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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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ncf10831090

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PublicationRestreint

Rate, timing, correlates, and outcomes of hemodynamic valve deterioration after bioprosthetic surgical aortic valve replacement

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.

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Lipid-mediated inflammation and degeneration of bioprosthetic heart valves

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.

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PublicationAccès libre

Impact of aortic stenosis severity and its interaction with prosthesis-patient mismatch on operative mortality following aortic valve replacement.

2012-03-02, Girerd, Nicolas, Charbonneau, Éric, Dumont, Éric, Magne, Julien, Baillot, Richard, Voisine, Pierre, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François, Mathieu, Patrick

The 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.

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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.

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Transvalvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis

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.

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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.

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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.

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Multimarker approach to identify patients with higher mortality and rehospitalization rate after surgical aortic valve replacement for aortic stenosis

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.

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Impact of prosthesis-patient mismatch on survival after mitral valve replacement

2007-03-05, Tanné, David, Magne, Julien, Doyle, Daniel, Pibarot, Philippe, Dumesnil, Jean G., Dagenais, François, Mathieu, Patrick

Background — 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.

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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%.