Personne : Dagenais, François.
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Département chirurgie, Faculté de médecine, Université Laval
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- PublicationRestreintDoes the use of stentless aortic valves in a subcoronary position prevent patient-prosthesis mismatch for small aortic annulus?(Futura Pub. Co., 2008-07-01) Lopez, Stéphane; Voisine, Pierre; Mohammadi, Siamak; Doyle, Daniel; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.; Mathieu, PatrickObjective : Freestyle stentless bioprostheses have shown excellent hemodynamic performance. However, small size subcoronary implants have yet to prove their clinical usefulness. The aim of this study was to determine the incidence of patient-prosthesis mismatch [PPM = Indexed Effective Orifice Area (iEOA) = 0.85 cm2/m2] after aortic valve replacement (AVR) with 19-mm and 21-mm stentless bioprostheses and to evaluate clinical and hemodynamic outcomes. Methods : From January 1993 to December 2000, 419 patients who had undergone Freestyle bioprostheses implantation were prospectively followed. Sixty-eight patients (16%) received a 19–21-mm prosthesis. The EOA was calculated and indexed to the patient's body surface area to obtain the iEOA. Clinical as well as echographic measures were recorded at discharge and at one and five years. Results : PPM was present in 91% and 80% of patients with 19-mm and 21-mm prostheses, respectively. Severe mismatch (iEOA = 0.65 cm2/m2) was present in 58% and 17%. Mean gradients at discharge were 22 ± 11 mmHg for the 19-mm prostheses and 14 ± 7 mmHg for the 21-mm prostheses. Perioperative mortality was 33% (4/12 pts) for 19-mm prosthesis and 7% (4/56 pts) for 21-mm prostheses. Five-year actuarial survival was 58% for patients with 19-mm prosthesis and 82% for patients with 21-mm prosthesis (p = 0.04). Conclusion : AVR with small size Freestyle subcoronary implants is associated with a high incidence of PPM and high mortality.
- PublicationRestreintRNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing(American Physiological Society, 2016-10-01) Gaudreault, Nathalie; Tremblay-Marchand, Joël; Kalavrouziotis, Dimitri; Droit, Arnaud; Guauque-Olarte, Sandra; Bossé, Yohan; Seidman, Jonathan G.; Pibarot, Philippe; Body, Simon C.; Dagenais, François.; Mathieu, PatrickThe molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.
- PublicationAccès libreSex-related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis : is valvular fibrosis the explanation?(Grune & Stratton, 2016-11-22) Trahan, Sylvain; Couture, Christian; Mohammadi, Siamak; Côté, Nancy; Joubert, Philippe; Bossé, Yohan; Clavel, Marie-Annick; Pagé, Sylvain; Dagenais, François.; Mathieu, Patrick; Simard, LouisRationale: Calcific aortic stenosis (AS) is characterized by calcium deposition in valve leaflets. However, women present lower aortic valve calcification (AVC) loads than men for the same AS hemodynamic severity. Objective: We thus aimed to assess sex-differences in aortic valve fibro-calcific remodelling. Methods and Results: One hundred and twenty-five patients underwent Doppler-echocardiography and multidetector-computed-tomography within 3 months prior to aortic valve replacement. Explanted stenotic tricuspid aortic valves were weighed and fibrosis degree was determined. Sixty-four men and 39 women were frequency-matched for age, body mass index (BMI), hypertension, renal disease, diabetes, and AS severity. Mean age was 75±9years, mean gradient (41±18mmHg) and indexed aortic valve area (0.41±0.12cm2/m2) were similar between men and women (all p=0.18). Median AVC (1973[1124-3490]AU) and mean valve weight (2.36±0.99g) were lower in women compared to men (both p<0.0001). AVC density correlated better with valve weight in men (r2=0.57; p<0.0001) than in women (r2=0.26; p=0.0008). After adjustment for age, BMI, AVC density and aortic annulus diameter, female sex was an independent risk factor for higher fibrosis score in AS valves (p=0.003). Picrosirius red staining of explanted valves showed greater amount of collagen fibers (p=0.01) and Masson's trichrome staining revealed a greater proportion of dense connective tissue (p=0.02) in women compared to men. Conclusions: In this series with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared to men. These findings suggest that the pathophysiology of the disease and thus potential targets for drug development may be different according to sex.
- PublicationRestreintThe impact of complete revascularization on long-term survival is strongly dependent on age(Little, Brown & Co., 2012-11-01) Charbonneau, Éric; Dumont, Éric; Magne, Julien; Baillot, Richard; Voisine, Pierre; Mohammadi, Siamak; Doyle, Daniel; Girerd, Nicolas; Pibarot, Philippe; Dagenais, François.; Rabilloud, Muriel; Mathieu, PatrickBACKGROUND: Complete revascularization during coronary artery bypass grafting (CABG) has been reported to be associated with better short-term and long-term outcomes. We hypothesized that the survival benefit of complete revascularization would be less in old patients than in young patients. METHODS: We analyzed data from 6,539 consecutive patients who had undergone a first isolated on-pump CABG procedure between 2000 and 2008. We investigated the impact of complete revascularization and its interaction with age on operative and long-term survival using propensity-score-based analyses. RESULTS: Patients with incomplete (versus complete) revascularization (n=318 [4.9%]) were sicker overall. During a mean follow-up of 5.8±2.2 years, 909 patients died. In the propensity-score-matched analysis, operative mortality was not significantly different between patients with complete revascularization and those with incomplete revascularization (1.9% versus 2.8%; odds ratio [OR], 1.46; 95% confidence interval [CI], 0.56-3.46; p=0.48). In contrast, incomplete revascularization had an independent negative impact on long-term survival, which was strongly age dependent (hazard ratio [HR] for interaction, 0.96 per year increment; p=0.02). In a propensity-score-matched analysis, incomplete revascularization was independently associated with higher long-term mortality in patients younger than 60 years (HR, 3.27; 95% CI, 1.21-8.86; p=0.02), whereas it was not in patients 60 to 70 years and 70 years of age and older (p=0.87 and p=0.24, respectively). CONCLUSIONS: Contrary to what is observed in patients younger than 60 years, complete revascularization does not seem to improve long-term survival in older patients. This suggests that elderly patients at high operative risk may be considered, when deemed clinically appropriate, for limited coronary revascularization
- PublicationAccès librePostoperative atrial fibrillation predicts long-term survival after aortic-valve surgery but not after mitral-valve surgery : a retrospective study.(BMJ Publishing, 2011-10-27) Magne, Julien; Voisine, Pierre; Girerd, Nicolas; Pibarot, Philippe; Dagenais, François.; Mathieu, PatrickBackground: Postoperative atrial fibrillation (POAF) has been reported to be associated with reduced long-term survival after isolated coronary artery bypass grafting surgery. The objective of this study was to determine the impact of POAF on long-term survival after valvular surgery. Methods: The authors retrospectively analysed the preoperative and operative data of 2986 consecutive patients with no preoperative history of atrial fibrillation undergoing first valvular surgery (aortic-valve replacement (AVR), mitral valve replacement or mitral valve repair (MVR/MVRp) with or without coronary artery bypass grafting surgery) in their institution between 1995 and 2008 (median follow-up 5.31 years, range 0.1-15.0). The authors investigated the impact of POAF on survival using multivariable Cox regression. Results: Patients with POAF were older, and were more likely to have hypertension or renal failure when compared with patients without POAF. The 12-year survival in patients with POAF was 45.7±2.8% versus 61.4±2.1% in patients without POAF (p<0.001). On a multivariable analysis, when adjusting for age and other potential confounding factors, POAF tended to be associated with lower long-term survival (HR for all-cause death (HR)=1.17, 95% CI 1.00 to 1.38, p=0.051). The authors also analysed this association separately in patients with AVR and those with MVR/MVRp. In the multivariable analysis, POAF was a significant predictor of higher long-term mortality in patients with AVR (HR=1.22, CI 1.02 to 1.45, p=0.03) but not in patients with MVR/MVRp (HR=0.87, CI 0.58 to 1.29, p=0.48). Conclusions: POAF is significantly associated with long-term mortality following AVR but not after MVR/MVRp. The underlying factors involved in the pathogenesis of POAF after MVR/MVRp may partially account for the lack of association between POAF and survival in these patients.
- PublicationRestreintMetabolic syndrome is associated with faster degeneration of bioprosthetic valves(American Heart Association, 2006-07-04) Briand, Martin.; Voisine, Pierre; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.; Després, Jean-Pierre; Mathieu, PatrickBACKGROUND: Several studies have reported similarities between calcification of the native aortic valve and atherosclerosis. Recent studies also suggested that hypercholesterolemia may be a risk factor for calcific degeneration of bioprosthetic valves. The metabolic syndrome (MS) is associated with a higher risk of vascular atherosclerosis. We thus hypothesized that the atherogenic features of MS could accelerate bioprosthetic valve degeneration. METHODS AND RESULTS: We included 217 patients who underwent aortic valve replacement with a bioprosthetic valve in the study. Of these patients, 71 patients (33%) had MS defined according to the modified criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III. The annualized increase in mean transprosthetic gradient and the worsening of transprosthetic regurgitation measured by Doppler echocardiography were used to assess the deterioration of valve hemodynamic function. Patients with MS had higher progression of gradient (+4+/-5 mm Hg/year versus +2+/-2 mm Hg/year, P<0.001), higher proportion of > or = 1/3 degree worsening of regurgitation (25% versus 12%, P=0.02), and higher proportion of valve function deterioration defined as regurgitation worsening and/or > or = 3 mm Hg/year increase in gradient (41% versus 25%, P=0.02) when compared with patients without MS. On multivariate analysis, MS was an independent predictor of gradient progression (P=0.01), regurgitation worsening (P=0.02), and valve function deterioration (P=0.02). The other independent predictors were diabetes, renal insufficiency, and higher mean gradient at baseline. CONCLUSIONS: This is the first study to report that the MS is independently associated with faster bioprosthetic valve degeneration. This study could pave the way for the development of a new medical therapy able to significantly reduce the structural valve deterioration of bioprostheses
- PublicationAccès libreDistribution of SPARC during neovascularisation of degenerative aortic stenosis(British Cardiac Society, 2006-05-18) Côté, Claude H.; Charest, Amélie.; Shetty, Rahul; Voisine, Pierre; Pépin, Andrée; Pibarot, Philippe; Dagenais, François.; Mathieu, PatrickObjective: To examine the hypothesis that degenerative aortic stenosis (AS) is associated with the development of blood vessels and the expression of the secreted protein, acidic and rich in cysteine/osteonectin (SPARC), a matricellular protein that is involved in ossification, the modulation of angiogenesis and the production of metalloproteinases. Methods: 30 surgically excised AS valves and 20 normal aortic valves were studied. Results: Blood vessels were detected in the aortic valves from patients with degenerative AS, whereas normal valves were avascular structures. Blood vessels in AS valves expressed endothelial nitric oxide synthase, CD34 and von Willebrand factor (vWF). Blood vessels were located in three distinct regions: near calcified nodules, under the leaflet border and in rich cellular areas forming cell islands. Blood vessels were predominantly present in early and intermediate grades of calcification. Cell islands were densely populated by CD45-positive cells where endothelial cells (CD34+, vWF+) forming cord-like structures were present. Immunoblotting detected SPARC only in AS valves and immunohistological analysis located SPARC in mature blood vessels. The proportion of blood vessels positive for SPARC was higher in valves with a lower grade of calcification. In cell islands, SPARC was distributed to mature blood vessels and to macrophages, where it co-located with matrix metalloproteinase-9, whereas no expression was detected in endothelial cells forming cord-like structures. Conclusion: The localisation of SPARC to mature blood vessels and its predominant expression in AS valves with a lower calcification grade suggest that the spatial and temporal distribution of this matricellular protein is tightly controlled to participate in the neovascularisation of AS valves.
- PublicationAccès libreExpression of bone-regulatory proteins in human valve allografts(BMJ Publishing Group, 2006-09-01) Shetty, Rahul; Voisine, Pierre; Perron, Jean; Doyle, Daniel; Charest, A.; Pépin, Andrée; Pibarot, Philippe; Dagenais, François.; Mathieu, PatrickObjective : To test the hypothesis that valve allograft (VA) calcification results from an ossification process in which bone-regulatory proteins are expressed. Methods : 15 VA that were explanted at the time of surgery for dysfunction were studied. VA were analysed and compared with normal aortic valves (n = 20). Results : All the VA (5 aortic, 10 pulmonary) exhibited heavy calcification and important fibrosis. Immunohistochemistry studies showed that the bone-specific transcription factor Cbfa-1 was expressed by stromal cells. Bone alkaline phosphatase was expressed in calcified regions. Immunostaining for a smooth muscle (a-SM) actin was increased in VA compared with normal valves and in 6 of the 15 valves formed cellular clusters close to the calcified nodules. In VA osteopontin and osteonectin were expressed by stromal cells, whereas osteocalcin was closely associated with the calcified regions. Furthermore, analysis of the bone-regulatory proteins that control bone resorption showed that receptor activator of nuclear factor kB ligand (RANKL), receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) were differentially expressed in calcified VA and normal valves. Normal valve leaflets expressed OPG, whereas OPG expression was absent or faint in calcified VA. RANKL and RANK were not detected in normal valves, whereas calcified VA expressed RANKL and RANK. Conclusion : These data suggest that calcification of VA results from an ossification process, which relies on tight control of bone-regulatory protein expression. The expression pattern of the RANKL/RANK/OPG system suggests that it may have a regulatory role not only in osteoclastogenesis but also in the calcification of human VA.
- PublicationRestreintDirection 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
- PublicationRestreintPreoperative posterior leaflet angle accurately predicts outcome after restrictive mitral valve annuloplasty for ischemic mitral regurgitation(American Heart Association, 2007-02-13) Sénéchal, Mario; Magne, Julien; Hachicha, Zeineb; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.BACKGROUND: Ischemic mitral regurgitation (MR) often persists after restrictive mitral valve annuloplasty, in which case it is associated with worse clinical outcomes. The goal of the present study was to determine whether persistence of MR and/or clinical outcome could be predicted from preoperative analysis of mitral valve configuration METHODS AND RESULTS : In 51 consecutive patients undergoing restrictive annuloplasty for ischemic MR, posterior leaflet (PL) angle, anterior leaflet angle, coaptation distance, and tenting area were quantified by echocardiography before surgery (6+/-3 days), and MR severity was assessed before and early after surgery (9+/-4 days). Postoperatively, persistence of mild to moderate MR (vena contracta > 3 mm) was observed in 11 (22%) of the patients. The best predictor of postoperative persistence of MR was a PL angle > or = 45 degrees (sensitivity 100%, specificity 97%, positive predictive value 92%, negative predictive value 100%). Patients with persistent MR had markedly lower 3-year event-free survival (26+/-20%) compared with those with nonpersistent MR (75+/-12%, P=0.01). Preoperative presence of a PL angle > or = 45 degrees also was associated with a markedly lower 3-year event-free survival (22+/-17% versus 76+/-12%; P<0.001). CONCLUSIONS: In patients undergoing restrictive annuloplasty for ischemic MR, persistence of MR and 3-year event-free survival can accurately be predicted by preoperative analysis of mitral valve configuration. Patients with a PL angle > or = 45 degrees (ie, with high PL restriction) should thus be considered poor candidates for this procedure, and concomitant or alternative procedures should be contemplated.