Search

Chloé Rauzier,1,2 Dominic J Chartrand,1,3 Natalie Alméras,1,3 Isabelle Lemieux,1 Eric Larose,1,4 Patrick Mathieu,1,5 Philippe Pibarot,1,4 Benoît Lamarche,6,7 Caroline Rhéaume,1,8,9 Paul Poirier,1,2 Jean-Pierre Després,1,3,9 Frédéric Picard1,2 1Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) – Université Laval, Québec, QC, Canada; 2Faculté de pharmacie, Université Laval, Québec, QC, Canada; 3Département de kinésiologie, Faculté de médecine, Université Laval, Québec, QC, Canada; 4Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada; 5Département de chirurgie, Faculté de médecine, Université Laval, Québec, QC, Canada; 6Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada; 7École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation, Université Laval, Québec, QC, Canada; 8Département de médecine familiale et de médecine d’urgence, Faculté de médecine, Université Laval, Québec, QC, Canada; 9VITAM – Centre de recherche en santé durable, Québec, QC, CanadaCorrespondence: Frédéric Picard; Jean-Pierre Després, Email Frederic.Picard@criucpq.ulaval.ca; jean-pierre.despres.ciussscn@ssss.gouv.qc.caAbstract: Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat > 5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.Keywords: humans, insulin-like growth factor-binding protein 2, waist circumference, hepatic fat, metabolic dysfunction-associated steatotic liver disease, biomarker, plasma, non-invasive

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Background Bicuspid aortic valve (BAV) is often associated with a concomitant aortopathy. However, few studies have evaluated the effect of the aortic valve (AV) phenotype on the rate of dilation of the aorta. This study aimed to compare the progression rate of aorta dimensions according to AV phenotype (BAV vs tricuspid AV (TAV)), fusion type and sex in patients with aortic stenosis (AS).Methods 310 patients with AS (224 TAV and 86 BAV) recruited in the Metabolic Determinants of the Progression of Aortic Stenosis study (PROGRESSA, NCT01679431) were included in this analysis. Doppler echocardiography was performed annually to assess AS severity and measure ascending aorta (AA) dimensions. Baseline and last follow-up visit measurements were used to assess the annualised change.Results Median AA annualised change was larger in BAV versus TAV (0.33±0.65 mm/year vs 0.21±0.56 mm/year, p=0.04). In the whole cohort, BAV phenotype and higher low-density lipoprotein (LDL) levels were significantly associated with fast progression of AA dilation in univariate analysis (OR 1.80, 95% CI 1.08 to 2.98, p=0.02; 1.37, 95% CI 1.04 to 1.80, p=0.03, respectively). AA dilation rate did not vary according to the BAV subtype (p=0.142). Predictors of AA progression rate were different between valve phenotypes, with higher apolipoprotein B/apolipoprotein A-I ratio, higher baseline peak aortic jet velocity (Vpeak) and smaller baseline AA diameter in the TAV cohort (all p

Background: Little is known about the effect of sex on functional status decline in aortic valve stenosis (AS) patients. Objectives: The purpose of this study was to examine the changes in functional status according to sex in patients with mild-to-moderate AS and its association with the composite of death or aortic valve replacement (AVR). Methods: We included patients with mild-to-moderate AS prospectively recruited in the PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis) study (NCT01679431). Functional status was assessed using the New York Heart Association classification and the Duke Activity Status Index (DASI). Results: A total of 244 patients (mean age 64 ± 14 years, 29% women) were included. The mean follow-up was 4.3 ± 2.4 years. Women with intermediate-to-fast AS progression rate (median change in peak aortic jet velocity ≥0.11 m/s/year) had significantly faster decline in DASI score compared to men with similar progression rate (P

Background: In patients with low-gradient (LG) aortic stenosis (AS), confirming disease severity and indication of intervention often requires dobutamine stress echocardiography (DSE) or aortic valve calcium scoring by computed tomography. We hypothesized that the mean transvalvular pressure gradient to effective orifice area ratio (MG/EOA, in mm Hg/cm2) measured during rest echocardiography identifies true-severe AS (TSAS) and is associated with clinical outcomes in patients with low-flow, LG-AS. Objectives: The purpose of this study was to evaluate the diagnostic and prognostic value of MG/EOA ratio. Methods: The diagnostic accuracy of MG/EOA ratio to identify TSAS was retrospectively assessed in: 1) an in vitro data set obtained in a circulatory model including 93 experimental conditions; and 2) an in vivo data set of 188 patients from the TOPAS (True or Pseudo-Severe Aortic Stenosis) study (NCT01835028). Receiver operating characteristic curves were used to assess the diagnostic accuracy of MG/EOA ratio for identifying TSAS, and Cox proportional hazards regression analyses were performed to assess its association with clinical outcomes. Results: The optimal cutoff of MG/EOA ratio to identify TSAS in patients with low-flow, LG-AS was ≥25 mm Hg/cm2 (correct classification 85%), as well as in vitro (100%). During a median follow-up of 1.41 ± 0.75 years, 146 (78%) patients met the composite endpoint of aortic valve replacement or all-cause mortality. A MG/EOA ratio ≥25 mm Hg/cm2 was independently associated with an increased risk of the composite endpoint (adjusted HR: 2.36 [95% CI: 1.63-3.42], P

AimsElevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown.Methods and resultsWe investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study (n = 18 226, 406 incident cases) and the UK Biobank (n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study (n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (50 mg/dL) and low CRP levels (50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30-2.67) and 2.08 (1.44-2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels.ConclusionLp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation.

Abstract There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.

Background Thresholds of aortic valve calcification (AVC) to define hemodynamically moderate aortic stenosis (AS) from mild are lacking. We aimed to establish a novel grading classification of AVC as quantified by computed tomography and determine its prognostic value. Methods and Results This study included 915 patients with at least mild AS (mean age 70±12 years, 30% women) from a multicenter prospective registry. All patients underwent Doppler‐echocardiography and noncontrast computed tomography within 3 months. Primary end point was the occurrence of all‐cause death. Receiver operating characteristic curves analyses were used to determine the sensitivity and specificity of sex‐specific thresholds of AVC to identify hemodynamically moderate AS. Optimal thresholds (ie, with best sensitivity/specificity) of AVC to distinguish moderate (aortic valve area 1.0–1.5 cm2 and mean gradient 20–39 mm Hg) from mild AS (aortic valve area >1.5 cm2 and mean gradient

Background Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. Methods and Results We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09–3.64]; ATTRv: SRR, 3.41; 95%CI [1.64–4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25–14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56–1.14]; ATTRv: SRR, 1.27; 95%CI [0.85–1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71–4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42–1.19]; P=0.19). Conclusions Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

Background The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all‐cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction). Methods and Results A systematic review and pooled meta‐analysis of Kaplan–Meier‐derived reconstructed time‐to‐event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15‐year overall survival rate was 23.3% (95% CI, 19.1%–28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%–59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46–2.64]; P

Este consenso de nomenclatura y clasificación para la válvula aórtica bicúspide congénita y su aortopatía está basado en la evidencia y destinado a ser utilizado universalmente por médicos (tanto pediatras como de adultos), médicos ecocardiografistas, especialistas en imágenes avanzadas cardiovasculares, cardiólogos intervencionistas, cirujanos cardiovasculares, patólogos, genetistas e investigadores que abarcan estas áreas de investigación clínica y básica. Siempre y cuando se disponga de nueva investigación clave y de referencia, este consenso internacional puede estar sujeto a cambios de acuerdo con datos basados en la evidencia1.

Background It remains controversial whether prosthesis‐patient mismatch (PPM) impacts long‐term outcomes after surgical aortic valve replacement. We aimed to evaluate the association of PPM with mortality, rehospitalizations, and aortic valve reinterventions. Methods and Results We performed a systematic review with meta‐analysis of reconstructed time‐to‐event data of studies published by March 2023 (according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses). Sixty‐five studies met our eligibility criteria and included 122 989 patients (any PPM: 68 332 patients, 55.6%). At 25 years of follow‐up, the survival rates were 11.8% and 20.6% in patients with and without any PPM, respectively (hazard ratio [HR], 1.16 [95% CI, 1.13–1.18], P

Objective: Novel tissue leaflets (RESILIA tissue) may improve durability of bioprosthetic heart valves. The COMMENCE trial is an ongoing prospective study to evaluate valve replacement using RESILIA tissue. This report describes mid-term outcomes in the mitral cohort of COMMENCE. Methods: Adult patients requiring mitral valve replacement were enrolled in a prospective, single-arm trial at 17 sites in the United States and Canada. An independent clinical events committee adjudicated safety events using definitions from established guidelines, and hemodynamic performance was evaluated by an independent echocardiographic core laboratory. Results: Eighty-two patients (median age 70 years) successfully underwent mitral valve replacement with the study valve. Five-year event-free probabilities for all-cause mortality, structural valve deterioration, and reoperation were 79.9%, 98.7%, and 97.1%, respectively. Hemodynamic valve function measurements were stable through the 5-year follow-up period; valvular leaks were infrequently observed and primarily clinically insignificant/mild. Conclusions: Mitral valve replacement patients implanted with a RESILIA tissue bioprosthesis had a good safety profile and clinically stable hemodynamic performance.

Background Concerns about discordance between echocardiographic and invasive mean gradients after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEVs) versus self-expanding valves (SEVs) exist. Methods and Results In a multicenter study, direct-invasive and echocardiography-derived transvalvular mean gradients obtained before and after TAVR were compared as well as post-TAVR and discharge echocardiographic mean gradients in BEVs versus SEVs in 808 patients. Pre-TAVR, there was good correlation (R=0.614; P

Background: Baseline left ventricular diastolic dysfunction (LVDD) is associated with poor health status in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but health status improvement after TAVR appears similar across all grades of LVDD. Here, we aim to examine the relationship between changes in LVDD severity and health status outcomes following TAVR. Methods: Patients who underwent TAVR and had evaluable LVDD at both baseline and 1 year in the PARTNER (Placement of Aortic Transcatheter Valves) 2 SAPIEN 3 registries and PARTNER 3 trial were analyzed. LVDD grade was evaluated using echocardiography core lab data and an adapted definition of American Society of Echocardiography guidelines. Health status was assessed using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score. The association between ΔLVDD severity and ΔKCCQ-OS was examined using linear regression models adjusted for baseline KCCQ-OS. Results: Of 1100 patients, 724 (65.8%), 283 (25.7%), and 93 (8.5%) had grade 0/1, 2, and 3 LVDD at baseline, respectively. At 1 year, LVDD severity was unchanged in 790 (71.8%) patients, improved in 189 (17.2%), and worsened in 121 (11.0%). Among 376 patients with baseline grade 2 or 3 LVDD, 50.3% had improvement in LVDD. In the overall cohort, KCCQ-OS score improved by 21.9 points at 1 year. There was a statistically significant association between change in LVDD severity (improved, unchanged, and worsened) and ΔKCCQ-OS at 1 year (p = 0.007). Conclusions: Change in LVDD grade was associated with change in health status 1 year following TAVR.

Background We performed a meta‐analysis of reconstructed time‐to‐event data from randomized controlled trials (RCTs) and propensity‐score matched (PSM) studies comparing transcatheter versus surgical aortic valve replacement (TAVR versus SAVR) to evaluate midterm outcomes in patients considered low risk for SAVR. Methods and Results Study‐level meta‐analysis of reconstructed time‐to‐event data from Kaplan–Meier curves of RCTs and PSM studies published by December 31, 2022 was conducted. Eight studies (3 RCTs, 5 PSM studies) met our eligibility criteria and included 5444 patients; 2639 patients underwent TAVR, and 2805 patients underwent SAVR. TAVR showed a higher risk of all‐cause mortality at 8 years of follow‐up (hazard ratio [HR] 1.22, [95% CI, 1.03–1.43], P=0.018). Up to 2 years of follow‐up, TAVR was not inferior to SAVR (HR, 1.08 [95% CI, 0.89–1.31], P=0.448); however, we observed a statistically significant difference after 2 years with higher mortality with TAVR (HR, 1.51 [95% CI, 1.14–2.00]; P=0.004). This difference was driven by PSM studies; our sensitivity analysis showed a statistically significant difference between TAVR and SAVR when we included only PSM studies (HR, 1.41 [95% CI, 1.16–1.72], P=0.001) but no statistically significant difference when we included only RCTs (HR, 0.89 [95% CI, 0.69–1.16], P=0.398). Conclusions In comparison with TAVR, SAVR appeared to be associated with improved survival beyond 2 years in low‐risk patients. However, the survival benefit of SAVR was observed only in PSM studies and not in RCTs. The addition of data from ongoing RCTs as well as longer follow‐up in previous RCTs will help to confirm if there is a difference in mid‐ and long‐term survival between TAVR versus SAVR in the low‐risk population.

Lay summaryObesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms.Aim/hypothesisAlthough excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes.MethodsA sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL).ResultsIndividuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001).ConclusionIn the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

The novel coronavirus disease-2019 (COVID-19) pandemic has created uncertainty in the management of patients with severe aortic stenosis. This population experiences high mortality from delays in treatment of valve disease but is largely overlapping with the population of highest mortality from COVID-19. The authors present strategies for managing patients with severe aortic stenosis in the COVID-19 era. The authors suggest transitions to virtual assessments and consultation, careful pruning and planning of necessary testing, and fewer and shorter hospital admissions. These strategies center on minimizing patient exposure to COVID-19 and expenditure of human and health care resources without significant sacrifice to patient outcomes during this public health emergency. Areas of innovation to improve care during this time include increased use of wearable and remote devices to assess patient performance and vital signs, devices for facile cardiac assessment, and widespread use of clinical protocols for expedient discharge with virtual physical therapy and cardiac rehabilitation options.

Amyloidosis concomitant to aortic stenosis usually occurs with myocardial infiltration by the transthyretin protein. To our knowledge, this is the first report of localized amyloidosis of indeterminate type in a severely calcified and functionally unicuspid aortic valve. Isolated dystrophic valvular amyloidosis is believed to be related to fibrocalcific valve disease. In light of the literature on this topic, the present case raises new hypotheses on pathophysiology and further supports the contributory role of unusual non-tricuspid valve morphology in the development of dystrophic amyloid, likely secondary to altered hemodynamic stress. Résumé: Une amyloïdose associée à une sténose aortique survient généralement avec infiltration du myocarde par la protéine transthyrétine. Le cas que nous décrivons est, à notre connaissance, le premier cas rapporté d’amyloïdose localisée de type indéterminé dans une valve aortique sévèrement calcifiée et fonctionnellement unicuspide. L’amyloïdose valvulaire dystrophique isolée serait liée à l'atteinte fibrocalcique de la valve. À la lumière de la littérature à ce sujet, le cas décrit ici permet de soulever de nouvelles hypothèses physiopathologiques et appuie le lien entre une morphologie valvulaire inhabituelle (non tricuspide) et l’apparition de substances amyloïdes dystrophiques, probablement secondaire à une altération des contraintes hémodynamiques.

Background A total of 40% of patients with severe aortic stenosis (AS) have low‐gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline‐endorsed to aid in such cases. The performance of different CT‐derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography

BackgroundLipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification.MethodsWe recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Québec City, Canada. In a second group of individuals with high (≥75 nmol/L, n = 27) or low (

Background: Bicuspid aortic valve (BAV) is associated with a faster progression of aortic stenosis (AS). Whether the determinants of AS progression are the same or different in patients with BAV vs tricuspid aortic valve (TAV) is unknown. The aim of this study was to identify the factors associated with the progression of AS in patients with BAV vs patients with TAV. Methods: Patients with AS were prospectively recruited in the Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA) study (ClinicalTrials.gov Identifier: NCT01679431). The haemodynamic progression rate of AS was assessed by the annualized progression rate of peak aortic jet velocity (Vpeak). Univariable and multivariable linear regression analyses were used to identify the factors associated with a faster progression of AS in patients with BAV vs patients with TAV. Results: There were 79 patients with BAV and 208 patients with TAV. The baseline severity of AS was similar between the 2 groups of patients as well as the annualized progression rate of AS. In patients with BAV, obesity (β = 0.25, P = 0.04), diabetes (β = 0.26, P = 0.02), and BAV with right-noncoronary cusp fusion (β = 0.29, P = 0.01) were found to be independently associated with a faster progression of AS, whereas in patients with TAV, AS baseline severity (baseline Vpeak, β = 0.14, P = 0.04) and chronic kidney disease (β = 0.16, P = 0.02) were significantly associated with AS progression. Conclusion: Factors associated with progression rate of AS are different in BAV and TAV. The main factors associated with a faster progression of AS appear to be obesity, diabetes, right-noncoronary cusp fusion in patients with BAV vs chronic kidney disease in patients with TAV. Résumé: Contexte: La bicuspidie valvulaire aortique (BVA) est associée à une progression plus rapide de la sténose aortique (SA). On ignore toutefois si les facteurs en cause dans la progression de la SA sont les mêmes chez les patients qui présentent une BVA et chez ceux qui présentent une valve aortique tricuspide. Le but de cette étude était de déterminer les facteurs associés à la progression de la SA chez les patients présentant une BVA par rapport à ceux ayant une valve aortique tricuspide. Méthodologie: Des patients présentant une SA ont été recrutés dans l’étude PROGRESSA (Metabolic Determinants of the Progression of Aortic Stenosis), une étude prospective sur les déterminants métaboliques de la progression de la SA (ClinicalTrials.gov : NCT01679431). Pour calculer le taux de progression hémodynamique de la SA, on a utilisé les mesures annualisées de la vélocité maximale du jet transaortique (Vmax). Des analyses de régression linéaire univariées et multivariées ont permis de mettre en évidence les facteurs associés à une progression plus rapide de la SA en présence d’une BVA par rapport à une valve aortique tricuspide. Résultats: Parmi les patients évalués, 79 présentaient une BVA et 208, une valve aortique tricuspide. La gravité de la SA au départ était comparable entre les deux groupes de patients, tout comme le taux de progression annualisé de la SA. Chez les patients avec BVA, l’obésité (β = 0,25, P = 0,04), le diabète (β = 0,26, P = 0,02) et la BVA avec fusion des feuillets coronaire droit et non coronaire (β = 0,29, P = 0,01) ont été associés de manière indépendante à une progression plus rapide de la SA, tandis que chez les patients ayant une valve tricuspide, la gravité de la SA au départ (Vmax initiale, β = 0,14, P = 0,04) et la présence d’une néphropathie chronique (β = 0,16, P = 0,02) ont été significativement associées à une progression de la SA. Conclusion: Les facteurs associés au taux de progression de la SA sont différents selon qu’il y a ou non présence d’une BVA. Les principaux facteurs associés à une progression plus rapide de la SA semblent être l’obésité, le diabète et la fusion des feuillets coronaire droit et non coronaire pour la BVA, tandis que la néphropathie chronique serait le facteur aggravant chez les patients présentant une valve aortique tricuspide.

Background: Paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) is frequent and the impact of mild PVL on outcomes remains uncertain. Our study aimed to evaluate the impact of PVL on TAVI outcomes. Methods: To analyze late outcomes of patients after TAVI according to the presence and severity of PVL, PubMed/MEDLINE, EMBASE and Google Scholar were searched for studies that reported rates of all-cause mortality/survival and/or rehospitalization and/or cardiovascular mortality accompanied by at least one Kaplan-Meier curve for any of these outcomes. We adopted a 2-stage approach to reconstruct individual patient data based on the published Kaplan-Meier graphs. Results: Thirty-eight studies with Kaplan-Meier curves met our eligibility criteria including over 25,000 patients. Patients with any degree of PVL after TAVI had a significantly higher risk of overall mortality (hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.43-1.61; p < 0.001), rehospitalization (HR, 1.81; 95% CI, 1.54-2.12; p < 0.001), and cardiovascular mortality (HR, 1.52; 95% CI, 1.33-1.75; p < 0.001) over time. These findings remained consistent when we stratified the results for the methods of assessment of PVL (i.e., echocardiography vs. angiography) and PVL severity. Both moderate/severe PVL and mild PVL were associated with increased risk of overall mortality (p < 0.001), rehospitalization (p < 0.001), and cardiovascular mortality (p < 0.001) during follow-up. Conclusions: Patients with PVL, even if mild, experience higher risk of all-cause mortality, rehospitalization, and cardiovascular mortality following TAVI. These findings provide support to the implementation of procedural strategies to prevent any degree of PVL at the time of TAVI.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.

As bioprosthetic aortic valve replacement (AVR) extends to younger cohorts, tissue durability is of paramount importance. We report 7-year outcomes from an AVR bioprosthesis utilizing novel tissue. This was an international investigational device exemption trial for novel AVR with annual follow-up and a subset re-consented at 5 years for extended 10-year follow-up. Safety end points and echocardiographic measurements were adjudicated by an independent clinical events committee and by a dedicated core laboratory, respectively. Between January 2013 and March 2016, 689 patients underwent AVR with the study valve. Mean age was 66.9 ± 11.6 years, Society of Thoracic Surgeons risk score was 2.0% ± 1.8%, and 74.3% of patients were New York Heart Association functional class II and III. Five-year follow-up was completed by 512 patients, and 225 re-consented for extended follow-up. Follow-up duration was 5.3 ± 2.2 years (3665.6 patient-years), and 194 and 195 patients completed 6- and 7-year follow-ups, respectively. One-, 5-, and 7-year freedom from all-cause mortality was 97.7%, 89.4%, and 85.4%, respectively. Freedom from structural valve deterioration at 7 years was 99.3%. At 7 years, effective orifice area and mean gradients were 1.82 ± 0.57 cm2 (n = 153), and 9.4 ± 4.5 mm Hg (n = 157), respectively. At 7 years, predominantly none (96.8% [152 out of 157]) or trivial/trace (2.5% [4 out of 157]) paravalvular regurgitation and none (84.7% [133 out of 157]) or trivial/trace (11.5% [18 out of 157]) transvalvular regurgitation were observed. We report the longest surgical AVR follow-up with novel tissue in an investigational device exemption trial utilizing an independent clinical events committee and an echocardiography core laboratory. This tissue demonstrates excellent outcomes through 7 years and is the benchmark for future surgical and transcatheter prostheses. [Display omitted] [ABSTRACT FROM AUTHOR]

CONTEXT:. Right ventricular (RV) dysfunction is a major cause of morbidity and mortality in intensive care and cardiac surgery. Early detection of RV dysfunction may be facilitated by continuous monitoring of RV waveform obtained from a pulmonary artery catheter. The objective is to evaluate the extent to which RV pressure monitoring can detect changes in RV systolic performance assess by RV end-systolic elastance (Ees) following the development of an acute RV ischemic in a porcine model. HYPOTHESIS:. RV pressure monitoring can detect changes in RV systolic performance assess by RV Ees following the development of an acute RV ischemic model. METHODS AND MODELS:. Acute ischemic RV dysfunction was induced by progressive embolization of microsphere in the right coronary artery to mimic RV dysfunction clinically experienced during cardiopulmonary bypass separation caused by air microemboli. RV hemodynamic performance was assessed using RV pressure waveform-derived parameters and RV Ees obtained using a conductance catheter during inferior vena cava occlusions. RESULTS:. Acute ischemia resulted in a significant reduction in RV Ees from 0.26 mm Hg/mL (interquartile range, 0.16–0.32 mm Hg/mL) to 0.14 mm Hg/mL (0.11–0.19 mm Hg/mL; p < 0.010), cardiac output from 6.3 L/min (5.7–7 L/min) to 4.5 (3.9–5.2 L/min; p = 0.007), mean systemic arterial pressure from 72 mm Hg (66–74 mm Hg) to 51 mm Hg (46–56 mm Hg; p < 0.001), and mixed venous oxygen saturation from 65% (57–72%) to 41% (35–45%; p < 0.001). Linear mixed-effect model analysis was used to assess the relationship between Ees and RV pressure-derived parameters. The reduction in RV Ees best correlated with a reduction in RV maximum first derivative of pressure during isovolumetric contraction (dP/dtmax) and single-beat RV Ees. Adjusting RV dP/dtmax for heart rate resulted in an improved surrogate of RV Ees. INTERPRETATION AND CONCLUSIONS:. Stepwise decreases in RV Ees during acute ischemic RV dysfunction were accurately tracked by RV dP/dtmax derived from the RV pressure waveform.

Abstract 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.

Background: Transcatheter aortic valve implantation is safe and effective for high-risk patients with bioprosthetic valve failure (BVF) but has not been studied in low- and intermediate-risk patients. One year outcomes of the PARTNER 3 Aortic Valve-in-valve (AViV) Study were evaluated. Methods: This prospective, single-arm, multicenter study enrolled 100 patients from 29 sites with surgical BVF. The primary endpoint was a composite of all-cause mortality and stroke at 1 year. The key secondary outcomes included mean gradient, functional capacity, and rehospitalization (valve-related, procedure-related, or heart failure related). Results: A total of 97 patients underwent AViV with a balloon-expandable valve from 2017 to 2019. Patients were 79.4% male with a mean age of 67.1 years and Society of Thoracic Surgeons score of 2.9%. The primary endpoint occurred in 2 patients (2.1%) who had strokes; there was no mortality at 1 year. Five patients (5.2%) had valve thrombosis events, and 9 patients (9.3%) had rehospitalizations, including 2 (2.1%) for strokes, 1 (1.0%) for heart failure, and 6 (6.2%) for aortic valve reinterventions (3 explants, 3 balloon dilations, and 1 percutaneous paravalvular regurgitation closure). From baseline to 1 year, New York Heart Association class III/IV decreased from 43.3% to 4.5%, mean gradient from 39.1 ± 18.2 mm Hg to 19.7 ± 7.6 mm Hg, and ≥moderate aortic regurgitation from 41.1% to 1.1%. Conclusions: AViV with a balloon-expandable valve improved hemodynamic and functional status at 1 year and can provide an additional therapeutic option in selected low- or intermediate-risk patients with surgical BVF, although longer term follow-up is necessary.

Background: Transcatheter valve-in-valve replacement (ViV-TAVR) has emerged as an alternative to redo-surgical aortic valve replacement (Redo-SAVR) for the treatment of failed surgical aortic bioprostheses. However, the benefit of ViV-TAVR compared with Redo-SAVR remains debated with regard to short-term hemodynamic results and short- and long-term clinical outcomes. Objective: This study aimed to compare short-term hemodynamic performance and long-term clinical outcomes of ViV-TAVR vs. Redo-SAVR in patients treated for surgical aortic bioprosthetic valve failure. Methods: We retrospectively analyzed the data prospectively collected in 184 patients who underwent Redo-SAVR or ViV-TAVR. Transthoracic echocardiography was performed before and after the procedure and analyzed in an echocardiography core laboratory using the new Valve Academic Research Consortium-3 criteria. An inverse probability of treatment weighting was used to compare the outcomes between both procedures. Results: ViV-TAVR showed lower rate of intended hemodynamic performance (39.2% vs. 67.7%, p < 0.001) at 30 days, which was essentially driven by a higher rate (56.2% vs. 28.8%, p = 0.001) of high residual gradient (mean transvalvular gradient ≥20 mm Hg). Despite a trend for higher 30-day mortality in the Redo-SAVR vs. ViV-TAVR group (8.7% vs. 2.5%, odds ratio [95% CI]: 3.70 [0.77-17.6]; p = 0.10), the long-term mortality was significantly lower (24.2% vs. 50.1% at 8 years; hazard ratio [95% CI]: 0.48 [0.26-0.91]; p = 0.03) in the Redo-SAVR group. After inverse probability of treatment weighting analysis, Redo-SAVR remained significantly associated with reduced long-term mortality compared with ViV-TAVR (hazard ratio [95% CI]: 0.32 [0.22-0.46]; p < 0.001). Conclusions: ViV-TAVR was associated with a lower rate of intended hemodynamic performance and numerically lower mortality at 30 days but higher rates of long-term mortality compared with Redo-SAVR.

Background: Lipoprotein(a) (Lp[a]), which consists of a low-density lipoprotein (LDL) bound to apolipoprotein(a), is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases. Few studies have performed hypothesis-free direct comparisons of the Lp(a) and the LDL proteomes. Our objectives were to compare the Lp(a) and the LDL proteomic profiles and to evaluate the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile. Methods: We performed a label-free analysis of the Lp(a) and LDL proteomic profiles of healthy volunteers in a discovery (n = 6) and a replication (n = 9) phase. We performed inverse variance weighted Mendelian randomization to document the effect of lifelong exposure to elevated Lp(a) or LDL cholesterol levels on the plasma proteomic profile of participants of the INTERVAL study. Results: We identified 15 proteins that were more abundant on Lp(a) compared with LDL (serping1, pi16, itih1, itih2, itih3, pon1, podxl, cd44, cp, ptprg, vtn, pcsk9, igfals, vcam1, and ttr). We found no proteins that were more abundant on LDL compared with Lp(a). After correction for multiple testing, lifelong exposure to elevated LDL cholesterol levels was associated with the variation of 18 plasma proteins whereas Lp(a) did not appear to influence the plasma proteome. Conclusions: Results of this study highlight marked differences in the proteome of Lp(a) and LDL as well as in the effect of lifelong exposure to elevated LDL cholesterol or Lp(a) on the plasma proteomic profile. Résumé: Contexte: La lipoprotéine(a) (Lp[a]), qui est constituée d’une lipoprotéine de basse densité (LDL) liée à une apolipoprotéine(a), est l’un des plus importants facteurs de risque génétiques de survenue d’une maladie cardiovasculaire athéroscléreuse. Peu d’études comparatives directes sans hypothèse ont porté sur le protéome de la Lp(a) et celui des LDL. Nos objectifs étaient de comparer les profils protéomiques de la Lp(a) et des LDL et d’évaluer l’effet d’une exposition à vie à un taux élevé de Lp(a) ou de cholestérol LDL sur le profil protéomique plasmatique. Méthodologie: Nous avons réalisé une analyse sans marquage des profils protéomiques de la Lp(a) et des LDL chez des volontaires en bonne santé dans le cadre d’une phase de découverte (n = 6) et d’une phase de réplication (n = 9). Pour rendre compte de l’effet d’une exposition à vie à un taux élevé de Lp(a) ou de cholestérol des LDL sur le profil protéomique plasmatique des participants de l’étude INTERVAL, nous avons utilisé une analyse de randomisation Mendélienne avec pondération par l’inverse de la variance. Résultats: Nous avons relevé 15 protéines associées en plus grande abondance à la Lp(a) qu’aux LDL (serping1, pi16, itih1, itih2, itih3, pon1, podxl, cd44, cp, ptprg, vtn, pcsk9, igfals, vcam1 et ttr). Nous n’avons noté aucune protéine associée en plus grande abondance aux LDL qu’à la Lp(a). Après correction pour tenir compte de la multiplicité des tests, l’exposition à vie à un taux élevé de cholestérol LDL a été associée à la variation de 18 protéines plasmatiques, tandis que le taux de Lp(a) ne semblait pas influencer le protéome plasmatique. Conclusions: Les résultats de notre étude font ressortir les différences marquées entre le protéome de la Lp(a) et celui des LDL, ainsi qu’entre l’effet sur le profil protéomique plasmatique de l’exposition à vie à un taux élevé de cholestérol LDL et celui de l’exposition à vie à un taux élevé de Lp(a).

BACKGROUND: Transcatheter mitral valve-in-valve replacement offers a less-invasive alternative for high-risk patients with bioprosthetic valve failure. Limited experience exists in intermediate-risk patients. We aim to evaluate 1-year outcomes of the PARTNER 3 mitral valve-in-valve study. METHODS: This prospective, single-arm, multicenter study enrolled symptomatic patients with a failing mitral bioprosthesis demonstrating greater than or equal to moderate stenosis and regurgitation and Society of Thoracic Surgeons score ≥3% and <8%. A balloon-expandable transcatheter heart valve (SAPIEN 3, Edwards Lifesciences) was used via a transeptal approach. The primary end point was the composite of all-cause mortality and stroke at 1 year. RESULTS: A total of 50 patients from 12 sites underwent mitral valve-in-valve from 2018 to 2021. The mean age was 70.1±9.7 years, mean Society of Thoracic Surgeons score was 4.1%±1.6%, and 54% were female. There were no primary end point events (mortality or stroke) through 1 year, and no left-ventricular outflow tract obstruction, endocarditis, or mitral valve reintervention was reported. Six patients (12%) required rehospitalization, including heart failure (n=2), minor procedural side effects (n=2), and valve thrombosis (n=2; both resolved with anticoagulation). An additional valve thrombosis was associated with no significant clinical sequelae. From baseline to 1 year, all subjects with available data had none/trace or mild (grade 1+) mitral regurgitation and the New York Heart Association class improved in 87.2% (41/47) of patients. CONCLUSIONS: Mitral valve-in-valve with a balloon-expandable valve via transseptal approach in intermediate-risk patients was associated with improved symptoms and quality of life, adequate transcatheter valve performance, and no mortality or stroke at 1-year follow-up. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

This study investigated the safety and effectiveness of surgical aortic valve replacement with RESILIA tissue (Edwards Lifesciences) through 5 years in patients with native bicuspid aortic valves. Outcomes were compared with those for patients with tricuspid aortic valves. Of 689 patients from the COMMENCE (ProspeCtive, nOn-randoMized, MulticENter) trial who received the study valve, 645 had documented native valve morphology and core laboratory-evaluable echocardiograms from any postoperative visit, which were used to model hemodynamic outcomes over 5 years. Linear mixed-effects models were used to estimate longitudinal changes in mean gradient and effective orifice area. Patients with native bicuspid aortic valves (n = 214) were more than a decade younger than those with tricuspid aortic valves (n = 458; 59.8 ± 12.4 years vs 70.2 ± 9.5 years; P <.001). The bicuspid aortic valve cohort exhibited no structural valve deterioration over 5 years, and rates of paravalvular leak and transvalvular regurgitation were low (0.7% and 2.9%, respectively [all mild] at 5 years). These outcomes mirrored those in patients with native tricuspid aortic valves. The model-estimated postoperative mean gradient and effective orifice area, as well as the rate of change of these outcomes, adjusted for age, body surface area, and bioprosthesis size, did not differ between the 2 cohorts. Among patients with bicuspid aortic valves, RESILIA tissue valves demonstrated excellent outcomes to 5 years, including no structural valve deterioration and very low rates of paravalvular and transvalvular regurgitation. These results are encouraging for RESILIA tissue durability in young patients. [ABSTRACT FROM AUTHOR]

Conduction disturbances requiring a permanent pacemaker (PPM) are a frequent complication of transcatheter aortic valve replacement (TAVR) with few reports of rates, predictors, and long-term clinical outcomes following implantation of the third-generation, balloon-expandable SAPIEN 3 (S3) transcatheter heart valve (THV). The aim of this study was to investigate the rates, predictors, and long-term clinical outcomes of PPM implantation following TAVR with the S3 THV. The current study included 857 patients in the PARTNER 2 S3 registries with intermediate and high surgical risk without prior PPM, and investigated predictors and 5-year clinical outcomes of new PPM implanted within 30 days of TAVR. Among 857 patients, 107 patients (12.5%) received a new PPM within 30 days after TAVR. By multivariable analysis, predictors of PPM included increased age, pre-existing right bundle branch block, larger THV size, greater THV oversizing, moderate or severe annulus calcification, and implantation depth >6 mm. At 5 years (median follow-up 1,682.0 days [min 2.0 days, max 2,283.0 days]), new PPM was not associated with increased rates of all-cause mortality (Adj HR: 1.20; 95% CI: 0.85-1.70; P = 0.30) or repeat hospitalization (Adj HR: 1.22; 95% CI: 0.67-2.21; P = 0.52). Patients with new PPM had a decline in left ventricular ejection fraction at 1 year that persisted at 5 years (55.1 ± 2.55 vs 60.4 ± 0.65; P = 0.02). PPM was required in 12.5% of patients without prior PPM who underwent TAVR with a SAPIEN 3 valve in the PARTNER 2 S3 registries and was not associated with worse clinical outcomes, including mortality, at 5 years. Modifiable factors that may reduce the PPM rate include bioprosthetic valve oversizing, prosthesis size, and implantation depth. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Determinants of coronary artery calcification (CAC) prevalence and severity in heterozygous familial hypercholesterolemia (HeFH) remain understudied. The objective of this cross-sectional study was to investigate correlates of CAC in patients with HeFH. Methods: A CAC score was calculated by a noncontrast computed tomography scan in women (n = 68) and men (n = 78) with genetically defined HeFH. We classified CAC prevalence and severity using 3 categories: CAC score = 0 Agatston Unit (AU), CAC score = 1-100 AU, and CAC score > 100 AU. Information on potential correlates of CAC including familial and personal health history, cardiovascular risk factors, lipid-lowering medication, and lifestyle habits was collected. Results: A total of 95 patients had prevalent CAC. Independent correlates of CAC prevalence and severity included age (odds ratio [OR] per 10 years: 5.06, 95% confidence interval [CI]: 3.19, 7.93, P < 0.0001), family history of premature cardiovascular disease (OR: 3.88, 95% CI: 1.71, 8.81, P = 0.001), male sex (OR: 3.40, 95% CI: 1.49, 7.78, P = 0.004), statin use (OR: 15.5, 95% CI: 1.89, 126, P = 0.01), diet quality assessed with the Alternative Healthy Eating Index score (OR per 1 standard deviation: 0.59, 95% CI: 0.39, 0.90, P = 0.01), ever smoking (OR: 3.06, 95% CI: 1.20, 7.81, P = 0.02), receptor-negative genotype (OR: 3.17, 95% CI: 1.16, 8.66, P = 0.02), lipoprotein(a) year-score (OR per 1 standard deviation of log-transformed year-score: 1.53, 95% CI: 0.99, 2.36, P = 0.05). Conclusions: In individuals with HeFH, age, family history of premature cardiovascular disease, sex, statin use, diet quality, smoking status, the LDLR genotype, and lipoprotein(a) concentrations were independently associated with CAC prevalence and severity. Résumé: Contexte: Les déterminants de la prévalence et de la sévérité de la calcification des artères coronaires (CAC) dans l'hypercholestérolémie familiale hétérozygote (HFHe) demeurent peu étudiés. L’objectif de cette étude transversale était d'identifier les corrélats de la CAC chez des patients atteints d’HFHe. Méthodologie: Un score calcique coronarien (SCC) a été calculé par un examen de tomodensitométrie sans contraste chez des femmes (n = 68) et des hommes (n = 78) avec HFHe génétiquement définie. Nous avons classé la prévalence et la gravité de la CAC en trois catégories : SCC = 0 unité d’Agatston (UA), SCC = 1 à 100 UA et SCC > 100 UA. Des renseignements ont été recueillis sur des corrélats potentiels de la CAC, dont les antécédents médicaux familiaux et personnels, les facteurs de risque cardiovasculaire, les médicaments hypolipidémiants et les habitudes de vie. Résultats: Au total, 95 patients présentaient une CAC. Les corrélats indépendants de la prévalence et de la gravité de la CAC comprenaient l’âge (rapport de cotes [RC] par tranche de 10 ans : 5,06; intervalle de confiance [IC] à 95 % : 3,19 à 7,93; p < 0,0001), des antécédents familiaux de maladie cardiovasculaire précoce (RC : 3,88; IC à 95 % : 1,71 à 8,81; p = 0,001), le sexe masculin (RC : 3,40; IC à 95 % : 1,49 à 7,78; p = 0,004), l’emploi de statines (RC : 15,5; IC à 95 % : 1,89 à 126; p = 0,01), la qualité du régime alimentaire évaluée selon le score AHEI (Alternative Healthy Eating Index) (RC par écart-type : 0,59; IC à 95 % : 0,39 à 0,90; p = 0,01), le tabagisme (RC : 3,06; IC à 95 % : 1,20 à 7,81; p = 0,02), le génotype récepteur-négatif (RC : 3,17; IC à 95 % : 1,16 à 8,66; p = 0,02) et le score lipoprotéine(a)-année (RC par écart-type du score-année transformé en logarithme : 1,53; IC à 95 % : 0,99 à 2,36; p = 0,05). Conclusions: Chez les personnes atteintes d’HFHe, l’âge, les antécédents familiaux de maladie cardiovasculaire précoce, le sexe, l’emploi de statines, la qualité du régime alimentaire, le statut de tabagisme, le génotype du LDLR et les concentrations de lipoprotéine(a) ont été associés de façon indépendante à la prévalence et à la gravité de la CAC.

Objective To use echocardiographic and clinical features to develop an explainable clinical risk prediction model in patients with aortic stenosis (AS), including those with low-gradient AS (LGAS), using machine learning (ML).Methods In 1130 patients with moderate or severe AS, we used bootstrap lasso regression (BLR), an ML method, to identify echocardiographic and clinical features important for predicting the combined outcome of all-cause mortality or aortic valve replacement (AVR) within 5 years after the initial echocardiogram. A separate hold out set, from a different centre (n=540), was used to test the generality of the model. We also evaluated model performance with respect to each outcome separately and in different subgroups, including patients with LGAS.Results Out of 69 available variables, 26 features were identified as predictive by BLR and expert knowledge was used to further reduce this set to 9 easily available and input features without loss of efficacy. A ridge logistic regression model constructed using these features had an area under the receiver operating characteristic curve (AUC) of 0.74 for the combined outcome of mortality/AVR. The model reliably identified patients at high risk of death in years 2–5 (HRs ≥2.0, upper vs other quartiles, for years 2–5, p

Background: Optimal timing for intervention remains uncertain in asymptomatic patients with primary mitral regurgitation (MR). We aimed to assess the prognostic value of a new cardiac damage staging classification in patients with asymptomatic moderate or severe primary MR. Methods: Clinical, Doppler-echocardiographic, and outcome data prospectively collected in 338 asymptomatic patients (64 ± 15 years, 68% men) with at least moderate primary MR were retrospectively analyzed. Patients were hierarchically classified as per the following staging classification: no cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate or severe left ventricular or left atrial damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), or right ventricular damage (stage 4). Results: There was a stepwise increase in 10-year mortality rates as per cardiac damage stage: 20.0% in stage 0, 25.6% in stage 1, 31.5% in stage 2, and 61.3% in stage 3-4 (p < 0.001). The staging classification was significantly associated with increased risk of mortality (hazard ratio = 1.41 per one-stage increase, 95% confidence interval: 1.07-1.85, p = 0.015) and the composite of cardiovascular mortality or hospitalization (hazard ratio = 1.51 per one-stage increase, 95% confidence interval: 1.07-2.15, p = 0.020) in multivariable analysis adjusted for EuroSCORE II, mitral valve intervention as a time-dependent variable, and other risk factors. The proposed scheme showed incremental value over several clinical variables (net reclassification index = 0.40, p = 0.03). Conclusions: The new staging classification provides independent and incremental prognostic value in patients with asymptomatic moderate or severe MR.

Background: Sex-specific thresholds of computed tomography (CT)–derived aortic valve calcification (AVC) or AVC density (AVCd) to identify severe aortic stenosis (AS) have been established in populations that consisted mainly of Caucasians with a tricuspid aortic valve. The objective of this study was to evaluate the accuracy (i.e., sensitivity and specificity) of previously established thresholds to identify severe AS in patients with bicuspid aortic valve (BAV) and according to ethnicity: Caucasian vs. Asian. Methods: We built a multicenter registry of echocardiographic and CT data collected in BAV patients with at least mild AS and preserved left ventricular ejection fraction from 7 different centers. Anatomic severity of AS obtained by CT-derived AVC and AVCd was compared to hemodynamic severity of AS obtained by echocardiography. Results: Among 485 BAV patients (60% men, 73% Asians), the best thresholds of AVC and AVCd to identify severe AS in BAV patients were 2315 arbitrary units (AU) (sensitivity [Se]/specificity [Spe] = 82/78%) in men, 1103 AU (Se/Spe = 80/82%) in women, and 561 AU/cm2 (Se/Spe = 86/91%) in men, and 301 AU/cm2 (Se/Spe = 83/82%) in women, respectively. According to ethnicity, thresholds for severe AS in Caucasian patients were, respectively, in men and women: 2208 AU (Se/Spe = 83/83%) and 1230 AU (Se/Spe = 87/82%) for AVC and 474 AU/cm2 (Se/Spe = 88/83%) and 358 AU/cm2 (Se/Spe = 80/82%) for AVCd. In Asian patients, they were 2582 AU (Se/Spe = 76/78%) and 924 AU (Se/Spe = 84/80%) for AVC and 640 AU/cm2 (Se/Spe = 82/89%) and 255 AU/cm2 (Se/Spe = 86/80%) for AVCd. Conclusions: The optimal thresholds to identify hemodynamically severe AS in BAV patients are similar in Caucasians but appear to be higher in Asian men, compared with thresholds previously reported in tricuspid aortic valve patients. Nonetheless, the thresholds currently proposed in the guidelines have good accuracy and can be applied in BAV patients to confirm AS severity.