Recurrent vasovagal syncope: classification into two phenotypes with different anxiety sensitivity profile and differing blood pressure response to head-up tilt

Abstract Background/Introduction The pathophysiology of recurrent vasovagal syncope (VVS) is complex and not fully understood. A significant proportion of patients exhibit a specific, stress-related personality trait, anxiety sensitivity (assessed by a 16-item questionnaire), while another significant proportion belong to the hypotensive phenotype, characterized by reduced venous return and stroke volume, reflected by lower blood pressure, though not yet fully characterized as a distinct phenotype. Purpose To further elucidate the pathophysiology of recurrent VVS, by classifying typical VVS episodes into a central type (mainly CNS-mediated) or a peripheral one (possibly related to non-adaptive peripheral vasoactive mechanisms). In order to assess whether this classification uncovers two groups with different hemodynamic responses to a positive HUTT, we examined possible differences in clinical hemodynamic parameters prior to and during the initial, stabilization phase of tilt testing between the two patient groups. Methods One hundred twenty patients with at least 2 typical VVS episodes during the preceding 6 months and a positive head-up tilt test were studied. They were classified into i) those with central-type VVS, and ii) patients with peripheral-type VVS, based on a positive or negative 16-item anxiety sensitivity screening questionnaire, respectively. We examined possible differences in clinical characteristics and whether blood pressure and heart rate parameters prior to and during the stabilization phase of tilt test (5th min) could differentiate between these 2 groups. Results No differences were observed between groups regarding baseline demographic and clinical characteristics, systolic blood pressure or heart rate prior to and during the stabilization phase of HUTT (5th min of tilt). On the contrary, significant differences were observed between the 2 patient groups regarding diastolic blood pressure and its pattern of changes after 5 mins of HUTT relative to supine values (Figure). Conclusion Among patients with typical, recurrent VVS, a central or peripheral VVS phenotype can be identified through a simple, 16-item anxiety sensitivity questionnaire. The 2 phenotypes seem to show differential hemodynamic responses to a subsequently positive HUTT. This finding may have important therapeutic consequences; peripheral vasoactive substances (i.e. midodrine) may be more efficient for the peripheral phenotype, while centrally acting treatments (i.e. centrally-acting drugs, psychotherapy) may be a better first-line option for the central phenotype.Figure