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Early Aortic Valve Replacement vs. Conservative Management in Asymptomatic Severe Aortic Stenosis Patients With Preserved Ejection Fraction: A Meta-Analysis.

ABSTRACT: Background: Aortic stenosis (AS) is the most common valvular disease in developed countries. Until now, the specific timing of intervention for asymptomatic patients with severe aortic stenosis and preserved ejection fraction remains controversial. Methods: A systematic search of four databases (Pubmed, Web of science, Cochrane library, Embase) was conducted. Studies of asymptomatic patients with severe AS or very severe AS and preserved left ventricular ejection fraction underwent early aortic valve replacement (AVR) or conservative care were included. The end points included all-cause mortality, cardiac mortality, and non-cardiac mortality. Results: Four eligible studies were identified with a total of 1,249 participants. Compared to conservative management, patients who underwent early AVR were associated with lower all-cause mortality, cardiac mortality, and non-cardiac mortality rate (OR 0.16, 95% CI 0.09-0.31, P < 0.00001; OR 0.12, 95% CI 0.02-0.62, P = 0.01; OR 0.36, 95% CI 0.21-0.63, P = 0.0003, respectively). Conclusions: Early AVR is preferable for asymptomatic severe AS patients with preserved ejection fraction.

SUBMITTER: Yuan T

PROVIDER: S-EPMC7887283 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Early Aortic Valve Replacement vs. Conservative Management in Asymptomatic Severe Aortic Stenosis Patients With Preserved Ejection Fraction: A Meta-Analysis.

Yuan Tan T Lu Yi Y Bian Chang C Cai Zhejun Z

Frontiers in cardiovascular medicine 20210203

<b>Background:</b> Aortic stenosis (AS) is the most common valvular disease in developed countries. Until now, the specific timing of intervention for asymptomatic patients with severe aortic stenosis and preserved ejection fraction remains controversial. <b>Methods:</b> A systematic search of four databases (Pubmed, Web of science, Cochrane library, Embase) was conducted. Studies of asymptomatic patients with severe AS or very severe AS and preserved left ventricular ejection fraction underwent ...[more]

PMID: 33614743

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Project description:BACKGROUND:In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (LV-GLS) to treadmill stress echocardiography. METHODS AND RESULTS:We studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age-sex predicted metabolic equivalents [%AGP-METs]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[LV-stroke volume index]) and LV-GLS (measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and LV-GLS were 0.46±0.1 cm2/m2, 4.5±0.9 mm Hg/mL per m2 and -16±4%, respectively; only 50% achieved >100% AGP-METs. Sixty-four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or HR 1.06), lower % AGP-METS (HR 1.16), higher Zva (HR 1.25) and lower LV-GLS (HR 1.12) were associated with higher longer-term mortality, while aortic valve replacement (HR 0.45) was associated with improved survival (all P<0.01). Sequential addition of ZVa and LV-GLS to clinical model (Society of Thoracic Surgeons score and %AGP-METs) increased the c-statistic from 0.65 to 0.69 and 0.75, respectively, both P<0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement. CONCLUSIONS:In asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography, LV-GLS and ZVa offer incremental prognostic value.

Project description:BackgroundIn patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), studies have suggested that reduced left ventricular (LV) ejection fraction (LVEF) and low aortic valve gradient (AVG) are associated with worse long-term outcomes. Because these conditions commonly coexist, the extent to which they are independently associated with outcomes after TAVR is unknown.ObjectivesThe purpose of this study was to evaluate the impact of LVEF and AVG on clinical outcomes after TAVR and to determine whether the effect of AVG on outcomes is modified by LVEF.MethodsUsing data from 11,292 patients who underwent TAVR as part of the Transcatheter Valve Therapies Registry, we examined rates of 1-year mortality and recurrent heart failure in patients with varying levels of LV dysfunction (LVEF <30% vs. 30% to 50% vs. >50%) and AVG (<40 mm Hg vs. ≥40 mm Hg). Multivariable models were used to estimate the independent effect of AVG and LVEF on outcomes.ResultsDuring the first year of follow-up after TAVR, patients with LV dysfunction and low AVG had higher rates of death and recurrent heart failure. After adjustment for other clinical factors, only low AVG was associated with higher mortality (hazard ratio: 1.21; 95% confidence interval: 1.11 to 1.32; p < 0.001) and higher rates of heart failure (hazard ratio: 1.52; 95% confidence interval: 1.36 to 1.69; p <0.001), whereas the effect of LVEF was no longer significant. There was no evidence of effect modification between AVG and LVEF with respect to either endpoint.ConclusionsIn this series of real-world patients undergoing TAVR, low AVG, but not LV dysfunction, was associated with higher rates of mortality and recurrent heart failure. Although these findings suggest that AVG should be considered when evaluating the risks and benefits of TAVR for individual patients, neither severe LV dysfunction nor low AVG alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR.

Project description:BackgroundWhy some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition.MethodsWe recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ≥55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and 31P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy.ResultsIn the absence of failure, CK flux was lower in the presence of AS (by 32%, P=0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, P<0.001), with CK kf unchanged (P=0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group (P>0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower (P<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (r=0.86, P=0.003).ConclusionsTotal CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.

Project description:ImportanceTranscatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce.ObjectiveTo compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS.Design, setting, and participantsThis retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts.ExposuresPrimary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization.Main outcomes and measuresThe primary outcomes were 30-day and 3-year survival.ResultsOverall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not.Conclusions and relevanceTranscatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.

Project description:Background Moderate aortic stenosis ( MAS ) has not been extensively studied and characterized, as no published study has been specifically devoted to this condition. Methods and Results We aimed to describe the characteristics of patients with MAS and to evaluate their long-term survival compared with that of the general population. This study included 508 patients (mean±SD age, 75±11 years) with MAS (aortic valve area between 1 and 1.5 cm2; mean±SD aortic valve area, 1.2±0.15 cm2) and preserved left ventricular ejection fraction. Patients were mostly (86.4%) asymptomatic or minimally symptomatic, 78.3% had hypertension, 36.2% were diabetics, and 48.3% had dyslipidemia. Each patient with MAS was matched for the average survival (per year) of all patients of the same age and same sex from our region (Somme department, north of France). During follow-up (median 47 months), 113 patients (22.2%) underwent aortic valve replacement for severe AS. The mean±SD time between inclusion and surgery was 37±22 months. During follow-up, 255 patients (50.2%) died. The 6-year survival of patients with MAS was lower than the expected survival (53±2% versus 65%). In multivariate analysis, age (hazard ratio, 1.04 [95% CI, 1.02-1.05]; P<0.001), prior atrial fibrillation (hazard ratio, 1.35 [95% CI, 1.05-1.73]; P=0.019), and Charlson comorbidity index (hazard ratio, 1.11 [95% CI, 1.05-1.18]; P=0.002) were associated with increased mortality. Aortic valve replacement was associated with better survival (hazard ratio, 0.38 [95% CI, 0.27-0.54]; P<0.001). Conclusions The results of this study show that patients with MAS present many cardiovascular risk factors, a high rate of surgery during follow-up, and increased mortality compared with the general population mainly related to associated comorbidities. Patients with MAS should, therefore, be managed for their cardiovascular risk factors and comorbidities. They require close follow-up, especially when the aortic valve area is close to 1 cm2, as aortic valve replacement performed when patients transition to severe AS and develop indications for surgery during follow-up is associated with better survival.

Dataset Information

Early Aortic Valve Replacement vs. Conservative Management in Asymptomatic Severe Aortic Stenosis Patients With Preserved Ejection Fraction: A Meta-Analysis.

Publications

Early Aortic Valve Replacement vs. Conservative Management in Asymptomatic Severe Aortic Stenosis Patients With Preserved Ejection Fraction: A Meta-Analysis.

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