Hemodynamic, autonomic and neurohormonal behaviour of familial amyloidotic polyneuropathy and neurally mediated syncope patients during supine and orthostatic stress.

Orthostatic intolerance (OI) syndromes are frequent and share symptoms like dizziness and orthostatic syncope. Their pathophysiology however seems to be different. The aim of our work was to evaluate autonomic and hemodynamic behaviour in patients with familial amyloidotic polyneuropathy and neurally mediated syncope in supine position and after acute orthostatic passive stress. We studied 12 patients with autonomic failure (group A), 12 patients with neurally mediated syncope (group B) and 16 aged matched normal controls (group C), in supine position and during the first 10 min of head-up tilt test (HUTT). Beat-by-beat blood pressure and heart rate were continuously monitored and digitised at 500 Hz. The baroreceptor alfa-index gain (vagal reflex-BRG), high frequency of RR variability (HFRR, vagal tonus) and low frequency of systolic arterial pressure variability (LFSAP, sympathetic tone) were calculated. Catecholamines, plasma brain (BNP) and atrial natriuretic (ANP) peptides were also measured. Hemodynamic data were derived and calculated by the non-invasive modelflow method. During supine position, cardiac output (CO) and stroke volume (SV) were similar in all groups. Mean arterial pressure (MAP) and BNP were higher in group A. Noradrenaline (NOR), BRG, HFRR and LFSAP were extremely low in this group. BRG and adrenaline (ADR) were higher in group B than in controls. Within the first 10 min of HUTT, there was a huge drop of CO, SV and MAP in group A, maintenance of very low levels of neurohormones and lack of autonomic function. HR, LFSAP and ADR had a higher rise at HUTT in group B compared with controls (p<0.01) but a significant decrease of BRG was noted (p<0.05). ANP or BNP did not change with tilt in any group. Different orthostatic intolerance syndromes may show important hormonal, autonomic and hemodynamic differences during supine rest and enhanced after passive orthostatism.

Diurnal blood pressure variation in progressive autonomic failure.

To investigate the role of the autonomic nervous system (ANS) in the generation of the circadian blood pressure (BP) variation, the degree of impairment of the ANS was related to the results of ambulatory BP recordings in 212 patients with progressive autonomic failure due to familial amyloid polyneuropathy. On the basis of BP and/or heart rate (HR) responses to the Valsalva maneuver, 60 degrees head-up tilting, deep-breathing tests, and plasma norepinephrine levels, 4 groups of patients were distinguished. In all patients and in 38 age-matched control subjects, ambulatory BP was monitored. Patients of group I (n=40, aged 32+/-3 y), with no evidence yet of impairment of their ANS, had circadian BP and HR variations indistinguishable from controls. Patients of group II (n=41, aged 34+/-5 y) had a variable degree of impairment of their parasympathetic ANS, but their sympathetic ANS was still intact. Twenty-four-hour HR was higher in these patients than in controls (88+/-11 versus 78+/-7 bpm, P<0.01). Their circadian HR variation was maintained, but their circadian BP variation was diminished (10+/-6/11+/-4 versus 17+/-6/16+/-4 mm Hg in controls, P<0.01) because of an attenuation of the nocturnal BP decline. Patients of group III (n=69, aged 36+/-6 y), with parasympathetic failure and intermediate sympathetic dysfunction, had a blunted diurnal BP variation, whereas patients of group IV (n=62, aged 38+/-6 y), with parasympathetic failure and severe sympathetic dysfunction, had an absent diurnal BP variation. In patients of groups III and IV, a decrease in daytime BP accounted for the blunted circadian BP variation. This extensive study in progressive autonomic failure confirms the important role of the ANS in the generation of circadian BP variation. For the maintenance of a normal circadian BP pattern, not only an intact sympathetic but also an intact afferent parasympathetic ANS is a prerequisite.

Impaired arterial baroreceptor sensitivity before tilt-induced syncope.

Autonomic dysfunction seems to play a central role in the pathophysiology of neurocardiogenic syncope (NCS) but conflicting data have recently become available. We evaluated autonomic nervous system (ANS) function (heart rate variability (HRV), systolic blood pressure variability (SBPV) and baroreceptor gain (BRG)) and non-invasive haemodynamics (cardiac output and total peripheral resistance) in patients with neurocardiogenic syncope. Retrospectively, we evaluated 12 NCS patients (positive head-up tilt without pharmacological provocation) in the basal state and at initial tilt, 12 non-NCS patients with tilt-negative syncope and 12 aged-matched normal controls. Prospectively, we evaluated 16 NCS patients to analyse the haemodynamics and ANS activity throughout the tilt test (beginning of tilt and before syncope occurs). HRV and SBPV were accessed by fast Fourier transforms (FFT) and spontaneous BRG by temporal sequences, slope and a index. Modelflow was used to quantify the non-invasive haemodynamics. None of the autonomic and haemodynamic parameters at baseline or in the first 10 min of tilt was different among the respective NCS, non-NCS syncope and normal control groups, except for SBP, which was higher at baseline in controls. Throughout the tilt test in the prospective NCS group, the heart rate increased (88-95 beats x min(-1), P<0.05), systolic blood pressure decreased (123-109 mmHg, P<0.01), and arterial baroreceptor gain was reduced (7.6 to 5.5 ms mmHg(-1), P<0.01) and the absolute high frequency component of HRV (HF HRV) decreased (150-80 ms(-2), P<0.05), before syncope occurred. There was no change in the low frequency component of HRV (LF HRV), SBPV, cardiac output (CO) or total peripheral resistance (TPR). Tilt-induced syncope could not be predicted by non-invasive haemodynamic or autonomic parameters at rest or in the initial minutes of tilt. The decrease in arterial baroreceptor gain could be a precocious expression of the transient autonomic dysfunction that characterizes the occurrence of neurocardiogenic syncope.

High altitude-related neurocardiogenic syncope.

This report presents a well-documented link between vasodepressor syncope, a marked increase of LF/HF ratio response to orthostasis (sympathetic dominance), and the efficacy of beta blockers in preventing orthostatic symptoms and absence of tilt-induced syncope, with normalization of the LF/HF ratio response.