Case Presentation: An 81-year-old man with a history of paroxysmal atrial fibrillation and angiosarcoma on immunotherapy presented with acute onset of shortness of breath, chest pressure and lower extremity edema. He had been started on ipilimumab and nivolumab 1 year prior to presentation and had developed immune checkpoint inhibitor (ICI) thyroiditis, hepatitis, and pneumonitis while on dual immunotherapy. He was now only on nivolumab and his last infusion was 10 days prior to presentation. On exam he was hemodynamically stable, but showed clinical signs of heart failure with a JVP of 15cm of H2O and rales on pulmonary exam. Cardiac biomarkers were elevated, chest radiograph showed pulmonary edema and ECG was at his baseline. Transthoracic echocardiogram demonstrated a preserved ejection fraction with diastolic dysfunction and elevated filling pressures. Following diuresis to euvolemia, troponin levels were unchanged indicating ongoing myocardial injury. Cardiac MRI demonstrated diffuse myocardial late gadolinium enhancement, suggestive of myocarditis. He was treated with pulse-dose steroids followed by a prolonged prednisone taper with improvement in his symptoms. His Nivolumab is being held indefinitely.
Discussion: Immune checkpoint inhibitors (ICI) are increasingly used for the treatment of some malignancies and are associated with serious immune-related adverse events (IRAEs). ICI myocarditis is less common than other IRAEs, but it is associated with the greatest morbidity and mortality. ICI myocarditis is reported to occur in 1% of patients on therapy and is associated with a 50% mortality rate. This case illustrates that ICI myocarditis can have a varied presentation in terms of both ejection fraction and the temporal relationship to the initiation of immunotherapy. Up to 51% of confirmed ICI myocarditis cases present with preserved ejection fraction based on a case series of 35 patients with confirmed ICI myocarditis. While most patients with ICI myocarditis present early in the treatment course, the time can vary widely and initial presentation can occur up to 2 years after initiating of therapy. Diagnosis of ICI myocarditis can be made based on a combination of the clinical syndrome, echocardiographic findings, cardiac biomarkers, cardiac MRI and in some cases myocardial biopsy. Given the high morbidity and mortality associated with ICI myocarditis, patients should be empirically treated with pulse-dose steroids while awaiting further workup if this diagnosis is suspected.
Conclusions: We describe a case of ICI myocarditis that presented with a preserved ejection fraction on echocardiography in a patient who had been on the offending immunotherapy for 1 year in order to illustrate how heterogenous the clinical presentation of the disease can be. A high clinical suspicion for ICI myocarditis should be maintained in any patients presenting with cardiopulmonary symptoms while on ICI therapy. Given the high mortality associated with ICI myocarditis empiric treatment with pulse dose steroids should be initiated while awaiting further diagnostic testing to confirm the diagnosis.