The incidence and clinical features of anticancer therapy induced atrial fibrillation in patients with breast cancer without previously established cardiac disorder

Abstract

Abstract Background/Introduction Anthracyclines (ATC), alkylating (AAg) and anti-microtubule (AMA) agents are established chemotherapeutics in management of breast cancer. Both agents might reveal cardiotoxicity, as well as cancer treatment–induced-arrhythmias at varying established rates and by complex mechanisms. Atrial fibrillation (AF) is one of the debilitating dysrhythmias encountered throughout the cancer treatment with a significant impact on mortality and morbidity. Purpose To reveal the incidence and clinical features of new onset AF episodes detected in breast cancer patients using different conventional chemotherapeutic regiments. Methods All consecutive adult women diagnosed with breast-carcinoma and getting the first chemotherapy treatment with either ATC+AMA or AAg+AMA were prospectively evaluated for 6 months. Clinical, echocardiographic and ECG parameters (QTc by Bazett's-formula) were obtained and evaluated on baseline, first month and 6th month. Patients with Structural/coronary-heart-disease, complete-bundle-branch-block, non-sinus-rhythms and acute-coronary-syndrome in follow-up were excluded. “AF” is diagnosed on 12-lead-ECG or at least 30s of AF on Rhythm/Holter monitoring indicated by palpitation symptoms. Results Of 192 cases, 140 women ([mean±SD] age, 64±12, [range] 36–86 years) were enrolled for analysis. 76 patients received the AAg (cyclophosphamide) and 64 received ATC (daunorubicin) in addition to AMA (docetaxel). Mean follow up time was 4.2±2 months (Min–Max 1–6 months). Incident AF was diagnosed in 38 patients (27.1%) at the end of the 6 month follow up. The clinical findings are presented in picture-1. In patients receiving ATC treatment, incident AF was significantly more common (35.9% vs 19.7, p=0,032) and mostly observed in the first month of ATC-chemotherapy compared with AAg-regiments respectively (69% vs 33% of AF events occurred in first month, P<0,001). Incident AF patients were significantly older, and ATC-receiving patients demonstrated significantly greater heart-rate and PR-interval changes from baseline. Age, ATC use, Delta-PR >10 ms, Delta-QTC >50 ms and Delta HR >10 ms from baseline significantly predicted incident AF in the 6 month follow up in univariate-regression-analysis. However, only age and more significantly Anthracyclin use was found to predict Incident AF in multivariate regression analyses (picture 2) [(OR 3.7 (95% CI 1.2–10) (p=0.02)]. Conclusion(s) Compared with alkylating-agents, anthracycline-regimens seem to induce significantly more incident-AF-events and profound ECG changes on the acute phase of chemotherapy for breast-cancer in women. They seem to exert their effects irrespective of conventional AF risk-factors apart from advanced-age. Affected ECG-parameters of delayed-conduction and repolarization-heterogeneity might be suggested as a surrogate for multiple-ion-channel-interactions and a possible mechanism underlying higher incident-AF. Funding Acknowledgement Type of funding sources: None.