It's not just the QT interval, stupid!

Traditionally we look to the QT interval to assess the risk of Torsades des pointes ventricular tachycardia when monitoring the effects of certain drugs. Moreover, QT interval prolongation, rather than “twisting about the point” morphology, has been the defining characteristic of Tdp. But as pointed out in a recent post over at Clinical Correlations, that thinking is simplistic. Even correcting the QT interval for rate (QTc) is of limited value. While it's true that prolonged repolarization is at fault that's only part of the story, as reflected in the post and as exemplified by amiodarone, which prolongs the QTc but does not cause Tdp. In actuality the abnormal repolarization that characterizes Tdp has other components and these may better lend themselves to the subjective “eyeball test” than to a single measurement. That said, some of the references cited in the Clinical Correlations post deal with attempts at quantitative treatment of the various components.

None of this is new mind you. I blogged this very concern over two years ago and said this:

Although the traditional assessment for prolongation of repolarization is the measurement of the QT interval, that assessment is simplistic and fraught with error due to controversy about normal limits and rate corrections, poor T wave demarcation, poor distinction between the T wave and the U wave and cycle length dependency. More subjective features including pause dependency, particularly in short-long cycle sequences, splayed T waves (or TU fusion) and macroscopic T wave alternans may be more important.

Among drugs that prolong the QT interval amiodarone has a uniquely low risk of producing TdP because the prolongation of repolarization it induces is homogeneous. Heterogeneous repolarization abnormality is the more likely substrate for TdP.