JACC Advances · Nov 3, 2026

The Impact of Clinical and Biochemical Frailty on Outcomes following Transcatheter Aortic Valve Replacement

By Butala AD, Hogarty J, Nanayakkara S et al.

Background Frailty results from declining reserve and function and is a modifiable cardiovascular risk-factor. Despite this, there is limited evidence surrounding its role in lower-risk TAVR cohorts. Objectives This study aimed to evaluate frailty among contemporary TAVR patients, delineate the impact of biochemical and clinical frailty, and understand its additive value to existing risk-prediction tools. Methods Analysis of a multicenter Australian registry. Biochemical frailty (BF) was defined as serum albumin <35 g/L and clinical frailty (CF) as a Rockwood Clinical Frailty Scale ≥5. Patients meeting BF or CF criteria were categorized as frail. Results Of the 2,661 patients, the median age 82 (IQR: 77-86), 60% male, and median STS 3.3 (2-5.2), 920 patients (35%) were considered frail. A total of 171 (19%) of frail patients fulfilled both BF and CF criteria. The frail group was older (83 vs 81, P < 0.001), more females (43% vs 38%; P = 0.016) with higher STS scores (4 vs 3, P < 0.001). Kaplan-Meier analysis showed a stepwise increase in 12-month mortality with increasing frailty (no frailty 4% vs BF or CF 7% vs BF + CF 16%, Log-rank P < 0.001). In Cox proportional hazards regression BF or CF (adjusted HR: 1.6; 95% CI: 1.0-2.4; P = 0.033) and BF + CF (adjusted HR: 3.3; 95% CI: 1.9-5.6; P < 0.001) independently predicted 12-month mortality. Addition of frailty to STS Score improved mortality prediction (area under the receiver-operating characteristic curve: 0.608 vs 0.664; DeLong’s P = 0.021), with Shapley analysis demonstrating significant contribution from frailty. Conclusions Frailty is common with significant implications in TAVR. Patients with biochemical and clinical frailty criteria are highest risk. Development of strategies to address frailty is critical.

doi.org/10.1016/j.jacadv.2026.103416 Open access PubMed 42971036 Biomarkers