Epinephrine-Nonsensitive Long QT Syndrome: A Treatment-Resistant Phenotype

Congenital long QT syndrome (LQTS) is an inherited disorder characterized by an increased risk of ventricular arrhythmias. However, identifying treatment-resistant patients remains challenging.

The authors aimed to investigate whether QT interval changes during epinephrine (Epi) infusion could predict cardiac events during follow-up in LQTS patients.

Forty-eight patients with LQTS at Hiroshima University Hospital were included. QTc was measured at baseline, peak, and steady state during Epi infusion. Patients were categorized as Epi-sensitive LQTS if the increase in QTc from baseline to peak was ≥80 ms or the increase from baseline to steady state was ≥35 ms; the remaining were categorized as Epi-nonsensitive LQTS. A subset underwent landiolol infusion after Epi administration to assess β-blocker responsiveness. Cardiac events during follow-up were defined as a composite of life-threatening arrhythmic events and syncope.

Twenty-five patients were categorized as Epi-sensitive LQTS, and 23 as Epi-nonsensitive LQTS. QTc shortening with landiolol was significantly greater in the Epi-sensitive group than in the Epi-nonsensitive group (-32 [Q1-Q3: -47 to -16] ms vs 8 [Q1-Q3: -9 to 30] ms; P < 0.001). During a median follow-up of 61 (Q1-Q3: 30-115) months, the cardiac event rate was significantly higher in the Epi-nonsensitive group than in the Epi-sensitive group (39% [95% CI: 22%-59%; 9 of 23] vs 4% [95% CI: 1%-20%; 1 of 25]; P = 0.004).

Among LQTS patients, blunted QTc prolongation during Epi infusion was associated with a higher risk of cardiac events during follow-up. Epi sensitivity may help identify treatment-resistant patients in LQTS.