Personne : Annabi, Mohamed Salah
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Université Laval. Faculté de médecine
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- PublicationAccès libreImpact of sex and sex hormones on pathophysiology and progression of aortic stenosis in a murine model(Physiological reports, 2022-08-27) Fleury, Marie-Ange; Annabi, Mohamed Salah; Voisine, Martine; Hervault, Maxime; Boilard, Anne-Julie; Shen, Mylène; Marette, André; Côté, Nancy; Clavel, Marie-AnnickThe lesions observed in AS have been shown to be sex specific, with women presenting extensive fibrotic remodeling while men developing more calcification deposit. We thus aimed to evaluate the influence of sex and sex hormones on the pathophysiology of aortic valve stenosis (AS) in our mouse model of AS. LDLr-/- ApoB100/100 IGF-II+/- mice (n = 210) were separated in six different groups: (1) intact male (IM), (2) intact female (IF), (3) castrated male (CM), (4) ovariectomized females (OF), (5) CM with testosterone supplementation (CMT), and (6) OF with 17β-estradiol supplementation (OFE). Mice were fed a high-fat/high-sucrose/high-cholesterol diet for 6 months. Hemodynamic progression of AS was followed by transthoracic echocardiography (at 12 and 36 weeks) and analyzed in all mice alive at 36 weeks. Aortic valves were collected for histological and digital droplet PCR* analysis. Increases in peak velocity were comparable in IF and IM (24.2 ± 5.7 vs. 25.8 ± 5.3 cm/s; p = 0.68), but IF presented with less severe AS. Between the three groups of male mice, AS progression was more important in IM (increase in peak velocity: 24.2 ± 5.7 cm/s; p < 0.001) compared to CM (6.2 ± 1.4; p = 0.42), and CMT (15.1 ± 3.5; p = 0.002). In the three groups of female mice, there were no statistical differences in AS progression. Digital PCR analysis revealed an important upregulation of the osteogenic gene RunX2 in IM (p < 0.0001) and downregulation of the pro-calcifying gene ALPL in IF (p < 0.05). Male sex and testosterone play an important role in upregulation of pro-calcifying genes and hemodynamic progression of AS. However, female mice appeared to be protected against calcification, characterized by downregulation of pro-osteogenic genes, but presented a similar AS hemodynamic progression
- PublicationAccès libreLa fraction amino-terminale du peptide natriurétique de type B pour prédire le devenir des patients ayant une sténose aortique à bas débit : sa supériorité au peptide natriurétique de type B et son rôle pour aider la décision thérapeutique(2018) Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-AnnickLa stratégie thérapeutique actuelle pour la sténose aortique à bas débit (SA-BD) n’intègre pas la gradation de la sévérité de la maladie du ventricule gauche (SMVG) pour sélectionner les meilleurs candidats au remplacement valvulaire aortique (RVA). MÉTHODE La SMVG a été gradée par le ratio d’activation du peptide natriurétique de type-B (BNP-ratio) et par celui de la fraction N-terminale de son précurseur (NT-proBNP-ratio). Leurs performances pronostiques ont été étudiées séparément puis en comparaison directe (sous-population avec les deux biomarqueurs). Le meilleur biomarqueur a été utilisé pour étudier le bénéfice cardiovasculaire du RVA en fonction de la SMVG. RÉSULTATS Le NT-proBNP-ratio prédisait la mortalité à 12 et 36 mois avec une aire sous la courbe d’efficacité du récepteur (ASCER) à 0.67±0.04 et 0.66±0.05, respectivement (p=0.001). Il a été indépendamment corrélé à la mortalité (risque relatif ajusté [RRa]=1.39, [1.11-1.74], p=0.004). Le BNP-ratio était significativement discriminant pour la mortalité à 12 mois seulement et tendait à prédire le temps au décès en utilisant un seuil>7.4 (RRa=2.14 [1.00- 4.58], p=0.05). La supériorité du NT-proBNP-ratio a été vérifiée en comparaison directe: i) les ASCER pour la mortalité à 12 et 36 mois étaient supérieures (p<0.009); ii) le NT-proBNP-ratio, contrairement au BNP-ratio, prédisait indépendamment la mortalité; iii) il améliorait significativement l’efficacité prédictive d’un modèle de base (Mb) incluant l’âge, le sexe, la présence de SA réellement sévère (SARS), l’euroSCORE et le RVA (p=0.0003); iv) l’index de reclassification nette associé au NT-proBNP-ratio était de 0.71 (p=0.008) contre 0.38 (p=0.15) pour le BNP-ratio. Enfin, le NTproBNP-ratio>11 prédisait un grand bénéfice de survie par RVA (RRa=0.52 [0.31-0.85], p=0.009), tandis qu’avec NT-proBNP-ratio<11, la survie était excellente sans RVA durant la première année. CONCLUSION: Cette étude démontre pour la première fois que la gradation de la SMVG par le NT-proBNP-ratio, et pas le BNPratio, a une grande valeur pronostique dans la SA-BD et peut guider la stratégie thérapeutique
- PublicationRestreintOutcomes from transcatheter aortic valve replacement in patients with low-flow, low-gradient aortic stenosis and left ventricular ejection fraction less than 30% : a substudy from the TOPAS-TAVI registry(JAMA Network, 2018-12-19) Maes, Frédéric; Dahou, Abdellaziz; Lerakis, Stamatios A.; Côté, Mélanie; Nombela-Franco, Luis; Gilard, Martine; Rodés-Cabau, Josep; Cavalcante, João L.; Annabi, Mohamed Salah; Makkar, Rajendra; Pelletier Beaumont, Émilie; Herrmann, Howard C.; Pibarot, Philippe; Windecker, Stephan; Clavel, Marie-Annick; Enriquez-Sarano, Maurice; Puri, Rishi; Cheema, Asim; Barbosa Ribeiro, Henrique; Muñoz, Antonio; García del Blanco, Bruno; Zajarias, Alan; Lisko, John C.; Hayek, Salim; Babaliaros, Vasilis; Le Ven, Florent; Gleason, Thomas G.; Chakravarty, Tarun; Szeto, Wilson; Agustin, Alberto de; Serra, Vicenç; Schindler, John ThomasImportance: In low-flow, low-gradient aortic stenosis (LFLG AS), the severity of left ventricular dysfunction remains a key factor in the evaluation of aortic valve replacement. Objective: To evaluate the clinical outcomes and changes in left ventricular ejection fraction (LVEF) after transcatheter aortic valve replacement (TAVR) in patients with LFLG AS and severe left ventricular dysfunction. Design, setting, and participants: This multicenter registry is a substudy of the True or Pseudo-Severe Aortic Stenosis-TAVI registry that included patients with classic LFLG AS, defined as a mean transvalvular gradient less than 35 mm Hg, an effective orifice area less than 1.0 cm2, and an LVEF of 40% or less. Patients were divided in groups with very low (<30%) LVEF and low (30%-40%) LVEF. Dobutamine stress echocardiography (DSE) was performed before TAVR in a subset with very low LVEF, and presence of contractile reserve was defined as an increase of 20% or more in stroke volume. Clinical outcomes were assessed at 1 and 12 months and yearly thereafter, and echocardiography was performed at 1-year follow-up. Retrospective data were collected from 2007 to 2013 and prospective data from January 2013 to March 2018. Data were analyzed from March to October 2018. Exposures: Transcatheter aortic valve replacement in patients with LFLG AS. Main outcomes and measures: Changes in LVEF over time; periprocedural and late mortality. Results: A total of 293 patients were included, including 128 (43.7%) with very low LVEF and 165 with low LVEF (56.3%). Their mean (SD) age was 80 (7) years, and most (214 [73.0%]) were men. The mean (SD) LVEF in the very low LVEF group was 22% (5%), compared with 37% (7%) in the low LVEF group (P < .001). There were no differences between groups in rates of periprocedural mortality and late mortality (median [interquartile range], 23 [6-38] months). Patients with very low LVEF displayed a greater increase in LVEF at the 1-year follow-up examination (mean absolute increase, 11.9% [95% CI, 8.8%-15.1%]), than the low LVEF group (3.6% [95% CI, 1.1%-6.1%]; P < .001). In 92 patients with very low LVEF who had preprocedural DSE, results showed a lack of contractile reserve in 45 (49%), but this had no effect on clinical outcomes or changes in LVEF over time. Conclusions and relevance: In patients with LFLG AS and severe left ventricular dysfunction, TAVR was associated with similar clinical outcomes as in counterparts with milder left ventricular dysfunction. The TAVR procedure was associated with a significant increase in LVEF, irrespective of contractile reserve. These results support TAVR for LFLG AS, irrespective of the severity of left ventricular dysfunction and DSE results.
- PublicationAccès libreMitral regurgitation in low-flow, low-gradient aortic stenosis patients undergoing TAVR : insights from the TOPAS-TAVI registry(Elsevier, 2020-02-12) Freitas Ferraz, Afonso; Dahou, Abdellaziz; Lerakis, Stamatios A.; Nombela-Franco, Luis; Rodés-Cabau, Josep; Gilard, Martine; Le Ven, Florent; Cavalcante, João L.; Amat Santos, Ignacio J.; Makkar, Rajendra; Annabi, Mohamed Salah; Herrmann, Howard C.; Pelletier Beaumont, Émilie; Windecker, Stephan; Pibarot, Philippe; Enriquez-Sarano, Maurice; Clavel, Marie-Annick; Cheema, Asim; Barbosa Ribeiro, Henrique; Muñoz, Antonio; García del Blanco, Bruno; Zajarias, Alan; Lisko, John C.; Hayek, Salim; Babaliaros, Vasilis; Gleason, Thomas G.; Chakravarty, Tarun; Szeto, Wilson Y.; Agustin, Alberto de; Serra, Vicenç; Schindler, John ThomasObjectives : This study sought to determine the incidence, clinical impact, and changes over time of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis (LFLG-AS) undergoing transcatheter aortic valve replacement (TAVR). Background : Few data exist on the clinical impact and changes in severity over time of MR in patients with LFLG-AS undergoing TAVR. Methods : A total of 308 TAVR candidates with LFLG-AS were included. Patients were categorized according to MR severity at baseline, and presence of MR improvement at 12-month follow-up. Clinical outcomes were assessed at 1 and 12 months (+ echocardiography), and yearly thereafter. Results : Baseline mild and moderate-to-severe MR were present in 118 (38.3%) and 115 (37.3%) patients, respectively. MR was of functional and mixed etiology in 77.2% and 22.7% of patients, respectively. A total of 131 patients (42.5%) died after a median follow-up of 2 (1 to 3) years. Baseline moderate-or-greater MR had no impact on mortality (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 0.72 to 2.48) or heart failure hospitalization (HR: 1.02; 95% CI: 0.49 to 2.10). At 1-year follow-up, MR improved in 44.3% of patients and remained unchanged/worsened in 55.7%. The lack of MR improvement was associated with a higher risk of all-cause and cardiac mortality (HR: 2.02; 95% CI: 1.29 to 3.17; HR: 3.03; 95% CI: 1.27 to 7.23, respectively), rehospitalization for cardiac causes (HR: 1.50; 95% CI: 1.04 to 2.15), and an increased overall-mortality/heart failure rehospitalization (HR: 1.94; 95% CI: 1.25 to 3.02). A higher baseline left ventricular end-diastolic diameter and a higher increase in left ventricular ejection fraction were found to be independent predictors of MR improvement at 1-year follow-up (odds ratio: 0.69; 95% CI: 0.51 to 0.94; and odds ratio: 0.81; 95% CI: 0.67 to 0.96, respectively). Conclusions : Most TAVR candidates with LFLG-AS had some degree of MR, of functional origin in most cases. MR improved in about one-half of patients, with larger left ventricular size and a higher increase in left ventricular ejection fraction post-TAVR determining MR improvement over time. The lack of MR improvement at 1 year was associated with poorer outcomes.
- PublicationAccès libreSex-related differences in Low-Gradient, low-ejection fraction aortic stenosis results from the multicenter TOPAS study(ScienceDirect, 2019-01-07) Bartko, Philipp Emanuel; Dahou, Abdellaziz; Rodés-Cabau, Josep; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-Annick
- PublicationAccès libreImpact of metabolic syndrome and/or diabetes mellitus on left ventricular mass and remodeling in patients with aortic stenosis before and after aortic valve replacement(ScienceDirect, 2019-01-01) Guzzetti, Ezequiel; Shen, Mylène; Voisine, Pierre; Annabi, Mohamed Salah; Poirier, Paul; Piché, Marie-Eve; Zenses, Anne-Sophie; Pibarot, Philippe; Clavel, Marie-Annick; Ong, Géraldine; Dagenais, François.; Tastet, Lionel; Salaun, ErwanBackground: In aortic stenosis (AS), metabolic syndrome (MetS) and diabetes mellitus (DM) are associated with more pronounced left ventricular hypertrophy (LVH) and more concentric remodeling. We aimed to assess the impact of MetS and DM on left ventricular (LV) mass, remodeling and LV mass regression after aortic valve replacement (AVR) in patients with severe AS. Method: We included 177 patients with severe AS and preserved LVEF (>50%). All patients had comprehensive echocardiography before and one year after AVR. Results: Twenty-seven percent (27%) of patients had MetS, 21% DM and 52% neither MetS nor DM (No MetS-DM). Prior to AVR, indexed LV mass (LVMi) was higher in MetS and DM groups compared to NoMetS-DM group (56.1±14.2, 56.2±18.2 vs. 49.2±14.1 g/m2.7 respectively; p<0.01). Prevalence of LV hypertrophy was higher in MetS and DM than in NoMetS-DM patients (66%, 65% vs 44%, p<0.01) as well as LV mass to-end-diastolic volume ratio (2.10±0.44 and 2.21±0.63 vs 1.96±0.41 g/ml respectively, p=0.03). One year after AVR, decrease in LVMi was significant (p<0.001) in all 3 groups. DM and MetS were independently associated with higher baseline LVMi (p<0.05). MetS was independently associated with less LVM regression and higher LVMi 1 year after AVR. MetS and DM groups showed more residual LV hypertrophy than NoMetS-DM patients (57%, 38% and 17%, p<0.01). Conclusions: MetS and DM were independently associated with a higher preoperative LVMi and more concentric remodeling. One year after AVR, MetS was associated with less LVMi regression and higher LVMi. MetS and DM patients remained with more residual LV hypertrophy
- PublicationRestreintPre- and post-operative stroke volume impact after surgical aortic valve replacement for severe aortic stenosis(Elsevier Biomedical, 2020-10-19) Guzzetti, Ezequiel; Poulin, Anthony; Kalavrouziotis, Dimitri; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-Annick; Dagenais, François.
- PublicationAccès libreProsthesis-patient mismatch after aortic valve replacement in the PARTNER 2 trial and registry(Elsevier, 2021-07-05) Dahou, Abdellaziz; Guzzetti, Ezequiel; Herrmann, Howard C.; Beaudoin, Jonathan; Kodali, Susheel; Annabi, Mohamed Salah; Leipsic, Jonathon; Bernier, Mathieu; Blanke, Philipp; Pibarot, Philippe; Jaber, Wael; Clavel, Marie-Annick; Mack, Michael J.; Salaun, Erwan; Ternacle, Julien; Khalique, Omar K.; Weissman, Neil J.; Douglas, Pamela; Bax, Jeroen; Xu, Ke; Alu, Maria; Rogers, Erin; Leon, Martin; Thourani, Vinod H.; Abbas, Amr E.; Hahn, Rebecca T.Objectives This study aimed to compare incidence and impact of measured prosthesis-patient mismatch (PPMM) versus predicted PPM (PPMP) after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). Background TAVR studies have used measured effective orifice area indexed (EOAi) to body surface area (BSA) to define PPM, but most SAVR series have used predicted EOAi. This difference may contribute to discrepancies in incidence and outcomes of PPM between series. Methods The study analyzed SAVR patients from the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and TAVR patients from the PARTNER 2 SAPIEN 3 Intermediate Risk registry. PPM was classified as moderate if EOAi ≤0.85 cm2/m2 (≤0.70 if obese: body mass index ≥30 kg/m2) and severe if EOAi ≤0.65 cm2/m2 (≤0.55 if obese). PPMM was determined by the core lab–measured EOAi on 30-day echocardiogram. PPMP was determined by 2 methods: 1) using normal EOA reference values previously reported for each valve model and size (PPMP1; n = 929 SAVR, 1,069 TAVR) indexed to BSA; and 2) using normal reference EOA predicted from aortic annulus size measured by computed tomography (PPMP2; n = 864 TAVR only) indexed to BSA. Primary endpoint was the composite of 5-year all-cause death and rehospitalization. Results The incidence of moderate and severe PPMP was much lower than PPMM in both SAVR (PPMP1: 28.4% and 1.2% vs. PPMM: 31.0% and 23.6%) and TAVR (PPMP1: 21.0% and 0.1% and PPMP2: 17.0% and 0% vs. PPMM: 27.9% and 5.7%). The incidence of severe PPMM and severe PPMP1 was lower in TAVR versus SAVR (P < 0.001). The presence of PPM by any method was associated with higher transprosthetic gradient. Severe PPMP1 was independently associated with events in SAVR after adjustment for sex and Society of Thoracic Surgeons score (hazard ratio: 3.18;95% CI: 1.69-5.96; P < 0.001), whereas no association was observed between PPM by any method and outcomes in TAVR. Conclusions EOAi measured by echocardiography results in a higher incidence of PPM following SAVR or TAVR than PPM based on predicted EOAi. Severe PPMP is rare (<1.5%), but is associated with increased all-cause death and rehospitalization after SAVR, whereas it is absent following TAVR.
- PublicationRestreintClinical value of stress transaortic flow rate during dobutamine echocardiography in reduced left ventricular ejection fraction(Lippincott Williams & Wilkins, 2021-11-08) Vamvakidou, Anastasia; Dahou, Abdellaziz; Guzzetti, Ezequiel; Annabi, Mohamed Salah; Plonska-Gosciniak, Edyta; Pibarot, Philippe; Almeida, Ana G.; Clavel, Marie-Annick; Burwash, Ian G.; Koschutnik, Matthias; Bartko, Philipp E.; Bergler-Klein, Jutta; Mascherbauer, Julia; Orwat, Stefan; Baumgartner, Helmut; Cavalcante, João L.; Pinto, Fausto J.; Kukulski, Tomasz; Kasprzak, Jaroslaw D.; Flachskampf, Frank A.; Senior, RoxyBackground: Low rest transaortic flow rate (FR) has been shown previously to predict mortality in low-gradient aortic stenosis. However limited prognostic data exists on stress FR during low-dose dobutamine stress echocardiography. We aimed to assess the value of stress FR for the detection of aortic valve stenosis (AS) severity and the prediction of mortality. Methods: This is a multicenter cohort study of patients with reduced left ventricular ejection fraction and low-gradient aortic stenosis (aortic valve area <1 cm2 and mean gradient <40 mm Hg) who underwent low-dose dobutamine stress echocardiography to identify the AS severity and presence of flow reserve. The outcome assessed was all-cause mortality. Results: Of the 287 patients (mean age, 75±10 years; males, 71%; left ventricular ejection fraction, 31±10%) over a mean follow-up of 24±30 months there were 127 (44.3%) deaths and 147 (51.2%) patients underwent aortic valve intervention. Higher stress FR was independently associated with reduced risk of mortality (hazard ratio, 0.97 [95% CI, 0.94–0.99]; P=0.01) after adjusting for age, chronic kidney disease, heart failure symptoms, aortic valve intervention, and rest left ventricular ejection fraction. The minimum cutoff for prediction of mortality was stress FR 210 mL/s. Following adjustment to the same important clinical and echocardiographic parameters, among the three criteria of AS severity during stress, ie, the guideline definition of aortic valve area <1cm2 and aortic valve mean gradient ≥40 mm Hg, or aortic valve mean gradient ≥40 mm Hg, or the novel definition of aortic valve area <1 cm2 at stress FR ≥210 mL/s, only the latter was independently associated with mortality (hazard ratio, 1.72 [95% CI, 1.05–2.82]; P=0.03). Furthermore aortic valve area <1cm2 at stress FR ≥210 mL/s was the only severe aortic stenosis criterion that was associated with improved outcome following aortic valve intervention (P<0.001). Guideline-defined stroke volume flow reserve did not predict mortality. Conclusions: Stress FR during low-dose dobutamine stress echocardiography was useful for the detection of both AS severity and flow reserve and was associated with improved prediction of outcome following aortic valve intervention.
- PublicationAccès libreComparison of early surgical or transcatheter aortic valve replacement versus conservative management in low-flow, low-gradient aortic stenosis sing Inverse Probability of Treatment Weighting: Results From the TOPAS Prospective Observational Cohort Study(John Wiley & Sons, 2020-12-08) Dahou, Abdellaziz; Côté, Nancy; Rodés-Cabau, Josep; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-AnnickBACKGROUND: No randomized comparison of early (ie, ≤3 months) aortic valve replacement (AVR) versus conservative management or of transcatheter AVR (TAVR) versus surgical AVR has been conducted in patients with low-flow, low-gradient (LFLG) aortic stenosis (AS). METHODS AND RESULTS: A total of 481 consecutive patients (75±10 years; 71% men) with LFLG AS (aortic valve area ≤0.6 cm2/m2 and mean gradient <40 mm Hg), 72% with classic LFLG and 28% with paradoxical LFLG, were prospectively recruited in the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. True-severe AS or pseudo-severe AS was adjudicated by flow-independent criteria. During follow-up (median [IQR] 36 [11–60] months), 220 patients died. Using inverse probability of treatment weighting to address the bias of nonrandom treatment assignment, early AVR (n=272) was associated with a major overall survival benefit (hazard ratio [HR], 0.34 [95% CI, 0.24–0.50]; P<0.001). This benefit was observed in patients with true-severe AS but also with pseudo-severe AS (HR, 0.38 [95% CI, 0.18–0.81]; P=0.01), and in classic (HR, 0.33 [95% CI, 0.22–0.49]; P<0.001) and paradoxical LFLG AS (HR, 0.42 [95% CI, 0.20–0.92]; P=0.03). Compared with conservative management in the conventional multivariate model, trans femoral TAVR was associated with the best survival (HR, 0.23 [95% CI, 0.12–0.43]; P<0.001), followed by surgical AVR (HR, 0.36 [95% CI, 0.23–0.56]; P<0.001) and alternative-access TAVR (HR, 0.51 [95% CI, 0.31–0.82]; P=0.007). In the inverse probability of treatment weighting model, trans femoral TAVR appeared to be superior to surgical AVR (HR [95% CI] 0.28 [0.11–0.72]; P=0.008) with regard to survival. CONCLUSIONS: In this large prospective observational study of LFLG AS, early AVR appeared to confer a major survival benefit in both classic and paradoxical LFLG AS. This benefit seems to extend to the subgroup with pseudo-severe AS. Our findings suggest that TAVR using femoral access might be the best strategy in these patients.