Arrhythmias & electrophysiologyDiagnostic or prognostic study

Epinephrine Challenge

JACC Clin ElectrophysiolPublished

  • Diagnostic test performance study in a registry
  • consecutive patients
  • long-term follow-up

Authors' conclusion

A positive epinephrine challenge demonstrated mild-moderate agreement with a final diagnosis of LQTS and CPVT. Most patients with an initial positive test result had their diagnosis revised to UCA, unaffected, or an alternative diagnosis over long-term follow-up. This study suggests that epinephrine challenge has limited utility as a "rule-in" test but may retain value in its negative predictive value for the UCA population.

Study context

Population
Consecutive patients undergoing epinephrine challenge in the Hearts in Rhythm Organization registry: patients with unexplained cardiac arrest (UCA) and first-degree relativesconsecutive patients undergoing epinephrine challenge · patients with unexplained cardiac arrest [UCA] 250 · first-degree relatives 176
Participants
376 patients
Comparison
Epinephrine challenge for the diagnosis of long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT), comparing to final working diagnosis according to guideline-derived diagnostic criteria

Performance

As reported in the abstract

Test performance of epinephrine for the diagnosis of LQTS · mean follow-up 8.6 ± 5.3 years
Test or modelsensitivityspecificityLR+Likelihood ratio (LR-)
epinephrine challenge90%79%4.4 (95% CI: 3.4-5.6)0.1 (95% CI: 0.0-0.4)

Further findings

Outcomeepinephrine challengefinal working diagnosis
Test performance of epinephrine for the diagnosis of CPVT · compared with final working diagnosis
sensitivity62%Not reported in the abstract
specificity93%Not reported in the abstract
LR+8.9 (95% CI: 5.2-16.6)Not reported in the abstract
LR-0.4 (95% CI: 0.2-0.8)Not reported in the abstract

QT prolongation with epinephrine vs end-recovery QTc on exercise stress testing

No significant correlation

Pathogenic variant yield among patients with a positive epinephrine challenge

pathogenic LQTS variant, of genotyped patients with a positive epinephrine challenge for LQTS
15%
pathogenic CPVT variant, of patients with a positive epinephrine challenge for CPVT
13%

Final working diagnosis of patients with a positive epinephrine challenge

Most had a "non-LQTS/CPVT" final working diagnosis (either UCA, unaffected, or an alternative Inherited arrhythmia syndrome)

Original publication

Epinephrine Challenge. JACC Clin Electrophysiol. Published 14 May 2026. doi:10.1016/j.jacep.2026.03.033

Summarised from the published abstract; every number is checked against it