Prognostic value of urinary titin N-fragment in patients with heart failure: a retrospective cohort study

Background Urinary titin N-fragment normalized to urinary creatinine (U-titin) is a proposed biomarker of skeletal muscle degradation and has been linked to frailty/sarcopenia. However, evidence for its prognostic utility in heart failure (HF) remains limited. Purpose To investigate whether U-titin predicts 1-year clinical outcomes in patients with HF. Methods This single-center retrospective study included 96 patients with HF who underwent U-titin measurement between February 2023 and October 2024. Frailty-, nutrition-, and quality-of-life–related assessments were collected, including the Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT) score, Mini Nutritional Assessment (MNA), Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12), Barthel Index, and Clinical Frailty Scale. The primary endpoint was a 1-year composite of all-cause death and hospitalization for HF. Patients were stratified into high vs low U-titin groups using a receiver operating characteristic–derived cutoff of 3.3 pmol/mg Cr. Time-to-event outcomes were analyzed using the Kaplan–Meier method and a Cox proportional hazards model with stepwise selection based on the Bayesian information criterion. Clinical variables (age, sex, NYHA class, NT-proBNP, and LVEF), medications, and the aforementioned assessments were included as candidate covariates. Results Median age was 79 years (IQR 71–82); 41% were women. Median LVEF was 47.4% (IQR 35.6–60.3). All patients received an SGLT2 inhibitor and 54% received an ARNI. Most participants were NYHA class II (80%) and the remainder class III (20%). During 1-year follow-up, 8 patients met the primary endpoint. The high U-titin group showed a significantly higher event rate than the low U-titin group (log-rank p=0.016). In the Cox proportional hazards model, high U-titin was independently associated with the endpoint (hazard ratio [HR], 5.89; 95% CI, 1.23 to 28.26; P = .027). A Barthel Index <85 was also independently associated with the endpoint (HR, 16.47; 95% CI, 1.33 to 203.50; P = .029), whereas male sex was associated with a lower risk of the endpoint (HR, 0.02; 95% CI, 0.002 to 0.33; P = .005). Conclusion U-titin, a biomarker reflecting skeletal muscle degradation, was independently associated with 1-year adverse outcomes in patients with HF. Larger, prospective studies are warranted to validate these findings and clarify the mechanisms linking U-titin to HF prognosis.