QT prolongation

On an electrocardiogram, the QT interval measures how long it takes the heart's lower chambers to fire and then fully reset for the next beat. QT prolongation means that reset takes too long: the electrical recovery, called repolarization, is delayed. Picture a runner who is slow to catch their breath between sprints; the timing of the whole race gets thrown off.

The most common cause in drug discovery is block of the hERG potassium channel, the main current that repolarizes heart cells. Because heart rate affects the raw QT, it is corrected for rate to give the QTc, which is what clinicians actually monitor. A drug that meaningfully lengthens QTc carries a recognized arrhythmia risk.

The danger is that excessive QT prolongation can trigger torsades de pointes, a chaotic ventricular rhythm that may collapse into sudden cardiac death. This single liability has ended many development programs and prompted strict regulatory testing. That said, a small QTc increase is not automatically catastrophic; the concern scales with the size of the change and the drug's exposure margin.