High Gradient Severe Aortic Stenosis Research Articles

Invasive hemodynamic response to exercise in hemodynamically significant aortic stenosis with preserved left ventricular ejection fraction

Abstract Background Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. Purpose To describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%, and to identify the variables associated with the steepness of the pulmonary capillary wedge pressure (PCWP)/cardiac output (CO) slope defined as (peak exercise PCWP-rest PCWP)/(peak exercise CO-rest CO). Methods Patients with aortic valve area (AVA) ≤1.5 cm² underwent right heart catheterization at rest and during maximal exercise measuring pulmonary artery pressures, PCWP, CO and PCWP/CO slope. Patients were stratified in three groups: 1) discordant LG AS (AVA ≤1.0 cm² and mean gradient <40 mmHg); 2) moderate AS (AVA >1.0 cm²) and 3) high-gradient severe AS (AVA ≤1.0 cm² and mean gradient ≥40 mmHg). Results Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) high-gradient severe AS. The PCWP/CO slope was significantly steeper in discordant LG: median 3.3 mmHg/L/min (interquartile range: 2.2 mmHg/L/min) and high-gradient severe AS: 2.7 mmHg/L/min (1.5 mmHg/L/min) compared to moderate AS: 1.9 mmHg/L/min (2.0 mmHg/L/min), p=0.004. In a linear regression model adjusted for age, sex and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO slope. Furthermore, patients with discordant LG AS had a leftward and upward shift in the PCWP/CO slope. Conclusions Discordant LG and high-gradient severe AS had similar hemodynamic response to exercise with steeper PCWP/CO slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left-upward shift in PCWP/CO slope for discordant LG compared to high-gradient severe AS indicates that, this group also has latent heart failure with preserved ejection fraction physiology.

Aortic valve tract dynamics in normal-flow low-gradient and normal-flow high-gradient severe aortic stenosis

Abstract Introduction Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Severe AS is defined as a mean pressure gradient (MG) ≥ 40 mmHg, a maximum aortic jet velocity≥4 m/s and an aortic valve area (AVA)≤1 cm2. However, classification of AS severity may be challenging due to discordant results on echocardiography. The normal-flow low-gradient severe AS (NFLG-AS) is defined as AVA≤1 cm2, MG<40 mmHg, left ventricular ejection fraction ≥ 50%, and stroke volume index (SVi) ≥ 35 ml/m2, whereas in the presence of MG > 40mmHg the condition is described as normal-flow high-gradient AS (NFHG-AS). Purpose The purpose of this study was to seek differences in the dynamic changes of the aortic valve tract throughout the cardiac cycle between the two clinical entities: NFHG-AS (Group 1) and NFLG-AS (Group 2). Methods In total, 130 patients with normal flow severe AS who underwent TAVI and had 3D transoesophageal echocardiographic data sets were screened. 38 patients with NFHG-severe AS and 40 patients with NFLG-severe AS with matching clinical characteristics and aortic valve area were identified. A custom-made semi-automated application developed by SQ was used. The application allows tracking of the aortic valve tract surface throughout the cardiac cycle in 3D transoesophageal echocardiograms and provides measurements of the geometrical planes at 4 levels: left ventricular outflow tract (LVOT), aortic annulus (AoA), sinuses of Valsalva (SoV) and sinotubular junction (STJ). Results The echocardiographic characteristics and the dynamic changes of the aortic valve tract between the two groups are shown in Tables 1 and 2. Both groups had comparable echocardiographic characteristic apart from the mean aortic valve pressure gradient as expected. With regards to the aortic valve tract geometrical dynamic changes, the relative LVOT and AoA area changes were bigger in Group 1 (36.8±15.9% vs 29.1±11.9%; p=0.017 and 21.0±8.39% vs 17.1±6.6%; p=0.028). The SoV and STJ relative changes were similar between the two groups. The same applies to aortic stiffness parameters, namely compliance and distensibility of the ascending aorta, systemic arterial compliance, and valvulo-arterial impedance. Conclusion The LVOT and aortic annulus area demonstrate more prominent dynamic changes in patients with normal-flow high-gradient severe AS compared to individuals with normal-flow low-gradient severe AS. While the SoV and the STJ geometry does not change significantly through the cardiac cycle, a more elastic outflow tract allows larger expansion in systole and higher pressure gradients across the aortic valve, whereas a stiffer outflow tract and annulus result in lower pressure gradients, despite the presence of severe aortic stenosis (AVA<1.0cm2). These differences in dynamic LVOT and aortic annulus changes may explain the discrepancy between aortic valve area and pressure gradients in patients with normal-flow low-gradient AS.

Transcatheter aortic valve replacement outcomes in patients with high gradient versus low ejection fraction low gradient severe aortic stenosis: A meta-analysis of randomized controlled trials

BackgroundThe outcome of Low Flow-Low Gradient (LF-LG) severe aortic stenosis (AS) patients who underwent Transcatheter Aortic Valve Replacement (TAVR) procedure is not well defined. We conducted a systematic review of the literature to compare the outcomes of TAVR in LF-LG AS patients to the more traditional high gradient (HG) aortic stenosis. MethodsWe comprehensively searched for controlled randomized and non-randomized studies from 4 online databases. We are presenting the data using risk ratios (95 % confidence intervals) and measuring heterogeneity using Higgins' I2 index. ResultsOur analysis included 4380 patients with 3425 HG patients and 955 LF-LG patients from 6 cohort (5 retrospective and 1 prospective) studies. When compared to LFLG; TAVR was associated with significantly lower 30 days mortality in HG patients (5.1 % vs 7.4 %; relative risk [RR]: 0.55; 95 % confidence interval [CI]: 0.35 to 0.86; p < 0.01). Similar findings were also observed in 12-month cardiovascular (CV) mortality (5.5 % vs. 10.4 %; RR: 0.47; 95 % CI: 0.38 to 0.60; p < 0.01 and 12-month all-cause mortality (15.9 % vs 20.9 %; RR: 0.70; 95 % CI: 0.49 to 1.00; p < 0.05). There was no significant difference in myocardial infarction (MI) after TAVR between HG and LF-LG at 30 days (0.16 % vs. 0.95 %; p < 0.09) or 12 months (0.43 % vs. 0.95 %; p = 0.20). Similarly, there was no difference in stroke rates at 30 days (2.9 % vs. 2.86 %) or at 12 months (3.6 % vs. 3.06 %). Conclusions and relevancePatients with LF-LG severe AS who underwent TAVR had worse 1-year all-cause mortality, 30-day all-cause, and 1-year CV mortality when compared to TAVR in HG severe AS. There was no difference in MI or stroke rates. Therefore, with heart team discussion and informed patient decision regarding the risk and benefit, TAVR would still offer better outcomes in LFLG AS compared to conservative medical management.

Surgical aortic valve replacement etiologies, hemodynamics, and outcomes in 1346 patients from the Malaysian heart centre

BackgroundThis study examined the characteristics and outcomes of surgical aortic valve replacement (SAVR) both isolated and in combination with other cardiac surgery in Malaysia from 2015 to 2021.MethodsThis was a retrospective study of 1346 patients analyzed on the basis of medical records, echocardiograms and surgical reports. The overall sample was both considered as a whole and divided into aortic stenosis (AS)/aortic regurgitation (AR)-predominant and similar-severity subgroups.ResultsThe most common diagnosis was severe AS (34.6%), with the 3 most common etiologies being bicuspid valve degeneration (45.3%), trileaflet valve degeneration (36.3%) and rheumatic valve disease (12.2%). The second most common diagnosis was severe AR (25.5%), with the most common etiologies being root dilatation (21.0%), infective endocarditis (IE) (16.6%) and fused prolapse (12.2%). Rheumatic valve disease was the most common mixed disease. A total of 54.5% had AS-predominant pathology (3 most common etiologies: bicuspid valve degeneration valve, degenerative trileaflet valve and rheumatic valve disease), 36.9% had AR-predominant pathology (top etiologies: root dilatation, rheumatic valve disease and IE), and 8.6% had similar severity of AS and AR. Overall, 62.9% of patients had trileaflet valve morphology, 33.3% bicuspid, 0.6% unicuspid and 0.3% quadricuspid. For AS, the majority were high-gradient severe AS (49.9%), followed by normal-flow low-gradient (LG) severe AS (10.0%), paradoxical low-flow (LF)-LG severe AS (6.4%) and classical LF-LG severe AS (6.1%). The overall in-hospital and total 1-year mortality rates were 6.4% and 14.8%, respectively. Pure severe AS had the highest mortality. For AS-predominant pathology, the etiology with the highest mortality was trileaflet valve degeneration; for AR-predominant pathology, it was dissection. The overall survival probability at 5 years was 79.5% in all patients, 75.7% in the AS-predominant subgroup, 83.3% in the AR-predominant subgroup, and 87.3% in the similar-severity subgroup.ConclusionsThe 3 most common causes of AS- predominant patients undergoing SAVR is bicuspid valve degeneration, degenerative trileaflet valve and rheumatic and for AR-predominant is root dilatation, rheumatic and IE. Rheumatic valve disease is an important etiology in our SAVR patients especially in mixed aortic valve disease.Study registration IJNREC/562/2022.

Is there an outcome penalty linked to guideline-based class-I indications for valvular surgery? long-term analysis of patients with high gradient severe aortic stenosis

Abstract Background Current ACC/AHA guidelines recommend aortic valve replacement (AVR) as class-I triggers in patients with high-gradient severe aortic stenosis (HGSAS) in presence of symptoms and/or left ventricular dysfunction (LVEF&amp;lt;50%). Whether waiting for these triggers could be associated with long-term outcome penalty after AVR remains poorly studied. Objective To examine the impact of guideline-based class-I triggers on long-term post-operative survival in patients with HGSAS. Methods We used an international registry including consecutive patients operated on for HGSAS between 2000 and 2017. 2030 Patients were included in the analysis and retrospectively classified according to the guideline-based indication: no Class-I trigger (no symptoms and LVEF&amp;gt;50%, n=853), Symptoms with LVEF&amp;gt;50% (n=965), or LVEF&amp;lt;50% (regardless of symptoms, n=212). Survival was compared in a multivariate Cox-model and after inverse probability weighting-[IPW] for relevant variables. Finally, we explored the most sensitive left ventricular ejection fraction threshold for predicting mortality risk. Results 10-years survival was better among patients without any class-I trigger than with symptoms or LVEF&amp;lt;50% (67±3 vs 56±3 vs 53±7% respectively, p&amp;lt;0.001). After adjustment for covariates, risk of death increased significantly when patients were operated on with symptoms (HR: 1.48, [95%CI: 1.17-1.86]) or with LVEF&amp;lt;50% (HR: 1.47, [95%CI: 1.05-2.06]) compared to patients with no class-I trigger. Furthermore, LVEF&amp;lt;55% emerged as a more sensitive threshold for the prediction of post-operative mortality in comparison with LVEF&amp;lt;50% (see table), allowing a better separation of survival curves and indicating that patients with LVEF 50-55% are already at risk with long term consequences even after AVR. Interestingly, among asymptomatic patients with LVEF &amp;gt;55%, performing AVR restituted a normal life expectancy (comparable to the Belgian population of same age, see figure). Finally, the outcome penalty after AVR when waiting for symptoms or LVEF&amp;lt;55% was confirmed in IPW analysis (HR: 1.43, [95%CI: 1.13-1.82] and HR: 1.63, [95%CI: 1.19-2.23], respectively). Conclusions Guideline-based Class-I triggers for AVR in patients with HGSAS is associated with profound outcome consequences on long-term postoperative mortality. Our data argue that patients with HGSAS should be operated on before the onset of these triggers. Finally, our data suggest that a threshold of LVEF&amp;lt;55% is a stronger predictor of outcome than LVEF&amp;lt;50%.

Sex differences and survival after TAVI for severe aortic stenosis

Abstract Background There is still controversy about survival rates and clinical response of women versus men who undergo transcatheter aortic valve implantation (TAVI) for the treatment of severe aortic stenosis (SAS). Purpose Assess mortality and heart failure (HF) symptoms following TAVI for SAS, according to sex. Methods A retrospective analysis of a single-center database including all TAVI performed in 2011-2019 was performed. Clinical, echocardiographic, and blood-analysis data were determined, and all-cause mortality over the five years after the procedure was compared based on sex. A reduction of at least one New York Heart Association (NYHA) class after TAVI was the secondary endpoint. Results Of the 488 cases analyzed, 252 (51.6%) were women. They were older (84 vs. 80 years-old, p&amp;lt;0.001), had a lower body surface area, and had a higher estimated surgical risk, as determined by EuroSCORE II (4.5 vs. 3.8, p=0.011) and STS-mortality (4.46 vs. 3.44, p&amp;lt;0.001). However, they had a lower prevalence of diabetes mellitus, coronary artery disease, and peripheral artery disease, a lower estimated creatinine clearance, and a lower frequency of previous pacemaker implantation. Women had more frequently a phenotype of high gradient severe aortic stenosis, with lower functional aortic valve areas. While there was no difference in TAVI design, smaller valves were implanted in women. Median follow-up was 46 months and there was a 40% mortality rate over the five years after treatment, with no statistically significant differences according to sex in both univariate and multivariate analysis, after adjusting for estimated surgical risk. EuroSCORE II had a statistically significant association with the primary endpoint (hazard ratio 1.03 (1.01-1.05), p=0.004). Despite having a similar NYHA class before TAVI, women experienced a lower frequency of functional class improvement (61% vs. 72%, p=0.034). Conclusions Although women had a higher estimated surgical risk, no differences were found regarding survival after TAVI for SAS. However, improvement in HF symptoms was less frequent in this subset.Table 1Figure 1

Exploring the mechanisms responsible for reduced systolic function in high-gradient aortic stenosis

ObjectiveTo characterise the mechanics responsible for the reduced ejection fraction (rEF) in high-gradient severe aortic stenosis (AS).Methods21 patients with high-gradient severe AS (aortic valve area (AVA) <1.0 cm2 and mean...

3D histopathology of stenotic aortic valve cusps using ex vivo microfocus computed tomography.

Calcific aortic stenosis (AS) is the most prevalent heart valve disease in developed countries. The aortic valve cusps progressively thicken and the valve does not open fully due to the presence of calcifications. In vivo imaging, usually used for diagnosis, does not allow the visualization of the microstructural changes associated with AS. Ex vivo high-resolution microfocus computed tomography (microCT) was used to quantitatively describe the microstructure of calcified aortic valve cusps in full 3D. As case study in our work, this quantitative analysis was applied to normal-flow low-gradient severe AS (NF-LG-SAS), for which the medical prognostic is still highly debated in the current literature, and high-gradient severe AS (HG-SAS). The volume proportion of calcification, the size and number of calcified particles and their density composition was quantified. A new size-based classification considering small-sized particles that are not detected with in vivo imaging was defined for macro-, meso- and microscale calcifications. Volume and thickness of aortic valve cusps, including the complete thickness distribution, were also determined. Moreover, changes in the cusp soft tissues were also visualized with microCT and confirmed by scanning electron microscopy images of the same sample. NF-LG-SAS cusps contained lower relative amount of calcifications than HG-SAS. Moreover, the number and size of calcified objects and the volume and thickness of the cusps were also lower in NF-LG-SAS cusps than in HG-SAS. The application of high-resolution ex vivo microCT to stenotic aortic valve cusps provided a quantitative description of the general structure of the cusps and of the calcifications present in the cusp soft tissues. This detailed description could help in the future to better understand the mechanisms of AS.

Prognostic Implications of Discordant Low-Gradient Severe Aortic Stenosis: Comprehensive Analysis of a Large Multicenter Registry

BackgroundUp to 30% of patients with severe aortic stenosis (SAS) (indexed aortic valve area [AVAi] <0.6 cm2/m2) exhibit low-transvalvular gradient despite normal ejection fraction. There is intense debate regarding the prognostic significance of this entity. ObjectivesThe purpose of this study was to compare the outcome of patients with discordant low-gradient SAS (DLG-SAS) vs moderate aortic stenosis (MAS) and high-gradient SAS (HG-SAS). MethodsWe used the BEL-F-ASt (Belgium-France-Aortic Stenosis) registry including consecutive patients with AS. Survival was compared overall and after matching (inverse probability weighting and propensity-score matching) for clinical and imaging variables. The analysis was first performed in the overall population (n = 2,582) and then in the population of unoperated patients (n = 1,812). ResultsAfter-inverse probability weighting-matching, the 3 groups were balanced. Five-year survival was better in MAS than in DLG-SAS and HG-SAS-patients (58.9% vs 47% vs 41.2%, P < 0.001). Similar results were obtained in unoperated patients (54.1% vs 37.9% vs 28.1%, P < 0.001). To explore the impact of MG (≤40 vs >40 mmHg) and AVAi (<0.6 vs ≥0.6 cm2/m2) on outcomes, survival of propensity score-matched cohorts of HG-vs DLG-SAS and MAS vs DLG-SAS were compared. After matching for MG, survival was better in MAS than in DLG-SAS (52% vs 40%, P < 0.001). After matching for AVAi, survival was better in DLG-SAS than in HG-SAS patients (45% vs 33%, P < 0.001). ConclusionsSurvival of DLG-SAS is better than that of HG-SAS and worse than that of MAS patients. At comparable MG, the lower the AVAi, the worse the prognosis, whereas at comparable AVAi, the higher the MG, the worse the prognosis. These data argue that DLG-SAS is an intermediate form in the disease continuum.

Esperanza de vida después del recambio valvular debido a estenosis aórtica de bajo gradiente con función ventricular conservada

Introduction and objectivesSurgical aortic valve replacement (SAVR) can modify the natural history of severe aortic stenosis (SAS). However, compared with the general population, these patients have a loss of life expectancy. The life expectancy of patients who undergo SAVR due to low-gradient SAS with preserved left ventricular ejection fraction (LVEF) is unknown. MethodsWe included all patients between 50 and 65 years who underwent isolated SAVR in 27 Spanish centers during an 18-year period. We analyzed observed and expected survival at 18 years in patients with low-gradient SAS with preserved LVEF and all other types of SAS. We used propensity score matching to compare the life expectancy of patients with low-gradient SAS with preserved LVEF vs those with high-gradient SAS with preserved LVEF. ResultsWe analyzed 5084 patients, of whom 413 had low-gradient SAS with preserved LVEF. For these patients, observed survival at 10, 15 and 18 years was 86.6% (95%CI, 85.3-87.8), 75% (95%CI, 72.7-77.2), and 63.5% (95%CI, 58.8-67.8). Expected survival at 10, 15 and 18 years was 90.2%, 82.1%, and 75.7%. In the matched sample, survival of patients with low-gradient SAS with preserved LVEF was similar to that of patients with high-gradient with preserved LVEF, log-rank test, P=.95; HR=1 (95%CI, 0.7–1.4; P=.95). ConclusionsThere is a loss of life expectancy in patients with all types of SAS undergoing SAVR. This loss is higher in patients with left ventricular dysfunction and lower in patients with low-gradient or high-gradient aortic stenosis with preserved LVEF. The benefit of surgery is similar between these last 2 groups.

Life expectancy after surgical aortic valve replacement for low-gradient aortic stenosis with preserved ejection fraction

Introduction and objectivesSurgical aortic valve replacement (SAVR) can modify the natural history of severe aortic stenosis (SAS). However, compared with the general population, these patients have a loss of life expectancy. The life expectancy of patients who undergo SAVR due to low-gradient SAS with preserved left ventricular ejection fraction (LVEF) is unknown. MethodsWe included all patients between 50 and 65 years who underwent isolated SAVR in 27 Spanish centers during an 18-year period. We analyzed observed and expected survival at 18 years in patients with low-gradient SAS with preserved LVEF and all other types of SAS. We used propensity score matching to compare the life expectancy of patients with low-gradient SAS with preserved LVEF vs those with high-gradient SAS with preserved LVEF. ResultsWe analyzed 5084 patients, of whom 413 had low-gradient SAS with preserved LVEF. For these patients, observed survival at 10, 15 and 18 years was 86.6% (95%CI, 85.3-87.8), 75% (95%CI, 72.7-77.2), and 63.5% (95%CI, 58.8-67.8). Expected survival at 10, 15 and 18 years was 90.2%, 82.1%, and 75.7%. In the matched sample, survival of patients with low-gradient SAS with preserved LVEF was similar to that of patients with high-gradient with preserved LVEF, log-rank test, P=.95; HR=1 (95%CI, 0.7–1.4; P=.95). ConclusionsThere is a loss of life expectancy in patients with all types of SAS undergoing SAVR. This loss is higher in patients with left ventricular dysfunction and lower in patients with low-gradient or high-gradient aortic stenosis with preserved LVEF. The benefit of surgery is similar between these last 2 groups.

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.

Severe low-gradient aortic stenosis: impact of inadequate left ventricular responses to high afterload on diagnosis and therapeutic decision-making.

The fact that nearly 50% of patients with an aortic valve (AV) area < 1.0 cm2, consistent with severe aortic stenosis (AS), can have mean trans-AV pressure gradients < 40mmHg, consistent with non-severe AS, indicates that "low-gradient" (LG) severe AS, which is often associated with poor prognosis, deserves particular consideration. Inadequate left ventricular (LV) adaptation to severe AV stenosis resulting from preexistent intrinsic myocardial damages and/or maladaptive LV responses to increased afterload are typical features of severe LG-AS. The diagnosis and management of patients with severe LG-AS are particularly challenging because the discrepancy between the AV area and the trans-AV pressure gradient raises doubts concerning the actual severity of AS and therefore also about the necessity of AV replacement (AVR). LG-AS diagnosis requires integrative multimodality evaluation of both the AV and the LV and therapeutic decision-making necessitates careful individual benefit-risk estimation. Although patients with severe LG-AS associated with low trans-AV flow (i.e., stroke volume ≤ 35ml/m2) have worse outcomes after AVR than those with high-gradient severe AS, even those with reduced LV ejection fraction (LVEF) can have a significant survival benefit particularly by transcatheter AVR. Dobutamine stress echocardiography facilitates distinction between true-severe and pseudo-severe low-flow LG-AS with reduced LVEF. The review aimed to provide an updated theoretical and practical basis for those engaged in this demanding and still current topic due to the new aspects which have emerged in conjunction with both the evolving scientific knowledge about the various LV responses to the increased afterload and the increasing use of the less invasive transcatheter AVR.

Echocardiographic predictors of left ventricular reverse remodeling after aortic valve replacement in patients with paradoxical aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Paradoxical aortic stenosis (AS) is low-flow (SVi ≤ 35ml/m2) , low- gradient (Mean PG ≤ 40mmHg) severe aortic stenosis (AVA &amp;lt; 1cm2) in patients with preserved ejection fraction (EF ≥ 50%) usually associated with female gender, advanced age, small body size and history of hypertension. Left ventricular (LV) reverse remodeling presents with LV hypertrophy reversal following aortic valve replacement (AVR) and is associated with better long term prognosis. Purpose The purpose of our study was to asses echocardiographic predictors of better outcome in patients with paradoxical severe AS following AVR. Methods Detailed transthoracic echocardiographic (TTE) evaluation with left ventricular strain analysis was performed using 2D Philips Epique 7 in patients with severe aortic stenosis with AVR indication before and 4 months after the intervention. Results Among 75 patients with severe AS and indication for AVR, 20 (31, 7%) were paradoxical AS with low- flow, low –gradient and preserved ejection fraction. Sixty percent were female and eighty percent had hypertension where all echocardiographic parameters improved following AVR including improvement of LV global longitudinal strain (LS) as well as reduction of left ventricular mass indicating left ventricular reverse remodeling (Figure 1). The patients with paradoxical AS compared to the other forms of severe AS had the lowest values for MAPSE and s’TDI before and after AVR. Independent predictors of LV reverse remodeling before AVR were end systolic LV volume (ESV) , AVA/BSA and the number of segments with LS &amp;lt; 13%. Conclusion Paradoxical severe AS is associated with worse post AVR prognosis compared to the high gradient severe AS. Echocardiographic predictors of LV reverse remodeling in patients with paradoxical severe AS following AVR are LV ESV, AVA/BSA and number of segments with LS &amp;lt; 13%. Timely diagnosis and AVR referral of patients with paradoxical severe AS is of major importance in the management of aortic valvular disease. Abstract Figure. Descriptive of 20pts with paradoxical AS Abstract Figure. Predictors of LV reverse remodeling

Comparison of Transcatheter Aortic Valve Implantation Outcomes Between Normal-Flow, Low-Gradient Severe Aortic Stenosis and Normal-Flow, High-Gradient Severe Aortic Stenosis

BackgroundNormal flow low gradient severe aortic stenosis (NFLG-AS) with preserved ejection fraction is the most prevalent form of low gradient severe aortic stenosis. Despite the increased prevalence, the clinical outcomes and management strategy of NFLG-AS remain controversial. Therefore, our study aimed to evaluate transcatheter aortic valve implantation (TAVI) outcomes of patients with NFLG-AS compared with normal flow high gradient severe aortic stenosis (NFHG-AS). MethodsWe performed a retrospective analysis of 394 patients who underwent TAVI between January 2011 to September 2020. Among 394 patients, 232 patients had NFLG-AS, and 162 patients had NFHG-AS. The primary outcomes included all-cause mortality and cardiovascular mortality. In addition, multiple secondary outcomes were evaluated, including stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, symptom improvement, and repeat hospitalizations due to any cardiac disease. ResultsThe cumulative six months incidence of all-cause mortality and cardiovascular mortality were similar between and NFLG-AS and NFHG-AS (4.32% vs. 5.17%, P = 0.71 and 2.47% vs. 2.59%, P = 0.94 respectively). There was no difference in the rates of stroke, myocardial infarction, duration of hospital stay, new-onset atrial fibrillation, temporary or permanent pacemaker requirement, major bleeding, blood transfusion, vascular complications, acute kidney injury, hemodialysis requirement, and symptom improvement between the two groups. However, patients with NFLG-AS compared to NFHG-AS had more frequent cardiac-related repeat hospitalizations (19.14% vs. 11.64%, P = 0.04%). ConclusionThere was no significant difference in all-cause mortality and cardiovascular mortality between NFLG-AS and NGHG-AS six months post-TAVI. However, patients undergoing TAVI with NFLG-AS had significantly higher rates of cardiac-related repeat hospitalizations.

Cardiac damage staging classification and prognosis in low flow low gradient severe aortic stenosis

Abstract Introduction There are currently no established prognostic models for low-flow, low-Gradient (LFLG) severe aortic stenosis (AS). The Cardiac Damage Staging Classification, has been validated as a clinically useful prognostic tool in high-gradient severe AS, but not specifically in LFLG severe AS. Objective To assess and confirm the prognostic utility of the Cardiac Damage Staging Classification, in LFLG severe AS patients. Methods We analysed data from the National Echocardiography Database of Australia (NEDA), a national multicentre registry with individual data linkage to mortality. Of 192,060 adults (aged 62.8±17.8 years) with comprehensive ultrasound profiling of the native aortic valve studied between 2000–2019, 12,013 (6.3%) had severe AS. Based on standard echocardiographic parameters, 611 classical and 959 paradoxical LFLG patients were identified. Mean follow-up was 70±41 months. All-cause and cardiovascular-related mortality were assessed for each LFLG group on an adjusted basis (age and sex), according to cardiac damage classification staging. Results Paradoxical LFLG patients were younger (mean age 74.3 vs 76.2, p=0.006) and more often female (62.8% vs 36.3%, p&amp;lt;0.001). Classical LFLG patients had greater associated cardiac damage at diagnosis (76% vs. 49%, for Stage ≥2, p&amp;lt;0.001). Compared to Stage 0 paradoxical LFLG patients, adjusted 1- and 5-year cardiovascular-related mortality was 200% (HR 2.82, 95% CI 1.12–7.11) and 120% (HR 2.42, 95% CI 1.46–4.02) higher in Stage 2 patients and 350% (HR 4.23, 95% CI 1.68–10.63) and 175% (HR 3.18, 95% CI 1.90–5.34) higher in Stage 3/4 patients, respectively. Compared to Stage 1 classical LFLG patients, adjusted 1- and 5-year cardiovascular-related mortality was 58% (HR 1.66, 95% CI 0.95–2.90) and 24% (HR 1.35, 95% CI 0.91–1.99) higher in Stage 2 patients and 125% (HR 2.48, 95% CI 1.43–4.28) and 52% (HR 1.87, 95% CI 1.26–2.78) higher in Stage 3/4 patients, respectively. Conclusion In patients with LFLG severe AS identified by echocardiography, increasing severity denoted by the cardiac damage staging classification is strongly associated with increasing medium- to long-term mortality. Funding Acknowledgement Type of funding sources: None. Stages + Classical LFLG 5 year mortalityParadoxical LFLG 5 year mortality curves

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

Value of non-apical echocardiographic views in the up-grading of patients with aortic stenosis

Purpose. Echocardiography assessment from apical five-chamber view (A5CV) is the standard technique for aortic stenosis (AS) grading. Data on non-apical views, such as right parasternal (RPV), subcostal (SCV) and suprasternal notch (SSNV), is scarce and constitutes the aim of our study. Methods. We designed an observational study that included patients with AS recruited prospectively in whom the stenosis was graded by echocardiography from A5CV and non-apical view. The value of non-apical views in up-grading the stenosis severity (primary objective), the prognostic relevance of such reclassification and the feasibility and reproducibility of non-apical views assessment (secondary objectives) was evaluated. Results. Feasibility of AS appraisal from RPV, SCV and SSNV was 78%, 81% and 56%, respectively (SCV vs SSNV, p = .009). AS were up-graded from non-apical views according to peak gradient, mean gradient, area and indexed area by 24%, 17%, 24% and 22%, respectively (p < .0001). Non-apical views reclassified from non-severe to severe AS, from low gradient severe to high gradient severe AS and from non-critical to critical AS 19%, 23% and 3% of cases (p < .0001). The 4-years hard cardiac events rate was 41% in patients with non-severe AS, 67% in patients with severe AS from non-apical views, 68% in patients with severe AS from A5CV and 80% in patients with severe AS from A5CV and non-apical views (p < .001). Reproducibility of AS evaluation from non-apical views was fair to excellent (intraclass correlation coefficients: SSNV = 0.44, RPV = 0.61, SCV = 0.92). Conclusion. Assessment of AS from non-apical views is feasible, reproducible and valuable over A5CV; its use is encouraged.

Cardiac Damage Staging Classification Predicts Prognosis in All the Major Subtypes of Severe Aortic Stenosis: Insights from the National Echo Database Australia

There are currently no established prognostic models for "low-gradient" severe aortic stenosis (AS), including those with low-flow, low-gradient (LFLG) or normal-flow, low-gradient (NFLG) severe AS. The "cardiac damage staging classification" has been validated as a clinically useful prognostic tool for high-gradient severe AS but not yet for these other common subtypes of severe AS, LFLG and NFLG. The authors analyzed data from the National Echo Database of Australia, a large national, multicenter registry with individual data linkage to mortality. Of 192,060 adults (mean age, 62.8±17.8years) with comprehensive ultrasound profiling of the native aortic valve studied between 2000 and 2019, 12,013 (6.3%) had severe AS. On the basis of standard echocardiographic parameters, 5,601 patients with high-gradient, 611 with classical and 959 with paradoxical LFLG, and 911 with NFLG severe AS were identified. Mean follow-up was 88±45months. All-cause and cardiovascular-related mortality were assessed for each group on an adjusted basis (age and sex) and analyzed by cardiac damage stage. Patients with LFLG AS had greater associated cardiac damage at diagnosis (stages 3 and 4 in 34% of those with classical LFLG, 22.5% of those with paradoxical LFLG, 15.5% of those with NFLG, and 14% of those with high-gradient AS; P<.001). For all four major subtypes of severe AS, there was a progressive increase in 1- and 5-year mortality with increasing cardiac damage score. For example, for paradoxical LFLG severe AS, compared with stage 0 patients, adjusted 1-year all-cause mortality was 22% higher in stage 1 patients, 55% higher in stage 2 patients (P=.095), and 155% higher in stage 3 and 4 patients (P<.001). Among patients with classical LFLG severe AS, compared with stage 1 patients, adjusted 1-year all-cause mortality was 55% higher in stage 2 patients (P=.018) and 100% higher in stage 3 and 4 patients (P<.001). Regardless of severe AS subtype, increasing severity denoted by the cardiac damage staging classification is strongly associated with increasing mortality risk.

Impact of surgical aortic valve replacement on global and regional longitudinal strain across four flow gradient patterns of severe aortic stenosis.

To evaluate the impact of surgical aortic valve replacement (SAVR) on global (GLS) and regional longitudinal strain (RLS) across four flow-gradient patterns of severe aortic stenosis (AS) 3 months after surgery.A total of 103 patients with severe AS (aortic valve area < 1.0 cm2) were examined by speckle tracking echocardiography the day before SAVR and at 3-months follow-up. Patients were stratified into four flow-gradient patterns by stroke volume index (>35 mL/m2 vs. ≤35 mL/m2) and mean transaortic gradients (>40 mmhg vs. ≤40 mmhg): normal-flow, high gradient (NF/HG); low-flow, high gradient (LF/HG); normal-flow, low gradient (NF/LG); low-flow, low gradient (LF/LG). Strain analysis comprised GLS and RLS at a basal (BLS), mid-ventricular (MLS) and apical level (ALS).Patients with high gradients improved GLS (NF/HG: 16.1 ± 3.5 % vs. 17.3 ± 3.4 %, p = 0.03 and LF/HG: 15.4 ± 3.6 % vs. 16.9 ± 3.1 %, p = 0.03), BLS (NF/HG: 12.7 ± 3.1 % vs. 14.2 ± 3.1 %, p = 0.003 and LF/HG: 11.4 ± 3.2 % vs. 13.8 ± 2.7 %, p = 0.005) and MLS (NF/HG: 15.4 ± 3.3 % vs. 16.5 ± 3.3 %, p = 0.04 and LF/HG: 14.5 ± 3.1 % vs. 16.2 ± 2.7 %, p = 0.01) whereas patients with low gradients showed no improvements three months after SAVR. ALS did not change significantly in any group. Patients with high gradients demonstrated a reduction in left ventricular (LV) mass index (p < 0.001) and N-terminal pro-Brain Natriuretic Peptide levels (p < 0.001) following SAVR in contrast to patients with low gradients.Patients with high gradient severe AS improve GLS and RLS three months after SAVR with concomitant reduction of LV mass and neurohormonal activation whereas patients with low gradients do not improve longitudinal strain, LV mass or neurohormonal activation.