Cardiovascular Challenges in Chronic Lymphocytic Leukemia ( CLL ) Patients Undergoing Bruton Tyrosine Kinase ( BTK ) Inhibitor Therapy

BACKGROUND/OBJECTIVES: Bruton tyrosine kinase inhibitors (BTKis) have revolutionized treatment for chronic lymphocytic leukemia (CLL), but cardiovascular (CV) toxicities pose significant challenges. Second-generation BTKis offer improved target specificity, yet CV risks persist. This expert opinion review evaluates current evidence and offers guidance for managing BTKi-associated CV events, particularly in patients with comorbidities. METHODS: A hematologist, specialist in CLL, and a cardiologist with specific expertise in managing cardiac complications arising from oncologic therapies conducted a systematic literature review. Subsequently, clinical findings synthesized through multidisciplinary expert discussions led to the development of practical recommendations for CV risk stratification and management in patients with CLL receiving BTKi therapy. RESULTS: Regular CV monitoring is essential for early detection of atrial fibrillation (AF), hypertension, and ventricular arrhythmias. A multidisciplinary approach between hematologists and cardiologists is recommended for comprehensive care. Identifying hematological biomarkers for predicting cardiotoxicity and exploring cardioprotective therapies for high-risk patients should be prioritized. CONCLUSIONS: It is essential to educate healthcare providers about the CV risks associated with BTKis. Additionally, clinical guidelines should be regularly updated to reflect the latest evidence, ensuring effective prevention and management strategies. In patients with a heightened risk of CV complications, the use of second-generation BTKis should be prioritized. Ongoing cardiovascular monitoring is also recommended to reduce the risk of adverse events and minimize treatment discontinuation.