Valve Replacement Research Articles

Continuation of beta-blockers at discharge is associated with improved outcome in patients with HFpEF and concomitant moderate aortic stenosis

Abstract Background In patients with severe aortic stenosis or decompensated heart failure with preserved ejection fraction (HFpEF), beta-blockers are usually discontinued despite the absence of unequivocal evidence. The data on the effect of beta-blockers in patients with moderate aortic stenosis (MAS) are scarce. Aim To investigate the relationship between beta-blocker use and outcome in patients with MAS, who were hospitalized for decompensated HFpEF. Methods The current study includes 61 patients admitted for decompensated HFpEF with concomitant MAS. The mean age of the population was 82.7±7.59 years old and 41% were females. The diagnosis MAS was established on criteria including aortic valve area between 1-1.5 cm², mean gradient - 20-39 mmHg, and max velocity between 3-3.9 m/s. For those with borderline measurements, the Doppler Velocity Index (DVI) was calculated (DVI < 0.25 indicates severe aortic stenosis). All echocardiographic data were assessed by an experienced echocardiographer. Patients with previous aortic valve replacement and a severe mixed of multivalvular disease were excluded. Result The median follow-up was 52 months (interquartile range 34-63 months). During this period 38 patients (62.3%) died from any cause while 42 (68.9%) individuals experienced a composite endpoint, of all-cause death or hospitalization due to worsening HFpEF. In survivors, we observed higher prescription of beta-blockers at hospital discharge (66% vs. 34%, p<0,05) and better diastolic function than in patients with endpoints. In multivariate Cox regression analysis the use of beta-blockers (HR = 0,27; 95% CI 0,13-0,57; p<0.01) and better diastolic function, defined as higher septal e` (HR=0,76; 95% CI 0,61-0,94; p=0.01) were identified as independent predictors for both - survival and composite endpoint (Figure 1). Advanced age was recognized as an associated factor for outcomes. Conclusion In the present study, continuation of beta-blockers at discharge was independently associated with better survival in patients with decompensated HFpEF and concomitant MAS. It remains to be addressed in future studies, whether or not beta-blockers should be started in these patients or if there is any prognostic interaction between beta-blockers and aortic valve intervention for MAS.Figure 1.Kaplan-Meier survival curve

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

Differences between stenotic bicuspid and tricuspid aortic valves: a histological comparison

Abstract Background Aortic valve stenosis is a narrowing of the aortic valve opening due to leaflet calcification and thickening. Thickening of the leaflets involves the original leaflet but also the presence of a superimposed tissue (SIT), defined as an extra layer of tissue on top of the original leaflet which has been shown to form mainly in response to mechanical stress. Patients with bicuspid aortic valve (BAV) are known to be at higher risk of developing aortic stenosis and at an early age as compared to patients with tricuspid aortic valves (TAV). However to date, no systematic histo-morphometric comparison has been made between BAV and TAV in order to unravel potential difference in the underlying mechanisms of valve degeneration. Purpose Aim of this study was to compare the extent and distribution of calcifications and SIT between stenotic BAV and TAV. Methods BAV (n=14) and TAV (n=12) samples were collected from patients undergoing aortic valve replacement due to aortic stenosis. Of each patient, at least one leaflet was used for analyses, for a total of 27 BAV leaflets and 17 TAV leaflets. Samples were fixed in 4% paraformaldehyde solution, and sectioned in the midline of the leaflet. In case of a leaflet with raphe, the leaflet was sectioned in the midline between the raphe and the commissure side of the leaflet. Sections were stained for elastin fibers using Weighert’s Resorcin Fuchsin. Thickness of the leaflets was calculated by dividing the cross sectional area by the length of the leaflet. Calcifications were visualized using Alizarin Red staining and quantified as a percentage of the total cross sectional area of one section. SIT was defined as an extra layer of tissue outside the elastin lamina (Figure). Results BAV samples showed in average thicker leaflets as compared to TAV (1.92 vs 1.31 mm, p <0.001). Although the thickness of the original leaflet was the same between the two groups, SIT formation was significantly thicker in the BAV as compared to TAV (0.67 vs 0.30 mm, p <0.001). This difference was mostly due to a significant thicker SIT in the free edge of BAV samples as compared to TAV (0.78 vs 0.39 mm, p=0.003), while the SIT at the level of the leaflet body was comparable between the two groups. The percentage of leaflet calcification was similar between BAV and TAV (23% vs 20% respectively, p=0.669). Interestingly, while calcification in TAV samples was observed only on the aortic side, in BAV samples calcification was also observed on the ventricular side (n=5; 36% Figure). Conclusions BAV showed thicker leaflets as compared to TAV due to a larger contribution of SIT formation particularly at the free edge. Extent of calcification was similar between BAV and TAV but calcification at the ventricular side of the leaflets was found only in BAV samples. These observations suggest significant differences in the mechanisms underlying BAV and TAV pathology possibly in relation to distinct mechanical stress.

Transcatheter versus surgical aortic valve replacement in patients younger than 65 years: analysis from the national inpatient sample database

Abstract Background Data on the relative utilization and outcomes of transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) in patients <65 years are limited. Purpose To compare the relative utilization and outcomes of TAVR versus SAVR in patients <65 years in the United States. Methods We queried the National Inpatient Sample (2016-2020) to identify patients <65 years hospitalized for isolated AVR. In-hospital outcomes of TAVR versus SAVR were compared using multivariable regression and propensity-matching analyses. Results Of 74,155 patients aged <65 years hospitalized for isolated AVR, 17,300 (23.3%) underwent isolated TAVR, and 56,855 (76.7%) underwent isolated SAVR. From 2016-2020, the use of TAVR increased, while the use of SAVR decreased in patients <65 years (both ptrend<0.01). Factors independently associated with TAVR selection in patients <65 years included female sex, congestive heart failure, pulmonary disease, renal failure, liver disease, cancer, and prior revascularization. Factors independently associated with SAVR selection included bicuspid aortic valve. After adjustment for baseline characteristics, TAVR was associated with lower odds of in-hospital mortality (adjusted odds ratio [aOR] 0.61, 95% confidence interval [CI] 0.38-0.97), stroke (aOR 0.58, 95% CI 0.38-0.90), acute kidney injury (aOR 0.41, 95% CI 0.34-0.49), and major bleeding (aOR 0.62, 95% CI 0.38-0.96), and higher vascular complications compared with SAVR (aOR 2.39, 95% CI 1.75-3.24). Length of stay was shorter and nonhome discharges were lower with TAVR (all p<0.01). Similar findings were observed in the propensity-matched cohort. Conclusions This nationwide observational analysis showed that TAVR is a feasible treatment option for patients <65 years with lower in-hospital mortality and resource utilization compared with SAVR.Central Illustration

Polymorphic size of Lipoprotein (a) and structural bioprosthetic valve degeneration

Abstract Background The use of biological heart valves (BHV) is constantly growing for the treatment of patients with aortic stenosis and their durability arises as a main concern in the field. Structural valve deterioration (SVD) of the BHV occurs gradually post-implantation and seems to reiterate, at least in part, the pathophysiological processes described in native valve stenosis. Lipoprotein (a) [Lp(a)] is an important genetically determine cardiovascular risk factors, associated with native valve calcification. The shorter polymorphic sizes of Lp(a), defined as low of apolipoprotein (a) [apo(a)] Kringle-IV copy number, have been associated with more deleterious cardiovascular phenotype. However, the association of Lp(a) plasma levels and/or its polymorphic sizes with SVD remains unclear. Purpose To determine whether Lp(a) plasma levels and/or the Lp(a) polymorphic size were associated with SVD. Methods 332 patients who underwent aortic valve replacement (AVR) with BHV from the Translink trial were included in this study. Clinically significant SVD has been defined as Stage 3 SVD based on the VARC-3 definition. Lp(a) concentration was determine by immunoturbidimetry method and the apo(a) Kringle-IV copy number by liquid chromatography-tandem mass spectrometry. Univariable and multivariable models, adjusted for clinically relevant and statistically significant variables, were used to determine the independent association between Lp(a) concentrations or apo(a) Kringle-IV copy numbers with SVD. Results Among the 332 patients included in this study, the mean age was 78 ±8 years and 71% were males. 76 patients (23%) presented clinically significant SVD. Low apo(a) Kringle-IV copy number was associated with an increased risk of SVD (per log decrease: OR=2.71 [1.34-5.50], p=0.006), but not Lp(a) plasma concentration (OR=0.99 [0.84-1.15], p=0.85). This association remained significant after comprehensive multivariable adjustments, including Lp(a) concentration (OR=3.21 [1.31-7.84], p=0.01). The analysis of the transprosthetic mean gradient, as a surrogate marker of SVD, provided consistent results (all p≤0.03). Conclusion This cross-sectional study from the Translink trial demonstrates the association between Lp(a) polymorphic size and SVD, highlighting a potential therapeutic option to limit the occurrence of SVD in selected patients who underwent AVR with surgical or transcatheter BHV.

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment

Prognostic impact of echocardiographic predictors of subclinical systolic dysfunction in patients with moderate aortic stenosis

Abstract Introduction Moderate aortic stenosis (AS) marks a critical point in AS severity spectrum, paralleled by significant cardiac structural changes. Concentric left ventricular (LV) hypertrophy, in response to the increased afterload, enables the preservation of a normal ejection fraction (EF) despite significant underlying myocardial dysfunction. Reductions in LVEF may serve as early indicators of the LV's diminished capacity to withstand this increased afterload, potentially leading to LV fibrosis and irreversible myocardial damage. Research has shown that LVEF may not recover in some patients following aortic valve replacement (AVR). Consequently, there is a growing debate concerning higher LVEF thresholds for triggering AVR in patients with severe AS, aiming to intervene before clinical systolic dysfunction ensues and irreversible damage occurs. Meanwhile, a combination of objective indicators may help to identify those patients AS at high risk before a decline in LVEF occurs. Aim To explore the role of baseline left ventricle global longitudinal strain (GLS) and strain rate (SR) as markers of subclinical LV dysfunction, as predictors of LVEF depression, and their impact on survival of patients with moderate AS. Methods Patients with moderate AS and LVEF ≥ 50% at least in 2 echocardiograms were retrospectively identified. Prosthetic and bicuspid valves were excluded. Baseline LV GLS and SR were used as covariates in cox regression models to predict the cumulative incidence of LVEF depression over 5 years and overall survival after multivariable adjustment including time-dependent AVR. Results 574 patients were included (age 76 ± 9 years; 51% female; median follow-up time of 8.97 years). The average baseline aortic peak velocity was 3.4±0.8 m/s, mean pressure gradient was 25±9 mmHg, aortic valve area was 1.1± 0.3 cm2, and LVEF 60±5%. The average GLS was -17±7 % while the peak systolic SR was 1.2 ± 0.5/s. Both baseline GLS (HR= 0.88 for each -1%; 95% CI= 079-0.99; p= 0.04) and SR (HR= 0.89 for each +0.1/s; 95% CI= 0.80-0.99; p=0.03) were associated with 5-year incidence of LVEF depression (<50%). Risk discrimination improved by incorporating SR on top of GLS (increase in area under curve from 0.78 to 0.84; 95% CI= 0.01-0.10; p= 0.04). Furthermore, a nonlinear relation was found between GLS (optimal boundary <-15.8%; p=0.35) and SR (optimal boundary >0.96/s; p=0.34) and overall survival. Conclusions This study identifies baseline GLS and SR as predictors of LVEF depression in moderate AS underscoring their importance in detecting subclinical LV dysfunction. The combination of GLS and SR may enhance the prediction of cardiac function decline, suggesting their potential utility in guiding early intervention strategies. Although their direct relationship with survival needs further exploration, these findings advocate for incorporating GLS and SR in AS management to inform timely AVR decisions and improve patient outcomes.

Comparison of mortality scores performance in transcatheter aortic valve replacement: suiting up to percutaneous intervention

Abstract Introduction As transcatheter aortic valve replacement (TAVR) is increasingly relevant for patients with severe symptomatic aortic stenosis, having a reliable procedure specific risk-prediction tool is paramount to provide high-quality care. Surgical scores as the EuroScore II and the Society of Thoracic Surgeons (STS) score II have been widely used to identify patients with high surgical risk in whom percutaneous treatment might be more favorable. However, current literature lacks a consensual specific predictive model for short-term and mid-term prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). Purpose We aimed to access short and midterm (30 days and one year) mortality and to access the ability of a directly adapted score in estimating mortality in a real-world population. Methods We conducted a retrospective observational study in patients who implanted TAVR in a single center. Surgical mortality scores – EUROSCORE II and STS score II – and adapted score Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) transcatheter valve therapy (TVT) score were used to estimate mortality. Predictive abilities of these three scores were compared using area under the receiver operating characteristics (ROC) curve for 30-day and one year mortality. Results From January 2018 to December 2021, 416 patients were submitted to TAVR procedure in our center. The mean age was 83+-6 years old and 229 (55%) were female. 94% had hypertension, 80% dyslipidemia, 40% diabetes mellitus, 35% coronary artery disease, 32% chronic kidney disease. Mean ejection fraction was 56%. During a mean follow-up (FUP) of 816 ± 492 days, 30-day mortality was 1,7% and after 1 year mortality rate was 12,2% (higher than reported in PARTNER 3 trial, 8,5%). The Mean EuroSCORE was 3,4±3,2, mean STS-II 3,9±1,8 and mean value for STS/ACC-TVT score was 3,55±1,34. ROC curve analysis showed a significantly higher discriminative power of STS/ACC-TVT (AUC 0,749, 95% CI 0,681-0,818) compared with surgical scores (p=0,001) – figure 1. We also divided population into quartiles and compared the mortality rate at 30 days and 1 year in each quartile using either STSII or STS/ACC-TVT; As can be seen in figure 2, mortality rates correlated better with the STS/ACC-TVT score than with the STS score. Conclusion A score adapted to a TAVI population showed better predictive capacity than traditional surgical scores. Less preponderance of previous surgical status, relevance of access site and more adapted weight of age might explain the best performance of STS/ACC-TVT score. Surgical scores are helpful in choosing treatment option, but adapted scores are better to predict pos-TAVR mortality.

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP >40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

Temporal trends of aortic valve replacement modalities by age group in the United-States 2015 - 2023

Abstract Background/Introduction Transcatheter aortic valve implantation (TAVI) has led to a paradigm shift in treating aortic stenosis (AS) across patients of all surgical-risk categories. To guide the clinical decision, the ACC/AHA guidelines recommended an age group classification; with SAVR being recommended in patients < 65 years, and TAVI being favored over SAVR in patients > 80 years. In patients between 65-80 years, both modalities are to be considered after shared decision making. The impact of those guidelines-derived age group classification on the contemporary AVR practice remains of interest and is dynamically changing. Purpose This study aims to examine the temporal trends in the modality of AVR (TAVI vs SAVR) in the U.S. among different age groups using a contemporary nationwide database. Methods We conducted a retrospective study using de-identified data from the Vizient Clinical Database, which gathers patient and hospital data from more than 1000 medical Centre. We analysed TAVI and SAVR procedures from October 1, 2015, to November 30, 2023, excluding patients under 18. We examined the national trends of TAVI vs SAVR in 3 age groups (<65, 65-80, >80 years) with AS. Trend analysis was performed using linear regression. This study was deemed exempt from the requirements of 45 CFR 46.104(d) by The Miriam Hospital Institutional Review Board given that it involved de-identified data. Results During the study period, 467,832 underwent AVR (TAVI n= 252,834, SAVR n= 214,998). The patient and hospital characteristics by age group are summarized in the Table. We observed a significant rise in TAVI adoption from 33.5% in 2015 to 59.96% in 2023. However, the pattern of temporal trends varied among different age groups. In patients > 80 years, TAVI showed a steep rise from 69.95% in 2015 to 92.96% in 2023 (p<0.002). The 65-80 years age cohort demonstrated the most pronounced growth in TAVI, rising from 26.23% in 2015 to about 60% in 2020 (p.001), after which a plateau in percentage was observed. TAVI in patients <65 years has also been increasingly adopted, rising from 7.18% in 2015 to 19.12% in 2020 (p<0.002), however, followed with a slight downtrend to 16.36% in 2023 (Figure). Conclusion In this most contemporary analysis from the U.S., we demonstrate an increase in the adoption of TAVI across all age groups over the study period, with the steepest rise observed in patients between 65-80 years of age. Since the 2020 ACC/AHA guidelines, there has been a gradual downtrend in the utilisation of TAVI in patients <65 years of age indicating a possible change in practice based on scientific societal recommendations. The stabilization in TAVI percentage in the age groups 65-80 years and > 80 years in the last few years may hint towards approaching equilibrium between TAVI and SAVR for these age groups.Proportions of AVR across age groups

Five-year outcomes with self-expanding versus balloon-expandable transcatheter aortic valve replacement in patients with left ventricular systolic dysfunction

Abstract Background The importance of transcatheter heart valve (THV) design on clinical outcome in patients with aortic stenosis (AS) and left ventricular (LV) systolic dysfunction remains unknown. Objectives We aimed to compare 5-year outcomes of patients with severe AS and reduced LV ejection fraction (LVEF), undergoing transcatheter aortic valve replacement (TAVR) with balloon-expandable vs. self-expanding THVs. Methods In an institutional TAVR registry, patients with LVEF <50% who underwent TAVR with either balloon-expandable or self-expanding THVs were included. A 1:1 propensity-score matching was performed to account for baseline differences between groups. Results A total of 759 patients were included between August 2007 and December 2022, and propensity-score matching resulted in 134 pairs. Technical success was achieved in over 85% of patients, and was similar in both groups. Self-expanding THVs were associated with a lower mean transvalvular gradient (7.1 ± 3.7 mmHg vs. 9.9 ± 4.3 mmHg; P <0.001) and a higher incidence of ³mild-to-moderate paravalvular regurgitation (36.3% vs. 11.3%; P <0.001) compared to balloon-expandable THVs. At 5 years, patients treated with a self-expanding THV had higher all-cause mortality than those with a balloon-expandable THV (67.8% vs. 55.8%, Adjusted Hazard Ratio: 1.44; 95% CI: 1.02-2.03; P = 0.037). There were no significant differences in other clinical outcomes up to 5 years between groups. Conclusions In the setting of LV systolic dysfunction, patients treated with a self-expanding THV had higher risk of 5-year mortality compared to patients treated with a balloon-expandable THV.

Racial, ethnic, and sex disparities in the utilization and outcomes of tricuspid valve surgery

Abstract Background Data on racial/ethnic and sex disparities in the utilization and outcomes of tricuspid valve surgery (TVS) in the United States are scarce. Purpose We aimed to evaluate the impact of race/ethnicity and sex on the utilization and outcomes of TVS. Methods We analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for tricuspid valve surgery. Racial/ethnic and sex disparities in tricuspid valve surgery outcomes were determined using logistic regression models. Results Between 2016 and 2020, 19,395 hospitalizations for tricuspid valve surgery were identified. The utilization rates (defined as the number of tricuspid valve surgery performed per 100,000 US hospitalizations) were lower in Black and Hispanic patients compared with White patients for surgical tricuspid valve repair (331 versus 493 versus 634, p<0.01) and surgical tricuspid valve replacement (312 versus 601 versus 728, p<0.01). Similarly, the utilization rates were lower for women compared with men for surgical tricuspid valve repair (1,021 versus 1,364, p<0.01) and surgical tricuspid valve replacement (930 versus 1,316, p<0.01). Compared to White men undergoing tricuspid valve surgery, all women had lower odds of acute kidney injury (aOR 0.65, 95% CI 0.55-0.78) and higher odds of blood transfusion (aOR 1.30, 95% CI 1.07-1.59), and Black men had higher odds of blood transfusion (aOR 1.59, 95% CI 1.08-2.35). In-hospital mortality and other surgical complications were similar between all groups (all p>0.05). Conclusions Significant racial/ethnic and sex disparities exist in the utilization of tricuspid valve surgery in the United States. Further studies are needed to understand the reasons for these disparities and to identify effective strategies for their mitigation.

A new wearable cardiac acoustic monitoring technology for the evaluation of subclinical leaflet thrombosis after transcatheter aortic valve replacement: a pilot study

Abstract Background Subclinical leaflet thrombosis characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) is a common complication after transcatheter aortic valve replacement (TAVR), whether it affects hemodynamic change is still debated. Purpose We attempted to use a novel wearable heart acoustic monitoring device, and combined multi-dimensional computed tomography (MDCT) and echocardiography to diagnose SLT and analyze the changes of transvalvular hemodynamics after TAVR. Methods Patients with severe symptomatic aortic stenosis and underwent successful TAVR were consecutively enrolled. Clinical data, acoustic cardiographic parameters including the frequency, amplitude, and energy of heart sounds , and imaging results were collected and analyzed by Core laboratory at pre- and post TAVR, and follow-up at one month and six month. According to severity of SLT at one month follow-up, we divided the patients into three groups: Group1: no SLT, Group2: mild SLT, defined as existed HALT did not qualify for Group 3, and Group 3: moderate to severe SLT, defined as at least 1 leaflet with HALT of grade 3 or 4 or RLM of ≥50%, or 2 leaflets with HALT of grade 2 or RLM of ≥50%. A consistency analysis of SLT presence between MDCT findings and acoustic cardiographic variables was performed using Kappa statistics. Results The study included 116 TAVR patients. The prevalence of SLT as detected by MDCT at one-month follow-up was 25%, with moderate to severe SLT representing 11.2% of cases. A significant decrease in aortic valve orifice area (AVA) (-0.2±0.48cm2 vs. -0.1±0.33cm2, p=0.009) and an increase in mean gradient (MG) (3.5±5.85 mmHg vs. 0.1±11.34mmHg, p=0.028) were observed in moderate to severe SLT group at one-month follow-up versus post-TAVR via echocardiography. However, no significant differences were found in the mild SLT or no SLT group. Acoustic cardiographic characteristics exhibited a distinct pattern with early systolic, baseless, and high-energy murmurs in patients with moderate to severe SLT, but not in the mild SLT or no SLT group. The sensitivity, specificity, and Kappa values for acoustic cardiography in diagnosing moderate to severe SLT were 81.82%, 83.33%, and 0.41, respectively. At the 6-month follow-up, MDCT showed that 11 (85%) patients with moderate to severe SLT who received anticoagulant therapy reached complete dissolution of SLT. Conclusion Moderate to severe SLT presented notably transvalvular hemodynamic influences following TAVR. Acoustic cardiography demonstrated specific characteristics of moderate to severe SLT, providing a valuable tool for SLT diagnosis and evaluation in clinical follow-up.Figure 1.Baseline characteristicsFigure 2.SLT and acoustic cardiography

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

Wire injury induced moderate aortic valve stenosis in mice is accompanied by a chronic systemic inflammatory reaction

Abstract Background Patients with aortic valve stenosis (AS) have elevated serum levels of inflammation markers, and blood cytokine levels correlate with ventricular recovery after transcatheter aortic valve replacement. While presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon AS has been performed, yet. Purpose Hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods AS was induced by wire injury (WI) or sham surgery was performed in 3-4 months old male C57Bl/6J mice. AS severity, left ventricular (LV) function and hypertrophy indices were assessed with echocardiography (echo). After four weeks, explanted organs were weighted, and flow cytometry identified total leukocyte numbers in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes) and uptake of Cy5-labelled perfluorocarbon nanoemulsions by whole blood leukocytes. Costimulatory molecules (flow cytometry, RT-qPCR) and cytokines (RT-qPCR, Multiplex Immunoassay) were analysed in heart, peripheral immune organs and blood. Results R-values were positive for spleen weight correlation with AS severity, cardiac function and mass suggesting cardiac hypertrophy to preserve heart function. Myocardial myeloid and T cell r-values were positive or negative, respectively, for correlation with spleen and liver weight, hinting at T cell recruitment from peripheral stores. Immune cell numbers in peripheral lymph nodes and spleen showed negative r-values for correlation with heart hypertrophy indices; number of liver myeloid cells correlated negatively with LV wall thickness (monocytes=-0.8571, p=0.0238) suggesting immune cell recruitment to hypertrophic hearts. Cytokine mRNA levels trended mainly towards increase in heart and regional lymph nodes and reduction in spleen and liver after WI. Correlation with echo was more homogeneous after WI, with r-values mainly positive, except of T cell activation markers, for aortic valves, but negative for myocardium, hinting at mechanisms preserving heart function. Correlating unchanged cytokine protein levels in myocardium and plasma with echo, r-values were mostly positive for myocardium, and were more positive than in sham for plasma. Echo and costimulatory molecule correlation showed a more homogeneous pattern in WI, with mostly positive r-values in myocardium and periphery, while most r-values were negative in sham. Together with reduced PFC-uptake by lymphatic cells, this hints at systemic immune cell activation in AS. Conclusion The results suggest that number and activation state of leukocytes in peripheral organs are directly linked to cardiac processes in AS. Considering the pathological value of inflammation, it is crucial to in future studies find out if modulation of the systemic inflammatory reaction relieves severity of AS and prevents development of heart failure.

Acute changes in right ventricular geometry and function following transcatheter tricuspid valve interventions

Abstract Background Little is known about acute changes in right ventricular (RV) function and geometry following transcatheter tricuspid edge-to-edge repair (T-TEER) or transcatheter tricuspid valve replacement (TTVR). Pressure-strain-volume loop-derived myocardial work metrics showed associations with myocardial energetics and contractility in conditions accompanied by volume overload, suggesting their potential utility in patients with tricuspid regurgitation (TR). Purpose To define acute changes in RV volumes and RV myocardial work following T-TEER and TTVR using conventional and pressure-strain-volume derived RV work metrics. Methods In this multicenter, observational study, 3D echocardiographic datasets and invasively acquired RV pressures were collected before and after transcatheter tricuspid valve procedure. Using dedicated software (ReVISION, Argus Cognitive) 3D RV volumes and strains were quantified and decomposed to longitudinal, radial and anterio-posterior motion. Forward stroke volume (SV) was calculated by subtracting TR volumes from RV 3D end-diastolic volume (EDV) and end-systolic volume (ESV) difference. Three-dimensional pressure-strain-volume loops were constructed and global RV work-index (RV-Wi) was calculated. Changes in RV parameters before and after the intervention were compared using paired-samples t test. Results Of 37 patients included in this study (65% male), 20 underwent T-TEER and 17 underwent TTVR. Compared to T-TEER patients, patients undergoing TTVR had higher prevalence of torrential TR at baseline but also achieved a higher reduction in TR volumes after the intervention (44 ± 11 ml vs 60 ± 16ml; p = 0,001). Following T-TEER there was a significant reduction in RV EDV (240 ± 93 ml vs 200 ± 80 ml; p < 0.001) and increase in SV (55 ± 34 ml vs 68 ± 26 ml; p = 0.036). Following TTVR there was a significant increase in RV ESV (121 ± 46 vs 146 ± 48, p = 0.003) and no significant change in SV (47 ± 24 ml vs 55 ± 20 ml; p = 0.143). There was significant reduction in RV strain and ejection fraction (EF) (all p < 0.001) primarily driven by reduction of radial motion component in both groups. RV-Wi increased in 35% (7/20) of T-TEER patients and in 18% of (3/17) TTVR patients. Conclusion An acute reduction in RV EF was observed in all patients and was mainly caused by decrease in RV EDV in T-TEER patients and increase in RV ESV in TTVR patients. Despite decrease of conventional metrics of RV function in both groups, an increase in RV-Wi was observed in 27% of all patients.Baseline and follow-up characteristicsCentral Figure

Unlocking the future: machine learning models for predicting in-hospital mortality after transcatheter aortic valve replacement: a single-arm meta-analysis

Abstract Background Transcatheter aortic valve replacement (TAVR) continues to be increasingly performed. While machine learning has demonstrated utility in predicting adverse outcomes in various cardiovascular procedures, its effectiveness in predicting in-hospital mortality in TAVR remains uncertain. Purpose We aimed to examine the accuracy of machine learning in predicting in-hospital mortality in TAVR. Methods We searched PubMed and Cochrane databases up to February 2024 for observational studies assessing the diagnostic accuracy of machine learning for predicting in-hospital mortality in TAVR. Extracted data included study characteristics, patient demographics, type of predictive model used, and area under the receiver operating characteristic curves (AUC). Predictive accuracy was assessed by pooling AUC of machine-learning models across studies. AUC values ranging from 0.80 to 0.90, 0.70 to 0.80, 0.60 to 0.70, and 0.50 to 0.60 corresponded to excellent, good, fair, and poor discrimination ability, respectively (1). We used a random effects model to estimate the overall effect size with a 95% confidence interval (CI). Heterogeneity was evaluated with the I2 test.We conducted subgroup analyses based on the type of machine-learning model utilized to assess for any potential differences in predictive accuracy. Results A total of three studies were identified, comprising a study population of 70,714 patients. Across studies, eight machine learning models were utilized, consisting of three artificial neural network models, one logistic regression model, one naive Bayes model, two random forest models, and one support vector machine model. Pooled AUC showed excellent accuracy of machine learning in predicting in-hospital mortality in TAVR (0.92; 95% CI 0.90 - 0.95). Subgroup analyses revealed similar yet excellent accuracy across all types of machine learning models utilized: artificial neural network (0.92; 95% CI 0.86-0.99), logistic regression (0.92; 95% CI 0.89-0.95), naive Bayes (0.90; 95% CI 0.88-0.92), random forest (0.94; 95% CI 0.87-1.00), and support vector machine (0.94; 95% CI 0.91-0.96). Conclusion Our study suggests that utilizing machine learning can accurately predict in-hospital mortality in TAVR. Operators of TAVR procedures may benefit from incorporating machine learning prediction models in their clinical practice. Further exploration of machine learning on outcomes in TAVR is needed to verify our findings.

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.

Transcatheter vs. surgical aortic valve replacement in patients with aortic stenosis and cardiogenic shock.

Patients with aortic stenosis (AS) and cardiogenic shock (CS) are an extremely high-risk population with a poor prognosis in the absence of definitive therapy. We aimed to compare the outcomes of transcatheter aortic valve replacement (TAVR) with those of surgical aortic valve replacement (SAVR) in patients with AS-CS. We queried the Nationwide Readmission Database (2016-21) to identify patients hospitalized for AS-CS who underwent isolated TAVR or SAVR. In-hospital outcomes of TAVR vs. SAVR were compared using multivariable regression and propensity-matching analyses. Ninety-day readmissions were compared using a Cox proportional hazards regression model. A total of 16 161 patients were hospitalized for AS-CS, of whom 6470 (40.0%) underwent isolated TAVR and 9691 (60.0%) underwent isolated SAVR. From 2016 through 2021, the proportion of TAVR increased from 29.5 to 46.5% and the proportion of SAVR correspondingly decreased in AS-CS (Ptrend < 0.01). After adjustment for baseline characteristics, TAVR was associated with lower odds of stroke [adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.47-0.84], acute kidney injury (aOR 0.80, 95% CI 0.69-0.93), and major bleeding (aOR 0.54, 95% CI 0.40-0.71) and higher odds of vascular complications (aOR 1.56, 95% CI 1.23-1.97) compared with SAVR. In-hospital mortality, myocardial infarction, permanent pacemaker placement, and 90-day all-cause and heart failure readmissions showed similar rates between TAVR and SAVR. However, hospital length of stay was shorter and total costs and non-home discharges were lower with TAVR than with SAVR. This nationwide observational analysis showed that TAVR is increasingly performed in patients with AS-CS and is associated with similar rates of in-hospital mortality and 90-day readmissions but lower rates of in-hospital complications and resource utilization compared with SAVR.

Concomitant left atrial appendage occlusion and transcatheter aortic valve replacement among patients with atrial fibrillation: an updated systematic review and meta-analysis

Abstract Background Atrial fibrillation (AF) is a prevalent arrhythmia in patients undergoing transcatheter aortic valve replacement (TAVR). Left atrial appendage occlusion (LAAO) has emerged as a viable strategy to prevent stroke in selected patients with AF. While both devices can be implanted simultaneously during a single procedure, the safety and efficacy of this approach remain uncertain. Purpose This study aims to evaluate the efficacy and safety of concomitant LAAO in patients with AF and aortic valve disease undergoing TAVR. Methods We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies that compared concomitant TAVR and LAAO with isolated TAVR. The study's primary outcomes were all-cause mortality, stroke or transient ischemic attack (TIA), and major bleeding. We established a minimum follow-up time of six months. Results Three studies met our eligibility criteria, including one randomized controlled trial and two observational studies. The meta-analysis included 570 patients, 249 (44%) who underwent LAAO and TAVR, with a mean follow-up of 16.3 months. In the overall population, there was no significant difference between the groups in all-cause mortality (relative risk [RR] 0.95; 95% confidence interval [CI] 0.67-1.35; p = 0.78; figure 1A), major bleeding (RR 1.15; 95% CI 0.75-1.77; p = 0.51; 1B), and stroke or TIA (RR 0.70; 95% CI 0.33-1.45; p = 0.33; figure 1C). Conclusion In conclusion, concomitant LAAO and TAVR did not demonstrate discernible clinical differences compared to isolated TAVR in patients with AF and aortic valve disease. We recommend that this therapeutic approach be individualized until more robust data become available.