TY - JOUR
T1 - Epinephrine-induced QT interval prolongation
T2 - A gene-specific paradoxical response in congenital long QT syndrome
AU - Ackerman, Michael J.
AU - Khositseth, Anant
AU - Tester, David J.
AU - Hejlik, Joseph B.
AU - Shen, Win Kuang
AU - Porter, Co Burn J.
PY - 2002
Y1 - 2002
N2 - Objective: To determine the effect of epinephrine on the QT interval in patients with genotyped long QT syndrome (LQTS). Patients and Methods: Between May 1999 and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3 LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27 (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at baseline and during gradually increasing doses of intravenous epinephrine infusion (0.05, 0.1, 0.2, and 0.3 μg · kg-1 · min-1). The 12-lead electrocardiogram was monitored continuously, and heart rate, QT, and corrected QT interval (QTc) were measured during each study stage. Results: There was no significant difference in resting heart rate or chronotropic response to epinephrine between LQTS patients and controls. The mean ± SD baseline QTc was greater in LQTS patients (500±68 ms) than in controls (436±19 ms, P<.001). However, 9 (47 %) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting QTc (<460 milliseconds), whereas 11 (41 %) of 27 controls had a resting QTc higher than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested prolongation of the QT interval (paradoxical response), whereas healthy controls and patients with either LQT2 or LQT3 tended to have shortened QT intervals (P<.001). The maximum mean ± SD change in QT (ΔQT [epinephrine QT minus baseline QT]) was -5±47 ms (controls), +94±31 ms (LQT1), and -87±67 ms (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals (ΔQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05 μg · kg-1 · min-1) completely discriminated LQT1 patients (ΔQT, +82±34 ms) from controls (ΔQT, -7±13 ms; P<.001). Epinephrine-triggered nonsustained ventricular tachycardia occurred in 2 patients with LQTS and in 1 control. Conclusions: Epinephrine-induced prolongation of the QT interval appears pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus, epinephrine provocation may help unmask some patients with concealed LQTS and strategically direct molecular genetic testing.
AB - Objective: To determine the effect of epinephrine on the QT interval in patients with genotyped long QT syndrome (LQTS). Patients and Methods: Between May 1999 and April 2001, 37 patients (24 females) with genotyped LQTS (19 LQT1, 15 LQT2, 3 LQT3, mean age, 27 years; range, 10-53 years) from 21 different kindreds and 27 (16 females) controls (mean age, 31 years; range, 13-45 years) were studied at baseline and during gradually increasing doses of intravenous epinephrine infusion (0.05, 0.1, 0.2, and 0.3 μg · kg-1 · min-1). The 12-lead electrocardiogram was monitored continuously, and heart rate, QT, and corrected QT interval (QTc) were measured during each study stage. Results: There was no significant difference in resting heart rate or chronotropic response to epinephrine between LQTS patients and controls. The mean ± SD baseline QTc was greater in LQTS patients (500±68 ms) than in controls (436±19 ms, P<.001). However, 9 (47 %) of 19 KVLQT1-genotyped LQT1 patients had a nondiagnostic resting QTc (<460 milliseconds), whereas 11 (41 %) of 27 controls had a resting QTc higher than 440 milliseconds. During epinephrine infusion, every LQT1 patient manifested prolongation of the QT interval (paradoxical response), whereas healthy controls and patients with either LQT2 or LQT3 tended to have shortened QT intervals (P<.001). The maximum mean ± SD change in QT (ΔQT [epinephrine QT minus baseline QT]) was -5±47 ms (controls), +94±31 ms (LQT1), and -87±67 ms (LQT2 and LQT3 patients). Of 27 controls, 6 had lengthening of their QT intervals (ΔQT >30 milliseconds) during high-dose epinephrine. Low-dose epinephrine (0.05 μg · kg-1 · min-1) completely discriminated LQT1 patients (ΔQT, +82±34 ms) from controls (ΔQT, -7±13 ms; P<.001). Epinephrine-triggered nonsustained ventricular tachycardia occurred in 2 patients with LQTS and in 1 control. Conclusions: Epinephrine-induced prolongation of the QT interval appears pathognomonic for LQT1. Low-dose epinephrine infusion distinguishes controls from patients with concealed LQT1 manifesting an equivocal QTc at rest. Thus, epinephrine provocation may help unmask some patients with concealed LQTS and strategically direct molecular genetic testing.
KW - ECG = electrocardiogram
KW - LQTS = long QT syndrome
KW - NSVT = nonsustained ventricular tachycardia
KW - PVCs = premature ventricular contractions
KW - QTc = corrected QT interval
KW - TWA = T-wave alternans
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U2 - 10.4065/77.5.413
DO - 10.4065/77.5.413
M3 - Article
C2 - 12004990
AN - SCOPUS:0036237833
SN - 0025-6196
VL - 77
SP - 413
EP - 421
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 5
M1 - 62209
ER -