OBJECTIVES: Prior studies have demonstrated that frailty, characterized by a patient's burden of chronic medical comorbidities, is predictive of adverse outcomes across surgical specialties. This study utilizes the clinical frailty score (CFS) to assess the impact of phenotypic frailty on long-term mortality and return to preoperative functional status following fenestrated and branched endovascular repair (F/BEVAR) for thoracoabdominal aortic aneurysm (TAAA). METHODS: All patients enrolled in a prospective, physician-sponsored IDE clinical trial from 2012 to 2023 following F/BEVAR for TAAA were included. Patients were assigned to a standard or high-risk category, if they had one or more of the following criteria: CFS >
4, metabolic equivalent (MET) <
2, prior spinal cord injury or stroke, CHF, COPD with oxygen requirement, CKD Stage IV/V, peripheral artery disease, active cancer with life expectancy greater than 1-year, heavy aortic atheroma burden, history of cirrhosis and/or substance use disorder. Long-term survival and return to preoperative functional status were assessed using Kaplan-Meier analysis and Cox regression analysis based on high-risk status. A secondary survival analysis based on CFS (CFS >
4 and <
4) was performed with adjustment for age, sex, CHF, COPD with oxygen requirement, CKD Stage IV/V. RESULTS: 213 patients underwent F/BEVAR, including 96 standard-risk (45%) and 117 high-risk patients (55%). Other than high-risk classifiers, there were no differences in comorbidities, operative presentation, or maximum aneurysm diameter. Within the high-risk study cohort, a total of 57 patients had a CFS >
4 (48.7%), 49 patients had CKD stage IV/V (41.9%), and 33 patients had a MET >
2 (28.2%). Higher CFS (HR 1.37, 95% CI 1.07-1.74), lower BMI (HR 0.87, 95% CI 0.82-0.99), larger aneurysm size (HR 1.03, 95% CI 1.01-1.05), COPD with oxygen requirement (HR 2.64, 95% CI 1.62-4.30) and CKD Stage IV/V (HR 2.85, 95% CI 1.29-6.28) were associated with reduced long-term survival in multivariable analysis. Standard-risk patients were more likely to return to preoperative functional status (92.7% vs. 68.4%, p<
0.01), while higher CFS (OR 0.49, 95% CI 0.34-0.72) and COPD with oxygen requirement (OR 0.42, 95% CI 0.20-0.88) were associated with a lower likelihood of return to preoperative functional status. High-risk patients had reduced survival at 1-year (76% vs. 95%) and 5-years (39% vs. 58%, p<
0.01). When stratified by CFS, differences in survival persisted. Patients with CFS >
4 also had reduced survival at 1-year (70% vs. 90%) and 5-years (33% vs. 53%, p=0.01), respectively. CONCLUSION: Patients with higher CFS have worse long-term survival and are less likely to return to preoperative functional status, even after adjustment for medical comorbidities. Given these findings, identification of high-risk patients, including direct measurement of phenotypic frailty utilizing the clinical frailty scale is an important tool for preoperative risk stratification and patient selection prior to F/BEVAR.