Publications by authors named "Marie-Annick Clavel"

226 Publications

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

Am J Cardiol 2022 Jun 28. Epub 2022 Jun 28.

Cardiology Department, des Hôpitaux G-G de l'Institut Catholique de Lille (Lille Catholic Hospital) Heart Valve Center, Lille Catholic University, Lille, France. Electronic address:

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.
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http://dx.doi.org/10.1016/j.amjcard.2022.05.019DOI Listing
June 2022

Long-Term Outcomes of Ross Procedure versus Mechanical Aortic Valve Replacement: Meta-Analysis of Reconstructed Time-To-Event Data.

Trends Cardiovasc Med 2022 Jun 22. Epub 2022 Jun 22.

Department of Cardiothoracic Surgery, Lankenau Heart Institute, Lankenau Medical Center, Main Line Health, Wynnewood, Pennsylvania, USA; Department of Cardiothoracic Surgery Research, Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, USA.

In the era of lifetime management of aortic valve disease, the Ross procedure emerged as an alternative to prosthetic heart valves for young adults; however, more long-term data are warranted. We performed a meta-analysis of reconstructed time-to-event data to compare long-term outcomes between the Ross procedure and mechanical aortic valve replacement (mAVR) in young adults. PubMed/MEDLINE, EMBASE and GoogleScholar were searched for studies comparing Ross procedure with mAVR that reported mortality/survival rates and/or reoperation rates accompanied by at least one Kaplan-Meier curve for any of the outcomes. Six observational studies (5 with propensity score matching) including 5024 patients (Ross: 1737; mAVR: 3287) met our inclusion criteria. Patients who underwent Ross had a significantly lower risk of mortality in the overall population (HR 0.38, 95%CI 0.30-0.49, P<0.001; median follow-up of 7.2 years) and in the propensity score matched cohorts (HR 0.55, 95%CI 0.42-0.73, P<0.001; median follow-up of 10.2 years); however, the incidence function for the cumulative risk of reoperation was higher for the Ross procedure (HR 1.91, 95%CI 1.36-2.70, P<0.001; median follow-up of 9.3 years). Data from observational studies suggest that the Ross procedure is associated with lower all-cause mortality compared with mAVR; however, there is a higher risk of reoperation. Besides serving as basis to inform patients about benefits and risks involved in this choice, these results call for further randomized clinical trials to determine whether the Ross procedure can achieve its potential benefits in young patients in need of AVR.
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http://dx.doi.org/10.1016/j.tcm.2022.06.005DOI Listing
June 2022

Progression of aortic stenosis after an acute myocardial infarction.

Open Heart 2022 Jun;9(1)

Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada

Background: Myocardial infarction (MI) has been shown to induce fibrotic remodelling of the mitral and tricuspid valves. It is unknown whether MI also induces pathological remodelling of the aortic valve and alters aortic stenosis (AS) progression. We thus compared AS progression after an acute MI and in patients with/without history of MI, and assessed post-MI pathobiological changes within the aortic valve leaflets in a sheep model.

Methods: Serial echocardiograms in human patients with AS were retrospectively analysed and compared between 3 groups: (1) acute MI at baseline (n=68), (2) prior history of MI (n=45) and (3) controls without MI (n=101). Annualised progression rates of AS severity were compared between these 3 groups. In addition, aortic valves were harvested from 15 sheep: (1) induced inferior MI (n=10) and (2) controls without MI (n=5), for biological and histological analyses.

Results: In humans, the acute MI, previous MI and control groups had comparable baseline AS severity. Indexed aortic valve area (AVA) declined faster in the acute MI group compared with controls (-0.07±0.06 vs -0.04±0.04 cm/m/year; p=0.004). After adjustment, acute MI status was significantly associated with faster AVA progression (mean difference: -0.013 (95% CI -0.023 to -0.003) cm/m/year, p=0.008). In the post-MI experimental animal model, aortic valve thickness and qualitative/quantitative expression of collagen were significantly increased compared with controls.

Conclusions: The results of this study suggest that AS progression is accelerated following acute MI, which could be caused by increased collagen production and thickening of the aortic valve after the ischaemic event.
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http://dx.doi.org/10.1136/openhrt-2022-002046DOI Listing
June 2022

Temporal trends of aortic stenosis and comorbid chronic kidney disease in the province of Quebec, Canada.

Open Heart 2022 Jun;9(1)

Division of Nephrology, Endocrinology and Nephrology Axis, CHU de Quebec Research Center, Quebec, Quebec, Canada

Objective: To investigate temporal trends of chronic kidney disease (CKD) among patients with incident aortic stenosis (AS) and to compare these trends with that of a matched control population.

Methods: Using the Quebec Integrated Chronic Disease Surveillance System, we performed a population-based nested case-control study including 108 780 patients newly hospitalised with AS and 543 900 age-matched, sex-matched and fiscal year-matched patients without AS from 2000 to 2016 in Quebec (Canada). Three subgroups were considered. Dialysis subgroup had at least two outpatient billing codes of dialysis. The predialysis subgroup had at least one hospital or two billing diagnostic codes of CKD. The remaining individuals were included in the non-CKD subgroup. We estimated overall and sex-specific standardised annual proportions of CKD subgroups through direct standardisation using the 2016-2017 age structure of the incident AS cohort. The trends overtime were estimated through fitting robust Poisson regression models. Age-specific distribution of AS and control population were assessed for each subgroup.

Results: From 2000 to 2016, age-standardised proportions of patients with AS with dialysis and predialysis increased by 41% (99% CI 12.0% to 78.1%) and by 45% (99% CI 39.1% to 51.6%), respectively. Inversely, age-standardised proportions of dialysis and pre-dialysis among non-AS patients decreased by 63% (99% CI 55.8% to 68.7%) and by 32% (99% CI 29.9% to 34.6%), respectively, during the same study period. In patients with and without AS, age-standardised annual proportions of males in predialysis were significantly higher than females in most of the study period. Patients with AS on dialysis and predialysis were younger than their respective controls (dialysis: 29.6% vs 45.1% had ≥80 years, predialysis: 60.8% vs 72.7% had ≥80 years).

Conclusions: Over time, the proportion of patients with CKD increased significantly and remained consistently higher in incident AS individuals compared with controls. Our results highlight the need to investigate whether interventions targeting CKD risk factors may influence AS incidence in the future.
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http://dx.doi.org/10.1136/openhrt-2021-001923DOI Listing
June 2022

Comprehensive myocardial characterization using cardiac magnetic resonance associates with outcomes in low gradient severe aortic stenosis.

Eur Heart J Cardiovasc Imaging 2022 May 25. Epub 2022 May 25.

Cardiovascular Imaging Research Center and Core Lab, Minneapolis Heart Institute Foundation, 920 E 28th Street, Suite 100, 55407 Minneapolis, MN, USA.

Aims: This study sought to compare cardiac magnetic resonance (CMR) characteristics according to different flow/gradient patterns of aortic stenosis (AS) and to evaluate their prognostic value in patients with low-gradient AS.

Methods And Results: This international prospective multicentric study included 147 patients with low-gradient moderate to severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). All patients were classified as followings: classical low-flow low-gradient (LFLG) [mean gradient (MG) < 40 mmHg and left ventricular ejection fraction (LVEF) < 50%]; paradoxical LFLG [MG < 40 mmHg, LVEF ≥ 50%, and stroke volume index (SVi) < 35 ml/m2]; and normal-flow low-gradient (MG < 40 mmHg, LVEF ≥ 50%, and SVi ≥ 35 ml/m2). Patients with classical LFLG (n = 90) had more LV adverse remodelling including higher ECV, and higher LGE and volume, and worst LVGLS. Over a median follow-up of 2 years, 43 deaths and 48 composite outcomes of death or heart failure hospitalizations occurred. Risks of adverse events increased per tertile of LVGLS: hazard ratio (HR) = 1.50 [95% CI, 1.02-2.20]; P = 0.04 for mortality; HR = 1.45 [1.01-2.09]; P < 0.05 for composite outcome; per tertile of ECV, HR = 1.63 [1.07-2.49]; P = 0.02 for mortality; HR = 1.54 [1.02-2.33]; P = 0.04 for composite outcome. LGE presence also associated with higher mortality, HR = 2.27 [1.01-5.11]; P < 0.05 and composite outcome, HR = 3.00 [1.16-7.73]; P = 0.02. The risk of mortality and the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV, and LGE) with multivariate adjustment.

Conclusions: In this international prospective multicentric study of low-gradient AS, comprehensive CMR assessment provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics.
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http://dx.doi.org/10.1093/ehjci/jeac089DOI Listing
May 2022

Sex-Related Factors in Valvular Heart Disease: JACC Focus Seminar 5/7.

J Am Coll Cardiol 2022 04;79(15):1506-1518

Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.

Numerous sex-based differences are observed across the spectrum of valvular heart disease, starting with pathophysiology and progression of disease, moving on to compensation and comorbidities (both cardiovascular such as coronary artery disease and noncardiovascular such as frailty), assessment of severity and hemodynamics including timing of intervention, and procedural risks/benefits and outcomes. The aortic valve is perhaps best understood with sex differences in both pathologic changes and response to volume and pressure overload, yet large gaps in our understanding still exist. Studies of other valve diseases have focused on differences in prevalence, presentation, and outcomes for surgical or transcatheter therapies. Defining sex-specific responses to valvular heart disease may improve disease recognition, define treatment strategies, and improve outcomes.
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http://dx.doi.org/10.1016/j.jacc.2021.08.081DOI Listing
April 2022

The Canadian Women's Heart Health Alliance Atlas on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 5: Sex- and Gender-Unique Manifestations of Cardiovascular Disease.

CJC Open 2022 Mar 23;4(3):243-262. Epub 2021 Nov 23.

Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada.

This Atlas chapter summarizes sex- and some gender-associated, and unique aspects and manifestations of cardiovascular disease (CVD) in women. CVD is the primary cause of premature death in women in Canada and numerous sex-specific differences related to symptoms and pathophysiology exist. A review of the literature was done to identify sex-specific differences in symptoms, pathophysiology, and unique manifestations of CVD in women. Although women with ischemic heart disease might present with chest pain, the description of symptoms, delay between symptom onset and seeking medical attention, and prodromal symptoms are often different in women, compared with men. Nonatherosclerotic causes of angina and myocardial infarction, such as spontaneous coronary artery dissection are predominantly identified in women. Obstructive and nonobstructive coronary artery disease, aortic aneurysmal disease, and peripheral artery disease have worse outcomes in women compared with men. Sex differences exist in valvular heart disease and cardiomyopathies. Heart failure with preserved ejection fraction is more often diagnosed in women, who experience better survival after a heart failure diagnosis. Stroke might occur across the lifespan in women, who are at higher risk of stroke-related disability and age-specific mortality. Sex- and gender-unique differences exist in symptoms and pathophysiology of CVD in women. These differences must be considered when evaluating CVD manifestations, because they affect management and prognosis of cardiovascular conditions in women.
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http://dx.doi.org/10.1016/j.cjco.2021.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978072PMC
March 2022

Evolution of the burden of aortic stenosis by sex in the province of Quebec between 2006 and 2018.

Heart 2022 Mar 21. Epub 2022 Mar 21.

Institut Universitaire de Cardiologie et de Pneumologie de Québec/Quebec Heart and Lung Institute - Université Laval, Quebec, Quebec, Canada

Objectives: To evaluate the evolution of the burden of aortic stenosis (AS) by sex in the province of Quebec from 2006-2007 to 2018-2019 and compare the percentage of mortality between people who underwent aortic valve intervention and those who did not.

Methods: Persons aged ≥20 years were identified from the Quebec Integrated Chronic Disease Surveillance System using International Classification of Diseases and intervention codes in the hospital files.

Results: In 2018, the crude prevalence and incidence of AS were 0.89% (99% CI 0.89 to 0.90) (n=59 025) and 1.39 per 1000 (1.35 to 1.43) (n=9105), respectively. Age-standardised prevalence and incidence of AS diagnosis increased between 2006 and 2018 from 0.67% (0.66 to 0.68) to 0.75% (0.74 to 0.76) and from 0.91 per 1000 (0.88 to 0.95) to 1.20 per 1000 (1.17 to 1.23), respectively. Among incident AS, the age-standardised percentage of valve interventions increased from 11.7% (10.9 to 12.6) to 14.5% (13.9 to 15.3). This increase was only observed in men. The 30-day mortality was stable among patients with incident AS treated conservatively, from 6.9% (6.5 to 7.4) to 7.3% (6.9 to 7.6), and decreased from 7.6% (6.1 to 9.3) to 3.8% (3.1 to 4.7) among operated patients with incident AS. This decrease was only observed in women. However, from 2010, the age-adjusted mortality among prevalent AS tended to be higher in women.

Conclusions: In the province of Quebec, age-standardised prevalence and incidence of AS diagnosis increased between 2006 and 2018. Among incident AS, there was an increase in valve intervention in men and a decrease in 30-day mortality in women who underwent valve intervention. Overall and age-standardised mortality remained higher in women.
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http://dx.doi.org/10.1136/heartjnl-2021-319848DOI Listing
March 2022

Stress exercise haemodynamic performance and opening reserve of a stented bovine pericardial aortic valve bioprosthesis.

J Card Surg 2022 Mar 12;37(3):618-627. Epub 2022 Jan 12.

Department of Cardiac Surgery, Heart and Lung University Institute, Quebec City, Quebec, Canada.

Objectives: Despite unusual high rates of patient-prosthesis mismatch (PPM), excellent midterm clinical outcomes have been reported after surgical aortic valve replacement (SAVR) with the Avalus™ bioprosthetic valve (Medtronic). To elucidate this "PPM conundrum," the Avalus valve haemodynamics were assessed during exercise testing.

Methods: Of the 148 patients who had undergone SAVR with the Avalus valve at our institution, 30 were randomly selected among those in whom stress test was deemed feasible and underwent a resting transthoracic echocardiography immediately followed by exercise echocardiography. Severe PPM was defined as indexed effective orifice area (iEOA) 0.65 cm /m and moderate PPM as iEOA 0.65 and 0.85 cm /m . Measured PPM was determined with the use of the measured iEOA at rest or stress, while the estimated PPM was based on the estimated iEOA, derived from the mean EOA reported for each valve size in the manufacturer chart.

Results: Measured EOA significantly increased from rest to peak exercise in all PPM groups (p < .05) and the rates of moderate and severe measured PPM decreased from 40% and 20% to 27% and 0%, respectively. The patients with low-flow state (flow < 250 ml/s) had significantly lower measured rest EOA (p = .03). On the basis of the estimated iEOA, there was no severe PPM and 19 patients had moderate PPM (63.3%), with a significantly lower opening reserve than the patients without estimated PPM (p = .04). The estimated iEOA was more reliably correlated to the measured iEOA at maximal stress than the measured iEOA at rest, especially in patients with a low-flow state.

Conclusions: This study supports the concept of an opening reserve of the Avalus valve to explain the PPM conundrum and promotes the use of exercise Doppler-echocardiography to complete the assessment of mismatch, especially in patients with a low-flow state. Published estimated EOA seems reliable to predict the haemodynamic performance of the Avalus valve, whether the flow conditions at rest.
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http://dx.doi.org/10.1111/jocs.16220DOI Listing
March 2022

Clinical Value of Stress Transaortic Flow Rate During Dobutamine Echocardiography in Reduced Left Ventricular Ejection Fraction, Low-Gradient Aortic Stenosis: A Multicenter Study.

Circ Cardiovasc Imaging 2021 11 8;14(11):e012809. Epub 2021 Nov 8.

Department of Echocardiography, Royal Brompton Hospital, London, United Kingdom (A.V., R.S.).

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 cm 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]; =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 <1cm 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 cm at stress FR ≥210 mL/s, only the latter was independently associated with mortality (hazard ratio, 1.72 [95% CI, 1.05-2.82]; =0.03). Furthermore aortic valve area <1cm at stress FR ≥210 mL/s was the only severe aortic stenosis criterion that was associated with improved outcome following aortic valve intervention (<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.
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http://dx.doi.org/10.1161/CIRCIMAGING.121.012809DOI Listing
November 2021

Accuracy of stroke volume measurement with phase-contrast cardiovascular magnetic resonance in patients with aortic stenosis.

J Cardiovasc Magn Reson 2021 11 4;23(1):124. Epub 2021 Nov 4.

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, 2725 Chemin Sainte-Foy, Québec, QC, G1V-4G5, Canada.

Background: Phase contrast (PC) cardiovascular magnetic resonance (CMR) in the ascending aorta (AAo) is widely used to calculate left ventricular (LV) stroke volume (SV). The accuracy of PC CMR may be altered by turbulent flow. Measurement of SV at another site is suggested in the presence of aortic stenosis, but very few data validates the accuracy or inaccuracy of PC in that setting. Our objective is to compare flow measurements obtained in the AAo and LV outflow tract (LVOT) in patients with aortic stenosis.

Methods: Retrospective analysis of patients with aortic stenosis who had CMR and echocardiography. Patients with mitral regurgitation were excluded. PC in the AAo and LVOT were acquired to derive SV. LV SV from end-systolic and end-diastolic tracings was used as the reference measure. A difference ≥ 10% between the volumetric method and PC derived SVs was considered discordant. Metrics of turbulence and jet eccentricity were assessed to explore the predictors of discordant measurements.

Results: We included 88 patients, 41% with bicuspid aortic valve. LVOT SV was concordant with the volumetric method in 79 (90%) patients vs 52 (59%) patients for AAo SV (p = 0.015). In multivariate analysis, aortic stenosis flow jet angle was a strong predictor of discordant measurement in the AAo (p = 0.003). Mathematical correction for the jet angle improved the concordance from 59 to 91%. Concordance was comparable in patients with bicuspid and trileaflet valves (57% and 62% concordance respectively; p = 0.11). Accuracy of SV measured in the LVOT was not influenced by jet eccentricity. For aortic regurgitation quantification, PC in the AAo had better correlation to volumetric assessments than LVOT PC.

Conclusion: LVOT PC SV in patients with aortic stenosis and eccentric jet might be more accurate compared to the AAo SV. Mathematical correction for the jet angle in the AAo might be another alternative to improve accuracy.
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http://dx.doi.org/10.1186/s12968-021-00814-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567621PMC
November 2021

Echocardiographic Variables Associated with Transvalvular Gradient After a Transcatheter Edge-To-Edge Mitral Valve Repair.

J Am Soc Echocardiogr 2022 01 12;35(1):86-95. Epub 2021 Oct 12.

Quebec Heart and Lung Institute, Laval University, Quebec, Quebec, Canada. Electronic address:

Background: Transcatheter edge-to-edge mitral valve repair may lead to a reduction in mitral valve area (MVA) and elevated mean transmitral gradient (TMG). The objectives of this study were to assess the value of baseline MVA by different imaging methods and to explore the associations between MVA indexed to body surface area or left ventricular forward stroke volume and postprocedural TMG.

Methods: Preprocedural echocardiographic images from 76 consecutive patients were retrospectively reviewed. MVA planimetry from two-dimensional (2D) transthoracic echocardiography (MVA), 2D transesophageal echocardiography in the transgastric view (MVA), and three-dimensional (3D) transesophageal echocardiography (MVA) were measured. Postprocedural TMGs were assessed at 1 to 3 months and all-cause mortality at 1 year.

Results: Postprocedural mean TMG > 5 mm Hg was associated with a 3.42-fold (95% confidence interval [CI], 1.08-10.87; P = .04) increased risk for 1-year all-cause mortality. Patients with postprocedural TMG > 5 mm Hg (25% [19 of 76]) had significantly smaller preprocedural MVA (3.9 ± 0.8 vs 5.2 ± 1.3 cm, P < .01) and MVA (4.9 ± 1.1 vs 5.8 ± 1.5 cm, P = .01) compared with patients without elevated TMG. No significant difference was found for MVA (P = .20). The best threshold values for MVA and MVA to be associated with postprocedural TMG > 5 mm Hg were, respectively, 3.9 cm (area under the curve [AUC] = 0.80; 95% CI, 0.66-0.94; sensitivity 62%, specificity 87%) and 4.6 cm (AUC = 0.68; 95% CI, 0.54-0.82; sensitivity 53%, specificity 80%). MVA indexed to body surface area and to stroke volume showed overall the best associations with postprocedural mean TMG > 5 mm Hg, with optimal thresholds, respectively, of 2.5 cm/m (AUC = 0.88; 95% CI, 0.77-0.98; sensitivity 92%, specificity 74%) and 95 cm/L (AUC = 0.87; 95% CI, 0.77-0.97; sensitivity 85%, specificity 82%).

Conclusions: Elevated TMG following transcatheter edge-to-edge mitral valve repair was associated with increased mortality. The present results indicate that MVA, MVA indexed to body surface area, and MVA indexed to stroke volume may be considered potential predictors of postprocedural TMG > 5 mm Hg and could help optimize patient selection, while the use of 2D methods for valve area were poorly associated with TMG.
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http://dx.doi.org/10.1016/j.echo.2021.09.015DOI Listing
January 2022

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

J Am Coll Cardiol 2021 08;78(6):545-558

Department of Radiology and Nuclear Medicine, German Heart Center Munich, Munich, Germany.

Background: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined.

Objectives: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality.

Methods: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome.

Results: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m) and small (LVEDVi ≤55 mL/m) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort.

Conclusions: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.
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http://dx.doi.org/10.1016/j.jacc.2021.05.047DOI Listing
August 2021

Aortic Stenosis and Cardiac Amyloidosis: Watch Out for Traps!

JACC Case Rep 2020 Nov 18;2(14):2210-2212. Epub 2020 Nov 18.

Québec Heart and Lung Institute, Laval University, Québec, Canada.

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http://dx.doi.org/10.1016/j.jaccas.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299971PMC
November 2020

Sex-Specific Associations of Genetically Predicted Circulating Lp(a) (Lipoprotein(a)) and Hepatic Gene Expression Levels With Cardiovascular Outcomes: Mendelian Randomization and Observational Analyses.

Circ Genom Precis Med 2021 08 19;14(4):e003271. Epub 2021 Jul 19.

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (J.G., H.M., N.P., R.B., C.C., Y.B., P.P., P.M., M.-A.C., S.T., B.J.A.).

Background: Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results.

Methods: To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the locus) and hepatic expression (using 80 single nucleotide polymorphisms at the locus associated with mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively).

Results: Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted expression levels were associated with prevalent CAD and CAVS in men and women but not with IS.

Conclusions: Genetically predicted blood Lp(a) and hepatic gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials.
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http://dx.doi.org/10.1161/CIRCGEN.120.003271DOI Listing
August 2021

Prosthesis-Patient Mismatch After Aortic Valve Replacement in the PARTNER 2 Trial and Registry.

JACC Cardiovasc Interv 2021 07;14(13):1466-1477

Columbia University Medical Center/NewYork-Presbyterian Hospital, New York, New York, USA; Cardiovascular Research Foundation, New York, New York, USA.

Objectives: This study aimed to compare incidence and impact of measured prosthesis-patient mismatch (PPM) versus predicted PPM (PPM) 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 cm/m (≤0.70 if obese: body mass index ≥30 kg/m) and severe if EOAi ≤0.65 cm/m (≤0.55 if obese). PPM was determined by the core lab-measured EOAi on 30-day echocardiogram. PPM was determined by 2 methods: 1) using normal EOA reference values previously reported for each valve model and size (PPM; n = 929 SAVR, 1,069 TAVR) indexed to BSA; and 2) using normal reference EOA predicted from aortic annulus size measured by computed tomography (PPM; 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 PPM was much lower than PPM in both SAVR (PPM: 28.4% and 1.2% vs. PPM: 31.0% and 23.6%) and TAVR (PPM: 21.0% and 0.1% and PPM: 17.0% and 0% vs. PPM: 27.9% and 5.7%). The incidence of severe PPM and severe PPM was lower in TAVR versus SAVR (P < 0.001). The presence of PPM by any method was associated with higher transprosthetic gradient. Severe PPM 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 PPM is rare (<1.5%), but is associated with increased all-cause death and rehospitalization after SAVR, whereas it is absent following TAVR.
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http://dx.doi.org/10.1016/j.jcin.2021.03.069DOI Listing
July 2021

Doppler Velocity Index Outcomes Following Surgical or Transcatheter Aortic Valve Replacement in the PARTNER Trials.

JACC Cardiovasc Interv 2021 07 30;14(14):1594-1606. Epub 2021 Jun 30.

Department of Medicine, Laval University, Quebec City, Quebec, Canada.

Objectives: The aim of this study was to assess the association between Doppler velocity index (DVI) and 2-year outcomes for balloon-expandable SAPIEN 3 transcatheter aortic valve replacement (TAVR) and for surgical aortic valve replacement (SAVR).

Background: DVI >0.35 is normal for a prosthetic valve, but recent studies suggest that DVI <0.50 is associated with poor outcomes following TAVR.

Methods: Patients with severe aortic stenosis enrolled in the PARTNER (Placement of Aortic Transcatheter Valve) 2 (intermediate surgical risk) or PARTNER 3 (low surgical risk) trial undergoing TAVR (n = 1,450) or SAVR (n = 1,303) were included. Patients were divided into 3 DVI groups on the basis of core laboratory-assessed discharge or 30-day echocardiograms: DVI (≤0.35), DVI (>0.35 to ≤0.50), and DVI (>0.50). Two-year outcomes were assessed.

Results: Following TAVR, there were no differences among the 3 DVI groups in composite outcomes of death, stroke, or rehospitalization or in any individual components of 2-year outcomes (P > 0.70 for all). Following SAVR, there was no difference among DVI groups in the composite outcome (P = 0.27), but there was a significant association with rehospitalization (P = 0.02). Restricted cubic-spline analysis for combined outcomes showed an increased risk with post-SAVR DVI ≤0.35 but no relationship post-TAVR. DVI ≤0.35 was associated with increased 2-year composite outcome for SAVR (HR: 1.81; 95% CI: 1.29-2.54; P < 0.001), with no adverse outcomes for TAVR (P = 0.86).

Conclusions: In intermediate- and low-risk cohorts of the PARTNER trials, DVI ≤0.35 predicted worse 2-year outcomes following SAVR, driven primarily by rehospitalization, with no adverse outcomes associated with DVI following TAVR with the balloon-expandable SAPIEN 3 valve.
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http://dx.doi.org/10.1016/j.jcin.2021.04.007DOI Listing
July 2021

Validation of aortic valve calcium quantification thresholds measured by computed tomography in Asian patients with calcific aortic stenosis.

Eur Heart J Cardiovasc Imaging 2022 04;23(5):717-726

Institut Universitaire de Cardiologie et de Pneumologie de Québec/Quebec Heart & Lung Institute, Laval University, 2725 Chemin Sainte-Foy, Quebec City, Quebec G1V-4G5, Canada.

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.
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http://dx.doi.org/10.1093/ehjci/jeab116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016361PMC
April 2022

Moderate Aortic Stenosis in Patients With Heart Failure and Reduced Ejection Fraction.

J Am Coll Cardiol 2021 06;77(22):2796-2803

Institut universitaire de cardiologie et de pneumologie, Université Laval, Québec, Québec, Canada. Electronic address:

Background: The study investigators previously reported that moderate aortic stenosis (AS) is associated with a poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). However, the respective contribution of moderate AS versus HFrEF to the outcomes of these patients is unknown.

Objectives: This study sought to determine the impact of moderate AS on outcomes in patients with HFrEF.

Methods: The study included 262 patients with moderate AS (aortic valve area >1.0 and <1.5 cm; and peak aortic jet velocity >2 and <4 m/s, at rest or after dobutamine stress echocardiography) and HFrEF (LVEF <50%). These patients were matched 1:1 for sex, age, estimated glomerular filtration rate, New York Heart Association functional class III to IV, presence of diabetes, LVEF, and body mass index with patients with HFrEF but no AS (i.e., peak aortic jet velocity <2 m/s). The endpoints were all-cause mortality and the composite of death and HF hospitalization.

Results: A total of 262 patients with HFrEF and moderate AS were matched with 262 patients with HFrEF and no AS. Mean follow-up was 2.9 ± 2.2 years. In the moderate AS group, mean aortic valve area was 1.2 ± 0.2 cm, and mean gradient was 14.5 ± 4.7 mm Hg. Moderate AS was associated with an increased risk of mortality (hazard ratio [HR]: 2.98; 95% confidence interval [CI]: 2.08 to 4.31; p < 0.0001) and of the composite of HF hospitalization and mortality (HR: 2.34; 95% CI: 1. 72 to 3.21; p < 0.0001). In the moderate AS group, aortic valve replacement (AVR) performed in 44 patients at a median follow-up time of 10.9 ± 16 months during follow-up was associated with improved survival (HR: 0.59; 95% CI: 0.35 to 0.98; p = 0.04). Notably, surgical AVR was not significantly associated with improved survival (p = 0.92), whereas transcatheter AVR was (HR: 0.43; 95% CI: 0.18 to 1.00; p = 0.05).

Conclusions: In this series of patients with HFrEF, moderate AS was associated with a marked incremental risk of mortality. AVR, and especially transcatheter AVR during follow-up, was associated with improved survival in patients with HFrEF and moderate AS. These findings provide support to the realization of a randomized trial to assess the effect of early transcatheter AVR in patients with HFrEF and moderate AS.
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http://dx.doi.org/10.1016/j.jacc.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091313PMC
June 2021

Impact of sex on the management and outcome of aortic stenosis patients.

Eur Heart J 2021 07;42(27):2683-2691

Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart & Lung Institute), 2725 Chemin Sainte-Foy, Quebec, QC G1V-4G5, Canada.

Objective: The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity.

Introduction: Sex differences in the management and outcome of AS are poorly understood.

Methods: Doppler echocardiography data of patients with at least mild-to-moderate AS [aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg] were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded.

Results: Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 [1.14-3.22]; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 [0.82-0.96]; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 [0.63-1.68]; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 [0.71-2.21]; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 [1.19-3.95]; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 [0.73-0.95]; P = 0.009).

Conclusion: In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.
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http://dx.doi.org/10.1093/eurheartj/ehab242DOI Listing
July 2021

A Machine-Learning Framework to Identify Distinct Phenotypes of Aortic Stenosis Severity.

JACC Cardiovasc Imaging 2021 09 19;14(9):1707-1720. Epub 2021 May 19.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

Objectives: The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity.

Background: In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty.

Methods: Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier's prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts.

Results: In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning-based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS.

Conclusions: Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.
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http://dx.doi.org/10.1016/j.jcmg.2021.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434951PMC
September 2021

Flexibility of microstructural adaptations in airway smooth muscle.

J Appl Physiol (1985) 2021 05 15;130(5):1555-1561. Epub 2021 Apr 15.

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec, Canada.

The airway smooth muscle undergoes an elastic transition during a sustained contraction, characterized by a gradual decrease in hysteresivity caused by a relatively greater rate of increase in elastance than resistance. We recently demonstrated that these mechanical changes are more likely to persist after a large strain when they are acquired in dynamic versus static conditions; as if the microstructural adaptations liable for the elastic transition are more flexible when they evolve in dynamic conditions. The extent of this flexibility is undefined. Herein, contracted ovine tracheal smooth muscle strips were kept in dynamic conditions simulating tidal breathing (sinusoidal length oscillations at 5% amplitude) and then subjected to simulated deep inspirations (DI). Each DI was straining the muscle by either 10%, 20%, or 30% and was imposed at either 2, 5, 10, or 30 min after the preceding DI. The goal was to assess whether and the extent by which the time-dependent decrease in hysteresivity is preserved following the DI. The results show that the time-dependent decrease in hysteresivity seen pre-DI was preserved after a strain of 10%, but not after a strain of 20% or 30%. This suggests that the microstructural adaptations liable for the elastic transition withstood a strain at least twofold greater than the oscillating strain that pertained during their evolution (10% vs. 5%). We propose that a muscle adapting in dynamic conditions forges microstructures exhibiting a substantial degree of flexibility. This study confirms that airway smooth muscle undergoes an elastic transition during a sustained contraction even when it operates in dynamic conditions simulating breathing at tidal volume. It also demonstrates that the microstructural adaptations liable for this elastic transition withstand a strain that is at least twice as large as the oscillating strain that pertains during their evolution. This degree of flexibility might be an asset with major significant impact for a tissue such as the airway smooth muscle that displays an everchanging shape due to breathing.
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http://dx.doi.org/10.1152/japplphysiol.00894.2020DOI Listing
May 2021

Early benefits of bariatric surgery on subclinical cardiac function: Contribution of visceral fat mobilization.

Metabolism 2021 06 8;119:154773. Epub 2021 Apr 8.

Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, Québec, Canada; Faculty of Pharmacy, Laval University, Québec, Canada. Electronic address:

Aims: We explored the early effects of bariatric surgery on subclinical myocardial function in individuals with severe obesity and preserved left ventricular (LV) ejection fraction.

Methods: Thirty-eight patients with severe obesity [body mass index (BMI) ≥35 kg/m] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) (Surgery group), 19 patients with severe obesity managed with usual care (Medical group), and 18 age and sex-matched non-obese controls (non-obese group) were included. Left ventricular global longitudinal strain (LV GLS) was evaluated with echocardiography speckle tracking imaging. Abnormal myocardial function was defined as LV GLS <18%.

Results: Age of the participants was 42 ± 11 years with a BMI of 48 ± 8 kg/m (mean ± standard deviation); 82% were female. The percentage of total weight loss at 6 months after bariatric surgery was 26.3 ± 5.2%. Proportions of hypertension (61 vs. 30%, P = 0.0005), dyslipidemia (42 vs. 5%, P = 0.0001) and type 2 diabetes (40 vs. 13%, P = 0.002) were reduced postoperatively. Before surgery, patients with obesity displayed abnormal subclinical myocardial function vs. non-obese controls (LV GLS, 16.3 ± 2.5 vs. 19.6 ± 1.7%, P < 0.001). Six months after bariatric surgery, the subclinical myocardial function was comparable to non-obese (LV GLS, 18.2 ± 1.9 vs. 19.6 ± 1.7%, surgery vs. non-obese, P = NS). On the contrary, half of individuals with obesity managed medically worsened their myocardial function during the follow-up (P = 0.002). Improvement in subclinical myocardial function following bariatric surgery was associated with changes in abdominal visceral fat (r = 0.43, P < 0.05) and inflammatory markers (r = 0.45, P < 0.01), whereas no significant association was found with weight loss or change in insulin sensitivity (HOMA-IR) (P > 0.05). In a multivariate model, losing visceral fat mass was independently associated with improved subclinical myocardial function.

Conclusions: Bariatric surgery was associated with significant improvement in the metabolic profile and in subclinical myocardial function. Early improvement in subclinical myocardial function following bariatric surgery was related to a greater mobilization of visceral fat depot, linked to global fat dysfunction and cardiometabolic morbidity.
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http://dx.doi.org/10.1016/j.metabol.2021.154773DOI Listing
June 2021

Low-Flow Aortic Stenosis: Flow Rate Does Not Replace But Could Refine Stroke Volume Index.

JACC Cardiovasc Imaging 2021 05 17;14(5):928-930. Epub 2021 Mar 17.

Institut Universitaire de cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada.

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http://dx.doi.org/10.1016/j.jcmg.2021.01.026DOI Listing
May 2021
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