Impact of sex on the management and outcome of aortic stenosis patients: a female aortic valve stenosis paradox, and a call for personalized treatments?
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ABSTRACT:
SUBMITTER: Goliasch G
PROVIDER: S-EPMC8282323 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Impact of sex on the management and outcome of aortic stenosis patients: a female aortic valve stenosis paradox, and a call for personalized treatments?
Goliasch Georg G Lang Irene M IM
European heart journal 20210701 27
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Project description:ObjectiveWomen with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study.MethodsDoppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality.ResultsThe annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex.ConclusionsIn the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders.Trial registration numberClinicalTrials.gov identifier: NCT00092677.
| S-EPMC4316939 | biostudies-literature
Project description:The impact of sex on pathophysiological processes, clinical presentation, treatment options, as well as outcomes of degenerative aortic stenosis remain poorly understood. Female patients are well represented in transfemoral aortic valve implantation (TAVI) trials and appear to derive favorable outcomes with TAVI. However, higher incidences of major bleeding, vascular complications, and stroke have been reported in women following TAVI. The anatomical characteristics and pathophysiological features of aortic stenosis in women might guide a tailored planning of the percutaneous approach. We highlight whether a sex-based TAVI management strategy might impact on clinical outcomes. This review aimed to evaluate the impact of sex from diagnosis to treatment of degenerative aortic stenosis, discussing the latest evidence on epidemiology, pathophysiology, clinical presentation, therapeutic options, and outcomes. Furthermore, we focused on technical sex-oriented considerations in TAVI including the preprocedural screening, device selection, implantation strategy, and postprocedural management.
| S-EPMC9673730 | biostudies-literature
Project description:ObjectivesTo compare device success and paravalvular leak rates of 3 new-generation transcatheter aortic valve replacement devices in patients with bicuspid aortic valve stenosis and to test their biomechanical performance in a computer-based simulation model of aortic root with increasing ellipticity.MethodsThis retrospective multicentre study included 56 bicuspid aortic valve patients undergoing transcatheter aortic valve replacement with new-generation devices: Lotus/Lotus Edge (N = 15; 27%), Evolut-R (N = 20; 36%) and ACURATE neo (N = 21; 37%). Three virtual simulation models of aortic root with increasing index of eccentricity (0-0.25-0.5) were implemented. Stress distribution, stent-root contact area and paravalvular orifice area were computed.ResultsDevice success was achieved in 43/56 patients (77%) with comparable rates among Lotus (87%), Evolut-R (60%) and ACURATE neo (86%; P = 0.085). Moderate paravalvular leak rate was significantly lower in the Lotus group as compared to Evolut-R group (0% vs 30%; P = 0.027) and comparable to the ACURATE neo group (0% vs 10%; P = 0.33). By index of eccentricity = 0.5, Lotus showed a uniform and symmetric pattern of stress distribution with absent paravalvular orifice area, ACURATE neo showed a mild asymmetry with small paravalvular orifice area (1.1 mm2), whereas a severely asymmetric pattern was evident with Evolut-R, resulting in a large paravalvular orifice area (12.0 mm2).ConclusionsTranscatheter aortic valve replacement in bicuspid aortic valve patients with new-generation devices showed comparable device success rates. Lotus showed moderate paravalvular leak rate comparable to that of ACURATE neo and significantly lower than Evolut-R. On simulation, Lotus and ACURATE neo showed optimal adaptability to elliptic anatomies as compared to Evolut-R.
| S-EPMC8906794 | biostudies-literature
Project description:We are looking at differential gene/protein expression in tissue from stenotic vs sclerotic human aortic valves in order to identify genetic predispositions for aortic valve disease, as well as novel targets for diagnostic and therapeutic strategies.
2019-10-08 | GSE138531 | GEO
Project description:To examine molecular mechanisms of aortic valve stenosis in mice with hypertension and hypercholesterolemia, RNA-Seq was used during the developmental phase of stenosis to identify new gene targets.
2016-03-07 | GSE71534 | GEO
Project description:BackgroundBicuspid 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).Methods310 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.ResultsMedian 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<0.05) versus absence of hypertension, higher LDL levels and smaller baseline AA diameter in the BAV cohort (all p<0.02). In men, higher baseline Vpeak and smaller baseline AA (p<0.001) were independently associated with increased annualised AA dilation, while in women, higher LDL levels (p=0.026) were independently associated with faster AA dilation.ConclusionThis study suggests that BAV is associated with faster dilation of the AA. Predictors of AA dilation are different between valve phenotype and sex, with higher LDL levels being associated with faster AA dilation in BAV.
| S-EPMC11487820 | biostudies-literature
Project description:The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.
| S-EPMC7549171 | biostudies-literature
Project description:BackgroundAortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis.ObjectivesTo evaluate the effectiveness and safety of statins in aortic valve stenosis.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions.Selection criteriaRandomised controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care.Data collection and analysisPrimary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalisation for any reason, overall mortality, adverse events and patient quality of life.Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table.Main resultsWe included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0.14; participants = 155; study = 1). Moderate-quality evidence showed no effect on freedom from valve replacement with statins (risk ratio (RR) 0.93, 95% CI 0.81 to 1.06; participants = 2360; studies = 4), and no effect on muscle pain as an adverse event (RR 0.91, 95% CI 0.75 to 1.09; participants = 2204; studies = 3; moderate-quality evidence). Low- and very low-quality evidence showed uncertainty around the effect of statins on death from cardiovascular cause (RR 0.80, 95% CI 0.56 to 1.15; participants = 2297; studies = 3; low-quality evidence) and hospitalisation for any reason (RR 0.84, 95% CI 0.39 to 1.84; participants = 155; study = 1; very low-quality evidence). None of the four included studies reported on overall mortality and patient quality of life.Authors' conclusionsResult findings showed uncertainty surrounding the effect of statins for aortic valve stenosis.The quality of evidence from the reported outcomes ranged from moderate to very low. These results give support to European and USA guidelines (2012 and 2014, respectively) that so far there is no clinical treatment option for aortic valve stenosis.
| S-EPMC6457620 | biostudies-literature
Project description:BackgroundBased on worldwide registries, approximately 50% of patients who underwent transcatheter aortic valve replacement (TAVR) are female patients. Although TAVR procedures have improved tremendously in recent years, differences in outcome including mortality between sexes remain. We aimed to investigate the trends in TAVR in the early and new eras of utilization and to assess TAVR outcomes in female patients vs. male patients.MethodsUsing the 2011-2017 National Inpatient Sample (NIS) database, we identified hospitalizations for patients with the diagnosis of aortic stenosis during which a TAVR was performed. Patients' sociodemographic and clinical characteristics, procedure complications, and mortality were analyzed. Piecewise regression analyses were performed to assess temporal trends in TAVR utilization in female patients and in male patients. Multivariable analysis was performed to identify predictors of in-hospital mortality.ResultsA total of 150,647 hospitalizations for TAVR across the United States were analyzed during 2011-2017. During the study period, a steady upward trend was observed for TAVR procedures in both sexes. From 2011 to 2017, there were significantly more TAVR procedures performed in men [80,477 (53.4%)] than in women [70,170 (46.6%)]. Male patients had significantly higher Deyo-CCI score and comorbidities. Differences in mortality rates among sexes were observed, presenting with higher in-hospital mortality in women than in men, OR 1.26 [95% CI 1.18-1.35], p < 0.001.ConclusionUtilization of TAVR demonstrated a steady upward trend during 2011-2017, and a similar trend was presented for both sexes. Higher in-hospital mortality was recorded in female patients compared to male patients. Complication rates decreased over the years but without effect on mortality differences between the sex groups.
| S-EPMC9623151 | biostudies-literature
Project description:Calcific aortic stenosis (CAS) is the most common cause of acquired valvular heart disease in adults with no available pharmacological treatment to inhibit the disease progression to date. This review provides an up-to-date overview of current knowledge of molecular mechanisms underlying CAS pathobiology and the related treatment pathways. Particular attention is paid to current randomized trials investigating medical treatment of CAS, including strategies based on lipid-lowering and antihypertensive therapies, phosphate and calcium metabolism, and novel therapeutic targets such as valvular oxidative stress, coagulation proteins, matrix metalloproteinases, and accumulation of advanced glycation end products.
| S-EPMC8708539 | biostudies-literature