Tilt testing in neurocardiogenic syncope : isosorbide versus isoproterenol

Objective - To compare the diagnostic value of pharmacological stimulation with sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing in patients with neurocardiogenic syncope and with a negative tilt test without pharmacological provocation. Methods and results - One hundred and twenty patients with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt (HUT). Those who did not develop syncope or presyncope during passive HUT for 30 minutes underwent repeated HUT with isoproterenol infusion at 4 μg/min (ISOP HUT), for 10 minutes, and, subsequently, were tilted after sublingual administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes. ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively. Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70% (95% C.I.55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and 88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to 84.6%). There were fewer side effects during ISDN HUT. Conclusion - Sublingual isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients with suspected neurocardiogenic syncope and with a negative tilt test without provocation. The low rate of side effects and the higher accuracy of ISDN HUT, along with the simplicity of this challenge compared to ISOP HUT, suggest that sublingual isosorbide dinitrate should be preferred as a provocative agent to evaluate neurocardiogenic syncope after a negative passive tilt test.