Mechanisms Underlying the Development of Cardiac Arrhythmias

Atrial Fibrillation Induced by Anticancer Drugs and Underling Mechanisms

“…55 Rapid focal sources are usually associated with intracellular calcium (Ca i 2+ ) abnormalities. 53 Pharmacological agents causing an augmentation of Ca i 2+ (such as isoproterenol) are known to acutely induce or promote AF. 57 Among the anticancer agents inducing AF, only doxorubicin and ibrutinib have been tested for their effect on Ca i 2+ , and both have been found to produce abnormalities in cardiac Ca i 2+ (as discussed later).…”

“…For a better understanding of cancer therapy–induced AF, it is worth briefly reviewing the mechanisms underlying AF and prime electrophysiological factors related to AF. 53 AF can be generated by abnormalities in impulse formation (ie, focal activity) and electrical conduction (ie, reentry). AF is initiated by focal sources, and the arrhythmia can be maintained by reentrant and focal activities.…”

“…AF is initiated by focal sources, and the arrhythmia can be maintained by reentrant and focal activities. 53 , 54 Until recently, it was strongly believed that AF was primarily maintained by a reentrant mechanism. However, with the improvement of mapping technologies, increasingly more researchers either record reentry only sporadically and short-lived or not record it at all (for review 55 ).…”

“… 58 , 59 Reentrant activities are caused by disturbances in electrical propagation of excitation. 53 , 54 It has not been determined if anticancer drugs inducing AF inhibit the sodium channel (thereby producing conduction abnormalities). Yet even if they do, it does not seem to be relevant to AF caused by drugs because sodium channel blockers typically prevent or terminate AF and do not or very rarely cause AF de novo.…”