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Dagenais, François

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Dagenais

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François

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Université Laval. Département de chirurgie

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  • 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.
  • 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.
  • 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.
  • PublicationAccès libre
    A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis
    (Nature Publishing Group, 2018-03-07) Gaudreault, Nathalie; Thériault, Sébastien; Rosa, Mickael; Boulanger, Marie-Chloé; Capoulade, Romain; Messika-Zeitoun, David; Bossé, Yohan; Lamontagne, Maxime; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François; Mathieu, Patrick
    Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease and the current treatment options cannot stop or delay its progression. A GWAS on 1009 cases and 1017 ethnically matched controls was combined with a large-scale eQTL mapping study of human aortic valve tissues (n = 233) to identify susceptibility genes for CAVS. Replication was performed in the UK Biobank, including 1391 cases and 352,195 controls. A tran- scriptome-wide association study (TWAS) reveals PALMD (palmdelphin) as significantly associated with CAVS. The CAVS risk alleles and increasing disease severity are both associated with decreased mRNA expression levels of PALMD in valve tissues. The top variant identified shows a similar effect and strong association with CAVS (P = 1.53 × 10−10) in UK Biobank. The identification of PALMD as a susceptibility gene for CAVS provides insights into the genetic nature of this disease, opens avenues to investigate its etiology and to develop much-needed therapeutic options.
  • PublicationAccès libre
    Percutaneous transcatheter edge-to-edge mitral valve repair with MitraClip system in the era of G4
    (Elsevier, 2022-11-12) Silva, Iria; Turgeon, Pierre-Yves; Paradis, Jean-Michel; Beaudoin, Jonathan; O'Connor, Kim; Ternacle, Julien; Alperi, Alberto; Panagides, Vassili; Mesnier, Jules; Gravel, Caroline; Clavel, Marie-Annick; Dagenais, François; Dumont, Éric; Mohammadi, Siamak; Pibarot, Philippe; Bernier, Mathieu; Rodés-Cabau, Josep; Salaun, Erwan
    The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.
  • PublicationAccès libre
    Impact of metabolic syndrome and/or diabetes mellitus on left ventricular mass and remodeling in patients with aortic stenosis before and after aortic valve replacement
    (ScienceDirect, 2019-01-01) Guzzetti, Ezequiel; Shen, Mylène; Voisine, Pierre; Annabi, Mohamed Salah; Poirier, Paul; Piché, Marie-Eve; Zenses, Anne-Sophie; Pibarot, Philippe; Clavel, Marie-Annick; Ong, Géraldine; Dagenais, François; Tastet, Lionel; Salaun, Erwan
    Background: In aortic stenosis (AS), metabolic syndrome (MetS) and diabetes mellitus (DM) are associated with more pronounced left ventricular hypertrophy (LVH) and more concentric remodeling. We aimed to assess the impact of MetS and DM on left ventricular (LV) mass, remodeling and LV mass regression after aortic valve replacement (AVR) in patients with severe AS. Method: We included 177 patients with severe AS and preserved LVEF (>50%). All patients had comprehensive echocardiography before and one year after AVR. Results: Twenty-seven percent (27%) of patients had MetS, 21% DM and 52% neither MetS nor DM (No MetS-DM). Prior to AVR, indexed LV mass (LVMi) was higher in MetS and DM groups compared to NoMetS-DM group (56.1±14.2, 56.2±18.2 vs. 49.2±14.1 g/m2.7 respectively; p<0.01). Prevalence of LV hypertrophy was higher in MetS and DM than in NoMetS-DM patients (66%, 65% vs 44%, p<0.01) as well as LV mass to-end-diastolic volume ratio (2.10±0.44 and 2.21±0.63 vs 1.96±0.41 g/ml respectively, p=0.03). One year after AVR, decrease in LVMi was significant (p<0.001) in all 3 groups. DM and MetS were independently associated with higher baseline LVMi (p<0.05). MetS was independently associated with less LVM regression and higher LVMi 1 year after AVR. MetS and DM groups showed more residual LV hypertrophy than NoMetS-DM patients (57%, 38% and 17%, p<0.01). Conclusions: MetS and DM were independently associated with a higher preoperative LVMi and more concentric remodeling. One year after AVR, MetS was associated with less LVMi regression and higher LVMi. MetS and DM patients remained with more residual LV hypertrophy
  • PublicationAccès libre
    Multimarker approach to identify patients with higher mortality and rehospitalization rate after surgical aortic valve replacement for aortic stenosis
    (Elsevier, 2018-11-05) Lindman, Brian R.; Bilodeau, Anthony; Dahou, Abdellaziz; Abu-Alhayja'a, Rami; Arsenault, Benoit; Voisine, Pierre; Côté, Nancy; Novak, Éric L.; Bossé, Yohan; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François; Desmeules***, Philippe; Tastet, Lionel; Mathieu, Patrick; Aldahoun, Khitam
    This study sought to evaluate whether a multimarker approach might identify patients with higher mortality and hospitalization rates after aortic valve replacement (AVR) for aortic stenosis (AS). BACKGROUND: The society valve guidelines include accepted triggers for AVR in patients with severe asymptomatic AS, but circulating biomarkers do not have a clear role. METHOD: From a prospective registry of patients undergoing cardiac surgery between 2000 and 2012, 665 treated with surgical AVR (441 isolated) were evaluated. Seven biomarkers were measured on blood samples obtained before AVR. Biomarker levels were adjusted to account for the influence of age, sex, body mass index, and renal function; the median was used to determine an elevated value. Endpoints included all-cause mortality and all-cause and cardiovascular hospitalizations. Mean follow-up was 10.7 years and 299 (45%) died. RESULTS: Patients with 0 to 1, 2 to 3, 4 to 6, and 7 biomarkers elevated had 5-year mortality of 10%, 12%, 24%, and 33%, respectively, and 10-year mortality of 24%, 35%, 58%, and 71%, respectively (log-rank p < 0.001). The association between an increasing number of elevated biomarkers and increased all-cause mortality was observed among those with minimal symptoms (New York Heart Association functional class I or II) and those with a low N-terminal pro-B-type natriuretic peptide (p < 0.01 for both). Compared with those with 0 to 1 biomarkers elevated, patients with 4 to 6 or 7 biomarkers elevated had an increased hazard of mortality after adjustment for clinical risk scores (p < 0.01) and a 2- to 3-fold higher rate of all-cause and cardiovascular rehospitalization after AVR. Similar findings were obtained when evaluating cardiovascular mortality. Among patients with no or minimal symptoms, 42% had ≥4 biomarkers elevated. CONCLUSIONS: Among patients with severe AS treated with surgical AVR, an increasing number of elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortality and a higher rate of repeat hospitalization. A multimarker approach may be useful in the surveillance of asymptomatic patients with severe AS to optimize surgical timing.
  • PublicationRestreint
    Direction of persistent ischemic mitral jet after restrictive valve annuloplasty: implications for interpretation of perioperative echocardiography
    (Elsevier, 2007-10-01) Dubois, Michelle; Magne, Julien; Sénéchal, Mario; Charbonneau, Éric; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François
    BACKGROUND: Ischemic mitral regurgitation (MR) often persists after restrictive mitral valve annuloplasty (MVA) and is associated with a poor prognosis. It was hypothesized that the anterior displacement of the posterior aspect of the annulus caused by annuloplasty could induce a change in the direction of MR jet. METHODS: The echocardiograms of 21 patients who underwent restrictive MVA for ischemic MR and who had detectable postoperative MR were analyzed before and early after surgery to evaluate the direction of MR jet. RESULTS: The MR jet direction was posterior in 15 patients (72%) and central or anterior in six patients (28%) before the operation, compared with four patients (20%) and 17 patients (80%), respectively, after MVA (P<0.001). Overall, the jet direction was modified in 16 of 21 7patients (76%) following MVA. Among the subset of 11 patients with clinically significant persistent MR (vena contracta width greater than 3 mm), the MR jet direction changed in nine patients (82%) compared with their preoperative evaluation. Importantly, the initial clinical interpretation, based on a subjective evaluation, had classified MR severity as nonsignificant in six of 11 patients (55%), likely due to the eccentricity of the jet and its change in direction. CONCLUSION: The direction of the persistent MR jet early after annuloplasty is often different from that of preoperative MR jet and may lead to significant misinterpretation of the postoperative echocardiogram
  • PublicationRestreint
    Lipid-mediated inflammation and degeneration of bioprosthetic heart valves
    (Springer, 2009-06-01) Shetty, Rahul; Audet, Audrey; Couture, Christian; Voisine, Pierre; Perron, Jean; Pibarot, Philippe; Dagenais, François; Després, Jean-Pierre; Mathieu, Patrick; Janvier, R.
    BACKGROUND: The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs. MATERIAL AND METHODS: Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets. CONCLUSIONS: These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.