Dynamic changes of P-wave duration and P-wave axis during head-up tilt test in patients with vasovagal syncope

BACKGROUND: The exact role of venous pooling in the pathogenesis of vasovagal syncope (VVS) is not fully elucidated. P-wave duration on an electrocardiogram can serve as a measure of atrial volume. METHODS: Sixty-six patients (15 men, 51 women, mean age 32 years) with unexplained syncope were enrolled in the study.P-wave duration and the P-wave axis (PWA) were measured during passive head-up tilt test (HUT) in order to evaluate dynamic changes of atrial filling in patients with VVS. RESULTS: HUT was positive in 40 patients (6 men, 34 women, mean age 32 +/- 9 years) and negative in 26 patients (9 men, 17 women, mean age 33 +/- 8 years). The P-wave duration was significantly reduced in HUT-positive patients at the onset of symptoms as compared to 5 minutes (88.8 +/- 11.9 vs 96.2 +/- 12.0 ms, P = 0.008), and baseline (88.8 +/- 11.9 vs 96.8 +/- 13.8 ms, P = 0.005). The P-wave duration was significantly shorter at the onset of presyncope in HUT-positive patients as compared to HUT-negative patients (88.8 +/- 11.9 vs 100.3 +/- 11.2 ms, P = 0.0002). In HUT-positive patients, a significant increase in PWA was found at the onset of symptoms when compared to baseline (67.7 +/- 22.1 degrees vs 47.9 +/- 14.9 degrees, P < 0.0001) and 5 minutes of HUT (67.7 +/- 22.1 degrees vs 54.4 +/- 14.9 degrees, P = 0.005). At the time of syncope, PWA was more inferior in HUT-positive patients than in HUT-negative patients (67.7 +/- 22.1 degrees vs 51.8 +/- 13.8 degrees, P = 0.015). CONCLUSIONS: VVS is associated with the reduction in P-wave duration and the increase in PWA, which can be a result of exaggerated venous pooling and reduction in atrial volume.     

Changes in the transthoracic impedance signal predict the outcome of a 70 degrees head-up tilt test

We determined whether early changes in central haemodynamics, as determined by transthoracic impedance, induced by a 70 degrees head-up tilt (HUT) test could predict syncope. Heart rate, arterial blood pressure and central haemodynamics [pre-ejection period and rapid left ventricular ejection time ( T (1)), slow ejection time ( T (2)) and d Z /d t (max) (where Z is thoracic impedance), assessed by the transthoracic impedance technique], were recorded during supine rest and during a 45 min 70 degrees HUT test in 68 patients (40+/-2 years) with a history of unexplained recurrent syncope. We found that 38 patients (42+/-3 years) had a symptomatic outcome to 70 degrees HUT (fainters) and 30 (39+/-2 years) had a negative outcome (non-fainters). When measured between 5 and 10 min of 70 degrees HUT, T (2) had increased significantly only in the fainters, and a change in T (2) of >40 ms from baseline predicted a positive outcome with a sensitivity of 68% and a specificity of 70%. During supine rest prior to 70 degrees HUT, the fainters exhibited a shorter T (2) than non-fainters (183+/-10 compared with 233+/-14 ms; P <0.01), and a T (2) of <199 ms predicted a positive outcome to 70 degrees HUT with a sensitivity of 68% and a specificity of 63%. Incorporation of the changes that occurred from rest to 70 degrees HUT in other haemodynamic variables (heart rate >11 beats/min, systolic pressure <2 mmHg, diastolic pressure <7 mmHg and pulse pressure <-3 mmHg) increased the specificity to 97% and the positive predictive value to 93%. Thus transthoracic impedance could detect differences in central haemodynamics between fainters and non-fainters during supine rest and during the initial period of 70 degrees HUT with a consistent sensitivity and specificity when combined with peripheral haemodynamic variables.     

Contrasting neurovascular findings in chronic orthostatic intolerance and neurocardiogenic syncope

Simple faint (neurocardiogenic syncope) and postural tachycardia syndrome (POTS) characterize acute and chronic orthostatic intolerance respectively. We explored the hypothesis that vascular function is similar in the two conditions. We studied 29 patients with POTS and compared them with 20 patients with neurocardiogenic syncope who were otherwise well, and with 15 healthy control subjects. We measured continuous heart rate, respiration and blood pressure, and used venous occlusion strain gauge plethysmography to measure calf and forearm blood flow, peripheral arterial resistance, peripheral venous resistance and venous pressure ( P (v)). Upright tilt was performed to 70 degrees for 10 min, during which calf blood flow and volume were measured. Calf P (v) was increased (to 27.2+/-2.0 mmHg) in a subgroup of POTS patients, who also had increased arterial resistance (57+/-6 mmHg.ml(-1).min(-1).100 ml(-1) tissue), increased venous resistance (2.4+/-0.3 mmHg.ml(-1).min(-1).100 ml(-1) tissue), and decreased peripheral flow (1.0+/-0.2 ml.min(-1).100 ml(-1) tissue) in the calf; other POTS patients with a normal P (v) had decreased arterial resistance (18+/-2 mmHg.ml(-1).min(-1).100 ml(-1) tissue) and increased blood flow (3.8+/-0.3 ml.min(-1).100 ml(-1) tissue). Syncope patients were not different from controls ( P (v)=11.4+/-0.5 mmHg; calf flow=3.1+/-0.2 ml.min(-1).100 ml(-1) tissue; arterial resistance=27+/-2 mmHg.ml(-1).min(-1).100 ml(-1) tissue; venous resistance=1.2+/-0.3 mmHg.ml(-1).min(-1).100 ml(-1) tissue). When upright, syncope patients and control subjects had similar increases in heart rate and calf volume, stable blood pressure, and decreases in blood flow. POTS patients had markedly increased heart rate and calf blood flow, unstable blood pressure, and pooling in the lower extremities, regardless of subgroup. We conclude that peripheral vascular physiology in patients with POTS is abnormal, in contrast with normal peripheral vascular physiology in neurocardiogenic syncope.     

Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress.

The relationship between aortic flow and pressure is described by a three-element model of the arterial input impedance, including continuous correction for variations in the diameter and the compliance of the aorta (Modelflow). We computed the aortic flow from arterial pressure by this model, and evaluated whether, under orthostatic stress, flow may be derived from both an invasive and a non-invasive determination of arterial pressure. In 10 young adults, Modelflow stroke volume (MFSV) was computed from both intra-brachial arterial pressure (IAP) and non-invasive finger pressure (FINAP) measurements. For comparison, a computer-controlled series of four thermodilution estimates (thermodilution-determined stroke volume; TDSV) were averaged for the following positions: supine, standing, head-down tilt at 20 degrees (HDT20) and head-up tilt at 30 degrees and 70 degrees (HUT30 and HUT70 respectively). Data from one subject were discarded due to malfunctioning thermodilution injections. A total of 155 recordings from 160 series were available for comparison. The supine TDSV of 113+/-13 ml (mean+/-S.D.) dropped by 40% to 68+/-14 ml during standing, by 24% to 86+/-12 ml during HUT30, and by 51% to 55+/-15 ml during HUT70. During HDT20, TDSV was 114+/-13 ml. MFSV for IAP underestimated TDSV during HDT20 (-6+/-6 ml; P<0.05), but that for FINAP did not (-4+/-7 ml; not significant). For HUT70 and standing, MFSV for IAP overestimated TDSV by 11+/-10 ml (HUT70; P<0.01) and 12+/-9 ml (standing; P<0.01). However, the offset of MFSV for FINAP was not significant for either HUT70 (3+/-8 ml) or standing (3+/-9 ml). In conclusion, due to orthostasis, changes in the aortic transmural pressure may lead to an offset in MFSV from IAP. However, Modelflow correctly calculated aortic flow from non-invasively determined finger pressure during orthostasis.     

Myocardial contractility and cardiac filling measured by impedance cardiography in patients with nitroglycerine-induced vasovagal syncope

OBJECTIVE: Increased myocardial contractility and inadequate cardiac filling leading to activation of the Bezold-Jarisch reflex were proposed as possible triggering mechanisms of vasovagal syncope (VVS). In the present study noninvasive hemodynamic measurements were performed in order to examine the role of myocardial contractility and cardiac filling in pathogenesis of VVS. METHODS: Hemodynamic parameters were measured during head-up tilt test (HUT) by impedance cardiography in 46 patients with unexplained syncope. Myocardial contractility was measured as index of contractility (IC), acceleration index (ACI), and ejection fraction (EF). Afterload was measured as systemic vascular resistance index (SVRI) and preload was expressed as end-diastolic index (EDI). Serial measurements were done 1 minute before HUT, during HUT at 1-minute intervals, and 1 minute after completion of HUT. RESULTS: HUT was positive in 30 patients (10 men, 20 women, mean age 36 +/- 16 years) and negative in 16 patients (8 men, 8 women, mean age 31 +/- 14 years). No significant differences were observed between HUT(+) and HUT(-) groups in hemodynamic parameters at supine rest and during HUT until the development of syncope. SVRI was lower in HUT(+) than in HUT(-) group at syncope (122.7 + 66.3 vs 185.6 + 51.4 dyn sec cm(-5)/m2, P = 0.002) and after syncope (117.0 + 61.1 vs 198.0 + 95.7 dyn sec cm(-5)/m2, P = 0.007). ACI, IC, EF, and EDI did not differ between groups at syncope. After syncope EF was higher in HUT(+) group compared to HUT(-) group (59.2 + 6.1 vs 52.7 + 9.4%, P = 0.02). CONCLUSION: The role of increased myocardial contractility and decreased cardiac filling is not confirmed in the present study.     

Assessment of orthostatic fluid shifts with strain gauge plethysmography

We evaluated the use of strain gauge plethysmography (SGP) for the assessment of orthostatic fluid shifts during head up tilt (HUT). Subjects wore a parachute harness fixed to the tilt table to avoid muscle tension in the lower limbs during HUT. 22 Healthy subjects (9 women) were tilted for 5 minutes. Calf volume changes as measured by SGP, surface EMG, heart rate and blood pressure were measured continuously. Ten subjects underwent a second tilt test during which circulation in one leg was occluded with a pressure cuff at 250 mmHg. During HUT with occlusion, calf volume increased in the non-occluded leg by 1.9+/-0.3% (mean +/- SEM) and 0.2+/-0.2% in the occluded leg (p<0.001). During HUT without occlusion a significant correlation (r = 0.9) was found between measurements of the left and right leg with a mean difference of 0.03+/-0.1%. HUT did not cause significant changes of surface EMG. An unexpected gender effect was found: calf volume increased significantly more in men than in women. Men were significantly taller, but the hemodynamic response to HUT did not differ between both sexes. The gender effect on orthostatic increases of calf volume remained significant after adjustment for heart-to-calf distance. SGP during HUT with a parachute harness is a new, promising method to assess orthostatic fluid shifts. The gender differences in orthostatic pooling in the calf may be explained by a higher calf compliance in men together with a greater hydrostatic pressure due to a greater height in men.     

Evaluation of a Single Stage Nitroglycerin Tilt Table Test for Diagnosis of Neurally Mediated Syncope

The purpose of this study was to compare clinical outcomes between a single stage head-up tilt table test (HUT) with infusion of 3.44 microg/kg per hour of nitroglycerin and a conventional multistage test with infusion of nitroglycerin from 1.72 microg/kg per hour to 5.16 microg/kg per hour in five successive stages. Thirty-seven patients with recurrent syncope underwent both tests in a prospective, randomized, crossoverfashion. During single stage HUT, a positive response occurred in 24 (64.9%) patients with unexplained syncope, an exaggerated response occurred in 3 (8.1%), a negative response in 7 (18.9%), and drug intolerance in 3 (8.1%). During the multistage HUT, these percentages were 62.2%, 16.2%, 13.5%, and 8.1%, respectively. Twenty healthy control subjects were involved in both tests, One of the control subjects had a positive response to single stage HUT, and two (10%) patients to multistage HUT. The duration of the test in single stage HUT was shorter than that in multistage HUT (8.6 +/- 10.3 vs 38.6 +/- 32.1 minutes, P < 0.01). The results showed that the single stage HUT was a fairly sensitive, specific, and a time-efficient test for provoking neurally mediated syncope.     

An association between anxiety and neurocardiogenic syncope during head-up tilt table testing

To study the association between anxiety and neurocardiogenic syncope as determined by head-up tilt table testing (HUT) in men and women with presyncope or syncope, patients with unexplained syncope or presyncope undergoing HUT were asked to complete the Burns Anxiety Inventory (BAI), a validated inventory of 33 questions with responses graded from 0 to 3. HUT consisted of a 30-minute tilt to 60 degrees, which if negative, was repeated with an isoproterenol infusion. A positive HUT was defined as symptomatic hypotension and/or bradycardia. Of the 66 patients who completed the BAI and underwent HUT, 33 were men and 33 were women. The mean age was 57 +/- 18 years (17-91 years). Patients with a positive HUT had a higher BAI score than those with a negative HUT (22 +/- 12 vs 14 +/- 13, P = 0.017). This association was stronger in women with a BAI score of 24 +/- 11 in those with a positive HUT versus 13 +/- 8 in those with a negative HUT (P = 0.005). In contrast, the mean BAI score for men with a positive HUT was 19 +/- 13, as compared to 15 +/- 16 for a negative HUT (P = 0.5). In conclusion, the present study demonstrates a statistical association between anxiety (as determined by BAI) and HUT result. Gender-based analysis revealed a more statistically significant relationship between anxiety and HUT outcome for women as compared to men.     

Frequency-domain analysis of heart rate variability during positive and negative head-up tilt test: importance of age

The study of autonomic behavior during a head-up tilt test (HUT) has been deemed important to understand the loss of consciousness mechanism. Though HRV in patients with HUT(+) and HUT(-) has been compared, few trials emphasized the importance of age. HRV in frequency domain was analyzed based on 5-minute samples in the supine position, and between 5 and 10 minutes during early tilt test (R1) in 102 patients with one or more episodes of syncope (mean age 44.3 +/- 20.8, range 15-85 years, 55 women). Two subgroups were selected afterwards: (1) young patients between 15 and 35 years of age (41 patients) and (2) elderly patients aged 60 or more (36 patients). The following parameters were taken into account: the sum of low (LF) and high frequency (HF) (LF and HF in absolute values and in normalized units), the LF/HF ratio (L/H ratio), and the percentage of change between baseline and R1 values. The HRV behavior in young and elderly patients with positive and negative HUT was established. We then analyzed the correlation between HRV and age and HUT outcome. A multiple regression analysis encompassing age, HUT outcome, gender, and number of syncope episodes was performed. In young patients, the LF and HF areas and the L/H ratio changed significantly between baseline and R1. The L/H ratio increases from baseline to R1. Conversely, these differences were not significant in the elderly. No differences between HUT(+) and HUT(-) within the same age group were observed. Age related significantly to practically all HRV parameters analyzed, whereas the tilt test outcome correlates poorly with HF normalized units and LF normalized units during R1, and the L/H ratio changes between baseline and R1. By means of a multivariate analysis, only age shows a significant correlation with the HRV values. Despite an all age triggering of vasovagal syncope during HUT, the young and elderly patients' autonomic behavior differs. The young considerably increase their sympathovagal balance during HUT, whereas the elderly have a mitigated autonomic response. No significant differences were observed during the first minutes of the test between those with a HUT(+) and those with a HUT(-) within the same age group. Age, and not the HUT response, is the major determinant of the autonomic behavior during early HUT.     

Syncope Is Predicted by Neuromonitoring in Patients with ICDs

Decisions regarding ability of ICD patients to function in the work environment or at home are based primarily on subjective judgement. We have described noninvasive neuromonitoring techniques that are capable of characterizing cerebral blood flow and cerebral oxygen saturation in conscious patients during ventricular tachycardia (VT). Upright tilt testing (HUT) was used to predict the hemodynamic response to VT in the upright and recumbent posture. Sixteen patients (66 ± 8 years) with pace-terminable VT and implanted ICD were tested during HUT with continuous measurement of arterial pressure, transcranial Doppler of the middle cerebral artery (TCD), and cerebral venous oxygen saturation (CVOS) determined noninvasively by applying a cutaneous patch with two infrared sensors from which a weighted venous percent oxygenated hemoglobin is continuously measured using INVOS 3100 (Somanetics). VT was induced via the implanted ICD and automatically terminated by ATP or cardioversion by the ICD, using the best treatment algorithm. HUT accentuated changes in cerebral blood flow and oxygen saturation and helped identify patients likely to experience syncope, whereas supine testing did not. These results suggest that HUT testing with noninvasive neuromonitoring is useful to predict ICD patients who are likely to remain conscious during VT.     

Enhanced plasma catecholamine and cAMP response during the head-up tilt test in patients with vasovagal syncope

AIMS: Vasovagal syncope appears related to transient changes in sympathetic neural outflow. Several studies have documented sympathetic inhibition at the time of syncope. However, data on the activity of the sympathetic nervous system a short time before the onset of syncope are controversial. The aim of the study was to examine sympathoadrenal activity by measuring levels of plasma catecholamines and plasma cAMP in patients with vasovagal syncope induced in the head-up tilt test (HUT). METHODS AND RESULTS: Sixty-one syncopal patients (age 35 +/- 15 years) underwent the passive HUT (60 degrees, 45 minutes). Blood samples for measurement of noradrenaline (NA), adrenaline (A) and dopamine (D) were obtained prior to tilt (0 minutes), at 5 minutes of tilt and at syncope or at the end of the HUT (45 minutes). Two samples were obtained for measurement of cAMP: at 0 minutes and at the end of the test. Plasma levels of NA, A and D were measured using high-performance liquid chromatography; plasma cAMP was measured using a radioimmunoassay technique. Thirty-three patients (15 men, age 35 +/- 16 years) developed vasovagal syncope during the test (HUT-positive); twenty-eight patients (15 men, age 34 +/- 14 years) completed the test without syncope (HUT-negative). No significant differences in NA, A and D were observed between the two groups at baseline or at 5 minutes of tilt. At the time of syncope, catecholamine levels in HUT-positive patients were higher than baseline levels (NA 428 vs. 209 pg/ml, A 90 vs. 55 pg/ml, D 297 vs. 142 pg/ml) and higher than in HUT-negative patients (NA 428 vs. 263 pg/ml, A 98 vs. 67 pg/ml, D 297 vs. 195 pg/ml). cAMP levels increased at syncope and were higher than in non-syncopal patients at the end of the HUT (607 +/- 460 vs. 328 +/- 297 nmol/ml). CONCLUSION: Vasovagal syncope induced by tilt testing is associated with increased levels of noradrenaline, adrenaline, dopamine and cAMP. These results suggest that sympathoadrenal activation antecedes development of vasovagal syncope and may play a role in its pathophysiology.     

Venous Dysfunction and the Change of Blood Viscosity During Head-Up Tilt

The precise stimulus that induces vasovagal syncope is still unclear. We have previously demonstrated that the peripheral distribution of blood volume (venous pooling) is a strong predictor of tilt induced vasovagal reaction. We hypothesized that an increase in venous pooling during tilt accentuates the measured increase in blood viscosity. This hypothesis is based on the previously demonstrated increase in venous pressure and subsequent increase in transcapillary fluid transudation during tilt. The increased blood viscosity, in turn, increases vascular shear rate, which may alter the vasoconstrictive and other cardiovascular responses to decreased preload. We measured blood viscosity (supine and tilt) in 56 patients with a history of orthostatic intolerance (37 with venous pooling [VP] and 19 without venous pooling [non-VP]). VP and non-VP were separated into subgroups based on blood pressure and heart rate response to tilt. There was a positive correlation between blood viscosity and plasma aldosterone in the supine. In the group as a whole, neither supine blood viscosity nor its increase during tilt differed between VP and non-VP. However, the tilt induced increase of blood viscosity was significant only in patients with tilt provoked tachycardia plus normal blood pressure response in VP group. We suggest that the increase of blood viscosity in this group led to the normal blood pressure response. The positive correlation between supine blood viscosity and supine plasma aldosterone indicates that the normal blood pressure response in this group possibly was via stimulation of the renin-angiotensin-aldosterone system.     

Late hemodynamic changes during a negative passive head-up tilt predict the symptomatic outcome to a nitroglycerin sensitized tilt

BACKGROUND: Sublingual nitroglycerin is advocated to sensitize the passive 70 degrees head-upright tilt test (HUTT) of patients with unexplained syncope. We hypothesized that a detailed analysis of hemodynamic responses recorded during a negative HUTT could predict the outcome to a subsequent nitroglycerin sensitized HUTT (NTG-HUTT). METHODS: Thirty-two patients (46 +/- 3 years, 17 males) with recurrent unexplained syncope but a negative HUTT were included. Heart rate, arterial blood pressure, and central hemodynamics assessed by transthoracic impedance (preejection and rapid left ventricular ejection time, slow ejection time, peak amplitude of first derivative, and cardiac index) were recorded during supine rest and 45 minutes HUTT. Changes from supine rest of the variables were retrospectively compared between patients with a negative (n = 15, NTG-HUTT(-)) and positive (n = 17, NTG-HUTT(+)) outcome to 10 minutes subsequent NTG-HUTT. RESULT: Significant differences between groups were observed during the 15th-20th minutes (Italian protocol) and during the last 5 minutes of passive HUTT (Westminster protocol). The combination of cutoff values, determined by receiver operating curves, on hemodynamic variables changes during the last 5 minutes predicted the outcome to a NTG-HUTT with a sensitivity of 76% and a specificity of 87%. The cutoff values determined during 15th-20th minutes gave an attractive sensitivity (85%) but a too weak specificity (53%) to shorten the 45 minutes passive HUTT at 20 minutes. CONCLUSION: Outcome to a NTG-HUTT can be reliably predicted by selected criteria determined from multiple hemodynamic variables recorded during a passive 70 degrees HUTT.     

Orthostatic challenge reveals impaired vascular resistance control,but normal venous pooling and capillary filtration in familial dysautonomia

Patients with familial dysautonomia (FD) frequently have profound orthostatic hypotension without compensatory tachycardia. Although the aetiology is presumed to be sympathetic impairment, peripheral vascular responses to orthostasis have not been assessed. The aim of this study was to evaluate the control of vascular responses to postural stress in FD patients. Measurements of heart rate, blood pressure, cardiac stroke volume and cardiac output (CO), by impedance cardiography, and calf-volume changes, by impedance plethysmography, were taken from nine FD patients and 11 control subjects while supine and during head-up tilt. During leg lowering, we also assessed the venoarteriolar reflex by measuring skin red-cell flux. Head-up tilting for 10 min induced sustained decreases in mean arterial pressure in the FD patients, but not in the controls. Total peripheral resistance (TPR, i.e. mean arterial pressure/CO) increased significantly in the controls (39.8+/-6.8%), but not in the FD patients. Calf-volume changes during tilting, when normalized for the initial calf volume, did not differ significantly between the patients (4.62+/-1.99 ml.100 ml(-1)) and the controls (3.18+/-0.74 ml.100 ml(-1)). The vasoconstrictor response to limb lowering was present in the patients (47.7+/-9.0% decrease in skin red-cell flux), but was impaired as compared with the controls (80.7+/-3.4%) ( P <0.05). The impaired vasoconstriction during limb lowering and absent increase of TPR during tilting confirm that orthostatic hypotension in FD is due primarily to a lack of sympathetically mediated vasoconstriction without evidence of abnormally large shifts in blood volume towards the legs during orthostasis. This may be due, in part, to a preserved myogenic response to increased vascular pressure in the dependent vascular beds.     

Inhibition of prostaglandin synthesis does not alter the decrease in pre-capillary resistance in the human calf in response to small cumulative increases in venous congestion

The decrease in pre-capillary resistance in the human calf during gradual cumulative increases in venous congestion pressure has been proposed to represent vasodilator signalling between the venous and arterial microcirculations. The present study investigated whether prostaglandins are involved in this local flow regulation by measuring calf blood flow and microvascular filtration capacity using strain gauge plethysmography in young male subjects before (baseline) and after taking either ibuprofen, an inhibitor of prostaglandin synthesis (1600 mg over 2 days), or placebo. At baseline, inflation of a thigh cuff to 50 mmHg in steps of 10 mmHg, each held for 5 min, did not decrease arterial inflow, confirming a reduction of pre-capillary resistance. Ibuprofen reduced resting calf blood flow by 35% (P<0.001), but flow at a Pcuff (cuff pressure) of 50 mmHg was 97% of this value, i.e. pre-capillary resistance had decreased to the same extent as before inhibition of prostaglandin synthesis. Ibuprofen also reduced microvascular filtration capacity (2.98+/-1.20 compared with 3.71+/-0.89 ml.min-1.100 ml-1.mmHg-1x10(-3); P<0.05), probably due to a combination of reduced arterial inflow and lower venous pressure (8.5+/-5.2 compared with 12.6+/-2.8 mmHg; P<0.05) that moderated capillary hydrostatic pressure to override direct effects of inhibition of prostaglandin synthesis on permeability. Placebo was without effect on any measurement. It is unlikely therefore that prostaglandin-mediated vasodilator signals, which have been demonstrated between paired veins and arteries, are important in local vasodilation in response to venous congestion.     

Reduced body mass index is associated with increased angiotensin II in young women with postural tachycardia syndrome

Altered peripheral haemodynamics, decreased cardiac output, decreased blood volume and increased AngII (angiotensin II) have been reported in POTS (postural tachycardia syndrome). Recent findings indicate that BMI (body mass index) may be reduced. In the present study, we investigated the hypothesis that reduced BMI is associated with haemodynamic abnormalities in POTS and that this is related to AngII. We studied 52 patients with POTS, aged 14-29 years, compared with 36 control subjects, aged 14-27 years. BMI was not significantly reduced on average in the POTS patients, but was reduced in patients with decreased peripheral blood flow. POTS patients were then subdivided on the basis of BMI, and supine haemodynamics were measured. There was no difference in blood volume or cardiac output once BMI or body mass were accounted for. When POTS patients with BMI <50th percentile were compared with controls, calf blood flow [1.63+/-0.31 compared with 3.58+/-0.67 ml(-1).min(-1).(100 ml of tissue)(-1)] and maximum venous capacity (3.87+/-0.32 compared with 4.98+/-0.36 ml/100 ml of tissue) were decreased, whereas arterial resistance [56+/-0.5 compared with 30+/-4 mmHg.ml(-1).min(-1).(100 ml of tissue)(-1)] and venous resistance [1.23+/-0.17 compared with 0.79+/-0.11 mmHg.ml(-1).min(-1).(100 ml of tissue)(-1)] were increased. Similar findings were also observed when POTS patients with BMI <50th percentile were compared with POTS patients with BMI >50th percentile. There was no relationship between blood flow, resistance or maximum venous capacity with BMI in control subjects. BMI was inversely related to plasma AngII concentrations in those POTS patients with decreased peripheral blood flow, consistent with cachectic properties of the octapeptide. Patients with low-flow POTS had decreased body mass, but decreased body mass alone cannot account for findings of peripheral vasoconstriction. In conclusion, the findings suggest that reduced body mass relates to increased plasma AngII.     

Heart Rate Variability During Head-up Tilt Testing in Patients with Suspected Neurally Mediated Syncope

The relation between heart rate variability (HRV) and outcome of head-up tilt testing (HUT) in patients with neurally mediated syncope (NMS) was studied in 30 patients with presumed NMS (33 ± 13 years) and in 11 age-matched controls. After 15 minutes of baseline supine observation, patients were tilted to 60± for 45 minutes or until syncope occurred. HRV parameters included RR intervals, standard deviation of normal-to-normal RR intervals (SDNN), and root mean square successive differences (RMSSD). HRV analysis was performed during 5-minute intervals in the supine position immediately after onset of HUT and before syncope or after 30–35 minutes of tilt in patients without syncope. Syncope occurred after a mean tilt duration of 32 minutes in 14 (47%) of 30 patients with presumed NMS, whereas all controls had an uneventful HUT. In the supine position, RR intervals and RMSSD were comparable among HUT-positive patients, HUT-negative patients, and controls (RR intervals: 799 ± 92, 854 ± 137, and 818 ± 128 ms, P = NS; RMSSD: 43 ± 40, 36 ± 34, and 53 ± 42 ms, P = NS). Baseline SDNN was also comparable in HUT-positive patients versus HUT-negative patients with presumed NMS (50 ± 26 vs 52 ± 20 ms, P = NS). Within 5 minutes preceding syncope or after 30–35 minutes of tilt, RR intervals and RMSSD were shorter in HUT-positive patients compared to HUT-negative patients, or to controls (RR intervals: 606 ± 86 vs 710 ± 117 and 739 ± 123 ms, P < 0.05; RMSSD: 12 ± 5 vs 23 ± 19 and 40 ± 32 ms, P < 0.05). Thus, HRV analysis in the baseline supine position was not a predictor of HUT outcome in patients with suspected NMS. Syncope during HUT seemed to be preceded by increased sympathetic activity manifested by an increase in heart rate and by a decreased parasympathetic tone manifested by a decrease in RMSSD measured for 5 minutes before the event, in comparison with HUT-negative patients and with controls.     

A "Dysautonomic" Head-Up Tilt Test Pattern in Elderly Patients with Neurocardiogenic Syncope

The characteristics of neurocardiogenic syncope (NCS) in elderly patients remain unclear. We compared the hemodynamic profiles of young and older patients with consecutive and positive head-up tilt tests (HUT). Continuous, noninvasive, and reliable monitoring of arterial pressure (AP) and heart rate (HR) was done throughout 46 consecutive positive HUTs of symptomatic patients. The population (12-82 years old) was divided into two groups: younger patients, Y (n = 25, < or = 65 years), and older patients, O (n = 21). Changes in AP and HR after the first minute of tilting, during the stable orthostatic phase and during syncope were compared. Except for systolic pressure, baseline hemodynamic parameters were similar in Y and O. No difference appeared in the mean time elapsed before syncope (19+/-9 vs 22+/-2 min). Asymptomatic hypotension was observed, only in O, 1 minute after tilting, followed by a progressive fall in the mean AP before syncope (0+/-0.9 vs -1+/-0.7 mmHg/min) without HR increase (0.7+/-1 vs 0+/-0.6 beats/min). This pressure slope was strongly related to age (r = 0.54, P < 0.001). Hemodynamic recording during HUT identifies a dysautonomic pattern in elderly patients with NCS and the abnormal AP/HR responses to orthostasis may be a feature specific to this population. Although the central mechanism of NCS is common to all ages, the age-related characteristics of the trigger event may indicate the need for specific management at different ages.     

Baroreflexes in vasovagal syncope: two types of abnormal response

Heart rate changes to hypotensive stimuli (baroreceptor sensitivity [BRS]) and forearm blood flow (FBF) reduction during head-up tilt are mediated by arterial and cardiopulmonary baroreceptors. Regarding baroreflexes in neurocardiogenic syncope (NCS), an apparent variation exists in findings reported in the literature. This may be due to the existence of different types of response. This study included 39 patients with NCS and positive tilt test and 26 normal subjects with negative test. Patients were grouped according to the type of tilt test response (mixed, cardioinhibitory, vasodepressor). BRS was noninvasively assessed in the supine position as an estimate of arterial baroreceptor sensitivity. As an estimate of cardiopulmonary baroreceptor reactivity, FBF was measured by venous occlusion plethysmography in the supine position and every 2.5 minutes during the first 15 minutes of tilt. BRS was related to percent of FBF changes. BRS was impaired in syncopal patients relative to controls (7.2 +/- 0.9 vs 10.4 +/- 0.3 ms/mmHg, P = 0.01), especially in vasodepressive type (4.9 +/- 1.0 ms/mmHg, P = 0.0001). FBF changes during tilt were subnormal in NCS, ascribed to two different patterns: one, characterized by impaired vasoconstriction (FBF during tilt showing < 10% mean reduction relative to baseline, especially in vasodepressive type) and another, characterized by a great variability across time (unstable response, especially in cardioinhibitory type). In controls, BRS was related to the percent of FBF changes after 2.5, 5, and 10 minutes of tilt (P values 0.0001, 0.004, and 0.008). In patients, BRS was uncoupled from FBF changes. In conclusion, baroreflexes in NCS are impaired, unstable, and disorganized. Impairment predominates in the vasodepressive type and instability in the cardioinhibitory. The results of this study are indicative of more than one baroreflex-mediated response types.     

Is Absolute Hypovolemia a Risk Factor for Vasovagal Response to Head-Up Tilt?

To test the hypothesis that hypovolemia is associated with an increased incidence of vasovagal syncope during head-up tilt (HUT) 45 patients with history of syncope or presyncope were studied. Blood volume (radio-iodinated serum albumin) was determined, then subjects underwent a graded HUT (from 15°–60° HUT) with cuff blood pressure and ECG monitoring. All patients were kept on their own medications during evaluation. Thirty patients (12 male, 18 female, mean age 50 ± 19 [SD] years) had hypovolemia, defined as blood volume < 90% of lab normal for corresponding sex, while 15 patients (7 male, 8 female, mean age 52 ± 21 years) were normovolemic with blood volume ranging from 91%-110% of sex-matched normal subjects. The normovolemic patients served as controls. During HUT, a vasovagal response was elicited in 5 of the 30 hypovolemics and in 4 of the 15 normovoiemic (16.7% and 26.7%, respectively, P = NS). In those who developed vasovagal response, the changes of heart rate and blood pressure during HUT were not significantly different between hypovolemics and normovolemics, neither at the endpoint (vasovagal response) nor immediately before the development of the vasovagal response. In patienis with nonvasovagal events, four types of hemodynamic responses to tilt were observed; normal blood pressure response associated with normal heart rate increase, normal blood pressure response in association with accentuated increase in heart rate, orthostatic hypotension with normal acceleration of heart rate, and orthostatic hypotension with accelerated increase in heart rate. The percent distribution of these responses were 44%, 20%. 0%, and 36% in the 25 nonvasovagal hypovoiemics versus 73%, 0%, 18%, and 9% in the 11 nonvasovagal normovolemics. The results demonstrate that supine total blood volume does not predict the occurrence of vasovagal response to HUT. However, accentuated orthostatic tachycardia was more prevalent in hypovolemics as compared to normovolemics with nonvasovagal response to tilt.