Familial vasovagal syncope.

Vasovagal syncope (VVS) is a common clinical problem characterized by transient episodes of loss of consciousness due to abnormal autonomic activity. This paper describes two groups of monozygotic twins, from different families, affected by VVS and a family with several members with this condition. Their clinical characteristics, haemodynamic response to tilt, treatment, and outcome are described.     

Clinical characteristics of patients with vasovagal reactions presenting as unexplained syncope.

OBJECTIVE: To describe the clinical characteristics of vasovagal syncope (VVS) in patients presenting to a tertiary referral centre with unexplained syncope, in whom the diagnosis of VVS was confirmed by tilt table testing (HUT) and in whom other causes of syncope excluded. DESIGN: Prospective study of 62 consecutive patients with more than two episodes of syncope in the past year. SETTING: A regional tertiary referral centre for patients with unexplained syncope. PATIENTS: Sixty-two patients, mean age 50 +/- 21 years, 39 female, were studied. Mean duration of symptoms was 5 years. Average frequency of attacks was one episode per week. INTERVENTIONS: Detailed semi-structured questionnaires were completed regarding presenting symptoms. RESULTS: In over one-third of patients, episodes occurred suddenly, with no prodromal features. In those with prodrome, 71% had autonomic symptoms, but 27% had palpitations or dyspnoea and 21% had chest pain. Eleven percent of patients denied known provocative features. In the remainder, the most common were prolonged standing (37%), hot weather (27%) and lack of food (23%). One-fifth had symptoms sitting and 5% whilst driving. Seventy-five percent of patients suffered after effects, the most common being severe fatigue. Over half sustained an injury during syncope, and 13% sustained a fracture. Unwitnessed episodes occurred in 25%. Pallor was reported in half the cases, sweating in 13% and myoclonus in 5%. CONCLUSIONS: Atypical presentations of VVS occur in many patients referred to a tertiary referral centre. Knowledge of the clinical characteristics of unexplained syncope for which VVS is the attributable diagnosis should assist in appropriate management of such patients.     

Comparison of provocative tests for unexplained syncope: isoprenaline and glyceryl trinitrate for diagnosing vasovagal syncope.

AIMS: To compare the sensitivity, specificity and adverse event profile of glyceryl trinitrate head-up tilt with isoprenaline head-up tilt in the diagnosis of vasovagal syncope in patients with unexplained syncope and healthy controls. METHODS AND RESULTS: Forty-eight patients with unexplained syncope and negative passive head-up tilt at 70 degrees for 40 min, and 14 healthy controls underwent glyceryl trinitrate head-up tilt and isoprenaline head-up tilt (maximum dose 5 microg x min(-1)) one week apart in random order. Outcome measures were production of symptoms (syncope, pre-syncope) with development of hypotension. In those with negative passive head-up tilt, the sensitivity of glyceryl trinitrate for diagnosing vasovagal syncope was 48% and the specificity was 71%. Glyceryl trinitrate was well tolerated. Isoprenaline sensitivity was 21% with specificity 64%. Side-effects prevented completion of the test in 68%. Commonest adverse events were the development of hypertension or tachycardia and intolerable flushing or nausea. CONCLUSIONS: Glyceryl trinitrate head-up tilt is as effective as isoprenaline head-up tilt as a provocative agent for vasovagal syncope and has a lower incidence of adverse events.     

Psychiatric profile, quality of life and risk of syncopal recurrence in patients with tilt-induced vasovagal syncope.

AIM: The aim of this study was to investigate the prevalence of psychiatric disorders and quality of life (QoL) in patients with tilt-induced vasovagal syncope and no other comorbidities, and their relationship with the syncopal burden and the risk of recurrence. METHODS: We studied 61 patients with recurrent syncope and positive tilt testing. Controls consisted of 61 sex- and age-matched healthy subjects. Psychiatric diagnoses were formulated on the basis of a structured interview and the Minnesota Multiphase Personality Inventory-2 questionnaire. QoL was assessed by means of the Short-Form Health Survey questionnaire. Patients were followed up for at least 1 year. RESULTS: The presence of psychiatric disorders was higher among patients than controls (71% vs. 23%, P < 0.001), with a prevalence of anxiety (28% vs. 5%), mood (18% vs. 3%), and somatization disorders (29% vs. 3%). The scores of all the QoL scales were statistically lower in patients than controls. An inverse correlation was found between QoL scale scores and syncopal burden. The presence of psychiatric disorders was predictive of syncopal recurrence during follow-up. CONCLUSION: Psychiatric disorders are common in patients with tilt-induced vasovagal syncope, and seem to predict the risk of recurrence. QoL is impaired in these patients, and is inversely correlated with the syncopal burden.     

Excessive myocardial contraction in vasovagal syncope demonstrated by echocardiography during head-up tilt test

The purpose of this study was to gain insight into the mechanism of vasovagal syncope and to test the efficacy of theophylline to prevent syncope. Twenty-six patients with vasovagal syncope underwent two-dimensional echocardiography and theophylline test during head-up tilt test. A standard parastemal short-axis view of echocardiography at the level of the papillary muscle was recorded to measure fraction shorting of the left ventricle, and left ventricular end-diastolic and end-systolic dimensions. Heart rate, blood pressure, and symptoms were recorded. There were three groups; Group 1: no syncope with and without isoproterenol (n = 5); Group 2: syncope only after the infusion of isoproterenol (n = 16); Group 3: syncope without isoproterenol (n = 5). Groups 2 and 3 proceeded to theophylline injection (250 mg). The study showed that the 80° tilt induced an increase in heart rate of 6.6 ± 4.0,12.4 ± 6.6, and 25.4 ± 4.5 beats/min in Groups 1,2, and 3, respectively (p < 0.05 in Groups 1 and 2, p < 0.05 in Groups 1 and 3). The addition of isoproterenol during posture change from supine to an 80° tilt made the significant change of fractional shortening from 0.4 ± 5% to 6 ± 13% in Group 2 (p = 0.05), compared with no significant change in Group 1. There were no significant differences in left ventricular end-diastolic dimension and end-systolic dimension in each group between baseline and isoproterenol infusion during posture change. Vasovagal syncope was associated with vigorous myocardial contraction, rather than with contraction against an empty left ventricle. The acute loading of theophylline was not effective in preventing vasovagal syncope.     

The effect of atropine in vasovagal syncope induced by head-up tilt testing.

AIMS: This single-blinded, randomized, placebo-controlled study was designed and undertaken to assess the efficacy of intravenous atropine administration on haemodynamic impairment induced by head-up tilt testing in patients with vasovagal syncope. METHODS AND RESULTS: One hundred and thirteen consecutive patients (62 male and 51 female, mean age 46.3 years) with recurrent syncope, no evidence of cardiac, neurological or metabolic disease and a positive head-up tilt test were included in the study. Within 2 weeks of the first head-up tilt test all patients underwent a second tilt test. During this second test, all patients were randomized to receive a bolus of either atropine (0.02 mg. kg(-1)) or placebo (isotonic saline solution). The administration of atropine or placebo was performed at the onset of the haemodynamic modifications (heart rate and/or blood pressure fall) in conjunction with typical vasovagal prodromal symptoms. Treatment was taken as effective when symptoms aborted and the test was completed. In 29 of 113 patients the second tilt test was negative and these patients were excluded from final data analysis. Forty-one patients received placebo, which was effective in nine cases (21.9%). Atropine was administered to 43 patients and was effective in 30 cases (69.7%, P<0.01 vs placebo). The effects of treatment were analysed further to consider the haemodynamic patterns of tilt-induced vasovagal reflex. In the cardio-inhibitory form, placebo was never effective (15 cases), while atropine was effective in 15 of 18 cases (83.3%, P<0.001 vs placebo). In the vasodepressor form, placebo was effective in nine of 26 patients (34.6%), while atropine was effective in 15 of 25 cases (60.0%, no significant difference vs placebo). CONCLUSIONS: Atropine is fully effective in the cardio-inhibitory form of tilt-induced vasovagal reflex, but is limited in the vasodepressor form.     

Venous pooling during nitrate-stimulated tilt testing in patients with vasovagal syncope.

AIMS: To investigate the importance of venous pooling and variation in venous tone during nitrate-stimulated tilt testing in patients. METHODS: Ten patients with a history of vasovagal syncope underwent an upright tilt test after an injection of 99mTc-labelled albumin. A gamma camera was positioned at the level of the lower legs. The patients were tilted to 90 degrees for 30 min or until symptoms developed. In those subjects who did not show any symptoms before the end of the 30-min period, isosorbide dinitrate (ISDN) 5 mg was given sublingually and the test was prolonged for a maximum of 15 min. RESULTS: Nine of 10 patients needed nitrate stimulation to develop symptoms, and one patient remained symptom free following ISDN administration. Measurement of radioactivity revealed no significant increase in calf volume after nitrate stimulation (the mean volume increase was 77% before ISDN stimulation and a further 0.9% afterwards). CONCLUSIONS: The higher sensitivity for vasovagal syncope during upright tilt testing after administration of sublingual ISDN is not due to an increase in venous pooling in the lower extremities.     

Simultaneous analysis of heart rate variability and myocardial contractility during head-up tilt in patients with vasovagal syncope

INTRODUCTION: The aim of this study was to evaluate simultaneously cardiac autonomic activity, through heart rate variability (HRV) analysis, and cardiac inotropic changes during head-up tilt (HUT) in patients with recurrent vasovagal syncope. METHODS AND RESULTS: Twelve subjects implanted with a permanent dual-chamber pacemaker for recurrent vasovagal syncope characterized by marked bradycardia were studied. The tip of the right ventricular electrode was equipped with a sensor that measured peak endocardial acceleration (PEA) as an index of myocardial contractility. RR interval and PEA signals were acquired simultaneously and processed in the time and frequency (low frequencies [LF] and high frequencies [HF] of RR signal) domain during early HUT (T1), late HUT, or before syncope (T2). In the six subjects with positive HUT: (1) Abnormal heart rate oscillations were evidenced at T1 and discriminated this group from the negative group (LF/HF decreased by 46% from supine to T1, but increased by 55% in the negative group; P < 0.01 positive vs negative HUT). (2) Gradual diminution of the HF component was associated with an increase in PEA index during HUT with a correlation between PEA/RR interval (R = -0.8, P < 0.001), PEA/HF components (R = -0.6, P < 0.05). (3) Sympathetic stimulation responsible for changes in both HRV and PEA parameters occurred immediately before the faint (LF/LF+HF: 0.6 +/- 0.2 to 0.8 +/- 0.09; P < 0.05 T2 vs T1; PEA: 0.62 +/- 0.10G to 0.83 +/- 0.22G; P < 0.01 T2 vs T1). CONCLUSION: Our findings showed that a homogeneous subgroup of patients with recurrent vasovagal syncope and positive HUT exhibited abnormal cardiac autonomic and inotropic responses to an orthostatic stimulus. Continuous changes over time of HRV and PEA parameters highlight the dynamic behavior of the mechanisms leading to syncope.     

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.     

血管迷走性晕厥直立倾斜试验反应类型研究

目的 观察首次直立倾斜试验阳性．并依据血流动力学特征表现为心脏抑制型和血管减压型晕鳜患者进行直立倾斜试验时血压和心率的反应。方法 对48例心脏抑制型性晕厥和20例血管减压型晕厥患者，间隔1～7d．在相同试验条件下再次行直立倾斜试验，观察血压和心率的再次反应。结果 ①48例心脏抑制型晕厥患者．40例诱发晕厥或晕厥前症状．阳性重复性为83.3％，其中30例仍表现为心脏抑制型晕厥，10例表现为血管减压型和／或混合型晕厥；②20例血管减压型晕厥患者，16例诱发晕厥或先兆晕厥症状，阳性重复性为80％．其中11例仍表现为血管减压型晕厥．5例表现为心脏抑制型和／或混合型晕厥。结论 心脏抑制型和血管减压型晕厥的反应类型可以改变．此类由心脏受体所激发的神经介质反应具有复杂性，有助于我们进一步阐明心脏血管神经源性晕厥的病理生理机制，为临床诊治提供了重要线索。     

Different treatments for different mechanisms in vasovagal syncope

The treatment of vasovagal syncope has been by far unsatisfactory. Beta-blockers may prevent vasovagal syncope, but they exacerbates heart asystole. Cardiac pacing prevents syncope but notpresyncope. The frequent, serious vasovagal syncope attacks of a 63- year-old woman patient were completely prevented by administration of 100 mg metoprolol (b.i.d) for 3 months until the patient experienced a complete heart block. A DDD pacemaker implantation abolished syncope but not the presyncope, which was eventually prevented in a follow-up period of 24 months by adding 75 mg atenalol twice a day. This case suggests a different mechanism involved in vasovagal syncope. (J Geriatr Cardiol; 2006; 3(1):61-64)     

Syncope recurrence can better be predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope

BACKGROUND: Head-up tilt testing is widely used in the evaluation of patientswith suspected neurally mediated syncope. Although it remainsunclear which patients require medical therapy to prevent recurrentsyncope, most centres initiate empiric medical therapy in allpatients in whom neurally mediated syncope has been diagnosed.To determine the natural history of this condition, we followed80 untreated patients. METHODS: All 80 study patients fulfilled the following inclusion criteria:(1) 1 syncope in the upright position, (2) absence of structuralheart disease, (3) unremarkable work-up for other known causesof syncope. Thirty-nine patients had a history of one episodeof syncope (group A) and 412 episodes of syncope (group B).Head-up tilting was performed in all patients at 60° fora maximum of 45 min without medical provocation (‘WestminsterProtocol’). RESULTS: Suspected neurally mediated syncope could be reproduced by tilttesting in four of 39 patients from group A vs 10 of 41 patientsfrom group B (10% vs 24%, P=0·1). Independent of theresult of head-up tilt testing, all patients were prospectivelyfollowed without medical therapy. During 23±8 monthsfollow-up, syncope recurred in four of 39 group A patients vs22 of 41 group B patients (10% vs 54%, P<0·05). Theincidence of syncope during follow-up was not significantlydifferent between patients with and without positive baselinetilt test (43% vs 30%, P=ns). CONCLUSIONS: (1) 90% of patients with a single episode of syncope remainfree of recurrent syncope without medical therapy irrespectiveof the result of tilt testing. (2) About half of patients witha history of 2 syncopal episodes have recurrent syncope and,thus, may be appropriate candidates for prophylactic medicaltherapy. (3) Although head-up tilt testing at 60° for upto 45 min does not appear to be useful to predict recurrentsyncope in untreated patients, it is still a useful test inits evaluation.     

直立倾斜试验联合心率变异性及核素脑血流测定对血管迷走性晕厥诊断及评估预后价值研究

特发性晕厥中以血管迷走性晕厥(VVS)最常见。目前认为VVS的发病机制与自主神经功能紊乱有关。心率变异性(HRV)是目前评估自主神经功能的重要手段。直立倾斜试验(HUTT)是目前公认的诊断VVS准金标准,本研究通过建立HUTT模     

The incidence of malignant vasovagal syndrome in patients with recurrent syncope

We reviewed 322 patients with recurrent syncope between 1984 and 1988. Investigation included limited intracardiac electrophysiological study in all cases with programmed extra-stimulus studies in 48 cases. In 93 patients (29%), all investigations were normal, (including negative extrastimulus in 30). In the other 229 cases syncope was explained by AV-block (n = 111, 34%), sinus node disease (n = 68, 21%), carotid sinus syndrome (n = 32, 10%) and inducible sustained tachyarrhythmia (n = 18, 6%). Prolonged 60 degrees head-up tilt was performed in 71 out of 93 patients with unexplained syncope, and reproduced vasovagal syncope and presenting symptoms in 53 (75%), or 16% of the whole population reported. These patients were diagnosed as having malignant vasovagal syndrome. Positive tilts were significantly less common in a group of 27 subjects of similar age without a history of syncope (7%), and a random sample of 37 patients with atrioventricular block (n = 16), sick sinus syndrome (n = 18) and inducible tachyarrhythmia (n = 3), (19%, 11% and 0% respectively, P less than 0.01). From this retrospective review it appears, therefore, that tilt testing is a valuable provocative tool for vasovagal syncope and may reduce the number of syncopal patients that remain undiagnosed, although these early observations do not allow an exact appraisal of the sensitivity and specificity of the tilt test.     

Reproducibility of head-up tilt test in patients with syncope

As the head-up tilt test (HUT) is employed to verify the efficacy of undertaking a treatment, we prospectively evaluated the reproducibility of positive and negative results, as well as that of the response type in 64 consecutive patients (mean age 34.6 ± 22.9 years) with syncope of unknown cause. Two HUTs (60 min, 75° ), separated by an interval of 9.77 ± 8.21 days, were performed on each patient. Positive responses were reproduced in the second HUT in 54.5% of the patients. A greater reproducibility (84.3%) was observed for negative responses. Of the 31 patients with a negative first test, 5 had a positive response during the second HUT. Using a multivariate analysis, no clinical variable correlated with the reproducibility of positive or negative results. Likewise, neither arterial pressure nor heart rate observed during the test were correlated with reproducibility. Of 18 patients who reproduced positive responses, 12 (66.6%) did so with the same response modality. In three patients with documented monomorphic sustained ventricular tachycardia, which was hemodynamically well tolerated, and in one patient with temporal spike wave activity in the electroencephalogram, HUT was also positive. It was concluded that the low reproducibility of HUT limits its usefulness as a tool for evaluating treatment efficacy. The variability of the type of response suggests a common mechanism leading to cardioinhibitory and vasodepressor reactions. A positive result in only the second study shows the rationale of performing two tests when the first one is negative.     

Impact of age and blood pressure on the lower arterial pressure limit for maintenance of consciousness during passive upright posture in healthy vasovagal fainters: preliminary observations.

Maintenance of consciousness importantly depends on systemic arterial blood pressure (BP) remaining above the lower pressure limit for cerebrovascular autoregulation. This study evaluated the impact of age and baseline arterial blood pressure (BP) on the BP recorded at onset of syncope in otherwise healthy individuals undergoing passive head-up tilt (HUT) testing for suspected vasovagal syncope. Since hypertension is thought to shift the lower autoregulation point to higher values, and since older healthy patients tend to have higher BP than younger individuals, we hypothesized that even among healthy individuals HUT-induced syncope would occur at higher BP in older compared with younger subjects. Three groups of otherwise healthy individuals who had positive HUT were identified: Group 1: <25 years, n=17; Group 2: 25-59 years, n=18; and Group 3: > or =60 years, n=7. As expected, baseline arterial systolic blood pressure of patients > or =60 years (162+/-37 mmHg) was significantly higher than in the other two groups (Group 1: <25 years, 116+/-15 mmHg; Group 2: 25-59 years, 128+/-12 mmHg). Further, the > or =60 age group tolerated upright posture for a longer period before syncope than did younger patients. However, despite a trend for BP at syncope to increase with age, differences were small (Group 3: > or =60 years, 61+/-15 mmHg, Group 2: 25-59 years, 58+/-6 mmHg, and Group 1: 54+/-16 mmHg) and were not statistically significant. Thus, in generally healthy individuals, age and baseline BP has only a minor effect on the lower limit of BP necessary for maintenance of consciousness. On the other hand, higher baseline BP provides older individuals a greater blood pressure 'reserve' for maintenance of consciousness compared with younger subjects.     

Troponin release after exertional vasovagal syncope

Troponin release following exertional vasovagal syncope has not previously been reported. A young man was investigated after being admitted twice with exertional syncope, each time followed by a 10‐fold spike in troponin I over 24 h. Treadmill exercise tests reproduced his symptoms and demonstrated a vasovagal mechanism. During recovery, despite lying supine, he remained hypotensive for 5 min, with profound bradycardia and ST segment depression. We suspected that intense cardiovagal neural activity may have caused the troponin leak.     

Age of first faint in patients with vasovagal syncope

INTRODUCTION: Understanding whether vasovagal syncope is a lifelong disorder might shed insight into its physiology and affect management strategies. Accordingly, we determined the age of the first syncopal spell in adult patients who sought care for syncope. METHODS AND RESULTS: Patients were 42 +/- 18 years old with 64% women. They had had a median 8 syncope spells (interquartile range [IQR]: 4, 20) with a median frequency of 1.0 syncopal spells per year. The range of syncopal spells was 1-3,375, and the range of duration of history of syncope was 0.003-70 years. The first syncopal spell occurred at ages 0-81 in a skewed distribution, with a marked mode age of 13 years, a median age of 18 years (IQR 12, 37), and a mean age of 26 +/- 20 years. The distributions were statistically indistinguishable across countries (P = 0.50), among Canadian regions (P = 0.69), and between the studies (P = 0.49). The same modal values were seen in males and females, and in patients <40 and > or =40 years old. However, patients > or =40 years had median ages of onset older than patients <40 years (36 +/- 23 vs 17 +/- 8 years). Patients had a recalled history of syncopal spells of median duration of 10 years (IQR: 2, 23), with a range of 0.003-70 years. An age of onset <44 years was 86% accurate for vasovagal syncope. CONCLUSION: The most common age at which vasovagal syncope first presents is 13 years, and patients remain at risk of syncope for many years. Lifelong coping strategies may be desirable.     

直立倾斜试验的严重反应类型及其预防和处理

目的总结直立倾斜试验的严重反应及其预防和处理。方法试验的倾斜角度为７５°，最长时间为４５分钟。整个过程中持续心电和血压监测，维持良好的静脉通路。身体用特殊护带保护以防意外。结果共有１８例患者接受了这一检查。其中１０例阳性，５例出现严重反应。５例中２例有颈内动脉粥样硬化，２例有慢性房颤。严重反应类型包括：心脏停搏５秒以上（２例），或严重心动过缓心室率慢于５０／ｍｉｎ达１分钟以上（２例），或严重低血压持续１分钟以上（１例）。所有患者在发生晕厥后立刻放回至平卧位，抬高下肢；心率慢者给阿托品静推。有１例做了胸外心脏按压。所有患者经处理神志很快转清，未发生并发症。结论直立倾斜试验虽然为一项无创性检查，但严重反应并不罕见。严格掌握适应证、术前充分准备和术中密切观察有助于避免意外的发生