Related Experiment Video
Updated: Sep 30, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Cardiotoxicity risk factors with immune checkpoint inhibitors
Zachary L Brumberger1, Mary E Branch2, Max W Klein3
1Department of Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC, 27157, USA.
Background:
Checkpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first described in murine models and, more recently, in numerous clinical case reports of pericarditis, myocarditis, pericardial effusion, cardiomyopathy, and new arrhythmias. The objective of our study was to determine the frequency of and associated risk factors for cardiotoxic events in patients treated with immune checkpoint inhibitors.
Methods:
Medical records of patients who underwent immunotherapy with durvalumab, ipilimumab, nivolumab, and pembrolizumab at Wake Forest Baptist Health were reviewed. We collected retrospective data regarding sex, cancer type, age, and cardiovascular disease risk factors and medications. We aimed to identify new diagnoses of heart failure, atrial fibrillation, ventricular fibrillation/tachycardia, myocarditis, and pericarditis after therapy onset. To assess the relationship between CVD risk factors and the number of cardiac events, a multivariate model was applied using generalized linear regression. Incidence rate ratios were calculated for every covariate along with the adjusted P-value. We applied a multivariate model using logistic regression to assess the relationship between CVD risk factors and mortality. Odds ratios were calculated for every covariate along with the adjusted P-value. Adjusted P-values were calculated using multivariable regression adjusting for other covariates.
Results:
Review of 538 medical records revealed the following events: 3 ventricular fibrillation/tachycardia, 12 pericarditis, 11 atrial fibrillation with rapid ventricular rate, 0 myocarditis, 8 heart failure. Significant risk factors included female gender, African American race, and tobacco use with IRR 3.34 (95% CI 1.421, 7.849; P = 0.006), IRR 3.39 (95% CI 1.141, 10.055; P = 0.028), and IRR 4.21 (95% CI 1.289, 13.763; P = 0.017) respectively.
Conclusions:
Our study revealed 34 significant events, most frequent being pericarditis (2.2%) and atrial fibrillation (2.0%) with strongest risk factors being female gender, African American race, and tobacco use. Patients who meet this demographic, particularly those with planned pembrolizumab treatment, may benefit from early referral to a cardio-oncologist. Further investigation is warranted on the relationship between CTLA-4 and PD-L1 expression and cardiac adverse events with ICIs, particularly for these subpopulations.
Insights
Immune checkpoint inhibitors (ICIs) can cause cardiotoxicity. Female gender, African American race, and tobacco use are significant risk factors for these events, particularly pericarditis and atrial fibrillation.
Area of Science:
- Cardio-Oncology
- Immunotherapy
- Cancer Treatment
Background:
- Immune checkpoint inhibitors (ICIs) revolutionized cancer therapy by enhancing T-cell responses.
- Cardiotoxicity is an emerging concern with ICIs, manifesting as pericarditis, myocarditis, and arrhythmias.
- Understanding the frequency and risk factors for ICI-related cardiotoxicity is crucial for patient management.
Purpose of the Study:
- To determine the incidence of cardiotoxic events in patients receiving ICIs.
- To identify demographic and clinical risk factors associated with ICI-induced cardiotoxicity.
- To inform clinical practice regarding monitoring and management of cardiovascular adverse events.
Main Methods:
- Retrospective review of 538 patient records treated with durvalumab, ipilimumab, nivolumab, or pembrolizumab.
- Data collection included patient demographics, cancer type, cardiovascular disease risk factors, and medications.
- Statistical analysis using generalized linear and logistic regression models to identify risk factors for cardiac events and mortality.
Main Results:
- 34 significant cardiac events were identified, with pericarditis (2.2%) and atrial fibrillation (2.0%) being most frequent.
- Significant risk factors for cardiotoxicity included female gender (IRR 3.34), African American race (IRR 3.39), and tobacco use (IRR 4.21).
- No cases of myocarditis were reported in this cohort.
Conclusions:
- Pericarditis and atrial fibrillation are the most common cardiac adverse events associated with ICIs.
- Female gender, African American race, and tobacco use are key risk factors for ICI-related cardiotoxicity.
- Early cardio-oncology referral is recommended for patients with these risk factors, especially those receiving pembrolizumab.
Related Concept Videos
01:14Myocarditis III: Medical Management
01:27Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...
01:30Coronary Artery Disease I: Introduction
01:27Tumor Immunotherapy
01:29Pulmonary Tuberculosis I
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
01:29Cardiomyopathy V: Interprofessional Care