Complete Heart Block in a Patient Undergoing Combination Immune Checkpoint Inhibitor Therapy.

Abstract

Combination immune checkpoint inhibitor(ICI) therapy is an emerging chemotherapy strategy for patients with solid tumor malignancies. Cardiotoxicity is a rare adverse effect of ICI therapy, most commonly presenting as acute myocarditis and, less frequently, as significant conduction abnormalities. We present a unique case of a 68-year-old female with urothelial cancer who developed shortness of breath and chest pain one week after receiving combination ICI therapy with ipilimumab and nivolumab. Biomarkers were elevated, including high-sensitivity troponinto 14,000 ng/L and creatine phosphokinase to 20,000 U/L. Due to suspicion of acute ICI-related myocarditis, a transthoracic echocardiogram (TTE) was obtained and demonstrated preserved ejection fraction (EF). Pulse-dose methylprednisolone therapy was initiated. However, the patient's clinical status continued to decline, and she developed bradycardia due to a complete heart block (CHB). This was initially treated with a dopamine infusion, but due to hypotension and hemodynamic instability, a transvenous pacemaker was placed. She continued to decline from a heart failure standpoint and developed acute hypoxic respiratory failure, requiring intubation due to pulmonary edema. A repeat TTE acquired three days following the initial echocardiogram demonstrated a newly reduced EF of 30%-35%. Additional anti-inflammatory agents were administered, including mycophenolate, infliximab, and anti-thymocyte globulin, with little improvement in clinical status. Unfortunately, she rapidly deteriorated, resulting in pulseless electrical activity (PEA) arrest and circulatory death. The autopsy revealed severe biventricular myocarditis with partial involvement of the atrioventricularnode, consistent with her clinical syndrome of acute heart failure and CHB. A literature review demonstrated very few cases of ICI-related CHB. This case highlights a rare instance of atrioventricular dissociation in a patient with cardiotoxicity due to combination ICI therapy.