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. 2018 Jun 11;11(1):79.
doi: 10.1186/s13045-018-0626-0.

Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study

Gianluigi Reda  1 , Bruno Fattizzo  2 , Ramona Cassin  3 , Veronica Mattiello  2 , Tatiana Tonella  4 , Diana Giannarelli  5 , Ferdinando Massari  4 , Agostino Cortelezzi  2
Affiliations

Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study

Gianluigi Reda et al. J Hematol Oncol. .

Abstract

Background: Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase, indicated for the treatment of chronic lymphocytic leukaemia. The drug is generally well tolerated; however, not infrequent side effects are reported, with the major two being bleeding and ibrutinib-related atrial fibrillation. Atrial fibrillation pathogenesis in this setting is not completely clear, and no prospective studies have evaluated the impact of previous cardiologic history and baseline characteristics.

Methods: We prospectively performed cardiologic assessment in 43 CLL patients before starting ibrutinib therapy. Cardiologic workup included comorbidity collection and electrocardiographic and echocardiographic baseline evaluation.

Results: After a median observation of 8 months, seven patients developed atrial fibrillation (16.3%). Cases developing atrial fibrillation were all elderly males (p = 0.04), and mostly with a history of previous arterial hypertension (p = 0.009). Atrial fibrillation occurrence also correlated with the presence of one or more pre-existent cardiologic comorbidities (p = 0.03), with a higher atrial fibrillation risk score (calculated with comorbidities and cardiologic risk factor evaluation p < 0.001), and with higher left atrial diameter (p = 0.02) and area (p = 0.03) by echocardiography. The occurrence of atrial fibrillation was managed after an integrated cardio-oncologic evaluation: anticoagulation was started in 4 (57.1%) patients and beta-blockers or amiodarone in 5 (71.4%). One patient underwent electric cardioversion and another patient pacemaker positioning to normalise heart rate in order to continue ibrutinib.

Conclusion: Our data show that echocardiography is a highly informative and reproducible tool that should be included in pre-treatment workup for patients who are candidates for ibrutinib therapy.

Keywords: Atrial fibrillation; Cardio-oncology; Chronic lymphocytic leukaemia; Ibrutinib.

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Conflict of interest statement

Ethics approval and consent to participate

The data collection on CLL patients had been approved by the local Ethical Committee and patients gave informed consent.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Upper panel: AF risk score according to IRAF incidence. AF risk score was calculated on age, gender, arterial hypertension, and valvular heart disease (Shanafelt et al.). Percentages of patients developing or not developing IRAF are shown divided into four risk categories. IRAF cases were mainly in the high risk group (≥ 5 RF), p < 0.001. AF atrial fibrillation. IRAF ibrutinib-related atrial fibrillation. RF risk factors. Lower panel: main echocardiographic characteristics associated with IRAF. LA diameter, area, and volume were increased in IRAF patients compared to the others, significantly for the former two parameters (p = 0.02 and p = 0.03, respectively). LA left atrium, IRAF ibrutinib-related atrial fibrillation
See this image and copyright information in PMC

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