Drug Challenge with Epinephrine or Isoproterenol for Diagnosing a Long QT Syndrome: Should We Try This at Home?

Diagnosing a congenital long QT syndrome (LQTS) is straightforward when a prolonged QT is present in a patient with arrhythmia-related symptoms and documented torsade de pointes.1 More often, however, a clear-cut diagnosis is not possible because: (1) QT-related arrhythmias are only rarely documented (except for patients with arrhythmic storms), and cannot be reliably and safely provoked. (2) Accurate measurement of the QT interval is not always easy2 and the presence of respiratory sinus arrhythmia complicates the estimation of the rate corrected QTc because the response of the QT interval to heart rate oscillations is not instantaneous. Consequently, the QTc calculated during heart rate deceleration will be shorter than the QTc calculated, only a few beats later, when the heart rate accelerates.3 (3) The QTc intervals of healthy individuals and that of patients with genetically proven LQTS overlap to such extent that one third of LQTS gene carriers and a similar number of healthy individuals have “borderline QT,” that is, a QTc between 430 and 460 ms.4 (4) Genetic testing is obviously useful when mutations are found but, with present technology, no mutations are identified in ≥25% of patients with LQTS. Furthermore, genetic analysis is only available in selected centers and often takes months to perform. Therefore, diagnostic and therapeutic decisions are still based, at least initially, on clinical grounds. Since symptoms in the common types of LQTS are commonly triggered by stress, it is only logical to use sympathetic stimulation, in the form of adrenaline or isoproterenol infusion, as a challenge test to unravel a LQTS in questionable cases. In fact, physicians have used such tests sporadically without rigorous control.5 Two groups of investigators finally evaluated the effects of an epinephrine challenge in LQTS patients in a controlled fashion.6-8 First, Ackerman6 studied 37 patients with LQTS (19 with LQT1, 15 with LQT2, and 3 with LQT3) as well as 27 healthy controls. Epinephrine was started at “low doses” (0.05 μg/kg/min) and the infusion rate was gradually increased to a “high dose” of 0.3 μg/kg/min. The absolute (uncorrected) QT interval increased in all patients with LQT1, decreased in LQT2/3 and increased or decreased in different controls. Since epinephrine also increased the heart rate, the rate-corrected QTc actually increased in all patient groups. This increment in QTc was greatest for LQT1 patients, intermediate for controls and smallest for LQT2/3 patients. Yet, there was significant overlap between the QTc