Markers for Cardiac Repolarization and Risk Assessment
The determination of whether an investigative pharmaceutical agent prolongs
repolarization in the heart (an effect equivalent to prolongation of the QT interval
on the surface electrocardiogram) has become a mandatory step in the drug
development process. Such a determination takes considerable preclinical and
clinical screening of cardiac biomarkers. This determination is rapidly evolving
as an increasing body of knowledge is gained on the mechanisms by which drugs
prolong cardiac repolarization and on identiﬁcation of high-risk populations.
Failure to recognize the potential of an investigative agent to prolong cardiac
repolarization places future drug recipients at risk for life-threatening ventricular
arrhythmias, particularly a distinctive polymorphic ventricular tachycardia
termed “torsade de pointes.” Appropriate market withdrawal of the drug may
result. In this chapter, an approach to understanding the regulatory background,
mechanisms, and the preclinical and clinical assessment of cardiac biomarkers in
the determination of drug effects on cardiac repolarization is undertaken.