ABSTRACT: 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:<h4>Background</h4>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.<h4>Methods and results</h4>Patients treated by transcatheter aortic valve replacement were primarily separated into normal flow (NF; stroke volume index >35 mL/m<sup>2</sup>) and low flow (LF; stroke volume index ?35 mL/m<sup>2</sup>). 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 (<i>P</i>=0.041) and 3-year (<i>P</i><0.001) mortality. LF was an independent predictor of all-cause (hazard ratio, 1.29; 95% confidence interval, 1.03-1.62; <i>P</i>=0.03) and cardiovascular (hazard ratio, 1.37; 95% confidence interval, 1.06-1.77; <i>P</i>=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%) (<i>P</i>=0.001). However, surviving patients showed a similar improvement in symptoms regardless of aortic stenosis entity.<h4>Conclusions</h4>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: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: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:AIMS:We reported that patients with small aortic valve area (AVA) and low flow despite preserved left ventricular ejection fraction (LVEF), i.e. 'paradoxical' low flow (PLF), have worse outcomes compared with patients with normal flow (NF), although they generally have a lower mean gradient (MG). The aortic valve weight (AVW) excised at the time of valve replacement is a flow-independent marker of stenosis severity. The objective of this study was to compare the AVW of patients with PLF and MG<40 mmHg with the AVW of patients with NF and MG?40 mmHg. METHODS AND RESULTS:We recruited 250 consecutive patients undergoing valve replacement (Cohort A) for severe stenosis. Among them, 33 (13%) were in PLF [LVEF > 50% but stroke volume index (SVi) ? 35 mL/m(2)] with MG < 40 mmHg (PLF-LG group) and 105 (42%) were in NF (LVEF > 50% and SVi > 35 mL/m(2)) with MG ? 40 mmHg (NF-HG group). Despite a much lower MG (29 ± 7 vs. 53 ± 10 mmHg; P < 0.0001), patients in the PLF-LG group had a similar AVA (0.73 ± 0.12 vs. 0.69 ± 0.13; P = 0.19) compared with those in the NF-HG group. The AVW [median (interquartile): 1.90 (1.63-2.50) vs. 2.60 (1.66-3.32)] and prevalence of bicuspid phenotype (15 vs. 42%) were lower in the PLF-LG group than in the NF-HG group. However, AVWs analysed separately in the tricuspid and bicuspid valves were similar in both groups [tricuspid valves: 1.80 (1.63-2.50) vs. 2.30 (1.58-3.00) g; P = 0.26 and bicuspid valves: 2.72 (1.73-3.61) vs. 2.60 (2.10-3.55) g; P = 0.93]. When using cut-point values of AVW established in another series of non-consecutive patients (n = 150, Cohort B) with NF and concordant Doppler-echocardiographic findings, we found that the percentage of patients with evidence of severe stenosis in Cohort A was 70% in patients with PLF-LG and 86% in patients with NF-HG. CONCLUSION:The aortic valve weight data reported in this study provide evidence that a large proportion of patients with PLF and low-gradient have a severe stenosis and that the gradient may substantially underestimate stenosis severity in these patients. A multi-parametric approach including all Doppler-echocardiographic parameters of valve function as well as other complementary diagnostic tests may help correctly identify these patients.
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 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:Aortic stenosis (AS) is a disease of the valve and the myocardium. A correct assessment of the valve disease severity is key to define the need for aortic valve replacement (AVR), but a better understanding of the myocardial consequences of the increased afterload is paramount to optimize the timing of the intervention. Transthoracic echocardiography remains the cornerstone of AS assessment, as it is universally available, and it allows a comprehensive structural and hemodynamic evaluation of both the aortic valve and the rest of the heart. However, it may not be sufficient as a significant proportion of patients with severe AS presents with discordant grading (i.e., an AVA ? 1 cm<sup>2</sup> and a mean gradient <40 mmHg) which raises uncertainty about the true severity of AS and the need for AVR. Several imaging modalities (transesophageal or stress echocardiography, computed tomography, cardiovascular magnetic resonance, positron emission tomography) exist that allow a detailed assessment of the stenotic aortic valve and the myocardial remodeling response. This review aims to provide an updated overview of these multimodality imaging techniques and seeks to highlight a practical approach to help clinical decision making in the challenging group of patients with discordant low-gradient AS.
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: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 cm<sup>2</sup>. 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]; <i>P</i>=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; <i>P</i>=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:Objectives the exact timing of aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS) remains a matter of debate. Therefore, we described the natural history of asymptomatic patients with severe AS, and the effect of AVR on long-term survival. <b>Methods:</b> Asymptomatic patients who were found to have severe AS between June 2006 and May 2009 were included. Severe aortic stenosis was defined as peak aortic jet velocity Vmax ≥ 4.0 m/s or aortic valve area (AVA) ≤ 1 cm<sup>2</sup>. Development of symptoms, the incidence of AVR, and all-cause mortality were assessed. <b>Results:</b> A total of 59 asymptomatic patients with severe AS were followed, with a mean follow-up of 8.9 ± 0.4 years. A total of 51 (86.4%) patients developed AS related symptoms, and subsequently 46 patients underwent AVR. The mean 1-year, 2-year, 5-year, and 10-year overall survival rates were higher in patients receiving AVR compared to those who did not undergo AVR during follow-up (100%, 93.5%, 89.1%, and 69.4%, versus 92.3%, 84.6%, 65.8%, and 28.2%, respectively; <i>p</i> < 0.001). Asymptomatic patients with severe AS receiving AVR during follow-up showed an incremental benefit in survival of up to 31.9 months compared to conservatively managed patients (<i>p</i> = 0.002). <b>Conclusions:</b> The majority of asymptomatic patients turn symptomatic during follow-up. AVR during follow-up is associated with better survival in asymptomatic severe AS patients.