Low-gradient Severe Aortic Stenosis Research Articles

Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis following transcatheter aortic valve replacement.

The aim of this study was to determine the prognostic value of contractile reserve (CR) at baseline in patients with low-flow, low-gradient severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Patients with severe AS, left ventricular dysfunction, and low transaortic gradient are at high risk for mortality during surgical aortic valve replacement (SAVR). Furthermore, patients without CR have been shown to have perioperative mortality comparable to that of patients treated medically for severe AS. We retrospectively analyzed patients who underwent TAVR with a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40 mmHg, LVEF < 50%, and AVA ≤ 1.0 cm2 or AVAi ≤ 0.6 cm2 ) and who had a pre-TAVR dobutamine stress echocardiogram (DSE). Patients were stratified by the presence or absence of CR, defined as an increase in stroke volume ≥ 20% during DSE. From 2008 to 2016, 61 patients with low-gradient severe AS underwent TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30 (49%). There was no significant difference between the two groups in baseline demographics, medical history, access site, or types of valves. All-cause mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P = 0.69). In patients with low-flow, low-gradient severe AS undergoing TAVR, the presence or absence of CR does not predict all-cause mortality at 30 days or 1 year.

Outcomes after transcatheter aortic valve replacement in patients with low versus high gradient severe aortic stenosis in the setting of preserved left ventricular ejection fraction.

Transcatheter aortic valve replacement (TAVR) for low gradient (LG) severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) remains an area of clinical uncertainty. Retrospective review identified 422 patients who underwent TAVR between September 4, 2014 and July 1, 2016. Procedural indication other than severe AS (n = 22) or LVEF <50% (n = 98) were excluded. Outcomes were defined by valve academic research consortium two criteria when applicable and compared between LG (peak velocity <4.0 m/s and mean gradient <40 mmHg; n = 73) and high gradient (HG) (n = 229) groups. The LG group was further categorized as low stroke volume index (SVI) (n = 41) or normal SVI (n = 32). Median follow-up was 747 days [interquartile range 220-1013]. Baseline thirty-day mortality risk (LG 6.2% [3.8-8.1] vs HG 5.7% [4.1-7.4], P = 0.43) did not differ between groups. Short-term outcomes, including procedural success rate (86.1% vs 88.8%, P = 0.53), peri-procedural complications (intra-procedural heart block: 6.8% vs 7.9%, P = 0.99; permanent pacemaker placement: 11.0% vs 13.6%, P = 0.69; moderate paravalvular regurgitation: 2.7% vs 1.3%, P = 0.60), and all-cause in-hospital mortality (2.7% vs 0.9%, P = 0.25) did not differ between LG and HG groups. On long-term follow-up, all-cause mortality also did not differ between LG and HG groups (6.8% vs 10.0%, plog-rank = 0.33) or between the LG low SVI (9.8%), LG normal SVI (3.1%), and HG (10.0%) groups (plog-rank = 0.39). Patients with preserved LVEF undergoing TAVR for severe AS with LG, including LG with low SVI, have no significant difference in adverse outcomes when compared to patients with HG.

Application of left ventricular strain in patients with aortic and mitral valve disease.

Left ventricular (LV) global longitudinal strain (GLS) is widely recognized as a more sensitive measure of LV systolic function compared with LV ejection fraction (LVEF). In addition, the measurement of LVGLS is more reproducible than two-dimensional LVEF. Current guidelines for diagnosis and treatment of valvular heart disease include LVEF as one of the parameters to take into consideration in the clinical decision-making. However, a large body of evidence is showing that LVGLS may be a better prognosticator than LVEF in various valvular heart diseases. In this timely state-of-the-art review, the evidence and role of LVGLS as a clinical tool in patients with aortic and mitral valve disease is appraised. Majority of research on LVGLS and valvular heart disease focused on high-gradient aortic stenosis. Increasingly, LVGLS has also been shown to be prognostic in low-flow, low-gradient severe aortic stenosis with preserved LVEF, and in low-flow, low-gradient severe aortic stenosis with reduced LVEF. The role of LV GLS in patients with aortic regurgitation and mitral regurgitation is less well established. LVGLS is increasingly used to identify subclinical myocardial dysfunction in patients with valvular heart disease to identify optimal timing for surgery and prognosticate outcomes after surgery.

TCT-840 The Impact of Transcatheter Aortic Valve Replacement on Short and Long-Term Outcomes in High Gradient Versus Low Flow – Low Gradient Versus Paradoxical Low Flow – Low Gradient Severe Aortic Stenosis: A network meta-analysis of randomized controlled trials

The ACC/AHA guidelines identified 3 different symptomatic AS groups. First called D1 with high gradient (HG) (≥40 mm Hg), Second called D2 defined as low flow (Stroke volume index <35 mL/m2) – low gradient (LF-LG) (<40 mmHg) with reduced EF (EF <50%), Third is D3 defined as paradoxical low

Transcatheter Aortic Valve Implantation in Patients With Paradoxical Low-Flow, Low-Gradient Aortic Stenosis

Controversial data exist on clinical outcomes of patients with paradoxical low-flow, low-gradient aortic stenosis (PLF-LG-AS) undergoing valve replacement. The objective of this study was to determine the clinical outcomes and treatment futility in patients with paradoxical low-flow (PLF), low-gradient (LG) severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). A total of 493 patients with severe symptomatic AS and preserved ejection fraction (>50%) undergoing TAVI were included. Patients were divided in two groups: high gradient AS group (HG-AS; mean gradient ≥40 mm Hg and stroke volume index >35 ml/m2, n = 396); and PLF, LG AS group (PLF-LG-AS; mean AV gradient <40 mm Hg and indexed stroke volume ≤35 ml/m2, n = 97). The primary endpoint was treatment futility defined as death or poor functional status (New York Heart Association class III and/or IV) at 6-month follow-up. There were no differences in mortality between groups (PLF-LG-AS: 5%, HG: 8%; adjusted odds ratio (OR): 0.85, 95% confidence interval (CI):0.29 to 2.46), but PLF-LG-AS patients remained more frequently in New York Heart Association class III to IV (20% vs 8% in the HG group, adjusted OR: 2.46, 95% CI:1.19 to 5.07). TAVI treatment futility was more frequent in the PLF-LG-AS group (24% vs 14%, adjusted OR: 1.90 [1.01 to 3.57]), and patients with PLF-LG-AS exhibited a higher rate of rehospitalization for cardiovascular causes (9% vs 5%, adjusted OR: 2.95, 95% CI:1.08 to 8.09). Previous myocardial infarction and chronic obstructive pulmonary disease were associated with treatment futility (p< 0.03 for both). In conclusion, TAVI was a futile treatment in one fourth of patients with PLF-LG-AS. These results underscore the complexity and need for improving the clinical decision-making process and management of patients with PLF-LG-AS.

Is myocardial fibrosis a hallmark of paradoxical low gradient aortic stenosis?

The pathophysiology and clinical significance of low gradient severe aortic stenosis [SAS] despite normal EF, also referred to as paradoxical low gradient [PLG]-SAS, is controversial. It has been suggested that PLG- SAS was associated with higher degree of interstitial myocardial fibrosis and worse outcome as compared to high-gradient (HG)-SAS. To verify this, we obtained myocardial biopsies and measured myocardial extravascular volume fraction (ECV, %) from cMR Modified Look-Locker imaging (MOLLI) T1 mapping at 3T in 155 consecutive patients with moderate to severe AS [22 moderate AS, 75 HG-SAS, 58 PLG-SAS, including 24 low flow (LF) and 34 normal flow (NF) PLG-SAS]. ECV values were compared to those measured in 33 normal age-matched controls. ECV correlated with the amount of interstitial fibrosis (IF) on histology ( r = 0.75, P < 0.01). By histology, the magnitude of IF was similar in all SAS subgroups (4.5 ± 3.3% in NFPLG-SAS, 6.2 ± 4.8% in LFPLG-SAS, 5.5 ± 5.3% in HG-SAS, P = 0.71). ECV was also similar in the different subgroups (29.1 ± 4.3% in moderate AS, 28.8 ± 4.0% in NFPLG-SAS, 29.6 ± 3.2% in LFPLG-SAS, 28.3 ± 5.5% in HG-SAS, P = 0.69), and was not different from that measured in controls (27 ± 4%, P = 0.33). A similar number of SAS patients had ECV values above 95% CI of control subjects HV [2/22 (9%) MAS, 3/24 (13%) LFPLG-SAS, 5/34 (14%) NFPLG-SAS and 9/75 (12%) HG-SAS, P = 0.95; Fig. 1 ]. Our results demonstrate that the amount of IF, measured by histology or MOLLI is similar among controls and patients with SAS. These data do not support the contention that PLG-SAS is associated with higher degree of IF.

Impact of low stroke volume on mortality in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

In patients with severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF), low flow (LF) is currently defined using Doppler-echocardiography by a stroke volume index (SVi)<35 mL/m2. However, the relationship between LF and outcome remains unclear as data on normal reference values defining LF are scarce, and previous studies did not explore the risk associated with other SVi cut-points. We analysed the relationship between LF and mortality in severe AS to establish prognostic LF values associated with mortality risk. This study included 1450 consecutive patients with severe AS (aortic valve area <1 cm2 and/or <0.6 cm2/m2) and preserved LVEF and 1645 controls with normal echocardiograms. Patients were stratified in three groups: (i) SVi > 35 mL/m2 or SV > 70 mL; (ii) SVi 30-35 mL/m2 or SV 55-70 mL; and (iii) SVi < 30 mL/m2 or SV < 55 mL. Mortality with medical and surgical management was analysed. Five-year survival was low for SVi < 30 mL/m2 and SV < 55 mL compared to the other groups (all P-values <0.001). After adjustment for outcome predictors, including aortic valve replacement, mortality risk was considerable with SVi < 30 mL/m2 vs. >35 mL/m2 [adjusted hazard ratio (HR) 1.60 (1.17-2.18)] and SV < 55 mL vs. >70 mL [adjusted HR 1.84 (1.32-2.58)]. Similar mortality risk was observed for SVi 30-35 mL/m2 vs. >35 mL/m2 [adjusted HR 1.05 (0.78-1.41)], and for SV 55-70 mL vs. >70 mL [adjusted HR 1.22 (0.94-1.58)]. The prognostic impact of SVi < 30 mL/m2 and SV < 55 mL was consistent in subgroups, including asymptomatic patients and patients with low-gradient severe AS. Low flow defined as SVi < 30 mL/m2 or SV < 55 mL is an important outcome predictor in severe AS with preserved LVEF under medical and surgical management. Further studies are needed to prospectively test these values for risk stratification and decision making.

Anatomic estimation of aortic stenosis severity vs “fusion” of data from computed tomography and Doppler echocardiography

Two-dimensional, transthoracic echocardiography does not account for the noncircular anatomy of the left ventricular outflow tract (LVOT) and may therefore underestimate LVOT area. Fusion of computed tomography (CT)-derived LVOT area and Doppler-derived flow data has been proposed to improve assessment of aortic valve area (AVA) and classification of aortic stenosis severity. For hemodynamic reasons, effective AVA has to be smaller than anatomic AVA. The aim of the study was to test the "fusion approach" by comparing effective CT-derived AVA with anatomic AVA from CT planimetry. Data of 244 consecutive patients (mean age 81±5years, 61% female) with aortic stenosis were retrospectively analyzed comparing effective AVA (calculated from the continuity equation using CT-LVOT and transthoracic Doppler measurements) with anatomic AVA based on CT planimetry. Substituting the LVOT area from transthoracic echocardiography (TTE) by the CT-LVOT resulted in an increase in AVA from 0.74±0.15 to 0.92±0.18cm² (P<.01), which was larger than anatomic AVA (0.82±0.15cm²). Similar results were obtained based on planimetry from transesophageal echocardiography (TEE; AVA 0.79±0.14cm², P<.01 vs CT-LVOT) and in the subgroup presenting with low-gradient severe aortic stenosis and preserved ejection fraction (n=67, AVA from TTE 0.76±0.09; from CT-LVOT 0.97±0.14; CT planimetry 0.86±0.12; TEE planimetry 0.82±0.13cm²). Fusion of CT-derived LVOT area with Doppler echocardiography results in a calculated effective AVA that is larger than the corresponding anatomic AVA. Therefore, adjustment of partition values may be warranted when using this approach.

PROGNOSTIC VALUE OF POST PROCEDURE STROKE VOLUME INDEX AFTER TRANCATHETER AORTIC VALVE REPLACEMENT IN LOW-GRADIENT SEVERE AORTIC STENOSIS

Recent studies showed that the low-flow or low-gradient severe aortic stenosis (AS) patients which were defined by stroke volume index (SVi) < 35 mL/m2 or an aortic valve mean pressure gradient < 40 mmHg had poor prognosis after transcatheter aortic valve replacement (TAVR). However, in low-gradient

THE REDUCTION OF LEFT VENTRICULAR MASS IS SMALLER IN PATIENTS WITH LOW PRESSURE GRADIENT SEVERE AORTIC STENOSIS AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION

Patients with low gradient (LG) severe aortic stenosis (AS) have poor improvement of hemodynamic performance after transcatheter aortic valve implantation (TAVI). Therefore, we hypothesized that LG would be associated with the smaller reduction of left ventricular mass after TAVI. We studied 94 AS

DOES LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN DIFFERENTIATE LOW-FLOW, LOW-GRADIENT SEVERE AORTIC STENOSIS PATIENTS IN ADDITION TO CONVENTIONAL CONTRACTILE RESERVE ASSESSMENT?

Patients with left ventricular (LV) dysfunction, low-flow low-gradient severe aortic stenosis represent a population of high risk, particularly when they do not have LV contractile reserve (CR). CR has been described as an increase in stroke volume index (SVi) ≥20% during dobutamine stress

Prospective assessment of the frequency of low gradient severe aortic stenosis with preserved left ventricular ejection fraction: Critical impact of aortic flow misalignment and pressure recovery phenomenon

The frequency of paradoxical low-gradient severe aortic stenosis (AS) varies widely across studies. The impact of misalignment of aortic flow and pressure recovery phenomenon on the frequency of low-gradient severe AS with preserved left ventricular ejection fraction (LVEF) has not been evaluated in prospective studies. To investigate prospectively the impact of aortic flow misalignment by Doppler and lack of pressure recovery phenomenon correction on the frequency of low-gradient (LG) severe aortic stenosis (AS) with preserved LVEF. Aortic jet velocities and mean pressure gradient (MPG) were obtained by interrogating all windows in 68 consecutive patients with normal LVEF and severe AS (aortic valve area [AVA] ≤1cm2) on the basis of the apical imaging window alone (two-dimensional [2D] apical approach). Patients were classified as having LG or high-gradient (HG) AS according to MPG <40mmHg or ≥40mmHg, and normal flow (NF) or low flow (LF) according to stroke volume index >35mL/m2 or ≤35mL/m2, on the basis of the 2D apical approach, the multiview approach (multiple windows evaluation) and AVA corrected for pressure recovery. The proportion of LG severe AS was 57% using the 2D apical approach alone. After the multiview approach and correction for pressure recovery, the proportion of LG severe AS decreased from 57% to 13% (LF-LG severe AS decreased from 23% to 3%; NF-LG severe AS decreased from 34% to 10%). As a result, 25% of patients were reclassified as having HG severe AS (AVA ≤1cm2 and MPG ≥40mmHg) and 19% as having moderate AS. Hence, 77% of patients initially diagnosed with LG severe AS did not have "true" LG severe AS when the multiview approach and the pressure recovery phenomenon correction were used. Aortic flow misevaluation, resulting from lack of use of multiple windows evaluation and pressure recovery phenomenon correction, accounts for a large proportion of incorrectly graded AS and considerable overestimation of the frequency of LG severe AS with preserved LVEF.

CRT-700.13 Increased Mortality in Patients with Low Gradient and Normal Ejection Fraction Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

There is an increased awareness of the existence of patients with severe aortic stenosis (AS) (aortic valve area 50%). In a study performed in a surgical population s/p aortic valve replacement

Aortic valve replacement improves survival in severe aortic stenosis with gradient-area mismatch.

To investigate whether and in which patients with catheter-derived low pressure gradient (PG, <40 mmHg) severe (aortic valve area ≤ 1 cm2) aortic stenosis and preserved left ventricular ejection fraction, early aortic valve replacement (AVR) might improve survival. We investigated a total of 506 consecutive patients (age 75 ± 9 years, 58% men) with either moderate aortic stenosis (MAS) or severe aortic stenosis (SAS) and preserved left ventricular ejection fraction (≥50%) as defined at catheterization. Propensity score matching was used to select matched pairs of patients with and without AVR in each group. A 100% complete follow-up of all cause death was obtained after a median of 6.6 years (interquartile range 3.4-8.8 years). There were 62 (12%) patients with MAS, 119 (24%) patients with SAS and low (<40 mmHg) PG and 325 (64%) patients with SAS and high PG. Significantly less patients with MAS and low-gradient SAS underwent AVR compared to patients with high gradient SAS (58% vs 60% vs 83%, P < 0.001). In propensity score-matched patients, AVR was independently associated with a decrease in all-cause mortality in all groups (P < 0.05) regardless of the PG, stroke volume or aortic valve area. The present data indicate a that AVR improves survival in SAS regardless of the gradient and flow. This advocates an 'early-AVR' rather than a 'watchful waiting' strategy.

Hemodynamic Response to Nitroprusside in Patients With Low-Gradient Severe Aortic Stenosis and Preserved Ejection Fraction

BackgroundLow-gradient severe aortic stenosis (LGSAS) with preserved ejection fraction (EF) is incompletely understood. The influence of arterial afterload and diastolic dysfunction on the hemodynamic presentation of LGSAS remains unknown. ObjectivesThe authors sought to determine the acute hemodynamic response to sodium nitroprusside in LGSAS with preserved EF. MethodsSymptomatic patients with LGSAS and preserved EF underwent cardiac catheterization with comparison of hemodynamic measurements before and after nitroprusside. ResultsForty-one subjects (25 with low flow [LF], stroke volume index [SVI] ≤35 ml/m2, 16 with normal flow [NF]) were included. At baseline, LF patients had lower total arterial compliance (0.36 ± 0.12 ml/m2/mm Hg vs. 0.48 ± 0.16 ml/m2/mm Hg; p = 0.01) and greater effective arterial elastance (2.77 ± 0.84 mm Hg · m2/ml vs. 1.89 ± 0.82 mm Hg · m2/ml; p = 0.002). In all patients, nitroprusside reduced elastance, left ventricular filling pressures, and pulmonary artery pressures and improved compliance (p < 0.05). Aortic valve area increased to ≥1.0 cm2 in 6 LF (24%) and 4 NF (25%) subjects. Change in SVI with nitroprusside varied inversely to baseline SVI and demonstrated improvement in LF only (3 ± 6 ml/m2; p = 0.02). ConclusionsNitroprusside reduces afterload and left ventricular filling pressures in patients with LGSAS and preserved EF, enabling reclassification to moderate stenosis in 25% of patients. An inverse relationship between baseline SVI and change in SVI with afterload reduction was observed, suggesting that heightened sensitivity to afterload is a significant contributor to LF-LGSAS pathophysiology. These data highlight the utility of afterload reduction in the diagnostic assessment of LGSAS.

Impact of stroke volume assessment by integrating multi-detector computed tomography and Doppler data on the classification of aortic stenosis

BackgroundThe prevalence of low flow low gradient (LFLG) severe aortic stenosis (AS) may be overrated due to underestimation of stroke volume in two-dimensional (2D) echocardiography. The implications of 3D imaging on stroke volume calculation for AS classification have not been elucidated. Integrating multi-detector computed tomography (MDCT) and Doppler data may improve diagnostic accuracy in patients with LFLG AS. MethodsA total of 186 patients with severe AS evaluated for transcatheter aortic valve replacement were classified according to indexed stroke volume (SVI, cut-off 35mL/m2) and mean transaortic pressure gradient (cut-off 40mmHg). SVI was calculated using a) the biplane Simpson's method, b) left ventricular outflow tract (LVOT) velocity time integral (VTI) and LVOT diameter determined by 2D echocardiography, or c) LVOT VTI and LVOT area planimetered by MDCT. ResultsSVI assessed by the biplane Simpson's method was smaller than that obtained from 2D echocardiography LVOT diameter (29.5±0.6 vs 34.9±0.8mL/m2, p<0.001). The latter was smaller than SVI calculated by integrating MDCT and Doppler data (47.5±1.4mL/m2, p<0.001). LFLG and paradoxical LFLG severe AS were diagnosed in 42.5% and 27.4% of patients using the biplane Simpson's method, in 30.1% and 16.7% using 2D echocardiography LVOT diameter, and in 17.2% and 8.1% when integrating MDCT and Doppler data. ConclusionsThe prevalence of LFLG and paradoxical LFLG severe AS was overestimated by 2.5- and 3.4-fold based on 2D echocardiography alone. Integration of MDCT and Doppler data should be considered for stroke volume assessment in the classification of severe AS.

Acceleration Time and Ratio of Acceleration Time to Ejection Time in Aortic Stenosis: New Echocardiographic Diagnostic Parameters

Inconsistencies between gradients and aortic valve area are frequent in the echocardiographic evaluation of aortic stenosis (AS). Assessing AS severity is essential for the correct management of the disease. The aim of this study was to evaluate whether ejection dynamics, particularly acceleration time (AT) and the ratio of AT to ejection time (ET), could be diagnostic parameters in patients withAS. Patients with AS (aortic peak velocity>2m/sec) were prospectively enrolled. Quantitative echocardiographic Doppler parameters including ejection dynamics (AT, ET, and AT/ET ratio) as well as conventional and clinical parameters were analyzed. AT, ET, and AT/ET ratio were calculated in different stages ofAS. A receiver operating characteristic curve was plotted to determine the best cutoff value to identify severe AS. Two hundred sixty-two patients were included (mean age, 75±8years; 54% women), of whom 109(42%) had severe AS, 99 (38%) had moderate AS, 22 (8%) had mild AS, 24 (9%) had classical low-flow, low-gradient severe AS, and eight (3%) had paradoxical low-flow, low-gradient severe AS. AT was higher in patients with higher levels of severity of AS (65±16 vs 82±19 vs 109±23msec, P<.001) as well as AT/ET ratios (0.22±0.05 vs 0.29±0.07 vs 0.37±0.06, P<.001). Using a cutoff of 94msec, AT had sensitivity of 71% and specificity of 81% for severe AS; using a cutoff of 0.35, the AT/ET ratio had sensitivity of 59% and specificity of 86%. On multivariate analysis, AT was associated with effective orifice area (B=-0.64, P<.001) and ET with heart rate (B=-0.62, P<.001) and age (B=0.30, P=.04). Ejection dynamics parameters, such as AT and AT/ET, can help evaluate AS severity.

P1646Paradoxical low flow low gradient severe aortic stenosis with preserved left ventricular ejection fraction. impact of medical, transcatheter and surgical management

P1646Paradoxical low flow low gradient severe aortic stenosis with preserved left ventricular ejection fraction. impact of medical, transcatheter and surgical management

P1641Reclassification of low-gradient severe aortic stenosis by three-dimensional transthoracic echocardiography

P1641Reclassification of low-gradient severe aortic stenosis by three-dimensional transthoracic echocardiography

P4227Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis patients following transcatheter aortic valve replacement

P4227Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis patients following transcatheter aortic valve replacement