Table 2.

Summary of approach and treatment strategies for ICI induced cardiotoxicities.¹²

Cardiac toxicity	Clinical presentation	Mechanism of cardiotoxic effects	Clinical approach	Clinical management
Myocarditis	Presentation can be challenging. Can present with HF, pulmonary edema, cardiogenic shock, multiorgan failure, ventricular arrhythmias.	Not fully understood. Post-mortem analysis has shown inflammatory cell infiltrate, increase in extracellular space volume, and loss of cardiomyocytes. Studies have confirmed the presence of both CD4-positive and CD8-positive T cells.	Depends on the presentation (asymptomatic to fulminant myocarditis). Diagnostic tests include EKG, biomarkers, cardiac imaging (ECHO or cardiac MRI). If still uncertain, endomyocardial biopsy can be preformed.	1st: Stop ICI depending on the severity of toxicity. 2nd: IV methylprednisolone 500–1000 mg daily until clinically stable, followed by oral prednisone 1 mg/kg daily, and wean as tolerated. For non-steroid responders, consider mycophenolate mofetil or infliximab, anti-thymocyte globulin or intravenous immunoglobulin. 3rd: Use of conventional cardiac treatments per standard ACC guidelines.
Pericardial disease	Can occur in isolation with typical pericardial pain or alongside with myocardial involvement with perimyocarditis, and can be complicated by pericardial effusion and tamponade.	Not fully understood.	Diagnostic tests include EKG, cardiac biomarkers and cardiac imaging.	1st: Stop ICI therapy, and consider re-challenging with ICI therapy only if clinically stable and when clinical pericarditis is excluded. 2nd: Consider intravenous methylprednisolone 500–1000 mg daily until clinically stable, followed by oral prednisone 1 mg/kg once daily, and wean as tolerated.
Arrhythmias	Can present in wide ranges, from complete atrioventricular block (third degree heart block) to atrial and ventricular tachyarrhythmias.	Underlying myocarditis with inflammation being the substrate for triggered arrhythmias, inflammation of the His-Purkinje system being the trigger for re-entry arrhythmias, increased systemic inflammation leading to arrhythmias without myocarditis.	Diagnostic test: EKG	1st: Stop ICI therapy, and consider re-challenging with ICI therapy only if clinically stable and after myocarditis is excluded. Immune suppression is not applicable in the absence of myocarditis. 2nd: Management of arrhythmias per ACC guidelines.

ICIs: immune checkpoint inhibitors; HF: heart failure; CD: cluster of differentiation; EKG: electrocardiogram; ECHO: echocardiogram; MRI: magnetic resonance imaging; IV: intravenous; ACC: American College of Cardiology.