Impact of sex on the management and outcome of aortic stenosis patients: a female aortic valve stenosis paradox, and a call for personalized treatments?
Ontology highlight
ABSTRACT:
SUBMITTER: Goliasch G
PROVIDER: S-EPMC8282323 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Women 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.Doppler 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.The 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.In 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.ClinicalTrials.gov identifier: NCT00092677.
| S-EPMC4316939 | biostudies-literature
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: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: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:Studies assessing the differential impact of sex on outcomes of aortic valve replacement (AVR) yielded conflicting results. We sought to investigate sex-related differences in AVR utilization, patient risk profile, and in-hospital outcomes using the Nationwide Inpatient Sample.In total, 166 809 patients (63% male and 37% female) who underwent AVR between 2003 and 2014 were identified, and 48.5% had a concomitant cardiac surgery procedure. Compared with men, women were older and had more nonatherosclerotic comorbid conditions including hypertension, diabetes mellitus, obstructive pulmonary disease, atrial fibrillation/flutter, and anemia but fewer incidences of coronary and peripheral arterial disease and prior sternotomies. In-hospital mortality was significantly higher in women (5.6% versus 4%, P<0.001). Propensity matching was performed to assess the impact of sex on the outcomes of isolated AVR and yielded 28 237 matched pairs of male and female participants. In the propensity-matched groups, in-hospital mortality was higher in women (3.3% versus 2.9%, P<0.001). Along with vascular complications and blood transfusion (6% versus 5.6%, P=0.027 and 40.4% versus 33.9%, P<0.001, respectively). Rates of stroke, permanent pacemaker implantation, and acute kidney injury requiring dialysis were similar (2.4% versus 2.4%, P=0.99; 6% versus 6.3%, P=0.15; and 1.4% versus 1.3%, P=0.14, respectively). Length of stay median and interquartile range were both similar between groups (7±6 days). Rates of nonhome discharge were higher among women (27.9% versus 19.6%, P<0.001).Women have worse in-hospital mortality following AVR compared with men. Coupled with the accumulating evidence suggesting higher magnitude of benefit of transcatheter AVR over AVR in women, women should perhaps be offered transcatheter AVR over AVR at a lower threshold than men.
| S-EPMC5634288 | biostudies-other
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
Project description:BackgroundFirst-phase ejection fraction (EF1), the left ventricular (LV) ejection fraction (EF) until the time of peak transaortic velocity, is a novel marker of subclinical LV dysfunction able to predict adverse events in aortic stenosis (AS). This study investigated the association between end-systolic wall stress (ESWS) and EF1 in severe AS, as well as the prognostic value of EF1 in severe asymptomatic AS.MethodsTwo prospectively gathered cohorts of 94 asymptomatic patients and 108 symptomatic patients scheduled for aortic valve replacement (AVR), all with severe AS (aortic valve area <1 cm2) were stratified according to the median value of EF1 (33%). EF1 was defined as the EF at peak transaortic velocity. Asymptomatic patients were followed up for 3 years for the combined end-point of death, AVR or admission with heart failure.ResultsEF1 correlated with EF and was inversely associated with ESWS. In multivariate regression analysis, ESWS (p<0.001) and replacement fibrosis measured by MRI (p=0.02) were associated with EF1. Among asymptomatic patients, EF1 above the median was associated with the combined primary endpoint (HR=0.53 (95% CI 0.33 to 0.87)), while global longitudinal strain and EF were not. Among 42 patients with discordant AS (mean gradient <40 mm Hg), EF1 above median was associated with the primary endpoint (HR 0.28 (95% CI 0.12 to 0.61)).ConclusionEF1 is an afterload-dependent measure that is associated with events in patients with asymptomatic severe AS. The afterload dependency of EF1 may be useful in timing of risk stratification in patients with discordant AS.Trial registration numbersNCT02395107 and NCT02316587.
| S-EPMC7880107 | biostudies-literature
Project description:BackgroundReversibility of left ventricular (LV) dysfunction in high-risk aortic stenosis patient and its impact on survival after transcatheter aortic valve replacement (TAVR) are unclear. We aimed to evaluate longitudinal changes of LV structure and function after TAVR and their impact on survival.Methods and resultsWe studied 209 patients with aortic stenosis who underwent TAVR from May 2006 to December 2012. Echocardiograms were used to calculate LV end-diastolic volume index (LVEDVi), LV ejection fraction, LV mass index (LVMi), and global longitudinal strain before, immediately (<10 days), late (1-3 months), and yearly after TAVR. During a median follow-up of 1345 days, 118 patients died, with 26 dying within 1 year. Global longitudinal strain, LVEDVi, LV ejection fraction, and LVMi improved during follow-up. In patients who died during the first year, death was preceded by LVEDVi and LVMi increase. Multivariable longitudinal data analysis showed that aortic regurgitation at baseline, aortic regurgitation at 30 days, and initial LVEDVi were independent predictors of subsequent LVEDVi. In a joint analysis of longitudinal and survival data, baseline Society of Thoracic Surgeons score was predictive of survival, with no additive effect of longitudinal changes in LVEDVi, LVMi, global longitudinal strain, or LV ejection fraction. Presence of aortic regurgitation at 1 month after TAVR was the only predictor of 1-year survival.ConclusionsLV reverse remodeling was observed after TAVR, whereas lack of LVEDVi and LVMi improvement was observed in patients who died during the first year after TAVR. Post-TAVR, aortic regurgitation blocks reverse remodeling and is associated with poor 1-year survival after TAVR.
| S-EPMC5586298 | biostudies-literature
Project description:ObjectiveTranscatheter aortic valve replacement (TAVR) reduces left ventricular (LV) afterload and improves prognosis in aortic stenosis (AS) patients. However, LV afterload consists of both valvular and arterial loads, and the benefits of TAVR may be attenuated if the arterial load dominates. We proposed a new hemodynamic index, the Relative Valve Load (RVL), a ratio of mean gradient (MG) and valvuloarterial impedance (Zva), to describe the relative contribution of the valvular load to the global LV load, and examined whether RVL predicted patient outcome following TAVR.MethodsA total of 258 patients with symptomatic severe AS (indexed aortic valve area (AVA)<0.6cm2/m2, AR?2+) underwent successful TAVR at the University of Ottawa Heart Institute and had clinical follow-up to 1-year post-TAVR. Pre-TAVR MG, AVA, percent stroke work loss (%SWL), Zva and RVL were measured by echocardiography. The primary endpoint was all cause mortality at 1-year post TAVR.ResultsThere were 53 deaths (20.5%) at 1-year. RVL?7.95ml/m2 had a sensitivity of 60.4% and specificity of 75.1% for identifying all cause mortality at 1-year post-TAVR and provided better specificity than MG<40 mmHg, AVA>0.75cm2, %SWL?25% and Zva>5mmHg/ml/m2 despite equivalent or better sensitivity. In multivariable Cox analysis, RVL?7.95ml/m2 was an independent predictor of all cause mortality (HR 3.2, CI 1.8-5.9; p<0.0001). RVL?7.95ml/m2 was predictive of all cause mortality in both low flow and normal flow severe AS.ConclusionsRVL is a strong predictor of all-cause mortality in severe AS patients undergoing TAVR. A pre-procedural RVL?7.95ml/m2 identifies AS patients at increased risk of death despite TAVR and may assist with decision making on the benefits of TAVR.
| S-EPMC5919479 | biostudies-literature