Author + information
- Richard L. Verrier, PhD* ( and )
- Tuomo Nieminen, MD, PhD
- ↵*Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard-Thorndike Electrophysiology Institute, 99 Brookline Avenue, RN-301, Boston, Massachusetts 02215
We read with keen interest the excellent scientific statement on the prevention of torsade de pointes in hospital settings (1). The authors underscore the importance of averting potentially catastrophic events due to torsade de pointes resulting from excessive drug-induced QT-interval prolongation. They also indicate that while this event is generally rare, its occurrence is more prevalent among hospitalized patients who have other risk factors for arrhythmia, including underlying cardiac disease, renal or hepatic dysfunction, and electrolyte abnormalities.
Whereas the consensus statement focuses on QT-interval prolongation as a precursor of torsade de pointes, the authors draw attention in Figure 2 to a nefarious fellow traveler, specifically, macroscopic T-wave alternans (TWA). Many agents, such as amiodarone, almokalant, arsenic trioxide, and pentamidine, which induce QT-interval prolongation, may also provoke TWA and torsade de pointes (2). It is relevant that underlying cellular and ionic mechanisms are common to the triad of QT-interval prolongation, torsade de pointes, and TWA, namely, transmural dispersion of repolarization and excess intracellular calcium.
Because TWA reflects a continuum of electrical instability linked to arrhythmia risk (3,4), the presence of macroscopic TWA may, in fact, represent the tip of the iceberg of risk associated with proarrhythmic agents. In subjects during daily activity (5) as well as in hospitalized patients (6), a crescendo in TWA magnitude from nonvisible to visible levels consistently occurs before the onset of life-threatening ventricular tachyarrhythmias. Quantification of TWA magnitude in ambulatory patients may allow even earlier warning of impending arrhythmia on the basis of more subtle, microvolt levels of TWA. Prompt detection is critical because TWA is not only a marker but also a trigger of arrhythmia risk, as it enhances repolarization heterogeneity, facilitating unidirectional block and re-entry. Thus, the potential utility of quantitative TWA in hospitalized patients deserves systematic study.
In the future, real-time, continuous in-hospital monitoring of subtle, microvolt levels of TWA could complement existing electrocardiography-based indicators for early warning of impending arrhythmia to avert occurrence of drug-induced torsade de pointes.
- American College of Cardiology Foundation
- Drew B.J.,
- Ackerman M.J.,
- Funk M.,
- et al.
- Shusterman V.,
- Goldberg A.,
- London B.
- Nearing B.D.,
- Wellenius G.A.,
- Mittleman M.A.,
- Burger A.J.,
- Verrier R.L.