Reversible Complete Atrioventricular Block in Immune Checkpoint Inhibitor–Associated Triple-M Overlap Syndrome: A Case Report
Sonal Prasad, Michael Dicaro, Thomas Iida, Tina Frisch, Mutsumi KiokaAbstract
Background
Immune checkpoint inhibitor (ICI)–associated myocarditis is a rare but potentially life-threatening immune-related adverse event. Overlap syndromes involving myocarditis, myositis, and myasthenia gravis (Triple-M overlap syndrome) have been reported; however, reversible high-grade atrioventricular block remains uncommon.
Case presentation
A 74-year-old woman with ovarian cancer treated with pembrolizumab presented with dyspnea, myalgia, and right-sided ptosis 22 days after ICI therapy. Initial workup showed elevated high-sensitivity troponin. On the following day, ECG demonstrated ST-segment elevation, prompting evaluation for acute myocardial infarction, and coronary angiography revealed no obstructive coronary artery disease. The clinical course was complicated by sustained ventricular tachycardia followed by complete atrioventricular block requiring temporary transvenous pacing. Laboratory evaluation showed markedly elevated creatine kinase, and neurological findings were consistent with neuromuscular junction involvement. Immune-mediated Triple-M overlap syndrome was suspected, and high-dose corticosteroids and intravenous immunoglobulin were initiated. The patient demonstrated progressive clinical improvement, with resolution of arrhythmias and recovery of atrioventricular conduction.
Conclusion
This case highlights a rare presentation of ICI-associated Triple-M overlap syndrome complicated by reversible complete atrioventricular block. Immune-mediated conduction abnormalities may progress despite improving cardiac biomarkers, and early immunomodulatory therapy may enable reversibility of high-grade atrioventricular block.