Paradoxical Low-flow, Low-gradient Research Articles

High- versus low-gradient aortic stenosis: Is our evaluation limited by aorto-mitral angle on cardiovascular CT?

BackgroundAccurate assessment of aortic valve (AV) stenosis (AS) on transthoracic echocardiogram is crucial for appropriate clinical management. However, discordance between aortic valve area (AVA) and Doppler can complicate the diagnosis of severe AS in low-gradient (LG) AS phenotypes. MethodsWe reviewed 220 consecutive patients with suspected severe AS and AVA ≤1.0 cm2 on transthoracic echocardiogram who were evaluated for transcatheter AV replacement (TAVR) within a large health system from 2015 to 2019. We compared AV calcium score and aorto-mitral angle (AMA) on 3-chamber views from ECG-gated cardiovascular CT among patients with high-gradient (HG) AS (N = 19), paradoxical low-flow low-gradient (PLFLG) AS (N = 24) and normal-flow low-gradient (NFLG) AS (N = 14). ResultsAll groups had comparable age, comorbidities, and AV calcium scores. Compared to patients with HG AS (mean AMA 120 ± 10°), those with PLFLG AS (104 ± 12°; p < 0.001) and NFLG AS (106 ± 13°; p = 0.008) had narrower mean AMA values on cardiovascular CT. ConclusionLG AS patients have significantly narrower AMA than HG AS patients on cardiovascular CT. Due to difficulty obtaining parallel Doppler alignment, narrower AMA may contribute to AVA-Doppler discordance on echocardiogram. These findings emphasize the need for additional information in the setting of LG AS.

Paradoxical low flow-low gradient aortic stenosis: lights and shadows

Paradoxical low flow-low gradient aortic valve stenosis (AVS) is an increasing phenotype in the general population, particularly after the seventh decade of life. It is an AVS in which, despite the preserved ejection fraction, the mean transvalvular gradient is not suggestive of severe AVS (<40 mmHg). The pathophysiology is often intertwined with conditions resulting in heart failure with preserved ejection fraction, such as arterial hypertension and cardiac amyloidosis. Its management is rather controversial about the diagnosis and therapeutic management. The aims of this focus are: to clarify the role and reliability of the main available diagnostic methods, the efficacy of surgical and percutaneous treatments, and to develop a diagnostic-therapeutic algorithm for managing this condition in clinical practice. This algorithm will involve a multi-parametric evaluation, integrating standard echocardiographic assessment with three-dimensional planimetric valve area calculation, determination of the energy loss index), and calcium score calculation by computed tomography scan. This approach aims to ascertain the severity of the stenosis and determine the appropriate therapeutic management.

Right-ventricular/pulmonary artery coupling predicts long-term mortality in aortic stenosis patients with different flow types

Abstract Background Right-ventricular (RV) dysfunction in aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVI) has long been neglected. Right-ventricular to pulmonary artery coupling (RV/PAc), a parameter of RV function, can be determined by echocardiography (tricuspid annular plane systolic excursion over systolic pulmonary artery pressure). Its use for mortality prediction in contemporary AS patients warrants further evaluation, data for different flow types of AS are lacking. Purpose To assess the impact of pathological RV/PAc on long-term mortality in AS patients with different flow types. Methods All 1577 consecutive patients from our registry from 2018 to 2020 were assessed. Patients without tricuspid regurgitation (n=523) or inconclusive echocardiography images (n=111) were excluded. RV/PAc could be analysed in 862 patients. To dichotomize the cohort, a receiver operator curve (ROC) analysis for 2-year mortality was used. Primary endpoint was 2-year mortality. Patients were further analysed according to the Valve Academic Research Consortium (VARC) 3 endpoint definitions. Results By ROC analysis, 0.512 mm/mmHg was defined as a cut-off, dividing the cohort into 428 patients with physiological RV/PAc (above cut-off) and 434 patients with pathological RV/PAc. Patients with pathological RV/PAc were more often male, had more comorbidities, a lower ejection fraction (50% [40-55%] vs. 55% [53-58%], p&amp;lt;0.01) and a higher Society of Thoracic Surgeons (STS) score (4.0 [2.5-6.0] vs. 2.8 [2.0-4.0], p&amp;lt;0.01). Procedural outcomes according to VARC-3 were comparable: the composite endpoints technical failure and device failure at 30 days occurred in 3.9% and 3.5% (p=0.75) and 11.3% and 13.3% (p=0.42) in the pathological and physiological group, respectively. Clinical outcomes in terms of New York Heart Association functional class were comparable at follow-up, with an improvement by at least one class in 76.2% (pathological group) and 79.9% (physiological group, p=0.33). All-cause 2-year mortality was significantly higher in the pathological group (34.9% [30.2-39.2%] vs. 15.4% [11.9-18.8%], p&amp;lt;0.01, hazard ratio, HR, 2.5 [1.9-3.4], Figure 1). The result persisted when adjusted for STS score (HR 2.3 [1.7-3.1]) or in a multivariate Cox regression. Cardiovascular mortality was increased too (pathological, 23.7% [19.3-27.8%], vs. physiological, 8.5% [5.8-11.2%], HR 2.9 [2.0-4.2], p&amp;lt;0.01). The fraction of patients with pathological RV/PAc differed significantly across the AS flow types (high-gradient, 40.3%, classical low-flow low-gradient (LFLG), 73.9%, paradoxical LFLG, 58.9%, and normal-flow low-gradient, 36.6%, p&amp;lt;0.01). Mortality differences persisted in high-gradient and LFLG groups (Figure 2A-D), which was consistent after statistical adjustment. Conclusions RV dysfunction defined as low RV/PAc is a strong predictor for long-term mortality in TAVI patients, with a strong prognostic value also in LFLG AS.

Outcomes of Transcatheter Aortic Valve Replacement Patients With Different Transvalvular Flow-Gradient Patterns

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40mm Hg, LVEF ≥50%, stroke volume index <35ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40mm Hg, LVEF <50%, stroke volume index <35ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p=0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

Clinical Outcomes in High-Gradient, Classical Low-Flow, Low-Gradient, and Paradoxical Low-Flow, Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Implantation: A Report From the SwissTAVI Registry.

Background In view of the rising global burden of severe symptomatic aortic stenosis, its early recognition and treatment is key. Although patients with classical low-flow, low-gradient (C-LFLG) aortic stenosis have higher rates of death after transcatheter aortic valve implantation (TAVI) when compared with patients with high-gradient (HG) aortic stenosis, there is conflicting evidence on the death rate in patients with severe paradoxical low-flow, low-gradient (P-LFLG) aortic stenosis. Therefore, we aimed to compare outcomes in real-world patients with severe HG, C-LFLG, and P-LFLG aortic stenosis undergoing TAVI. Methods and Results Clinical outcomes up to 5 years were addressed in the 3 groups of patients enrolled in the prospective, national, multicenter SwissTAVI registry. A total of 8914 patients undergoing TAVI at 15 heart valve centers in Switzerland were analyzed for the purpose of this study. We observed a significant difference in time to death at 1 year after TAVI, with the lowest observed in HG (8.8%) aortic stenosis, followed by P-LFLG (11.5%; hazard ratio [HR], 1.35 [95% CI, 1.16-1.56]; P<0.001) and C-LFLG (19.8%; HR, 1.93 [95% CI, 1.64-2.26]; P<0.001) aortic stenosis. Cardiovascular death showed similar differences between the groups. At 5 years, the all-cause death rate was 44.4% in HG, 52.1% in P-LFLG (HR, 1.35 [95% CI, 1.23-1.48]; P<0.001), and 62.8% in C-LFLG aortic stenosis (HR, 1.7 [95% CI, 1.54-1.88]; P<0.001). Conclusions Up to 5 years after TAVI, patients with P-LFLG have higher death rates than patients with HG aortic stenosis but lower death rates than patients with C-LFLG aortic stenosis.

Aortic valve calcification and myocardial fibrosis determine outcome following transcatheter aortic valve replacement.

There is evidence to suggest that the subtype of aortic stenosis (AS), the degree of myocardial fibrosis (MF), and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Because little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as their association with adverse cardiac events following transcatheter aortic valve replacement (TAVR). One hundred consecutive patients with severe AS and indication for TAVR were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multidetector computed tomography, and left ventricular endomyocardial biopsies at the time of TAVR. The final study cohort consisted of 92 patients with a completed study protocol, 39 (42.4%) of whom showed a normal ejection fraction (EF) high-gradient (NEFHG) AS, 13 (14.1%) a low EF high-gradient (LEFHG) AS, 25 (27.2%) a low EF low-gradient (LEFLG) AS, and 15 (16.3%) a paradoxical low-flow, low-gradient (PLFLG) AS. The high-gradient phenotypes (NEFHG and LEFHG) showed the largest amount of AVC (807±421 and 813±281mm3 , respectively) as compared with the low-gradient phenotypes (LEFLG and PLFLG; 503±326 and 555±594mm3 , respectively, P<0.05). Conversely, MF was most prevalent in low-output phenotypes (LEFLG>LEFHG>PLFLG>NEFHG, P<0.05). This was paralleled by a greater cardiovascular (CV) mortality within 600days after TAVR (LEFLG 28%>PLFLG 26.7%>LEFHG 15.4%>NEFHG 2.5%; P=0.023). In patients with a high MF burden, a higher AVC was associated with a lower mortality following TAVR (P=0.045, hazard ratio 0.261, 95% confidence interval 0.07-0.97). MF is associated with adverse CV outcome following TAVR, which is most prevalent in low EF situations. In the presence of large MF burden, patients with large AVC have better outcome following TAVR. Conversely, worse outcome in large MF and relatively little AVC may be explained by a relative prominence of an underlying cardiomyopathy. The better survival rates in large AVC patients following TAVR indicate TAVR induced relief of severe AS-associated pressure overload with subsequently improved outcome.

Abstract 12772: Transcatheter Aortic Valve Replacement Improves Functional and Quality Of Life Outcomes in Patients With Low Gradient Aortic Stenosis

Introduction: Aortic stenosis (AS) is the most common valvular disease, and severe disease can significantly impact morbidity. Less data exists examining the functional and quality of life (QOL) effects of transcatheter aortic valve replacement (TAVR) in patients with severe low-gradient AS in both low-flow and normal-flow states. Hypothesis: Patients with symptomatic, severe, low-gradient AS would have improvements in functional and QOL outcomes at 30-days and 1-year following TAVR procedures. Methods: A single center, retrospective study examined symptomatic, severe, low-gradient AS variants. These had an aortic valve area of ≤1.0 cm 2 , mean transvalvular gradient &lt;40 mmHg, and peak aortic valve velocity of &lt;4 m/s. Classical low-flow low-gradient (CLFLG) AS was defined as a left ventricular ejection fraction (LVEF) &lt;50%. CLFLG group underwent dobutamine stress echo to assess AS severity (Stage D2). Paradoxical low-flow low-gradient (PLFLG) AS was defined as LVEF ≥50% and a stroke volume index (SVi) ≤35mL/m 2 (Stage D3). Normal-flow low-gradient (NFLG) AS was defined as LVEF ≥50% and SVi &gt;35mL/m 2 (Stage D4). The primary outcome was change in New York Heart Association (NYHA) classification and a 12-item Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS) at 30-days and 1-year following TAVR. Results: A total of 191 patients were included for analysis: 46 CLFLG, 83 PLFLG, and 62 NFLG AS. At baseline, 130 (68%) had NYHA class III or IV symptoms. Mean baseline KCCQ-OS for all groups was 38±23 (Figure 1). The mean KCCQ-OS at 30-days and 1 year were 62±22 and 68±20. There were no significant differences in KCCQ-OS between the groups at 30-days and 1-year. Following TAVR, 92% and 88% of the cohort had NYHA class I or II symptoms at 30-days and 1 year. Conclusions: Patients with symptomatic, severe low-gradient AS had significant and sustained improvements in their functional and QOL metrics at 30-days and 1-year following TAVR procedures regardless of flow-state.

Long-term survival after TAVR in patients with low flow-low gradient vs high gradient aortic valve stenosis

Abstract Introduction Transcatheter aortic valve replacement (TAVR) has become the treatment of choice in elderly patients affected by severe aortic stenosis (AS). In patients with low-flow low-gradient (LFLG) AS, a clear benefit of TAVR over conservative treatment has been demonstrated. Notwithstanding, patients with classical LFLG (cLFLG) AS have shown worse early post-procedural outcomes compared to those with high-gradient (HG) AS. Purpose Given the absence of data, we aimed to evaluate long-term survival (up to 10 years) after TAVR in patients with cLFLG and paradoxical LFLG (pLFLG) AS as compared to those with HG-AS. Methods Consecutive patients undergoing TAVR at our center with a minimum 5-year follow up (i.e. treated between June 2007 and December 2016) were considered for this analysis. According to baseline echocardiography, patients were divided in three groups: 1) HG-AS (MG &amp;gt;40 mmHg); 2) cLFLG-AS (MG &amp;lt;40 mmHg, EF &amp;lt;50%); and 3) pLFLG-AS (MG &amp;lt;40 mmHg, EF &amp;gt;50%). The study endpoint was post-procedural all-cause mortality. To test differences in long-term outcomes among groups, survival curves using the Kaplan Meier estimator were plotted and compared with the log-rank test. To adjust for possible baseline confounders, a propensity score weighted survival analysis was then performed (standard mean deviation &amp;lt;0.1 for all the considered covariates). Results A total of 574 subjects were included in the analysis (419 [73%] HG-AS; 91 [15%] pLFLG-AS; and 64 [11%] cLFLG-AS). Median survival time was 4.8 years [IQR 2.3–6.2], with a maximum of 12.3 years. Patients with cLFLG-AS presented higher baseline cardiovascular risk compared to those with both HG-AS and pLFLG-AS. At unadjusted survival analysis, patients with cLFLG-AS showed the worst long-term prognosis after TAVR (overall log-rank test p=0.023). However, after propensity weighted adjustment, the long-term survival of patients with cLFLG-AS was similar to those with HG-AS (p=0.77). Patients with pLFLG and HG-AS presented similar survival rate. Unadjusted (Panels A and C) and adjusted (Panels B and D) survival curves are reported in Figure 1. Out of 64 patients with cLFLG-AS, 43 (67%) presented an improvement in LV-EF (&amp;gt;15% from the baseline value) within the first year after TAVR. LV-EF improvement, but not baseline LV-EF, was apparently related to longer post-TAVR survival (Figure 2). Conclusion In the current study, patients with cLFLG-AS had worse long-term survival after TARV as compared to either HG or pLFLG-AS subjects. This difference was not present after adjusting for possible baseline confounders. Thus, the low-flow state condition per se might have a lower impact on long term prognosis of TAVR patients than previously hypothesized. Post-TAVR LV-EF recovery was common among patients with cLFLG-AS and was associated with improved long-term survival. Funding Acknowledgement Type of funding sources: None.

Comprehensive myocardial characterization using cardiac magnetic resonance associates with outcomes in low gradient severe aortic stenosis.

This study sought to compare cardiac magnetic resonance (CMR) characteristics according to different flow/gradient patterns of aortic stenosis (AS) and to evaluate their prognostic value in patients with low-gradient AS. This international prospective multicentric study included 147 patients with low-gradient moderate to severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). All patients were classified as followings: classical low-flow low-gradient (LFLG) [mean gradient (MG) < 40 mmHg and left ventricular ejection fraction (LVEF) < 50%]; paradoxical LFLG [MG < 40 mmHg, LVEF ≥ 50%, and stroke volume index (SVi) < 35 ml/m2]; and normal-flow low-gradient (MG < 40 mmHg, LVEF ≥ 50%, and SVi ≥ 35 ml/m2). Patients with classical LFLG (n = 90) had more LV adverse remodelling including higher ECV, and higher LGE and volume, and worst LVGLS. Over a median follow-up of 2 years, 43 deaths and 48 composite outcomes of death or heart failure hospitalizations occurred. Risks of adverse events increased per tertile of LVGLS: hazard ratio (HR) = 1.50 [95% CI, 1.02-2.20]; P = 0.04 for mortality; HR = 1.45 [1.01-2.09]; P < 0.05 for composite outcome; per tertile of ECV, HR = 1.63 [1.07-2.49]; P = 0.02 for mortality; HR = 1.54 [1.02-2.33]; P = 0.04 for composite outcome. LGE presence also associated with higher mortality, HR = 2.27 [1.01-5.11]; P < 0.05 and composite outcome, HR = 3.00 [1.16-7.73]; P = 0.02. The risk of mortality and the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV, and LGE) with multivariate adjustment. In this international prospective multicentric study of low-gradient AS, comprehensive CMR assessment provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics.

Classification of severe aortic stenosis and outcomes after aortic valve replacement

Aortic valve calcium scoring by cardiac computed tomographic (CT) has been recommended as an alternative to classify the AS (aortic stenosis) severity, but it is unclear that whether CT findings would have additional value to discriminate significant AS subtypes including high gradient severe AS, classic low-flow, low gradient (LF-LG) AS, paradoxical LF-LG AS, and moderate AS. In this study, we examined the preoperative clinical and cardiac CT findings of different subtypes of AS in patients with surgical aortic valve replacement (AVR) and evaluated the subtype classification as a factor affecting post-surgical outcomes. This study included 511 (66.9 ± 8.8 years, 55% men) consecutive patients with severe AS who underwent surgical AVR. Aortic valve area (AVA) was obtained by echocardiography (AVAecho) and by CT (AVACT) using each modalities measurement of the left ventricular outflow tract. Patients with AS were classified as (1) high-gradient severe (n = 438), (2) classic LF-LG (n = 18), and (3) paradoxical LF-LG (n = 55) based on echocardiography. In all patients, 455 (89.0%) patients were categorized as severe AS according to the AVACT. However, 56 patients were re-classified as moderate AS (43 [9.8%] high-gradient severe AS, 5 [27.8%] classic LF-LG AS, and 8 [14.5%] paradoxical LF-LG AS) by AVACT. The classic LF-LG AS group presented larger AVACT and aortic annulus than those in high-gradient severe AS group and one third of them had AVACT ≥ 1.2 cm2. After multivariable adjustment, old age (hazard ratio [HR], 1.04, P = 0.049), high B-type natriuretic peptide (BNP) (HR, 1.005; P < 0.001), preoperative atrial fibrillation (HR, 2.75; P = 0.003), classic LF-LG AS (HR, 5.53, P = 0.004), and small aortic annulus on CT (HR, 0.57; P = 0.002) were independently associated with major adverse cardiac and cerebrovascular events (MACCE) after surgical AVR.

TAVI in patients with low-flow low-gradient aortic stenosis–short-term and long-term outcomes

ObjectivesThe study objective was to characterize different groups of low-flow low-gradient (LFLG) aortic stenosis (AS) and determine short-term outcomes and long-term mortality according to Valve Academic Research Consortium-3 (VARC-3) endpoint definitions.BackgroundCharacteristics and outcomes of patients with LFLG AS undergoing transcatheter aortic valve implantation (TAVI) are poorly understood.MethodsAll patients undergoing TAVI at our center between 2013 and 2019 were screened. Patients were divided into three groups according to mean pressure gradient (dPmean), ejection fraction (LVEF), and stroke volume index (SVi): high gradient (HG) AS (dPmean ≥ 40 mmHg), classical LFLG (cLFLG) AS (dPmean < 40 mmHg, LVEF < 50%), and paradoxical LFLG (pLFLG) AS (dPmean < 40 mmHg, LVEF ≥ 50%, SVi ≤ 35 ml/m2).ResultsWe included 1776 patients (956 HG, 447 cLFLG, and 373 pLFLG patients). Most baseline characteristics differed significantly. Median Society of Thoracic Surgeons (STS) score was highest in cLFLG, followed by pLFLG and HG patients (5.0, 3.9 and 3.0, respectively, p < 0.01). Compared to HG patients, odds ratios for the short-term VARC-3 composite endpoints, technical failure (cLFLG, 0.76 [95% confidence interval, 0.40–1.36], pLFLG, 1.37 [0.79–2.31]) and device failure (cLFLG, 1.06 [0.74–1.49], pLFLG, 0.97 [0.66–1.41]) were similar, without relevant differences within LFLG patients. NYHA classes improved equally in all groups. Compared to HG, LFLG patients had a higher 3-year all-cause mortality (STS score-adjusted hazard ratios, cLFLG 2.16 [1.77–2.64], pLFLG 1.53 [1.22–193]), as well as cardiovascular mortality (cLFLG, 2.88 [2.15–3.84], pLFLG, 2.08 [1.50–2.87]).ConclusionsWhile 3-year mortality remains high after TAVI in LFLG compared to HG patients, symptoms improve in all subsets after TAVI.Graphical abstract

Aortic valve calcification and endomyocardial fibrosis determine adverse outcomes following transcatheter aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: None. Aims There is evidence to suggest that subtype of aortic stenosis (AS), degree of myocardial fibrosis (MF) and level of aortic valve calcification (AVC) are associated with adverse cardiac outcome in AS. Since little is known about their respective contribution, we sought to investigate their relative importance and interplay as well as association with adverse cardiac events. Methods 100 consecutive patients with severe AS and indication for transfemoral transcatheter aortic valve replacement (TAVR) were prospectively enrolled between January 2017 and October 2018. Patients underwent transthoracic echocardiography, multi detector computed tomography (MDCT) and left ventricular endomyocardial biopsy at the time of TAVR. Results The final study cohort consisted of 92 patients with completed study protocol comprising of 39 (42.4 %) normal ejection fraction high gradient (NEFHG), 13 (14.1 %) low EF high gradient (LEFHG), 25 (27.2 %) low EF (flow) low gradient (LEFLG) and 15 (16.3 %) paradoxical low flow low gradient (PLFLG) AS. The high gradient phenotypes (NEFHG and LEFHG) showed the largest amount of AVC (807 ± 421; 813 ± 281 mm³ respectively) as compared to the low gradient phenotypes (LEFLG and PLFLG; 503 ± 326; 555 ± 594 mm³ respectively, p &amp;lt; 0.05). Conversely, MF was most prevalent in low output phenotypes (LEFLG &amp;gt; LEFHG &amp;gt; PLFLG &amp;gt; HEFHG, p &amp;lt; 0.05). This was paralleled by larger cardiovascular mortality within 600 days post TAVR (LEFLG n = 7 &amp;gt; PLFLG n = 4 &amp;gt; LEFHG n = 2 &amp;gt; NEFHG n = 1). In Patients with high MF burden a higher AVC was associated with a lower mortality (p = 0.045, HR = 0.261, 95%CI 0.07-0.97). Within LEFLG AS, patients with larger AVC (&amp;gt;476.8 mm³) had larger MF (40.2%) and higher cardiovascular mortality (n = 5) as compared to patients with lower AVC (£476.8 mm³, 17.1% MF, p = 0.027, cardiovascular mortality n = 2). Conclusion MF is associated with adverse cardiovascular outcome following TAVR which is most prevalent in low ejection fraction situations. In the presence of large MF burden patients with large AVC have better outcome following TAVR. Conversely worse outcome in large MF and relatively little AVC may be explained by a relative prominence of an underlying cardiomyopathy while better survival rates in large AVC patients may indicate severe AS associated pressure overload relief and subsequently improved survival following TAVR.

Low-Gradient Aortic Stenosis; the Diagnostic Dilemma.

ABSTRACTLow-gradient (LG) aortic valve stenosis (AS) constitutes a significant subset among patients with severe aortic stenosis. This entity represents one of the most challenging heart conditions when it comes to diagnosis and management, mainly because of the discrepancy between the small aortic valve area (≤1.0 cm2) that is considered a severe AS, and low mean transvalvular pressure gradient (<40 mmHg), which is one of the criteria for nonsevere AS. LG AS is divided according to transvalvular aortic flow rate into normal-flow LG AS and low-flow LG (LFLG) AS; the latter category can be divided further according to left ventricular ejection fraction (LVEF) into classical LFLG AS if LVEF is depressed or paradoxical LFLG AS if LVEF is preserved. The primary diagnostic challenge in patients with LG AS is to confirm that AS is truly severe and not pseudosevere, which is assessed mainly by either dobutamine stress echocardiography or multidetector computed tomography. The management of symptomatic true severe LG AS is mainly by aortic valve replacement (AVR), whether surgical or transcatheter approach. Patients with LG severe AS have a generally worse prognosis and higher mortality compared with patients with high-gradient severe AS. Despite the survival benefit of AVR in patients with true severe LG AS, these patients have higher surgical risk post-AVR compared with high-gradient AS patients. Early recognition and correct diagnosis of a patient with LG AS is crucial to improve their mortality and morbidity.

199 Lower aortic valve calcium scores by computed tomography scan. A potential new red flag of concomitant cardiac amyloidosis in patients with severe aortic stenosis

Abstract Aims Cardiac amyloidosis (CA) and degenerative aortic stenosis (AS) are two diseases often combined but the diagnosis of both these conditions is challenging because these two illnesses share common echocardiographic characteristics. Different predictors have been proposed in the last few years, including clinical, ECG-graphic, and echocardiographic features. To identify a new marker of concomitant CA in patients with severe AS using computed tomography scan (CT). Methods and results Fifty-five patients with severe AS and suspicion of concomitant CA were retrospectively enrolled. Patients with a bicuspid aortic valve, previous aortic valve replacement, or an incomplete diagnostic workup for CA were excluded. Thirty-three patients underwent CT-scan and were included in the final analysis. None of the patients had at laboratory tests suspicion for AL amyloidosis; 12 patients (AS-CA) had positive 99 m Tc-DPD bone scintigraphy (two with visual score 1, eight score 2 and two score 3), 21 patients (AS-alone) had negative bone scintigraphy (visual score 0). AS-CA patients had a median age of 85.5 years (vs. 82) with only one female patient (vs. 8 in the AS-alone group). AVA indexed were almost comparable between AS-CA and AS-alone groups (0.4 vs. 0.3 mm2/m2, P = 0.25). Stroke volume evaluated by pulsed Doppler, maximum and mean gradient were significatively lower in AS-CA group (respectively 30 vs. 41 ml/m2, P = 0.017, 62 vs. 74 mmHg, 0.038 and 33 vs. 46 mmHg, P = 0.022) with a higher percentage of paradoxical low flow-low gradient aortic stenosis in AS-CA group (7 patients, 58% vs. 3 patients in AS-alone 14%, P = 0.027), in line with the literature. ECG at first presentation in AS-CA group showed atrial fibrillation in eight patients (67%), vs. two patients in the AS-alone group (10%), and lower QRS voltages (peripheral QRS score 40 mV vs. 51 mV, P-value = 0.017; total QRS score 113 mV vs. 155 mV, P-value = 0.005). The echocardiogram showed a more thickened IVS and PW in AS-CA patients (17 vs. 15 mm, P = 0.05 and 15 vs. 14 mm, P = 0.013), an increased left ventricular mass (441 vs. 356 g, P = 0.036) with a reduction of longitudinal systolic function (septal S wave at TDI 4.4 vs. 5.2 cm/s, P = 0.026, lateral S wave 4.1 vs. 5.6 cm/s, P = 0.024) and a lower myocardial contraction fraction (12% vs. 14%, P = 0.036). CT-aortic valve calcium was valued and quantified by an experienced operator. A statistically significant difference between AS-CA and AS-alone groups was observed in calcium score (3345 vs. 4785 Hounsfield units, P = 0.037) calcium volume (2411 vs. 3626 mm2, P = 0.03) and calcium mass (687 vs. 1147 g, P = 0.023). Conclusions This study is the first to our knowledge to use relative aortic valve calcium score evaluation from CT imaging to define patients with severe AS with or without concomitant CA in addition to the classical clinical, ECG graphic, and echocardiographic features. CT-aortic valve calcium burner was significatively lower in patients with concomitant CA.

Severe aortic stenosis echocardiographic thresholds revisited.

In view of inconsistencies in threshold values of severe aortic stenosis (AS) hemodynamic indices, it is unclear what is the relative contribution of each variable in a binary classification of AS based on aortic valve replacement (AVR) indication. We aimed to assess relative discriminative value and optimal threshold of each constituent hemodynamic parameter for this classification and confirm additional prognostic value. Echocardiography studies of 168 patients with ≥ moderate AS were included. AS types were dichotomized into Group-A, comprising moderate and Normal-Flow Low-Gradient (NFLG), and Group-B, comprising High-Gradient(HG), Low Ejection Fraction Low-Flow Low-Gradient(Low EF-LFLG), and Paradoxical Low-Flow Low-Gradient(PLFLG) AS. Aortic valve area (AVA), Doppler velocity index (DVI), peak aortic velocity, mean gradient, stroke volume index and transaortic flow rate(TFR) were assessed for A/B Group discrimination value and optimal thresholds were determined. Dichotomized values were assessed for predictive value for AVR or death. C-statistic values for binary AS classification was .74-.9 for the tested variables. AVA and DVI featured the highest score, and SVI the lowest one. AVA≤.81 cm2 and DVI≤.249 had 87.6% and 86% respective sensitivity for Group B patients, and a similar specificity of 80.9%. During a mean follow-up of 9.1±10.1 months, each of the tested dichotomized variables except for SVI predicted AVR or death on multivariate analysis. An AVA value ≤.81 cm2 or a DVI ≤ .249 threshold carry the highest discriminative value for severe AS in patients with aortic stenosis, translating into an independent prognostic value, and can be helpful in making clinical decisions.

Proposal criteria of paradoxical low-flow low-gradient aortic stenosis for predicting prognosis in patients undergoing transcatheter aortic valve implantation.

Paradoxical low-flow, low-gradient (PLF-LG) aortic stenosis (AS) is associated with poor prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). This study aimed to verify the conventional criteria of PLF-LG AS (left ventricular ejection fraction [LVEF] > 50%, mean aortic valve pressure gradient [AVPG] < 40mm Hg and stroke volume index [SVI] < 35ml/m2 by measuring Doppler method) compatible for predicting prognosis in patients undergoing TAVI. A total of 128 consecutive patients who underwent TAVI for AS with LVEF > 50% were enrolled. The primary endpoint was the hospital readmission due to heart failure (HRHF) and the secondary endpoint was all-cause mortality after hospital discharge. The patients were classified by both the conventional criteria of PLF-LG AS and the proposal criteria of PLF-LG AS if mean aortic valve pressure gradient (AVPG) < 40mmHg and SVI by measuring Simpson's method < cut off value based on the ROC curve for predicting HRHF. According to the conventional criteria, only 6 patients were diagnosed with PLF-LG AS. However, according to the proposal criteria, 16 patients were diagnosed with PLF-LG AS. Fourteen patients developed HRHF during the follow-up period after TAVI. Based on the ROC curves, SVI by measuring Simpson's method (cut off value = 25ml/m2) had higher sensitivity and specificity for predicting HRHF (AUC = 0.74, p = 0.0013) than SVI by measuring Doppler method (AUC = 0.63, p = 0.045). The multivariate analysis revealed that PLF-LG AS defined by the proposal criteria (HR: 5.25; 95% CI: 1.60-17.16; p = 0.0073) but not by the conventional criteria was independently associated with HRHF. PLF-LG AS defined by the conventional criteria and the proposal criteria were not associated with all-cause mortality in the univariate analysis. Our results demonstrated that new criteria of PLF-LG AS defined as SVI < 25ml/m2 measured by Simpson's method could predict HRHF in patients with severe AS who underwent TAVI.

Abstract 11588: Variation in Reader-Reported Severity of Paradoxical Low-Flow Low Gradient Aortic Stenosis: Observations from AaLarge Academic Health System

Introduction: Paradoxical low-flow low-gradient (PLFLG) aortic stenosis (AS) is frequently reported as non-severe AS on transthoracic echocardiogram (TTE) in clinical practice. It is uncertain how reader characteristics are associated with reporting of AS severity in patients with PLFLG AS. Methods: We identified all adults ≥ 18 years old from 9/2015-11/2019 with PLFLG AS on TTE within a large academic health system, and included only readers with ≥10 TTEs in this cohort. We determined the proportion of TTEs reported as either severe or moderate-severe and non-severe, and evaluated differences in reporting based on years of experience, volume of PLFLG AS studies interpreted per year, and quaternary vs. non-quaternary care site. We performed unadjusted and adjusted analyses using multivariable logistic regression. Results: Among 1329 patients meeting TTE criteria for PLFLG AS, only 37.3% were reported as severe/moderate-severe AS. Among 53 readers, the median proportion of patients reported as having severe/moderate-severe AS was 31.6% (25 th -75 th percentile 20.0%-50.0%, range 0.0-91.7%). There were differences in reporting between quartiles based on reader years of experience (33.3-40.9% across Q1-Q4 for proportion of patients reported with severe/moderate-severe AS; p = 0.01) but not volume (34.3-43.1% across Q1-Q4; p = 0.10). Quaternary care readers reported severe/moderate-severe AS for a much higher proportion of patients than non-quaternary care readers (64.3% [reader median 55.2%] vs. 30.9% [reader median 27.3%]; p &lt; 0.001) (Figure), and this was the strongest reader-associated predictor of reporting severe-range AS (adjusted OR 7.6, 95% CI 5.1-11.5). Conclusions: Among patients with PLFLG AS, quaternary care TTE readers report severe AS much more commonly than non-quaternary care readers. Greater focus on TTE reporting of PLFLG AS at non-quaternary sites is likely needed to address underreporting of severe AS in this population.

Abstract 11543: Assessing Reporting of Low-Gradient Severe Aortic Stenosis Based on Race and Ethnicity: Observations from a Large Academic Health System

Introduction: Though low-gradient (LG) aortic stenosis (AS) is common and frequently reported as non-severe on transthoracic echocardiogram (TTE) in real world practice, the association of race and ethnicity with LG AS type and reported severity is not well understood. Methods: We identified all adults ≥ 18 years old from 9/2015-11/2019 with AS, aortic valve area &lt; 1.0cm 2 , and mean gradient &lt;40mmHg on TTE within a large academic health system. We determined frequency of LG AS type (classical low-flow LG [CLFLG], paradoxical low-flow LG [PLFLG], and normal-flow LG [NFLG]) by race and ethnicity. We assessed whether race and ethnicity were associated with reporting severe-range AS on TTE using multivariable logistic regression accounting for age, sex, body mass index, mean gradient, aortic valve area, AS type, and quaternary vs. non-quaternary TTE site. Results: Among 2740 adults with LG AS, 92.4% were white, 4.3% were black, and 3.7% were Hispanic. PLFLG AS was the most common LG AS type among white and black patients and the least common among Hispanic patients (Figure). Among those with PLFLG AS, black patients had the highest proportion of TTEs reported as severe-range AS, while Hispanic patients had the lowest; there were no differences in reporting for CLFLG or NFLG AS (Figure). After multivariable adjustment, there were no significant differences in reporting severe-range AS based on black race (adjusted OR 1.63, 95% CI 0.95-2.82) or Hispanic ethnicity (adjusted OR 1.05, 95% 0.39-2.75) compared to white patients. Quaternary site was a strong independent predictor of reporting severe-range AS (adjusted OR 4.97, 95% CI 3.81-6.54). Conclusions: There are race- and ethnicity-based differences in frequency of LG AS type, and in reporting severe AS on TTE for PLFLG AS in particular. Differences in reporting for PLFLG AS are attenuated after accounting for factors such as TTE site. Additional factors influencing reporting of LG AS in real-world practice should be investigated.

Prevalence and Outcomes of Low-Gradient Severe Aortic Stenosis-From the National Echo Database of Australia.

BackgroundThe prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized.Methods and ResultsData were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS.ConclusionsApproximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS.

Relative prevalence and outcomes of low gradient severe aortic stenosis in routine clinical practice

Abstract Background The prevalence and outcomes of low-gradient severe aortic stenosis (AS), in particular low-flow low-gradient (LFLG) severe AS, have not been well characterized. Objectives We sought to delineate the relative prevalence and outcomes of patients with low-gradient severe AS in routine clinical cardiology practice. Methods Data were derived from the National Echocardiography Database of Australia (NEDA), a national multicentre clinical registry with data linkage to mortality. A total of 192,060 adults with native aortic valve profiling from 2000–2019 were identified, of whom 12,013 (6.3%) had severe AS (aged 75.3±13.1 years, 53.5% men). Severe AS subtypes were determined using standard echocardiographic criteria. All-cause and cardiovascular-related mortality were assessed on an adjusted basis (age and sex) in 8,162 patients with classifiable severe AS subtypes, during mean follow-up of 88±45 months. Additionally, rates of recorded Aortic Valve Replacement (AVR) during follow-up were compared between AS groups. Results 5,601 patients (47%) had high-gradient and 6,412 patients (53%) had low-gradient severe AS. In the low-gradient group, Stroke Volume Index data was recorded in 2,741 patients; 1,750 (64%) had LFLG and 991 (36%) had normal-flow low-gradient (NFLG). For LFLG patients, 1,570 had LV ejection fraction recorded; 959 (61%) had paradoxical LFLG and 651 (39%) had classical LFLG. Adjusted 5-year cardiovascular mortality rates were 28% in high-gradient, 24% in NFLG, 27% in paradoxical LFLG and 50% in classical LFLG patients (p&amp;lt;0.001). Rates of recorded AVR per mean follow-up years were 5.2% for high-gradient, 4.0% for NFLG, 3.1% for classical LFLG and 2.4% for paradoxical LFLG severe AS (p&amp;lt;0.001). Conclusions Approximately half the subjects with echocardiographic features of severe AS in routine clinical practice have low-gradient haemodynamics, associated with long-term mortality comparable to or worse than high-gradient severe AS. The poorest survival was associated with classical LFLG severe AS. Funding Acknowledgement Type of funding sources: None. Summary illustration5 year mortality curves