Plasma troponin T reflects lower motor neuron involvement on electromyography in amyotrophic lateral sclerosis

Cardiac troponin T (cTnT) is elevated in neuromuscular conditions without apparent cardiac disease, including Amyotrophic Lateral Sclerosis (ALS). The reason for this increase is unclear. Since cTnT is found in both cardiomyocytes and skeletal muscle cells, we aimed to investigate the latter as a possible cTnT source. We examined the correlation of cTnT in venous blood to lower motor neuron (LMN) involvement on Electromyography (EMG). A positive correlation between EMG findings and cTnT levels would indicate that cTnT is a biomarker for LMN involvement in ALS. This observational cohort study was conducted on a tertiary referral centre for neuromuscular diseases in Stockholm, Sweden. Consecutive patients with ALS were included. EMG was performed during diagnostic work-up, and high-sensitive cardiac troponin T (hs-cTnT), plasma creatine kinase (CK), and serum neurofilament light (NfL) were analysed within 6 months of the EMG. King's stage and score on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) closest to hs-cTnT sampling were noted. In total, 50 ALS patients diagnosed between 1 January 2014 and 31 December 2018 were included and followed until death, invasive ventilation, or the 14 August 2024. Hs-cTnT correlated positively with the number of muscular regions involved (tau = 0.283, P = 0.009) and percentage of muscles involved on EMG (rho = 0.367, P = 0.009). Hs-cTnT was associated with the percentage of muscles involved in EMG in the adjusted linear regression. Patients with higher hs-cTnT had more advanced King's stage, both when numerical hs-cTnT and subgrouping high (>= 15 nanogram/L) versus normal hs-cTnT was used (tau = 0.253, P = 0.021 and U = 197.5, P = 0.022, respectively). Hs-cTnT was neither correlated to ALSFRS-R total score (rho = -0.176, P = 0.220 and U = 249.5, P = 0.233, respectively) nor ALSFRS-R excluding respiratory domain score (rho = -0.069, P = 0.632 and U = 280.5, P = 0.558, respectively). High versus normal hs-cTnT did not predict survival (univariate analysis, HR = 1.824, P = 0.060). Numerical hs-cTnT was associated with shorter survival (univariate analysis, HR = 1.635, P = 0.017) but not after adjusting for age at diagnosis (HR = 1.413, P = 0.105). This study illustrates that ALS patients with higher hs-cTnT have more spread disease as evidenced by the positive correlation between hs-cTnT and both EMG and King's stage. This is not true for established biomarkers of muscle damage (CK) and neuroaxonal damage (NfL). These findings need to be confirmed in larger studies but suggest that hs-cTnT is a biomarker of LMN involvement in patients with ALS and could be used in clinical trials. Chamoun et al. report that cardiac troponin T in plasma is positively correlated with lower motor neuron involvement on EMG in patients with amyotrophic lateral sclerosis. They conclude that this is a possible novel biomarker reflecting the degree of denervation and spreading, to be used in future clinical trials.