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A New Scoring System for the Evaluation of Ibrutinib-Associated Arrhythmias in Chronic Lymphocytic Leukemia: The ACEF
İlhan Koyuncu1, Betül Koyuncu2, Mehmet Can Uğur3
1Bakırçay University, Çiğli Training and Research Hospital, Clinic of Cardiology, İzmir, Türkiye
Insights
Bruton tyrosine kinase inhibitors increase arrhythmia risk in CLL patients. The Age-Creatinine-Ejection Fraction (ACEF) score effectively predicts paroxysmal atrial fibrillation (PAF) risk in these patients.
Area of Science:
- Cardiology
- Oncology
- Pharmacology
Background:
- Bruton tyrosine kinase (BTK) inhibitors, like ibrutinib, are used for chronic lymphocytic leukemia (CLL).
- BTK inhibition can disrupt cardiac protective pathways (PI3K-AKT), potentially increasing arrhythmia risk.
- Predictive tools for cardiac adverse events in CLL patients on ibrutinib are needed.
Purpose of the Study:
- To evaluate the predictive capability of the Age-Creatinine-Ejection Fraction (ACEF) score for arrhythmia development.
- To assess the incidence of paroxysmal atrial fibrillation (PAF) in CLL patients treated with ibrutinib compared to controls.
Main Methods:
- Retrospective analysis of CLL patients receiving ibrutinib (≥1 year) and a control group.
- Echocardiography and Holter monitoring were performed.
- ACEF score calculated using age, creatinine, and ejection fraction.
Main Results:
- No significant difference in overall arrhythmia types between groups, except for PAF.
- PAF occurred more frequently in ibrutinib users (22%) vs. non-users (8%).
- An ACEF score >1.21 predicted PAF development in ibrutinib users with 77% sensitivity and 75% specificity (AUC=0.830).
Conclusions:
- The ACEF score is a valuable tool for predicting PAF risk in CLL patients initiating ibrutinib therapy.
- Early identification of high-risk patients can guide clinical management and monitoring.
- Further research may explore interventions to mitigate BTK inhibitor-associated cardiac risks.
Objective:
Bruton tyrosine kinase inhibition in cardiac tissue causes inhibition of the PI3K-AKT signaling pathway, which is responsible for protecting cardiac tissue during stress. Therefore, there is an increase in the risk of arrhythmia. This study explores the prediction of that risk with the Age-Creatinine-Ejection Fraction (ACEF) score as a simple scoring system based on the components of age, creatinine, and ejection fraction.
Materials And Methods:
Patients diagnosed with chronic lymphocytic leukemia (CLL) and receiving ibrutinib treatment for at least 1 year were evaluated with echocardiography and Holter electrocardiography and the results were compared with a control group of CLL patients who had not received treatment. ACEF score was calculated with the formula age/left ventricular ejection fraction+1 (if creatinine >2.0 mg/dL).
Results:
When the arrhythmia development of the patients was evaluated, no statistically significant difference was found between the control and ibrutinib groups in terms of types of arrhythmias other than paroxysmal atrial fibrillation (PAF). PAF was found to occur at rates of 8% versus 22% (p=0.042) among ibrutinib non-users versus users. For patients using ibrutinib, an ACEF score of >1.21 predicted the development of PAF with 77% sensitivity and 75% specificity (area under the curve: 0.830, 95% confidence interval: 0.698-0.962, p<0.001).
Conclusion:
The ACEF score can be used as a risk score that predicts the development of PAF in patients diagnosed with CLL who are scheduled to start ibrutinib.
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