Clinical manifestation and management of immune checkpoint inhibitor‐associated cardiotoxicity

Abstract

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) have revolutionized cancer treatment by recovering the attack of T lymphocytes on the malignant cells. They have improved clinical outcomes dramatically in multiple types of advanced-stage malignancies. Even though the tolerance and safety profiles are generally good, it has been widely reported that ICIs can cause severe or fatal immune-related adverse events (irAEs), since the activated T lymphocytes are not specific for tumor cells. Cardiac irAEs appear to occur less frequently than irAEs in other organ systems but are notorious for high mortality. Here, we aim to identify and characterize the ICI-associated cardiotoxicity and summarize the optional diagnosis and treatment strategies.

Immune Checkpoint Inhibitors and Cardiac Toxicity in Patients Treated for Non-Small Lung Cancer: A Review

“…ECG abnormalities were reported in 89% of patients diagnosed with ICI-associated myocarditis. ECG findings include Q wave formation, ST-T changes, R wave decrease, QRS widening, and possible various arrhythmias (sinus tachycardia, supraventricular and ventricular premature beats, atrial fibrillation, ventricular tachycardia, and fibrillation) or conduction disturbances (from bundle-branch block to complete atrioventricular block) [ 49 , 71 ]. Atallah-Yunes et al [ 72 ] reported complete atrioventricular block as the most common complication of ICI-related myocarditis.…”

“…Laboratory tests (including cardiac troponin and natriuretic peptides) and repetitive ECGs are suggested for the early diagnosis of subclinical cardiotoxicity associated with ICI, combined with prompt access to TTE in doubtful cases [ 43 , 71 ]. At each visit during ICI treatment, the patient should be inquired about cardiac symptoms and a careful physical examination should be performed.…”

“…Puzanov et al recommended cTn measurements at baseline and weekly for 6 weeks [ 32 ]. Gou et al [ 71 ] suggested that noninvasive tests, including cardiac troponin I (cTnI), BNP/NT-proBNP, and ECG, should be performed every 1–2 weeks in the first six weeks of ICI treatment. As cardiac troponin T (cTnT) and creatine kinase (CPK) levels can also be increased in patients with myositis, cTnI is preferred to identify cardiac injury [ 93 ].…”

“…Previous chest radiation therapy prior to or concurrent with systemic therapy should also be considered. Patients with NSCLC are often elderly, so cardiovascular disease is to be expected [ 43 , 71 ].…”

“…The principal strategy to treat ICI-associated cardiotoxicity is to suppress the hyperactive T cell response. For this purpose, corticosteroid therapy is now the first line of immunosuppressive treatment [ 32 , 43 , 70 , 71 ]. Depending on the hemodynamic status, in most patients, oral or intravenous prednisone (1–2 mg/kg) is administered and intravenous methylprednisolone (0.5–1.0 g) is recommended for patients with life-threatening conditions (fulminant myocarditis, ventricular tachyarrhythmias, pericarditis with cardiac tamponade).…”