Association Between Transcatheter Aortic Valve Replacement for Bicuspid vs Tricuspid Aortic Stenosis and Mortality or Stroke Among Patients at Low Surgical Risk

Key Points

Question  Are there differences in mortality and stroke between patients at low surgical risk who undergo transcatheter aortic valve replacement (TAVR) for bicuspid compared with tricuspid aortic stenosis?

Findings  In this registry-based cohort study that included 3168 propensity-matched pairs of patients at low surgical risk undergoing TAVR for bicuspid vs tricuspid aortic stenosis, there was no significant difference in death at 30 days (0.9% vs 0.8%), death at 1 year (4.6% vs 6.6%), stroke at 30 days (1.4% vs 1.2%), or stroke at 1 year (2.0% vs 2.1%).

Meaning  Patients at low surgical risk who underwent TAVR for bicuspid aortic stenosis compared with tricuspid aortic stenosis had no significant difference in mortality or stroke at 30 days or 1 year. Because of the potential for selection bias, randomized trials would be needed to adequately assess the efficacy and safety of TAVR for bicuspid aortic stenosis.

Importance  There are limited data on outcomes of transcatheter aortic valve replacement (TAVR) for bicuspid aortic stenosis in patients at low surgical risk.

Objective  To compare the outcomes of TAVR with a balloon-expandable valve for bicuspid vs tricuspid aortic stenosis in patients who are at low surgical risk.

Design, Setting, and Participants  Registry-based cohort study of patients undergoing TAVR at 684 US centers. Participants were enrolled in the Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapies Registry from June 2015 to October 2020. Among 159 661 patients (7058 bicuspid, 152 603 tricuspid), 37 660 patients (3243 bicuspid and 34 417 tricuspid) who were at low surgical risk (defined as STS risk score <3%) were included in the analysis.

Exposures  TAVR for bicuspid vs tricuspid aortic stenosis.

Main Outcomes and Measures  Coprimary outcomes were 30-day and 1-year mortality and stroke. Secondary outcomes included procedural complications and valve hemodynamics.

Results  Among 159 661 patients (7058 bicuspid; 152 603 tricuspid), 3168 propensity-matched pairs of patients with bicuspid and tricuspid aortic stenosis at low surgical risk were analyzed (mean age, 69 years; 69.8% men; mean [SD] STS-predicted risk of mortality, 1.7% [0.6%] for bicuspid and 1.7% [0.7%] for tricuspid). There was no significant difference between the bicuspid and tricuspid groups’ rates of death at 30 days (0.9% vs 0.8%; hazard ratio [HR], 1.18 [95% CI, 0.68-2.03]; P = .55) and at 1 year (4.6% vs 6.6%; HR, 0.75 [95% CI, 0.55-1.02]; P = .06) or stroke at 30 days (1.4% vs 1.2%; HR, 1.14 [95% CI, 0.73-1.78]; P = .55) and at 1 year (2.0% vs 2.1%; HR 1.03 [95% CI, 0.69-1.53]; P = .89).There were no significant differences between the bicuspid and tricuspid groups in procedural complications, valve hemodynamics (aortic valve gradient: 13.2 mm Hg vs 13.5 mm Hg; absolute risk difference [RD], 0.3 mm Hg [95% CI, −0.9 to 0.3 mm Hg]), and moderate or severe paravalvular leak (3.4% vs 2.1%; absolute RD, 1.3% [95% CI, −0.6% to 3.2%]).

Conclusions and Relevance  In this preliminary, registry-based study of propensity-matched patients at low surgical risk who had undergone TAVR for aortic stenosis, patients treated for bicuspid vs tricuspid aortic stenosis had no significant difference in mortality or stroke at 30 days or 1 year. Because of the potential for selection bias and absence of a control group treated surgically for bicuspid aortic stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis in patients at low surgical risk.

In 2018, bicuspid aortic valve was estimated to be present in as much as 1% of the population^1,2 and was associated with early degeneration leading to aortic stenosis or regurgitation.³ Of patients undergoing surgery for aortic stenosis, 15% to 29% have been reported to have bicuspid aortic valve.^4-6 The recent pivotal low-risk randomized clinical trials expanded the indication of transcatheter aortic valve replacement (TAVR) toward aortic stenosis patients who have lower surgical risk and are younger^7,8; however, these trials excluded bicuspid anatomy. Previously published registries on outcomes of TAVR in bicuspid aortic stenosis were limited to small sample size⁹ or older patients who were at higher risk for surgery.^10,11 Given that bicuspid anatomy was frequently present in younger and low-risk patients undergoing surgery, the data on outcomes of TAVR in bicuspid aortic stenosis are crucial to guide the treatment of bicuspid aortic stenosis in these low-risk patients.

Since the US Food and Drug Administration’s 2019 approval of TAVR in patients at low surgical risk, an increasing number of patients at low surgical risk and bicuspid aortic stenosis have undergone TAVR. The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry includes all TAVR procedures performed in the US. The present study evaluated the outcomes of TAVR with contemporary balloon-expandable transcatheter heart valves for bicuspid aortic stenosis in this national registry, with a focus on patients at low surgical risk.

All consecutive patients undergoing TAVR with contemporary balloon-expandable transcatheter heart valves (third-generation SAPIEN 3 and fourth-generation SAPIEN 3 Ultra valve [Edwards Lifesciences]) in the US, since commercial approval in June 2015 through October 2020, were evaluated in the present study. Patient follow-up ended on October 16, 2020. Clinical data was site-reported, according to the TVT Registry data dictionary. The registry protocol was granted a waiver of informed consent by Advarra, a centralized institutional review board (https://www.advarra.com/).

The primary population of interest comprised patients at low surgical risk undergoing TAVR (Figure 1). Low surgical risk was defined as having an STS predicted risk of mortality (STS-PROM) score of less than 3% (score range, 0%-100% [higher scores indicate higher risk of death within 30 days after surgery]). The secondary population comprised all patients, irrespective of surgical risk, undergoing TAVR for aortic stenosis (overall cohort). The outcomes of TAVR for bicuspid and tricuspid aortic stenosis in patients at low surgical risk, as well as patients in the overall cohort were compared.

The primary outcomes were the rates of death and stroke at 30 days and 1 year. The secondary outcomes included procedural and in-hospital outcomes, echocardiographic outcomes, functional status (New York Heart Association [NYHA] heart failure class), and health status (the Kansas City Cardiomyopathy Questionnaire overall summary score [KCCQ-OS]; score range, 0-100 [higher scores indicate less symptom burden and better quality of life]).^12,13

A detailed statistical analysis methodology is summarized in the eAppendix in the Supplement. Continuous variables were presented as mean (SD) or median interquartile ranges (IQR) and were compared between groups using 2-sample t tests or Wilcoxon rank-sum tests. Categorical variables were given as frequencies and percentages and were compared using χ² or 2-tailed Fisher exact tests. The 30-day and 1-year adverse event rates were based on Kaplan-Meier estimates and all comparisons were made using the log-rank test.

It was anticipated that patients with bicuspid and tricuspid aortic stenosis would have significantly different baseline and procedural characteristics. The statistical analysis plan prespecified the use of propensity score–based matching to account for these differences between patients with bicuspid and tricuspid aortic stenosis.¹⁴ Propensity scores were calculated using a logistic regression model based on 29 baseline patient characteristics (covariates) with aortic valve type (bicuspid or tricuspid) as the dependent variable. The covariates included age, male sex, body mass index (calculated as weight in kilograms divided by height in meters squared), access site, prior percutaneous coronary intervention, prior coronary artery bypass graft surgery, prior stroke, carotid stenosis, peripheral arterial disease, hypertension, diabetes, chronic lung disease, immunocompromised status, porcelain aorta, atrial fibrillation, creatinine level, hemoglobin level, estimated glomerular filtration ratio, aortic valve mean gradient, left ventricular ejection fraction, mitral regurgitation, tricuspid regurgitation, NYHA functional class III/IV, 5-meter walk test time, STS-PROM score, shock within 24 hours prior to TAVR, hemodialysis, hostile chest, and KCCQ-OS score. The missing baseline values were imputed using the Markov Chain Monte Carlo method prior to modeling with a single imputation (eTable 1 in the Supplement). The primary analysis was performed with imputed data. Patients with bicuspid aortic stenosis were matched 1 to 1 to those with tricuspid aortic stenosis using a greedy matching strategy with a caliper of 0.01, producing 2 patient cohorts. Balance between the groups was assessed by calculating standardized differences for which an absolute difference of less than 0.10 was considered to indicate good balance.

Sensitivity analyses were performed to investigate the robustness of the results. The outcomes were assessed in 3 additional propensity score–matched cohorts: (1) patients determined to be at low surgical risk by the multidisciplinary heart team at the treating sites; (2) patients younger than 65 years; and (3) patients who reached 1 year prior to the data collection date. The sensitivity analyses were performed without imputation. The outcomes were also compared between propensity-matched patient pairs undergoing TAVR with the third- and fourth-generation balloon-expandable transcatheter heart valves for bicuspid aortic stenosis.

Multiple imputation was performed to account for missing outcomes data with the following assumptions¹⁵: (1) all patients with bicuspid aortic stenosis from the matched population who did not have a primary end point event and were missing 1-year follow-up were imputed based on missing data at random assumption (ie, they were considered to be similar to the observed patients with bicuspid aortic stenosis who either had primary end point events or completed the 1-year follow-up); and (2) all patients with tricuspid aortic stenosis from the matched population who did not have a primary end point event and were missing 1-year follow-up were imputed based on missing data at random assumption (ie, they were considered to be similar to the observed patients with tricuspid aortic stenosis who either had primary end point events or completed the 1-year follow-up). For missing follow-up primary end points (death and stroke), the imputed results (event and day of event) were generated from a uniform distribution probability in comparison with the observed conditional cumulative hazard function following the missing assumptions defined previously. First, a random number x from the uniform distribution between 0 and 1 was generated. If the value of x was less than the cumulative hazard function of patients with complete information at the end of follow-up time (1 year) then the event binary variable was imputed as yes; if otherwise, it was imputed as no. If the imputed event binary variable was yes, then the failure time of event was further imputed based on the value of x (impute failure time as t if value of x was between cumulative hazard function of time t and t +1). The overall multiple imputation estimate event rates and rate difference between patients with bicuspid and tricuspid aortic stenosis were obtained by averaging the event rate for each imputation. The overall estimated variance was the mean of the sum of all the estimated variances of each imputation. The statistical inference of the planned primary analysis was applied to estimate event rate and hazard ratio (HR) with 95% CI. For missing data on secondary end points (KCCQ score, NYHA functional class, and perivalvular leak), the missing baseline (discharge), 30-day and 1-year values were imputed using the Markov Chain Monte Carlo method based on missing data at random assumption.

Cox regression analysis was performed to assess the adjusted HR of patients with bicuspid vs tricuspid aortic stenosis on primary end points. The candidate covariates were identical to those used in the propensity score model (except the STS PROM score). The model was checked for violation of the proportional hazard assumption by Kolmogorov-type supremum test, and no relevant violations were found.

All P values were 2-sided, and P < .05 was considered significant for all tests. No adjustment for multiple testing was undertaken. Because of the potential for type I error due to multiple comparisons, all findings of this study should be interpreted as exploratory. All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc). SAS Proc MI was used for multiple imputation, Proc Phreg for Cox regression model, and Proc logistics for propensity score calculation.

Between June 2015 and October 2020, a total of 159 661 (7058 bicuspid, 152 603 tricuspid) patients underwent TAVR for aortic stenosis with balloon-expandable transcatheter heart valves at 684 institutions in the US. A total of 37 660 patients (3243 with bicuspid aortic stenosis and 34 417 with tricuspid aortic stenosis) were included in the primary analysis. Propensity-score matching between patients with bicuspid and tricuspid aortic stenosis was performed, generating 3168 low surgical-risk pairs and 6995 all-risk pairs (Figure 1). The temporal trends in the use of TAVR for bicuspid aortic stenosis are summarized in eFigures 1 and 2 in the Supplement. The proportion of patients at low surgical risk who underwent TAVR increased from 9.6% in 2015 to 43.8% in 2020 (eFigure 1 in the Supplement). The proportion of patients with bicuspid aortic stenosis undergoing TAVR increased from 2.8% in 2015 to 6.8% in 2020 (eFigure 2 in the Supplement). The proportion of patients with bicuspid aortic stenosis undergoing TAVR was 8.6% in the low-surgical risk group and 20.7% in patients younger than 65 years.

There were significant differences in baseline and procedural characteristics in unmatched patients with bicuspid and tricuspid aortic stenosis (Table 1). In the propensity score–matched cohorts, baseline and procedural characteristics were balanced with mean age of 69 years and STS-PROM score of 1.7% in both groups (Table 1).

In the propensity score–matched population, there was no significant difference in the rates of death between bicuspid and tricuspid populations at 30 days (0.9% vs 0.8%; HR, 1.18 [95% CI, 0.68 to 2.03]; P = .55) or 1 year (4.6% vs 6.6%; HR, 0.75 [95% CI, 0.55 to 1.02]; P = .06) (Figure 2A; Table 2). There was no significant difference in the rates of stroke between bicuspid and tricuspid populations at 30 days (1.4% vs 1.2%; HR, 1.14 [95% CI, 0.73 to 1.78]; P = .55) or 1 year (2.0% vs 2.1%; HR, 1.03 [95% CI, 0.69 to 1.53]; P = .89) (Figure 2B; Table 2). There was no significant difference in the rates of death or stroke between bicuspid and tricuspid populations at 30 days (2.2% vs 1.9%; HR, 1.14 [95% CI, 0.81 to 1.62]; P = .45) or 1 year (6.4% vs 8.4%; HR, 0.85 [95% CI, 0.66 to 1.08]; P = .18) (Figure 2C; Table 2). In the unadjusted population of patients at low surgical risk, mortality at 1 year was significantly lower in patients with bicuspid aortic stenosis compared with tricuspid aortic stenosis, and stroke rates were not significantly different between the 2 groups (eTable 2 in the Supplement). These rates were consistent, when adjusted for missing data by multiple imputation (eTable 3 in the Supplement). The in-hospital and clinical outcomes in the unmatched population are summarized in eTables 4 and 5 in the Supplement.

In 1310 propensity score–matched pairs of patients deemed low surgical risk by the multidisciplinary heart team at the treating sites (eTables 6, 7, 8, and 9 and eFigure 3 in the Supplement) as well as in 1573 propensity score–matched pairs of patients younger than 65 years (eTables 10, 11, 12, and 13 and eFigure 4 in the Supplement), no significant differences were noted in death and stroke rates at 30 days and 1 year. Findings were consistent in 1803 propensity score–matched pairs of patients who underwent TAVR 1 year prior to data extraction date (eTables 14, 15, 16, and 17 and eFigure 5 in the Supplement). By multivariable analysis, death and stroke were not significantly different between the bicuspid and tricuspid groups (eTables 18, 19, 20, 21, and 22 in the Supplement).

There was no significant difference between groups in in-hospital death (0.6% bicuspid vs 0.4% tricuspid) or stroke (1.1% bicuspid vs 0.9% tricuspid) (Table 3). Serious procedural complications were uncommon in the bicuspid and tricuspid groups: conversion to surgery (0.4% vs 0.4%), coronary compression or obstruction (0.2% vs 0.1%), need for second valve implantation (0.3% vs 0.1%), perforation with or without tamponade (0.8% vs 0.5%), device embolization into aorta/ventricle (0.03% vs 0.1%), or new permanent pacemaker implantation (6.2% vs 5.2%). The 30-day and 1-year secondary clinical outcomes are summarized in eTable 23 in the Supplement.

Aortic valve hemodynamics improved significantly in patients with bicuspid and tricuspid aortic stenosis (eTables 24 and 25 in the Supplement). The mean aortic valve gradients did not significantly differ between the 2 groups at 30 days (12.7 mm Hg for bicuspid vs 12.9 mm Hg for tricuspid) and 1 year (13.2 mm Hg for bicuspid vs 13.5 mm Hg for tricuspid) (eFigure 6 in the Supplement). Moderate or severe paravalvular regurgitation was uncommon in both groups without significant difference between the groups at 30 days (1.8% for bicuspid vs 1.1% for tricuspid; absolute risk difference [RD], 0.7% [95% CI, −0.1 to 1.4%]) and 1 year (3.4% for bicuspid vs 2.1% for tricuspid; absolute RD, 1.3% [95% CI, −0.6 to 3.2%]) (eFigure 7 in the Supplement). Among patients with bicuspid aortic stenosis, the incidence of mild paravalvular regurgitation at 30 days was significantly less with the fourth-generation balloon-expandable valves compared with the third-generation balloon-expandable valves (13.1% for fourth-generation balloon-expandable valves vs 24.4% for third-generation balloon-expandable valves) (eTables 26, 27, and 28 in the Supplement).

Both bicuspid and tricuspid groups had significant improvements in NYHA functional class I or II symptoms at 30 days (96.0% vs 96.1%; absolute RD, 0.1% [95% CI, −1.3 to 1.0%]) and 1 year (94.3% vs 96.8%; absolute RD, 2.5% [95% CI, −4.6 to −0.4%]) (eFigure 8 in the Supplement). Health status had improved in both groups at 30 days (mean increase from baseline in KCCQ-OS score, 27.9 for bicuspid vs 28.1 for tricuspid; absolute RD, 0.2 [95% CI, −1.6 to 1.2]), which persisted up to 1 year without significant difference between the groups (30.2 for bicuspid vs 31.7 for tricuspid; absolute RD, 1.5 [95% CI, −4.0 to 1.1]) (eFigure 9 and eTables 29 and 30 in the Supplement).

The baseline characteristics and clinical outcomes in the unmatched and matched population in the overall cohort are summarized in eTables 31, 32, 33, 34, 35, and 36 in the Supplement). In the 6995 propensity-matched pairs of bicuspid and tricuspid patients undergoing TAVR, irrespective of the surgical risk, there was no significant difference in the incidence of death between bicuspid and tricuspid populations at 30 days (2.0% vs 1.7%; HR, 1.17 [95% CI, 0.91 to 1.51]; P = .21) or 1 year (8.6% vs 9.8%; HR, 0.90 [95% CI, 0.78 to 1.04]; P = .16) (eFigure 10A in the Supplement); or stroke at 30 days (1.9% vs 1.7%; HR, 1.10 [95% CI, 0.85 to 1.41]; P = .46) or 1 year (2.8% vs 3.1%; HR, 0.96 [95% CI, 0.78 to 1.20]; P = .75) (eFigure 10B in the Supplement). In the unadjusted overall cohort, mortality at 1 year was significantly lower in patients with bicuspid aortic stenosis compared with tricuspid aortic stenosis, and stroke rates were not significantly different between the 2 groups (eFigure 11 in the Supplement).

In this registry-based study of propensity-matched patients at low surgical risk who had undergone TAVR for aortic stenosis, patients who had bicuspid aortic stenosis, compared with tricuspid aortic stenosis, had no significant difference in 30-day or 1-year mortality or stroke. There were no significant differences in valve hemodynamics (aortic valve areas and gradients) or the rates of moderate or severe paravalvular regurgitation between the 2 groups at 30 days and 1 year. Patients with bicuspid and tricuspid aortic stenosis had significant and comparable improvement in functional status and quality of life measures.

This is the first report from the STS/ACC TVT Registry on outcomes of TAVR in patients at low surgical risk and bicuspid aortic stenosis. There are currently no ongoing randomized trials of TAVR vs surgery for the treatment of bicuspid aortic stenosis. Given the paucity of data, patients with bicuspid aortic stenosis, especially those at low surgical risk, are often considered more suitable for surgery. The present study included patients at low surgical risk who underwent TAVR for bicuspid aortic stenosis (mean age, 69 years), had an STS-PROM predicted 30-day mortality of 1.7%, and who demonstrated a 30-day mortality of 0.9%. Other procedural outcomes such as conversion to surgery, aortic root injury, aortic dissection, and significant paravalvular regurgitation occurred less than 1% of the time and were comparable to the outcomes of TAVR for tricuspid aortic stenosis. These outcomes were also comparable with published surgical series on bicuspid aortic stenosis and reported 30-day mortality ranging from 0.4% to 2.5% in younger patients with a mean age of 55 to 61 years.^16-21 However, the surgical series were from select medical centers in contrast to all consecutive patients undergoing TAVR in the United States included in this analysis. The largest series of surgery for bicuspid aortic stenosis in 1042 consecutive patients from 3 Swedish hospitals had a median age of 63 years and a 30-day mortality of 1%.²¹ The 30-day death and stroke rates in the present study were also comparable to the outcomes of surgery and TAVR in the pivotal low-risk randomized trials of tricuspid aortic stenosis.^7,8 Mortality rates at 1 year of 4% in patients with bicuspid aortic stenosis and 6% in patients with tricuspid aortic stenosis were higher than the observed rates in the pivotal low-risk studies and are reflective of the all-comer nature of this registry, which enrolled all consecutive patients undergoing TAVR in the US, irrespective of coexisting clinical conditions and challenging anatomic considerations, many of which were exclusions in the pivotal low-risk studies. Similarly, higher mortality rates were observed at 1 year in patients at low surgical risk (defined as having an STS-PROM score <4%) who underwent surgery or transcatheter aortic valve replacement for severe aortic stenosis in an all-inclusive German national registry, compared with the pivotal randomized trials of patients at low surgical risk.²²

Prior reports from the same registry in patients at higher surgical risk have reported higher rates of stroke, paravalvular regurgitation, and permanent pacemaker implantation after TAVR in patients with bicuspid aortic stenosis. In the present study of patients at low surgical risk and severe aortic stenosis, the rates of stroke, paravalvular regurgitation, and permanent pacemaker implantation were not significantly different between patients with bicuspid vs tricuspid aortic stenosis. Possible explanations for better outcomes in this population include better patient selection due to availability of surgical alternative in patients at low surgical risk, evolution of device technology (fourth-generation balloon-expandable transcatheter heart valves associated with decreased paravalvular regurgitation), and procedural technique (higher valve implantation associated with decreased pacemaker rates).

The present study used an STS-PROM score of less than 3%, instead of the local multidisciplinary heart team assessment, as an objective measure to define low surgical risk. The multidisciplinary heart team assessment of surgical risk in a clinical setting may differ across sites, depending on the local surgical and TAVR expertise.²³ The results were consistent in sensitivity analyses evaluating outcomes in patients deemed low risk by the multidisciplinary heart team at the treating sites, as well as in patients younger than 65 years of age.

A recent multicenter study in patients undergoing TAVR for bicuspid aortic stenosis with central computed tomography core laboratory assessment demonstrated that anatomic phenotyping of the bicuspid valve was predictive of procedural and intermediate-term outcomes.²⁴ The patients with a combination of calcified raphe and excess leaflet calcium had higher rates of aortic root injury, paravalvular regurgitation, and death at 2 years compared with patients with none or 1 of these features. Unfavorable computed tomography phenotype was present in approximately one-quarter of patients. Despite an increase in the use of TAVR in patients with bicuspid aortic stenosis, bicuspid aortic stenosis accounted for only 10% of patients in the current low surgical–risk cohort. Since a bicuspid aortic valve is present in 30% of patients undergoing aortic valve surgery,^6,25 the patients with bicuspid aortic stenosis included in this study may represent a select group with more favorable anatomy or a referral bias against TAVR in patients with bicuspid aortic stenosis in the absence of meaningful clinical outcomes data. Hence, the findings of the current analysis cannot be generalized to the entire population with bicuspid aortic stenosis.

Younger patients with bicuspid aortic stenosis are likely to require more than 1 aortic valve procedure due to limited durability of bioprosthetic valves. In selecting TAVR vs surgery in patients at low surgical risk and bicuspid aortic stenosis, anatomic suitability for index procedure, feasibility of repeat TAVR or repeat surgery, coronary access for future interventions, pacemaker rates, and valve thrombosis should be carefully considered to optimize lifetime management of treatment for these patients. Further, factors such as presence of extensive coronary artery disease, concomitant aortopathy, or atrial fibrillation requiring surgical treatment may determine the choice of surgical aortic valve replacement over TAVR in some patients. While the short-term outcomes with TAVR for bicuspid aortic stenosis in this study were not significantly different from those for tricuspid aortic stenosis, randomized clinical trials comparing TAVR vs surgery with longer-term follow-up data are needed to direct the optimal interventional or surgical management of aortic stenosis in these patients.

This study has several limitations. First, it had the inherent limitations of an observational study, including lack of center-independent adjudication of adverse events, lack of an independent imaging core laboratory to confirm bicuspid anatomy or valve function, potential underreporting of adverse events, and incomplete follow-up. The incomplete follow-up was likely exaggerated by the COVID-19 pandemic. Second, details from computed tomography of the aortic valve anatomy were not collected in the registry; thus, the study does not provide guidance on patient selection based on anatomic characteristics of the aortic valve. Third, the study did not assess the relationship between the presence of aortopathy and procedural complications. Fourth, the results of the study cannot be generalized to other valve types since the study only included balloon-expandable valves. Fifth, since the study had 4 primary end points, all findings in the present study should be interpreted as exploratory.

In this preliminary, registry-based study of propensity-matched patients at low surgical risk who had undergone TAVR for aortic stenosis, patients treated for bicuspid vs tricuspid aortic stenosis had no significant difference in mortality or stroke at 30 days or 1 year. Because of the potential for selection bias and absence of a control group treated surgically for bicuspid stenosis, randomized trials are needed to adequately assess the efficacy and safety of transcatheter aortic valve replacement for bicuspid aortic stenosis in patients at low surgical risk.

Corresponding Author: Raj R. Makkar, MD, Cedars-Sinai Heart Institute, 8700 Beverly Blvd, Los Angeles, CA 90048 (Raj.Makkar@cshs.org).

Accepted for Publication: July 24, 2021.

Author Contributions: Dr Makkar had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Makkar, Yoon, Chakravarty, Kapadia, Cheng, Mack, Leon, Thourani.

Acquisition, analysis, or interpretation of data: Makkar, Yoon, Chakravarty, Krishnaswamy, Shah, Kaneko, Skipper, Rinaldi, Babaliaros, Vemulapalli, Trento, Kodali, Mack, Leon.

Drafting of the manuscript: Makkar, Yoon, Chakravarty.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Makkar, Yoon, Skipper, Trento, Thourani.

Administrative, technical, or material support: Makkar, Leon, Thourani.

Supervision: Makkar, Chakravarty, Kapadia, Kaneko, Rinaldi, Cheng, Leon.

Conflict of Interest Disclosures: Dr Makkar reported receiving research grants from Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific; receiving personal fees from Edwards Lifesciences for travel. Dr Chakravarty reported other from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific (consultant and proctor) during the conduct of the study. Dr Shah reported personal fees from Edwards Lifesciences; and grants from Medtronic and Abbott during the conduct of the study. Dr Kaneko reported personal fees from Edwards Lifesciences during the conduct of the study; and personal fees from Medtronic and Abbott outside the submitted work. Dr Rinaldi reported personal fees from Edwards Lifesciences, Abbott Vascular, and Boston Scientific during the conduct of the study. Dr Babaliaros reported personal fees from Edwards Lifesciences and Abbott Vascular (consultant); and other from Transmural Systems (owns equity) outside the submitted work. Dr Vemulapalli reported grants from the American College of Cardiology (ACC), the Society of Thoracic Surgeons (STS), Boston Scientific, and Abbott Vascular outside the submitted work; grants or contracts from the US Food and Drug Administration, National Institutes of Health, and Cytokinetics; and serving on an advisory board or consulting for Janssen, HeartFlow, Boston Scientific, and the American College of Physicians. Dr Kodali reported grants from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott Vascular (research support); personal fees from Admedus (consultant) and Dura Biotech (senior advisory board); other from Thubrikar Aortic Valve and MicroInterventional Devices (owns equity and senior advisory board), and TriFlo, Adona, and Supira (owns equity and consultant) outside the submitted work. Dr Mack reported nonfinancial support from Abbott, Edwards Lifesciences, and Medtronic during the conduct of the study. Dr Leon reported grants from Edwards Lifesciences during the conduct of the study. Dr Thourani reported grants from Edwards Lifesciences outside the submitted work. No other disclosures were reported.

Funding/Support: This research was supported by the Edwards Lifesciences.

Role of the Funder/Sponsor: Edwards Lifesciences was not involved in the design and conduct of the study; collection, management, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The statistical analysis of the data was conducted by the sponsor.

Disclaimer: The views or opinions presented in this publication are solely those of authors and do not represent those of the ACC, the STS, or the STS/ACC Transcatheter Valve Therapy (TVT) Registry.

Additional Contributions: The authors thank Faouzi Kallel, PhD (Edwards Lifesciences) for ensuring technical accuracy of the manuscript; Ke Xu, PhD (Edwards Lifesciences) for assistance with the statistical analysis; and James Mun, PhD (Edwards Lifesciences) for data preparation for the manuscript. These individuals were not compensated for their role in this study.

Additional Information: The TVT Registry is an initiative of the STS and the ACC.