Direct Comparison of Outcomes After Transcatheter Aortic Valve Replacement in Veterans and Non-Veterans Using the Transcatheter Valve Therapy Registry

Abstract

Objectives. This study aims to compare veterans and non-veterans undergoing transcatheter aortic valve replacement (TAVR) using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) registry. Methods. Patients undergoing TAVR at George Washington University (GWU) and veterans treated at Washington DC Veterans Affairs Medical Center (VAMC) who underwent TAVR at GWU from 2014-2020 were included. All patients were reported in the TVT registry. Emergency and valve-in-valve TAVR were excluded. Cohorts were divided based on veteran status. Operators were the same for both groups. Outcomes were compared at 30 days and 1 year. The primary outcome was mortality and secondary outcomes were morbidity metrics. Results. A total of 299 patients (91 veterans, 208 non-veterans) were included. Veterans had higher rates of hypertension (87.9% vs 77.9%; P=.04), diabetes (46.7% vs 28.9%; P<.01), and lung disease (2.4% vs 11.0%; P<.001). Outcomes were not significantly different between veterans and non-veterans, including 30-day mortality (0% vs 2.9%, respectively; P=.18), 1-year mortality (9.8% vs 10.7%, respectively; P=.61), stroke incidence (0% vs 2.5%, respectively; P=.73), median intensive care unit stay (24 hours in both groups), and overall hospital stay (2 days in both groups). Conclusions. The affiliation between a VAMC and an academic medical center allowed for direct comparison between veterans and non-veterans undergoing TAVR by the same operators using the TVT registry. Despite significantly higher rates of comorbidities, veterans had equivalent outcomes compared with non-veterans. This may be in part due to the comprehensive care that veterans receive in the VAMC and this institution’s integrated heart center team.

Keywords: long-term results, transcatheter implantation, valve replacement

Transcatheter aortic valve replacement (TAVR) for severe aortic stenosis is gradually being adopted as the standard of care for a variety of patients.¹ The PARTNER trial, published in 2011, demonstrated that TAVR was an appropriate alternative to surgical aortic valve replacement in patients that are at high surgical risk.² More recent data from the PARTNER2 and PARTNER3 trials suggest that expanding TAVR eligibility to medium-risk and low-risk patients may also be warranted in the appropriate clinical setting.^3-5 While the use of TAVR in the general population in the United States has been thoroughly investigated and increasingly adopted, there are few data on specific outcomes of TAVR in veterans.

United States veterans are a unique population that warrants special consideration. Previous studies have shown that veterans may be at higher risk of cardiovascular disease when compared with non-veterans.⁶ Veteran status has also shown associations with numerous other comorbidities, such as higher rates of tobacco use, increased prevalence of diabetes, and higher rates of interstitial lung disease, which are all relevant to outcomes after intervention for cardiac valve disease.^7-9

Through an affiliation between The Washington DC Veterans Affairs Medical Center (VAMC) heart team and The George Washington University (GWU) Structural Heart Disease Program, the same team of operators and staff performs TAVR for veterans and civilians alike. Veterans receive their usual care at VAMC, undergo the TAVR procedure at GWU, and return for their health care to the VAMC. This allows for a unique opportunity to directly compare the impact of veteran status as it pertains to postprocedural outcomes after this procedure. The purpose of this study was to directly compare 30-day and 1-year outcomes between veterans vs non-veterans undergoing TAVR.

Methods

This was a retrospective cohort study, performed using prospectively collected data from the Transcatheter Valve Therapy (TVT) registry. Patients with severe aortic stenosis who underwent TAVR from 2014-2020 at the partnering university affiliate of the VAMC were included. Emergency and valve-in-valve TAVR were excluded (emergency operations were defined as patients with hemodynamic instability). Cohorts were divided based on veteran status. The primary outcome was mortality. Secondary outcomes were morbidity metrics, as defined by the TVT registry, including incidence of stroke, need for transfusion, length of stay, and time in the intensive care unit (ICU) (Table 1, Part 1 and Table 1, Part 2).

Operators and hospital were the same between groups for the TAVR procedure. Veterans had their entire evaluation, procedure, and postprocedure care performed by VAMC providers with dual appointments at GWU. In addition, the pre-TAVR evaluation, including clinical assessment, imaging, multidisciplinary valve clinic meetings, and TAVR planning for veterans, was undertaken at the VAMC, whereas non-veterans had their workup performed at GWU. All patients were presented in a joint VAMC/GWU multidisciplinary conference for final recommendations prior to TAVR. This VAMC instituted a combined valve clinic in 2005 involving noninvasive cardiology and cardiothoracic surgery; in 2014, this partnership matured into a multidisciplinary heart center.¹⁰ This formal collaboration combined both structural cardiology and cardiothoracic surgery into a single comprehensive program and performed all TAVR cases. This study was approved by the institutional review board of both the Washington DC VAMC and GWU. A waiver of informed consent was obtained due to the retrospective, deidentified nature of the study.

Preoperative demographics, patient characteristics, clinical comorbidities, 30-day outcomes, and 1-year outcomes were compared between veteran and non-veteran cohorts at the univariable level. Chi-square and Fisher’s exact tests were used for adequate and low cell count comparisons (≥25% of cell counts ≤5), respectively. Independent samples t test and Mann-Whitney U test were used for parametric and nonparametric continuous comparisons, respectively. Corresponding frequencies with percentages were reported for categorical comparisons, while mean ± standard deviation was reported for parametric continuous comparisons and median (quartile 1-quartile 3) was reported for nonparametric continuous comparisons. Normality of continuous variable distributions was assessed using measures of skew and kurtosis coupled with the Kolmogorov-Smirnov test.

Comparisons of demographics, patient characteristics, and clinical comorbidities resulting in a P-value <.20 were considered potential confounding covariates and were adjusted for in multivariable analysis to better elucidate the independent effect of veteran status on outcomes of interest. All multivariable models implemented a backward stepwise selection procedure of covariates triangulated with a purposeful selection approach using stay criteria of α=0.1. Confounding covariates for adjustment that were entered into our multivariable models included sex, race, prior coronary artery bypass grafting, number of previous cardiac surgeries, prior stroke, carotid stenosis assessment, smoking status, hypertension, diabetes, preoperative albumin, chronic lung disease, immunosuppressive medication, prior myocardial infarction, heart failure, preoperative ejection fraction, New York Heart Association class, aortic regurgitation, and proximal left anterior descending artery >70% stenosis.

Multivariable logistic regression models were used to analyze categorical outcomes, while multivariable generalized linear models were used to analyze continuous outcomes. Nonparametric continuous outcomes were natural logarithm transformed in order to reduce bias caused by skew and kurtosis before generalized linear model analysis. Adjusted odds ratios with 95% confidence intervals were reported for categorical outcomes from multivariable logistic regression analysis, while adjusted parameter estimates and standard errors were reported for continuous outcomes from multivariable generalized linear modeling. Multivariable analysis was performed on both 30-day and 1-year outcomes. Multicollinearity of covariates was assessed in all multivariable models using a variance inflation factor analysis, with a factor <2 considered acceptable. A subanalysis that eliminated females from each cohort was also performed. The methodology outlined above was repeated for an additional separate comparison of male veterans vs male non-veterans. All statistical analyses were performed using SAS, version 9.4 (SAS Institute, Inc) and a 2-sided P-value <.05 was considered statistically significant.

Results

A total of 299 patients (91 veterans and 208 non-veterans) met the inclusion criteria. Veteran status was significantly associated with male gender (98.9% vs 57.2%; P<.001), hypertension (87.9% vs 77.9%; P=.04), diabetes (46.7% vs 28.9%; P<.01), lower preoperative albumin (4.0 ± 0.5 g/dL vs 3.9 ± 0.5 g/dL; P=.03), chronic lung disease (34.1% vs 14.9%; P<.001), immunosuppressive medication use (12.2% vs 4.3%; P=.01), heart failure within 2 weeks prior to surgery (93.4% vs 84.1%; P=.03), a lower preoperative left ventricular ejection fraction (51.4 ± 11.6% vs 57.3 ± 13.5%; P<.001), higher New York Heart Association class (P<.01), and aortic regurgitation (P<.01) (Table 1, Part 1 and Table 1, Part 2). Veteran status had a trend level association with African American race, prior coronary artery bypass grafting, more previous cardiac surgeries, more smokers, and more prior myocardial infarction (all respective P<.20) (Table 1, Part 1 and Table 1, Part 2).

Univariable comparisons of 30-day outcomes of interest between veteran status cohorts did not significantly differ (Table 2). Notably, 30-day mortality was 0% in the veteran cohort and 2.9% in the non-veteran cohort (P=.18). Median intensive care unit length of stay was 2 days in both cohorts (P=.44). Thirty-day readmissions were lower in veterans (4.4% vs 9.1%; P=.16), which is of clinical interest despite not reaching statistical significance. Additionally, median creatinine at discharge was statistically higher in veterans (1.0 mg/dL vs 0.9 mg/dL; P=.03), but this absolute difference is clinically negligible.

Univariable comparisons of 1-year outcomes of interest between veteran status cohorts also did not significantly differ (Table 3). This includes 1-year mortality (12.9% vs 13.0%; P=.99) and stroke (0% vs 3%; P=.77). Ejection fraction was found to be higher in non-veterans after 1 year (61.5% vs 52.7%; P<.001); however, this disparity was also present preoperatively and both groups saw an improvement in their respective ejection fractions after TAVR.

After controlling for confounding covariates in multivariable analysis of 30-day (Table 4) and 1-year outcomes (Table 5), ­almost no significant differences between cohorts were detected. The only difference found in the multivariable model was that veteran’s length of hospital stay would be expected to be 2.89 days shorter than non-veterans if comorbidities were otherwise equal. However, 21 veterans (23%) were transferred to the VAMC for additional rehabilitation after TAVR, and their total combined length of stay is not captured in the TVT registry.

The results of the subanalysis that isolated only males between groups and the corresponding univariate and multivariable analyses are included on the respective tables listed above. A total of 209 males met the inclusion criteria, with 119 subjects in the non-veteran group and 90 subjects in the veteran group. Age was significantly higher in the veteran group (80.7 ± 7.5 years vs 78.1 ± 8.8 years; P=.03). The veteran group also had significantly more African American patients (24.4% vs 10.1%; P=.005), more hypertension (87.7% vs 76.5%; P=.04), more diabetes (46.1% vs 30.3%; P=.02), lower body mass index (24.4 ± 9.8 kg/m² vs 27.6 ± 9.3 kg/m²; P=.02), and more severe chronic lung disease (10.0% vs 3.4%; P<.01). Veterans also had a higher Society of Thoracic Surgeons (STS) risk score (4.7 ± 4.2 vs 3.6 ± 2.9; P=.03) (Table 1, Part 1 and Table 1, Part 2).

Similar to the overall cohort, univariable comparisons of 30-day outcomes and 1-year outcomes between male-only veteran status cohorts had very few statistically different results (Table 2 and Table 3). However, after controlling for confounding covariates in multivariable analysis of 30-day (Table 4) and 1-year outcomes (Table 5), no significant differences between cohorts were detected aside from overall length of stay, which as described previously does not account for veterans transferred post TAVR from GWU to VAMC for further recovery and thus is not truly representative.

Discussion

This study showed that despite significantly higher rates of comorbidities representing a sicker patient population, veterans undergoing TAVR performed by the same team of operators had no difference in 30-day and 1-year outcomes compared with non-veteran patients. This research adds to a growing body of literature emphasizing the successes of the Veterans Health Administration (VHA) in perioperative care. In addition, our findings corroborate other studies suggesting that the VHA is well equipped to implement advanced procedural programs, such as TAVR care centers. Similar to what other studies have reported, the comorbidity profile of veterans was significantly worse in our cohort when compared with non-veterans.^6-10 Rates of hypertension, diabetes, severe chronic lung disease (measured as forced expiratory volume in 1 second <50% predicted), immunosuppression medications, and lower serum albumin were all observed in higher proportions in the veteran cohort relative to the non-veteran cohort. Incidence of prior coronary artery bypass grafting, stroke, and smoking status were also proportionally higher in veterans on a trend level, but this did not reach statistical significance, which was likely due to a lack of power. Unsurprisingly, many of these comorbidities have been associated with worse outcomes after TAVR. The BRAVO-3 trial showed that patients with diabetes had higher adjusted odds of bleeding complications after TAVR,¹¹ but we did not observe a high rate of blood transfusions in either cohort. A subanalysis of the PARTNER trial found that oxygen-dependent lung disease predicts worse outcomes after TAVR—yet, despite higher rates of severe chronic lung disease, veterans in this study showed no ill effects as a result of this disparity.¹² Gassa et al found that lower preoperative albumin was associated with worse outcomes after TAVR.¹³ Although our veterans had a statistically significant lower albumin level, their outcomes after TAVR did not suffer as a result; however, it is worth noting that the difference in albumin between groups was only 0.1 g/dL, which is likely not clinically significant.

Despite a higher rate of relevant comorbidities, the outcomes after TAVR in veterans were equivalent to non-veterans. A potential contributing factor could be the comprehensive care that patients receive at VHA centers. Lynch et al found that among veterans with diabetes, those enrolled in the VHA system with diabetes had higher rates of foot exams compared with veterans that did not utilize the VHA for healthcare, and overall had fewer adverse effects from their disease.⁸ Another possible explanation could lie in the impact of racial/ethnic disparities and VHA care. Wong et al recently found that the worse outcomes that racial minorities typically suffer in health care might be improved by equal-access systems such as the VHA.¹⁰ Since African Americans comprised significant portions of each cohort (24.2% of veteran patients and 16.8% of non-veteran patients), the universal access offered by the VHA system may mitigate some of the previously demonstrated racial health disparities observed nationally. In turn, this may have served to offset some of the differences in comorbidities between cohorts.

It is worth noting that the STS risk score was not statistically different between groups in the full cohort analysis in this study, but was higher in the veteran group when only the male populations were compared. Equivalent STS risk scores could be interpreted as a reason that outcomes after TAVR did not differ between the full cohort groups—their risk profile was similar, and as a result they had similar outcomes. However, it is important to appreciate that the general TVT registry does not typically capture veterans, nor cases performed at VHA centers. Thus, the STS risk-score calculator was created without consideration of the unique comorbidity profile of veterans, and therefore may not accurately reflect TAVR risk in this population.^14,15 Furthermore, this score is a calculator for risk after surgical aortic valve replacement, limiting its applicability to TAVR. Other studies have aimed to provide a risk-score calculator specific to TAVR,¹⁴ but these scores were not included in the database of this study.

There have been previous studies that have also compared the outcomes of veterans with non-veterans after TAVR and shown similar results to our research. Hall et al used the VA Clinical Assessment, Reporting, and Tracking System database to create a visual comparison of TAVR outcomes in veterans to the TVT registry, and found that veterans had both similar preoperative demographics as well as similar morbidity and mortality outcomes at 8 VA centers compared with the national averages from the TVT database.¹⁶ Burke et al also performed an analysis comparing the outcomes of their VA centers with that of pre-existing TVT data, and they also found that veterans perform favorably after TAVR.¹⁷ One of the limitations of this study, however, is that the TAVR procedures and some baseline characteristics were identified from administrative records, which have inherent limitations.

Our data add an additional level of novelty because of the unique arrangement we share between the VAMC and our academic affiliate, GWU. The Heart Center at Washington DC VAMC performs the TAVR procedures at GWU Hospital with the same team that performs TAVR for civilians, and all patients including outcomes are reported equally in the TVT registry.¹⁸ Procedures performed by a single team of operators allow us to reduce certain biases that other studies have cited. Moreover, this study permits a more direct comparison in veterans vs non-veterans undergoing TAVR compared to studies published previously and adds credence to the previous evidence that despite having more comorbidities, veterans do as well as non-veterans after TAVR.

Since our veteran population is almost exclusively male and the civilian population in the affiliate medical center is mixed, we felt it necessary to perform an additional subanalysis comparing only males between groups. The findings correlated well with the full cohort analysis and our overall findings were unchanged. The preprocedural differences were even more pronounced in the male-only comparison, especially considering the significantly higher STS risk score in veteran males. But, despite having more comorbidities, veteran males had mostly equivalent outcomes compared with their non-veteran male counterparts.

The comprehensive Heart Center at the DC VAMC that combines both structural cardiology and cardiothoracic surgery has a multidisciplinary approach to TAVR that also includes a valvular disease clinic, in addition to weekly conferences to discuss cases and procedural planning. This format, which has been in place for almost a decade, has centralized the approach to valvular disease and management and has facilitated access for veterans as well as referring providers.¹⁰ This may serve as a template for other transcatheter valve programs throughout the VHA.

Study limitations. Although this research compares veterans with non-veterans in a unique way, this study has several limitations. The inherent shortcomings of database research and retrospective analysis are present. Furthermore, since this is a single-center study, the sample size is relatively small and our analyses are underpowered as a result. Moreover, these findings only represent a single VHA center in collaboration with an academic institution and we are unable to extrapolate these results to the VHA as a whole with respect to TAVR outcomes. It is also important to consider the differences in gender and outcomes after TAVR, since the majority of veterans are male.

Conclusion

In this study, the affiliation between the VHA and an academic medical center allowed for direct comparison of veterans with non-veterans undergoing TAVR using the TVT registry. Despite significantly higher comorbidity rates, veterans had equivalent outcomes compared with non-veterans. It is likely that the comprehensive care provided by VHA contributes to improved outcomes following TAVR. If further research corroborates these results, then the VHA care system might serve as a model that should be replicated for the care of other vulnerable populations.

Acknowledgments. Special thank you to Eduard Shaykhinurov for his data stewardship.

Affiliations and Disclosures

From the ¹Division of Cardiology, Cardiothoracic Surgery and Heart Center, Veterans Affairs Medical Center, Washington, DC; ²Department of Surgery, George Washington University Hospital, Washington DC; ³Division of Cardiology, Medical Faculty Associates, George Washington University, Washington, DC; ⁴Department of Cardiothoracic Surgery, George Washington University Hospital, Washington, DC; ⁵Department of Surgery, MedStar Georgetown University Hospital, Washington, DC; and ⁶Department of Biomedical Engineering, George Washington University, Washington, DC.

The views expressed in this report are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Najam is a speaker and consultant for Liva Nova. Drs Napolitano, Holleran, Morrissette, Antevil, Trachiotis and Nagy are employed by and receive a salary from the Department of Veterans Affairs. The remaining authors report no conflicts of interest regarding the content herein.

This research was presented as a virtual podium presentation at the Association of Veterans Affairs Surgeons National Meeting on April 26, 2021.

Manuscript accepted November 29, 2021.

Address for correspondence: Christian D. Nagy, MD, Medical Faculty Associates, The George Washington University, 2150 Pennsylvania Ave NW, Suite 4-417, Washington, DC. Email: cnagy@mfa.gwu.edu

References

1. Young MN, Elmariah S, Kennedy KF, Inglessis I, Yeh RW. Utilization and outcomes of transcatheter aortic valve replacement in the United States shortly after device approval. Catheter Cardiovasc Interv. 2017;90(5):830-838. doi:10.1002/ccd.27018

2. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198. doi:10.1056/NEJMoa1103510

3. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380(18):1695-1705. doi:10.1056/NEJMoa1814052

4. Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609-1620. doi:10.1056/NEJMoa1514616

5. Makkar RR, Thourani VH, Mack MJ, et al. Five-year outcomes of transcatheter or surgical aortic-valve replacement. N Engl J Med. 2020;382(9):799-809. doi:10.1056/NEJMoa1910555

6. Assari S. Veterans and risk of heart disease in the united states: a cohort with 20 years of follow up. Int J Prev Med. 2014;5(6):703-709.

7. Odani S, Agaku IT, Graffunder CM, Tynan MA, Armour BS. Tobacco product use among military veterans - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2018;67(1):7-12. doi:10.15585/mmwr.mm6701a2

8. Lynch CP, Strom JL, Egede LE. Effect of veterans administration use on indicators of diabetes care in a national sample of veterans. Diabetes Technol Ther. 2010;12(6):427-433. doi:10.1089/dia.2009.0171

9. Bedoya A, Pleasants RA, Boggan JC, et al. Interstitial lung disease in a veterans affairs regional network; a retrospective cohort study. PLoS One. 2021;16(3):e0247316. doi:10.1371/journal.pone.0247316

10. Endicott K, Lambdin J, Morrisette J, et al. Heart valve clinic: a model for treatment of structural heart disease. World J Cardiovasc Surgery. 2017;7(1):1-9. doi:10.4236/wjcs.2017.71001

11. Wong MS, Hoggatt KJ, Steers WN, et al. Racial/ethnic disparities in mortality across the Veterans Health Administration. Health Equity. 2019;3(1):99-108. doi:10.1089/heq.2018.0086

12. Goel R, Power D, Tchetche D, et al. Impact of diabetes mellitus on short term vascular complications after TAVR: results from the BRAVO-3 randomized trial. Int J Cardiol. 2019;297:22-29. Epub 2019 Oct 11. doi:10.1016/j.ijcard.2019.09.063

13. Arnold SV, Reynolds MR, Lei Y, et al. Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (placement of aortic transcatheter valve) trial. Circulation. 2014;129(25):2682-2690. doi:10.1161/CIRCULATIONAHA.113.007477

14. Gassa A, Borghardt JH, Maier J, et al. Effect of preoperative low serum albumin on postoperative complications and early mortality in patients undergoing transcatheter aortic valve replacement. J Thorac Dis. 2018;10(12):6763-6770. doi:10.21037/jtd.2018.11.30

15. Edwards FH, Cohen DJ, O’Brien SM, et al. Development and validation of a risk prediction model for in-hospital mortality after transcatheter aortic valve replacement. JAMA Cardiol. 2016;1(1):46-52. doi:10.1001/jamacardio.2015.0326

16. Reiff C, Gurevich S, Bertog S, Sorajja P, Kelly R, Garcia S. Validation of STS/ACC TVT-TAVR score in veterans undergoing transcatheter aortic valve replacement. J Invasive Cardiol. 2018;30(12):447-451. Epub 2018 Sep 15.

17. Hall PS, O’Donnell CI, Mathew V, et al. Outcomes of veterans undergoing TAVR within Veterans Affairs medical centers: insights from the Veterans Affairs clinical assessment, reporting, and tracking program. JACC Cardiovasc Interv. 2019;12(21):2186-2194. doi:10.1016/j.jcin.2019.04.040

18. Burke L, Gozdecki L, Doukas D, et al. Patient risk assessment for transcatheter aortic valve replacement at Veterans Health Administration hospitals. J Invasive Cardiol. 2020;32(8):302-309.