What does this research mean for the field?

Sublingual nitroglycerin-potentiated head-up tilt testing is a safe and effective method for diagnosing neurally mediated syncope in children, achieving a 63% positive diagnostic rate and 86% specificity. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to evaluate the effectiveness of sublingual nitroglycerin in head-up tilt testing for diagnosing unexplained syncope in children.

June 7, 2026

Tilt testing potentiated with sublingual nitroglycerin in children with unexplained syncope

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Unexplained syncope (n=193). Intervention: Sublingual nitroglycerin (NTG) potentiated head-up tilt (HUT) testing vs. Control children. Primary outcome: Positive response to tilt testing.

Key Result

Sublingual nitroglycerin-potentiated head-up tilt testing effectively unmasked neurally mediated syncope in children, demonstrating a positive rate of 63% and a specificity of 86%.

Key Points

This study aims to evaluate the effectiveness of sublingual nitroglycerin in head-up tilt testing for diagnosing unexplained syncope in children.
Prospective study with 164 paediatric patients and 29 control children.
Participants underwent head-up tilt testing at 60 degrees for 20 minutes followed by sublingual nitroglycerin administration (400 mcg) and a further tilt for 15 minutes.
Diagnostic responses were recorded during and after the NTG administration.
During the drug-free phase, 13 patients (8%) had a positive response; after NTG administration, 88 patients (55%) had a positive response.
The positive rate of the tilt test was 63% and specificity was 86%.
No significant adverse events were noted during the testing process.

Study Design

Type

Case-Control (n=193)

Structured PICO

Does sublingual nitroglycerin-potentiated head-up tilt testing improve the diagnostic yield for unexplained syncope in children?

Population

164 pediatric patients (mean age 13 years) with unexplained syncope and 29 control children evaluated using a sublingual nitroglycerin-potentiated tilt testing protocol.

Exposure

Head-up tilt testing at 60 degrees for 20 min, followed by 15 min after sublingual 400 mug spray nitroglycerin administration if no symptoms occurred.

Comparator

Passive tilt testing (drug-free phase) and healthy control children.

Outcome

Positive rate and specificity of the sublingual NTG HUT test.surrogate

Sublingual nitroglycerin-potentiated tilt testing is an effective and safe method to unmask neurally mediated syncope in children, significantly increasing the diagnostic yield with acceptable specificity.

Main Result

Absolute Event Rate: 63% vs 14%

Abstract

AIMS: The aim of this prospective study was to assess the diagnostic value of a sublingual nitroglycerin (NTG) potentiated head-up tilt (HUT) testing protocol in children with unexplained syncope. METHODS AND RESULTS: One hundred and sixty-four consecutive paediatric patients with syncope of unknown origin and no evidence of organic heart disease (115 female, mean age 13 +/- 3 years) and 29 control children underwent a sublingual NTG-potentiated tilt testing protocol. Paediatric patients and controls were tilted at 60 degrees for 20 min and, if no symptom occurred, for other 15 min after sublingual 400 mug spray NTG administration. During the drug-free phase of the test, 13 patients (8%) and no controls had a positive response. After drug administration, a positive response occurred in another 88 patients (55%) and in four controls (14%), whereas an exaggerated response was observed in nine patients (5%) and in four controls (14%). Thus, the positive rate and specificity of sublingual NTG HUT test in children were 63 and 86%, respectively. No relevant adverse events were observed during the test. CONCLUSION: Tilt testing potentiated with sublingual NTG has proved to be effective and safe in unmasking the neurally mediated origin of unexplained syncope in children. The NTG challenge greatly increased the positive rate of passive tilt, with a small decrease in specificity.

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