Chemotherapy-Induced Arrhythmias

Abstract

:Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.

Drug-Induced QT Prolongation and Torsade de Pointes in Spontaneous Adverse Event Reporting: A Retrospective Analysis Using the Japanese Adverse Drug Event Report Database (2004–2021)

“…The risk of QT prolongation with arsenic trioxide, which is used to treat acute promyelocytic leukemia, is well known to be the most relevant [ 25 , 26 ]. It is also known that QT prolongation/TdP can occur with small-molecule targeted anticancer drugs including tyrosine kinase inhibitors (e.g., nilotinib, gilteritinib, Osimertinib, and crizotinib) and proteasome inhibitors (e.g., carfilzomib) [ 21 , 27 ]. As many anticancer drugs with new mechanisms have been developed in recent years, such as antineoplastic monoclonal antibodies and protein kinase inhibitors, there has been an increase in their use [ 28 ]; this may be an explanation for the number of patients who experienced QT prolongation/TdP who were also being treated with anticancer drugs.…”

Characteristics of patients with newly diagnosed hematological malignancies referred for echocardiography

“…Cardiac arrhythmias, especially atrial fibrillation and other tachyarrhythmias, may indicate subclinical left ventricle dysfunction in hemato-oncology ( 33 ). The complex proarrhythmic mechanism in this group of patients results from water and electrolyte disorders, advanced age, coexisting cardiovascular diseases, and the direct effect of anticancer drugs ( 34 ).…”

Cardiac Monitoring Guidelines in Clinical Trials and Post-Approval Surveillance for Patients Exposed to Anticancer Treatments: Do the Data Support the Recommendations?

“…Changes in the electrocardiogram may be a harbinger of impending cardiac adverse events. Alteration of the electrocardiographic intervals has become a matter of increasing scrutiny, perhaps propelled by incidences of sudden death resulting from torsades de pointe following arsenic trioxide administration and the concern of atrial fibrillation associated with ibrutinib (Westervelt et al, 2001, Essa et al 2022, Ganatra et al, 2018. Electronic measurement of the corrected QT and the PR interval as well as intraventricular conduction delays has been hugely important in identifying these abnormalities, however concerns persist.…”