From the Guidelines
Immunotherapy for cancer is associated with an increased risk of heart rhythm abnormalities, particularly atrial fibrillation, with a reported incidence of 2.1% in patients treated with immune checkpoint inhibitors (ICIs) 1.
Heart Rhythm Abnormalities Associated with Immunotherapy
The most common heart rhythm abnormalities associated with immunotherapy for cancer include:
- Atrial fibrillation (AF)
- Ventricular tachycardia
- Heart blocks
- QT interval prolongation
- Conduction disturbances These abnormalities are often triggered by immune-mediated myocarditis, which can lead to electrical conduction disturbances.
Immune Checkpoint Inhibitors (ICIs) and Heart Rhythm Abnormalities
ICIs, such as pembrolizumab, nivolumab, ipilimumab, and atezolizumab, are most frequently associated with these cardiac side effects 1. The risk of heart rhythm abnormalities is highest within the first few weeks to months of treatment initiation, particularly with combination immunotherapy regimens.
Management and Underlying Mechanism
Management of heart rhythm abnormalities associated with immunotherapy typically involves:
- Cardiac monitoring during treatment
- Prompt ECG evaluation for any cardiac symptoms
- In severe cases, immunotherapy interruption and corticosteroid administration (typically prednisone 1-2 mg/kg/day) The underlying mechanism involves T-cell mediated inflammation of cardiac tissue, leading to electrical conduction disturbances 1. Patients with pre-existing cardiovascular disease may be at higher risk for developing these complications.
Evidence from Recent Studies
A recent study published in 2024 found that AF was present in 2.1% of patients treated with ICIs, and that the occurrence of ICI-associated AF seems relatively low, given that ICI-induced cardiotoxicity occurs in 1-5% of patients 1. Another study published in 2016 identified various cancer drug agents associated with cardiac arrhythmias, including anthracyclines, alkylating agents, and taxanes 1. However, the most recent and highest quality study suggests that ICIs are the primary culprits behind heart rhythm abnormalities in cancer patients 1.
From the FDA Drug Label
A fatal adverse reaction of myocardial infarction occurred in one patient who received OPDIVO.
The heart rhythm abnormality related to immunotherapy for cancer is myocardial infarction. 2
From the Research
Heart Rhythm Abnormalities Associated with Immunotherapy for Cancer
- Atrial fibrillation (AF) has been reported in patients treated with immune checkpoint inhibitors (ICIs) 3
- Torsades de pointes, a specific type of abnormal heart rhythm, has been associated with pembrolizumab-induced myocarditis 4
- Complete atrioventricular block has been reported in patients with pembrolizumab-induced myocarditis 5, 6
- Supraventricular and ventricular arrhythmias are also recognized as potential cardiotoxicities associated with ICIs 7
- Bradycardia, including bigeminal bradycardia, has been observed in patients with myocarditis induced by pembrolizumab 4, 5
Risk Factors and Monitoring
- Patients with pre-existing atrial fibrillation may be at risk of recurrence during ICI treatment and should be monitored accordingly 3
- Close cardiac monitoring is necessary for patients receiving ICIs, particularly those with high-risk features or pre-existing cardiac conditions 5, 6, 7
- Baseline echocardiography and troponin monitoring may help identify cardiac complications promptly 5