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Guzzetti, Ezequiel

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Ezequiel
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Université Laval
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  • Publication
    Restreint
    Left ventricular asymmetric remodeling and subclinical left ventricular dysfunction in patients with calcific aortic valve stenosis : results from a subanalysis of the PROGRESSA study
    (Elsevier Science Publishers, 2021-03-13) Clisson, Marine; Guzzetti, Ezequiel; Bernard, Jérémy; Larose, Éric; Shen, Mylène; Bédard, Élisabeth; Côté, Nancy; Capoulade, Romain; Pibarot, Philippe; Clavel, Marie-Annick; Tastet, Lionel; Arsenault, Marie
    Background: LV asymmetric remodeling (LVAR) is a feature commonly found in AS patients and it is presumed to be mainly related to the severity of valve stenosis. The aim of this study was to determine the associated factors and impact on left ventricular (LV) systolic function of LVAR in patients with mild and moderate aortic valve stenosis (AS). Methods: Clinical, Doppler-echocardiographic and computed-tomographic data of 155 AS patients with preserved LV ejection fraction (≥50%) prospectively recruited in the PROGRESSA study (NCT01679431) were analyzed. LVAR was defined as a septal wall thickness ≥ 13 mm and a ratio of septal/posterior wall thickness > 1.5. LV global longitudinal strain (LV-GLS) was available in 129 patients. Plasma levels of N-terminal natriuretic B-type peptides (Nt-proBNP) were also measured. Results: Mean age was 63 ± 15 years (70% men). LVAR was present in 21% (n = 33) of patients. A series of nested multivariate analysis revealed that age was the only factor associated with LVAR (all p ≤ 0.03). Additionally, these patients had higher baseline Nt-proBNP ratio (median [25–75 percentiles]: 1.04 [0.66–2.41] vs. 0.65 [0.33–1.19], p = 0.02), and significantly reduced LV-GLS (17.9[16.6–19.5] vs. 19.3[17.4–20.7] |%|, p = 0.04). A 1:1 matched analysis showed a significant association of LVAR with reduced LV-GLS (17.9[16.6–19.5] vs. 19.8[18.1–20.7] |%|, p = 0.02) and elevated Nt-proBNP (134[86–348] vs. 83[50–179]pg/ml, p = 0.03). Multivariable analysis also revealed that LVAR remains significantly associated with reduced LV-GLS (p = 0.03) and elevated Nt-proBNP (p = 0.001). LVAR was significantly associated with increased risk of major adverse cardiac events and death (Hazard ratio [95% confidence interval]: 2.32[1.28–4.22], p = 0.006). Conclusions: LVAR was found in ~20% of patients with mild or moderate AS and was not related to the degree of AS severity or concomitant comorbidities, but rather to older age. LVAR was significantly associated with reduced LV longitudinal systolic function, increased Nt-proBNP levels, and higher risk of major adverse events and death. These findings provide support for closer clinical and echocardiographic surveillance of patients harboring this adverse LV remodeling feature.
  • Publication
    Accès libre
    Transvalvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis
    (Elsevier, 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.
  • Publication
    Accès libre
    Usefulness of energy loss index for adjudication of low-gradient aortic stenosis severity
    (Oxford University Press, 2020-04-07) Guzzetti, Ezequiel; Pibarot, Philippe; Clavel, Marie-Annick
    Up to 40% of patients with aortic stenosis (AS) present with a low gradient (i.e., a mean transvalvular gradient [MG] <40 mmHg) despite a small aortic valve area (AVA≤1 cm2) at echocardiography or cardiac catheterization. This ‘discordant grading’ situation raises uncertainty about the true severity of AS and therefore about therapeutic decision making (1). A thorough, integrative approach including assessment of flow status and quantitation of aortic valve calcium score by multidetector computed tomography (MDCT) has been proposed in the 2017 European guidelines for discriminating true versus pseudo-severe AS in the patients with low-gradient AS (2). It is, indeed, estimated that 50 to 70% of patients with low-gradient AS have a true-severe AS and thus an indication (Class I or IIa) for aortic valve replacement. However, it remains crucial to identify patients with pseudo-severe AS, who should be managed conservatively.
  • Publication
    Restreint
    Validation of aortic valve calcium quantification thresholds measured by computed tomography in Asian patients with calcific aortic stenosis
    (Oxford University Press, 2021-06-25) Guzzetti, Ezequiel; Oh, Kyung Jin; Shen, Mylène; Pibarot, Philippe; Dweck, Marc R.; Clavel, Marie-Annick; Poh, Kian Keong; Tastet, Lionel; Abbas, Amr E.; Mando, Ramy; Pressman, Gregg; Brito, Daniel; Pawade, Tania; Falconi, Mariano Luis; Arenaza, Diego Perez de; Kong, William
    Aims Sex-specific thresholds of aortic valve calcification (AVC) have been proposed and validated in Caucasians. Thus, we aimed to validate their accuracy in Asians. Methods and results Patients with calcific aortic stenosis (AS) from seven international centres were included. Exclusion criteria were ≥moderate aortic/mitral regurgitation and bicuspid valve. Optimal AVC and AVC-density sex-specific thresholds for severe AS were obtained in concordant grading and normal flow patients (CG/NF). We included 1263 patients [728 (57%) Asians, 573 (45%) women, 837 (66%) with CG/NF]. Mean gradient was 48 (26–64) mmHg and peak aortic velocity 4.5 (3.4–5.1) m/s. Optimal AVC thresholds were: 2145 Agatston Units (AU) in men and 1301 AU in women for Asians; and 1885 AU in men and 1129 AU in women for Caucasians. Overall, accuracy (% correctly classified) was high and comparable either using optimal or guidelines’ thresholds (2000 AU in men, 1200 AU in women). However, accuracy was lower in Asian women vs. Caucasian women (76–78% vs. 94–95%; P < 0.001). Accuracy of AVC-density (476 AU/cm2 in men and 292 AU/cm2 in women) was comparable to absolute AVC in Caucasians (91% vs. 91%, respectively, P = 0.74), but higher than absolute AVC in Asians (87% vs. 81%, P < 0.001). There was no interaction between AVC/AVC-density and ethnicity (all P > 0.41) with regards to AS haemodynamic severity. Conclusion AVC thresholds defining severe AS are comparable in Asian and Caucasian populations, and similar to those proposed in the guidelines. However, accuracy of AVC to identify severe AS in Asians (especially women) is sub-optimal. Therefore, the use of AVC-density is preferable in Asians.
  • Publication
    Accès libre
    Importance of flow in risk stratification of aortic stenosis.
    (Elsevier, 2020-01-01) Guzzetti, Ezequiel; Pibarot, Philippe; Clavel, Marie-Annick
  • Publication
    Restreint
    Clinical 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, Roxy
    Background: 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.
  • Publication
    Restreint
    Estimation of stroke volume and aortic valve area in patients with aortic stenosis : a comparison of echocardiography versus cardiovascular magnetic resonance
    (Elsevier, 2020-06-21) Guzzetti, Ezequiel; Garcia, Julio; Larose, Éric; Le Ven, Florent; Capoulade, Romain; Pibarot, Philippe; Bédard, Élisabeth; Clavel, Marie-Annick; Tastet, Lionel; Arsenault, Marie
    Background: In aortic stenosis, accurate measurement of left ventricular stroke volume (SV) is essential for the calculation of aortic valve area (AVA) and the assessment of flow status. Current American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines suggest that measurements of left ventricular outflow tract diameter (LVOTd) at different levels (at the annulus vs 5 or 10 mm below) yield similar measures of SV and AVA. The aim of this study was to assess the effect of the location of LVOTd measurement on the accuracy of SV and AVA measured on transthoracic echocardiography (TTE) compared with cardiovascular magnetic resonance (CMR). Methods: One hundred six patients with aortic stenosis underwent both TTE and CMR. SV was estimated on TTE using the continuity equation with LVOTd measurements at four locations: at the annulus and 2, 5, and 10 mm below annulus. SV was also determined on CMR using phase contrast acquired in the aorta (SVCMR-PC), and a hybrid AVACMR-PC was calculated by diving SVCMR-PC by the transthoracic echocardiographic Doppler aortic velocity-time integral. Comparison between methods was made using Bland-Altman analysis. Results: Compared with the referent method of phase-contrast CMR for the estimation of SVCMR-PC and AVACMR-PC (SVCMR-PC 83 6 16 mL, AVACMR-PC 1.27 6 0.35 cm2 ), the best agreement was obtained by measuring LVOTd at the annulus or 2 mm below (P = NS), whereas measuring 5 and 10 mm below the annulus resulted in significant underestimation of SV and AVA by up to 15.9 6 17.3 mL and 0.24 6 0.28 cm2 , respectively (P < .01 for all). Accuracy for classification of low flow was best at the annulus (86%) and 2 mm below (82%), whereas measuring 5 and 10 mm below the annulus significantly underperformed (69% and 61%, respectively, P < .001). Conclusions: Measuring LVOTd at the annulus or very close to it provides the most accurate measures of SV and AVA, whereas measuring LVOTd 5 or 10 mm below significantly underestimates these parameters and leads to significant overestimation of the severity of aortic stenosis and prevalence of low-flow status.
  • Publication
    Accès libre
    Contrast-enhanced computed tomography assessment of aortic stenosis.
    (2021-01-29) Timothy Robert, Graham Cartlidge; Guzzetti, Ezequiel; Bing, Rong; Couture, Christian; Kwiecinski, Jacek; Pibarot, Philippe; Clavel, Marie-Annick; Pawade, Tania; Doris, Mhairi K; Adamson, Philip D; Massera, Daniele; Lembo, Maria; Peeters, Frederique E. C. M.; Berman, Daniel S; Dey, Damini; Slomka, Piotr; Newby, David E; Dweck, Marc R
    Abstract Objectives Non-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT. Methods This was a post hoc analysis of 164 patients (median age 71 (IQR 66–77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight. Results Contrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p<0.001) and peak aortic jet velocity (r=0.55, p<0.001). The fibrocalcific ratio decreased with increasing aortic stenosis severity (mild: 1.29 (0.98–2.38), moderate: 0.87 (1.48–1.72), severe: 0.47 (0.33–0.78), p<0.001) while the fibrocalcific volume increased (mild: 109 (75–150), moderate: 191 (117–253), severe: 274 (213–344) mm3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, p<0.001). Compared with the Agatston score, fibrocalcific volume demonstrated a better correlation with peak aortic jet velocity (r=0.59 and r=0.67, respectively), particularly in females (r=0.38 and r=0.72, respectively). Conclusions Contrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.
  • Publication
    Restreint
    Measuring progression of aortic stenosis : computed tomography versus echocardiography
    (BMJ Pub. Group, 2020-10-09) Guzzetti, Ezequiel; Clavel, Marie-Annick
  • Publication
    Accès libre
    Effect of regional upper septal hypertrophy on echocardiographic assessment of left ventricular mass and remodeling in aortic stenosis
    (ScienceDirect, 2020-10-14) Guzzetti, Ezequiel; Garcia, Julio; Larose, Éric; Shen, Mylène; Le Ven, Florent; Bédard, Élisabeth; Capoulade, Romain; Annabi, Mohamed Salah; Pibarot, Philippe; Clavel, Marie-Annick; Tastet, Lionel; Arsenault, Marie
    Background: Transthoracic echocardiography (TTE) is the reference method for evaluation of aortic stenosis (AS), and it is extensively used to quantitate left ventricular (LV) mass and volumes. Regional upper septal hypertrophy (USH) or septal bulge is a frequent finding in patients with AS and may lead to overestimation of LV mass when using linear measurements. The objective of this study was to compare estimates of LV mass obtained by two-dimensional transthoracic echocardiographic LV dimensions measured at different levels of the LV cavity with those obtained by cardiovascular magnetic resonance (CMR). Methods: One hundred six patients (mean age, 63 ± 15 years; 68% men) with AS were included in this subanalysis of the PROGRESSA study. Two-dimensional transthoracic echocardiographic measurements of LV dimensions were obtained at the basal level (BL; as recommended in guidelines), immediately below the septal bulge (BSB), and at a midventricular level (ML). Regional USH was defined as a basal interventricular septal thickness ≥ 13 mm and >1.3 times the thickness of the septal wall at the ML. Agreement between transthoracic echocardiographic and CMR measures was evaluated using Bland-Altman analysis. Results: The distribution of AS severity was mild in 23%, moderate in 57%, and severe in 20% of patients. Regional USH was present in 28 patients (26%). In the whole cohort, two-dimensional TTE overestimated LV mass (bias: BL, +60 ± 31 g; BSB, +59 ± 32 g; ML, +54 ± 32 g; P = .02). The biplane Simpson method slightly but significantly underestimated LV end-diastolic volume (bias -10 ± 20 mL, P < .001) compared with CMR. Overestimation of LV mass was more marked in patients with USH when measuring at the BL and was significantly lower when measuring LV dimensions at the ML (P < .025 vs BL and BSB). Conclusions: Two-dimensional TTE systematically overestimated LV mass and underestimated LV volumes compared with CMR. However, the bias between TTE and CMR was less important when measuring at the ML. Measurements at the BL as suggested in guidelines should be avoided, and measurements at the ML should be preferred in patients with AS, especially in those with USH.