Case Presentation: An 80-year-old male with a history of atrial fibrillation post-ablation on apixaban, COPD, hypertension, and Stage IIIC malignant melanoma post-immunotherapy with nivolumab complicated by non-resolving pneumonitis presented with worsening dyspnea and tachycardia. In the ED, he was found to have atrial flutter with rapid ventricular response (RVR), elevated high-sensitivity troponin, and brain natriuretic peptide (BNP). Initial treatment with adenosine and diltiazem temporarily improved his heart rate, but it rebounded to 170s. He was admitted for pneumonitis and Aflutter with RVR. The patient underwent TEE with cardioversion for atrial fibrillation but continued to experience recurrent atrial fibrillation episodes and multifocal atrial tachycardia. He was also noted to have a newly decreased left ventricular ejection fraction, raising suspicion for immune checkpoint inhibitor-related cardiomyopathy. Left and right heart catheterization showed non-obstructive CAD and normal right heart pressures, while cardiac MRI ruled out immunotherapy-induced cardiomyopathy. The patient received empirical antibiotics for possible community-acquired pneumonia and was discharged on a prolonged prednisone taper for pneumonitis. His arrhythmia was ultimately attributed to pneumonitis and secondary cardiomyopathy due to a rapid heart rate.
Discussion: Immune checkpoint inhibitors (ICIs), such as nivolumab, recently became widely used in cancer therapy, which can cause immune-related adverse events (irAEs) in various organs. Among these, pneumonitis and cardiac complications are significant due to their potential severity. Pneumonitis is one of the most common pulmonary irAEs, occurring in approximately 3-5% of patients treated with ICIs. It involves immune-mediated inflammation of the lung parenchyma, with symptoms ranging from mild cough and dyspnea to severe respiratory failure. Risk factors include combination ICI therapy, underlying lung disease, and smoking history. Management involves prompt diagnosis via imaging, bronchoscopy to exclude infection, and immunosuppression, such as corticosteroids our patient was on. Cardiac irAEs, although less common (< 1% incidence), are increasingly recognized and can manifest as myocarditis, pericarditis, arrhythmias, and heart failure. Myocarditis, the most severe, typically presents within weeks of ICI initiation. Cardiac MRI and endomyocardial biopsy are key for diagnosis. Our patient’s ICIs were initiated months before presentation, which made cardiac irAEs less likely, though cardiac MRI was essential for confirming.Meanwhile, pneumonitis-triggered arrhythmia represents a less defined yet plausible complication. Hypoxemia and systemic inflammation associated with pneumonitis can exacerbate cardiac irritability, leading to arrhythmias such as atrial fibrillation or flutter, especially in patients with underlying arrhythmia. Inflammation-induced electrical remodeling, combined with ICI-related myocardial involvement, increases vulnerability to arrhythmias.
Conclusions: Awareness of immune-related adverse events, such as pneumonitis, is crucial for timely diagnosis and multidisciplinary management, emphasizing collaboration between oncology and other teams.