Comparison of diagnostic accuracy of sublingual nitroglycerin test and low-dose isoproterenol test in patients with unexplained syncope

Despite the widespread use of head-up tilt testing as a means for diagnosing vasovagal syncope, standardization of test methodology remains a controversial issue. The aim of this study was to compare the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin with that of head-up tilt testing potentiated with low-dose isoproterenol. For this purpose, 71 patients with unexplained syncope (mean age 43 years) and 30 asymptomatic controls were studied. All underwent the sublingual nitroglycerin and low-dose isoproterenol tests on separate days in a randomized fashion. The protocol of the 2 tests was similar and consisted of 2 phases. Initially, subjects were tilted at 60 degrees for 20 minutes without medication; then, if syncope did not occur, patients and controls received sublingual nitroglycerin (300 microg) or low-dose intravenous isoproterenol (mean infusion rate 1.3 +/- 0.5 microg/min) and continued to be tilted at 60 degrees for a further 20 minutes. During the sublingual nitroglycerin test, a positive response (syncope associated with sudden hypotension and bradycardia) occurred in 35 patients (49%), a negative response in 36 (51%), and drug intolerance in none (0%). During the low-dose isoproterenol test, these percentages were 41%, 59%, and 6%, respectively. A concordant response was observed in 53 cases (75%). Among controls, 3 subjects (10%) had a positive response to the sublingual nitroglycerin test and 4 (13%) to the low-dose isoproterenol test. It is concluded that sublingual nitroglycerin and low-dose isoproterenol are equivalent tests for evaluating patients with unexplained syncope. The sublingual nitroglycerin test, however, is simpler, better tolerated, and safer than the low-dose isoproterenol test and, thus, more suitable for routine clinical use.     

Methodology of head-up tilt testing potentiated with sublingual nitroglycerin in unexplained syncope

Shortened head-up tilt testing (HUT) potentiated with sublingual nitroglycerin (60 degrees passive standing for 20 minutes followed, if negative, by 400 microg of sublingual nitroglycerin spray with the test continuing for another 20 minutes) differs from conventional nitroglycerin HUT for a shorter drug-free phase (20 vs 45 minutes). To compare the positivity rate of the 2 protocols, both tests were performed in a randomized sequence in 10 patients with unexplained syncope (study 1), and another 42 patients were randomly assigned either to conventional or to shortened nitroglycerin HUT (study 2). To evaluate the reproducibility of the shortened nitroglycerin HUT, another 38 patients with unexplained syncope underwent 2 consecutive tests within a 7+/-8 day interval (study 3). Finally, to evaluate the specificity of the test, 47 control subjects underwent shortened nitroglycerin HUT (study 4). Seven positive responses were observed during shortened nitroglycerin HUT, and there were 8 positive responses during conventional nitroglycerin HUT (p = NS) in the study 1 group. Fifteen positive (71%) responses, 5 negative responses, and 1 exaggerated response were observed during shortened nitroglycerin HUT; 16 positive (76%, p = NS vs. shortened nitroglycerin HUT), 3 negative, and 2 exaggerated responses were observed during conventional nitroglycerin HUT in the study 2 group. During the first test, 21 patients (55%) had a positive, 15 patients had a negative, and 2 patients had an exaggerated response in study group 3. During the second test, 15 positive (39%), 19 negative, and 4 exaggerated responses were observed. Thus, the reproducibility was 67% for a positive and 94% for a negative test. In control subjects, 2 positive (4%) responses, 38 negative, and 7 exaggerated responses were observed with a specificity of 96% in study group 4. In patients with unexplained syncope, shortened nitroglycerin HUT allowed a positivity rate similar to that of the conventional test. Moreover, the shortened test provided a high specificity and adequate reproducibility for both the positive and the negative responses.     

'Front-loaded' head-up tilt table testing: validation of a rapid first line nitrate-provoked tilt protocol for the diagnosis of vasovagal syncope

Head-up tilt testing is the investigation of choice in the diagnosis of vasovagal syncope. The test is time consuming and labour intensive, with conventional tilt testing taking up to 45 min. We compared a shortened 'front-loaded' 20-min glyceryl trinitrate-provoked head-up tilt (FLGTN-HUT) with the standard 40-min passive tilt (HUT) as first line investigations in patients with unexplained syncope and asymptomatic controls. In the study, 149 consecutive patients with unexplained syncope and 83 asymptomatic controls were enrolled. Subjects were randomly assigned to FLGTN-HUT (800 mcg, metred spray) or HUT, then the opposite tilt-test 1 week later. Seventeen (11.4%) patients had diagnostic haemodynamic changes and symptom reproduction during HUT and 54 (36.2%) during FLGTN-HUT. A total of 24.8% more patients had a positive test with FLGTN-HUT than with passive HUT (95% CI: 16.3%, 33.4%). Nine (10.8%) controls had significant haemodynamic changes during HUT and 23 (27.7%) during GTN provocation. Seven controls had haemodynamic changes on both HUT and FLGTN-HUT testing. The controls group had 16.8% more significant haemodynamic changes with FLGTN-HUT than with HUT (95% CI: 0.06, 27.4). The front-loaded GTN protocol provided a higher diagnostic rate than passive tilt testing, and provides a rapid alternative to conventional methods, though false positivity rates are higher.     

Specificity and total positive rate of head-up tilt testing potentiated with sublingual nitroglycerin in older patients with unexplained syncope

The aim of this study was to assess the specificity and total positive rate of head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin in detecting the vasovagal origin of unexplained syncope in the elderly, since the diagnostic value of this non-invasive test has not yet been proven in this age group. In a period of 3 years, 128 elderly patients (mean age 71.6+/-5.1 years, 50% males) with syncope of unknown origin, and 101 control subjects matched for age and gender were tilted upright to 60 degrees for 45 minutes. If syncope did not occur, sublingual nitroglycerin (0.4 mg) was administered, and observation was continued for 20 minutes. The positive response was defined as the reproduction of syncope or pre-syncope according to VASIS definition. During the unmedicated phase, syncope occurred in 26 patients (20.3%) and in no members of the control group. After nitroglycerin, 53 patients (41.4%) and 2 control subjects (2%) displayed syncope. The total positive rate of the test was 61.8% with a specificity of 98.0%. In conclusion, HUTT potentiated with sublingual nitroglycerin provides an adequate specificity and total positive rate in old patients with unexplained syncope; therefore it can be proposed as a useful diagnostic tool to detect the vasovagal origin of syncope not only in middle but also in advanced age.     

Reproducibility of head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope.

Head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin has gained acceptance as means of diagnosing neurally mediated syncope. To evaluate the reproducibility of HUTT potentiated with sublingual nitroglycerin, 48 patients with unexplained syncope prospectively underwent 2 consecutive tests 1 to 28 days apart. The initial test ended in syncope in 34 patients (71%). In 9 patients (19%) the test was positive during the drug-free phase, whereas 25 patients (52%) had syncope after nitroglycerin administration. Of these 34 patients with an initial positive test result, 27 (79%) had a reproducible outcome on repeat testing. Of 12 patients (25%) with an initial negative test result, 10 (83%) had a reproducible outcome on repeat testing. Of 2 patients (4%) with a first test ending in exaggerated response, both had a negative repeat test response. The overall reproducibility of sublingual nitroglycerin tilt-table testing was 77%. In a group of 23 patients with both positive tests, 19 (83%) had the same response modality (2 vasodepressor, 4 cardioinhibitory, 13 mixed response). In the same group of patients, individual trough heart rates correlated well with each other between tests. Finally, in the 27 patients with both positive tests, intrapatient time of onset of symptoms did not significantly correlate between tests. Thus, in patients with syncope of unknown origin, HUTT potentiated with sublingual nitroglycerin provides an adequate reproducibility when repeated on different days.     

Tilt testing potentiated with sublingual nitroglycerin in children with unexplained syncope: reply

We really appreciate Dr Jastrzebska-Maj et al.'s interest inour work, dealing with the diagnostic management of childrenwith unexplained syncope.¹ Head-up tilt testing (HUT) potentiatedwith sublingual nitroglycerin (NTG) is an accepted examinationin     

'The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope.

Head-up tilt testing potentiated by sublingual nitroglycerin (NTG), advocated by an Italian group, is a simple and safe but still not a standardized, diagnostic tool for the investigation of syncope. In fact, owing to its rapid spread, the original protocol received, often arbitrarily, many subsequent modifications. We now define the best methodology of the test on strictly evidence-based criteria as: stabilization phase of 5 min in the supine position; passive phase of 20 min at a tilt angle of 60 degrees; provocation phase of further 15 min after 400 micrograms NTG sublingual spray. Test interruption is made when the protocol is completed in the absence of symptoms, or there is occurrence of syncope, or occurrence of progressive (> 5 min) orthostatic hypotension. We intend that this protocol, named by us as 'The Italian Protocol', will be accepted as the standard methodology of the tilt test potentiated by sublingual nitrates.     

Usefulness and safety of shortened head-up tilt testing potentiated with sublingual glyceryl trinitrate in older patients with recurrent unexplained syncope

OBJECTIVES: To evaluate the sensitivity and tolerability of shortened, glyceryl trinitrate (GTN)-potentiated, head-up tilt test (HUT) in patients older and younger than 65 with unexplained syncope and to compare the specificity of GTN-potentiated HUT (GTN-HUT) in older and younger controls. DESIGN: Methodological study. SETTING: Syncope units in secondary and tertiary hospitals. PARTICIPANTS: Three hundred twenty-four consecutive patients with unexplained syncope (100 aged > or =65 (mean age +/- standard deviation 73 +/- 6; 35 men) and 224 aged <65 (41 +/- 15; 111 men)) and 64 controls (29 aged > or =65 (73 +/- 6; 13 men) and 35 aged <65 (42 +/- 13; 16 men)). INTERVENTION: Patients and controls were tilted upright to 60 degrees for 20 minutes. If syncope did not occur, sublingual GTN (400 microg) was administered and 60 degrees HUT was continued for 15 minutes. Responses were classified as positive, negative, or exaggerated (slow decrease in blood pressure with a slight decrease in heart rate after GTN). MEASUREMENTS: Electrocardiogram and arterial pressure were monitored continuously. RESULTS: GTN-HUT was positive in 60% and 66% (NS), negative in 29% and 33% (NS), and exaggerated in 11% and 1% (P <.001) of older and younger patients, respectively. In older and younger controls, the GTN-HUT was negative in 70% and 86% and exaggerated in 28% and 9% of cases, respectively, (P <.05). The overall specificity (considering as negative also the exaggerated responses) was 97% in older and 94% in younger subjects. No patient or control experienced serious side effects. CONCLUSION: The shortened GTN-HUT provides satisfactory positivity rate and specificity in older patients. This test may be considered as a diagnostic tool in assessing recurrent unexplained syncope in older patients.     

倾斜试验对原因不明晕厥诊断价值的探讨

对２１例原因不明晕厥患者（晕厥组）行倾斜试验并以正常人作对照（正常对照组）。晕厥组基础倾斜试验阳性９例（４２．９％），多阶段异丙肾上腺素－倾斜试验阳性１０例（８３．０％），总阳性率为９０．５％（１９／２１）。对照组基础倾斜试验无一例阳性，与晕厥组比较，Ｐ＜０．００１；多阶段异丙肾上腺素－倾斜试验有２例为阳性，假阳性率１０％。结果显示：倾斜试验采用倾斜８０°、持续４５ｍｉｎ、异丙肾上腺素用量为４～６μｇ／ｍｉｎ，对不明原因晕厥的诊断，其敏感性为９０．５％、特异性为９０％、准确性为９０．２％。倾斜试验是诊断血管迷走性晕厥、指导临床治疗的一种有价值的方法。     

舌下含服硝酸甘油直立倾斜试验对血管迷走性晕厥的诊断价值

为寻找使用方便、省时、耐受性良好的倾斜方案 ,将不明原因晕厥者 91例、无晕厥史者 5 2例 (对照 )分别随机分为异丙肾上腺素组 (A组 ,患者 45例、对照 2 6例 )和硝酸甘油组 (B组 ,患者 46例、对照 2 6例 )。每组首先行 70°30min的基础倾斜试验 (BHUT) ,若为阴性则加用药物激发。A组在BHUT结束后将倾斜床放回水平位 ,静脉注射异丙肾上腺素 (剂量 3μg/min) 5min ,再次倾斜 70° 10min。B组在BHUT结束后同一倾斜角度给予硝酸甘油 0 .2mg舌下含服 ,持续倾斜 2 0min。结果 :A组BHUT阳性率为 11.1% (5 / 45 ) ,加用药物后阳性率为 42 .2 % (19/ 45 ) ;总敏感性5 3 .3 %、特异性 88.5 % ;3例 (6 .7% )出现胸闷、胸痛不能耐受试验。B组BHUT阳性率为 10 .9% (5 / 46 ) ,加用药物后阳性率为 45 .7% (2 1/ 46 ) ;总敏感性 5 6 .5 %、特异性 92 .3%。结论 :含服硝酸甘油激发试验具有良好的敏感性和特异性 ,且使用方便、省时、耐受性好 ,可做为诊断血管迷走性晕厥的常规方法。     

Tilt testing in neurocardiogenic syncope: isosorbide versus isoproterenol

OBJECTIVE: To compare the diagnostic value of pharmacological stimulation with sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing in patients with neurocardiogenic syncope and with a negative tilt test without pharmacological provocation. METHODS AND RESULTS: One hundred and twenty patients with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt (HUT). Those who did not develop syncope or presyncope during passive HUT for 30 minutes underwent repeated HUT with isoproterenol infusion at 4 microg/min (ISOP HUT), for 10 minutes, and, subsequently, were tilted after sublingual administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes. ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively. Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70% (95% C.I. 55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and 88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to 84.6%). There were fewer side effects during ISDN HUT. CONCLUSION: Sublingual isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients with suspected neurocardiogenic syncope and with a negative tilt test without provocation. The low rate of side effects and the higher accuracy of ISDN HUT, along with the simplicity of this challenge compared to ISOP HUT, suggest that sublingual isosorbide dinitrate should be preferred as a provocative agent to evaluate neurocardiogenic syncope after a negative passive tilt test.     

Tilt test in elderly patients with syncope of unknown etiology: experience with pharmacological stimulation with nitroglycerin.

The importance of head-up tilt testing has been demonstrated in the evaluation of patients with unexplained syncope. In elderly patients, the prevalence of syncope increases, is associated with a worse outcome and frequently requires several complementary tests. OBJECTIVES: To evaluate the utility of head-up tilt testing with sublingual nitroglycerin as a provocative agent, in elderly patients with unexplained syncope. METHODS: We studied 46 consecutive patients aged >65 years (74 +/- 6 years, 56.5% female) with unexplained syncope. In 25 patients (54%), we found no cardiac anomaly. The remaining patients had hypertensive (14 patients) or ischemic (7 patients) heart disease. The protocol included carotid sinus massage in decubitus and after passive orthostatism. Tilt testing was performed with continuous electrocardiographic and blood pressure monitoring, at a 70 degrees tilt for 20 minutes. In the absence of syncope, we administered 500 mcg of nitroglycerin with an additional 20 minutes monitoring. The tilt test was considered positive when there was reproduction of symptoms associated with bradycardia and/or arterial hypotension (cardioinhibitory, vasodepressor or mixed response). We considered orthostatic hypotension to be present when systolic blood pressure decreased by >20 mmHg or diastolic blood pressure decreased by >10 mmHg during the first 3 minutes after orthostatism; patients with symptoms associated with a progressive and parallel decrease of systolic and diastolic blood pressure during passive tilt testing were considered to have a dysautonomic profile; patients with symptoms and a gradual decrease of blood pressure after nitroglycerin were considered to have an exaggerated response to nitrates. RESULTS: Symptoms were reproduced in 34 patients (73.9%): 19.6% during passive tilting (neurocardiogenic vasodepressor response--3 patients, carotid sinus hypersensitivity--1 patient, orthostatic hypotension--1 patient, dysautonomic profile--4 patients) and 54.3% after nitroglycerin (neurocardiogenic vasodepressor response--12 patients, mixed--5 patients, cardioinhibitory--2 patients and exaggerated response to nitrates--6 patients). Syncope was neurocardiogenic in 47.8% (passive test--13.6%, after nitroglycerin--86.4%). There was an exaggerated response to nitrates in 16.2% of the patients given nitroglycerin. There were no complications during the test. CONCLUSIONS: Tilt testing in the elderly with syncope of unknown origin: (1) helps differential diagnosis in etiological study of the syncope and (2) when potentiated by nitroglycerin, it produces a significant increase in positive responses, and identifies a considerable number of patients with an exaggerated response to nitrates.     

Single-stage adenosine tilt testing in patients with unexplained syncope

INTRODUCTION: We previously have shown that a 3-minute single-stage adenosine tilt test has a diagnostic yield comparable to a two-stage protocol consisting of a 30-minute drug-free tilt followed by a 15-minute isoproterenol tilt. In this study, we sought to further define the clinical utility of adenosine tilt testing in patients with unexplained syncope by prospectively evaluating test specificity and determining predictors of a positive test response. METHODS AND RESULTS: The specificity of single-stage adenosine tilt testing was determined using 30 control subjects. To determine the diagnostic yield of this protocol, adenosine tilts were performed in 129 patients with unexplained syncope. The adenosine tilt test protocol had high specificity (100%) but a low overall diagnostic yield (18%). However, the yield was affected significantly by age. In patients /=65 years of age (2/41 patients [5%], P < 0.0001). CONCLUSION: These data support single-stage adenosine tilt testing in patients 40 years of age is low, suggesting that the clinical utility of this protocol is limited in these patients.     

Head-up tilt testing for diagnosing vasovagal syncope: A meta-analysis

Background

A systematic evaluation focused on sensitivity and specificity of head-up tilt testing (HUT) for diagnosing vasovagal syncope has not been previously performed. We conducted a meta-analysis of studies comparing HUT outcome between patients with syncope of unknown origin and control subjects without previous syncope.

Methods

We searched Pubmed and Embase databases for all English-only articles concerning case-control studies estimating the diagnostic yield of HUT, and selected 55 articles, published before March 2012, including 4361 patients and 1791 controls. The influence of age, test duration, tilt angle, and nitroglycerine or isoproterenol stimulation on tilt testing outcome was analyzed.

Results

Head-up tilt testing demonstrated to have a good overall ability to discriminate between symptomatic patients and asymptomatic controls with an area under the summary receiver-operating characteristics curve of 0.84 and an adjusted diagnostic odds ratio of 12.15 (p < 0.001). A significant inverse relationship between sensitivity and specificity of tilt testing for each study was observed (p < 0.001). At multivariate analysis, advancing age and a 60° tilt angle showed a significant effect in reducing sensitivity and increasing specificity of the test. Nitroglycerine significantly raised tilt testing sensitivity by maintaining a similar specificity in comparison to isoproterenol.

Conclusions

The results from this meta-analysis show the high overall performance of HUT for diagnosing vasovagal syncope. Our findings provide useful information for evaluating clinical and instrumental parameters together with pharmacological stressors influencing HUT accuracy. This could allow the drawing of tilt testing protocols tailored on the diagnostic needs of each patient with unexplained syncope.     

The Changes of Baroreflex Sensitivity During Head - up Tilt Test and Its Clinical Significance in the Patients with Vasovagal Syncope

Objective To study thechanges of baroreflex sensitivity (BRS) during head - up tilt test (HUT) in patients with vasovagal syncope (VS), and to examine the relationship between baroreflex sensitivity and neurohormonal factors. Furthermore, to investigate the effects of the changes of BRS on VS. Methods Forty - two patients with unexplained syncope (Among the 42 patients, there were 22 patients with positive HUT and 20 patients with negative HUT respectively) and 20 healthy volunteers (with negative HUT) underwent passive head - up tilt testing, Ante-cubital vein blood samples were taken before and after HUT, or at syncope. The fasting plasma endothelin , serum nitric oxide (NO), serum NE were measured, the BRS was assessed on the basis of the linear regression slope the RR interval versus systolic arterial blood pressure during the increment in blood pressure after intravenous administration of phenylephrine. Results (1) During the syncope, the BRS significantly reduced in HUT( + ) group than baseline. At     

血管迷走性晕厥三种反应类型的心率变异分析

目的对倾斜试验(HUT)中三种不同反应类型的血管迷走性晕厥(VVS)患者进行心率变异分析(HRV)，探讨其不同的发病机制。方法54例不明原因晕厥患者倾斜75度进行持续45min的基础倾斜试验(BHUT)或只到发生晕厥，阴性患者于BHUT结束时恢复到平卧位，含服硝酸甘油0．3mg，然后倾斜75度进行持续20min的硝酸甘油诱导的倾斜试验(NTHUT)或只到发生晕厥，试验过程中进行间隔3min的心率变异分析。结果VVS患者中，血管抑制型(VD)和心脏抑制型(CI)均为8例，阳性率为14．8l％；混合型(MX)10例，阳性率为18．52％。倾斜75度后三组VVS患者的LFn值均增大，HFn值均减小；晕厥前3min时三组VVS的LFn值均升至最高，HFn值降至最低；晕厥时三组VVS患者的LFn值与晕厥前3min相比明显下降，但与倾斜前相比无明显差异；CI和MX组的HFn值与晕厥前3min相比明显增高，与倾斜前相比变化不大，VD组的HFn值与晕厥前3min相比无明显差异；未晕厥组在HUT过程中交感神经活性逐渐增大，试验结束时达到最大，迷走神经活性逐渐减小，试验结束时达到最小。结论VVS的发生与自主神经功能障碍有关，不同类型的VVS患者具有不同的神经调节障碍。     

Age and gender differences in basal and isoprenaline protocols for head-up tilt table testing.

AIMS: Syncope is a common occurrence, the prevalence of which increases with age, and among the multiple causes of syncope, neurally mediated syncope is thought to be a frequent cause in the young and in the elderly. Head-up tilt table testing (HUT) has become the diagnostic test of choice for neurally mediated syncope, the response to which varies clearly with age. The purpose of this study is to report the differences among patients suffering syncope referred for HUT, and the influence of age and gender on HUT results (percentage of positive responses and response patterns) in two study protocols (basal and isoprenaline). METHODS AND RESULTS: One thousand, two hundred and nineteen patients with syncope were referred to the authors' Cardiology Department for HUT from September 1990 to April 2000; 1061 undergoing basal HUT (Group A) and 158 undergoing isoprenaline tilt table testing (Group B). Complications were noted in neither protocol. Females were more frequent among young people, and males in the elderly (P<0.05). Head-up tilt table testing was abnormal in 259 (24.4%) patients in Group A and in 85 (53.7%) patients in Group B (P<0.05), and no gender differences were observed. The positive rate of tests in men and women significantly declined with age in Group A (P<0.05), but not in Group B (P=ns). There were no differences in the patterns of haemodynamic collapse in both groups. CONCLUSIONS: In the study of syncope, basal HUT has a high positive rate in young people; a decrease in positive rate with age suggests, however, the need for using another protocol with a similar diagnostic accuracy in the elderly.     

Head-up tilt testing potentiated with oral nitroglycerin: a randomized trial of the contribution of a drug-free phase and a nitroglycerin phase in the diagnosis of neurally mediated syncope.

BACKGROUND: Since the pharmacological challenge with nitroglycerin (NTG) follows the initial drug-free phase in current tilt testing protocols, the effects of nitroglycerin alone and the appropriate duration of the basal phase are unknown. METHODS: To optimize the test, a randomized intra-patient comparison of two protocols was undertaken: a conventional nitroglycerin test (cHUT) consisting of passive upright posture at 60 degrees for 45 min followed, if negative, by sublingual NTG 0.4 mg spray, with the test continued for 20 min; and, accelerated nitroglycerin test (aHUT) consisting of passive upright posture at 60 degrees for 5 min--to rule out orthostatic hypotension--followed by sublingual NTG 0.4 mg spray, with the test continued for 20 min. Eighty-four consecutive patients (33 males; mean age 55+/-22) with unexplained syncope underwent both cHUT and aHUT in a randomized sequence with a 24-72 h interval between them. Additionally, 25 age-matched control subjects underwent aHUT. RESULTS: In the drug-free phase, cHUT was positive in 15/84 patients (18%) and aHUT in 1/84 patients (1%). After NTG, cHUT and aHUT showed the same positivity rate of 33% (28/84 patients). The overall positivity rate was therefore higher with cHUT than with aHUT (51% vs 35%, P=0.04). Times to syncope were 29+/-12 min, (range 2-44) for cHUT drug-free phase, 5+/-2 min (range 2-9) for cHUT NTG phase, and 5+/-2 min (range 2-9) for aHUT. Only one (4%) of the control subjects had a positive response to aHUT. CONCLUSIONS: The contribution of NTG to the diagnosis is independent of the presence of an unmedicated phase. The appropriate duration of the NTG phase is 10 min. aHUT has good specificity, but a positivity rate lower than cHUT; thus a drug-free phase is necessary to increase the sensitivity of the test.     

Head-up tilt test without intravascular cannulation in children and adolescents

Previous studies of head-up tilt test have shown that testing at high degrees lacks specificity in children. We suspected that the high false positive rate might be related to the intravascular catheter and other maneuvers incorporated in the test and therefore studied the sensitivity and specificity of standing and HUT at 80 degrees without any invasive procedure and other maneuvers in children and adolescents. Twenty three patients (11.8+/-2.7 years) with recurrent typical neurally mediated syncope and 35 normal control children (11.6+/-3.0 years) underwent motionless standing for 15 min and tilting to 80 degrees for 30 min. Continuous finger arterial pressure monitoring and ECG were performed during the test. Eight (35%) of the 23 patients developed symptoms of near syncope during motionless standing. Thirteen (57%) of them had positive results at 80 degrees tilting for 30 min. The symptoms of syncope were not always corresponding to excessive haemodynamic changes. None of the controls developed any symptoms or excessive hemodynamic changes. Without intravascular instrumentation and other autonomic maneuvers, active motionless standing or HUT at 80 degrees for 30 min is highly specific but of limited sensitivity for the investigation of vasovagal syncope.     

Comparing two different protocols for tilt table testing: sublingual glyceryl trinitrate versus isoprenaline infusion

OBJECTIVE: To assess the diagnostic value and safety of sublingual glyceryl trinitrate tilt testing compared with isoprenaline infusion in patients with unexplained syncope. DESIGN: Glyceryl trinitrate and isoprenaline tilt tests were performed in two successive days on a random basis in cases and controls. SETTING: Outpatient cases with syncope referred to Shahid Rajaii Heart Hospital. SUBJECTS: 65 consecutive patients with unexplained syncope after thorough work up; 20 healthy volunteers. RESULTS: Positive responses were observed in 20 patients during the passive phase. Of the other 45 patients, positive responses occurred in 25 cases during the glyceryl trinitrate phase and in 26 cases during the isoprenaline phase. In the control group, positive responses during the passive, glyceryl trinitrate, and isoprenaline phases occurred in one, one, and two cases, respectively. The sensitivity and specificity of the protocols were 55% and 94.7%, respectively, for glyceryl trinitrate v 58% and 89.4% for isoprenaline. Owing to discordant responses in 75% of the cases, the sequential use of the tests (if one was negative) would increase the sensitivity to 84% while decreasing the specificity slightly (to 84%). Side effects were less frequent with glyceryl trinitrate. CONCLUSIONS: Sublingual glyceryl trinitrate tilt testing is an effective and safe alternative to the isoprenaline infusion test and can be used as a complementary test.