Effects of Aortic Valve Replacement on Severe Aortic Stenosis and Preserved Systolic Function: Systematic Review and Network Meta-analysis.
ABSTRACT: The survival benefits of aortic valve replacement (AVR) in the different flow-gradient states of severe aortic stenosis (AS) is not known. A comprehensive search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were conducted to identify studies that investigated the prognosis of severe AS (effective orifice area ?1.0?cm2) and left ventricular ejection fraction ?50%. Severe AS was stratified by mean pressure gradient [threshold of 40?mmHg; high-gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35?ml/m2; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted to assess all-cause mortality among each AS sub-type with rate ratio (RR) reported. The effects of AVR on prognosis were examined using network meta-regression. In the pooled analysis (15 studies and 9,737 patients), LF states (both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88; 95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS; and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR 1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred different survival benefits: it was most effective in NFHG (RR with AVR /RR without AVR : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR with AVR /RR without AVR : 1.19; 95% CI: 0.74-1.94).
Project description:An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS.
Project description:Among patients with severe aortic stenosis (AS) and preserved ejection fraction, those with low gradient (LG) and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification.We examined 1704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved ejection fraction (?50%) using 2-dimensional and Doppler echocardiography. Patients were stratified by stroke volume index (<35 mL/m(2) [low flow, LF] versus ?35 mL/m(2) [normal flow, NF]) and aortic gradient (<40 mm?Hg [LG] versus ?40 mm?Hg [high gradient, HG]) into 4 groups: NF/HG, NF/LG, LF/HG, and LF/LG. NF/LG (n=352, 21%), was associated with favorable survival with medical management (2-year estimate, 82% versus 67% in NF/HG; P<0.0001). LF/LG severe AS (n=53, 3%) was characterized by lower ejection fraction, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2-year estimate, 60% versus 82% in NF/HG; P<0.001). In multivariable analysis, the LF/LG pattern was the strongest predictor of mortality (hazard ratio, 3.26; 95% confidence interval, 1.71-6.22; P<0.001 versus NF/LG). Aortic valve replacement was associated with a 69% mortality reduction (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P<0.0001) in LF/LG and NF/HG, with no survival benefit associated with aortic valve replacement in NF/LG and LF/HG.NF/LG severe AS with preserved ejection fraction exhibits favorable survival with medical management, and the impact of aortic valve replacement on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure, and reduced survival, and aortic valve replacement was associated with improved survival. These findings have implications for the evaluation and subsequent management of AS severity.
Project description:Impaired left ventricular (LV) ejection fraction is a common finding in patients with aortic stenosis and serves as a predictor of morbidity and mortality after transcatheter aortic valve replacement. However, conflicting data on the most accurate measure for LV function exist. We wanted to examine the impact of LV ejection fraction, mean pressure gradient, and stroke volume index on the outcome of patients treated by transcatheter aortic valve replacement.Patients treated by transcatheter aortic valve replacement were primarily separated into normal flow (NF; stroke volume index >35 mL/m2) and low flow (LF; stroke volume index ?35 mL/m2). Afterwards, patients were divided into 5 groups: "NF-high gradient," "NF-low gradient" (NF-LG), "LF-high gradient," "paradoxical LF-LG," and "classic LF-LG." The 3-year mortality was the primary end point. Of 1600 patients, 789 (49.3%) were diagnosed as having LF, which was characterized by a higher 30-day (P=0.041) and 3-year (P<0.001) mortality. LF was an independent predictor of all-cause (hazard ratio, 1.29; 95% confidence interval, 1.03-1.62; P=0.03) and cardiovascular (hazard ratio, 1.37; 95% confidence interval, 1.06-1.77; P=0.016) mortality. Neither mean pressure gradient nor LV ejection fraction was an independent predictor of mortality. Patients with paradoxical LF-LG (35.0%), classic LF-LG (35.1%) and LF-high gradient (38.1%) had higher all-cause mortality at 3 years compared with NF-high gradient (24.8%) and NF-LG (27.9%) (P=0.001). However, surviving patients showed a similar improvement in symptoms regardless of aortic stenosis entity.LF is a common finding within the aortic stenosis population and, in contrast to LV ejection fraction or mean pressure gradient, an independent predictor of all-cause and cardiovascular mortality. Despite increased long-term mortality, high procedural success and excellent functional improvement support transcatheter aortic valve replacement in patients with LF severe aortic stenosis.
Project description:To assess left-ventricular strain parameters before and after transcatheter aortic valve replacement (TAVR) by feature tracking cardiac magnetic resonance imaging (FT CMR) and to correlate the findings to hemodynamic state and left-ventricular remodeling.Patients with symptomatic AS underwent FT CMR before and after TAVR. Patients were carefully evaluated by a comprehensive work-up including CMR, echocardiography and left and right heart catheterization. Thirty patients formed the study population. High-flow/high-gradient (HF/HG) aortic stenosis was diagnosed in 11 patients (36.7%), 6 patients (20.0%) exhibited low-flow/low-gradient AS (LF/LG) and 13 patients (43.3%) were classified to have so-called paradoxical low-flow/low-gradient (PLF/LG) AS. The HF/HG patients had a significantly reduced longitudinal strain which recovered after TAVR (-12.67 ± 4.60 to -15.46 ± 5.61%, p = 0.048). In the LF/LG group, an even more pronounced reduction of longitudinal strain and also an impairment of longitudinal velocity could be observed. Both parameters improved after therapy (strain: -5.06 ± 4.25 to -8.02 ± 3.28%, p = 0.045; velocity: 25.33 ± 9.63 to 37.13 ± 11.64 mm/s, p = 0.042). Patients with PLF/LG showed preserved longitudinal strain but a reduction of longitudinal velocity similar to the LF/LG group. These patients did not show a significant improvement of strain parameters after TAVR. Longitudinal velocity exhibited the highest predictive power for the identification of a low-flow state (sensitivity 75%, specificity 80%).Improvement of longitudinal strain parameters after TAVR is dependent on the initial hemodynamically defined AS subgroup.
Project description:Background Normal-flow, low-gradient severe aortic stenosis (NF-LG-SAS), defined by aortic valve area <1 cm2, mean gradient <40 mm Hg, and indexed stroke volume >35 mL/m2, is the most prevalent form of low-gradient aortic stenosis (AS). However, the true severity of AS and the management of NF-LG-SAS are controversial. The aim of this study was to evaluate the outcome of patients with NF-LG-SAS compared with moderate AS (MAS) and with high-gradient severe-AS (HG-SAS). Methods and Results A total of 154 patients with NF-LG-SAS, 366 with MAS (aortic valve area between 1.0 and 1.3 cm2), and 1055 with HG-SAS were included. On multivariate analysis, after adjustment for covariates of prognostic importance, NF-LG-SAS patients did not exhibit an excess risk of mortality compared with MAS patients under medical management (hazard ratio=1.13 [95% CI, 0.82-1.56]; P=0.45) and under medical and surgical management (hazard ratio 1.06 [95% CI, 0.79-1.43]; P=0.70), even after further adjustment for aortic valve replacement (hazard ratio=1.09 [95% CI, 0.81-1.48]; P=0.56). The 6-year cumulative incidence of aortic valve replacement (performed in accordance with guidelines) was comparable between the 2 groups (39±4% for NF-LG-SAS and 35±3% for MAS, P=0.10). After propensity score matching (n=226), NF-LG-SAS and MAS patients also had comparable outcomes under medical (P=0.41) and under medical and surgical management (P=0.52). NF-LG-SAS had better outcomes than HG-SAS patients (adjusted hazard ratio 1.84 [95% CI, 1.18-2.88]; P<0.001). Conclusions This study shows that patients with NF-LG-SAS have a comparable outcome to those with MAS when aortic valve replacement is performed during follow-up according to guidelines, mostly at the stage of HG-SAS. Rigorous echocardiographic assessment to rule out measurement errors and close follow-up are essential to detect progression to true severe AS in NF-LG-SAS.
Project description:Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p?=?0.003) and miRNA 133 (p?=?0.03). LF condition was associated with higher levels of miRNA1 (p?=?0.02) and miRNA21 (p?=?0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p?=?0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p?=?0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes.
Project description:OBJECTIVE:First-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis. METHODS:EF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ?2 m/s) between 2012 and 2014. Linear regression models were constructed to examine variables associated with EF1. Cox proportional hazards were used to determine the prognostic power of EF1 for aortic valve replacement (AVR, performed as part of clinical care in accordance with international guidelines) or death. RESULTS:Total follow-up of the 149 participants (69.8% male, 70 (65-76) years, mean gradient 33 (21-42) mm Hg) was 238?029 person-days. Sixty-seven participants (45%) had a low baseline EF1 (<25%) despite normal ejection fraction (67% (62%-71%)). Patients with low EF1 had more severe aortic stenosis (mean gradient 39 (34-45) mm Hg vs 24 (16-35) mm Hg, p<0.001) and more myocardial fibrosis (indexed extracellular volume (iECV) (24.2 (19.6-28.7) mL/m2 vs 20.6 (16.8-24.3)?mL/m2, p=0.002; late gadolinium enhancement (LGE) prevalence 52% vs 20%, p<0.001). Zva, iECV and infarct LGE were independent predictors of EF1. EF1 improved post-AVR (n=57 with post-AVR EF1 available, baseline 16 (12-24) vs follow-up 27% (22%-31%); p<0.001). Low baseline EF1 was an independent predictor of AVR/death (HR 5.6, 95% CI 3.4 to 9.4), driven by AVR. CONCLUSION:EF1 quantifies early, potentially reversible systolic dysfunction in aortic stenosis, is associated with global afterload and myocardial fibrosis, and is an independent predictor of AVR.
Project description:Background Blood pressure (BP) guidelines for patients with aortic stenosis or a history of aortic stenosis treated with aortic valve replacement (AVR) match those in the general population, but this extrapolation may not be warranted. Methods and Results Among patients enrolled in the Medtronic intermediate, high, and extreme risk trials, we included those with a transcatheter AVR (n=1794) or surgical AVR (n=1103) who were alive at 30 days. The associations between early (average of discharge and 30 day post-AVR) systolic BP (SBP) and diastolic BP (DBP) measurements and clinical outcomes between 30 days and 1 year were evaluated. Among 2897 patients, after adjustment, spline curves demonstrated an association between lower SBP (<120 mm Hg, representing 21% of patients) and DBP (<60 mm Hg, representing 30% of patients) and increased all-cause and cardiovascular mortality and repeat hospitalization. These relationships were unchanged when patients with moderate-to-severe aortic regurgitation post-AVR were excluded. After adjustment, compared with DBP 60 to <80 mm Hg, DBP 30 to <60 mm Hg was associated with increased all-cause (adjusted hazard ratio 1.62, 95% CI 1.23-2.14) and cardiovascular mortality (adjusted hazard ratio 2.13, 95% CI 1.52-3.00), but DBP 80 to <100 mm Hg was not. Similarly, after adjustment, compared with SBP 120 to <150 mm Hg, SBP 90 to <120 mm Hg was associated with increased all-cause (adjusted hazard ratio 1.63, 95% CI 1.21-2.21) and cardiovascular mortality (adjusted hazard ratio 1.81, 95% CI 1.25-2.61), but SBP 150 to <180 mm Hg was not. Conclusions Lower BP in the first month after transcatheter AVR or surgical AVR is common and associated with increased mortality and repeat hospitalization. Clarifying optimal BP targets in these patients ought to be a priority and may improve patient outcomes. Clinical Trial Registration Information URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01586910, NCT01240902.
Project description:To assess the change in peak oxygen consumption (pVO2) and determine its outcome predictors after aortic valve replacement (AVR) for aortic stenosis (AS).Patients with AS and preserved left ventricular ejection fraction who were referred for single AVR had cardiopulmonary exercise testing prior to and 9 months post-AVR. Predictors of outcome for pVO2 were determined by multivariate linear and logistic regression analyses. A significant change in pVO2 was defined as a relative change that was more than twice the coefficient of repeatability by test-retest (>10%).The pre-AVR characteristics of the 37 study patients included the following: median age (range) 72 (46-83) years, aortic valve area index (AVAI) 0.41 (SD 0.11) cm(2)/m(2), mean gradient (MG) 49.1 (SD 15.3) mm Hg and New York Heart Association (NYHA)≥II 27 (73%). Pre-AVR and post-AVR mean pVO2 was 18.5 and 18.4 mL/kg/m(2) (87% of the predicted), respectively, but the change from pre-AVR was heterogeneous. The relative change in pVO2 was positively associated with the preoperative MG (β=0.50, p=0.001) and negatively associated with brain natriuretic peptide > upper level of normal according to age and gender (β=-0.40, p=0.009). A relative increase in pVO2 exceeding 10% was found in 9 (24%), predicted by lower pre-AVR AVAI (OR 0.18; 95% CI 0.04 to 0.82, p=0.027) and lower peak O2 pulse (OR 0.94; 95% CI 0.88 to 0.99, p=0.045). Decreases in pVO2 exceeding 10% were found in 11 (30%) and predicted by lower MG (OR 0.93; 95% CI 0.86 to 0.99, p=0.033).Change in pVO2 was heterogeneous. Predictors of favourable and unfavourable outcomes for pVO2 were identified.
Project description:BACKGROUND:Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS:In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS:Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm?Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS:In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.