QT prolongation and cancer therapeutics: a coming Tempest or Much Ado About Nothing?

This editorial refers to ‘Anticancer drug-induced life-threatening ventricular arrhythmias: a WHO pharmacovigilance study’, by J.E. Salem et al., doi:10.1093/eurheartj/ehab362. Over the last several decades, there has been a significant paradigm shift in the approach to cancer treatment, moving away from cytotoxic chemotherapies to targeted therapeutics and immunotherapies. The development of these novel treatments has led to significant improvements in both short- and long-term survival for patients that frequently had few treatment options; however, various treatment-related side effects can occur. Of particular concern are cardiovascular toxicities which frequently lead to either temporary or permanent cessation of the drug. Much of the attention of the field of cardio-oncology has focused on heart failure and left ventricular dysfunction; however, recently, arrhythmic toxicities are becoming increasingly recognized. Many cancer treatments can lead to drug-induced QT interval prolongation, and this can be a marker for an increased risk of torsade de pointes (TdP) and sudden cardiac death (SCD). While the first report of chemotherapy-induced QT interval prolongation was with anthracyclines,1 this phenomenon has been most associated with arsenic trioxide, a cytotoxic agent used to treat acute promyelocytic leukaemia, with >65% experiencing Bazett-corrected QT prolongation of >500 ms.2 With the explosion of novel therapeutics, QT prolongation is a frequently encountered issue; however, management has proven to be a challenge due to uncertain risk at various QT intervals.