Personne : Voisine, Pierre
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Université Laval. Département de chirurgie
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Publication RestreintRate, 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, ErwanBackground: 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. Publication RestreintDoes 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. Publication RestreintLipid-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. Publication RestreintMiddle-aged men with increased waist circumference and elevated C-reactive protein level are at higher risk for postoperative atrial fibrillation following coronary artery bypass grafting surgery(European Society of Cardiology, 2009-03-27) Fournier, Dominique; Voisine, Pierre; Daleau, Pascal; Girerd, Nicolas; Pibarot, Philippe; Després, Jean-Pierre; Mathieu, Patrick; O'Hara, GillesIntroduction: We recently demonstrated that metabolic syndrome (MetS) is an independent risk factor for postoperative atrial fibrillation (POAF) following coronary artery bypass grafting (CABG). In the present work, we sought to determine which feature of the MetS is associated with POAF. Methods and results: We retrospectively analysed the association between metabolic features and the incidence of new-onset POAF in a total of 2214 male patients <65 years who underwent first isolated CABG. Anthropometric data including waist circumference (WC) and complete preoperative lipid profile were available. We also conducted a nested case–control substudy including 147 patients who developed POAF, and were matched for age with a control population. In these patients, C-reactive protein, interleukin-6 (IL-6), and thiobarbituric acid-reactive substances (TBARS; evaluating the oxidative stress) blood levels were determined. In the whole cohort, 19.6% of patients developed POAF. On univariate analysis, body mass index (BMI; P = 0.002) and WC (P = 0.001) were the only anthropometric variables significantly associated with increased incidence of POAF. In the multivariable logistic model, the only independent predictors of POAF were a WC > 102 cm [odds ratio (OR) = 1.40, P = 0.04)] and older age (OR = 1.08, P < 0.001). In the nested case–control substudy C-reactive protein, IL-6, and TBARS levels were not significantly different in patients with or without POAF. Of particular significance, patients with elevated WC > 102 cm and C-reactive protein > 1.5 mg/L or IL-6 >2.2 pg/mL were at a high risk of developing POAF (respectively, OR = 2.32, P = 0.02 and OR = 2.27, P = 0.03). Conclusion: Patients with increased WC combined with elevated C-reactive protein levels are at higher risk for POAF. Thus, interventions targeting inflammation related to visceral obesity might help reducing the incidence of POAF. Publication RestreintMetabolic 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 Publication Accès 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. Publication Accès 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. Publication RestreintThe 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 Publication RestreintMitral repair versus replacement for ischemic mitral regurgitation : comparison of short-term and long-term survival(American Heart Association, 2009-09-15) Sénéchal, Mario; Charbonneau, Éric; Magne, Julien; Voisine, Pierre; Girerd, Nicolas; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François; Mathieu, PatrickBackground— When compared to mitral valve replacement (MVR), mitral valve repair (MVRp) is associated with better survival in patients with organic mitral regurgitation (MR). However, there is an important controversy about the type of surgical treatment that should be used in patients with ischemic MR. The objective of this study was to compare the postoperative outcome of MVRp versus MVR in patients with ischemic MR. Methods and Results— Preoperative and operative data of 370 patients with ischemic MR who underwent mitral valve surgery were prospectively collected and retrospectively analyzed. MVRp was performed in 50% of patients (n=186) and MVR in 50% (n=184). Although operative mortality was significantly lower after MVRp compared to MVR (9.7% versus 17.4%; P=0.03), overall 6-year survival was not statistically different between procedures (73±4% versus 67±4%; P=0.17). After adjusting for other risk factors and propensity score, the type of procedure (MVRp versus MVR) did not come out as an independent predictor of either operative (OR, 1.5; 95% CI, 0.7–2.9; P=0.34) or overall mortality (HR, 1.2; 95% CI, 0.7–1.9; P=0.52). Conclusion— As opposed to what has been reported in patients with organic MR, the results of this study suggest that MVRp is not superior to MVR with regard to operative and overall mortality in patients with ischemic MR. These findings provide support for the realization of a randomized trial comparing these 2 treatment modalities. Publication RestreintImpact of prosthesis-patient mismatch on long-term survival after aortic valve replacement : influence of age, obesity, and left ventricular dysfunction(Elsevier Inc., 2009-01-06) Mohty, Dania; Dumesnil, Jean G.; Voisine, Pierre; Echahidi, Najmeddine; Pibarot, Philippe; Dagenais, François; Mathieu, PatrickObjectives: This study was designed to evaluate the effect of valve prosthesis-patient mismatch (PPM) on late survival after aortic valve replacement (AVR) and to determine if this effect is modulated by patient age, body mass index (BMI), and pre-operative left ventricular (LV) function. Background: We recently reported that PPM is an independent predictor of operative mortality after AVR, particularly when associated with LV dysfunction. Methods: The indexed valve effective orifice area (EOA) was estimated in 2,576 patients having survived AVR and was used to define PPM as not clinically significant if it was >0.85 cm(2)/m(2), as moderate if >0.65 and < or =0.85 cm(2)/m(2), and severe if < or =0.65 cm(2)/m(2). Results: After adjustment for other risk factors, severe PPM was associated with increased late overall mortality (hazard ratio [HR]: 1.38; p = 0.03) and cardiovascular mortality (HR: 1.63; p = 0.0006) in the whole cohort. Severe PPM was also associated with increased overall mortality in patients <70 years old (HR: 1.77; p = 0.002) and in patients with a BMI <30 kg/m(2) (HR: 2.1; p = 0.006), but had no impact in older patients or in obese patients. Moderate PPM was a predictor of mortality in patients with LV ejection fraction <50% (HR: 1.21; p = 0.01), but not in patients with preserved LV function. Conclusions: Moderate PPM is associated with increased late mortality in patients with LV dysfunction, but with normal prognosis in those with preserved LV function. Notwithstanding the previously demonstrated deleterious effect of severe PPM on early mortality, this factor appears to increase late mortality only in patients <70 years old and/or with a BMI <30 kg/m(2) or an LV ejection fraction <50%.