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

Q: What are the key findings of this study?

Combined biochemical and clinical frailty independently predicted increased 12-month mortality after TAVR (16% vs 4%; adjusted HR 3.3; 95% CI 1.9-5.6; P<0.001).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Patients undergoing transcatheter aortic valve replacement (TAVR) (n=2661). Intervention: Biochemical and clinical frailty (BF + CF: serum albumin =5) vs. No frailty (serum albumin >=35 g/L and Rockwood Clinical Frailty Scale <5). Primary outcome: 12-month mortality (HR 3.3, 95% CI 1.9-5.6, p=<0.001).

Q: What does this research mean for the field?

In patients undergoing transcatheter aortic valve replacement, the combination of clinical and biochemical frailty independently predicts a more than three-fold increase in 12-month mortality and significantly enhances risk prediction beyond standard surgical scores. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the prevalence of biochemical and clinical frailty in patients undergoing transcatheter aortic valve replacement and assess their additive value to standard surgical risk scores.

Anant D. Butala; Joseph Hogarty; Shane Nanayakkara; Jason Bloom; Sonny C. Palmer; Samer Q. Noaman; David McGaw; David I. Blusztein; Rozanne Johnston; Ellen Gardner; Elisha Gartner; Jillian Pedetti; Nay Htun; David M. Kaye; Antony S. Walton; Dion A. Stub

doi:10.1016/j.jacadv.2026.103416

November 3, 2026JACC AdvancesOpen Access

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

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Key result

Combined biochemical and clinical frailty is linked to ~3.3-fold higher 12-month mortality after TAVR.

HR 3.3
95% CI 1.9-5.6
P<0.001
n=2,661

Graphical abstract published by JACC Advances — Graphical abstract · Published by JACC Advances · CC BY 4.0

Why the study?

Does biochemical and clinical frailty increase 12-month mortality and improve risk prediction in contemporary patients undergoing TAVR?

Key Points

To evaluate the prevalence of biochemical and clinical frailty in patients undergoing transcatheter aortic valve replacement and assess their additive value to standard surgical risk scores.
Analysis of an Australian multicenter registry including 2,661 patients undergoing transcatheter aortic valve replacement (median age 82 years; median STS score 3.3).
Biochemical frailty was defined as serum albumin <35 g/L and clinical frailty as a Rockwood Clinical Frailty Scale score ≥5.
Frailty was identified in 35% of patients (n=920), with 19% of frail individuals (n=171) meeting both biochemical and clinical frailty criteria.
Twelve-month mortality increased in a stepwise fashion: 4% in non-frail patients, 7% in those with biochemical or clinical frailty, and 16% in those with both (Log-rank P < 0.001).
After adjustment, 12-month mortality was independently predicted by either frailty type alone (adjusted HR: 1.6; 95% CI: 1.0–2.4; P = 0.033) and both combined (adjusted HR: 3.3; 95% CI: 1.9–5.6; P < 0.001), significantly improving the STS predictive model (AUC: 0.608 vs 0.664; DeLong's P = 0.021).

Study Design

Type

Cohort (n=2,661)

Multicenter

Yes

Structured PICO

Does biochemical and clinical frailty increase 12-month mortality and improve risk prediction in contemporary patients undergoing TAVR?

P

Population

2,661 contemporary TAVR patients (median age 82, 60% male, median STS 3.3) from a multicenter Australian registry followed for 12 months.

E

Exposure

Frailty, categorized as biochemical frailty (BF: serum albumin <35 g/L), clinical frailty (CF: Rockwood Clinical Frailty Scale >=5), or combined biochemical and clinical frailty (BF + CF).

C

Comparator

No frailty (patients meeting neither biochemical nor clinical frailty criteria).

O

Outcome

12-month mortalityhard clinical

Main Result

Hazard Ratio: 3.3 (95% CI 1.9–5.6)

Absolute Event Rate: 16% vs 4%

p-value: p=<0.001

Combined biochemical (albumin <35 g/L) and clinical (Rockwood >=5) frailty identifies a high-risk TAVR subgroup with a 3.3-fold higher risk of 12-month mortality and significantly improves risk prediction over the STS score alone.

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Implication

Frailty assessment may refine short-term mortality risk stratification in TAVR; leaves open whether targeted interventions improve outcomes.

Abstract

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.

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Cite This Study

Butala et al. (2026) conducted a cohort in Patients undergoing transcatheter aortic valve replacement (TAVR) (n=2,661). Biochemical and clinical frailty (BF + CF: serum albumin <35 g/L and Rockwood Clinical Frailty Scale >=5) vs. No frailty (serum albumin >=35 g/L and Rockwood Clinical Frailty Scale <5) was evaluated on 12-month mortality (HR 3.3, 95% CI 1.9-5.6, p=<0.001). Combined biochemical and clinical frailty independently predicted increased 12-month mortality after TAVR (16% vs 4%; adjusted HR 3.3; 95% CI 1.9-5.6; P<0.001).

synapsesocial.com/papers/6ae9c6869d131cdf5331c9ce https://doi.org/10.1016/j.jacadv.2026.103416

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

Key Points

Study Design

Structured PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Study Design

Structured PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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