KEY TAKEAWAY: Details a clinical case of fulminant immune checkpoint inhibitor-induced myocarditis following treatment with the PD-1 inhibitor nivolumab. It highlights the diagnostic challenges of immune-related cardiotoxicity and emphasizes the need for early immunosuppressive intervention.
Abstract
Background
Nivolumab is an anti-programmed cell death-1 antibody that has been approved for treatment of various advanced malignancies. Cardiac adverse events associated with nivolumab appear to be rare.
Case
A 59-year-old female with metastatic renal cell carcinoma, treated with nivolumab was found on routine examination to have a heart rate of 40 beats per minute. She reported only mild lightheadedness. Her electrocardiogram demonstrated complete atrioventricular block. An echocardiogram showed an EF of 70% with no regional wall motion abnormalities. Her high sensitivity troponin on serial measurements remained persistently 330-530 ng/L.
Decision-Making
A dual-chamber pacemaker was implanted uneventfully.
Two weeks post discharge; she was noted to have severe exercise intolerance associated with failure to capture. Ventricular lead microdislodgement was suspected and she was admitted for lead repositioning.
She then developed chest pain along with electrocardiographic changes suggestive of anterior ST elevation myocardial infarction. Urgent cardiac catheterization demonstrated no luminal coronary stenosis but identified complex wall motion abnormalities. Her left ventricular ejection fraction was estimated at 35-45%. Troponin concentration rose up to 86,845 ng/L.
Following her transfer to the coronary care unit, she developed ventricular fibrillation. Her resuscitation was unsuccessful. Her autopsy demonstrated myocarditis with lymphocytic myocardial infiltrate.
Conclusions
Reported cardiac side effects of anti-PD-1 therapy included myocarditis, pericardial effusion, cardiomyopathy, atrial and ventricular arrhythmias and occurred in <1% of treated patients. The association of complete heart block with anti-PD-1 therapy has not been reported before however.
This case highlights the diverse ways in which myocarditis associated with nivolumab may present. Nivolumab-related myocarditis should be suspected in patients with cardiac arrhythmia, especially if troponin concentration is elevated. The course of the myocarditis can be very aggressive, and there should be a low threshold for myocardial biopsy/cardiac magnetic resonance.