Patient- and Process-Related Contributors to the Underuse of Aortic Valve Replacement and Subsequent Mortality in Ambulatory Patients With Severe Aortic Stenosis.
ABSTRACT: Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area [Formula: see text]1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08-0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; P=0.01), low-flow, low-gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06-0.21]), and low-gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08-0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38-4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9-130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low-gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.
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:Background The optimal threshold of left ventricular ejection fraction (LVEF) that should prompt aortic valve replacement (AVR) in asymptomatic patients with high-gradient severe aortic stenosis (AS) is controversial. The aim of this study was to assess the relationship between LVEF and mortality benefit in comparing early AVR versus watchful waiting in asymptomatic patients with severe AS. Methods and Results MEDLINE, Embase, Web of Science, and Google Scholar were searched for observational studies and randomized controlled trials on adults with asymptomatic severe AS. Severe AS was defined by a peak aortic velocity ≥4 m/s and/or mean aortic valve gradient ≥40 mm Hg and/or calculated aortic valve area <1.0 cm<sup>2</sup> or an indexed valve area <0.6 cm<sup>2</sup>. Studies comparing AVR with conservative management were included and meta-analysis on all-cause mortality was performed. Ten eligible studies were identified with a total of 3332 patients. In 5 observational studies comparing early AVR versus watchful waiting, our meta-analysis showed early AVR was associated with lower mortality with a hazard ratio (HR) of 0.41 (CI, 0.23-0.71; <i>P</i><0.01). In 4 observational studies comparing AVR versus no AVR, our meta-analysis showed AVR was associated with lower mortality with a HR of 0.31 (CI, 0.17-0.58; <i>P</i><0.001). In a meta-regression analysis pooling all 10 studies, there was no statistically significant correlation between study mean LVEF and the size of mortality benefit of AVR (<i>P</i>=0.83). Conclusions Among asymptomatic patients with high-gradient severe AS, AVR was associated with a mortality benefit across the spectrum of LVEF. Our study calls into question the need of an LVEF threshold for recommending AVR in this patient population.
Project description:Background No randomized comparison of early (ie, ?3 months) aortic valve replacement (AVR) versus conservative management or of transcatheter AVR (TAVR) versus surgical AVR has been conducted in patients with low-flow, low-gradient (LFLG) aortic stenosis (AS). Methods and Results A total of 481 consecutive patients (75±10 years; 71% men) with LFLG AS (aortic valve area ?0.6 cm<sup>2</sup>/m<sup>2</sup> and mean gradient <40 mm Hg), 72% with classic LFLG and 28% with paradoxical LFLG, were prospectively recruited in the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. True-severe AS or pseudo-severe AS was adjudicated by flow-independent criteria. During follow-up (median [IQR] 36 [11-60] months), 220 patients died. Using inverse probability of treatment weighting to address the bias of nonrandom treatment assignment, early AVR (n=272) was associated with a major overall survival benefit (hazard ratio [HR], 0.34 [95% CI, 0.24-0.50]; <i>P</i><0.001). This benefit was observed in patients with true-severe AS but also with pseudo-severe AS (HR, 0.38 [95% CI, 0.18-0.81]; <i>P</i>=0.01), and in classic (HR, 0.33 [95% CI, 0.22-0.49]; <i>P</i><0.001) and paradoxical LFLG AS (HR, 0.42 [95% CI, 0.20-0.92]; <i>P</i>=0.03). Compared with conservative management in the conventional multivariate model, trans femoral TAVR was associated with the best survival (HR, 0.23 [95% CI, 0.12-0.43]; <i>P</i><0.001), followed by surgical AVR (HR, 0.36 [95% CI, 0.23-0.56]; <i>P</i><0.001) and alternative-access TAVR (HR, 0.51 [95% CI, 0.31-0.82]; <i>P</i>=0.007). In the inverse probability of treatment weighting model, trans femoral TAVR appeared to be superior to surgical AVR (HR [95% CI] 0.28 [0.11-0.72]; <i>P</i>=0.008) with regard to survival. Conclusions In this large prospective observational study of LFLG AS, early AVR appeared to confer a major survival benefit in both classic and paradoxical LFLG AS. This benefit seems to extend to the subgroup with pseudo-severe AS. Our findings suggest that TAVR using femoral access might be the best strategy in these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01835028.
Project description: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 cm<sup>2</sup>) 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/m<sup>2</sup>; 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 <sub>with AVR</sub> /RR <sub>without AVR</sub> : 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR <sub>with AVR</sub> /RR <sub>without AVR</sub> : 1.19; 95% CI: 0.74-1.94).
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.
Project description:Background Aortic valve replacement (AVR) is a life-saving treatment for patients with symptomatic severe aortic valve stenosis. We sought to determine whether transcatheter AVR has resulted in a more equitable treatment rate by race in the United States. Methods and Results A total of 32 853 patients with symptomatic severe aortic valve stenosis were retrospectively identified via Optum's deidentified electronic health records database (2007-2017). AVR rates in non-Hispanic Black and White patients were assessed in the year after diagnosis. Multivariate Fine-Gray hazards models were used to evaluate the likelihood of AVR by race, with adjustment for patient factors and the managing cardiologist. Time-trend and 1-year symptomatic severe aortic valve stenosis survival analyses were also performed. From 2011 to 2016, the rate of AVR increased from 20.1% to 37.1%. Overall, Black individuals were less likely than Whites to receive AVR (22.9% versus 31.0%; unadjusted hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; fully adjusted HR, 0.76; 95% CI, 0.67-0.85). Yet, during 2015 to 2016, AVR racial differences were attenuated (29.5% versus 35.2%; adjusted HR, 0.86; 95% CI, 0.74-1.02) because of greater uptake of transcatheter AVR in Blacks than Whites (53.4% of AVRs versus 47.3%; P=0.128). Untreated patients had significantly higher 1-year mortality than those treated (adjusted HR, 0.57; 95% CI, 0.53-0.61), which was consistent by race (interaction P value=0.52). Conclusions Although transcatheter AVR has increased the use of AVR in the United States, treatment rates remain low. Black patients with symptomatic severe aortic valve stenosis were less likely than White patients to receive AVR, yet these differences have recently narrowed.
Project description:Current ESC and ACC/AHA guidelines for the management of valvular heart disease assign a class Ia indication for aortic valve replacement (AVR) only to patients with symptomatic severe aortic valve stenosis and asymptomatic patients with depressed left ventricular ejection fraction (LVEF <50%) or positive exercise test. We examined the long-term outcomes for patients undergoing AVR for aortic stenosis over a 11-year period at our institution compared to current international guidelines for AVR. Patients who had undergone isolated AVR for severe aortic valve stenosis between January 2001 and December 2012 were selected. The population was divided into subgroups based on preoperative LVEF (< or ?50%) and on presence/absence of symptoms (NYHA =I or ?II, respectively). We identified 607 patients with a median follow-up (FU) time of 5.75 years (IQR 3.24-8.00 years). The presence of symptoms did not have a significant impact on cardiovascular mortality (P=0.201). Patients with LVEF <50% displayed a higher long-term cardiovascular mortality rate (P=0.015). Multivariate analysis showed that preserved LVEF was a protective factor for asymptomatic patients (P=0.021), while preoperative LVEF did not affect the mortality rate in symptomatic patients (HR 0.88; 95% CI, 0.54-1.44). Correspondingly, asymptomatic patients with reduced LVEF were found to be at a higher risk of long-term mortality compared to the other groups (P=0.011). The only other independent risk factor for death was age (HR 6.46; 95% CI, 2.22-18.76). According to our data, current international class I indications for symptomatic patients ensure good long-term survival, while class I indications for asymptomatic patients with reduced LVEF are associated with poor long-term survival. Our results suggest that early surgery should also be considered also for asymptomatic patients with preserved LVEF, particularly in cases of very low operative risk.
Project description:Background:Minimally invasive surgical techniques pose alternatives to conventional surgery for the treatment of aortic stenosis (AS). We present a Bayesian network analysis comparing Valve Academic Research Consortium-2 clinical outcomes between transcatheter aortic valve implantation (TAVI), sutureless (SL-AVR) and conventional aortic valve replacement (CAVR). Methods:Electronic searches of databases were conducted and seven two-arm randomized-controlled trials and 25 propensity-score-matched studies comparing clinical outcomes of TAVI, SL-AVR and CAVR for treatment of AS were identified. Bayesian Markov chain Monte Carlo modelling was used to analyze clinical outcomes. Results:The analysis included 16,432 patients who underwent TAVI [7,056], SL-AVR [1,238] or CAVR [8,138]. Compared to CAVR, TAVI and SL-AVR were associated with reduced postoperative major bleeding of 59% (OR 0.41, 95% CI: 0.28-0.59) and 44% (OR 0.56, 95% CI: 0.30-0.99) respectively. TAVI had a 41% reduction in postoperative myocardial infarction (OR 0.59, 95% CI: 0.40-0.86) and SL-AVR had a 40% reduction in postoperative acute kidney injury (AKI) (OR 0.62, 95% CI: 0.42-0.86). Compared to TAVI, CAVR and SL-AVR had a reduction in moderate/severe paravalvular regurgitation of 89% (OR 0.11, 95% CI: 0.07-0.16) and 92% (OR 0.08, 95% CI: 0.03-0.17). CAVR had a 67% decreased postoperative permanent pacemaker (PPM) implantation compared to TAVI (OR 0.33, 95% CI: 0.24-0.45) and a 63% reduction compared to SL-AVR (OR 0.37, 95% CI: 0.22-0.61). There were no differences in 30-day mortality or postoperative stroke between the groups. Conclusions:In selected patients, minimally invasive surgical interventions including TAVI and SL-AVR for severe AS are viable alternatives to conventional surgery. However, TAVI is associated with increased paravalvular regurgitation, whereas TAVI and SL-AVR are associated with increased conduction disturbances compared to CAVR.
Project description:Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ?50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm<sup>2</sup>, N=645; group 2: 0.8 cm<sup>2</sup> ?AVA >0.6 cm<sup>2</sup>, N=465; and group 3: AVA ?0.6 cm<sup>2</sup>, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ?5 m/s or mean aortic pressure gradient ?60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5-year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56-3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01-1.78, P=0.04, respectively). Conclusions AVA ?0.6 cm<sup>2</sup> would be a useful marker to identify those high-risk patients with asymptomatic severe AS, who might benefit from early AVR. Clinical Trial Registration URL: www.umin.ac.jp . Unique identifier: UMIN000012140.
Project description:<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 early aortic valve replacement (AVR) or conservative care were included. The end points included all-cause mortality, cardiac mortality, and non-cardiac mortality. <b>Results:</b> 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, <i>P</i> < 0.00001; OR 0.12, 95% CI 0.02-0.62, <i>P</i> = 0.01; OR 0.36, 95% CI 0.21-0.63, <i>P</i> = 0.0003, respectively). <b>Conclusions:</b> Early AVR is preferable for asymptomatic severe AS patients with preserved ejection fraction.