Rationale: Assessing the relative contributions of cardioinhibition and vasodepression to the blood pressure (BP) decrease in tilt-induced vasovagal syncope (T-VVS) requires methods that reflect BP physiology accurately. Objective: To assess the relative contributions of cardioinhibition and vasodepression to T-VVS using novel methods. Methods and Results: We studied the parameters determining BP, i.e. stroke volume (SV), heart rate (HR) and total peripheral resistance (TPR), in 163 patients with T-VVS documented by continuous ECG and video EEG monitoring. We defined the beginning of cardioinhibition as the start of a heart rate decrease (HR) before syncope, and used logarithms of SV-, HR- and TPR-ratios to quantify the multiplicative relation BP=SV·HR·TPR. We defined three stages before syncope and two after it based on direction changes of these parameters. The earliest BP decrease occurred nine minutes before syncope. Cardioinhibition was observed in 91% of patients at a median time of 58 s. before syncope. At that time SV had a strong negative effect on BP, TPR a lesser negative effect, while HR had increased (all p<0.001). At the onset of cardioinhibition, median HR was at 98 bpm higher than baseline. Cardioinhibition thus initially only represented a reduction of the corrective HR increase, but was nonetheless accompanied by an immediate acceleration of the ongoing BP decrease. At syncope, SV and HR contributed similarly to the BP decrease (p<0.001), while TPR did not affect BP. Conclusions: The novel methods allowed the relative effects of SV, HR and TPR on BP to be assessed separately, even though all act together. The two major factors lowering BP in T-VVS were reduced SV and cardioinhibition. We suggest that the term 'vasodepression' in reflex syncope should not be limited to reduced arterial vasoconstriction, reflected in TPR, but should also encompass venous pooling, reflected in SV.

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Aims: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. Methods and results: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. Conclusion: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

Purpose Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods We retrospectively studied TTT outcomes in suspected VVS. TTT consisted of supine rest, a maximum 20 min of head-up tilt without and, if nitroglycerin was needed, a further maximum 20 min after nitroglycerin administration. TTT was terminated if VVS occurred. We used binary logistic regression for the entire TTT and for each phase, with VVS as outcome and age and sex as predictors. Results TTT provoked vasovagal (pre)syncope in 494 out of 766 tests (64%). The proportion of men and women who fainted during the entire TTT did not differ significantly between the sexes (p = 0.13, corrected for age). A lower proportion of women than men had VVS in the phase without nitroglycerin (odds ratio 0.54; 95% confidence interval 0.37-0.79; p = 0.002, corrected for age), whereas a higher proportion of women than men fainted after nitroglycerin (odds ratio 1.58; 95% confidence interval 1.13-2.21; p = 0.008, corrected for age). These sex differences remained significant after correction for a history of orthostatic versus emotional triggers. The effect of sex on TTT outcome was closely associated with differences of blood pressure change upon tilt-up (lower in men in both TTT phases: without nitroglycerin p = 0.003; with nitroglycerin p = 0.05), but not with heart rate changes. Conclusion Men were more susceptible to induction of VVS without nitroglycerin and women after it. The unexpected findings may be due to sex-specific pathophysiological differences.

Objective To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). Methods Inclusion criteria for VVS were a history of VVS and tilt‐induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, “convex,” or decelerated, “concave”; (2) the time from head‐up tilt to when BP reached one‐half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. Results We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19–98 sec) than in VVS (median 1571 sec, IQR 1381–1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. Interpretation These new hemodynamic criteria reliably differentiate cOH from VVS.