Reversible complete atrioventricular block in immune checkpoint inhibitor-associated triple-M overlap syndrome: a...

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies but are associated with rare and potentially life-threatening immune-related adverse events. Overlap syndromes involving myocarditis, myositis, and myasthenia gravis-referred to as Triple-M overlap syndrome-have been reported; however, reversible high-grade atrioventricular block remains uncommon.

A 74-year-old woman with advanced ovarian cancer treated with pembrolizumab presented with dyspnoea, myalgia, and right-sided ptosis 22 days after ICI therapy. Electrocardiography demonstrated ST-segment elevation in the anterior leads with markedly elevated high-sensitivity troponin. On the following day, persistent ST-segment elevation prompted 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.

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.