke, Oke; Clavel, Marie-Annick; Dahl, Jordi S.
    Summary Background Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. Methods In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Findings Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4–2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8–2.3) and 1.5% (0.8–2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8–9.2) vs. 4.7% (3.2–6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Interpretation Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI.
  • PublicationRestreint
    Rate, timing, correlates, and outcomes of hemodynamic valve deterioration after bioprosthetic surgical aortic valve replacement
    (American Heart Association, 2018-08-13) Mahjoub, Haïfa; Rodés-Cabau, Josep; Kalavrouziotis, Dimitri; Voisine, Pierre; Mohammadi, Siamak; Côté, Nancy; Yanagawa, Bobby; Girerd, Nicolas; Pibarot, Philippe; Juni, Peter; Clavel, Marie-Annick; Verma, Subodh; Puri, Rishi; Dagenais, François; Mathieu, Patrick; Salaun, Erwan
    Background: The incidence of structural valve deterioration after bioprosthesis (BP) aortic valve replacement (AVR) established on the basis of reoperation may substantially underestimate the true incidence. The objective is to determine the rate, timing, correlates, and association between hemodynamic valve deterioration (HVD) and outcomes assessed by Doppler echocardiography after surgical BP AVR. Methods: A total of 1387 patients (62.2% male, 70.5±7.8 years of age) who underwent BP AVR were included in this retrospective study. Baseline echocardiography was performed at a median time of 4.1 (1.3–6.5) months after AVR. All patients had an echocardiographic follow-up ≥2 years after AVR (926 at least 5 years and 385 at least 10 years). HVD was defined by Doppler assessment as a ≥10 mm Hg increase in mean gradient or worsening of transprosthetic regurgitation ≥1/3 class. HVD was classified according to the timing after AVR: “very early,” during the first 2-years; “early,” between 2 and 5 years; “midterm,” between 5 and 10 years; and “long-term,” >10 years. Results: A total of 428 patients (30.9%) developed HVD. Among these patients, 52 (12.0%) were classified as “very early,” 129 (30.1%) as “early,” 158 (36.9%) as “midterm,” and 89 (20.8%) as “long-term” HVD. Factors independently associated with HVD occurring within the first 5 years after AVR were diabetes mellitus (P=0.01), active smoking (P=0.01), renal insufficiency (P=0.01), baseline postoperative mean gradient ≥15 mm Hg (P=0.04) or transprosthetic regurgitation ≥mild (P=0.04), and type of BP (stented versus stentless, P=0.003). Factors associated with HVD occurring after the fifth year after AVR were female sex (P=0.03), warfarin use (P=0.007), and BP type (P<0.001). HVD was independently associated with mortality (hazard ratio, 2.18; 95% CI, 1.86–2.57; P<0.001). Conclusions: HVD as identified by Doppler echocardiography occurred in one third of patients and was associated with a 2.2-fold higher adjusted mortality. Diabetes mellitus and renal insufficiency were associated with early HVD, whereas female sex, warfarin use, and stented BPs (versus stentless) were associated with late HVD.
  • PublicationRestreint
    Biomarkers of aortic bioprosthetic valve structural degeneration
    (Rapid Science Publishers, 2019-03-01) Côté, Nancy; Pibarot, Philippe; Clavel, Marie-Annick; Salaun, Erwan
    Purpose of review: Bioprosthetic valves are now used for the majority of surgical aortic valve replacements and for all transcatheter aortic valve replacements. However, bioprostheses are subject to structural valve deterioration (SVD) and have, therefore limited durability. Recent findings: Clinical, imaging, and circulating biomarkers may help to predict or indicate the presence of bioprosthetic valve SVD. The most important biomarkers of SVD includes: patient-related clinical biomarkers, such as diabetes and renal failure; valve-related biomarkers, such as absence of antimineralization process and severe prosthesis-patient mismatch; imaging biomarkers: the presence of valve leaflet mineralization on multidetector computed tomography or sodium fluoride uptake on positron emission tomography; and circulating biomarkers including: increased levels of HOMA index, ApoB/ApoA-I ratio, PCSK9, Lp-PLA2, phosphocalcic product. The assessment of these biomarkers may help to enhance risk stratification for SVD following AVR and may contribute to open novel pharmacotherapeutic avenues for the prevention of SVD. Summary: SVD may affect all bioprostheses after aortic valve replacement, and is the main cause of bioprosthetic valve failure and reintervention during the follow-up. Comprehensive assessment of clinical, imaging, and circulating biomarkers associated with earlier SVD could help strengthen the follow-up in high-risk patients and provide novel pharmacologic therapeutic strategies.
  • PublicationAccès libre
    Impact of vascular hemodynamics on aortic stenosis evaluation : new insights into the pathophysiology of normal flow - small aortic valve area - low gradient pattern
    (John Wiley & Sons, 2017-07-07) Clisson, Marine; Shen, Mylène; Côté, Nancy; Zenses, Anne-Sophie; Clavel, Marie-Annick; Tastet, Lionel; Simard, Louis
    Background: About 50% of normal‐flow/low‐gradient patients (ie, low mean gradient [MG] or peak aortic jet velocity and small aortic valve area) have severe aortic valve calcification as measured by computed tomography. However, they are considered to have moderate aortic stenosis (AS) in current American College of Cardiology/American Heart Association guidelines. The objective was thus to evaluate the effect of hypertension and reduced arterial compliance (rAC) on MG and Vpeak measurements. Methods and Results: Doppler‐echocardiography was performed in 4 sheep with experimentally induced severe and critical AS at: (1) normal aortic pressure, (2) during hypertension, and (3) with rAC. Hypertension and rAC induced a substantial decrease in MG/Vpeak compared with normal stage (both P≤0.03) despite a stable transvalvular flow (P>0.16). Hypertension and rAC resulted in a greater reduction of MG in critical (−42%) compared with severe (−35%) AS (P˂0.0001). Comprehensive Doppler‐echocardiography and computed tomography were performed in 220 AS patients (mean age: 69±13 years; MG 29±18 mm Hg) with normal flow. The population was divided in 3 groups according to the presence of hypertension and rAC. The slope of the linear association between MG/Vpeak and aortic valve calcification divided by the cross‐sectional area of the aortic annulus was significantly reduced in patients with hypertension and/or rAC compared with normotensive/normal AC patients (P<0.01). Accordingly, patients with normal‐flow/low‐gradient and severe aortic valve calcification density were more frequent in hypertension and rAC groups compared with the normotensive/normal‐AC group (16% and 12% compared with 2%; P=0.03). Conclusions: Hypertension and rAC are associated with a substantial reduction in MG/Vpeak for similar aortic valve calcification (ie, similar AS anatomic severity), which may lead to underestimation of AS hemodynamic severity
  • PublicationRestreint
    Low-flow aortic stenosis : flow rate does not replace but could refine stroke volume index
    (American College of Cardiology Foundation, 2021-03-17) Annabi, Mohamed Salah; Clavel, Marie-Annick
  • PublicationAccès libre
    Dobutamine stress echocardiography for management of low-flow, low-gradient aortic stenosis
    (Elsevier Biomedical, 2018-01-29) Dahou, Abdellaziz; Larose, Éric; Annabi, Mohamed Salah; Burwash, Ian G.; Touboul, Eden; Bergler-Klein, Jutta; Pibarot, Philippe; Enriquez-Sarano, Maurice; Clavel, Marie-Annick; Orwat, Stefan; Baumgartner, Helmut; Mascherbauer, Julia; Mundigler, Gerald; Cavalcante, João L.
    Background: Dobutamine stress echocardiography (DSE) is useful to differentiate true from pseudo severe aortic stenosis in patients with low left ventricular ejection fraction (LVEF), low-flow, low-gradient aortic stenosis (LF-LG AS). In the ACC/AHA guidelines, patients are considered having true-severe stenosis when the mean gradient (MG) is ≥40mmHg with an aortic valve area (AVA) ≤1cm2 during DSE. However these criteria have not been previously validated. The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with LFLG AS. Methods: In the TOPAS (“True or Pseudo-Severe Aortic Stenosis”) study, 186 patients with low LVEF LF-LG AS were prospectively recruited and underwent DSE with measurement of the MG, AVA and projected AVA, an estimate of the AVA at a standardized normal flow rate (AVAProj). Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients and by measurement of the aortic valve calcium by computed tomography in 25 patients and by both methods in 8. According to these assessments, 50/87 (57%) of the study cohort had true-severe stenosis. Results: Peak stress MG ≥40 mmHg, peak stress AVA ≤1cm2, and the combination of peak stress MG ≥40 mmHg and peak stress AVA≤1cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1cm2 was better than all the previous markers (p<0.007) with 70% of correct classification. Among the subset of 88 patients managed conservatively (47% of cohort), 52 died during a follow-up of 2.8±2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1cm2 was a strong predictor of mortality under medical management (HR: 3.65; p=0.0003). Conclusion: In patients with low LVEF LF-LG AS, the DSE criteria of peak stress MG≥40 mmHg, or the composite of peak stress MG≥40 mmHg and peak stress AVA≤1cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true from pseudo-severe aortic stenosis and is strongly associated with mortality in patients under conservative management.
  • PublicationAccès libre
    Transvalvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis
    (Elsevier, 2020-04-28) Bilodeau, Anthony; Guzzetti, Ezequiel; Kalavrouziotis, Dimitri; Zhang, Bin; Couture, Christian; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François
    Background : The respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are unknown. Objectives : This study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences. Methods : This study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women [37%]), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR. Results : In this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m2) and women (32 ml/m2). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines’ threshold (35 ml/m2) does not. Conclusions : Paradoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m2 for men and <32 ml/m2 for women) to define low-flow outperforms the guidelines’ threshold of 35 ml/m2 in risk stratification after AVR.
  • PublicationAccès libre
    Genetic association analyses highlight IL6, ALPL, and NAV1 as three new susceptibility genes underlying calcific aortic valve stenosis
    (American Heart Association, 2019-10-15) Gaudreault, Nathalie; Dina, Christian; Thériault, Sébastien; Messika-Zeitoun, David; Arsenault, Benoit; Le Scouarnec, Solena; Capoulade, Romain; Boureau, Anne-Sophie; Bossé, Yohan; Rigade, Sidwell; Lamontagne, Maxime; Li, Zhonglin; Pibarot, Philippe; Simonet, Floriane; Clavel, Marie-Annick; Dagenais, François; Mathieu, Patrick; Lecointe, Simon; Baron, Estelle; Bonnaud, Stéphanie; Karakachoff, Matilde; Charpentier, Eric; Fellah, Imen; Roussel, Jean-Christian; Verhoye, Jean Philippe; Baufreton, Christophe; Probst, Vincent; Roussel, Ronan; Redon, Richard; Le Tourneau, Thierry; Schott, Jean-Jacques
    Background: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. Methods: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. Results: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. Conclusions: Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.
  • PublicationAccès libre
    Progression 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-Annick
    Background 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.
  • PublicationRestreint
    Stress exercise haemodynamic performance and opening reserve of a stented bovine pericardial aortic valve bioprosthesis
    (Wiley, 2022-01-12) Porterie, Jean; Salaun, Erwan; Ternacle, Julien; Clavel, Marie-Annick; Dagenais, François
    Objectives: Despite unusual high rates of patient-prosthesis mismatch (PPM), excellent midterm clinical outcomes have been reported after surgical aortic valve replacement (SAVR) with the Avalus™ bioprosthetic valve (Medtronic). To elucidate this "PPM conundrum,"the Avalus valve haemodynamics were assessed during exercise testing. Methods: Of the 148 patients who had undergone SAVR with the Avalus valve at our institution, 30 were randomly selected among those in whom stress test was deemed feasible and underwent a resting transthoracic echocardiography immediately followed by exercise echocardiography. Severe PPM was defined as indexed effective orifice area (iEOA) ≤0.65 cm2 /m2 and moderate PPM as iEOA >0.65 and ≤0.85 cm2 /m2. Measured PPM was determined with the use of the measured iEOA at rest or stress, while the estimated PPM was based on the estimated iEOA, derived from the mean EOA reported for each valve size in the manufacturer chart. Results: Measured EOA significantly increased from rest to peak exercise in all PPM groups (p < .05) and the rates of moderate and severe measured PPM decreased from 40% and 20% to 27% and 0%, respectively. The patients with low-flow state (flow < 250 ml/s) had significantly lower measured rest EOA (p = .03). On the basis of the estimated iEOA, there was no severe PPM and 19 patients had moderate PPM (63.3%), with a significantly lower opening reserve than the patients without estimated PPM (p = .04). The estimated iEOA was more reliably correlated to the measured iEOA at maximal stress than the measured iEOA at rest, especially in patients with a low-flow state. Conclusions: This study supports the concept of an opening reserve of the Avalus valve to explain the PPM conundrum and promotes the use of exercise Doppler-echocardiography to complete the assessment of mismatch, especially in patients with a low-flow state. Published estimated EOA seems reliable to predict the haemodynamic performance of the Avalus valve, whether the flow conditions at rest.