Personne : Dagenais, François.
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Département chirurgie, Faculté de médecine, Université Laval
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- PublicationRestreintMitral 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.
- PublicationRestreintImpact 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%.
- PublicationRestreintRestrictive annuloplasty for ischemic mitral regurgitation may induce functional mitral stenosis(American College of Cardiology, 2008-04-22) Sénéchal, Mario; Magne, Julien; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.; Mathieu, PatrickObjectives : The purpose of this study was to evaluate mitral valve hemodynamic performance and functional capacity in patients with ischemic mitral regurgitation (MR) who underwent restrictive mitral valve annuloplasty (MVA). Background : Restrictive MVA combined with coronary artery bypass graft is the conventional approach for the surgical management of patients with ischemic MR. We hypothesized that the restriction of the mitral annulus could cause an obstruction to antegrade mitral flow that may affect the patient's functional capacity. Methods : A dobutamine stress echocardiography (DSE) and a 6-min walk test (6MWT) were performed in 24 patients with ischemic MR 13 ± 3 months after restrictive MVA and coronary artery bypass graft and in 20 control patients with coronary artery disease matched for age, gender, and left ventricular ejection fraction. Results : None of the 24 MVA patients had significant MR after operation. Compared with control patients, MVA patients had significantly (p < 0.001) higher resting and stress peak gradients (rest: 13 ± 4 mm Hg vs. 4 ± 1 mm Hg; DSE: 19 ± 6 mm Hg vs. 6 ± 3 mm Hg) and systolic pulmonary arterial pressures (PAP) (rest: 42 ± 13 mm Hg vs. 27 ± 8 mm Hg; DSE: 58 ± 12 mm Hg vs. 38 ± 11 mm Hg) and lower (p = 0.01) 6MWT distance (358 ± 95 m vs. 433 ± 61 m). The resting peak mitral gradient correlated with systolic PAP (r = -0.67; p = 0.001) and 6MWT distance (r = -0.78; p < 0.0001) in the MVA group. Conclusions : The results suggest that performing a restrictive MVA in patients with ischemic MR may create a functional mitral stenosis. This hemodynamic sequel is associated with higher PAP and a worse functional capacity
- 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.
- PublicationRestreintLipid-mediated inflammation and degeneration of bioprosthetic heart valves(Springer, 2009-06-01) Lavoie, Michel; Shetty, Rahul; Audet, Audrey; Couture, Christian; Voisine, Pierre; Perron, Jean; Pibarot, Philippe; Dagenais, François.; Després, Jean-Pierre; Mathieu, PatrickBACKGROUND: 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.
- PublicationAccès libreImpact of aortic stenosis severity and its interaction with prosthesis-patient mismatch on operative mortality following aortic valve replacement.(ICR, 2012-03-02) Girerd, Nicolas; Charbonneau, Éric; Dumont, Éric; Magne, Julien; Baillot, Richard; Voisine, Pierre; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.; Mathieu, PatrickThe optimal timing of aortic valve replacement (AVR) in patients with severe aortic stenosis (AS) is a source of debate. Moreover, it has been shown previously that prosthesis-patient mismatch (PPM) is an independent predictor of operative mortality after AVR. The study aim was to assess the effect of the preoperative severity of AS and its interaction with PPM with respect to operative mortality after AVR.
- PublicationRestreintImpact of prosthesis-patient mismatch on survival after mitral valve replacement(American Heart Association, etc., 2007-03-05) Tanné, David; Magne, Julien; Doyle, Daniel; Pibarot, Philippe; Dumesnil, Jean G.; Dagenais, François.; Mathieu, PatrickBackground — We recently reported that valve prosthesis-patient mismatch (PPM) is associated with persisting pulmonary hypertension after mitral valve replacement. Thus, the objective of this study was to evaluate the impact of PPM on mortality in patients undergoing mitral valve replacement. Methods and Results— The indexed valve effective orifice area was estimated for each type and size of prosthesis being implanted in 929 consecutive patients and used to define PPM as not clinically significant if >1.2 cm2/m2, as moderate if >0.9 and =1.2 cm2/m2, and as severe if =0.9 cm2/m2. Moderate PPM was present in 69% of patients; severe PPM was seen in 9%. For patients with severe PPM, 6-year survival (74±5%) and 12-year survival (63±7%) were significantly less than for patients with moderate PPM (84±1% and 76±2%; P=0.027) or nonsignificant PPM (90±2% and 82±4%; P=0.002). On multivariate analysis, severe PPM was associated with higher mortality (hazard ratio, 3.2; 95% confidence interval, 1.5 to 6.8; P=0.003). Conclusions— Severe PPM is an independent predictor of mortality after mitral valve replacement. As opposed to other independent risk factors, PPM may be avoided or its severity may be reduced with the use of a prospective strategy at the time of operation. For patients identified as being at risk for severe PPM, every effort should be made to implant a prosthesis with a larger effective orifice area.
- 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