Background: Myocarditis is a rare but potentially devastating toxicity of immune checkpoint inhibitor (ICI) therapy for treatment of certain malignancies. Electrical complications, including complete heart block and lethal ventricular arrhythmias, have been reported but are not well understood.
Results: A 90-year-old male with metastatic melanoma of the scalp presented with generalized weakness and inability to transfer out of bed 22 days after receiving his first dose of Nivolumab (480mg).
Fifth generation troponin T peaked at 1828 ng/L (normal <22), CK-MB at 247 ng/mL (<4.8), and total CK was 8,350 U/L (<175). Initial ECG demonstrated normal sinus rhythm without conduction abnormalities. Echocardiogram showed preserved systolic function. He was diagnosed with ICI-associated myositis and myocarditis and started on IV methylprednisolone 1gram/day. Subsequent ECGs showed progression to bifascular block then complete heart block. Complete heart block was intermittently demonstrated on telemetry, and a temporary transvenous pacemaker was placed while a permanent pacemaker was considered. Given lack of improvement with continued corticosteroid therapy he ultimately received a dual chamber pacemaker. Five days later he went into ventricular fibrillation followed by asystole, and then expired.
Conclusion: The true incidence of cardiotoxicity following ICI therapy is unknown. Data from clinical trials and case series are mixed, with estimates ranging from <0.1% to 1% of patients. The incidence of electrical complications is also unknown. Complete heart block and ventricular arrhythmias have been reported in up to 36% and 27% of patients with ICI-associated myocarditis, respectively.
High dose glucocorticoid therapy has been shown to reverse cardiotoxicity due to systolic dysfunction in up to two-thirds of cases. The reversibility of conduction abnormalities with has not been well described. In patients who develop complete heart block due to ICI-associated myocarditis, the utility and timing of permanent pacemaker placement is not well understood. Given the high risk of ventricular arrhythmias in this population, an ICD may be considered if permanent pacing is indicated.