Cardiac safety of low-dose ACTH therapy in infantile spasms: Evidence from electrocardiography and advanced echocardiography.

OBJECTIVE

Infantile epileptic spasms syndrome (IESS) is a catastrophic epileptic encephalopathy of infancy. While adrenocorticotropic hormone (ACTH) remains the most effective first-line therapy, its cardiac safety profile, particularly at low doses, has not been systematically evaluated. This study aimed to investigate the effects of low-dose ACTH therapy on cardiac conduction and function using electrocardiography (ECG) and advanced echocardiography.

METHODS

This prospective controlled study included 24 infants with IESS and 24 age- and sex-matched healthy controls. All patients received low-dose ACTH (Synacthen® Depot, intramuscular; 0.5 mg/kg if < 10 kg, 1 mg/kg if ≥ 10 kg; 18 injections over 8 weeks). Serial 12-lead ECGs and echocardiographic assessments, including M-mode, Doppler, tissue Doppler imaging (TDI), and speckle-tracking strain, were performed at baseline and at 2, 4, and 6 months. Controls underwent single baseline assessments.

RESULTS

No patient developed overt arrhythmia or hypertension during treatment. However, ECG analysis revealed progressive prolongation of PR, QRS, QT, QTc, Tp-Te, and Tp-Te-related ratios (p < 0.001). Echocardiography demonstrated significant increases in LVEDD, LVESD, LV mass, and MPI, with impaired diastolic relaxation and progressive deterioration of longitudinal and circumferential strain (p < 0.05). Subgroup analyses showed no significant differences among genetic, hypoxic-ischemic, and hypoxia-related etiologies.

CONCLUSION

Even short-term, low-dose ACTH therapy is associated with subclinical conduction abnormalities and myocardial dysfunction in IESS patients. Routine cardiac monitoring, including advanced imaging modalities, should be integrated into ACTH protocols. Multidisciplinary management and larger multicenter studies are warranted to clarify the long-term cardiovascular implications of ACTH therapy in IESS.