Sick sinus syndrome associated with anti-programmed cell death-1

Area of Science:

• Oncology
• Immunology
• Cardiology

Background:

• Anti-programmed cell death-1 (anti-PD-1) therapy is effective for various cancers but can cause immune-related adverse events.
• Immune-related cardiotoxicity, though rare, is a serious concern, with myocarditis being a frequent cause of dysrhythmia.
• Sick sinus syndrome has not previously been reported as an anti-PD-1-induced immune-related adverse event.

Observation:

• A 42-year-old male with metastatic hepatocellular carcinoma developed SSS after receiving pembrolizumab.
• The patient presented with bradycardia (lowest heart rate of 38 bpm), fatigue, dizziness, anorexia, and hypotension.
• Laboratory findings revealed low cortisol and ACTH levels, suggesting anti-PD-1-induced adrenal insufficiency.

Findings:

• Treatment with low-dose cortisone rapidly improved the patient's symptoms, hypotension, and SSS.
• Upon discontinuation of cortisone, SSS did not relapse, and cortisol and ACTH levels normalized.
• This case highlights SSS as a potential irAE of anti-PD-1 therapy, possibly mediated by immune or adrenal dysfunction.

Implications:

• Sick sinus syndrome induced by anti-PD-1 therapy is a rare but significant adverse event.
• Myocarditis should be considered in the differential diagnosis of SSS in patients receiving anti-PD-1 agents due to its potential lethality.
• Glucocorticoid supplementation can effectively reverse SSS in cases associated with immune- or adrenal insufficiency-mediated sinus node dysfunction.