Personne : Clavel, Marie-Annick
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Université Laval. Faculté de médecine
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Publication Accès libreOutcomes of patients with asymptomatic aortic stenosis followed up in heart valve clinics(American Medical Association, 2018-10-03) Lancellotti, Patrizio; Magne, Julien; Dulgheru, Raluca; Capoulade, Romain; Pibarot, Philippe; Donal, Erwan; Clavel, Marie-Annick; Vannan, Mani A.; Tastet, Lionel; Chambers, John; Rosenhek, Raphael; Habib, Gilbert; Lloyd, Guy; Nistri, Stefano; Garbi, Madalina; Marchetta, Stella; Fattouch, Khalil; Coisne, Augustin; Montaigne, David; Modine, Thomas; Davin, Laurent; Gach, Olivier; Radermecker, Marc; Liu, Shizhen; Gillam, Linda; Rossi, Andrea; Galli, Elena; Ilardi, Federica; Zilberszac, Robert; Vollema, E. Mara; Delgado, Victoria; Cosyns, Bernard; Lafitte, Stephane; Bernard, Anne; Pierard, Luc A.; Bax, Jeroen J.; Oury, CécileImportance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27  months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients. Publication RestreintStress 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, FrançoisObjectives: 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. Publication Accès libreImaging and impact of myocardial fibrosis in aortic stenosis(American College of Cardiology Foundation, 2019-02-04) Bing, Rong; Clavel, Marie-Annick; Cavalcante, João L.; Everett, Russell J.; Newby, David E.; Dweck, Marc R.Aortic stenosis is characterized both by progressive valve narrowing and the left ventricular remodeling response that ensues. The only effective treatment is aortic valve replacement, which is usually recommended in patients with severe stenosis and evidence of left ventricular decompensation. At present, left ventricular decompensation is most frequently identiﬁed by the development of typical symptoms or a marked reduction in left ventricular ejection fraction <50%. However, there is growing interest in using the assessment of myocardial ﬁbrosis as an earlier and more objective marker of left ventricular decompensation, particularly in asymptomatic patients, where guidelines currently rely on non- randomized data and expert consensus. Myocardial ﬁbrosis has major functional consequences, is the key pathological process driving left ventricular decompensation, and can be divided into 2 categories. Replacement ﬁbrosis is irreversible and identiﬁed using late gadolinium enhancement on cardiac magnetic resonance, while diffuse ﬁbrosis occurs earlier, is potentially reversible, and can be quantiﬁed with cardiac magnetic resonance T1 mapping techniques. There is a substantial body of observational data in this ﬁeld, but there is now a need for randomized clinical trials of myocardial imaging in aortic stenosis to optimize patient management. This review will discuss the role that myocardial ﬁbrosis plays in aortic stenosis, how it can be imaged, and how these approaches might be used to track myocardial health and improve the timing of aortic valve replacement. Publication RestreintAssociation of aortic valve leaflet calcification on hemodynamic and clinical outcomes(Elsevier Biomedical, 2020-10-05) Zhang, Bin; Dahou, Abdellaziz; Clisson, Marine; Mahjoub, Haïfa; Côté, Nancy; Zenses, Anne-Sophie; Pibarot, Philippe; Clavel, Marie-Annick; Mathieu, Patrick; Salaun, ErwanBackground: The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR). Objectives: The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex. Methods: From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention. Results: There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm2 was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p < 0.001). The AVCd threshold combined with an MG progression threshold of 10 mm Hg amplified the stratification of patients at risk (log-rank, p < 0.001). The addition of AVCd threshold into the prediction model including traditional risk factors improved outcome prediction (net classification improvement: 0.25, p = 0.04; likelihood ratio test, p < 0.001). Conclusions: Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes. Publication RestreintConcomitant mitral regurgitation and aortic stenosis one step further to low-flow preserved ejection fraction aortic stenosis.(Oxford University Press, 2018-05-01) Benfari, Giovanni; Clavel, Marie-Annick; Nistri, Stefano; Maffeis, Caterina; Vassanelli, Corrado; Enriquez-Sarano, Maurice; Rossi, AndreaAims: Patients with severe aortic stenosis (AS) and normal ejection fraction (EF) can paradoxically present low-transaortic flow and worse prognosis. The role of co-existing mitral regurgitation (MR) in determining this haemodynamic inconsistency has never been quantitatively explored. The hypothesis is that MR influences forward stroke volume and characterizes the low-flow AS pattern. Methods and results: Consecutive patients with indexed aortic valve area (AVA) ≤0.6 cm2/m2 and EF > 50% formed the study population. Complete echocardiographic data were collected, and mitral effective regurgitant orifice area (ERO) and regurgitant volume were obtained with proximal isovelocity surface area method. Patients were divided into subgroups according to indexed stroke volume (SV index). Included patients were 273 [age 79 ± 10 years, 53% female, EF 65 ± 7%, indexed AVA 0.47 ± 0.09 cm2/m2, mean transaortic gradient (MG) 32 ± 17 mmHg]. Mitral regurgitation was present in 89 (32%); ERO was 0.12 ± 0.08 cm2 (range 0.02–0.49 cm2). A low-flow state (SV index ≤35 mL/m2) was diagnosed in 41 (15%) patients. The prevalence of MR was higher in with low-flow vs. normal-flow group (56 vs. 28%, P = 0.03). Effective regurgitant orifice was associated to low-flow state univariately (OR: 1.75 [1.59–2.60]; P = 0.004) and after comprehensive adjustment (OR:1.76 [1.12–2.75]; P = 0.01). When MG was forced in the model, ERO remained significant (P < 0.009). On average, there was a 6 mL reduction in forward SV appeared per each 0.1 cm2 of ERO. Conclusion In patients with severely reduced AVA and preserved EF, MR is a major determinant of the low-flow condition. Furthermore, MR quantification by ERO predicts the presence of reduced flow independently of chamber volumes, systolic function, and transaortic gradient. Publication Accès libreAssessment of aortic stenosis severity : a multimodality approach(Elsevier, 2019-11-18) Clavel, Marie-Annick; Ternacle, JulienSevere aortic stenosis (AS) is associated with a progressive cardiac remodeling that ultimately leads to heart failure and death if the valve is not replaced. The confirmation of AS severity is therefore crucial to adequately manage patients with AS. Transthoracic echocardiography is the first-line examination to confirm AS severity, but it may be inconclusive in discordant cases. In this setting, AS severity should be confirmed using a multimodality imaging approach. This review gives an overview of how to assess and/or confirm AS severity, especially in case of discordance. Publication RestreintBiomarkers of aortic bioprosthetic valve structural degeneration(Rapid Science Publishers, 2019-03-01) Côté, Nancy; Pibarot, Philippe; Clavel, Marie-Annick; Salaun, ErwanPurpose 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. Publication RestreintCalcium Scoring to classify aortic valve stenosis severity : what is the current data?(Current Science, 2023-07-28) Powers, Andréanne; Clavel, Marie-AnnickPurpose of review: This review explores current clinical value of aortic valve calcification (AVC) in classifying aortic valve stenosis (AS) severity, refining patient's follow-up, as well as novel and potential applications of this highly accurate marker in improving outcomes for AS patients. AVC limitations and important particularities regarding sex, valve phenotype, and ethnicity will also be addressed. Recent findings: Sex-specific AVC cut-offs have been included in current guidelines to identify severe AS when echocardiography is inconclusive. AVC is also associated with AS progression and could help refine the timing for patient's follow-up. In patients with AS, Doppler echocardiography is the gold standard for the assessment of AS severity. However, in more than one-third of patients, echocardiographic parameters are discordant, casting shadow on the true severity of the disease. Considering active leaflet calcification is the driving mechanism of AS, quantification of AVC has been shown to be of great interest for distinguishing true-severe from pseudo-severe AS. Moreover, AVC is closely associated with AS progression and outcomes. Publication Accès libreGenetic 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-JacquesBackground: 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. Publication Accès libreDobutamine 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.