Cardiovascular complications with Bruton’s tyrosine kinase inhibitors in a structured cardio-oncology programme: a real-world cohort study

Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the management of lymphoproliferative disorders but are consistently associated with cardiovascular (CV) toxicities that may compromise optimal oncological treatment. Evidence guiding structured CV management in this setting remains limited. We aimed to evaluate the occurrence, clinical presentation, diagnosis and management of CV complications in patients receiving BTKi and managed within a dedicated cardio-oncology programme. We performed a single-centre retrospective cohort study including consecutive patients initiating BTKi therapy at a tertiary centre. Patients were managed according to a standardised multidisciplinary cardio-oncology surveillance protocol implemented in routine clinical practice. CV complications during BTKi treatment, particularly atrial fibrillation (AFib), hypertension (HTN) and heart failure (HF) were assessed. Among 114 patients (median BTKi treatment duration 13 [5–32] months), 44 (38.6%) developed at least one CV complication, including AFib in 19 (16.7%), HTN in 24 (21.1%), and HF in 12 (10.5%). The first CV complication rate was 28.68 per 100 person-years (95% CI 20.84–38.50). In exploratory univariable Cox analyses, older age, baseline HTN, left atrial dilatation and increased interventricular septal thickness were associated with specific CV complications, whereas older age, baseline HTN and baseline anticoagulant therapy were associated with bleeding. AFib occurred less frequently among patients receiving second-generation BTKi, although time to AFib occurrence did not differ significantly between BTKi generations (log-rank p=0.072). Despite the substantial burden of CV complications, permanent BTKi discontinuation due to CV toxicity was uncommon (3.5%), and CV mortality was low (2.6%). In this high-risk real-world population, a substantial burden of AFib, HTN and HF was observed during BTKi therapy. These findings highlight the need for systematic CV surveillance and provide real-world insights into the detection, characterisation and multidisciplinary management of CV complications in this population.