Abstracts

Rationale: Although adrenocorticotropic hormone (ACTH) therapy is effective for West syndrome, several adverse effects have been reported. Among these adverse effects, hypertension and cardiac hypertrophy represent the majority of cardiovascular specific effects. Sinus dysfunction, as described here, is a previously under reported and potentially lethal side effect of ACTH therapy for West syndrome. Methods: We report three cases of West syndrome presenting with marked bradycardia during ACTH therapy, and reviewed similar cases which were previously reported. Results: Case 1: 1-year-old male with multiple minor anomalies and chromosomal aberration developed West syndrome, for which ACTH therapy was initiated. By the 16th day of therapy, his heart rate decreased to 10-20 beats per minute, observed increasingly during sleep. Echocardiography revealed intraventricular septum and left ventricular free wall thickening, with preservation of biventricular function. ACTH therapy was suspect for causing both the marked sinus dysfunction and cardiac hypertrophy. ACTH therapy was withdrawn and treatment with oral beta-agonist was initiated, resulting in gradual improvement of sinus function. One month after the cessation of ACTH therapy bradycardia was completely resolved. Case 2: 11-month-old female with cerebral palsy developed West syndrome and ACTH therapy was started. Her heart rate decreased to approximately 40 beats per minute after 6 days of ACTH therapy, also predominantly presenting at night. ACTH therapy was withdrawn on the 14th day of therapy. Echocardiography revealed no abnormal findings. Again, bradycardia improved gradually over one month until complete resolution. Case 3: 1-year-old girl with Aicardi syndrome developed West syndrome and ACTH therapy was started. Like the previous cases, ACTH therapy initiation resulted in transient marked bradycardia during sleep. Echocardiography revealed no abnormal findings. In this case, she remained medically stable so ACTH therapy was continued. After ACTH therapy completion, normal cardiac rhythm was restored. Conclusions: We believe that in all 3 cases sinus bradycardia was caused by ACTH therapy. This is supported by the subacute nature of bradycardia onset after initiating ACTH therapy and by recovery after discontinuing ACTH therapy. The absence of other potential contributory factors such as infection or respiratory failure further supports our theory. The effect of ACTH on the cardiac sinus and autonomic nervous system was reported in a few cases of West syndrome during ACTH therapy. Although the mechanism of sinus dysfunction due to ACTH remains obscure, practitioners should be cautious of cardiac sinus dysfunction as an associated and potentially life-threatening side effect of ACTH therapy in West syndrome.