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,
=0.018). Up to 2 years of follow-up, TAVR was not inferior to SAVR (HR, 1.08 95% CI, 0.89-1.31,
=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;
=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,
=0.001) but no statistically significant difference when we included only RCTs (HR, 0.89 95% CI, 0.69-1.16,
=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.
In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area ...(AVA) ≤1 cm2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated.
The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS).
One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVAProj), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis.
Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm2, and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVAProj ≤1 cm2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVAProj ≤1 cm2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003).
In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVAProj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis TOPAS; NCT01835028)
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Abstract
Objective
The aim of this study was to assess the impact of sex on the management and outcome of patients according to aortic stenosis (AS) severity.
Introduction
Sex differences in the ...management and outcome of AS are poorly understood.
Methods
Doppler echocardiography data of patients with at least mild-to-moderate AS aortic valve area (AVA) ≤1.5 cm2 and peak jet velocity (VPeak) ≥2.5 m/s or mean gradient (MG) ≥25 mmHg were prospectively collected between 2005 and 2015 and retrospectively analysed. Patients with reduced left ventricular ejection fraction (<50%), or mitral or aortic regurgitation >mild were excluded.
Results
Among 3632 patients, 42% were women. The mean indexed AVA (0.48 ± 0.17 cm2/m2), VPeak (3.74 ± 0.88 m/s), and MG (35.1 ± 18.2 mmHg) did not differ between sexes (all P ≥ 0.18). Women were older (72.9 ± 13.0 vs. 70.1 ± 11.8 years) and had more hypertension (75% vs. 70%; P = 0.0005) and less coronary artery disease (38% vs. 55%, P < 0.0001) compared to men. After inverse-propensity weighting (IPW), female sex was associated with higher mortality (IPW-HR: 1.91 1.14–3.22; P = 0.01) and less referral to valve intervention (competitive model IPW-HR: 0.88 0.82–0.96; P = 0.007) in the whole cohort. This excess mortality in women was blunted in concordant non-severe AS initially treated conservatively (IPW-HR = 1.03 0.63–1.68; P = 0.88) or in concordant severe AS initially treated by valve intervention (IPW-HR = 1.25 0.71–2.21; P = 0.43). Interestingly, the excess mortality in women was observed in discordant low-gradient AS patients (IPW-HR = 2.17 1.19–3.95; P = 0.01) where women were less referred to valve intervention (IPW-Sub-HR: 0.83 0.73–0.95; P = 0.009).
Conclusion
In this large series of patients, despite similar baseline hemodynamic AS severity, women were less referred to AVR and had higher mortality. This seemed mostly to occur in the patient subset with discordant markers of AS severity (i.e. low-gradient AS) where women were less referred to AVR.
Graphical Abstract
Compared to men, women with low-gradient aortic stenosis have a worse survival, which could be partly explained by a lower rate of aortic valve replacement in women. IPW-HR, inverse-probability weighted hazard ratio.
Aortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical ...and Doppler echocardiographic AS characteristics, has not been studied.
This study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment.
In 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women.
During follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, p < 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio HR: 1.75; 95% confidence interval CI: 1.04 to 2.92; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI.
This large-scale, multicenter outcomes study of quantitative Doppler echocardiographic and MDCT assessment of AS shows that measuring AVC load provides incremental prognostic value for survival beyond clinical and Doppler echocardiographic assessment. Severe AVC independently predicts excess mortality after AS diagnosis, which is greatly alleviated by AVI. Thus, measurement of AVC by MDCT should be considered for not only diagnostic but also risk-stratification purposes in patients with AS.
Objectives
Despite unusual high rates of patient–prosthesis mismatch (PPM), excellent midterm clinical outcomes have been reported after surgical aortic valve replacement (SAVR) with the Avalus™ ...bioprosthetic valve (Medtronic). To elucidate this “PPM conundrum,” the Avalus valve haemodynamics were assessed during exercise testing.
Methods
Of the 148 patients who had undergone SAVR with the Avalus valve at our institution, 30 were randomly selected among those in whom stress test was deemed feasible and underwent a resting transthoracic echocardiography immediately followed by exercise echocardiography. Severe PPM was defined as indexed effective orifice area (iEOA)
≤0.65 cm2/m2 and moderate PPM as iEOA
>0.65 and
≤0.85 cm2/m2. Measured PPM was determined with the use of the measured iEOA at rest or stress, while the estimated PPM was based on the estimated iEOA, derived from the mean EOA reported for each valve size in the manufacturer chart.
Results
Measured EOA significantly increased from rest to peak exercise in all PPM groups (p < .05) and the rates of moderate and severe measured PPM decreased from 40% and 20% to 27% and 0%, respectively. The patients with low‐flow state (flow < 250 ml/s) had significantly lower measured rest EOA (p = .03). On the basis of the estimated iEOA, there was no severe PPM and 19 patients had moderate PPM (63.3%), with a significantly lower opening reserve than the patients without estimated PPM (p = .04). The estimated iEOA was more reliably correlated to the measured iEOA at maximal stress than the measured iEOA at rest, especially in patients with a low‐flow state.
Conclusions
This study supports the concept of an opening reserve of the Avalus valve to explain the PPM conundrum and promotes the use of exercise Doppler‐echocardiography to complete the assessment of mismatch, especially in patients with a low‐flow state. Published estimated EOA seems reliable to predict the haemodynamic performance of the Avalus valve, whether the flow conditions at rest.
With concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent ...physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected.
Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies.
Patients (n = 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi >0.6 cm²/m², MG <40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm(2)/m(2), MG <40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MG ≥40 mm Hg).
The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p < 0.0001) and systemic arterial compliance (p < 0.0001). The AVC-load (median interquartile range) was similar within patients with DG (low-MG: 1,619 965 to 2,528 arbitrary units AU; high-MG: 1,736 1,209 to 2,894 AU; p = 0.49), higher than CG-moderate-AS (861 427 to 1,519 AU; p < 0.0001) but lower than CG-severe-AS (2,931 1,924 to 4,292 AU; p < 0.0001). The AVC-load thresholds separating severe/moderate AS were defined in CG-AS with normal flow (stroke-volume-index >35 ml/m(2)). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curve ≥0.89, sensitivity ≥86%, specificity ≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow.
Among patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients.
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.
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,
<0.001). At 20 years of follow-up, the survival rates were 19.5%, 12.1%, and 8.8% in patients with no, moderate, and severe PPM, respectively (moderate versus no PPM: HR, 1.09 95% CI, 1.06-1.11,
<0.001; severe versus no PPM: HR, 1.29 95% CI, 1.24-1.35,
<0.001). PPM was associated with higher risk of cardiac death, heart failure-related hospitalizations, and aortic valve reinterventions over time (
<0.001). Statistically significant associations between PPM and worse survival were observed regardless of valve type (bioprosthetic versus mechanical valves), contemporary PPM definitions unadjusted and adjusted for body mass index, and PPM quantification method (in vitro, in vivo, Doppler echocardiography). Our meta-regression analysis revealed that populations with more women tend to have higher HRs for all-cause death associated with PPM.
The results of the present study suggest that any degree of PPM is associated with poorer long-term outcomes following surgical aortic valve replacement and provide support for implementation of preventive strategies to avoid PPM after surgical aortic valve replacement.
The respective impacts of transvalvular flow, gradient, sex, and their interactions on mortality in patients with severe aortic stenosis undergoing surgical aortic valve replacement (AVR) are ...unknown.
This study sought to compare the impact of pre-operative flow-gradient patterns on mortality after AVR and to examine whether there are sex differences.
This study analyzed clinical, echocardiographic, and outcome data prospectively collected in 1,490 patients (544 women 37%), with severe aortic stenosis and preserved left ventricular ejection fraction who underwent AVR.
In this cohort, 601 patients (40%) had normal flow (NF) with high gradient (HG), 405 (27%) NF with low gradient (LG), 246 (17%) paradoxical low flow (LF)/HG, and 238 (16%) LF/LG. During a median follow-up of 2.42 years (interquartile range: 1.04 to 4.29 years), 167 patients died. Patients with LF/HG exhibited the highest mortality after AVR (hazard ratio HR: 2.01; 95% confidence interval CI: 1.33 to 3.03; p < 0.01), which remained significant after multivariate adjustment (HR: 1.96; 95% CI: 1.29 to 2.98; p < 0.01). Both LF/LG and NF/LG patients had comparable outcome to NF/HG (p ≥ 0.47). Optimal thresholds of stroke volume index were obtained for men (40 ml/m2) and women (32 ml/m2). Using these sex-specific cutpoints, paradoxical LF was independently associated with increased mortality in both women (adjusted HR: 2.05; 95% CI: 1.21 to 3.47; p < 0.01) and men (adjusted HR: 1.54; 95% CI: 1.02 to 2.32; p = 0.042), whereas guidelines’ threshold (35 ml/m2) does not.
Paradoxical LF/HG was associated with higher mortality following AVR, suggesting that a reduced flow is a marker of disease severity even in patients with HG aortic stenosis. Early surgical AVR (i.e., before gradient attains 40 mm Hg) might be preferable in these patients. Furthermore, the use of sex-specific thresholds (<40 ml/m2 for men and <32 ml/m2 for women) to define low-flow outperforms the guidelines’ threshold of 35 ml/m2 in risk stratification after AVR.
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