Mechanistic explanation of test positivity
Recent studies have indicated that TT positivity is associated with
neuroendocrine activation characterized by excess epinephrine and
vasopressin release21,22, whereas adrenomedullin seems
to play a protective role, probably acting against intravascular volume
escape.21 Further, older age and higher resting SBP
have been suggested to be predictors of hemodynamic stability on
TT.11,21 These findings were corroborated by
Lindenberger et al. who also found upregulation of vasopressin release,
reduced cardiac filling and cardiac output in women prone to reflex
syncope.23 Despite these studies, there remains a
tenable possibility that the documented endocrine changes are
precipitated by the developing adverse hemodynamic picture.
Lower circulating blood volume and tendency to blood pooling in the
capacitance vessels during orthostatic challenge may have a critical
impact in abruptly reducing stroke volume during TT and compensatory HR
increase, as confirmed by Buszko et al.12 The higher
resting HR and DBP may signal better neuroendocrine preconditioning
against orthostatic challenge, engaging the entire sympathetic system.
In contrast, those with a more pronounced epinephrine and vasopressin
release during tilt testing appear to be in greater need of circulatory
compensation as their resting SBP and DBP are lower. This may provoke a
protective response from the central nervous system, leading to reflex
syncope in extreme situations.24,25 Typically, this
response occurs when cerebral tissue oxygenation is strongly
compromised.26
Interestingly, only younger age but not gender was independently
predictive of TT positivity. The protective factors against TT
intolerance were resting SBP above 128 mmHg, heart rate above 69 bpm and
presence of hypertension, even while on antihypertensive treatment.
These findings emphasize the crucial role of global hemodynamic reserve
for reflex triggering. Higher HR might indicate more efficient
chronotropic compensatory mechanisms. Higher SBP suggests greater
intravascular volume, well-functioning preload- and afterload-preserving
mechanisms, whereas hypertension implies chronic sympathetic activation
with increased total peripheral resistance and elevated arterial tone in
the precapillary vascular bed. Arterial hypertension, as a variant of
cardiovascular dysautonomia, is detrimental for long-term cardiovascular
integrity and promotes end-organ damage.27 On the
other hand, patients with syncope affected by hypertension seem to be
more resistant to orthostatic stress, either due to altered hemodynamic
reserve, increased circulating blood volume, chronic neuroendocrine
activation and arterial vasoconstriction or by baroreceptor resetting.