Usefulness of Urinary N-Terminal Fragment of Titin to Predict Mortality in Dilated Cardiomyopathy

Abstract

Titin is associated with myocardial stiffness and hypertrophy, and mutations in its gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DC). It has recently been reported that in damaged muscle, the N-terminal fragment of titin (Titin-N) is cleaved by calpain-3, and urinary Titin-N (U-TN) could be a marker of sarcomere damage. We aimed to investigate the impact of U-TN on prognosis of DC. We measured urinary levels of Titin-N/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 102 patients with DC, and followed up all the patients (mean 1,167 days). The patients were divided into 3 groups based on the U-TN/Cr: first (U-TN/Cr <3.35, n = 34), second (3.35 ≤ U-TN/Cr <7.26, n = 34), and third (7.26 ≤ U-TN/Cr, n = 34) tertiles. In the Kaplan-Meier analysis, cardiac and all-cause mortality progressively increased from the first to the second and third groups (p <0.05, respectively). In the Cox proportional hazard analyses, U-TN/Cr was a predictor of cardiac and all-cause mortality in patients with DC (p <0.05, respectively). U-TN, a possible marker of sarcomere damage, can identify high-risk patients with DC.