Gradients after transcatheter aortic valve replacements are impacted by both body mass index and valve size: a retrospective cohort study

Introduction

Background

Obesity, defined as a body mass index (BMI) greater than 30, is a common comorbidity in patients undergoing transcatheter aortic valve replacement (TAVR) (1). Obesity is associated with increased surgical risks, post-operative complications, and altered hemodynamics (2,3). TAVR is a widely used procedure for treating severe aortic stenosis, but the impact of BMI and valve size on post-TAVR gradients remains unclear (4). Gradients, reflecting the pressure difference across the valve, are routinely used as a measure of valve performance and procedural success (5). Persistently elevated gradients may indicate reduced effective orifice area, patient-prosthesis mismatch, poor durability, and could potentially lead to adverse long-term outcomes (5). Additionally, other research shows that post-procedural gradients can predict adverse long-term outcomes, with greater adverse events occurring in patients with gradients below 10 mmHg and above 30 mmHg (6). As the pressure gradient can be simplified as a function of flow rate and effective orifice size, understanding the clinical factors influencing flow rate and valve size is therefore essential for optimizing TAVR outcomes.

Rationale and knowledge gap

Patients with higher BMI require greater cardiac output to meet their metabolic demands. An increased cardiac output should result in higher transvalvular gradients. This is because higher the increased cardiac output pushes more blood through the heart, and this increased stroke volume should be associated with a higher gradient, even after TAVR. Valve size further modulates this effect: smaller valves restrict the orifice for blood flow, amplifying gradients, while larger valves mitigate these effects by providing a larger valve area. The interaction between BMI and valve size is therefore crucial for understanding post-TAVR gradients and outcomes.

Objective

Understanding the impact of BMI and TAVR valve size on valve gradients is critical for optimizing outcomes, especially given the increasing prevalence of obesity in patients undergoing TAVR. Considering that BMI is associated with greater cardiac output, and that smaller valve sizes have smaller effective orifice areas, we hypothesized that patients with higher BMI and smaller valve sizes will experience higher echo-derived gradients 30 days after TAVR. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-256/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of the University of North Carolina at Chapel Hill (UNCCH) (No. 18-0228) and individual consent for this retrospective analysis was waived. While all work was done at the UNCCH Medical Center, all researchers are employed by the school of medicine. We conducted a retrospective cohort study of 180 consecutive patients who received balloon-expandable TAVR between 2021 and 2023 at the University of North Carolina Hospital Cardiac Catheterization Lab. This was an all-comer study, and all patients who received balloon-expandable TAVR between 2021 and 2023 at our institution were included. Because this was a retrospective analysis of all eligible cases during that period, no formal sample size estimation was performed. We collected demographic data; baseline co-morbidities; previous cardiac medical history, pre-procedural computed tomography (CT) and echocardiographic data; procedural data such as valve size and type; pre-discharge mean gradients; and patients completed a 30-day follow-up echocardiogram to collect mean gradients. Percent oversizing was not controlled for. Height and weight were recorded in a preoperative clinic visit, and BMI was calculated from measured weight. Mean transvalvular gradients were measured using Doppler echocardiography, following standard clinical protocols. All patients received valve sizes were chosen based on instructions for use issued by the manufacturers. The distribution of valves used was as follows: 44 SAPIEN 3 (24.4%), 85 SAPIEN 3 Ultra (47.2%), 51 SAPIEN 3 RESILIA (28.3%).

Statistical analysis

Patients were stratified based on BMI (<30 vs. ≥30 kg/m²) and valve size (20/23 vs. 26/29 mm). This grouping was made due to smaller sample size to increase statistical power, and follows the rationale of the SMART trial, which compared balloon self-expanding valves in small annuli, which is defined as 20 and 23 mm annuli.

Univariate analysis was performed using Fisher’s exact test for categorical variables. Continuous variables were analyzed using independent t-tests. Multivariate linear regressions were performed in SAS JMP Pro 17.2 to evaluate predictors of 30-day change in mean transvalvular gradient after discharge. Model covariates included demographic and baseline clinical factors, such as BMI, age, and left ventricular ejection fraction (LVEF). Results are presented as parameter estimates with associated P values, with a threshold of ≤0.05 considered statistically significant.

Results

A total of 180 patients were identified and stratified into four groups based on BMI (<30 vs. ≥30 kg/m²) and valve size (20/23 vs. 26/29 mm). Baseline characteristics of the groups are summarized in Table 1. The groups were similar in most demographic and clinical characteristics, with the exception of age, which was significantly lower in the high BMI group compared to the low BMI group (mean age 72.9±10.5 vs. 78.3±10.0 years, P<0.001).

The mean 30-day echocardiogram gradients for each group are summarized in Table 2. The summary of the analysis is shown in Table 3 and shown in Figure 1. Patients with high-BMI and small valves had the highest mean gradients (15.5 mmHg). This is significantly greater than low-BMI patients with large valves who had the lowest gradients (10.4 mmHg, P=0.002). Among high-BMI patients, small valves were associated with significantly higher gradients compared to large valves (15.5 vs. 10.3 mmHg, P=0.009). In contrast, low-BMI patients exhibited similar gradients regardless of valve size (11.9 vs. 10.4 mmHg, P=0.16). A trend was observed toward higher gradients in high-BMI patients with small valves compared to low-BMI patients with small valves, though this difference did not reach statistical significance (P=0.057). These findings, as illustrated in Figure 1, demonstrate that both high BMI and small valve size contribute to elevated gradients, with valve size having a more pronounced impact in high-BMI patients. In patients receiving large valves, BMI had no impact on overall gradient (P=0.91). Similarly, in patients with a BMI <30 kg/m², valve size made little difference in overall gradient (P=0.16). Lastly, smaller patients (BMI <30 kg/m²) with small valves (20/23 mm) had similar gradients to larger patients (BMI ≥30 kg/m²) receiving larger valves (26/29 mm) (P=0.15).

Figure 1 Mean 30-day gradients stratified by BMI and valve size, illustrating significant differences across certain group comparisons. BMI, body mass index.

In multivariate linear regression modeling with 30-day mean gradient as the dependent variable, BMI analyzed as a continuous variable was independently associated with a higher mean gradient at 30 days [β =0.16, standard error (SE) =0.074, P=0.04], after controlling for age and baseline LVEF. However, when BMI was analyzed as a categorical variable using a cutoff of 30 kg/m², this association was no longer significant (β =0.06, SE =0.47, P=0.90). No other covariates were significantly associated with 30-day mean gradient in either multivariate model.

Discussion

Key findings

This study highlights the critical impact of BMI and valve size on 30-day echo-derived gradients following balloon-expandable TAVR. Our findings indicate that high BMI and smaller valve size are associated with significantly elevated gradients, while larger valves help attenuate this effect. In contrast, low-BMI patients demonstrated relatively consistent gradients regardless of valve size, suggesting a diminished influence of valve size in this population.

Explanations of findings

High-BMI patients with small valves experienced the highest gradients, which aligns with the physiological demand for increased cardiac output in individuals with higher body mass. Smaller valve sizes result in a restricted orifice for blood flow, amplifying the pressure gradient due to greater transvalvular velocity. In contrast, larger valves provide a larger valve area, allowing for lower gradients in high-BMI patients. This attenuation was not observed in low-BMI patients, where gradients remained stable across valve sizes, suggesting that the flow dynamics in this group are less sensitive to valve size. Finally, when treating BMI as a continuous variable, and controlling for confounding effects, BMI was still found to impact post-procedural gradients. While a BMI of 30 kg/m² cannot be used as a categorical cutoff, there is still an established relationship between BMI and post-procedural gradients.

Implications and actions needed

These findings underscore the importance of considering BMI when planning TAVR procedures. Although valve size selection is constrained by the patient’s native annular dimensions, understanding the relationship between BMI, valve size, and post-TAVR gradients may help guide treatment strategy to minimize gradients and optimize outcomes. For patients with high BMI and small annuli, alternative procedural approaches may help mitigate elevated gradients. There may also be a role for weight reduction before TAVR or surgical valve replacement with annular enlargement as part of a comprehensive treatment plan, however this study does not evaluate the efficacy of these, and these remain an important area for research. In a randomized, controlled trial, taking dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, after undergoing transcatheter aortic valve implantation was found to result in significantly lower mortality than receiving standard of care alone (7). A similar formal study could investigate combining glucagon-like peptide-1 (GLP-1) medications with TAVR treatment.

Comparison with similar research

This study adds to the existing literature examining procedural and patient-specific factors that impact TAVR outcomes. Recent reviews have examined using TAVR across diverse patient populations, from patients with lung transplants, to patients with asymptomatic aortic stenosis (8,9). Robotic aortic valve replacement (RAVR) is also a relatively new method of treatment for aortic valve disease, with the first case in 2020, and is much less invasive than normal surgical aortic valve replacement (10,11). As RAVR develops and becomes more accessible, it may become even more important to be able to determine which patients should receive surgical versus interventional treatment. And furthermore, as TAVR procedures have grown to account for over 80% of all aortic valve replacements, there is an even greater need to understand what factors impact the success of the procedure (12). Together, these studies contextualize the relevance of our findings by situating BMI and valve size within the larger landscape of evolving TAVR practice, procedural innovation, and patient-centered optimization.

Strengths and limitations

A key strength of this study is its stratified analysis of BMI and valve size, which provides valuable insights into their combined impact on post-TAVR gradients and allows for more precise clinical recommendations, particularly for high-BMI patients. However, the relatively small sample size and uneven subgroup divisions, along with restricting analysis to balloon expandable valves, may limit the statistical power and reduce the generalizability of this study. Data was not collected on valve calcification, which could impact valve gradients. Another limitation is that valve oversizing was not explicitly controlled for in this analysis—oversizing is a recognized factor influencing post-TAVR hemodynamics and may partially account for variation in mean gradient outcomes. Additionally, the study has inherent bias as a non-randomized, single-center, observational study.

This study focused exclusively on balloon-expandable valves to maintain a uniform cohort and minimize confounding related to device type. At University of North Carolina at Chapel Hill Hospitals, balloon-expandable valves are used in the vast majority of TAVR procedures, which aligns with current practice patterns across the United States (U.S.). As such, our findings are highly applicable to contemporary U.S. populations, where both balloon-expandable valve use and obesity prevalence are high. However, the impact of valve design on the relationship between BMI, valve size, and post-TAVR gradients remains to be fully understood.

This analysis was limited to gradients measured 30 days after TAVR, which allowed for the assessment of early hemodynamic performance but not long-term outcomes. Prior studies have shown that transvalvular gradients typically remain stable beyond 30 days, suggesting that early post-procedural measurements are representative of later hemodynamic trends (6). However, the persistence of these differences over time and their potential relationship to patient outcomes such as mortality and valve durability warrant further investigation.

In summary, this study demonstrates that both BMI and valve size significantly influence post-TAVR gradients, with high-BMI patients receiving small valves showing the highest gradients, and low BMI patients receiving large valves having the lowest gradients. In patients with low BMI, valve size has less of an effect on 30-day echo-derived gradients. Similarly, for patients receiving large valves, BMI has less of an effect on gradient.

Conclusions

Both BMI and valve size significantly impact 30-day echo-derived gradients following balloon-expandable TAVR. High-BMI patients with small valves experience the highest gradients, indicating that this combination poses the greatest challenge for optimizing outcomes. Conversely, with larger valves, the impact of BMI on valve gradients is attenuated, suggesting that larger valve sizes may help mitigate the effect of higher BMI. Notably, in low-BMI patients, valve size had no significant impact on gradients, indicating that BMI is a more critical factor in these cases. These findings highlight the importance of considering BMI as a key factor when selecting valve size for TAVR procedures and suggest a role for weight loss to achieve optimal outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-256/rc

Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-256/dss

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-256/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-256/coif). J.P.V. reports honoraria from Edwards Lifesciences and payment for expert testimony, unrelated to the submitted work. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the institutional review board of University of North Carolina at Chapel Hill (No. 18-0228) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Seo J, Kharawala A, Borkowski P, et al. Obesity and Transcatheter Aortic Valve Replacement. J Cardiovasc Dev Dis 2024;11:169. [Crossref] [PubMed]
2. Corcione N, Testa A, Ferraro P, et al. Baseline, procedural and outcome features of patients undergoing transcatheter aortic valve implantation according to different body mass index categories. Minerva Med 2021;112:474-82. [Crossref] [PubMed]
3. Lavie CJ, McAuley PA, Church TS, et al. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. J Am Coll Cardiol 2014;63:1345-54. [Crossref] [PubMed]
4. Abramowitz Y, Chakravarty T, Jilaihawi H, et al. Impact of body mass index on the outcomes following transcatheter aortic valve implantation. Catheter Cardiovasc Interv 2016;88:127-34. [Crossref] [PubMed]
5. Thyregod HGH, Ihlemann N. Measuring Transvalvular Aortic Pressure Gradients: Answering Questions or Asking New Ones? JACC Cardiovasc Interv 2022;15:1849-51. [Crossref] [PubMed]
6. Kherallah RY, Suffredini JM, Rahman F, et al. Impact of Elevated Gradients After Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Bioprostheses. Circ Cardiovasc Interv 2024;17:e013558. [Crossref] [PubMed]
7. Raposeiras-Roubin S, Amat-Santos IJ, Rossello X, et al. Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med 2025;392:1396-405. [Crossref] [PubMed]
8. Ragheb D, Yun J. Cardiac interventions in lung transplant patients: a narrative review with a focus on transcatheter valvular interventions. Curr Chall Thorac Surg 2025;7:25. [Crossref]
9. Gonze A, Gennart T, Perriens E, et al. Is early transcatheter aortic valve replacement for asymptomatic aortic stenosis justified?-critical analysis of the strategy. J Thorac Dis 2025;17:3484-6. [Crossref] [PubMed]
10. Jagadeesan V, Mehaffey JH, Darehzereshki A, et al. Surgical versus transcatheter aortic valve replacement: the future role of robotic aortic valve replacement. Ann Cardiothorac Surg 2025;14:182-91. [Crossref] [PubMed]
11. Murtaza G, Wei L. Lateral access fully robotic aortic valve replacement "RAVR": from novel to normal. Ann Cardiothorac Surg 2025;14:192-201. [Crossref] [PubMed]
12. Brescia AA, Kachroo P, Kaneko T. Transcatheter aortic valve replacement explant various techniques. Ann Cardiothorac Surg 2025;14:157-64. [Crossref] [PubMed]