Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation.

AIMS: Left ventricular (LV) and biventricular (BiV) pacing are potentially superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. METHODS AND RESULTS: Prospective randomized, single-blind, 3-month crossover comparison between RV and LV pacing (phase 1) and between RV and BiV pacing (phase 2) performed in 56 patients (70+/-8 years, 34 males) affected by severely symptomatic permanent atrial fibrillation, uncontrolled ventricular rate, or heart failure. Primary endpoints were quality of life and exercise capacity. Compared with RV pacing, the Minnesota Living with Heart Failure Questionnaire (LHFQ) score improved by 2 and 10% with LV and BiV pacing, respectively, the effort dyspnoea item of the Specific Symptom Scale (SSS) changed by 0 and 2%, the Karolinska score by 6 and 14% (P<0.05 for BiV), the New York Heart Association (NYHA) class by 5 and 11% (P<0.05 for BiV), the 6-min walked distance by 12 (+4%) and 4 m (+1%), and the ejection fraction by 5 and 5% (P<0.05 for both). BiV pacing but not LV pacing was slightly better than RV pacing in the subgroup of patients with preserved systolic function and absence of native left bundle branch block. Compared with pre-ablation measures, the Minnesota LHFQ score improved by 37, 39, and 49% during RV, LV, and BiV pacing, respectively, the effort dyspnoea item of the SSS by 25, 25, and 39%, the Karolinska score by 39, 42, and 54%, the NYHA class by 21, 25, and 30%, the 6-min walking distance by 35 (12%), 47 (16%), and 51 m (19%) and the ejection fraction by 5, 10, and 10% (all differences P<0.05). CONCLUSIONS: Rhythm regularization achieved with AV-junction ablation improved quality of life and exercise capacity with all modes of pacing. LV and BiV pacing provided modest or no additional favourable effect compared with RV pacing.

Management of patients with syncope referred urgently to general hospitals.

OBJECTIVE: To evaluate the incidence and the strategy of management of syncope admitted urgently to a general hospital. BACKGROUND: The management of patients with syncope is not standardized. METHODS: The study was a prospective observational registry from a sample of 28 general hospitals in Italy and enroled all consecutive patients referred to their emergency rooms from November 5th 2001 to December 7th 2001 who were affected by transient loss of consciousness as the principal symptom. RESULTS: The incidence of syncope was 0.95% (996 of 105,173 patients attending). Forty-six percent were hospitalized, mostly in the Department of Internal Medicine. The mean in-hospital stay was 8.1+/-5.9 days. A mean of 3.48 tests was performed per patient. A definite diagnosis was made in 80% of cases, neurally-mediated syncope being the most frequent. The findings of each of the 28 hospitals participating in the survey were separately evaluated. We observed great inter-hospital and inter-department heterogeneity regarding the incidence of emergency admission, in-hospital pathways, most of the examinations performed and the final assigned diagnosis. For example, the execution of carotid sinus massage ranged from 0% in one hospital to 58% in another (median 12.5%); tilt testing ranged from 0 to 50% (median 5.8%); the final diagnosis of neurally-mediated syncope ranged from 10 to 78.6% (median 43.3%). CONCLUSION: Great inter-hospital and inter-department heterogeneity in the incidence and management of syncope was observed in general hospitals. As a consequence, we were unable to describe a uniform strategy for the management of syncope in everyday practice.

Management of syncope referred urgently to general hospitals with and without syncope units.

OBJECTIVE: We tested the hypothesis that management of patients with syncope admitted urgently to a general hospital may be influenced by the presence of an in-hospital structured syncope unit. BACKGROUND: The management of syncope is not standardized. Methods We compared six hospitals equipped with a syncope unit organized inside the department of cardiology with six matched hospitals without such facilities. The study enroled all consecutive patients referred to the emergency room from 5 November 2001 to 7 December 2001 who were affected by transient loss of consciousness as their principal symptom. RESULTS: There were 279 patients in the syncope unit hospitals and 274 in the control hospitals. In the study group, 30 (11%) patients were referred to the syncope unit for evaluation. In the study group, 12% fewer patients were hospitalized (43 vs 49%, not significant) and 8% fewer tests were performed (3.3+/-2.2 vs 3.6+/-2.2 per patient, not significant). In particular, the study group patients underwent fewer basic laboratory tests (75 vs 86%, P=0.002), fewer brain-imaging examinations (17 vs 24%, P=0.05), fewer echocardiograms (11 vs 16%, P=0.04), more carotid sinus massage (13 vs 8%, P=0.03) and more tilt testing (8 vs 1%, P=0.000). In the study group, there was a +56% rate of final diagnosis of neurally mediated syncope (56 vs 36%, P=0.000). CONCLUSION: Although only a minority of patients admitted as an emergency are referred to the syncope unit, overall management is substantially affected. It is speculated that the use of a standardized approach, such as that typically adopted in the syncope unit, is able to influence overall practice in the hospital.

A standardized conventional evaluation of the mechanism of syncope in patients with bundle branch block.

BACKGROUND: The finding of bundle branch block in patients with syncope suggests that paroxysmal AV block may be the cause of syncope, even though its prevalence is unknown. METHODS: We evaluated 55 consecutive patients with syncope and bundle branch block (mean age 75 +/- 8 years; median of two syncopal episodes per patient) referred to three Syncope Units. The hierarchy and appropriateness of diagnostic tests and the definitions of the final diagnoses followed standardized predefined criteria. RESULTS: Cardiac syncope was diagnosed in 25 patients (45%): AV block in 20, sick sinus syndrome in 2, sustained ventricular tachycardia in 1, aortic stenosis in 2. Neurally mediated syncope was diagnosed in 22 (40%): carotid sinus syndrome in 5, tilt-induced syncope in 15, adenosine-sensitive syncope in 2. Syncope remained unexplained in 8 (15%). CONCLUSIONS: Less than half of the patients with bundle branch block have a final diagnosis of cardiac syncope; in these patients, paroxysmal AV block is the most frequent but not the only mechanism supposed.

The application of a standardized strategy of evaluation in patients with syncope referred to three syncope units.

BACKGROUND: The appropriate diagnostic work-up of patients with syncope is not well defined. We applied the guidelines of Italian 'Associazione Nazionale Medici Cardiologi Ospedalieri' to a group of consecutive patients with syncope referred to three Syncope Units. The aim of the study was to evaluate the applicability of those guidelines in the 'real world' and their impact on the use of the tests. METHODS: We evaluated 308 consecutive patients with syncope (mean age 61 +/- 20 years; median of three syncopal episodes per patient). The hierarchy and appropriateness of diagnostic tests and the definitions of the final diagnosis followed standardized predefined criteria. In brief, all patients underwent initial evaluation consisting of history, physical examination, supine and upright blood pressure measurement and standard electrocardiogram (ECG) (only in patients > 45 years or with history of heart disease). Any subsequent investigations were based on the findings of the initial evaluation. Priority was given to cardiological tests (prolonged ECG monitoring, exercise test, electrophysiological study), or to neurally mediated tests (carotid sinus massage, tilt test, ATP test), or to neuro-psychiatric tests, as appropriate. FINDINGS: The initial evaluation alone was diagnostic in 72 patients (23%). One further test was necessary for diagnosis in 65 patients (21%), > or = 2 tests in 64 (21%) and > or = 3 tests in 50 (16%). The diagnostic yield was 10% for ECG, 3% for echocardiogram, 16% for Holter, 5% for exercise test, 27% for electrophysiological study, 57% for carotid sinus massage, 52% for tilt testing and 15% for ATP test. At the end of the work-up the mechanism of syncope remained unexplained in 57 patients (18%). CONCLUSIONS: When standardized criteria based on the appropriateness of indications are used, few simple tests are usually needed for diagnosis of syncope.

Transthoracic and transesophageal echocardiographic indices predictive of sinus rhythm maintenance after cardioversion of atrial fibrillation: an echocardiographic study during direct current shock.

BACKGROUND: Up to 57% of atrial fibrillation (AF) recurrences after cardioversion take place during the first 30 days following direct current shock (DCS) delivery. Previous echocardiographic studies on sinus rhythm (SR) maintenance after cardioversion have focused mainly on parameters recorded before DCS, while other studies have reported on the indices recorded soon after delivery of the shock. METHODS: Therefore, we investigated 18 patients with nonrheumatic AF, selected to undergo DCS, by both transthoracic (TTE) and transesophageal (TEE) echocardiography performed within 10 minutes before and after the electrical shock delivery. TTE was utilized for the evaluation of left atrium and left ventricle shape as well as for mitral Doppler flow sampling, while TEE was used to evaluate left atrial appendage (LAA) morphology and function, to score the LAA spontaneous echo contrast, and to evaluate the flow of left superior pulmonary vein; the transesophageal probe was left in situ during the electrical procedure. Thirty days after cardioversion, 10 (55%) patients maintained SR (Group 1) while 8 (45%) reverted to AF (Group 2). We compared the mean values of the parameters recorded in the two groups both before and after DCS. RESULTS: Although many parameters of pre- and postcardioversion analysis proved to be significantly different between the two groups, the most marked differences were exhibited by the following postcardioversion indices: Peak Doppler flow velocity of the end-diastolic mitral flow (30.10 +/- 5.24 vs. 20.50 +/- 6.32 cm/sec, P = 0.003); sum of peak velocities of the end-diastolic contraction (A) and relaxation (A(1)) of LAA (A + A(1) = 58.20 +/- 17.02 vs. 31.25 +/- 9.27 cm/sec, P = 0.001); duration of A + A(1) (162.70 +/- 27.01 vs. 133.75 +/- 5.31 msec, P = 0.002); and sum of durations of the early diastolic forward (E) and reverse (E(1)) flow of LAA (101.90 +/- 35.15 vs. 53.33 +/- 16.33 msec, P = 0.006). CONCLUSIONS: Using a single echocardiographic examination during DCS and after induction of anesthesia, without further discomfort to patients, we were able to identify useful parameters for the prediction of future electrical activity of the heart before as well as soon after DCS. Postcardioversion indices, derived by both TTE and TEE, were even more predictive of SR maintenance after 1 month than precardioversion parameters.

The vasovagal Syncope and pacing (Synpace) trial: rationale and study design.

BACKGROUND: Though vasovagal syncope probably does not directly cause death, it is often associated with severe trauma and, when recurrent, significantly impairs the patient's quality of life. While drug therapy for vasovagal syncope is still controversial, recently two randomized studies revealed the efficacy of dual-chamber pacemaker implantation in decreasing recurrences in very symptomatic patients. However, since both studies were not placebo-controlled, the benefits observed might have been due to the placebo effect of the pacemaker. AIM OF THE STUDY: The aim of the vasovagal Syncope and pacing (Synpace) trial, a multicentre, prospective, randomized, double-blind, placebo-controlled trial, is to ascertain whether, in patients suffering from recurrent vasovagal syncope, the implantation of a dual-chamber pacemaker with rate drop response algorithm programmed to ON, will reduce syncope relapses compared with the implantation of a pacemaker programmed to OFF. Moreover, in order to evaluate the role of the haemodynamic response during tilt-induced syncope in identifying those patients who will benefit most from pacemaker implantation, enrolled patients will be divided into two groups on the basis of their haemodynamic behaviour during tilt-induced syncope: group 1, asystolic response (development of asystole >3 s), and group 2, mixed response (development of bradycardia <60 bpm, without asystole >3 s). The head-up tilt testing protocol will consist of 20 min at 60 degrees without drug potentiation, followed by 15 min at the same inclination after 400 microg of sublingual nitroglycerin. Results from the two groups will be analysed both separately and globally. The primary clinical endpoint of the study will be syncope. INCLUSION AND EXCLUSION CRITERIA: To be enrolled, patients will have to meet the following criteria: at least six syncopal episodes in the patient's lifetime; positive head-up tilt testing with asystolic or mixed response; at least one syncope recurrence following a positive head-up tilt test. The following constitute exclusion criteria: non-vasovagal syncope; other indications for pacing. SAMPLE SIZE: We hypothesize a risk of syncope recurrence of 70% after one year, and we estimate that--owing to the placebo effect alone--pacemaker will produce a 20% decrease in risk, which corresponds to a 50% risk of recurrence after one year, in those patients randomized to 'pacemaker OFF'. We calculate conservatively a risk decrease of 60% in patients with 'pacemaker ON'. This implies a 10% incidence of syncope recurrence after one year, vs 50% in patients with 'pacemaker OFF'. Fifty patients will need to be enrolled in the study: 25 patients for each group.

Long-term effects of spinal cord stimulation on myocardial ischemia and heart rate variability: results of a 48-hour ambulatory electrocardiographic monitoring.

BACKGROUND: Spinal cord stimulation (SCS) has analgesic properties and may be used to treat pain in patients with therapeutically refractory angina who are unsuitable for myocardial revascularization. Some studies have also demonstrated an anti-ischemic effect. The aim of this study was to evaluate the long-term persistence of the effects of SCS on myocardial ischemia and on heart rate variability. METHODS: Fifteen patients (9 males, 6 females, mean age 76 +/- 8 years, range 58-90 years) with severe refractory angina pectoris (Canadian class III-IV), on optimal pharmacological therapy, unsuitable for myocardial revascularization and treated with SCS for a mean follow-up of 39 +/- 27 months (range 9-92 months) were studied. Eleven patients had had a previous myocardial infarction and 5 a coronary artery bypass graft. The mean ejection fraction was 54 +/- 7% (range 36-65%). All patients underwent 48-hour ambulatory ECG monitoring and were randomly assigned to 24 hours without SCS (off period) and 24 hours with SCS (on period). The primary endpoints were: number of ischemic episodes, total duration of ischemic episodes (min), and total ischemic burden (mV*min). RESULTS: The heart rate was not statistically different during the off and on SCS periods (median 64 and 67 b/min respectively). The number of ischemic episodes decreased from a median of 6 (range 0-29) during the off period to 3 (range 0-24) during the on period (p < 0.05). The total duration of ischemic episodes decreased from a median of 29 min (range 0- 186 min) during the off period to 16 min (range 0-123 min) during the on period (p < 0.05). The total ischemic burden decreased from a median of 2.5 mV*min (range 0-19.5 mV*min) during the off period to 0.8 mV*min (range 0-13 mV*min) during the on period (p = NS). The heart rate variability parameters were similar during the on and off periods. CONCLUSIONS: SCS exerts long-term anti-ischemic effects.

Saphenous vein homograft: a superior conduit for the systemic arterial shunt in the Norwood operation.

BACKGROUND: Excessive pulmonary blood flow increases ventricular volume work in the face of inadequate systemic cardiac output, low diastolic blood pressure, and inadequate coronary perfusion. Using the smallest available 3-mm polytetrafluoroethylene shunts have been successful, although catastrophic shunt thrombosis has occasionally been observed. To avoid thrombosis with a smaller conduit, saphenous vein homografts (SVG) were used to construct the modified Blalock-Taussig (BT) shunts. METHODS: From January 1998 to April 1999, 25 patients weighing 3.1 kg (3.0 kg or less, n = 9), at a mean age of 8.9 days, underwent stage I Norwood using an SVG BT shunt. Common heart defects were aortic atresia (n = 8), mitral atresia and double-outlet right ventricle (n = 5), and unbalanced AVC (n = 5). Mean BT shunt size was 3.2 mm, with 12 patients having shunts that were 3 mm or smaller. RESULTS: Thirty-day hospital mortality was 8% (2 of 25). No shunt thrombosis was seen, despite banding the BT shunt in 3 patients. One patient had BT revision because of an anatomic issue not directly related to the shunt material. CONCLUSIONS: Excellent results may be achieved using SVG BT shunts in the Norwood operation. This conduit seems less likely to thrombose, both acutely and chronically, allowing the use of appropriately smaller-sized shunts in small neonates.

Diagnostic value of history in patients with syncope with or without heart disease.

OBJECTIVES: We sought to establish what historical findings are predictive of the cause of syncope. BACKGROUND: The clinical features of the various types of syncope have not been systematically investigated. METHODS: Three hundred forty-one patients with syncope were prospectively evaluated. Each patient was interviewed using a standard questionnaire. A cause of syncope was assigned using standardized diagnostic criteria. RESULTS: A cardiac cause of syncope was established in 23% of the patients, a neurally mediated cause in 58% and a neurologic or psychiatric cause in 1%, and in the remaining 18%, the cause of syncope remained unexplained. In a preliminary analysis including age, gender and the presence of suspected or certain heart disease after the initial evaluation, only heart disease was an independent predictor of a cardiac cause of syncope (odds ratio 16, p = 0.00001), with a sensitivity of 95% and a specificity of 45%. In contrast, the absence of heart disease allowed us to exclude a cardiac cause of syncope in 97% of the patients. In patients with certain or suspected heart disease, the most specific predictors of a cardiac cause were syncope in the supine position or during effort, blurred vision and convulsive syncope. Significant and specific predictors of a neurally mediated cause were time between the first and last syncopal episode >4 years, abdominal discomfort before the loss of consciousness and nausea and diaphoresis during the recovery phase. In the patients without heart disease, palpitation was the only significant predictor of a cardiac cause. CONCLUSIONS: The presence of suspected or certain heart disease after the initial evaluation is a strong predictor of a cardiac cause of syncope. A few historical findings are useful to predict cardiac and neurally mediated syncope in patients with and without heart disease.

Low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion: results and long-term follow-up.

AIM: Low-energy internal cardioversion is a new electrical treatment for patients with persistent atrial fibrillation. This paper evaluates the efficacy and safety of low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion, and the clinical outcome of such patients. METHOD AND RESULTS: The study population consisted of 55 patients [32 male, mean age 65 +/- 10 years, 48 (87%) with underlying heart disease] with long-lasting (mean 18 +/- 34 months) atrial fibrillation in whom external cardioversion had failed to restore sinus rhythm. Two custom-made catheters were used: one positioned in the right atrium and one in the coronary sinus or the left pulmonary artery. A standard catheter was inserted into the right ventricular apex to provide R wave synchronization. Sinus rhythm was restored in 52 patients (95%) with a mean defibrillating energy of 6.9 +/- 2.6 J (320 +/- 60 V). No complications were observed. During follow-up (mean 18 +/- 9 months), 16 patients (31%) suffered early recurrence (< or = 1 week) of atrial fibrillation and 20 patients (38%) had late recurrence (> 1 week, mean 3.5 +/- 3.6 months) of atrial fibrillation. Six patients with a late recurrence again underwent cardioversion and five of these maintained sinus rhythm. Therefore, a total of 21/52 patients (40%) were in sinus rhythm at the end of follow-up. No clinical difference was found between patients with and without recurrences. CONCLUSIONS: Low-energy internal cardioversion is a useful means of restoring sinus rhythm in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion. More than one-third of patients maintained sinus rhythm during long-term follow-up.

[A new organization model for hemodynamic cardiology diagnosis and intervention cardiology]. / Un nuovo modello organizzativo per la diagnostica cardiologica emodinamica e la cardiologia interventistica.

In centers without hemodynamic laboratories the quality of medical care may be suboptimal since the unavailability of these technologies may reduce medical experience in the treatment of heart disease, mostly in acute coronary syndromes, and may increase the need for referring some patients to other hospitals. The problem will be of great relevance in the case of expansion of the aggressive approach in the treatment of acute ischemic syndromes such as acute myocardial infarction and unstable angina. The impelling need for small centers of improving medical care may promote the spontaneous and uncontrolled proliferation of hemodynamic laboratories. The high number of hemodynamic laboratories may lead to a low institutional volume and, as a consequence, may negatively influence the outcome of coronary intervention and increase health care costs. The experience of operators and the costs are probably more relevant as regards angioplasty than coronary angiography. Therefore we propose the implementation of departments of interventional hemodynamic laboratories including different hospitals: diagnostic laboratories will be allocated in hospitals with coronary care units, while interventional laboratories will be allocated in referring hospitals.

Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized study. The Vasovagal Syncope International Study (VASIS) Investigators.

BACKGROUND-This study was performed to compare implantation of a DDI pacemaker with rate hysteresis with no implant in respect to syncopal recurrences in patients with severe cardioinhibitory tilt-positive neurally mediated syncope. METHODS AND RESULTS-Forty-two patients from 18 European centers were randomized to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19 patients) or no pacemaker (23 patients). Inclusion criteria were >/=3 syncopes over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope International Study types 2A and 2B) response to tilt testing. The median number of previous syncopal episodes was 6; asystolic response to tilt testing was present in 36 patients (86%) (mean asystole, 13.9+/-10.2 seconds). All patients were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean, 3.7+/-2.2). One patient (5%) in the pacemaker arm experienced recurrence of syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In the no-pacemaker arm, the median time to first syncopal recurrence was 5 months, with a rate of 0.44 per year. On repeated tilt testing performed within 15 days after enrollment, positive responses were observed in 59% of patients with pacemakers and in 61% of patients without pacemakers (P=NS). CONCLUSIONS-In a limited, select group of patients with tilt-positive cardioinhibitory syncope, DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the therapy was maintained over the long term. Even in untreated patients, the syncopal recurrence burden was low. A negative result of tilt testing was not a useful means to evaluate therapy efficacy.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

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.