Does an Early Increase in Heart Rate During Tilting Predict the Results of Passive Tilt Testing?

Head-up tilt testing is a useful but time-consuming procedure. If we could accurately predict the tilt testing results; we would be able to substantially shorten the duration of tilt protocol. To clarify the hypothesis that an early increase in heart rate (HR) during tilting can predict the passive tilt results in our protocol (80-degree angle for 30 minutes), we studied 115 consecutive patients (72 men, 43 women, mean age 46 +/- 19 years) who were clinically diagnosed with neurally mediated syncope. Twenty-nine (25%) patients had a positive tilt test (P group), whereas 86 (75%) patients had a negative test (N group). The early HR increase was defined as the maximum HR during the first 5 minutes of tilting minus the resting HR before tilting. The early HR increase was significantly higher in the P group (23.8 +/- 9.5 beats/min) than in the N group (17.5 +/- 8.2 beats/min, P = 0.0008), but it was negatively correlated with the tilt duration to positive response (r = -0.52, P = 0.0032) and the patient age in the entire study population (r = 0.62, P < 0.0001). Results of multiple regression analysis indicated that age, tilt result, and tilt duration were independently associated with the early HR increase. As a result, an early HR increase > or = 18 beats/min, the best apparent cut-off point obtained in our study, was a sensitive (100%) marker for prediction of a positive response at < or = 15 minutes of tilting, but it showed a low specificity (61%). In conclusion, an early HR increase during 80-degree tilting may be only predictive for a positive result < or = 15 minutes because it depends on the tilt duration to a positive response and patient age.     

Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt.

The pathophysiology of neurally mediated syncope is poorly understood. It has been widely assumed that excessive sympathetic activation in a setting of left ventricular hypovolemia stimulates ventricular afferents that trigger hypotension and bradycardia. We tested this hypothesis by determining if excessive sympathetic activation precedes development of neurally mediated syncope, and if this correlates with alterations in baroreflex function. We studied the changes in intraarterial blood pressure (BP), heart rate (HR), central venous pressure (CVP), muscle sympathetic nerve activity (MSNA), and plasma catecholamines evoked by upright tilt in recurrent neurally mediated syncope patients (SYN, 5+/-1 episodes/mo, n = 14), age- and sex-matched controls (CON, n = 23), and in healthy subjects who consistently experienced syncope during tilt (FS+, n = 20). Baroreflex responses were evaluated from changes in HR, BP, and MSNA that were obtained after infusions of phenylephrine and sodium nitroprusside. Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope. SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing. FS+ subjects had the largest decrease in CVP with tilt and had significant increases in MSNA and heart rate baroreflex slopes. These data challenge the view that excessive generalized sympathetic activation is the precursor of the hemodynamic abnormality underlying recurrent neurally mediated syncope.     

Responses to Tilt test in young and elderly patients with syncope of unknown origin.

The aim of the present study was to assess the cardiovascular autonomic function and responses to tilt test in young and elderly patients with syncope of unknown origin. We evaluated two groups of patients with previous unexplained syncope: 192 older subjects (112 males, 80 females, mean age 67.2 +/- 6.8 years) and 188 young subjects (102 males, 86 females, mean age 25 +/- 9 years). All patients underwent ambulatory electrocardiogram (ECG) monitoring, to evaluate time domain indices of heart rate variability (HRV), and head-up tilt test in the morning after an overnight fast. The responses of positive tilt test were classified using the VAsovagal Syncope International Study (VASIS) criteria: mixed (VASIS-1), cardioinhibition (VASIS-2A), severe cardioinhibition/asystole (VASIS-2B), pure vasodepression (VASIS-3). All the time-domain HRV indexes were lower in the older than in young subjects. The rate of positive responses was not different in the two groups. In elderly group the positive head-up tilt test responses showed: a pure vasodepressive response (VASIS 3) in 126 patients (65%), a mixed (VASIS-1) response in 25 patients (13%), a cardioinhibitory (VASIS-2A) response in 13 patients (7%). Only 28 (14.6%) of elderly group patients had negative head-up tilt test response. In contrast, in young group the positive head-up tilt test responses showed: 114 patients (61.2%) a mixed (VASIS-1) vasovagal response, 40 patients (22.3%) a cardioinhibitory (VASIS-2A) response, four (2.1%) patients a severe cardioinhibitory (VASIS-2B) and four (2.1%) patients a pure vasodepression (VASIS-3) response, respectively. The tilt test was negative in response in 26 young patients (12.2%). Our results confirm that the head-up tilt test may be useful in assessing unexplained syncope, since it is seen to be positive in 85% of elderly patients and 86% in young patients. In our subjects, vasodepressive response was the most frequent cause of syncope in older subjects, while vasovagal response is the commonest cause of syncope of young patients. This different behaviour in the elderly may be is explained with physiological aging, which is associated with a reduction of sympathetic-parasympathetic control on the cardiac rhythm, demonstrated by reduction in all the time domain HRV indices.     

Role of Vagal Control in Vasovagal Syncope

SUZUKI, M., et al .: Role of Vagal Control in Vasovagal Syncope. The vasovagal reaction is thought to be caused by sympathetic withdrawal and vagal augmentation. While measurements of muscle sympathetic nerve activity support sympathetic withdrawal in tilt induced syncope, the results of previous attempts to quantify vagal control using spectral analyses of heart rate variability (HRV) remain controversial. The sampling period used in the HRV studies is related to the discordant results. In the present study, HRV was computed every second using wavelet transformation to clarify the role of vagal control in tilt induced syncope during the 80-degree head-up tilt test (positive: 10 patients with vasovagal syncope; negative: 10 patients with vasovagal syncope, and 10 control subjects). Autonomic modulations were assessed using the absolute power of the low frequency (LF) (0.04–0.15 Hz) and high frequency (HF) (0.15–2.00 Hz) oscillatory components of R-R variability. Although the LF did not change during the tilt procedure, a decrease in the systolic arterial pressure (SAP) and increases in the R-R interval and HF were observed for the last 30 seconds before the tilt induced syncope in the tilt-positive group. Analyzing the hemodynamic measurements and spectral indices for the last 5 minutes preceding the tilt induced syncope, the study found that the SAP, R-R interval, and HF changed simultaneously during the 30-second period immediately before the tilt induced syncope. Further, the HF was positively correlated with the R-R interval and negatively correlated with the SAP. In conclusion, continuous spectral analysis of the R-R interval demonstrated increased vagal influence on the heart in tilt induced syncope. (PACE 2003; 26[Pt. I]:571–578)     

Heart rate variability and autonomic nervous system changes in children with vasovagal syncope

The aim of this study was to evaluate the HRV at rest and during tilt test (HUTT) in children with a history of vasovagal syncope and to link the HRV indices with the clinical results of the test. HRV indices were assessed in the supine position and during the initial 5 minutes of the 60-degree HUTT in 49 patients (33 females, 16 males, mean age of 13 +/- 2.8 years) who were evaluated for recurrent syncope. The positive to negative results of the test were 21 to 28. The normalized power of high frequency component (npHF) decreased, normalized power of low frequency component (npLF) and the LF:HF ratio increased during HUTT of tilt-positive patients (P < 0.05 for each parameter). Parallel changes, but to a lesser degree, were observed for similar HRV parameters of tilt-negative patients. In addition, the HF and all the time-domain indices decreased significantly (P < or = 0.05) during HUTT in the latter group. When the tilt-positive and -negative patients were compared, the npHF was lower (P = 0.002), npLF and LF:HF ratio were higher (P = 0.01 and P = 0.001, respectively) during the test in tilt-positive patients, reflecting increased sympathetic tone in this group. A cut-off point for LF:HF was assigned as 2.7 for differentiating tilt-negative and tilt-positive results. The specificity, sensitivity, and positive and negative predictive values of this cut-off point were calculated as 93%, 52%, 85%, and 41%, respectively. Patients with vasovagal syncope show variations in vagal autonomic tone and appear to be more prone to syncope when their sympathetic tone is elevated at the beginning of the test. LF:HF > 2.7 is a specific marker (specificity 93%) and can correctly predict a positive tilt test in 85% of patients.     

Neurally mediated susceptibility in individuals with Brugada-type ECG pattern

Background: Neurally mediated syncope and Brugada syndrome (BS) share common pathophysiologic mechanisms related to autonomic nervous system modulations, and particularly with increased vagal tone. This study aimed to investigate the incidence of neurally mediated susceptibility in individuals with Brugada-type electrocardiogram (ECG) pattern.
Methods and Results: Eight asymptomatic male individuals (mean age 41.6 ± 10.6 years) with spontaneous or procainamide-induced type 1 ECG pattern of BS and structurally normal hearts underwent a drug-free head-up tilt test. Twenty-five healthy male subjects (mean age 37.4 ± 14.1 years) with normal ECG and without structural heart disease were included in the study, and served as comparative controls. A positive tilt test response was observed in three out of eight subjects with the Brugada-type ECG pattern (37%) and in three out of 25 controls (12%) (P = 0.018).
Conclusions: This study demonstrates a high incidence of neurally mediated susceptibility in asymptomatic individuals with Brugada-type ECG pattern. Severe diagnostic and therapeutic dilemmas may rise from this coexistence. A positive tilt test in subjects with Brugada-type ECG displaying a history of syncope may mislead the physician to a false sense of security. Further studies are required to validate our findings and possibly evaluate the role of tilt test in risk stratification of patients with BS.     

Is Home Orthostatic Self‐Training Effective in Preventing Neurally Mediated Syncope?

BACKGROUND: Repeated orthostatic stress may prove to be of benefit in the regulation of neurally mediated syncope. But the role of home orthostatic self-training is not established to prevent symptoms in patients with neurally mediated syncope. We performed a prospective and randomized study to evaluate the effectiveness of repeated home orthostatic self-training in preventing tilt-induced neurally mediated syncope. METHODS AND RESULTS: Fourty-two consecutive patients (24 males and 18 females, mean age 39 years, 16-68 years) with recurrent neurally mediated syncope were randomized into the tilt training and control groups. The home orthostatic self-training program consisted of daily sessions for 7 days a week for 4 weeks. In order to determine the effects of home orthostatic self-training, we repeated the head-up tilt test in both groups 4 weeks later. Among the tilt-training group, 9 of 16 patients (56%) had a positive response on follow-up head-up tilt test. Among the untreated control group, 9 of 17 patients (53%) had a positive response on follow-up head-up tilt test. In subgroup analyses according to the number of tilt-training sessions or the classified type, we found no differences in the follow-up head-up tilt test responses. Spontaneous syncope or presyncope over mean follow-up of 16.9 months were observed in 42.9% versus 47.1% in the tilt-training and control group, respectively. CONCLUSIONS: Home orthostatic self-training was ineffective in reducing the positive response rate of head-up tilt test in patients with recurrent neurally mediated syncope.     

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.     

Heart rate and blood pressure variability in subjects with vasovagal syncope

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.     

Ambulatory blood pressure monitoring and endothelium-dependent vasodilation in the elderly athletes.

AIM: Regular exercise is a key component of cardiovascular risk prevention strategies, because it is associated with a variety of beneficial metabolic and vascular effects that reduce mortality and the incidence of cardiovascular adverse events. Endothelium plays an important role in the local regulation of vascular tone and structure, mainly by nitric oxide (NO) synthesis and action. Aim of the present study was to evaluate in elderly athletes the effect of regular aerobic exercise on arterial blood pressure (BP) and on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery. METHODS: The study population included 30 male subjects (mean age 65.6+/-5.6 years), who had practiced endurance running at a competitive level for at least 40 years, and 28 age- and sex-matched subjects (mean age 64.5+/-4.5 years) with sedentary lifestyle and free of cardiovascular disease. Athletes and control subjects underwent standard 12-lead ECG, clinic BP, 24-h ambulatory BP monitoring and endothelium-dependent FMD and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, in the brachial artery by high-resolution ultrasonography. RESULTS: Systolic clinic and ambulatory 24-h BP were significantly lower in the athletes, than in the controls (P<0.001, respectively). Systolic and diastolic 24-h BP variability, when assessed either by the standard deviation (S.D.), or by the coefficient of variation (CV), were also significantly lower in the athletes (P<0.01). The athletes also had a lower 24-h, day-time and night-time heart rate (HR) (P<0.01), as well as a lower HR variability (P<0.01). As regards circadian BP change, the %Delta was statistically significant greater in athletes (P<0.05). Elderly athletes showed higher FMD than elderly sedentary subjects (P<0.001), whereas no differences were shown in the response to GTN. CONCLUSIONS: Our results, suggest that long-term physical activity can counteract the age-related endothelial dysfunction that characterizes sedentary aging, preserving the capacity of the endothelium-dependent vasodilation and reduces BP values improving arterial pressure control.     

Syncope: The Diagnostic Value of Head-Up Tilt Testing

To determine the usefulness of prolonged head-up tilt in the diagnosis of neurally mediated syncope, 201 patients with history of syncope of unknown cause and 102 age and gender matched control subjects underwent a 40 minute 60 degree head-up tilt test. Head-up tilt elicited syncope (i.e., was positive) in 74 of the 201 patients (37%) with a history of unexplained syncope and in only 6 of the 102 controls (6%). The specificity of the test was 100% in patients 60 years of age and older. Symptoms during tilt-induced syncope were identified by the patients as similar to those they had suffered during their spontaneous episodes. All 80 subjects who had tilt-induced syncope recovered without sequelae. The positive predictive value of a positive response to head-up tilt was 93% and the negative predictive value was 43%. The results indicate that the prolonged head-up tilt test is a very specific procedure of high diagnostic value in patients with a history of unexplained syncope. It is particularly useful in the elderly age groups who have a high incidence of syncope.     

Cardiac vagal response to water ingestion in normal human subjects

In healthy young subjects there is direct evidence for sympathetic vasoconstrictor activation after drinking water, but this is not accompanied by an increase in arterial blood pressure. A marked pressor response to water ingestion has, however, been observed in elderly subjects and in patients with autonomic failure. We examined the effect of water ingestion on haemodynamic variables and heart rate variability (HRV) markers of cardiac vagal control in ten healthy young subjects and four cardiac transplant recipients with confirmed persistent cardiac vagal denervation. In a random order crossover protocol, changes in heart rate, blood pressure and measures of high frequency (HF) HRV were compared over time following the ingestion of 500 ml and 20 ml (control) of tap water. In healthy subjects, after drinking 500 ml of water the heart rate fell from 67.6+/-2.0 (mean+/-S.E.M.) to 60.7+/-2.4 beats/min (P<0.01), and the bradycardic response peaked between 20 and 25 min. There were no significant changes in arterial blood pressure. Over the same time course, water ingestion caused increases in measurements of HF HRV: root-mean-square of successive RR interval differences (RMSSD) increased by 13+/-2.7 ms after 500 ml versus 2+/-3.1 ms after 20 ml (P<0.05); HF power increased by 686+/-400 versus -63+/-322 (P<0.01). In transplant recipients water ingestion was followed by a pressor response (range 13 to 29 mmHg). These results provide evidence that water ingestion in normal subjects is followed by an increase in cardiac vagal control that may counteract the pressor effects of sympathetic activation. We suggest that in the elderly, in transplant recipients and in autonomic failure, loss of this buffering mechanism explains the pressor response to drinking water.     

Heart rate variability in arrhythmogenic right ventricular cardiomyopathy correlation with clinical and prognostic features

The identification of subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC) at higher risk for sudden death is an unresolved issue. An influence of the autonomic activity on the genesis of ventricular arrhythmias was postulated. Heart rate variability (HRV) analysis provides a useful method to measure autonomic activity, and is a predictor of increased risk of death after myocardial infarction. For these reasons, the aim of the study was to evaluate HRV and its correlations with ventricular arrhythmias, heart function, and prognostic outcome in patients with ARVC. The study included 46 patients with ARVC who were not taking antiarrhythmic medications. The diagnosis was made by ECG, echocardiography, angiography, and endomyocardial biopsy. Exercise stress test and Holter monitoring were obtained in all patients. Time-domain analysis of HRV was expressed as the standard deviation of all normal to normal NN intervals (SDNN) detected during 24-hour Holter monitoring. Thirty healthy subjects represented a control group for HRV analysis. The mean follow-up was 10.8 +/- 1.86 years. SDNN was reduced in patients with ARVC in comparison with the control group (151 +/- 36 vs 176 +/- 34, P = 0.00042). Moreover, there was a significant correlation of this index with the age of the patients (r = - 0.59, P < 0.001), with the left (r = 0.44, P = 0.002) and right (r = 0.47, P = 0.001) ventricle ejection fraction, with the right ventricular end diastolic volume (r = - 0.62, P < 0.001), and with the ventricular arrhythmias, detected during the same Holter record used for HRV analysis (patients with isolated ventricular ectopic beats < 1,000/24 hours, 184 +/- 34; patients with isolated ventricular ectopic beats > 1,000/24 hours and/or couplets, 156 +/- 25; patients with repetitive ventricular ectopic beats (> or = 3) and/or ventricular tachycardia, 129 +/- 25; P < 0.001). During follow-up two patients showed a transient but significant reduction of SDNN and a concomitant increase of the arrhythmic events. In eight patients an episode of sustained ventricular tachycardia occurred, but the mean SDNN of this subgroup did not differ from the mean value of the remaining patients (152 +/- 15 vs 150 +/- 39; P = NS). Only one subject died after heart transplantation during follow-up (case censored). Time-domain analysis of HRV seems to be a useful method to assess the autonomic influences in ARVC. A reduction of vagal influences correlates with the extent of the disease. The significant correlation between SDNN and ventricular arrhythmias confirmed the influences of autonomic activity in the modulation of the electrical instability in ARVC patients. However, SDNN was not predictive of spontaneous episodes of sustained ventricular tachycardia.     

Early heart rate variations during head-up tilt table testing as a predictor of outcome of the test

Head-up tilt table testing (HUTT) is a useful tool for the diagnosis of unknown origin of syncope. A setback is its duration. This study tries to establish a specific parameter that, according to the heart rate elevation in the test's initial phase, allows a reliable prediction of its outcome. In a prospective study, every patient being under unknown syncope workup was included. A two-phase 20-minute tilt table test was performed. The initial phase was passive, and the second required pharmacological stimulation with isoproterenol. The basal and 5- and 10-minute heart rate values of the passive phase were measured and compared within the group and against negative tests. During a 1-year period, 115 HUTT were performed: 88 were positive and 27 negative. The negative HUTT patients had an increase in HR of 5.05 (+/- 13.5) beats/min at 5 minutes, and 5.79 (+/- 12.9) beats/min at 10 minutes (P = 0.2). Those with a positive HUTT had an increase of 9.05 (+/- 14.5) beats/min at 5 minutes, and of 10 (+/- 13.4) beats/min at 10 minutes (P < 0.001). There were no significant changes in HR when comparing positive to negative HUTT. There is no specific number that allows predication of outcome early in HUTT. Within the group, variations are important. Only a group tendency can be established, which strongly correlates with the results obtained during the test.     

The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome

BACKGROUND: Studying patients with chronic fatigue syndrome (CFS), we have developed a method that uses a head-up tilt test (HUTT) to estimate BP and HR instability during tilt, expressed as a 'haemodynamic instability score' (HIS). Aim: To assess HIS sensitivity and specificity in the diagnosis of CFS. DESIGN:Prospective controlled study. METHODS: Patients with CFS (n=40), non-CFS chronic fatigue (n=73), fibromyalgia (n=41), neurally mediated syncope (n=58), generalized anxiety disorder (n=28), familial Mediterranean fever (n=50), arterial hypertension (n=28), and healthy subjects (n=59) were evaluated with a standardized head-up tilt test (HUTT). The HIS was calculated from blood pressure (BP) and heart rate (HR) changes during the HUTT. RESULTS: The tilt was prematurely terminated in 22% of CFS patients when postural symptoms occurred and the HIS could not be calculated. In the remainder, the median(IQR) HIS values were: CFS +2.14(4.67), non-CFS fatigue -3.98(5.35), fibromyalgia -2.81(2.62), syncope -3.7(4.36), generalized anxiety disorder -0.21(6.05), healthy controls -2.66(3.14), FMF -5.09(6.41), hypertensives -5.35(2.74) (p<0.0001 vs. CFS in all groups, except for anxiety disorder, p=NS). The sensitivity for CFS at HIS >-0.98 cut-off was 90.3% and the overall specificity was 84.5%. DISCUSSION: There is a particular dysautonomia in CFS that differs from dysautonomia in other disorders, characterized by HIS >-0.98. The HIS can reinforce the clinician's diagnosis by providing objective criteria for the assessment of CFS, which until now, could only be subjectively inferred.     

Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome

OBJECTIVE: Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS; We studied 24 obese subjects (9 men and 15 women, age 49.3 +/- 1.9 years, BMI 36.7 +/- 0.94 kg/m(2), mean +/- SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen. RESULTS: This intervention resulted in 6.6 +/- 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 +/- 0.36 vs. 1.9 +/- 0.33 [10(-4) x min(-1) x ( microU ml(-1))], P < 0.001). FMD significantly improved (12.9 +/- 1.2% vs. 7.9 +/- 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 +/- 7.7 vs. 265.6 +/- 9.3 ng/ml, P = 0.018 and 36.2 +/- 3.6 vs. 48.6 +/- 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R(2) = 0.47, P = 0.001). CONCLUSIONS: We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance.     

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.4 +/- 0.6 sites. After 24 hours, pacing was stopped and the electrophysiological study and recording of the AA intervals was repeated at 4, 8, 16, and 24 hours after cessation of pacing. Time- and frequency-domain parameters were computed from each 500 AA interval recording. After 24 hours of rapid pacing the AERP had shortened significantly (147 +/- 5.6 to 102+/- 6.4 ms, P < 0.0001). No significant changes in HRV and dispersion of refractoriness (AAERP) (47 +/- 7.1 to 44 +/- 4.2 ms) were observed. After cessation of pacing, the AERP prolonged again (102 +/-6.4 to 135+/-8.8 ms, P < 0.0001) and was paralleled by a significant increase in AAERP (44 +/- 4.2 to 63+/- 7.1 ms, P = 0.01). Furthermore, HRV increased significantly. At each time point an inverse relation between the logarithmically transformed vagal parameter HF (InHF) and AERP was observed. We calculated the mean InHF for each goat using all time points and used the median value to divide the 12 goats into high and low vagal tone groups. We compared the degree of ERA and recovery from ERA for both groups. The AERP shortened 47.4 +/- 6.5 versus 43.0+/-5.0 ms (NS) for goats with high and low vagal tone, respectively. During recovery from ERA the AERP lengthened 23.6 +/- 4.0 versus 42.5 +/- 1.7 ms (P = 0.001) for goats with high and low vagal tone, respectively. Multivariate regression analysis indicated a short AERP as the single independent determinant of the inducibility of AF during ERA and recovery from ERA (P < 0.0001). During recovery from ERA, the AERP prolonged and vagal tone and AAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.     

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.     

Head-Up Tilt Test in Patients with High Pretest Likelihood of Neurally Mediated Syncope: An Approximation to the "Real Sensitivity" of this Testing

This study was designed to examine the "true sensitivity" of a specific head-up tilt (HUT) testing protocol using clinical findings. The HUT protocol used 45 minutes at 60 degrees for the baseline portion and intermittent boluses of 2, 4, and 6 micrograms of isoproterenol in the second phase. Eighty-eight patients (40 men and 48 women; mean age of 33.8 +/- 16 years) with recurrent syncope and high pretest likelihood of neurally mediated syncope were included. The following were considerated as high pretest likelihood criteria: (1) at least two syncopal episodes; (2) no structural heart disease and normal baseline ECG; (3) age < 65 years; (4) a typical history of neurally mediated syncope, triggering factors plus premonitory signs; and (5) short duration of symptoms and fast recovery without neurological sequelae. Fifty-four patients (61%) had a positive tilt test (34/88 baseline [39%] and 20/50 with isoproterenol [40%]). The shorter time interval between the last syncopal episode and baseline HUT test was the only predictor for a positive response (P < 0.003). Conversely, this time interval was not predictor of positive responses during isoproterenol-tilt testing. In conclusion: (1) we claim a "sensitivity" for this combined protocol of 61%; and (2) our results indicate that patients with syncope of unknown origin must be tilted nearest as possible to the last syncope to increase the positive responses of HUT test.     

Upright Tilt Test: Correlation Between Results and Patient Clinical Features

The aim of our study was to analyze how the clinical history and the main clinical characteristics of patients suffering from loss of consciousness may influence the results of the upright tilt test. A series of 745 patients (333 males, 412 females; mean age 44 ± 18 years) with recurrent episodes of syncope or presyncope underwent complete clinical and noninvasive laboratory examination, including vagal maneuvers and upright tilt test (60° for 45 min). Cardiological and neurological findings were normal in every case. Upright tilt test was positive in 462 patients (62%). Patients with presyncope showed a lower positivity compared to patients with syncope (70.2% vs 42.9%, P < 0.001). Younger patients (< 25 years) displayed highest upright tilt test positivity (68.5%), while familial occurrence of syncope or presyncope, results of vagal maneuvers, and different gender did not correlate with the results of the test. The time interval between the last syncopal episode and the day of upright tilt test negatively influenced the proportion of positive tests (> 30 days = 45.1 % vs < 30 days = 77.2%; P < 0.001). Patients with more than three syncopal episodes in the 2 months preceding the test showed a higher upright tilt test positivity (83.9% vs 64.5%, P < 0.001). In conclusion, upright tilt test seems to be more sensitive in young patients with syncopal episodes during symptomatic periods. These findings suggest both an individual and temporal variability in autonomic nervous system activity, the implication of which are relevant to the indications for testing as well as the analysis of results.