Pseudo-severe Aortic Stenosis Research Articles

Carotid Duplex Ultrasonography to Assess Severity of Low-Flow Low-Gradient Aortic Stenosis

BackgroundPatients with low-flow, low-gradient aortic valve stenosis constitute a substantial subset of all severe aortic stenosis patients. However, assessment of true severity of these patients can be challenging. In this analysis, we study the utility of the common carotid artery waveforms to distinguish true from pseudo-severe low-flow low-gradient aortic stenosis. MethodsThis is an observational analysis that included patients who underwent a transthoracic echocardiogram (TTE) and duplex carotid ultrasonography (DCUS) and had low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction (LVEF) on the index TTE (LVEF <50%, calculated aortic valve area [AVA] of ≤1.0 cm2, mean and peak gradient of <40 and <64 mm Hg, respectively, and stroke volume index <35 mL/m2). Patients were classified as pseudo-severe and true-severe aortic stenosis based on additional subsequent testing. Differences in various TTE and DCUS waveform parameters across the aortic valve and the common carotid artery were compared between the 2 groups. ResultsThe study included 30 patients (60 carotid arteries). Fifteen patients were categorized as pseudo-severe and 15 as true severe aortic stenosis. There were no significant differences in calculated AVA, LVEF, stroke volume/stroke volume index, and Doppler Velocity Index in the 2 groups. Mean and peak gradient were higher in patients with true-severe aortic stenosis. Carotid acceleration time (cAT) was significantly prolonged in patients with true-severe compared with pseudo-severe aortic stenosis. A cAT ≥80 ms was 83.3% sensitive and 83.3% specific for true-severe aortic stenosis. ConclusioncAT acceleration time may be used to distinguish true from pseudo-severe low-flow, low-gradient aortic valve stenosis.

Dobutamine stress echocardiography in low-gradient aortic stenosis

Abstract Background Dobutamine stress echocardiography (DSE) is recommended to distinguish between true-severe and pseudo-severe aortic stenosis (AS) in patients with low flow low-gradients and left ventricular ejection fraction (LVEF) &amp;lt;50%. However, DSE has mostly been tested in the setting of LVEF&amp;lt;35%. Purpose The purpose of this study was to examine the diagnostic accuracy of DSE according to aortic valve calcification (AVC) score, in patents with low-flow, low-gradient AS across a wide range of LVEF. Methods Patients with aortic mean gradient &amp;lt;40 mmHg, aortic valve area (AVA) &amp;lt;1.0 cm2, and stroke volume index (SVi) ≤35 mL/m2 undergoing DSE were identified from three prospectively collected patient cohorts, and stratified according to LVEF; &amp;lt;35%, 35-50% and &amp;gt;50%. Severe AS was defined as AVC score ≥2000 AU among men, and ≥1200 AU for women. Recommendation for severe AS according to DSE, are an AVA &amp;lt;1.0 cm2 combined with an aortic mean gradient ≥40 mmHg or peak velocity ≥4 m/s. Receiver operating characteristic curves for DSE-derived AVA, mean gradient and Vmax were used to identify optimal cut-off points for each LVEF subgroup. Results Of the 221 patients included in the study, 78 (35%) presented with LVEF &amp;lt;35%, 67 (30%) with LVEF 35-50%, and 76 (34%) with LVEF &amp;gt;50%. Baseline characteristics are presented in the table. Based on AVC, severe AS was present in 102 (46%) of patients. Using recommended thresholds for severe AS for AVC and DSE, led to a sensitivity of 49%, a specificity of 84% and an accuracy of 67% for DSE for all patients with LVEF &amp;lt;50%, but with significant heterogeneity between groups figure. AVA performed rather uniformly across LVEF subgroups; (AUC =0.68 vs 0.62 vs 0.54, p=0.36) LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50% respectively and displayed a rather uniform optimal cut-off (1.0 cm2 vs 0.9 cm2 vs 0.8 cm2). However, mean gradient and Vmax during DSE, both showed significantly diagnostic heterogeneity across LVEF groups (AUC= 0.90 vs 0.67 vs 0.65, p=&amp;lt;0.001 and AUC= 0.90 vs 0.66 vs 0.60, p=&amp;lt;0.001) with different optimal thresholds (30 mmHg &amp; 3.8 m/s, 45 mmHg &amp; 4.3 m/s and 37mmHg &amp; 4 m/s, LVEF&amp;lt;35%, LVEF 35-50%, LVEF&amp;gt;50%, respectively). Conclusion Our study shows, that the association between DSE gradients and AS severity assessed by AVC demonstrates important heterogeneity depending on LVEF. While DSE had the highest accuracy in patients with LVEF&amp;lt;35% both patients with LVEF 35-50%, and patients with LVEF&amp;gt;50% showed significantly less concordance between DSE and AVC.

Dobutamine stress echocardiography remains indispensable for the diagnosis of low-flow low-gradient severe aortic stenosis

Abstract Background In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, current guidelines recommend dobutamine stress echocardiography (DSE) to determine valve stenosis severity. Additionally, aortic valve calcification (AVC) scores are also used with this intent. Previous studies have determined cut-off values of ≥2000AU for men and ≥1200AU for women to distinguish between true severe AS and pseudosevere AS. Purpose To assess the relationship between AVC and DSE in low-flow low-gradient aortic stenosis. Methods We performed a multicenter international registry study including patients that underwent DSE to determine AS severity and multi-slice computed tomography (MSCT) of sufficient quality to determine AVC scores. Severe AS was diagnosed when resting peak aortic valve velocity was ≥4.0 m/s, or stress aortic valve area (AVA) remained &amp;lt;1.0cm2 at peak dobutamine stress levels; moderate AS was diagnosed when resting AVA was ≥1.0cm2 and peak velocity was &amp;lt; 4.0m/s or stress AVA exceeded 1.0cm² at peak stress. Using the previous cut-off values, MSCT-AVC scores were compared to DSE-derived AS diagnoses to determine sensitivity and specificity of AVC, and the positive and negative predictive values of high and low scores. Subsequently, we performed a receiver-operating characteristics (ROC)-curve analysis for men and women separately. Results We included 271 patients from 8 centers, of which 231 patients had sufficiently interpretable DSE and MSCT. Median age was 79 years (Interquartile range (IQR): 71-84), median BMI was 26.4 kg/m2 (IQR: 24.1-30.0) and median BSA was 1.9 m2(IQR: 1.8-2.1). Left ventricular ejection fraction was reduced (&amp;lt;50%) in 209 (90.5%) patients. Bicuspid valve morphology was present in 20 patients (8.7%). DSE confirmed severe AS in 103 patients, 4 of whom already had resting peak aortic valve velocity ≥4.0m/s. Moderate AS was diagnosed in 128 patients, of which 76 had a resting AVA ≥ 1.0cm2. Characteristics of these patients are summarized the table. Of the patients with severe AS, 49 (47.6%) had a high AVC score (≥2000 for men or ≥1200 for women) and of patients with moderate AS, 75 (58.6%) had an AVC score below those cut-off values. This corresponds to a sensitivity of 47.6%, a specificity of 58.4% and positive and negative predictive values of 53.5% and 51.6%, respectively. The ROC-curves are shown in the figure; the area under the curve was 0.55 for men and 0.52 for women, signifying poor discriminative performance. Conclusion In this multicenter international registry we found that aortic valve calcification scores correlated poorly with AS severity and therefore DSE remains the preferred technique to assess borderline AS severity.Table.Patient characteristicsFigure.ROC curve

Risk prediction in patients with classical low-flow, low-gradient aortic stenosis undergoing surgical intervention.

Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR. This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm2, mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated. All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p = 0.038), while there was no difference in mortality regarding FR status (log-rank p = 0.114). In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

Transcatheter Aortic Valve Replacement in Patients With Reduced Ejection Fraction and Nonsevere Aortic Stenosis.

The potential benefit of transcatheter aortic valve replacement (TAVR) in patients with nonsevere aortic stenosis (AS) and heart failure is controversial. This study aimed to assess outcomes of patients with nonsevere low-gradient AS (LGAS) and reduced left ventricular ejection fraction undergoing TAVR or medical management. Patients undergoing TAVR for LGAS and reduced left ventricular ejection fraction (<50%) were included in a multinational registry. True-severe low-gradient AS (TS-LGAS) and pseudo-severe low-gradient AS (PS-LGAS) were classified according to computed tomography-derived aortic valve calcification thresholds. A medical control group with reduced left ventricular ejection fraction and moderate AS or PS-LGAS was used (Medical-Mod). Adjusted outcomes between all groups were compared. Among patients with nonsevere AS (moderate or PS-LGAS), outcomes after TAVR and medical therapy were compared using propensity score-matching. A total of 706 LGAS patients undergoing TAVR (TS-LGAS, N=527; PS-LGAS, N=179) and 470 Medical-Mod patients were included. After adjustment, both TAVR groups showed superior survival compared with Medical-Mod patients (all P<0.001), while no difference was found between TS-LGAS and PS-LGAS TAVR patients (P=0.96). After propensity score-matching among patients with nonsevere AS, PS-LGAS TAVR patients showed superior 2-year overall (65.4%) and cardiovascular survival (80.4%) compared with Medical-Mod patients (48.8% and 58.5%, both P≤0.004). In a multivariable analysis including all patients with nonsevere AS, TAVR was an independent predictor of survival (hazard ratio, 0.39 [95% CI, 0.27-0.55]; P<0.0001). Among patients with nonsevere AS and reduced left ventricular ejection fraction, TAVR represents a major predictor of superior survival. These results reinforce the need for randomized-controlled trials comparing TAVR versus medical management in heart failure patients with nonsevere AS. URL: https://www. gov; Unique identifier: NCT04914481.

Appropriate Use Criteria for the Management of Aortic Stenosis: Insight From the Japanese Expert Panel

BackgroundThe indication for transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) significantly varies among physicians and institutions. ObjectivesThis study aims to develop a set of appropriate use criteria for AS management to assist physicians in decision-making. MethodsThe RAND-modified Delphi panel method was used. A total of >250 common clinical scenarios were identified in terms of whether to perform the intervention for AS and the mode of intervention (surgical aortic valve replacement vs TAVR). Eleven nationally representative expert panelists independently rated the clinical scenario appropriateness on a scale of 1-9, as “appropriate” (7-9), “may be appropriate” (4-6), or “rarely appropriate” (1-3); the median score of the 11 experts was then assigned to an appropriate-use category. ResultsThe panel identified 3 factors that were associated with a rarely appropriate rating in terms of performing the intervention: 1) limited life expectancy; 2) frailty; and 3) pseudo-severe AS on dobutamine stress echocardiography. Clinical scenarios that were deemed rarely appropriate for TAVR were also identified: 1) patients with low surgical risk and high TAVR procedural risk; 2) patients with coexistent severe primary mitral regurgitation or rheumatic mitral stenosis; and 3) bicuspid aortic valve that was not suitable for TAVR. Importantly, any TAVRs for patients who were older than 75 years of age were not rated as rarely appropriate. ConclusionsThese appropriate use criteria provide a practical guide for physicians regarding clinical situations commonly encountered in daily practice and elucidates scenarios deemed rarely appropriate that are clinical challenges for TAVR.

The diagnostic role of "acceleration time" measurement in patients with classical low flow low gradient aortic stenosis with reduced left ventricular ejection fraction.

In our study, we aimed to assess the role of acceleration time (AT), ejection time (ET), and AT/ET ratio to distinguish between true and pseudo severe AS in patients with classical low flow-low gradient (LF-LG) aortic stenosis (AS) with reduced left ventricular ejection fraction (LVEF). Sixty-seven classical LF-LG AS with reduced LVEF patients who underwent dobutamine stress echocardiography (DSE) were included in the study. According to DSE results, all patients were divided into two groups; true AS and pseudo severe AS. Aortic valve calcium score was measured in patients with inconclusive DSE results. AT and other ejection dynamics (ET and AT/ET) were calculated by taking baseline echocardiographic records into account for all patients. The predictive power of AT and other ejection dynamics were evaluated to estimate true and pseudo severe AS. According to DSE results, out of 67 patients, 44 (65.7%) was diagnosed as true severe AS. There was a statistically significant relation between baseline AT and true AS [adjusted OR 4.47 (95% CI 1.93-10.4), p = 0.001]. The best cutoff value of AT was measured as 100 msec according to the Youden index. This value had a sensitivity value of 77%, specificity value of 87%, positive predictive value of 92%, and a negative predictive value of 67%. The measurement of AT can predict the DSE outcome and can be used for diagnostic purposes to distinguish between true and pseudo severe AS in classical LF-LG AS patients with reduced LVEF.

Abstract 12136: Multiple Blood Biomarker Approach for Risk Stratification in Patients With Low-Flow Low-Gradient Aortic Stenosis

Background and Objectives: Previous studies have shown that a multiple blood biomarker strategy prior to aortic valve replacement (AVR) may be useful for risk stratification in patients undergoing surgical AVR (SAVR). The usefulness of this approach in patients with low-flow low-gradient aortic stenosis (LF-LG AS) has not been examined. The objective of this study was to determine the prognostic value of combined measures of multiple blood biomarkers in patients with LF-LG AS treated conservatively or by AVR. Methods: 168 patients were prospectively enrolled in the TOPAS (Truly or Pseudo-severe Aortic Stenosis) study at our institute. Clinical and echocardiographic data were collected for each patient. Eight biomarkers of myocardial stress, inflammation, renal function (brain natriuretic peptide, creatine kinase-mb, interleukin-6, alanine transaminase, lactate dehydrogenase, alkaline phosphatase, procalcitonin, ferritin) were measured from blood samples collected at baseline. The cohort was divided into 3 groups according to the number of elevated biomarkers. Uni- and multivariable survival analyses were performed to evaluate the association between the number of elevated biomarkers and all-cause mortality. Results: Mean age was 73 years (68% male). After a median follow-up of 3.41 years, 69 (35%) patients died. Patients with 0-3, 4-6, and &gt;6 elevated biomarkers had 8 years survival estimates of 75%, 52%, and 19%, respectively (log-rank p&lt;0.0001). Using multivariable Cox analysis adjusted for age, sex, BMI, AVR as a time-dependent variable, renal function and STS score, patients with &gt;6 elevated biomarkers had an increased risk of all-cause mortality as compared to the group of patients with 0-3 elevated biomarkers (referent group), HR=3.82, p&lt;.0001, and as compared to the group of patients with 4-6 elevated biomarkers HR=2.81, p&lt;.0001. There was no significant difference in all-cause mortality between patients with 4-6 elevated biomarkers and the referent group p=0.38. Conclusion: In this series of patients with LF-LG AS, a higher number of elevated biomarkers was associated with an increased rate of mortality. These results suggest that a multiple blood biomarkers approach may be useful to enhance the risk stratification in this cohort.

Increasing transvalvular flow with passive leg rise as an add-on to dobutamine in patients with paradoxical low-flow, low-gradient aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Gottfried und Julia Bangerter-Rhyner Foundation Background Projected aortic valve area (AVA), used in case of low-flow, low-gradient aortic stenosis is reliable if the transvalvular flow can be substantially augmented. Moreover it depends on the calculated valve compliance, which should remain constant, irrespective of the change in transvalvular flow. Methods We prospectively compared 3 different stress methods to increase transvalvular flow in patients with low-flow, low-gradient aortic stenosis: maximal dobutamine infusion rate ("Dmax"), passive leg-raise ("PLR") and the combination of the two ("Dmax + PLR") with the velocity time integral (VTI) method. The primary endpoint was the percentage of patients with ΔQ ≥20%. The percentage of patients with the pseudosevere classification and the mean slope between transvalvular flow and AVA - corresponding to the valve compliance - for each stress methods were the secondary endpoints. Results "Dmax + PLR" yielded the highest percent of patient with Δtransvalvular flow ≥20% implying the highest validity to the projected AVA between all the stress methods. In the "Paradox" group (LVEF ≥50%, n = 25), the percentage of patients classified as pseudosevere aortic stenosis was the lowest using "Dmax + PLR". This was also the case in the "lowEF" group with the Simpson’s method (LVEF &amp;lt;50%, n = 20). The mean slope of Q with respect to AVA consistently decreased with higher Δtransvalvular flow. Conclusion Projected AVA was obtained with the highest reliability with the "Dmax + PLR" stress method. This same stress method yielded the lowest percentage of classification in pseudosevere in the "Paradox" group. This implies that the valve compliance, capturing the relationship between transvalvular flow and AVA might be non-constant and rather inversely proportional to translvalvular flow. Abstract Figure. Echo parameters and classification Abstract Figure. Projected AVA and valve compliance

Ejection dynamics in native aortic valve stenosis using echocardiography: can it be helpful?

Abstract Background The assessment of aortic stenosis (AS) severity has a major impact on the management of affected patients. Ejection dynamics, including acceleration time (AT), ejection time (ET), and acceleration time/ejection time ratio (AT/ET) measured using doppler echocardiography are established in the evaluation of prosthetic aortic valve stenosis with high sensitivity and specificity. However, their clinical utility in native AS has not been well described. Purpose The aim of this systematic review was to evaluate the diagnostic accuracy of ejection dynamics to identify severe AS and to assess whether ejection dynamics can differentiate low flow, low gradient severe AS from pseudo-severe AS. Methods We conducted a systematic review of Medline, Embase, and Web of Science from database inception until January 2021. We included observational studies and randomized controlled trials (RCTs) in which the diagnostic accuracy of ejection dynamics by doppler echocardiography for severe AS was compared with standard echocardiographic diagnostic criteria including peak velocity, mean pressure gradient, aortic valve area, and dimensionless index. Studies were eligible if they included AS of at least mild severity. Two authors independently screened and extracted data. Results We included 12 studies in the review (RCT=1, observational=11) with a total of 5182 participants. There was significant inconsistency in outcome measurement and reporting of results therefore a meta-analysis was not suitable. We used narrative synthesis to report our results. All included studies used standard echocardiographic criteria to ascertain the presence of severe AS. Mean age was 72 years and 53% of the participants were male. 1983 participants (38.3%) were classified as having severe AS. AT &amp;gt;94–109ms had sensitivity of 74–92% and specificity of 72–89% at identifying severe AS. AT/ET &amp;gt;0.34–0.35 showed sensitivity of 67–77% and specificity of 68–100%. Only one study compared low-flow, low-gradient AS with pseudo-severe AS, showing that an AT &amp;gt;100ms had sensitivity 62%, specificity 76%; and AT/ET &amp;gt;0.33, sensitivity 65%, specificity 84%. Data for ET showed insufficient consistency and diagnostic accuracy. Conclusions AT and AT/ET may be useful to corroborate the presence of severe AS. However, more research is needed to understand whether these parameters add incremental prognostic value to standard echocardiographic measures of AS severity. Funding Acknowledgement Type of funding sources: None. Summary of evidence search and selection

Diagnostic and Prognostic Accuracy of Aortic Valve Calcium Scoring in Patients With Moderate-to-Severe Aortic Stenosis.

Background: Assessing the true severity of aortic stenosis (AS) remains a challenge, particularly when echocardiography yields discordant results. Recent European and American guidelines recommend measuring aortic valve calcium (AVC) by multidetector row computed tomography (MDCT) to improve this assessment.Aim: To define, using a standardized MDCT scanning protocol, the optimal AVC load criteria for truly severe AS in patients with concordant echocardiographic findings, to establish the ability of these criteria to predict clinical outcomes, and to investigate their ability to delineate truly severe AS in patients with discordant echocardiographic AS grading.Methods and Results: Two hundred and sixty-six patients with moderate-to-severe AS and normal LVEF prospectively underwent MDCT and Doppler-echocardiography to assess AS severity. In patients with concordant AS grading, ROC analysis identified optimal cut-off values for diagnosing severe AS using different AVC load criteria. In these patients, 4-year event-free survival was better with low AVC load (60–63%) by these criteria than with high AVC load (23–26%, log rank p < 0.001). Patients with discordant AS grading had higher AVC load than those with moderate AS but lower AVC load than those with severe high-gradient AS. Between 36 and 55% of patients with severe LG-AS met AVC load criteria for severe AS. Although AVC load predicted outcome in these patients as well, its prognostic impact was less than in patients with concordant AS grading.Conclusions: Assessment of AVC load accurately identifies truly severe AS and provides powerful prognostic information. Our data further indicate that patients with discordant AS grading consist in a heterogenous group, as evidenced by their large range of AVC load. MDCT allows to differentiate between truly severe and pseudo-severe AS in this population as well, although the prognostic implications thereof are less pronounced than in patients with concordant AS grading.

Diagnosis and management of low-flow, low-gradient aortic stenosis

The severity of low-flow, low-gradient aortic stenosis cases continue to be misunderstood because of challenging diagnosis, and treatment remains complex. We discuss current diagnostic and treatment modalities for low-flow, low-gradient aortic stenosis. This article summarizes current guidelines and best practices for the management of low-flow, low-gradient aortic stenosis. Low-flow, low-gradient aortic stenosis is a difficult entity to diagnose and treat. Various diagnostic modalities are needed to accurately determine the severity of aortic stenosis and potential treatment benefit. True-severe classical and paradoxical low-flow, low-gradient aortic stenosis can be distinguished from pseudo-severe aortic stenosis by dobutamine stress echocardiography and/or multidetector computed tomography. Once the distinction is made, aortic valve replacement results in better outcomes compared with conservative management. Although both surgical and transcatheter aortic valve replacement result in adequate outcomes, the decision between the two treatment strategies is based on patient characteristics, valve morphology, and other risk factors.

P1303 Pseudo-severe aortic stenosis due to mechanical dyssynchrony in a patient with low contractile reserve

Abstract Introduction Aortic stenosis characterization in patients with low flow – low gradient stenosis (LF-LG) and reduced left ventricular (LV) ejection fraction (EF) is challenging. In this subgroup, pseudo- severe stenosis should be properly identified, as these patients are treated conservatively with heart failure therapy. Its identification relies mainly on preserved contractile reserve seen during dobutamine echocardiography. We present a patient with low contractile reserve and pseudo-severe stenosis due to mechanical dyssynchrony. Case presentation 83-years old patient with ischemic heart disease and chronic kidney disease was admitted to our department due to progressive exertional dyspnea. In 2014 he underwent dual-chamber pacemaker (PM) implantation due to sick sinus syndrome and was programmed to asynchronous pacing mode (VVI mode) in 2016 as atrial electrode dysfunction was observed. Coronary angiogram was normal. Echocardiography showed enlarged left ventricle (LV EDV 180 ml), reduced EF (33%) and signs of mechanical dyssynchrony. Peak aortic valve velocity was 2.5 m/s, mean pressure gradient (MPG) 13 mmHg and AVA 1.0 cm2. Stroke volume was reduced (SVI 28 ml/m2). LF-LG aortic stenosis was suspected. Stress echocardiography using dobutamine at peak infusion of 15 mcg/kg/min showed low contractile reserve (EF 37%, SVI 33 ml/m2) with no significant changes in aortic valve parameters (MPG 29 mmHg, AVA 0.9 cm2). However, significant masurement disparity was noted and at least partly contributed to atrio-ventricular (A-V) and inter-ventricular dyssynchrony because of asynchronous VVI pacing. To overcome A-V and intraventricular dyssynchrony we decided for atrial lead reposition and upgrade to cardiac resynchronization therapy (CRT-P). After six months of CRT, normalization of EF and improvement of exercise capacity were observed. Furthermore, additional evaluation of aortic valve showed only moderate stenosis (peak velocity 2,8 m/s, MPG 18 mmHg and AVA 1.4 cm2). Stroke volume was normal (SVI 48 ml/m2). Consequently, we postponed potential surgical or interventional treatment of the aortic valve. Conclusion Considerable LV mechanical dyssynchrony could interfere with determining the severity of aortic stenosis. As demonstrated in the present case report, special considerations should be taken in patients with notable LV dyssynchrony and low contractile reserve as it may not be overcome with dobutamine stress echocardiography as recommended by the current guidelines.

P6483Predictors of contractile reserve on dobutamine stress echocardiography in patients with classical low-flow, low-gradient aortic stenosis

Abstract Background There is a lack of information on factors that influence contractile reserve (CR) on dobutamine stress echocardiography (DSE) in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS). Purpose This study sought to evaluate the predictors of CR in patients with LFLG-AS. Methods Prospective study including 43 consecutive LFLG-AS patients (aortic valve area [AVA] ≤1.0 cm2, mean transaortic gradient &lt;40 mmHg, left ventricular ejection fraction [LVEF] &lt;50%) with true severe aortic stenosis. All patients underwent dobutamine stress echocardiography and T1-mapping cardiac magnetic resonance (CMR). CR was defined as an increase ≥20% in the left ventricular stroke volume at peak stress. Patients with pseudo-severe aortic stenosis were excluded. Results All of the patients in the study had degenerative aortic stenosis, with a median age of 67 [60–74] years, most of them being male (83.7%). A high prevalence of comorbidities was found, highlighted by diabetes (42%), hypertension (70%), atrial fibrillation (25%) and coronary artery disease (38%). Mean transaortic gradient was 25 [20–33] mmHg, AVA was 0.88 [0.68–0.95] cm2, LVEF was 35 [28–43]% and 32.6% had moderate/severe functional mitral regurgitation. CMR myocardium extracellular volume fraction (ECV) was 28.8 [26.3–33.0] %, indexed ECV was 35.4 [25.0–41.2] ml/m2, 32.6% had positive transmural delayed-enhancement images and 25.6% had positive mesocardial delayed-enhancement images. On DSE, 30 patients (69.7%) had CR and 13 patients (30.3%) had no CR. Global longitudinal strain was 10 [7–12] %, Δ indexed flow rate was 25 [3–38] ml/m2.seg and Δ mean gradient was 10 [3–16] mmHg. By multivariate analysis, moderate/severe functional mitral regurgitation (HR 0.122, 95% CI 0.020–0.759, p=0.024) and AVA (HR 0.606, 95% CI 0.396–0.925, p=0.020 [for each increase of 0.05 cm2]) were the only factors associated with CR. ECV, indexed ECV and positive transmural or mesocardial delayed-enhancement images were not associated with CR in the univariate analysis. Conclusions In our study, the absence of moderate/severe functional mitral regurgitation and AVA were predictors of CR on DSE in patients with LFLG-AS. As AVA was smaller in patients with CR, our finding contradicts the hypothesis that more severe aortic stenosis could also contribute to the lack of CR. Other possible factors that are surrogate of myocardium fibrosis, as ECV, indexed ECV and positive delayed-enhancement images, were not associated with the absence of CR. Acknowledgement/Funding FAPESP

Imaging Strategies for Evaluating Low-Flow, Low-Gradient Aortic Stenosis with Reduced and Preserved Left Ventricular Ejection Fraction.

Aortic stenosis (AS) is one of the most common valvular heart diseases, and aortic valve replacement (AVR) provides both symptomatic and survival benefit in symptomatic severe AS patients. The purpose of this review is to discuss low-flow low-gradient AS which is still a challenging diagnostic entity. Thirty-forty percent of patients with AS have low flow which makes it difficult to differentiate truly severe AS that benefits from AVR compared to pseudo-severe AS which is currently managed conservatively. Patients with low-flow low-gradient AS (LF-LG AS) include those with reduced left ventricular systolic function (classical LF-LG AS) and those with preserved left ventricular systolic function (paradoxical LF-LG AS). Low-dose dobutamine stress echocardiography (DSE) helps to identify truly severe stenosis in patients with classical LF-LG AS. Aortic valve calcium scoring with multidetector computed tomography plays a major role in patients with paradoxical LF-LG AS and also among classical LF-LG AS patients who have reduced contractile reserve on DSE. This article will provide an overview of imaging strategies for evaluating LF-LG AS with reduced and preserved left ventricular ejection fraction.

Aortic Valve Replacement is Superior to Conservative Management in Low-Flow, Low-Gradient Aortic Stenosis independently of the presence of true severe stenosis

The survival benefit of surgical (SAVR) or transcatheter (TAVR) aortic valve replacement over conservative management (ConsRx) remains unclear in patients with low-flow, low-gradient (LFLG) aortic stenosis (AS). 476 LFLG AS patients (mean age 75 ± 10 yo, 71% males, 71% classical and 29% paradoxical LFLG, aortic valve area = 0.79 ± 0.15 cm 2 and mean gradient = 26 ± 7 mmHg) were prospectively recruited. Survival was studied using Kaplan-Meier curves. Inverse probability-of-treatment-weighting (IPW) was used to balance patients’ characteristics between AVR and ConsRx groups. Cox proportional hazards regression was used to corroborate the findings and study the benefit associated with of SAVR, TAVR (including transfemoral and transapical accesses). During a median follow up of 32 months, 220 patients died and less than 5% were lost to follow up. AVR markedly reduced the risk of death ( Fig. 1 , Panel A). Interestingly, the benefit extended also to patients with pseudosevere AS ( Fig. 1 , Panel B). These results were consistent with non-weighted univariate and multivariate analyses. TAVR patients had significantly more comorbidities compared to ConsRx or SAVR patients, including older age, previous myocardial infarction, diabetes, renal failure, and more depressed left ventricular function as assessed by NT-proBNP (all with P < 0.05); all of these factors independently associated with increased mortality. After adjustment for these comorbidities and AS severity, TAVR was associated with a lower risk of mortality compared to ConsRx (HR = 0.40; 95%CI [0.22–0.71], P = 0.002), and a similar risk compared to SAVR (HR = 0.83, 95%CI [0.46–1.51], P = 0.52). There was no interaction ( P = 0.93) between treatment and the pattern of LFLG (paradoxical vs classical) with mortality. SAVR and TAVR were associated with better survival compared to ConsRx in both classical and paradoxical LFLG AS patients. The benefit extended to those with pseudosevere AS.

A Better Way to Predict Outcome in Low-Flow Aortic Stenosis

Distinguishing between true severe aortic stenosis (AS) and pseudo-severe AS in patients with low gradient, low left ventricular ejection fraction

B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin for Risk Stratification in Low-Flow, Low-Gradient Aortic Stenosis: A Substudy of the TOPAS Study

ObjectivesThe objective of this study was to determine the prognostic value of combined measures of B-type natriuretic peptide (BNP) and high-sensitivity cardiac troponin T (hsTnT) in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) who had either a preserved or reduced left ventricular ejection fraction (LVEF). BackgroundAn elevated BNP level is associated with increased risk of mortality in patients with LF-LG AS. The incremental prognostic value of hsTnT in these patients is unknown. MethodsNinety-eight patients (74 ± 10 years; 75% men) with LF-LG AS (LVEF <50% and/or stroke volume index <35 ml/m2, mean gradient <40 mm Hg, indexed aortic valve area <0.6 cm2/m2) who were prospectively enrolled in the TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study were included. The cohort was divided into 3 groups according to BNP and hsTnT levels: group A: BNP <550 pg/ml and hsTnT <15 ng/l; group B: BNP ≥550 pg/ml or hsTnT ≥15 ng/l; and group C: BNP ≥550 pg/ml and hsTnT ≥15 ng/l. The primary endpoint was all-cause mortality. ResultsTwenty-seven patients (27%) were in group A, 39 (40%) were in group B, and 32 (33%) were in group C. During a median follow-up of 2.8 years, 43 patients died. Two-year mortality was higher in group C (41 ± 9%) than in group B (23 ± 7%) and group A (5 ± 4%) (p = 0.002). In group B, there was no significant difference in 2-year mortality rates between the subgroup with hsTnT ≥15 ng/l (n = 29) and the subgroup with BNP ≥550 pg/ml (n = 10) (26 ± 9% vs. 11 ± 10%, respectively; p = 0.21). In multivariable analysis adjusted for age, type of treatment (aortic valve replacement vs. conservative therapy), coronary artery disease, and LVEF, being in group C remained independently associated with an increased risk of mortality (hazard ratio [HR]: 4.25; p = 0.023), and group B tended to have higher mortality (HR: 3.63; p = 0.058) compared with group A. ConclusionsThis study demonstrated the usefulness of combined measures of BNP and hsTnT to enhance risk stratification in patients with LF-LG AS. Patients with elevation of both BNP and hsTnT had a markedly increased risk of mortality. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)

HUMAN EPIDIDYMIS PROTEIN 4 (HE4) IS ASSOCIATED WITH OUTCOME IN LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS

Plasma level of Human Epididymis protein 4 (HE4) has been shown to be associated with increased risk of mortality in patients with heart failure. The objective of this study was to examine the prognostic value of HE4 in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) with either preserved or reduced LVEF. Eighty patients (mean age: 73±10 year; 75% men) with LF-LG AS (LVEF < 50% and/or stroke volume index [SVi] < 35 ml/m2, mean gradient < 40 mmHg, and indexed aortic valve area < 0.6 cm/m2) prospectively enrolled in the True or Pseudo-severe Aortic Stenosis (TOPAS) study were included in this analysis. Forty-seven patients (58%) underwent aortic valve replacement (AVR) within 3 months following inclusion. The cohort was divided into two groups according to the median value of HE4 plasma levels (90 pmol/l). The primary endpoint was all-cause mortality. Patients with higher HE4 plasma level were older and had lower LVEF (all p < 0.05). Twenty-seven patients died during a median follow-up of 2.8 years [IQR=1.2-4.0]. The 3-year survival rate was significantly lower in patients with higher HE4 plasma level (65±8% vs. 93±7%; p=0.0002). In Cox proportional hazard regression model adjusted for EuroSCORE and LVEF, HE4 ≥90 pmol/l was associated with increased risk of all-cause mortality (Model #1: HR=5.46; p=0.003). Further adjustment for type of treatment (AVR vs. conservative) provided similar results (Model #2: HR=4.78; p=0.007). HE4 remained associated with an increased mortality rate when adjusted for NTpro-BNP instead of LVEF in Model #2 (HR=4.04; p=0.01). In patients with LF-LG AS, elevated HE4 plasma level was associated with higher risk of mortality even after adjustment for clinical risk, type of treatment, LV function, and natriuretic peptide level. This new biomarker may be useful to enhance risk stratification in LF-LG AS patients.