Cardiac troponin T as a serum biomarker of respiratory impairment in amyotrophic lateral sclerosis

Abstract

Objective: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. Methods: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (nd = 298; nv = 49), serum neurofilament light chain (nd = 117; nv = 17), and respiratory tests (nd = 93; nv = 49). Results: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = −0.45, p = 0.001) and slow vital capacity % (r = −0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62–0.84) and <50% (AUC 0.80, 95% CI 0.68–0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61–0.83) and <50% (AUC 0.79, 95% CI 0.67–0.91). Interpretation: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function.