Increased orthostatic tolerance following moderate exercise training in patients with unexplained syncope.
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OBJECTIVE: To determine whether a programme of simple, moderate exercise training increases blood volume and improves orthostatic tolerance in patients with attacks of syncope or near syncope related to orthostatic stress. DESIGN: An open study in 14 patients referred with unexplained attacks of syncope, who were shown to have a low tolerance to an orthostatic stress test. Measurements were made of plasma and blood volumes, orthostatic tolerance to a test of combined head up tilt and lower body suction, and baroreceptor sensitivity by applying subatmospheric pressures to a chamber over the neck. Cardiorespiratory fitness was assessed from the relation between heart rate and oxygen uptake during a graded treadmill exercise test. Assessments were made before and after undertaking an exercise training programme (Canadian Air Force 5BX/XBX). RESULTS: After the training period, 12 of the 14 patients showed evidence of improved cardiorespiratory fitness. All 12 patients were symptomatically improved; they showed increases in plasma and blood volumes and in orthostatic tolerance, and decreases in baroreceptor sensitivity. Despite the improved orthostatic tolerance, values of blood pressure both while supine and initially following tilting were lower than before training. CONCLUSIONS: Exercise training has a role in the management of patients with syncope and poor orthostatic tolerance. It improves symptoms and increases orthostatic tolerance without increasing resting blood pressure. (+info)
System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy.
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We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN. (+info)
Induction of neurally mediated syncope with adenosine.
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BACKGROUND: Tilt testing is used to establish the diagnosis of neurally mediated syncope. However, applicability of the tilt test is limited by test sensitivity and length of time required to perform the test. We hypothesized that adenosine could facilitate the induction of neurally mediated syncope through its sympathomimetic effects and therefore could be used as an alternative to routine tilt testing. METHODS AND RESULTS: In protocol 1, the yield of adenosine tilt testing (12 mg while upright, followed by 60 degrees tilt for 5 minutes) and a 15-minute isoproterenol tilt test were compared in 84 patients with a negative 30-minute drug-free tilt test. In protocol 2, 100 patients underwent an initial adenosine tilt test followed by our routine tilt test (30-minute drug-free tilt followed by a 15-minute isoproterenol tilt). Six additional control patients underwent microneurography of the peroneal nerve to compare the sympathomimetic effects during bolus administration of adenosine and continuous infusion of isoproterenol. In protocol 1, the yields of adenosine (8 of 84, 10%) and isoproterenol (7 of 84, 8%) tilt testing were comparable (P=NS). In protocol 2, the yields of adenosine (19 of 100, 19%) and routine (22 of 100, 22%) tilt testing were also comparable (P=NS). Although the yield of adenosine tilt testing was comparable in both protocols, patients with a negative adenosine tilt test but a positive routine tilt test usually required isoproterenol to elicit the positive response. Microneurography confirmed discordant sympathetic activation after adenosine and isoproterenol administration. CONCLUSIONS: Adenosine is effective for the induction of neurally mediated syncope, with a diagnostic yield comparable to routine tilt testing. However, the discordant results obtained with adenosine and the isoproterenol phase of routine tilt testing suggest that adenosine and isoproterenol tilt testing may have complementary roles in eliciting a positive response. Therefore, a tilt protocol that uses an initial adenosine tilt followed, if necessary, by an isoproterenol tilt would be expected to increase the overall yield and reduce the duration of tilt testing. (+info)
Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study.
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BACKGROUND: Etilefrine is an alpha-agonist agent with a potent vasoconstrictor effect, which is potentially useful in preventing vasovagal syncope by reducing venous pooling and/or by counteracting reflex arteriolar vasodilatation. The present multicenter, randomized, placebo-controlled study was designed to evaluate the efficacy of this drug for the long-term management of patients with recurrent vasovagal syncope. METHODS AND RESULTS: In the 20 participating centers, 126 patients with recurrent vasovagal syncope (at least 3 episodes in the last 2 years) and a positive baseline head-up tilt response were randomly assigned to placebo (63 patients) or etilefrine at a dosage of 75 mg/d (63 patients) and were followed up for 1 year or until syncope recurred. The primary end-point of the study was the first recurrence of syncope. There were no differences between the 2 study groups in the patients' baseline characteristics. During follow-up, the group treated with etilefrine had a similar incidence of first syncopal recurrence to that of placebo group both in the intention-to-treat analysis (24% versus 24%) and in on- treatment analysis (26% versus 24%). Moreover, the median time to the first syncopal recurrence did not significantly differ between the 2 study groups (106 days in the etilefrine arm and 112 days in the placebo arm). CONCLUSIONS: Oral etilefrine is not superior to placebo in preventing spontaneous episodes of vasovagal syncope. Randomized controlled studies are essential to assess the real usefulness of any proposed therapy for patients with vasovagal syncope. (+info)
Utility of a single-stage isoproterenol tilt table test in adults: a randomized comparison with passive head-up tilt.
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OBJECTIVES: This study was conducted to develop a time-efficient tilt table test. BACKGROUND: Current protocols of tilt table testing are quite time-consuming. This study was designed to assess the diagnostic value, tolerance and procedural time of a single-stage isoproterenol tilt table protocol. METHODS: A single-stage isoproterenol tilt table test was compared with the passive tilt table test. The study was prospectively designed in a randomized and crossover fashion. RESULTS: The study population consisted of 111 patients with a history of syncope (mean age 55 +/- 20 years). Of the total, 62 patients (56%; 95% confidence interval, 46% to 65%) had a positive vasovagal response during isoproterenol tilt table testing and 35 (32%; 23% to 41%) during passive tilt table testing (p = 0.002). The mean procedural times of the study population were 11.7 +/- 3.6 min and 36.9 +/- 13.3 min for isoproterenol and passive tilt table testing, respectively (p < 0.001). All patients tolerated single-stage isoproterenol testing. In the 23 control subjects (mean age 34 +/- 11 years), the apparent specificities were 91% (72% to 99%) and 83% (61% to 99%) for passive and single-stage tilt table testing, respectively. CONCLUSIONS: The single-stage isoproterenol tilt table test was more effective in inducing a positive vasovagal response in an adult population than the standard passive tilt table test, and it significantly reduced the procedural time. The increase in positive yield was associated with a moderate decrease in apparent specificity. These observations support the conclusion that single-stage tilt table testing could be a reasonable diagnostic option in patients undergoing syncope evaluation. (+info)
Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study.
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OBJECTIVES: The purpose of the study was to determine whether the well tolerated serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal syncope in patients resistant to or intolerant of previous traditional therapies. BACKGROUND: Serotonergic mechanisms play a major role in the processes leading to neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been reported to be effective in preventing refractory syncope. METHODS: Sixty-eight consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with recurrent syncope and positive head-up tilt test and in whom standard therapies with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral corticoid agents were ineffectual or poorly tolerated were referred for study. Patients randomly received either paroxetine at 20 mg once a day or a placebo. A head-up tilt test was then reperformed after one month of treatment, and the clinical effect was noted over a mean follow-up of 25.4+/-7.9 months. RESULTS: The response rates (negative tilt test) after one month of treatment were 61.8% versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively. During follow-up spontaneous syncope was reported in six patients (17.6%) in the paroxetine group as compared to 18 patients (52.9%) in the placebo group (p < 0.0001). Only one patient (2.9%) asked to be discontinued from the drug for severe side effects. CONCLUSIONS: Paroxetine was found to significantly improve the symptoms of patients with vasovagal syncope unresponsive to or intolerant of traditional medications and was well tolerated by patients. (+info)
Sympathovagal balance: how should we measure it?
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There are complex interactions between the sympathetic and parasympathetic nervous system inputs to the sinus node. The concept of "sympathovagal balance" reflects the autonomic state resulting from the sympathetic and parasympathetic influences. Despite widespread usage of a variety of heart rate (HR) variability parameters as indexes of sympathovagal balance, no index has been validated as a measure of sympathovagal balance. This study evaluated the utility of HR, HR variability, and a new parameter termed the vagal-sympathetic effect (VSE) as indexes of sympathovagal balance. The ideal parameter had to satisfy the following criteria: 1) the index should vary similarly among subjects in response to different autonomic conditions; 2) the variability in the index among subjects exposed to the same autonomic conditions should be small; and 3) the response of the index to various autonomic conditions should reflect the underlying changes in physiological state and have a meaningful interpretation. Volunteers [8 men, 6 women; mean age 28.5 +/- 4.8 (SD) yr] were evaluated for the effects of sympathetic and parasympathetic stimulation and blockade on HR and HR variability. VSE was defined as the ratio of the R-R interval to the intrinsic R-R interval. VSE and R-R interval consistently changed in the expected directions with parasympathetic and sympathetic stimulation and blockade. A general linearized model was used to evaluate the response of each parameter. VSE and R-R interval had r2 values of 0.847 and 0.852, respectively. Natural logarithm of the low-frequency power had an r2 value of 0.781 with lower r2 values for all the other HR variability parameters. The coefficient of variation was also lowest for each condition tested for the VSE and the R-R interval. VSE and R-R interval best satisfy the criteria for the ideal index of sympathovagal balance. Because it is impractical under most conditions to measure the VSE as the index of sympathovagal balance, the most suitable index is the R-R interval. (+info)
Contribution of head-up tilt testing and ATP testing in assessing the mechanisms of vasovagal syndrome: preliminary results and potential therapeutic implications.
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BACKGROUND: In patients with vasovagal syndrome, head-up tilt testing may reproduce symptoms generally associated with vasodepression. Recent research suggests ATP testing identifies patients with abnormal vagal cardiac inhibition. This preliminary study examined the joint contribution of both tests in identifying underlying mechanisms in the general population with vasovagal syndrome. METHODS AND RESULTS: Both tests were performed in random order during 1 session and outside of predominant sympathetic periods in 72 patients hospitalized for syncope (n=56) or presyncope (n=16) for whom no cardiac or extracardiac cause was found. For passive and isoproterenol-provocative tilt testing by standard protocol, reproduction of symptoms defined a positive test. The ATP test consisted of injecting ATP 20 mg IV at bedside, continuously monitoring ECG and blood pressure; a vagal cardiac pause >10 seconds defined a positive test. For most patients (64%), >/=1 test was positive. Of the 41 patients (57%) with a positive tilt test (either passive or provoked by isoproterenol), 32% had cardiac disease; none had significant bradycardia (<50 bpm). Of the 8 patients (11%) with a positive ATP test, 62% had cardiac disease; the probability of a positive result increased with age (P=0.015). Both tests were positive in 3 patients and negative in 26 patients; the tilt and ATP test results were uncorrelated (P=0.28). CONCLUSIONS: Results suggest tilt and ATP tests individually and jointly determine the mechanism of vasovagal symptoms in most patients and that vagal cardiac inhibition increases with age. (+info)