Effects of doxorubicin and ibrutinib on atrial arrhythmogenity: ex-vivo assessment in human myocardium

Abstract Introduction The cytostatic drugs doxorubicin (Dox) and ibrutinib (Ibr) are established in the treatment of various tumor diseases. In (pre-) clinical studies, both chemotherapeutic agents showed cardiotoxic side effects, including atrial fibrillation [1]. this context, patients with limited cardiac performance or diabetes might be particularly vulnerable, as these pre-existing conditions represent independent risk factors for complications [2]. Objectives dose-dependency acute pro-arrhythmogenic effects Dox Ibr on contractile activity human muscle tissue was investigated. Patients methods Atrial samples were taken intraoperatively during procedures. Functional strips prepared from trabeculae, followed by incubation different concentrations 30 minutes. Subsequently, functional measurements performed. Isometric contraction force arrhythmogenic occurrences recorded. consecutively exposed to external stressors measurement (Fig. 1). We evaluated overall occurrence contractions which phase protocol they occurred. latter expressed degree arrhythmogenesis Following measurements, conserved at −80°C. Results isolated 127 29 patients. Highest rates arrhythmic observed 10μM 0.5μM (77.8 & 100% vs. 58.4% (control)). Mean increased 1.63 (control) 2.17 (10μM Dox) 3.11 (0.5μM Ibr). Analyzing our data according included individuals, enhanced majority 2) Conclusion Our is suitable investigating drug related myocardium. Treatment myocardium its susceptibility occurrences. Optimal Ibr. treated higher occurred earlier within protocol. Outlook will correlate experimentally obtained patient data, such LVEF, BMI diabetic status. analyzed using standardized assays comparing post-translational modification (e.g. phosphorylation oxidation) key regulators excitation coupling PKA, CaMKII, Ca2+ channels). Funding Acknowledgement Type funding sources: Other. Main source(s): DZHK (German Centre Cardiovascular Research), partner site Berlin