Sympathomimetic Infusion and Cardiac Repolarization: The Normative Effects of Epinephrine and Isoproterenol in Healthy Subjects

Catecholamines are known to affect cardiac repolarization, and provocation with either isoproterenol or epinephrine has been proposed as a tool for uncovering latent repolarization abnormalities. This study systematically compares the effects of isoproterenol and epinephrine infusions on QT interval (QT), T waves and U waves in normal subjects. Methods and Results: Twenty‐four normal subjects (29 ± 8 years) were evaluated during graded infusions of up to 0.30 μg/kg/minute epinephrine and 5.0 μg/minute isoproterenol. Heart rates at peak doses were 81 ± 13 bpm at 0.28 ± 0.04 μg/kg/minute epinephrine and 104 ± 5 bpm at 2.4 μg/minute isoproterenol. The longest absolute QT increase was 4 ± 5 msec above baseline during isoproterenol (P < 0.001) and 12 ± 23 msec during epinephrine (P = 0.07), while the longest corrected QT interval (QTc) increase was 67 ± 28 msec (P < 0.0001) and 79 ± 40 msec (P < 0.0001) above baseline during isoproterenol and epinephrine, respectively (P = 0.12 for difference). There was a 2‐fold increase in U‐wave amplitude during each intervention (P < 0.001). The specificity of paradoxical QT prolongation (≥30 msec at 0.05 μg/kg/minute or ≥35 msec at 0.10 μg/kg/minute epinephrine) and an increase in QTc ≥600 msec at any dose epinephrine were 100%. However, the specificity of other proposed criteria that utilized QTc measurement (≥30 msec at 0.10 μg/kg/minute or ≥65 msec at any dose) was poor whether all leads or only lead II were assessed. Conclusion: Both epinephrine and isoproterenol are associated with QTc prolongation and amplification of the U wave in normal subjects. The specificity of proposed criteria for epinephrine provocation in diagnosis of the long‐QT syndrome is variable; however, paradoxical QT prolongation at low‐dose epinephrine or a QTc ≥600 msec is highly specific.