Diagnostic value of short-duration head-up tilt test for unexplained syncope: a non-inferiority study

The traditional head-up tilt test (HUTT) is time-consuming, imposing a noticeable burden on patients and on high-throughput syncope clinics. A 20-minute "Fast Italian Protocol," introduced in 2023, promises to streamline the procedure, yet its diagnostic reliability-particularly the optimal length of the sublingual nitroglycerin head-up tilt test (SNHUT) segment-remains unclear.

Between 2019 and 2025 we assessed 1,218 consecutive patients with unexplained syncope. Individuals were allocated non-randomly to a short protocol (10-minute baseline head-up tilt test (BHUT) + 20-minute SNHUT; n = 393) or the conventional protocol (20-minute BHUT + 20-minute SNHUT; n = 825). A one-sided non-inferiority analysis (α = 0.025; margin = - 10%) provided 90.7% statistical power.

Overall positivity did not differ between the short and conventional protocols (53.4% vs. 57.3%, p = 0.20), nor did the distribution of vasovagal reaction types (all p > 0.05). In the abbreviated arm, 86.4% of positive responses emerged within the first 10 min of tilt or nitroglycerin exposure, and 98.9% appeared within 15 min-proportions virtually identical to those observed with the conventional protocol (88.9% and 98.9%, respectively; p = 0.49).

A 10-minute BHUT followed by a 20-minute SNHUT is diagnostically non-inferior to the standard 40-minute test. Furthermore, curtailing the SNHUT phase to 15 min retains 98.9% of positive findings while trimming total test time by 37.5%. This streamlined approach could ease patient burden and significantly boost throughput in high-volume syncope centers.