Severe Aortic Stenosis Patients Research Articles

Machine Learning-Based Predictive Model of Aortic Valve Replacement Modality Selection in Severe Aortic Stenosis Patients.

The current recommendation for bioprosthetic valve replacement in severe aortic stenosis (AS) is either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). We evaluated the performance of a machine learning-based predictive model using existing periprocedural variables for valve replacement modality selection. We analyzed 415 patients in a retrospective longitudinal cohort of adult patients undergoing aortic valve replacement for aortic stenosis. A total of 72 clinical variables including demographic data, patient comorbidities, and preoperative investigation characteristics were collected on each patient. We fit models using LASSO (least absolute shrinkage and selection operator) and decision tree techniques. The accuracy of the prediction on confusion matrix was used to assess model performance. The most predictive independent variable for valve selection by LASSO regression was frailty score. Variables that predict SAVR consisted of low frailty score (value at or below 2) and complex coronary artery diseases (DVD/TVD). Variables that predicted TAVR consisted of high frailty score (at or greater than 6), history of coronary artery bypass surgery (CABG), calcified aorta, and chronic kidney disease (CKD). The LASSO-generated predictive model achieved 98% accuracy on valve replacement modality selection from testing data. The decision tree model consisted of fewer important parameters, namely frailty score, CKD, STS score, age, and history of PCI. The most predictive factor for valve replacement selection was frailty score. The predictive models using different statistical learning methods achieved an excellent concordance predictive accuracy rate of between 93% and 98%.

Impact of chronic kidney disease on fractional flow reserve accuracy in severe aortic stenosis.

Impact of chronic kidney disease on fractional flow reserve accuracy in severe aortic stenosis.

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

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

Effect of Sinotubular Junction Size on TAVR Leaflet Thrombosis: A Fluid-Structure Interaction Analysis.

TAVR has emerged as a standard approach for treating severe aortic stenosis patients. However, it is associated with several clinical complications, including subclinical leaflet thrombosis characterized by Hypoattenuated Leaflet Thickening (HALT). A rigorous analysis of TAVR device thrombogenicity considering anatomical variations is essential for estimating this risk. Clinicians use the Sinotubular Junction (STJ) diameter for TAVR sizing, but there is a paucity of research on its influence on TAVR devices thrombogenicity. A Medtronic Evolut® TAVR device was deployed in three patient models with varying STJ diameters (26, 30, and 34mm) to evaluate its impact on post-deployment hemodynamics and thrombogenicity, employing a novel computational framework combining prosthesis deployment and fluid-structure interaction analysis. The 30mm STJ patient case exhibited the best hemodynamic performance: 5.94mmHg mean transvalvular pressure gradient (TPG), 2.64 cm2 mean geometric orifice area (GOA), and the lowest mean residence time (TR)-indicating a reduced thrombogenic risk; 26mm STJ exhibited a 10 % reduction in GOA and a 35% increase in mean TPG compared to the 30mm STJ; 34mm STJ depicted hemodynamics comparable to the 30mm STJ, but with a 6% increase in TR and elevated platelet stress accumulation. A smaller STJ size impairs adequate expansion of the TAVR stent, which may lead to suboptimal hemodynamic performance. Conversely, a larger STJ size marginally enhances the hemodynamic performance but increases the risk of TAVR leaflet thrombosis. Such analysis can aid pre-procedural planning and minimize the risk of TAVR leaflet thrombosis.

Daily Physical Activity Measured by Wearable Smartwatch for Patients Undergoing Transcatheter Aortic Valve Replacement: Insights From the SMART TAVR Study.

This study aims to evaluate limited data about daily physical activity patterns, influential factors, and their association with 1-year mortality or rehospitalization after transcatheter aortic valve replacement (TAVR) through smartwatches. Consecutive severe aortic stenosis patients undergoing elective transfemoral TAVR in a Chinese tertiary hospital were enrolled from July 2021 to May 2022 and received a Huawei smartwatch at least 1 day before TAVR. The primary outcome was a composite of all-cause mortality or hospital readmission within 1 year. Linear mixed-effects models were applied to determine influential factors of daily step counts, and Cox proportional hazard regression models were to estimate the association between baseline step counts within 1 month since discharge and composite outcome from months 2 to 12. The dose-response association was assessed using restricted cubic spline curves. A total of 222 participants and 59 469 valid monitoring person-day records were included (mean age, 72.7 years; 61% women). Step counts increased rapidly within the first 2 months (P<0.001), followed by a slower increase for those without composite outcomes (P=0.029) and a gradual decrease for those who developed composite outcomes (P<0.001). In multivariate linear mixed models, a 1-m increase in baseline 6-minute walk test and a 1-month delay after discharge were associated with 4 (95% CI, 1-7) and 170 (95% CI, 145-194) additional step counts, respectively. In restricted cubic spline analysis, the hazard ratio declined progressively until ≈5000 steps per day, after which they leveled. Below 5000 steps, the adjusted hazard ratio of composite outcome associated with each 1000-step count increase was 0.67 (0.50-0.89; P=0.007). However, above 5000 steps, step counts were not significantly associated with the composite outcome (P=0.645), with a hazard ratio of 1.12 (0.70-1.79). Daily step counts rapidly increased within the first 2 months post-TAVR. Increased physical activity was associated with a lower risk of 1-year mortality or rehospitalization after TAVR for patients with daily step counts below 5000. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04454177.

Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial

For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients. EARLY TAVR is a prospective, randomized, controlled, and multicenter trial, with an event-based design. Asymptomatic severe AS patients (n=900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary end point is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines. EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance and the first to study the role of TAVR. NCT03042104.

Plasma Transforming Growth Factor-β1 (TGF-β1) Levels Increase with Age and Aortic Stenosis Progression and Low-Dose Galunisertib Attenuates Disease Progression in Mice

Objective: Aortic stenosis (AS) is an age-related degenerative valvular disease that ultimately leads to heart failure and sudden death. Platelet-derived TGF-β1 is a major source of plasma TGF-β1 and contributes to AS progression in LDLR -/-ApoB 100/100(LA100), a mouse model that spontaneously develops AS that simulates human pathology, including fibrosis and high shear gradient. Although risk factors, such as hypercholesteremia and hyperglycemia, are like those for coronary artery disease, lowering cholesterol and glucose has not been successful in stopping progression, and there is no biomarker for early detection of AS. In this study, we measured plasma TGF-β1 levels as a function of age in LA100 mice and human AS patients and tested a new approach of partial inhibition of TGF-β signaling to inhibit AS progression in LA100 mice, while limiting cardiotoxicity. Methods: We measured plasma TGF-β1 levels in controls, severe AS patients, and LA100 mice before they developed AS (2-months of age), when they developed moderate AS (1-year), and when they developed severe AS (2-years). LA100 mice at different stages of AS were treated with low-dose galunisertib, an inhibitor of the TGF-β receptor, ALK5. Results: Plasma levels of total TGF-β1 were significantly higher in AS patients (n=34) compared to healthy controls (n=22) and patient controls (n=47) (p&amp;lt;0.001 for AS patients vs. healthy controls and p=0.049 for AS patients vs. patient controls). Age was positively correlated with total TGF-β1 levels in AS patients (r=0.475; p=0.005), but not patient or healthy controls (r=0.12, p=0.43). LA100mice developed AS with aging and plasma TGF-β1 levels in LA100mice (n=21-52; ages 2 months-2 years) were significantly higher than those in age-matched WT mice (n=23); (p&amp;lt;0.0001). Plasma TGF-β1 levels correlated with age in LA100 mice (R=0.6, p=&amp;lt;0.0001). Low-dose oral galunisertib was administered at a concentration of 1 µM in drinking water, giving an average daily dose of ~0.06 mg/kg, compared to a human cancer treatment dose of ~4.2 mg/kg daily. Galunisertib treatment: a) halted AS progression at all stages in LA100 mice compared to vehicle-treated control mice (p&amp;lt;0.05, n=9-13), b) did not change plasma TGF-β1 levels, c) inhibited TGF-β1 signaling as shown by decreased Smad2 phosphorylation in valve cells compared to vehicle-treated animals. An age-dependent increase in neutrophil to lymphocyte ratio (NY/LY), a marker of inflammation, was observed in LA100 mice compared to control mice (n=12-31; p&amp;lt;0.01), and the NY/LY ratio correlated with total TGF-β1 plasma levels (R=0.16; p=0.020). Galunisertib treatment reduced NY/LY ratios in LA100 mice (p=0.03). Conclusions: 1. Increases in plasma TGF-β1 levels may be a valuable surrogate marker of AS progression. 2. Low-dose galunisertib attenuates AS progression in the LA100 mouse model without producing the cardiotoxicity associated with higher doses and thus may warrant further study in human AS patients.

Prognostic value of flow-status in severe aortic stenosis patients undergoing percutaneous intervention

PurposeLow-flow status is a mortality predictor in severe aortic stenosis (SAS) patients, including after transcatheter aortic valve implantation (TAVI) treatment. However, the best parameter to assess flow is unknown. Recent studies suggest that transaortic flow rate (FR) is superior to currently used stroke volume index (SVi) in defining low-flow states. Therefore, we aimed to evaluate the prognostic value of FR and SVi in patients undergoing TAVI.MethodsA single-centre retrospective analysis of all consecutive patients treated with TAVI for SAS between 2011 and 2019 was conducted. Low-FR was defined as < 200 mL/s and low-SVi as < 35 mL/m2. Primary endpoint was all-cause five-year mortality, analyzed using Kaplan-Meier curves and Cox regression models. Secondary endpoint was variation of NYHA functional class six months after procedure. Patients were further stratified according to ejection fraction (EF < 50%).ResultsOf 489 cases, 59.5% were low-FR, and 43.1% low-SVi. Low-flow patients had superior surgical risk, worse renal function, and had a higher prevalence of coronary artery disease. Low-FR was associated with mortality (hazard ratio 1.36, p = 0.041), but not after adjustment to EuroSCORE II. Normal-SVi was not associated with survival, despite a significative p-trend for its continuous value. No associations were found for flow-status and NYHA recovery. When stratifying according to preserved and reduced EF, both FR and SVi did not predict all-cause mortality.ConclusionIn patients with SAS undergoing TAVI, a low-FR state was associated with higher mortality, as well as SVi, but not at a 35 mL/m2 cut off.

Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New.

Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice.

Transcatheter aortic valve implantation versus surgical aortic valve replacement in severe aortic stenosis patients at low surgical mortality risk: a cost-effectiveness analysis in Belgium

Background Transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 device has recently shown significant clinical benefits, compared to surgical aortic valve replacement (SAVR), in patients at low risk for surgical mortality (PARTNER 3 trial, NCT02675114). Currently in Belgium, TAVI use is restricted to high-risk or inoperable patients with severe symptomatic aortic stenosis (sSAS). This cost-utility analysis aimed to assess whether TAVI with SAPIEN 3 could lead to potential cost-savings compared with SAVR, in the low-risk sSAS population in Belgium. Methods A previously published, two-stage, Markov-based cost-utility model was used. Clinical outcomes were captured using data from PARTNER 3 and the model was adapted for the Belgian context using cost data from the perspective of the Belgian National Healthcare System, indexed to 2022. A lifetime horizon was chosen. The model outputs included changes in direct healthcare costs, survival and health-related quality of life using TAVI versus SAVR. Results TAVI with SAPIEN 3 provides meaningful clinical and cost benefits over SAVR, in terms of an increase in quality-adjusted life years (QALYs) of 0.94 and cost-saving of €3 013 per patient. While initial procedure costs were higher for TAVI compared with SAVR, costs related to rehabilitation, disabling stroke, treated atrial fibrillation, and rehospitalization were lower. The cost-effectiveness of TAVI over SAVR remained robust in sensitivity analyses. Conclusion TAVI with SAPIEN 3 may offer a meaningful alternative intervention to SAVR in Belgian low-risk patients with sSAS, showing both clinical benefits and cost savings associated with post-procedure patient management.

Relative longitudinal strain apical sparing pattern and low albumin as detrimental factors of cardiovascular outcome after transcatheter aortic valve replacement

Abstract Background Relative apical sparing pattern (RASP) of longitudinal strain (LS), a typical echocardiographic feature of cardiac amyloidosis, is associated with cardiac death or heart failure admission in severe aortic stenosis (AS) patients, and associated with all-cause death among elderly patients with severe AS undergoing transcatheter aortic valve replacement (TAVR). Purpose Present study aimed to explore clinical and echocardiographic determinants of short-term and long-term CV outcome (including CV death and CV hospitalization) in symptomatic severe AS patients after TAVR, and to assess the independent and incremental prognostic value of RASP on CV outcome in TAVR patients. Methods This retrospective study comprised 598 consecutive AS patients underwent TAVR (mean age 81.7±5.7 years, 48.7% male). Pre-operative clinical and echocardiography data, including 2D speckle tracking imaging indexes, were analyzed. Clinical outcomes included CV death and procedure related complications at 30 days, 1 year, and at 2 years after TAVR. Results Relative apical sparing pattern (RASP) of longitudinal strain (LS) was defined as ≥3 LV wall segments with the apical-basal LS ratio &amp;gt;3.0. The prevalence of RASP was 19.2%. Compared with patients without RASP, patients with RASP were associated with higher risk of acute kidney injury (AKI, 10.4% vs. 3.3%, P=0.001) and new-onset left bundle branch block (LBBB) after TAVR (17.4% vs. 6.8%, P&amp;lt;0.001) and higher 2-year CV mortality (22.6% vs. 9.9%, P&amp;lt;0.001, Figure 1) after TAVR. Lower pre-procedural albumin level and RASP were identified as independent determinants of increased 2-year CV mortality (RASP: HR=2.178, P=0.002; albumin&amp;lt;4.0g/dl: HR= 2.548, P&amp;lt;0.001), regardless of TAVR approach and EuroSCORE II. After adjustment, the addition of RASP significantly improved prognostic power of a model including clinical variables and low albumin level for predicting 2-year CV death (χ2 from 28.179 to 40.699, P=0.001, Figure 2). Conclusion RASP is a significant determinant of AKI and new-onset LBBB after TAVR. RASP together with low pre-procedural albumin level serve as the strongest determinants of increased risk of 2-year CV mortality after TAVR.Figure 1Figure 2

Association of aortic valve size with the degree of aortic valve calcification in patients with severe aortic stenosis

Abstract Background The development and progression of aortic valve calcification (AVC) is a major contributor to the severity of aortic stenosis (AS). Currently, the 2021 ESC/EACTS Guidelines recommend the use of the Agatston AVC score to predict the likelihood of severe AS in patients with unclear echocardiographic AS severity. It has been shown that AS in women is associated with less AVC, thus lower AVC thresholds for the diagnosis of severe AS in women are recommended. It has furthermore been demonstrated that women generally have smaller hearts. However, whether small aortic valve (AV) size, independent from sex, is associated with less AVC in patients with severe AS has not been explored. Purpose The aim of this study was to assess the association of AV dimension and the degree of AVC in severe AS. Methods AVC was assessed on computed tomography using the Agatston score in consecutive patients with severe AS. AV diameter and indexed AV annulus area adjusted for body surface area were measured. To analyze the association with AVC, Spearman rank correlation as well as multivariate linear regression models adjusted for age, sex, left ventricular ejection fraction and cardiovascular risk factors were performed. Results In total 446 patients (mean age 81±6 years, 45% female) were included. Median Agatston Score was 2949 AU [2135-3986] in men and 1755 AU [1303-2571] in women. Mean AV diameter was 24±2mm and mean indexed annulus area was 248±43mm2. We observed a significant correlation between AV Agatston score and AV diameter (r=0.6; p&amp;lt;0.001 Figure 1 Panel A) as well as between AV Agatston score and indexed annulus area (r=0.5; p &amp;lt;0.001; Figure 1 Panel B). On multivariate analysis AV diameter (β=273; p&amp;lt;0.001), indexed annulus area (β=13; p&amp;lt;0.001) and sex (β=396; p&amp;lt;0.001) were independently associated with AVC by the Agatston score. In addition, separate regression analyses in men and women showed a significant association of AV diameter (β(men)=265; β(women)=275; both p&amp;lt;0.001) and indexed annulus area (β(men)=13; β(women)=11; both p&amp;lt;0.001) with the AV Agatston score. Hypertension, dyslipidemia, diabetes mellitus, smoking and chronic kidney disease showed no statistically significant association with the amount of AVC. Conclusion Our results indicate that patients with severe AS and larger AV dimensions present with more AVC on Agatston scoring, independent from sex. From surgical data, it is known that smaller aortic bioprostheses cause higher gradients, consequently we hypothesize here, that less calcification is required in small valves to cause significant narrowing. Thus, AVC cut-offs for the diagnosis of AS should be indexed for AV size rather than sex.

The traditional classification of aortic stenosis: impact on mortality

Abstract Background The clinical course of patients with aortic stenosis (AS) depends on the stage of the disease which is defined by the degree of the aortic valve stenosis and left ventricular (LV) function. Objectives This study sought to analyze the mortality of different stages of the AS defined by the traditional classification, based on aortic valve area (AVA; cm2), peak velocity across the aortic valve (VP; m/sec), mean pressure gradient across the aortic valve (MGP; mmHg), left ventricular ejection fraction (EF; %) and stroke volume (SV; ml). Methods Single-center, retrospective study. Patients were classified into four groups: Group 1 (moderate AS: 1≤AVA &amp;lt;1.5 cm2 and (20&amp;lt;mg&amp;lt;= 3&amp;lt;vp&amp;lt;="4)),"&amp;gt;40), Group 3 (paradoxical low flow, low gradient AS: AVA&amp;lt;1.0 and MPG≤40 and EF ≥50 and SV&amp;lt; 67) and Group 4 (classical low flow, low gradient AS: AVA&amp;lt;1. and MPG≤40 mmHg and EF&amp;lt;50 and SV&amp;lt;67). Results 2619 patients evaluated for AS between Jan 2014 and Dec 2021 in the central echocardiographic laboratory of the university medical center were initially analyzed. Of them, 1645 patients completed follow-ups and were included in this study. The basic patient characteristics were as follows: mean age 69.6±10.5 yrs, 59% were male, 33% had diabetes mellitus, 15% had atrial fibrillation. The baseline echocardiographic measurements were as follows: VP 4.06±1.4 m/s, PG 67±25 mmHg, MG 40±16 mmHg, AVA 0.83±0.28cm2, LV EDD 5.3±0.73cm, LA diameter 4.4±0.7cm, RV diameter 2.5±0.4cm, RVSP 40.5±12.9 mmHg, EF 60.0±11.8%, SV 70.7±23.7ml. The distribution of patients according to the stages of AS is Group 1: 30%, Group 2: 54%, Group 3: 11%, and Group 4: 5%. During the median 52 months of follow-up, 60% of patients had a surgical aortic valve replacement. In the whole cohort, during the first 5 years, 61.2% of patients died with a significant difference in mortality across the groups: Group 1 vs Group 2 vs Group 3 vs Group 4: 56.5% vs 63.8% vs 54.1% vs 79.4%, p=0.022. The survival analysis (Kaplan Meier) (Picture 1) confirmed significant differences in survival (for overall comparisons: Log Rank (Mantel-Cox) Chi-Square 16.263, p=0.001). The pairwise survival analysis between the groups revealed significant differences between Group 1 vs Group 2 (p=0.018), Group 1 vs Group 4 (p&amp;lt;0.001), Group 2 vs Group 3 (p=0.044), Group 2 vs Group 4 (p=0.021) and Group 3 vs Group 4 (p=0.001). Conclusion Patients with aortic stenosis have still significant mortality during long-term follow-up. It depends on the severity/stages (phenotype) of the disease defined by the traditional classification with an increasing mortality rate from moderate AS, towards classical severe AS and classical LF/LG severe AS, whereas patients with paradoxical LF/LG severe AS have similar survival compared to patients with moderate AS. The impact of early intervention in moderate and paradoxical LFF/LG severe AS patients deserves further investigation.

Prevalence and predictors of pacemaker implantation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: TAVI-NOR study

Abstract Background The transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS) asserts mechanical forces during valve expansion both on the aortic root and conduction system. TAVI is therefore frequently associated with the development of conduction abnormalities requiring a permanent pacemaker implantation (PMI). Purpose To identify predictors of new PMI in unselected patients with severe AS undergoing TAVI. Methods Among the 600 patients consecutively enrolled in TAVI-NOR study, 52 had PMI prior to TAVI and were excluded, remaining 548 patients eligible for this analysis. Predictors of PMI were identified in binary logistic regression analyses. Results A total of 189 patients (31.5%) required a new PMI post TAVI, evenly distributed between females and males (30.1% vs 32.9%, p=0.456). Higher age, comorbidities such as hypertension, chronic kidney disease, coronary artery disease, diabetes, and left ventricular hypertrophy on ECG or echocardiography, and the severity of AS had no association with the risk of PMI after TAVI (Table 1). In univariate logistic regression analyses, larger aortic root diameter was associated with a higher risk of new PMI (OR 1.66; 95% 1.07-2.58, p=0.024), but was no longer significant in multivariate model, and bioprosthesis size had no association with the need for a PMI following TAVI. Bundle branch block (BBB) (OR 1.52; 95% 1.00-2.31, p= 0.051), and especially right BBB (RBBB) (OR 2.05; 95% 1.14-3.70, p= 0.017) showed increased risk of a new PMI, also in a multivariable-adjusted analysis (OR 2.67; 95% 1.39-5.11, p=0.003). Lotus bioprosthesis with mechanical expansion was associated with an increased risk of PMI (OR 2.92; 95% CI 1.92-4.45, p&amp;lt;0.001), while balloon expandable Sapiens had a lower risk for PMI (OR 0.15; 95% CI 0.06-0.37, p&amp;lt;0.001). In a multivariable-adjusted analysis, the use of Lotus valve (OR 2.23; 95% CI 1.44-3.46, p&amp;lt;0.001) was still associated with a higher risk, and use of Sapien with a lower risk of PMI (OR 0.15; 95% CI 0.06-0.40, p&amp;lt;0.001) independent of non-significant association with atrial fibrillation (p=0.067), lower heart rate (0.077), aortic root (p=0.225) and stroke volume index (p=0.097). Adding age and gender to the same primary multivariable-adjusted model did not change our conclusions: Lotus (OR 2.28; 95% CI 1.46-3.57, p&amp;lt;0.001) and RBBB (OR 2.63; 95% CI 1.37-5.04, p=0.004) and Edward Sapien (OR 0.15; 95% 0.06-0.39, p&amp;lt;0.001) of post-procedural PMI. Conclusion Our data from less selected patients with severe AS patients show that pre-intervention RBBB and the use of bioprosthesis with mechanic expansion (Lotus) were associated with a higher risk, and the use of balloon expandable bioprothesis (Sapiens) with a lower risk of PMI after TAVI. We found no gender differences in risk of PMI.

Derivation and validation of risk score to predict mortality or heart failure-related hospitalisation based on clinical and echocardiographic factors in moderate or severe aortic stenosis

Abstract Background Multiple studies from echocardiographic databases have investigated association between moderate or severe aortic stenosis (AS) and poor cardiovascular outcomes. However, outcomes and treatment response are also dependent on the clinical picture. Purpose To improve prognostication and management response of patients with moderate or severe AS by development and validation of a new risk score algorithm that combines clinical and echocardiographic parameters to predict 5-year all-cause mortality or heart failure (HF)-related hospitalisation. Methods 3,452 consecutive patients diagnosed with moderate or severe AS [aortic valvular area &amp;lt;1.5 cm2, peak velocity &amp;gt; 3 m/s or dimensionless severity index &amp;lt; 1.5] were included in this observational cohort study. The least absolute shrinkage and selection operator (LASSO) and logistic regression was used to develop a risk score. This score provided an estimated probability of 5-year composite outcomes of all-cause mortality or HF-related hospitalisation in moderate or severe AS patients. The risk score was then validated with a geographically separate independent test cohort (n=1,788). Results Among 3,452 patients with at least moderate AS with median follow up of 7.3 years, 41 variables were important predictive parameters to be included in risk score (Figure 1). The most significant independent predictors were non-cardiac (Table 1). Areas under the receiver operating characteristic curves for the score were 0.80 (95% CI: 0.79-0.82) in the training set and 0.76 (95% CI: 0.73-0.80) in the test dataset, demonstrating good discrimination. Conclusions A risk score algorithm based on demographics, echocardiography, and clinical features was developed and validated with over 1000 patients. This risk score can be useful to predict outcomes beyond conventional echocardiographic parameters in patients with moderate or severe AS.Fig 1.Score vs 5-yr composite outcomesTable 1.OR for predictors in risk score

Survival in moderate and severe aortic stenosis patients with and without symptoms: a multicenter clinical cohort study

Abstract Background Untreated moderate and severe aortic stenosis (AS) is associated with poor long-term survival, however the association of symptom status with mortality risk remains unknown. Methods Echocardiography report data from an 80-site national cardiology service was extracted and classified into: No AS (mean AV gradient&amp;lt;10.0mmHg or peak AV velocity&amp;lt;2.0m/s, and AVA&amp;gt;1.5cm²), moderate AS (20.0-39.9mmHg/3.0-3.9m/s and AVA&amp;gt;1.0cm2) or severe AS (≥40.0mmHg/≥4.0m/s and/or ≤1.0cm2). Symptom status was extracted using Natural Language Processing of cardiologist reviews and mortality extracted from the National Deaths Index. Native valve AS severity, symptoms and survival were examined during a fixed 2-year follow-up. Results 29,368 individuals (mean age 60.9±17.4 years, 50.3% male) experienced 1,140 fatal events, more likely in severe than moderate AS, but not increased by the presence of symptoms: 16.8 deaths per 1000 person-years in no AS, 35.4 per 1000 person-years in asymptomatic moderate AS, 32.5 per 1000 person-years in symptomatic moderate AS, 68.7 per 1000 person-years in asymptomatic severe AS and 56.1 per 1000 person-year in symptomatic severe AS (p&amp;lt;0.001 compared with no AS). In adjusted models (including age, sex and cardiac damage score), symptomatic moderate and severe AS had similar mortality to asymptomatic moderate AS, with only asymptomatic severe AS showing increased mortality (HR 1.67, 95% CI 1.17-2.38, p=0.005). Conclusions Mortality is increased in both moderate and severe AS, with and without symptoms. The high rates of mortality in asymptomatic severe AS warrants re-examination of the role of symptoms in management decisions, including clinical trials to address whether earlier AVR in asymptomatic moderate and severe AS improves mortality.

Age disparity among severe aortic stenosis patients: AVR treatment rates and clinical outcomes among octogenarians

Abstract Introduction Aortic valve replacement (AVR) is considered one of the most effective disease-modifying procedures among patients with severe Aortic Stenosis (sAS). Accordingly, we can witness a consistent increase in procedure rates in recent years. Nevertheless, the elderly population, particularly octogenarians, remains relatively undertreated. Purpose The current study aims to document the baseline characteristics, disparities in AVR rates, and prognostic significance of AVR among octogenarian vs. non-octogenarian patients with sAS. Methods A vast database of Maccabi health services, the second largest health maintenance organization (HMO) in Israel, counting nearly 2.8 million members, was retrospectively analyzed from 2005 to 2021 for all patients over 60 years, with a detailed echocardiography report compatible with a diagnosis of sAS. Patients who underwent AVR previously or on the same day of their diagnostic echocardiography were excluded. The database was extracted using the MDClone ADAMS healthcare data platform, generating synthetic data reliably representing the original population. All-cause mortality was set to be the primary outcome, and survival models utilizing adjusted multivariable analyses for several clinical and echocardiographic parameters were applied. Results A total of 1359 patients with high-gradient sAS were included in the final analysis, of which 574 (42%) are octogenarians. The octogenarian group included more females (56% vs. 48%), and they had a significantly higher prevalence of hypertension (83% vs. 78%), atrial fibrillation (22% vs. 14%), previous myocardial infarction (12% vs. 8%) and heart failure (20% vs. 10%). Substantial differences were documented regarding AVR-treatment rates between the two groups, with the undertreatment of the octogenarian group (39% vs. 60% of AVR within 18 months from diagnosis of sAS, p&amp;lt;0.001). Differences remained significant in a fully adjusted time-to-event model (HR 0.54, 95% CI 0.46-0.64, p&amp;lt;0.001 for octogenarians) A time-dependent analysis showed that AVR was associated with reduced all-cause mortality (HR 0.30, 95% CI 0.23-0.41, p&amp;lt;0.001) within the octogenarian group in 5 years. A similar protective effect was shown in the non-octogenarian group (HR 0.32, 95% CI 0.22-0.46, p&amp;lt;0.001). Conclusions Despite having comparable survival benefits, octogenarian patients with sAS still receive lower AVR treatment rates than non-octogenarians

Myocardial work index and myofilament calcium sensitivity: possible hand in hand markers of contractility in aortic valve stenosis patients - a translational study

Abstract Background In aortic valve stenosis, conventional echocardiographic parameters, such as ejection fraction (EF), are heavily influenced by the increased afterload caused by the valvular disease. Myocardial work index (GWI) quantifies myocardial deformation depending on the momentary LV pressure, potentially serving as a marker of LV contractility independent of loading conditions. Similarly, myofilament Ca2+ sensitivity (pCa50) followed the alterations of LV contractility in a rat model of pressure overload-induced heart failure. Therefore, GWI and pCa50 may also show correlation, as both can be reliable measures of contractility in diseases of chronically elevated LV afterload. Purpose Accordingly, our first aim was to assess the association of pCa50 and GWI in a rat model of pressure overload-induced heart failure and sham operated animals. We also aimed to evaluate the changes in GWI after myocardial Ca2+ sensitizing with levosimendan in aortic valve stenosis patients. Methods Firstly, on the thoracic aortic banded (n=2) and sham operated (n=3) rats speckle-tracking echocardiography and invasive LV pressure measurements were performed to calculate GWI. Using single permeabilized cardiomyocytes, pCa50 was calculated by myofilament force measurement. Secondly, to test our hypothesis in a clinical setting, 23 severe aortic valve stenosis patients (age 76±9 years, 39% female) were enrolled who received levosimendan therapy. Conventional and advanced echocardiographic measurements were performed before and after a 24-hour intravenous loading dose. We determined global longitudinal strain by speckle-tracking echocardiography, then using LV pressure curves estimated from systolic blood pressure and mean transaortic gradient, we quantified non-invasive global myocardial work index (GWI). Results In the animal study, GWI and pCa50 strongly correlated in the rats (r=0.942; p=0.017). In the clinical study, patients with a baseline EF &amp;lt;35% (n=12) had significantly increased GWI after the levosimendan therapy (533±347 vs. 660±419 mmHg%; p=0.004), while those who initially had an EF &amp;gt;35% (n=11) did not show any change (998±342 vs. 1003±275 mmHg%; p= 0.788). Also, the pre-levosimendan GWI showed a strong inverse correlation with the relative GWI change after the loading dose (r=-0.708; p=0.003). Conclusions We showed in an experimental setting, that GWI and pCa50 correlated in a rat model of pressure overload-induced heart failure and in sham operated controls. In the clinical setting, patients with severely decreased baseline EF and GWI benefited more from the Ca2+ sensitizing therapy, having better LV function after it, while those with better baseline function did not show improvement. Therefore, patients with worse baseline GWI initially might have had decreased Ca2+ sensitivity, which implies a possible correlation between GWI and pCa50 in patients with aortic valve stenosis, resembling the experimental findings.Correlation of pCa50 - GWICorrelation of GWI - relative GWI change

Abstract 15422: Diffuse Myocardial Fibrosis Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Introduction: Patients with moderate or asymptomatic severe aortic stenosis (AS) are at increased risk of cardiovascular events, but markers to guide intervention are lacking. We investigated the use of cardiovascular magnetic resonance (CMR) to identify drivers of outcome. Methods: Moderate (aortic valve area [AVA] 1.0-1.5 cm2) or asymptomatic severe AS patients (AVA≤1.0 cm2 and NYHA functional class I-II) (n=457) were prospectively enrolled from five international sites and parameters including extracellular volume fraction (ECV%) and late gadolinium enhancement were analyzed on CMR. Clinical events were defined as all-cause mortality and admission for heart failure. Results: Moderate AS patients had smaller left ventricular (LV) mass and less diastolic dysfunction compared to asymptomatic severe AS patients, but showed no difference in the extent of myocardial fibrosis and scar. During median 5.7-years follow-up, 83 clinical events occurred. Patients with clinical events had smaller AVA, greater diastolic dysfunction, and higher ECV% (median [interquartile range] ECV% 26.3% [24.3-29.8] vs 28.2% [25.5-30.8], P=0.003). There was a stepwise increase of clinical events across ECV tertiles. ECV% was associated with clinical outcome (adjusted HR 1.05, 95% CI 1.00–1.09, P=0.035), independent of AVA and aortic valve replacement as a time-dependent covariate. The prognostic significance of ECV% was consistent when AS severity was alternatively defined using aortic peak velocity and mean pressure gradient, and also across subgroups by AS severity and symptoms, AVA, aortic peak velocity, mean pressure gradient, and left ventricular ejection fraction (Figure). Conclusions: Increased diffuse myocardial fibrosis is associated with poor outcomes in moderate and asymptomatic severe AS patients and can help identify those who require closer surveillance and possibly earlier intervention.

Abstract 17851: Prevalence and Predictors of Early Left Ventricular Functional Recovery After Transcatheter Aortic Valve Implantation: The TAVI-NOR Study

Introduction: Pre-intervention left ventricular (LV) ejection fraction (LVEF) in aortic stenosis (AS) patients has prognostic value. However, the hemodynamic changes early after TAVI (transcatheter aortic valve implantation) is not fully explored. Hypothesis: To what extent early functional recovery by a clinically significant increase (≥10%) in LVEF is achievable following TAVI, how it differs from baseline patient characteristics, and its potential prognostic impact. Methods: Between 2012 and 2019, 600 consecutive patients (age 81±6years, 49.3% females) with clinically significant AS underwent TAVI. Echocardiography was performed before and within 8 weeks after TAVI. Variables associated with &lt;10% LVEF improvement were identified. End-points were ≥10% LVEF improvement and all-cause mortality. Results: From baseline to follow-up; 28% of patients achieved ≥10% LVEF improvement. A ≥10% LVEF improvement was observed in 25% of patients with normal baseline flow (indexed stroke volume ≥35ml/m 2 ) versus 38% in low-flow (p=0.002). Impaired kidney function, higher blood pressure (BP), higher baseline LVEF and indexed stroke volume, and lower LV mass was more likely in patients with &lt;10% LVEF. In a multivariate logistic regression analysis, higher baseline systolic BP (OR 1.02; 95% CI 1.01-1.03, p=0.004) and lower LV mass (OR 1.25; 95% CI 1.02-1.54, p=0.031), and new pacemaker implantation (OR 1.55; 95% CI 0.99-2.42, p=0.055) were associated with a higher risk, and baseline LVEF &lt;50% with a lower risk (OR: 0.15; 95% CI: 0.09-0.25) for &lt;10% LVEF improvement following TAVI, independent of CKD, baseline troponin T and NT-proBNP. In a univariate Cox regression model, &lt;10% increase in LVEF in early phase after TAVI was not a significant predictor of mortality (HR 1.16; 95% CI 0.90-1.50, p=0.258). Conclusions: Clinically significant early LV functional recovery was evident in nearly one-third of severe AS patients, especially patients with reduced LVEF and more symptoms at baseline. Higher systolic BP, lower LV mass, and the need for new permanent pacemaker, were independently associated with a higher risk of not achieving early LV function recovery after TAVI. In long-term follow-up early LV functional recovery was not associated with all-cause mortality.