Epinephrine-induced QT interval prolongation: A gene-specific paradoxical response in congenital long QT syndrome

Michael John Ackerman, Anant Khositseth, David J. Tester, Joseph B. Hejlik, Win Kuang Shen, Co Burn J Porter

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalMayo Clinic Proceedings
Volume77
Issue number5
StatePublished - 2002

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Long QT Syndrome
Epinephrine
Genes
Romano-Ward Syndrome
Heart Rate
Genetic Testing
Ventricular Tachycardia
Intravenous Infusions
Molecular Biology
Electrocardiography

Keywords

  • ECG = electrocardiogram
  • LQTS = long QT syndrome
  • NSVT = nonsustained ventricular tachycardia
  • PVCs = premature ventricular contractions
  • QTc = corrected QT interval
  • TWA = T-wave alternans

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ackerman, M. J., Khositseth, A., Tester, D. J., Hejlik, J. B., Shen, W. K., & Porter, C. B. J. (2002). Epinephrine-induced QT interval prolongation: A gene-specific paradoxical response in congenital long QT syndrome. Mayo Clinic Proceedings, 77(5), 413-421.

Epinephrine-induced QT interval prolongation : A gene-specific paradoxical response in congenital long QT syndrome. / Ackerman, Michael John; Khositseth, Anant; Tester, David J.; Hejlik, Joseph B.; Shen, Win Kuang; Porter, Co Burn J.

In: Mayo Clinic Proceedings, Vol. 77, No. 5, 2002, p. 413-421.

Research output: Contribution to journalArticle

Ackerman, MJ, Khositseth, A, Tester, DJ, Hejlik, JB, Shen, WK & Porter, CBJ 2002, 'Epinephrine-induced QT interval prolongation: A gene-specific paradoxical response in congenital long QT syndrome', Mayo Clinic Proceedings, vol. 77, no. 5, pp. 413-421.
Ackerman, Michael John ; Khositseth, Anant ; Tester, David J. ; Hejlik, Joseph B. ; Shen, Win Kuang ; Porter, Co Burn J. / Epinephrine-induced QT interval prolongation : A gene-specific paradoxical response in congenital long QT syndrome. In: Mayo Clinic Proceedings. 2002 ; Vol. 77, No. 5. pp. 413-421.
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AU - Tester, David J.

AU - Hejlik, Joseph B.

AU - Shen, Win Kuang

AU - Porter, Co Burn J

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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.

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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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