Rates and Risk of Atrial Arrhythmias in Patients Treated With Ibrutinib Compared With Cytotoxic Chemotherapy

Fradley, Michael G.; Gliksman, Matthew; Emole, Josephine; Viganego, Federico; Rhea, Isaac; Welter-Frost, Allan; Armanious, Merna; Lee, Dae Hyun; Walko, Christine M.; Shah, Bijal; Chávez, Julio C.; McLeod, Howard L.; Pinilla‐Ibarz, Javier; Schabath, Matthew B.

doi:10.1016/j.amjcard.2019.05.029

Cited by 46 publications

(24 citation statements)

References 26 publications

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“…The rest of the chemotherapeutic agents studied were not associated with an increased risk of AF in our patient population. It is noteworthy that ibrutinib, a novel tyrosine kinase inhibitor, is notoriously associated with AF, with an incidence reported to range between 5 and 16% of patients, but this agent was not analyzed in our study (23,28). Finally, in addition to cancer chemotherapy, supportive medications used in cancer patients could also predispose patients to AF (29,30).…”

Section: Atrial Fibrillation and Cancer Therapiesmentioning

confidence: 93%

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Apte

Dherange

Mustafa

et al. 2021

Front. Cardiovasc. Med.

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Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial.Objectives: To study the association of AF with cancer subtypes and cancer therapies.Methods: We studied all patients aged 18–89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy.Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01).Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.

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Section: Atrial Fibrillation and Cancer Therapiesmentioning

confidence: 93%

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Apte

Dherange

Mustafa

et al. 2021

Front. Cardiovasc. Med.

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“…[1][2][3] Prior studies have shown that ibrutinib is an independent risk factor for the development of atrial arrhythmias with rates of atrial fibrillation in excess of 10% to 15%. [4][5][6] Aside from the development of frank arrhythmias, little is known about the potential effects of ibrutinib on electrocardiographic (ECG) parameters. Although significant QT prolongation was not identified during clinical trials, other ECG parameters have not been systematically evaluated.…”

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confidence: 99%

“…Details of this study population have been previously described. 4 In brief, patients diagnosed with B-cell malignancies were derived from the Moffitt Cancer Center (MCC) Malignant Hematology Program and those who completed at least one 28-day cycle of ibrutinib between January 1, 2010, and December 31, 2017, were selected. In this analysis, only patients with an ECG completed prior to and during ibrutinib therapy were included.…”

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confidence: 99%

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Electrocardiographic Changes Associated With Ibrutinib Exposure

et al. 2020

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Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib’s effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms ( P = .007), corrected QT interval shortening using Bazett’s formula from 446 ms to 437 ms ( P = .04), and corrected QT interval shortening using Fridericia’s formula from 425 ms to 407 ms ( P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.

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“…VEGF inhibitors prevent angiogenesis and were associated with decreased nitric oxide production, vasoconstriction and hypertension [ 12 , 14 ], thus potentiating endothelial dysfunction, atherosclerosis and thrombotic microangiopathy [ 15 , 16 ]. Other chemotherapeutics can cause atrial fibrillation, QT prolongation, ventricular arrhythmias and sudden cardiac death [ 17 , 18 ].…”

Section: Mechanism Of Cardiotoxicitymentioning

confidence: 99%

Cardiotoxicity Associated with Chemotherapy Used in Gastrointestinal Tumours

et al. 2021

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Cardiotoxicity is a well-recognised side effect of cancer-related therapies with a great impact on outcomes and quality of life in the cancer survivor population. The pathogenesis of chemotherapy-induced cardiotoxicity in patients with gastrointestinal cancers involves various molecular mechanisms, and the combined use of various chemotherapies augments the risk of each drug used alone. In terms of cardiotoxicity diagnosis, novel biomarkers, such as troponins, brain natriuretic peptide (BNP), myeloperoxidases and miRNAs have been recently assessed. Echocardiography is a noninvasive imaging method of choice for the primary assessment of chemotherapy-treated patients to generally evaluate the cardiovascular impact of these drugs. Novel echocardiography techniques, like three-dimensional and stress echocardiography, will improve diagnosis efficacy. Cardiac magnetic resonance (CMR) can evaluate cardiac morphology, function and wall structure. Corroborated data have shown the importance of CMR in the early evaluation of patients with gastrointestinal cancers, treated with anticancer drugs, but further studies are required to improve risk stratification in these patients. In this article, we review some important aspects concerning the cardiotoxicity of antineoplastic drugs used in gastrointestinal cancers. We also discuss the mechanism of cardiotoxicity, the role of biomarkers and the imaging methods used in its detection.

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Rates and Risk of Atrial Arrhythmias in Patients Treated With Ibrutinib Compared With Cytotoxic Chemotherapy

Cited by 46 publications

References 26 publications

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation

Electrocardiographic Changes Associated With Ibrutinib Exposure

Cardiotoxicity Associated with Chemotherapy Used in Gastrointestinal Tumours

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