Personne : Dagenais, François.
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Mitral repair versus replacement for ischemic mitral regurgitation : comparison of short-term and long-term survival
2009-09-15, Sénéchal, Mario, Charbonneau, Éric, Magne, Julien, Voisine, Pierre, Girerd, Nicolas, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François., Mathieu, Patrick
Background— 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.
Does the use of stentless aortic valves in a subcoronary position prevent patient-prosthesis mismatch for small aortic annulus?
2008-07-01, Lopez, Stéphane, Voisine, Pierre, Mohammadi, Siamak, Doyle, Daniel, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François., Mathieu, Patrick
Objective : 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.
Lipid-mediated inflammation and degeneration of bioprosthetic heart valves
2009-06-01, Lavoie, Michel, Shetty, Rahul, Audet, Audrey, Couture, Christian, Voisine, Pierre, Perron, Jean, Pibarot, Philippe, Dagenais, François., Després, Jean-Pierre, Mathieu, Patrick
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.
A single center experience with the freestyle bioprosthesis : midterm results at the Québec Heart Institute
2001-10-01, Desaulniers, Denis, Baillot, Richard, Bauset, Richard, Lemieux, Michel, Raymond, Gilles, Perron, Jean, Cartier, Paul C., Doyle, Daniel, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François.
Stentless bioprostheses show excellent early hemodynamic performance. However, longevity still remains unknown. This study reports midterm follow-up in 419 patients in which a Freestyle bioprosthesis (Medtronic Heart Valves, Minneapolis, MN) was inserted between January 1993 and January 2000 at the Quebec Heart Institute (Ste-Foy, Québec, Canada). Mean age at implantation was 68.0 +/- 8.2 years. Implantation was subcoronary in 81.9% of the patients, as a root replacement in 16.5%, and as a root inclusion in 1.7%. Mortality at 30 days was 6.2% for the whole cohort (2.8% for isolated subcoronary aortic valve replacement). Female gender, root implantation, valve sizes 19 to 21 mm, previous surgery, a history of stroke and diabetes were identified as predictors of 30-day mortality. Actuarial freedom from all death causes was 81.5% at 7 years; freedom from valve-related deaths 97.0%, and freedom from cardiac deaths 92.7%. Freedom from thromboembolic events was 86.1% at 7 years (55.1% of events were < 30 days). Freedom from endocarditis and hemorrhagic complications were respectively 98.5% and 95.6% at 7 years. Six patients required reoperations for valve explantation: 2 for endocarditis, 2 for structural dysfunction, and 2 for nonstructural dysfunction. Incidence of moderate or severe valve insufficiency at annual echocardiographic follow-up was: discharge: 0.6%; year 1: 0.7%; year 2: 1.3%; year 3: 3.3%; year 4: 3.7%; year 5: 2.6%; year 6: 0%. At 6 years after implantation, mean transvalvular gradient and effective valve orifice area were comparable to the year 1 values. This single center experience with the Medtronic Freestyle prosthesis shows preserved hemodynamic performance and low valve-related complications at midterm.
Impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement : influence of age, obesity, and left ventricular dysfunction
2009-01-06, Mohty, Dania, Dumesnil, Jean G., Voisine, Pierre, Echahidi, Najmeddine, Pibarot, Philippe, Dagenais, François., Mathieu, Patrick
Objectives: 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%.
RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing
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, Patrick
The 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.
Direction of persistent ischemic mitral jet after restrictive valve annuloplasty: implications for interpretation of perioperative echocardiography
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
Restrictive annuloplasty for ischemic mitral regurgitation may induce functional mitral stenosis
2008-04-22, Sénéchal, Mario, Magne, Julien, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François., Mathieu, Patrick
Objectives : 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
Sex-related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis : is valvular fibrosis the explanation?
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, Louis
Rationale: 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.
Preoperative posterior leaflet angle accurately predicts outcome after restrictive mitral valve annuloplasty for ischemic mitral regurgitation
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.
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