Aortic Stenosis Patients Research Articles

Abstract 4145834: Comparison of 30-Day Outcomes of TAVR vs. SAVR in Patients with Prior CABG: A Meta-Analysis

Introduction: Managing severe aortic stenosis in patients with a history of coronary artery bypass grafting (CABG) is challenging. Traditionally, surgical aortic valve replacement (SAVR) was the standard treatment, but transcatheter aortic valve replacement (TAVR) offers a less invasive alternative. This meta-analysis compares the 30-day outcomes of TAVR versus SAVR in patients with prior CABG. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Studies comparing TAVR and SAVR in patients with prior CABG were included. The primary outcomes were 30-day (cardiovascular) CV mortality, all-cause mortality, stroke, and myocardial infarction. Heterogeneity was assessed using the Chi-squared test and I-squared statistic. P value <0.05 was considered statistically significant. Results: Nine studies with a total of 8,487 patients were included for the 30-day outcomes. The pooled odds ratio (OR) for 30-day CV mortality was 1.00 (95% CI: 0.48-2.06), with no significant difference between TAVR and SAVR (p=0.99). For 30-day all-cause mortality, the pooled OR was 0.75 (95% CI: 0.51-1.10), also showing no significant difference between TAVR and SAVR (p=0.14). The pooled OR for 30-day myocardial infarction was 0.34 (95% CI: 0.09-1.27), indicating no significant difference between TAVR and SAVR (p=0.11). However, the pooled OR for 30-day stroke was 0.67 (95% CI: 0.50-0.90), showing a significantly lower incidence with TAVR compared to SAVR (p=0.007). Detailed results in Figure 1. Conclusion: In patients with a history of CABG, TAVR appears to have comparable 30-day outcomes to SAVR in terms of CV mortality, all-cause mortality, and myocardial infarction. However, TAVR is associated with a significantly lower incidence of 30-day stroke. These findings suggest that TAVR may be a safer option in the short term for this high-risk patient population. Further research is needed to confirm these results in larger, randomized controlled trials.

Abstract 4122134: Relationships between aortic valve area planimetry on four-dimensional cardiac computed tomography and survival following transcatheter aortic valve replacement

Background: Aortic valve area planimetry (AVA CT ) is feasible on four-dimensional computed tomography (4D-CT) for grading aortic stenosis severity, with superior spatial but inferior temporal resolution to echocardiography, however its prognostic utility is not well-established. We evaluated the prognostic value of AVA CT in patients with significant aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR). Methods: We studied 1035 native aortic valve stenosis patients (age 79.0±9.0 years, 429 (41.5%) women) undergoing TAVR during 2019-2020. AVA CT and indexed to body surface area (AVAi CT ) were retrospectively measured on contrast-enhanced 4D-CT at peak systole, and standard statistical analyses performed to evaluate its associations with all-cause mortality during follow-up. Results: Mean AVA CT and AVAi CT were 1.02±0.21 cm 2 and 0.53±0.12 cm 2 /m 2 respectively, with 240 (23.2%) deaths during mean follow-up of 2.1±0.9 years. Areas under curves and optimal thresholds for identifying severe aortic stenosis (defined as AVA<1.0 cm 2 on echocardiography) were 0.78 and <1.10 cm 2 for AVA CT and 0.83 and <0.65 cm 2 /m 2 for AVAi CT . AVA CT and AVAi CT below these thresholds representing severe aortic stenosis were independently associated all-cause mortality during follow-up, with hazards ratios (95% confidence intervals) of 1.84 (1.34-2.53) and 2.38 (1.48-3.81) respectively in multivariable analyses. The Figure illustrates Kaplan-Meier survival curves for the cohort based on A) AVA CT and B) AVAi CT thresholds. Conclusion: Optimal thresholds of AVA CT (<1.10 cm 2 ) and AVAi CT (<0.65 cm 2 /m 2 ) were independently associated with worse survival in patients undergoing TAVR, indicating that AVA CT and AVAi CT as potentially useful additional imaging biomarkers in the diagnostic and prognostic evaluation of aortic stenosis patients.

Abstract 4136704: Comparison of Early Clinical Outcomes with Balloon-Expanding Valves Versus Self-Expanding Valves in Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials

Background: Transcatheter aortic valve replacement (TAVR) is an effective percutaneous intervention in patients with severe aortic stenosis, particularly in those with contraindications for surgical repair. Currently, two types of aortic valves are used in clinical practice: balloon-expanding valves (BEV) and self-expanding valves (SEV). The current data comparing early (30-day) clinical outcomes of BEV to SEV in patients with severe aortic stenosis undergoing TAVR are inconsistent. Methods: A systematic literature search spanning PubMed, Embase, Cochrane, and Scopus databases was conducted to retrieve randomized controlled trials (RCTs) comparing balloon-expanding valves to self-expanding valves in patients undergoing TAVR. The DerSimonian and Laird random-effects model was used to pool the odds ratios (OR) with 95% confidence intervals. Statistical significance was set at p<0.05. Results: This meta-analysis included five RCTs with 2190 severe aortic stenosis patients (1097 in the BEV group and 3621 in the SEV group). BEV-TAVR was associated with a significantly lower risk of 30-day new permanent pacemaker (PPM) implantation [OR: 0.67; 95% CI: 0.48, 0.93; p=0.02] and 30-day re-hospitalization for heart failure [OR: 0.20; 95% CI: 0.04, 0.96; p=0.04] compared to SEV-TAVR. The risks of 30-day mortality, 30-day cardiac mortality, 30-day all-cause stroke, 30-day myocardial infarction, 30-day life-threatening bleeding, 30-day vascular complications, 30-day acute kidney injury, and 30-day repeat procedures for valve-related dysfunction were comparable between the two groups. Conclusion: TAVR in patients with severe aortic stenosis using BEV is advantageous over SEV in terms of 30-day new PPM implantation and 30-day rehospitalization for heart failure, with comparable risks for other outcomes. These findings underscore the safety and efficacy of newer generation valves, including Sapien 3 and EvolutPro, in TAVR. The choice of prosthetic aortic valve is dependent on individual anatomy and operator preference. Further RCTs are warranted to evaluate other newer-generation valves with varying severities of aortic stenosis.

Cost-effectiveness analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement in patients with severe aortic stenosis at low risk of surgical mortality in Sweden

Background: Transcatheter aortic valve implantation (TAVI) has shown similar or improved clinical outcomes compared with surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis at low risk for surgical mortality. This cost-utility analysis compared TAVI with SAPIEN 3 versus SAVR in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of the Swedish healthcare system. Methods: A published, two-stage, Markov-based cost-utility model that captured clinical outcomes from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated according to Recommended Therapies (SWEDEHEART) registry (2018–2020) was adapted from the perspective of the Swedish healthcare system using local general population mortality, utility and costs data. The model had a lifetime horizon. Model outputs included changes in direct healthcare costs and health-related quality of life from using TAVI as compared with SAVR. Results: TAVI with SAPIEN 3 resulted in lifetime costs per patient of 940,541 Swedish krona (SEK) and lifetime quality-adjusted life years (QALYs) per patient of 7.16, whilst SAVR resulted in lifetime costs and QALYs per patient of 821,380 SEK and 6.81 QALYs, respectively. Compared with SAVR, TAVI offered an incremental improvement of +0.35 QALY per patient at an increased cost of +119,161 SEK per patient over a lifetime horizon, resulting in an incremental cost-effectiveness ratio of 343,918 SEK per QALY gained. Conclusion: TAVI with SAPIEN 3 is a cost-effective option versus SAVR for patients with symptomatic severe aortic stenosis at low risk for surgical mortality treated in the Swedish healthcare setting. These findings may inform policy decisions in Sweden for the management of this patient group.

Cardiopulmonary exercise testing in aortic stenosis patients before and after aortic valve replacement

BackgroundKnowledge about how patients with symptomatic aortic stenosis (AS) perform on cardiopulmonary exercise testing (CPET) is sparse. Since exercise testing in patients with symptomatic AS is not advised, submaximal parameters...

Early Detection of Left Ventricular Dysfunction With Machine Learning-Based Strain Imaging in Aortic Stenosis Patients.

Aortic stenosis (AS) is a common cardiovascular condition where early detection of left ventricular (LV) dysfunction is essential for timely intervention and optimal management. Current echocardiographic measurements, such as ejection fraction (EF), are insensitive to minor changes in LV function, and strain imaging is typically limited to the global longitudinal strain (GLS) parameter due to robustness issues. This study introduces a novel, fully automatic algorithm to enhance the detection of LV dysfunction in AS patients using multiple strain imaging parameters. We applied supervised machine-learning techniques to classify data from 82 severe AS patients, 96 chest pain subjects, and 319 healthy volunteers. Our model significantly outperformed EF and GLS in distinguishing AS patients from healthy volunteers (area under the curve [AUC] = 0.97 vs. 0.88 and 0.82, respectively). It also surpassed EF and GLS in differentiating AS patients from chest pain subjects (AUC = 0.95 vs. 0.90 and 0.55, respectively). This novel, clinically interpretable model leverages the potential of strain imaging to enhance diagnostic accuracy and guide clinical decision-making in LV dysfunction, thereby improving clinical practice.

Progression of aortic stenosis in patients with diabetes mellitus type 2 compared with matched controls

Abstract Background Degenerative aortic stenosis (AS) and diabetes mellitus type 2 (DM) increase with age1,2 and their prevalence is expected to rise. Patients with DM have a higher risk to develop AS3 and the pathophysiological process leading from a normal aortic valve to AS involves factors associated with DM. AS develops over years, but it can evolve more rapidly. There is insufficient knowledge about risk factors for rapid progression in AS and monitoring strategies among patients at high risk for rapid progression. The aim of this project is to evaluate the AS progression towards combined outcome (incident heart failure, death, need for intervention) in patients with type 2 DM compared with matched controls. Methods From the Swedish National Diabetes Register (NDR) we identified all patients with type 2 DM between 01-01-2001- 31-12-2019 and for each patient 5 controls (matched for age, sex, region) from the Swedish Total Population Register. Afterwards we identified a cohort of individuals with AS from these two groups, by linking the NDR with the National Patient Register. The outcomes were: all- cause and cardiovascular mortality, and combined outcome (mortality, hospitalization for heart failure (HF) or aortic valve replacement (AVR)). We used Kaplan Meier survival curves to detect differences in all-cause mortality, cardiovascular mortality, time until AVR and combined outcome between cases and controls. Cox proportional hazards model adjusted for sex, age, obesity, renal failure, hyperparathyroidism, hypertension, hyperlipidemia was used to study the risk difference between the cases and controls for the combined outcome. Results We identified 16 144 individuals with type 2 DM and AS and 31 206 matched controls. The individuals with type 2 DM were predominately men (59% vs 53%), younger (mean age 70.6 vs 71.9), and had more comorbidities. In unadjusted analysis they were hospitalized for HF more often (8.2% vs 6.8%) and more often underwent AVR (surgically) (22.0% vs 19.0%) or transcatheter(6.6% vs 5.0%). Patients with AS and DM had higher all-cause and cardiovascular mortality and faster progression towards death, AVR or hospitalization for HF (see figure 1, A, B, C). The progression to AVR was significant, although the difference was small and not clinically relevant (plot D). In the adjusted model, the patients with AS and DM had 13% higher hazard to have the combined outcome compared with controls (see figure 2). Sex (female), hypertension and hyperlipidemia lowered the hazard for the combined event, while obesity, hyperparathyroidism and renal failure increased the hazard for the combined event. Conclusions Patients with concomitant AS and DM seem to have faster progression towards death (both all-cause and cardiovascular), and heart failure hospitalization or AVR compared with patients with AS without DM. Therefore, it might be appropriate to be more active regarding follow-up and intervention in these patients.Kaplan Meirer curvesForest plot for adjusted Cox model

Nitisinone attenuates progression of aortic stenosis in patients with alkaptonuria: an analysis of the SONIA 2 study

Abstract Background/introduction Alkaptonuria (AKU) is a rare metabolic disorder caused by a defective enzyme, resulting in deposition of unmetabolised homogentisic acid in various connective tissues throughout the body (also termed "ochronosis"). Ochronosis of the aortic valve leading to progressive aortic stenosis is a rare but serious complication. Nitisinone decreases urinary and serum homogentisic acid levels and has been shown to improve morbidity and slow disease progression in AKU but the effects of this treatment on the progression of aortic stenosis have not yet been described. This review extrapolated from the data set of the SONIA 2 study, a 4-year multi-centre, randomised controlled trial investigating the effect of nitisinone on a composite clinical measure of AKU disease activity, but looked more specifically at measures of aortic stenosis disease progression. Methods Data was obtained from echocardiograms performed on 138 patients at baseline, 12, 24, 36 and 48 months of follow-up. In measuring the degree of aortic stenosis, the peak trans-aortic velocity (Vmax) was examined. A linear mixed effects regression model was used to assess the association between treatment and Vmax and to ascertain the difference in this measure at baseline and 48 months between the treatment and control groups. The mixed effects model incorporated both fixed effects for population parameters (age, sex, baseline Vmax, follow-up time) and treatment; and random effects, to account for intra-subject correlation of longitudinal observations of Vmax, inter-subject variability of baseline measurements of Vmax, and centre. Results At baseline, 19/138 patients (13.8%) had aortic stenosis, as classified by echocardiogram findings in accordance with the European Society of Cardiology (ESC) guidance on valvular heart disease, with 9/19 having mild aortic stenosis, 6/19 having moderate aortic stenosis and 4/19 having severe aortic stenosis. 25/138 had aortic sclerosis (see figure 1). The prevalence of aortic valve disease increased with age. From the 4-year follow-up period, 613 longitudinal observations of 138 subjects across all sites were obtained. At baseline, the difference in Vmax between the control and treatment groups was 0.063 m/s [95% CI: -0.054 m/s to 0.18 m/s] and did not reach statistical significance (p=0.23). At the end of the 4-year treatment period, the difference in Vmax was 0.10 m/s [95% CI: -0.0007 m/s to 0.20 m/s] and was statistically significant (p=0.05) (see figure 2). Conclusion Nitisinone slowed progression of aortic stenosis in patients with AKU. This may be grounds for timely initiation of nitisinone in those deemed to be at high risk, as identified by echocardiography. Of note, this is the first time that any medical therapy has ever been shown to affect the natural history of aortic stenosis.

Phenotype of patients with severe aortic stenosis and small aortic annulus: how does it impact on hemodynamics and on transcatheter aortic valve implantation outcomes

Abstract Background Discordant grading of severe aortic stenosis can result from a tight aortic valve area (<1cm2) with a low transvalvular mean gradient (<40 mmHg). Small aortic annulus dimensions and low flow status may contribute to discordant grading of severe aortic stenosis. However, the frequency of patients with small aortic annulus and discordant grading, along with their characteristics and outcomes after intervention, remains unknown. Purpose To investigate the frequency of discordant grading severe aortic stenosis in patients with a small aortic annulus and to evaluate their clinical characteristics, as well as outcomes after transcatheter aortic valve implantation (TAVI). Methods Patients with an aortic annulus diameter < 23 mm determined by cardiac computed tomography who underwent TAVI between 2018 to 2023 were retrospectively evaluated. Patients were followed for the occurrence of the composite endpoint of of all-cause mortality, rehospitalizations for heart failure, non-fatal myocardial infarction, and non-fatal stroke. Results Among 230 patients with severe aortic stenosis and a small aortic annulus, 52 (23%) had discordant gradient (24 with low flow low gradient (LFLG) and 28 with normal flow low gradient (NFLG)) while 120 (52%) exhibited normal flow high gradient (NFHG) and 58 (25%) had low flow high gradient (LFHG). The majority of the patients were female (Table 1). Differences were noted among the three groups regarding aortic transvalvular gradients, stroke volume index and ejection fraction. During a median follow-up of 2 years, the composite endpoint occurred in 20% of the total cohort. Patients with discordant grading severe aortic stenosis experienced the worse outcome (Figure1). Conclusions Most patients with severe aortic stenosis and small annulus have high gradient and only 23% of patients presented discordant grading. Patients with discordant grading severe aortic stenosis showed worse outcomes, suggesting potential delays in referral due to challenges in diagnosing severe aortic stenosis among patients with small aortic annulus.Basal clinical characteristicsKaplan-Meier survival curves

Valvular heart disease and out-of-hospital cardiac arrest

Abstract Background The prevalence of valvular heart disease is on the rise. Severe valvular diseases are generally associated with high mortality, and aortic stenosis (AS) is associated with halved survival after out-of-hospital cardiac arrest (OHCA). Despite the severity of the prognosis of valvular heart diseases, their association with the risk of OHCA is not well-elucidated. Purpose The study aimed to examine the association between valvular heart disease and OHCA. Method We conducted a study using data from the nationwide Danish Cardiac Arrest Registry. We included adult OHCA patients with presumed cardiac origin. We compared OHCA cases with and without valvular heart disease, stratified by valvular disease type (AS, aortic regurgitation (AR), mitral stenosis (MS), and mitral regurgitation (MR) or multiple valvular diseases (more than 1 concomitant type of valvular disease)). We calculated the hazard ratios of OHCA using time-varying Cox regression models fitted with a nested case-control design. For each case, we matched up to five controls based on age, sex, year of OHCA, and two comorbidities: ischemic heart disease and congestive heart failure. Results We included 43,967 OHCA cases and 219,772 controls matched from the general population. In the total case population, the median age was 72 years, 68% were male, 26% had ischemic heart disease, 21% had congestive heart failure, and 57% had cardiovascular risk factors. We identified 1862 (4.23%) cases with AS, 336 (<1%) with AR, 31 with MS (<1%), 710 with MR (1.6%), and 605 with multiple valvular diseases (1.4%). Compared with cardiac arrest cases without valvular disease, cases with valvular disease were more likely to have ischemic heart disease (e.g., AS vs controls: 6.5% vs 1.7%, p<0.001) and congestive heart failure (e.g., MR vs controls: 3.5% vs 1%, p<0,001; AS vs controls: 8.2% vs 2.8%, p<0.001). AS, MS (HR: 1.67 [95%CI: 1.12; 2.51]), MR (HR: 1.38 [95%CI: 1.27; 1.50]) and multiple valvular diseases (HR: 1.36 [95%CI: 1.24; 1.49]) were significantly associated with higher hazard of OHCA (Figure 1); the strongest association was seen for AS (HR: 1.66 [95% CI: 1.58; 1.76]) (Figure 1). AR was not significantly associated with OHCA (HR: 1.05 [95%CI: 0.94; 1.19]). Conclusion In this Danish nationwide cardiac arrest cohort, aortic stenosis, aortic regurgitation, and mitral regurgitation were associated with increased rates of OHCA. The association was strongest in aortic stenosis patients. Focus on risk factors of OHCA in patients with valvular heart disease is warranted.Figure 1

Long-term outcomes of aortic stenosis patients with different flow/gradient patterns undergoing transcatheter aortic valve implantation

Abstract Background Few data exist on the comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of the pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI. Methods Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided into four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow—low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35 mL/m2 and mean gradient (MG) < 40 mmHg); (ii) normal flow—low gradient (NF-LG): SVi > 35 mL/m2 and MG < 40 mmHg; (iii) low flow—high gradient (LF-HG): Svi 35 mL/m2 and MG ≥ 40 mmHg and (iv) normal flow—high gradient (NF-HG): SVi > 35 mL/m2 and MG ≥ 40 mmHg. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow-up was complete for all patients. Results A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80 ± 7 years and the majority of patients (N = 138, 50.8%) were women. 62 patients (22.8% of the study population) were distributed in the LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, and 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log-rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%), and NF-LG patients (58.8%) (log-rank p: 0.029) (Figure 1). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918–0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645–5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456, 95% C.I.: 1.106–1.792) were significant independent predictors of late global mortality. Conclusions Patients with LF-LG AS have acceptable 1-year outcomes, but exhibit exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients.

Myocardial work and aortic valve stenosis cardiac damage stages are predictors of all-cause mortality in patients undergoing transcatheter aortic valve replacement

Abstract In aortic stenosis (AS) patients, assessment of left ventricular (LV) systolic function is complicated due to the significant impact of increased afterload on conventional parameters. Myocardial work (MW) analysis, a novel echocardiographic method adjusts myocardial deformation to instantaneous LV pressure which may better reflect the LV contractile state. Importantly, long-term LV pressure overload has marked backward effects beyond the LV: classification of this extravalvular cardiac damage effectively represents the involvement of the cardiopulmonary system in AS. Both MW and cardiac damage staging could hold remarkable prognostic power in the clinically complex population of transcatheter aortic valve replacement (TAVR) candidates. Accordingly, our aim was to assess the prognostic value of MW analysis and cardiac damage staging in patients undergoing TAVR. We enrolled 289 patients (79±6 years, 41% female) prior to TAVR. Echocardiographic measurements were performed one day before the procedure. We calculated LV ejection fraction (EF) and by speckle-tracking echocardiography global longitudinal strain (GLS), as well. Global constructive work (GCW) was quantified with dedicated software and LV pressure was estimated using transaortic mean gradient and systolic blood pressure. Based on the echocardiographic data, we also determined the extent of cardiac damage associated with AS: patients were classified as Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). Our primary outcome was all-cause mortality, reached by 68 patients (median follow-up: 26 months). In our cohort, preprocedural EF was 47±13 %, GLS was -12.3±4 %, while GCW was 2043±791 mmHg%. 14 (5%) patients were classified as Stage 0, 61 (21%) as Stage 1, 128 (44%) as Stage 2, 15 (5%) as Stage 3, and 71 (25%) as Stage 4. GCW showed a continuous decline through the AS Stages (from Stage 0-4: 2963±652 vs. 2154±652 vs. 2168±718 vs. 1988±969 vs. 1552±772 mmHg%; p<0.001). Using univariate Cox analysis GCW (HR 0.968 [95% CI 0.938-0.998] per 100 unit change; p=0.034) and AS Staging (HR 1.236 [95% CI 1.015-1.505]; p=0.035) were both associated with all-cause mortality, while EF (HR 0.984 [95% CI 0.966-1.002]; p=0.085) and GLS (HR 1.042 [95% CI 0.984-1.103]; p=0.160) were not. In multivariate Cox regression models, both GCW (HR 0.957 [95% CI 0.922-0.992] per 100 unit change; p=0.018) and AS cardiac damage staging (HR 1.263 [95% CI 1.029-1.549]; p=0.025) were proven to be significant independent predictors of all-cause mortality. In TAVR patients, preoperative GCW values exhibited a persistent decrease across AS Stages. As opposed to EF and GLS, GCW and AS Staging both showed strong association with all-cause mortality in our cohort. Moreover, GCW had higher prognostic value than any other conventional or advanced measure of LV function.

Baseline right ventricular-pulmonary artery uncoupling and mortality following transcatheter aortic valve replacement: a meta-analysis

Abstract Background In severe aortic stenosis (AS) patients, elevated left-sided filling pressures can lead to pulmonary hypertension and right ventricular (RV) systolic dysfunction. These conditions signal advanced disease and predict poor outcomes in transcatheter aortic valve replacement (TAVR) cases. However, recent studies indicate potential recovery post-TAVR, with improved prognosis. The newly recognized index, RV to pulmonary artery (RV-PA) coupling, reflects the RV's ability to handle pulmonary afterload and is associated with adverse outcomes. Purpose This study aimed to delineate the prognostic role of baseline RV-PA uncoupling in patients undergoing TAVR. Methods We conducted a systematic literature search for studies assessing RV-PA coupling indices at baseline in patients undergoing TAVR. We recorded the year of publication, method of RV-PA assessment, the proposed cutoffs, patients’ age-sex, and follow-up duration. The primary outcome of interest was all-cause mortality at maximal follow-up and the adjusted hazard ratios of RV-PA uncoupling for all-cause mortality were extracted. Pooling of the hazard ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being significant. Results We identified a total of 316 studies, of which 5 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All but one study utilized the Tricuspid Annular Plane Systolic Excursion/Pulmonary artery systolic pressure (TAPSE/PASP) as the method of RV-PA assessment. The mean age of the participants across the studies was approximately 81 years old, with a balanced male:female ratio. The median follow-up duration was 23 months (range: 6-40 months). According to the results of the meta-analysis, the presence of baseline RV-PA uncoupling was associated with a 2.8-fold increased risk of all-cause mortality at maximal follow-up (Figure). Significant between-study heterogeneity was detected. An asymmetric funnel plot was inspected, indicative of publication bias (Egger’s test intercept: 6.76, 95% confidence interval 5.07-8.44, p=0.004). The results, although attenuated, remained significant even after a trim-and-fill analysis (3 studies added, hazard ratio: 1.27, 95% confidence interval: 0.03-2.51, p=0.04). Furthermore, the results were unaffected following a sensitivity analysis with the leave-one-out method. Conclusion This meta-analysis suggests that baseline RV-PA uncoupling prior to TAVR is associated with all-cause mortality and it could serve as an imaging biomarker of prognosis in this patient population.Figure

The effect of transcatheter aortic valve implantation on fractional flow reserve and non-hyperemic pressure ratios

Abstract Background Coronary artery disease in patients undergoing transcatheter aortic valve implantation (TAVI) is a very frequent clinical issue. Complex coronary artery disease can negatively influence outcomes after TAVI, however, angiography-guided percutaneous coronary intervention (PCI) has not been shown to offer any prognostic benefit. Coronary pressure indices, to select which lesions need treatment, are promising but are currently underused in aortic stenosis (AS) patients due to many physiological pitfalls. Available studies are small and show conflicting results on the effect of transcatheter aortic valve implantation (TAVI) on these indices. Purpose The aims is to compare the effects of TAVI on fractional flow reserve (FFR) and Non-hyperemic pressure ratio’s (NHPRs). Both immediate and long-term effects were studied. Methods Lesion specific coronary pressure data was extracted from 6 studies resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Results Immediately after TAVI, FFR decreased significantly (-0.0130 ± 0.0406 standard deviation, p-value: 0.0002) while NHPR remained stable (0.0003 ± 0.0675, p-value: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230 ± 0.0747, p-value:0.0038) while NHPR increased non-significantly (0.0166 ± 0.0699, p-value: 0.0543). This increase in NHPRs became significant when only borderline NHPR lesions were considered (0.0249 ± 0.0441, p-value: 0.0015). All other results were confirmed in borderline-only lesions. Conclusions TAVI caused small significant, but opposite, changes in FFR and NHPR. In AS, FFR might underestimate lesion significance while NHPRs might overestimate its significance. This is only clinically relevant in borderline lesions, clear positive or negative physiological assessments can be trusted.Figure 1Figure 2

Echocardiographic evaluation of right ventricle to pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

Abstract Background Right Ventricle to Pulmonary Artery (RV/PA) uncoupling, which depicts the inability of RV contractility to match the increasing RV afterload, has recently gained recognition as a simple echocardiography parameter to aid prognosis judgment in patients with RV dysfunction. In Aortic Stenosis (AS) patients, the extent of RV dysfunction and Pulmonary Hypertension (PH) has been linked with poor outcomes, but the prognostic value of RV/PA uncoupling in AS patients undergoing TAVI has not been well-defined. Purpose To investigate the prognostic value of RV/PA uncoupling and its association with echocardiographic parameters in AS patients undergoing TAVI. Methods We conducted a systematic search through Pubmed and Embase to include studies up to February 2024. Studies were eligible if they evaluated the prognostic performance of RV/PA uncoupling in AS patients undergoing TAVI. Random-effects model were employed to pool the adjusted Hazard Ratio (aHR) with inverse-variance weighting method or Relative Risk (RR) with 95% Confidence Interval (95% CI) using Mantel-Haenszel test for categorical outcomes or Weighted Mean Difference (WMD) for numerical outcomes. Risk of bias assessment was conducted using the Newcastle Ottawa Scale (NOS). Results Thirteen studies were included. Out of 4,146 patients, 55.21% were reported to have RV-PA uncoupling prior to TAVI. RV/PA uncoupling was customarily assessed with TAPSE/PASP ratio, with threshold for uncoupling ranging between <0.31–<0.63 mm/mmHg. Follow-up period ranged between 6–65 months. Patients with baseline RV/PA uncoupling had lower LVEF (WMD -9.94% [-4.36– -15.53%]; I2 = 78%), lower TAPSE (WMD -4.98 mm [95% CI -1.15– -8.80]; I2 = 95%), and higher PASP (WMD 19.77 [95% CI 17.02–22.51]; I2 = 0%) compared to patients with RV/PA coupling at baseline. Baseline RV-PA uncoupling was an independent predictor of all-cause mortality (pooled aHR = 2.26 (95% CI 1.36–3.76); I2 = 77%) and composite endpoint of mortality and adverse cardiac or cerebrovascular events (pooled aHR = 2.07 (1.30–3.29); I2 = 24%). However, RV/PA uncoupling was not significantly associated with a higher risk of permanent pacemaker implantation after TAVI (pooled Risk Ratio 1.02 [0.70–1.47]; I2 = 0%). Conclusion Pre-procedural RV/PA uncoupling emerges as an independent predictor of worse prognosis in AS patients undergoing TAVI, contributing to a better understanding of the impact of this parameter on patient outcomes.

Predisposing and precipitating factors of post-operative delirium after transfemoral TAVI

Abstract Background Transcatheter aortic valve implantation (TAVI) represents the treatment of choice for aortic stenosis (AS) patients at higher age (> 75y) or with relevant comorbidities. Post-operative delirium (POD) is a frequent complication which has been associated with worse outcome. Thus, preventive options are highly needed. The aim of our single-center study was to investigate predisposing and precipitating factors of POD after transfemoral TAVI, with a focus on the influence of anaesthesia. Methods Risk factors for POD after TAVI were analysed in 2 merged cohorts of 480 study patients (43% women; mean age 80 years), enrolled in 2017-2022 (n=375, TAVI in 95% in general anaesthesia) and in 2022-2024 (n=105, TAVI in 91% in local anaesthesia). Incidence of POD was evaluated retrospectively by nursing documentation, medical records, and DRG coding. The association of demographics, comorbidities, echo parameters, procedural parameters, anaesthesia, and peri-procedural complications with POD incidence was investigated. Results In total, 29 patients (6%) developed POD, with a tendency towards a lower incidence in the later cohort (6.7% vs. 3.8%; p=0.28). Regarding baseline characteristics, patients experiencing POD were more likely to be male (p=0.03), frail (Katz Index <6, p=0.049), and to suffer from low-gradient AS (p=0.005 for paradoxical, p=0.02 for classical low-flow, low-gradient AS; see also fig. 1A). Total procedure time was significantly longer in patients with POD (median, 86 vs. 62 min, p=0.004; fig 1B), and a tendency towards a more frequent implantation of other than ballon-expandable valves could be observed (p=0.07). Concerning the role of anaesthesia, POD did not differ significantly after general anaesthesia (n=24/360, 6.7%), conscious sedation (n=1/19, 5.3%), and local anaesthesia (n=4/100, 4%) (p=0.38). Regarding procedural complications, POD patients were characterized by lower minimum hemoglobin post-TAVI (9.3 vs. 10.1 g/dl, p=0.05; fig. 1C) and higher incidences of intra-procedural resuscitation (11% vs. 2%, p=0.03), cerebrovascular accidents (10% vs. 2%, p=0.04) and new permanent pacemaker implantations (25% vs. 10%, p=0.02). In POD patients, long-term survival after TAVI was significantly reduced, with a median survival of only 2 years (Kaplan-Meier curves in fig. 2; p=0.001). Conclusions POD after TAVI stays common and unfavourable. The role of anaesthesia seems less pronounced than expected. Total procedure time and relevant anaemia after TAVI emerged as most important modifiable risk factors. Future research is warranted, since strategies to reduce precipitating factors for POD may have a significant impact on post-TAVI outcomes.Selected risk factors for PODConsequence of POD: Reduced Survival

Association between silent cerebral embolism and cognitive alterations following transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valve patients

Abstract Background Silent cerebral ischemic lesions (SCILs) is a common magnetic resonance imaging (MRI) finding in severe aortic stenosis patients post - transcatheter aortic valve replacement (TAVR). We evaluated the association between SCILs and cognitive alterations in patients with bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) post-TAVR. Methods This study enrolled 100 consecutive TAVR (45 with BAV and 55 TAV). DW-MRI and neurocognitive evaluation (MoCA score) were performed at baseline, discharge, and 1- and 12-month post-discharge. Results Ninety-two out of the 100 patients (92%) exhibited cognitive dysfunction at baseline. Post-TAVR, overall cognitive function significantly improved, the average MOCA score increased from 18.69±6.74 to 22.18±6.30. During the 1-year follow-up, 54 patients demonstrated improved cognitive function, and the number of patients with moderate-to-severe cognitive dysfunction (MoCA score < 18) significantly decreased from 32 to 16. Prevalence of SCILs was 14% and 72% at baseline and discharge, respectively. New SCILs were observed in 60 patients at discharge, distributed across all vascular territories, averaging 4 lesions with a total volume of 215.4±195.4mm3. Although no significant correlation existed between total volume of new SCILs and cognitive changes post-TAVR (R=-0.133, p=0.206), patients with SCILs still displayed significant cognitive improvement (MoCA score from 18.4±6.6 to 22.0±7.1), whereas patients who developed large SCILs (lesion diameter >9) showed less improvement compared to those with small or median SCILs (number of patients who had cognitive improvement: 32 vs. 52, p<0.05). Cognitive function improvement post-TAVR did not significantly differ between BAV and TAV patients, MoCA scores were comparable (BAV group, n=45, from 18.63±6.68 to 21.88±6.80 vs. TAV group, n=55, from 18.73±6.81 to 22.42±5.80; p>0.05). DW-MRI revealed more new SCILs in BAV patients post-TAVR compare to TAV patients (235 lesions vs. 150 lesions, respectively). In BAV patients, SCILs primarily manifested in small and medium sizes (224 lesions), despite more severe calcification (valvular calcium volume 956.5±644.0 mm vs. 634.4±508.0 mm3; p=0.028). The number of large lesions was similar in the two groups (11 in BAV group and 10 in TAV group). Conclusion TAVR demonstrates positive effects on improving cognitive function in aortic stenosis patients, despite common occurrence of SCILs in both BAV and TAV patients. Cognitive function post-TAVR was comparable between BAV and TAV patients. The cognitive improvement from TAVR may be less impacted by small- and medium-sized SCILs, while severe SCILs might impede or diminish the cognitive benefits of TAVR.table

Transcatheter versus surgical aortic valve replacement in aortic stenosis patients requiring mechanical circulation support: a nationwide Japanese study

Abstract Introduction Transcatheter aortic valve replacement (TAVR) has demonstrated comparable clinical outcomes to surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS). However, previous trials excluded patients who had required mechanical circulatory support (MCS) for cardiogenic shock. Thus, the clinical feature of aortic valve replacement requiring MCS and the efficacy of TAVR compared to SAVR has not been fully exhibited in AS patients. Purpose This study investigated the demography and clinical outcomes comparing TAVR and SAVR for AS demanding MCS. Methods The current study was an observational retrospective study using Japanese nationwide data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Between April 1, 2012, and March 31, 2022, AS patients undergoing TAVR or SAVR who required MCS were evaluated. The primary outcome was 30-day mortality. In addition, we assessed ischemic stroke, hemorrhagic stroke during hospitalization. Result During the period, 80,752 patients (TAVR=36,546 and SAVR=44,206) were identified. The frequency of MCS (intra-aortic balloon pumping and/or extracorporeal membrane oxygenation) was 3.0% (1,097 patients) of the TAVR group and 4.8% (2,133 patients) of the SAVR group. In the TAVR group, 78% of patients were implanted balloon-expandable valve and 7.1% of patients were transapical apical approach. TAVR was performed in older (median age: 85 years vs. 76 years, p<0.001), lower body mass index (BMI) (median BMI: 21.5 kg/m2 vs. 22.7 kg/m2, p<0.001), and more female patients (42% vs. 27%, p<0.001) than SAVR. The 30-day mortality was lower in TAVR than SAVR (12% in TAVR and 19% in SAVR, p<0.001) (Figure). After adjusting age, gender, TAVR was significantly associated with decreased 30-day mortality compared to SAVR (adjusted HR 0.52 (0.41–0.67), p<0.001). In contrast, the incidence of ischemic stroke and hemorrhagic stroke were comparable in 2 groups (ischemic stroke; 4.2% in TAVR vs. 4.1% in SAVR, p=0.93 and hemorrhagic stroke; 0.3% vs. 0.3%, respectively). Conclusion According to nationwide real-world clinical data on aortic valve replacement for AS, the frequency of patients requiring MCS due to cardiogenic shock was 3.0% in the TAVR group and 4.8% in the SAVR group. Our findings demonstrated short-term outcomes following TAVR for patients requiring MCS for cardiogenic shock was better than those following SAVR.

Mortality rates in patients undergoing urgent versus elective transcatheter aortic valve replacement: a systematic review and meta-analysis

Abstract Background Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, leading frequently to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR to elective procedures. Methods We systematically screened three databases searching for studies comparing urgent versus elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-day stroke, 30-day acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage and 30-day bleedings. Results Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality (RR: 2.53, 95% CI: 1.81 – 3.54), in-hospital mortality (RR: 2.67, 95% CI: 1.94 – 3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28 – 2.85) and AKI (RR: 2.83, 95% CI: 1.93 – 4.14), compared to elective procedure. No differences were observed in the rest secondary endpoints. Conclusions Urgent TAVR was associated with higher in-hospital and 30-day mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.

Transcatheter aortic valve implantation with SAPIEN 3 versus surgical aortic valve replacement in patients with symptomatic severe aortic stenosis at low risk of surgical mortality: a cost-utility analysis for Switzerland.

The 2021 European Society of Cardiology Guidelines on valvular heart disease recommend transcatheter aortic valve implantation (TAVI) for patients with symptomatic severe aortic stenosis at low surgical risk and age ≥75 years who are suitable for a transfemoral approach (recommendation class IA) based on two large randomised controlled trials (PARTNER 3 and Evolut Low Risk) comparing transcatheter aortic valve implantation with surgical aortic valve replacement (SAVR). Whether such an approach is cost-effective in Switzerland remains unclear. The aim of this cost-utility analysis was to compare transcatheter aortic valve implantation with SAPIEN 3 versus surgical aortic valve replacement in symptomatic severe aortic stenosis patients at low risk of surgical mortality from the perspective of Swiss compulsory health insurance using data from the PARTNER 3 trial (reflecting specifically the safety and efficacy of the SAPIEN 3 TAVI device). A previously published two-stage Markov-based model that captured clinical outcomes from the PARTNER 3 trial was adapted from the perspective of the Swiss compulsory health insurance system, using local or geographically close general population mortality and utility data, unit costs and medical resource use from publicly available sources and based on expert opinion. The model had a lifetime horizon with a 3% yearly discounting factor. The cost-utility analysis estimated changes in both direct healthcare costs and health-related quality-adjusted life years for transcatheter aortic valve implantation compared with surgical aortic valve replacement in patients with symptomatic severe aortic stenosis at low risk of surgical mortality. Overall, transcatheter aortic valve implantation with SAPIEN 3 resulted in lifetime costs per patient of CHF 79,534 and quality-adjusted life years per patient of 9.64, compared with surgical aortic valve replacement lifetime costs and quality-adjusted life years per patient of CHF 76,891 and 8.96, respectively. Compared with surgical aortic valve replacement, transcatheter aortic valve implantation was estimated to offer an incremental improvement of +0.68 quality-adjusted life years per patient at an increased cost of +CHF 2643 per patient over a lifetime horizon. The incremental cost-effectiveness ratio was CHF 3866 per quality-adjusted life year gained and remained below CHF 50,000 per quality-adjusted life year gained across several sensitivity analyses. This analysis suggests that transcatheter aortic valve implantation using the SAPIEN 3 device is likely to be a highly cost-effective alternative for symptomatic severe aortic stenosis patients at a low risk of surgical mortality, treated in the contemporary Swiss setting. These findings may help to inform a holistic approach when making policy decisions for the management of this patient group.