Personne : Dumesnil, Jean G.
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Université Laval. Faculté de médecine
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- PublicationRestreintImpact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis(Oxford University Press, 2017-01-07) Dahou, Abdellaziz; O'Connor, Kim; Thébault, Christophe; Shen, Mylène; Le Ven, Florent; Bédard, Élisabeth; Capoulade, Romain; Beaudoin, Jonathan; Bernier, Mathieu; Pibarot, Philippe; Dumesnil, Jean G.; Clavel, Marie-Annick; Tastet, Lionel; Arsenault, MarieAims: The objective of this study was to examine the association between the different patterns of left ventricular (LV) remodelling/hypertrophy on all-cause and cardiovascular mortality in patients with aortic stenosis (AS). Methods and results: In total, 747 consecutive patients (69 ± 14 years, 57% men) with AS and preserved LV ejection fraction were included in this study. According to LV mass index and relative wall thickness, patients were classified into four LV patterns: normal, concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). One hundred and sixteen patients (15%) had normal pattern, 66 (9%) had EH, 169 (23%) had CR, and 396 (53%) had CH. During a median follow-up of 6.4 years, 339 patients died (242 from cardiovascular causes). CH was associated with higher risk of all-cause mortality compared with the three other LV patterns (all P < 0.05). After multivariable adjustment, CH remained associated with higher risk of mortality (HR = 1.27, 95% CI 1.01–1.61, P = 0.046). There was a significant interaction (P < 0.05) between sex and CH with regards to the impact on mortality: CH was associated with worse outcome in women (P = 0.0001) but not in men (P = 0.22). In multivariable analysis, CH remained associated with higher risk of worse outcome in women (HR = 1.56, 95% CI 1.08–2.24, P = 0.018). Conclusions: This study shows that CH was independently associated with increased risk of mortality in AS patients with preserved ejection fraction. This association was observed in women but not in men. The pattern of LV remodelling/hypertrophy should be integrated in the risk stratification process in patients with AS.
- PublicationRestreintB-type natriuretic peptide in low-flow, low-gradient aortic stenosis : relationship to hemodynamics and clinical outcome : results from the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study.(American Heart Association, 2007-06-05) Bergler-Klein, Jutta; Fuchs, Christina; Mundigler, Gerald; Mohty, Dania; Hachicha, Zeineb; Burwash, Ian G.; Blais, Claudia; Pibarot, Philippe; Dumesnil, Jean G.; Beanlands, Robert S. B.; Walter-Publig, Nicole; Rader, Florian; Baumgartner, HelmutBACKGROUND: The prognostic value of B-type natriuretic peptide (BNP) is unknown in low-flow, low-gradient aortic stenosis (AS). We sought to evaluate the relationship between AS and rest, stress hemodynamics, and clinical outcome. METHODS AND RESULTS: BNP was measured in 69 patients with low-flow AS (indexed effective orifice area < 0.6 cm2/m2, mean gradient < or = 40 mm Hg, left ventricular ejection fraction < or = 40%). All patients underwent dobutamine stress echocardiography and were classified as truly severe or pseudosevere AS by their projected effective orifice area at normal flow rate of 250 mL/s (effective orifice area < or = 1.0 cm2 or > 1.0 cm2). BNP was inversely related to ejection fraction at rest (Spearman correlation coefficient r(s)=-0.59, P<0.0001) and at peak stress (r(s)=-0.51, P<0.0001), effective orifice area at rest (r(s)=-0.50, P<0.0001) and at peak stress (r(s)=-0.46, P=0.0002), and mean transvalvular flow (r(s)=-0.31, P=0.01). BNP was directly related to valvular resistance (r(s)=0.42, P=0.0006) and wall motion score index (r(s)=0.36, P=0.004). BNP was higher in 29 patients with truly severe AS versus 40 with pseudosevere AS (median, 743 pg/mL [Q1, 471; Q3, 1356] versus 394 pg/mL [Q1, 191 to Q3, 906], P=0.012). BNP was a strong predictor of outcome. In the total cohort, cumulative 1-year survival of patients with BNP > or = 550 pg/mL was only 47+/-9% versus 97+/-3% with BNP < 550 (P<0.0001). In 29 patients who underwent valve replacement, postoperative 1-year survival was also markedly lower in patients with BNP > or = 550 pg/mL (53+/-13% versus 92+/-7%). CONCLUSIONS: BNP is significantly higher in truly severe than pseudosevere low-gradient AS and predicts survival of the whole cohort and in patients undergoing valve replacement.
- 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, FrançoisBACKGROUND: 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.
- PublicationAccès libreA ventricular-vascular coupling model in presence of aortic stenosis(American Physiological Society, 2005-04-01) Garcia, Damien; Pibarot, Philippe; Barenbrug, Paul J. C.; Dumesnil, Jean G.; Dekker, André L. A. J.; Veen, Frederik H. van der; Maessen, Jos G.; Durand, Louis-GillesIn patients with aortic stenosis, the left ventricular afterload is determined by the degree of valvular obstruction and the systemic arterial system. We developed an explicit mathematical model formulated with a limited number of independent parameters that describes the interaction among the left ventricle, an aortic stenosis, and the arterial system. This ventricular-valvular-vascular (V(3)) model consists of the combination of the time-varying elastance model for the left ventricle, the instantaneous transvalvular pressure-flow relationship for the aortic valve, and the three-element windkessel representation of the vascular system. The objective of this study was to validate the V(3) model by using pressure-volume loop data obtained in six patients with severe aortic stenosis before and after aortic valve replacement. There was very good agreement between the estimated and the measured left ventricular and aortic pressure waveforms. The total relative error between estimated and measured pressures was on average (standard deviation) 7.5% (SD 2.3) and the equation of the corresponding regression line was y = 0.99x - 2.36 with a coefficient of determination r(2) = 0.98. There was also very good agreement between estimated and measured stroke volumes (y = 1.03x + 2.2, r(2) = 0.96, SEE = 2.8 ml). Hence, this mathematical V(3) model can be used to describe the hemodynamic interaction among the left ventricle, the aortic valve, and the systemic arterial system.
- PublicationRestreintMitral annulus velocities by doppler tissue imaging : practical implications with regard to preload alterations, sample position, and normal values(C.V. Mosby, 2002-10-01) Coulombe, Denis; Paulin, Chantal; Pibarot, Philippe; Dumesnil, Jean G.; Arsenault, MarieBecause it appears to be less affected by changes in preload, mitral annulus Doppler tissue imaging (DTI) has been proposed as an alternate mean of identifying pseudonormal patterns of left ventricular filling. We thus studied the practical implications of DTI in 40 patients classified according to the Canadian Consensus on Diastolic Function (9 control participants, 9 with impaired relaxation, and 22 pseudonormal participants). Using DTI, the early diastolic velocity (Ea) was the most reproducible parameter whereas the late diastolic velocity (Aa) and Ea/Aa ratio varied significantly. Nonetheless, Ea missed 23% of pseudonormal participants and its sensitivity, specificity, and positive and negative predictive values to identify diastolic dysfunction were 81%, 89%, 96%, and 57%, respectively; improving to 94%, 89%, 97%, and 80%, respectively, if used during Valsalva's maneuver. Thus, DTI is not totally preload independent and should be interpreted in light of the other Doppler parameters and the use of Valsalva's maneuver. Moreover, consistent with recent studies, these results suggest that the threshold value of Ea used to identify diastolic dysfunction should be approximately 12.5 cm/s.
- PublicationRestreintIs the hemodynamic performance of the carpentier-edwards perimount valve really equivalent to that of stentless valves?(Society of Thoracic Surgeons, 2003-07-30) Pibarot, Philippe; Dumesnil, Jean G.
- PublicationRestreintA single center experience with the freestyle bioprosthesis : midterm results at the Québec Heart Institute(W.B. Saunders, 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, FrançoisStentless 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.
- PublicationRestreintHemodynamic and clinical impact of prosthesis-patient mismatch in the aortic valve position and its prevention(Elsevier Biomedical, 2000-10-01) Pibarot, Philippe; Dumesnil, Jean G.Prosthesis-patient mismatch is present when the effective orifice area of the inserted prosthetic valve is less than that of a normal human valve. This is a frequent problem in patients undergoing aortic valve replacement, and its main hemodynamic consequence is the generation of high transvalvular gradients through normally functioning prosthetic valves. The purposes of this report are to present an update on the concept of aortic prosthesis-patient mismatch and to review the present knowledge with regard to its impact on hemodynamic status, functional capacity, morbidity and mortality. Also, we propose a simple approach for the prevention and clinical management of this phenomenon because it can be largely avoided if certain simple factors are taken into consideration before the operation
- PublicationRestreintToward optimal treatment in women : the effect of sex on metoprolol-diphenhydramine interaction(British Pharmacological Society, 2010-02-01) Pilote, Sylvie; Hamelin, Bettina; Bélanger, Pierre Maxime; Sharma, Ashish; Pibarot, Philippe; Dumesnil, Jean G.; Meibohm, Bernd; Arsenault, MarieThe objective of this study was to determine if sex influences the pharmacokinetics and hemodynamics of the CYP2D6 substrate metoprolol and its interaction with diphenhydramine (CYP2D6 inhibitor) in healthy young participants with high (extensive metabolizer [EM]) or low (poor metabolizer [PM]) CYP2D6 activities. A prespecified comparative analysis of data from 2 sequential clinical trials that included 16 EM and 4 PM women and 10 EM and 6 PM men was performed. The participants in the 2 trials were administered a single oral dose of 100 mg metoprolol in the presence of steady-state diphenhydramine or placebo. Serial plasma and urine samples were obtained for 48 hours, and hemodynamic data was obtained for 12 hours after metoprolol. In the placebo arm, EM and PM women had 62% and 59% higher S-metoprolol AUC0–8 and 26% and 71% lower CL/F, respectively, compared to men with the same phenotype (all Ps < .05 women compared to men). These differences dissipated on body weight (WT) correction. Women (especially PMs) experienced greater negative chronotropic effects of metoprolol than men (P < .0001 women compared to men). Diphenhydramine coadministration increased S-metoprolol AUC by 84% in EM women and 45% in EM men (P < .009 women compared to men). In the diphenhydramine arm, sex differences in pharmacokinetics persisted even after WT correction, resulting in greater negative chronotropic effects in women (all Ps < .05 women compared to men). Metoprolol dose should be adjusted for body weight, particularly in women. Coadministration of a CYP2D6 inhibitor such as diphenhydramine, by a patient at similar doses in the 2 sexes, could result in a greater inhibition of clearance of CYP2D6 substrates with a resulting higher risk of pronounced pharmacological and adverse effects in women compared to men.
- PublicationRestreintParadoxical low flow and/or low gradient severe aortic stenosis despite preserved left ventricular ejection fraction : implications for diagnosis and treatment(European Society of Cardiology, 2009-09-08) Pibarot, Philippe; Dumesnil, Jean G.; Carabello, BlaseParadoxical low flow, low gradient, severe aortic stenosis (AS) despite preserved ejection fraction is a recently described clinical entity whereby patients with severe AS on the basis of aortic valve area have a lower than expected gradient in relation to generally accepted values. This mode of presentation of severe AS is relatively frequent (up to 35% of cases) and such patients have a cluster of findings, indicating that they are at a more advanced stage of their disease and have a poorer prognosis if treated medically rather than surgically. Yet, a majority of these patients do not undergo surgery likely due to the fact that the reduced gradient is conducive to an underestimation of the severity of the disease and/or of symptoms. The purpose of this article is to review and further analyse the distinguishing characteristics of this entity and to present its implications with regards to currently accepted guidelines for AS severity.