High incidence of atrial fibrillation in patients treated with ibrutinib.

Objective: Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome. Methods: A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib. Results: 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants. Conclusions: This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.

Impact of the time-to-treatment concept on the outcome of acute heart failure: A pilot study.

BACKGROUND: An optimal maximum time of 60minutes has been recommended in recent guidelines for the first evaluation and treatment of patients with acute heart failure (AHF); however, this has not been tested prospectively. AIM: To analyze the impact of a time-to-treatment (TTT) strategy of <60minutes on the in-hospital outcome of patients with AHF. METHODS: During a single 1-month period, we consecutively enrolled all patients hospitalized with AHF in a prospective cohort. In this pilot study, TTT was defined as the time between the first medical contact to the onset of the first medical intervention. The primary outcome was a composite including in-hospital death or worsening AHF. RESULTS: Of the 74 patients included, 23 (31%) had a TTT of <60minutes. Although these patients were more likely to have a more severe episode of AHF, the primary outcome occurred only in patients with a TTT of ≥60minutes. The primary outcome was significantly associated with a TTT of ≥60minutes (P=0.036), low systolic blood pressure (P<0.01), rales more than halfway up the lung fields (P=0.02), infectious precipitating factor (P=0.04) and high serum concentrations of B-type natriuretic peptide (P<0.01) and urea (P=0.03). No significant differences were observed in the rate of treatment-induced acute renal insufficiency or in the long-term rates of death or rehospitalization for heart failure according to TTT. CONCLUSIONS: This study suggests that the recently recommended TTT strategy of <60minutes in the setting of AHF might be associated with a better prognosis during hospitalization. Further large prospective works are needed to confirm these preliminary results, and to define more precisely which types of AHF could benefit from this strategy.