Cardiac Troponin T is a Serum Biomarker of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis

ObjectiveInformative biomarkers are an urgent need in management and therapy development of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in most amyotrophic lateral sclerosis patients and not correlated with neurofilaments. We sought to delineate the functional implications and the informative value of serum troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis. MethodsWe analyzed two independent hospital-based amyotrophic lateral sclerosis cohorts (d=discovery cohort; v= validation cohort) with data available on serum cardiac troponin T levels (nd=297; nv=49), serum neurofilament light chain levels (nd=116; nv=17), and routine respiratory test results (nd=86; nv=49). ResultsSerum cardiac troponin T levels, unlike serum neurofilaments, were strongly associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating score (rd = - 0.29, pd = 0.001; rv= - 0.48, pv = 0.007) and with relevant pulmonary function parameters (nd), namely SVC% (r = - 0.45; p = 0.001), FVC% (r = - 0.43; p = 0.001), FEV1% (r = -0.37, p = 0.007), and PEF (r = - 0.34, p = 0.027). Serum cardiac Troponin T reliably discriminated benchmarks of SVC% < 80%: (AUC 0.75, p = 0.003), FVC % < 80%: (AUC 0.72, p = 0.011) and PEF% <75%: (AUC 0.72, p = 0.015). InterpretationOur findings confirm cardiac Troponin T as an informative serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments. Serum Troponin T can flag compromised respiratory function in amyotrophic lateral sclerosis and might prove useful as a proxy of respiratory impairment with prognostic implications.