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J Hematol Oncol. 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.

Author information

1
UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, via Francesco Sforza 35, 20135, Milan, Italy. gianluigi.reda@policlinico.mi.it.
2
UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, via Francesco Sforza 35, 20135, Milan, Italy.
3
UOC Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, via Francesco Sforza 35, 20135, Milan, Italy.
4
UOC Malattie Cardiovascolari, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Università degli Studi di Milano, via Francesco Sforza 35, 20135, Milan, Italy.
5
Bio-statistical Unit, Regina Elena National Cancer Institute, via Elio Chianesi 53, 00144, Roma, Italy.

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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