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 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.

Haemodynamic changes early in prodromal symptoms of vasovagal syncope.

AIMS: Vasovagal syncope (VVS) is often preceded by prodromal symptoms. The haemodynamic changes occurring during the prodrome have not been systematically investigated. The aim of the present study was to investigate the behaviour of blood pressure (BP), heart rate (HR) and sympathetic activity at the beginning of the prodrome in patients with tilt-induced VVS. METHODS AND RESULTS: Sixty-three patients with VVS underwent tilt testing. BP and HR were measured and blood samples for plasma catecholamine determination were obtained during the test. Twenty-seven patients developed syncope of whom all had a prodrome. From the last scheduled measurement before prodromal symptoms to the beginning of the prodrome, both systolic and diastolic BP decreased in all patients (from 105 +/- 16 to 74 +/- 20 mmHg, P<0.001, and from 68 +/- 13 to 51 +/- 12 mmHg, P<0 001, respectively) and HR decreased in 18 (67%) (from 89 +/- 22 to 80 +/- 25 beats/ min P<0 02). At the onset of loss of consciousness both BP and HR showed a further decrease (P<0.001). Plasma adrenaline significantly increased from the last sample before prodromal symptoms to the beginning of the prodrome (P<0.01) and showed a further increase during loss of consciousness (P<0.05), whereas plasma noradrenaline did not increase, as an expression of inhibition of sympathetic neural outflow. CONCLUSION: These results demonstrate that in patients with tilt-induced VVS, BP is consistently decreased at the beginning of prodromal symptoms because of the withdrawal of sympathetic activity, and HR is often reduced, probably because of increased vagal activity. We may infer that similar haemodynamic features also occur during spontaneous VVS.

An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation.

AIMS: Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. METHODS AND RESULTS: In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16+/-4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P=0.02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations (P=0.05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. CONCLUSION: Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing.

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.

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.

A semi-automatic algorithm for reducing the time spent on routine follow-up of cardioverter defibrillators.

BACKGROUND: The routine follow-up of cardioverter defibrillators (CD) is a time-consuming procedure. AIM of the STUDY and METHODS: The present study was a prospective randomized cross-over evaluation on the clinical usefulness of a specific semi-automatic software algorithm (Quick Check) for CD follow-up, available in CPI Guidant systems (CD and programmer). Time-saving, while ensuring all the required data and patient safety, was evaluated in a large group of patients (105), recruited in different centers. In the same session and under a physician's supervision all patients underwent a follow-up with the aid of Quick Check or a standard follow-up, in a randomized sequence. Each patient served as his own control. RESULTS: In the overall population of 105 patients, the time spent for follow-up was reduced by Quick Check from 186+/-105 sec to 106+/-67 sec (p<0.0001) (43% reduction). The reduction in time spent for follow-up with Quick Check was the same (43% reduction) in patients with detected episodes (n=38) (from 241+/-144 sec to 138+/-95 sec (p<0.0001)) and in patients without detected episodes (n=67) (from 154+/-52 sec to 88+/-34 sec (p<0. 0001)). No adverse events or deletion of potentially useful data was detected by the supervising physician. CONCLUSIONS: Use of a specific software algorithm for routine follow-up of implanted CDs allows a significant shortening of the time spent on routine follow-up, thus reducing costs. The supervision of a physician is a guarantee of patient safety.

A semiautomated objective technique for applying the proximal isovelocity surface area method to quantitate mitral regurgitation: Clinical studies with the digital flow map.

BACKGROUND: Clinical application of the color Doppler proximal isovelocity surface area (PISA) method to quantify mitral regurgitation (MR) has been limited by the often inaccurate assumption that isovelocity surfaces are hemispheric. This study applied an objective method for selecting the region where the hemispheric geometry holds best on the basis of mathematic analysis of results at different distances from the orifice. We aimed to demonstrate this approach can be applied accurately in the clinical setting and can be semiautomated to promote routine use by extracting velocities from the digital Doppler output and then performing all the calculations automatically. METHODS: In 75 patients with isolated MR, centerline velocities (V(r)) at each distance (r) from the orifice in the proximal flow field were extracted digitally. The automated analysis calculated peak MR flow rates as 2pir(2)V(r) and plotted these against their respective velocities. The optimal value for peak flow rate was obtained mathematically at the site where the slope of this curve was minimal (least inaccuracy). This value was combined with continuous wave Doppler data to provide regurgitant stroke volume (RSV) and orifice area (ROA), which were compared with quantitative Doppler in 75 patients and angiography in 42. RESULTS: RSV and ROA by this optimized, semiautomated PISA method correlated and agreed well with values from quantitative Doppler (y = 0.9x + 1.9, r = 0.90, standard error of the estimate [SEE] = 8.1 mL, mean difference = -0.7 +/- 8.5 mL for RSV; y = 0.9x + 0.02, r = 0.90, SEE = 0.048 cm(2), mean difference = -0.005 +/- 0.1 cm(2) for ROA) and correlated well with angiography (rho = 0.90 for both RSV and ROA). CONCLUSIONS: This objective PISA method for quantifying MR is accurate in the clinical setting and has been semiautomated by use of analysis of digital velocity data to provide a rapid and practical technique suitable to facilitate more extensive application in routine practice.

Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia.

OBJECTIVES: We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes. BACKGROUND: Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT). METHODS: Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long-lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days. RESULTS: Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001). CONCLUSIONS: The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences.

Development of heart failure in bradycardic sick sinus syndrome.

Mounting evidence shows that elevated resting sinus rate is an independent predictor of cardiovascular morbidity and mortality in the general population, in elderly subjects, and in patients with myocardial infarction or hypertension. Therefore, a rather slow sinus rate appears to be a protecting factor acting through several mechanisms. The present contribution focuses on the relationship between sinus rate and heart failure. Its major objectives are to discuss whether in patients with heart failure a rather slow heart rate is advisable and whether a sinus bradycardia secondary to sinus node dysfunction can facilitate the development of heart failure. It has been reported that among patients with left ventricular dysfunction, increased sinus rate was a predictor of cardiovascular death at univariate analysis; however, a multivariate analysis to verify whether sinus rate was an independent predictor of mortality was not performed. Randomized trials carried out by utilizing beta-blockers or amiodarone in patients with heart failure showed that heart rate reduction by these drugs was a marker of their ability to reduce mortality. However, beta-blockers and amiodarone have additional pharmacological effects which interfere with the disease substrate. So, at present, though the results of these trials show that a rather slow sinus rate is advisable, we do not know whether in patients with heart failure sinus rate represents an independent predictor of mortality as in patients with myocardial infarction or hypertension and whether the reduction of sinus rate per se is beneficial. The results of the recent randomized THEOPACE trial showed, for the first time, that in a patient population with symptomatic sinus bradycardia (sinus rate < 50 b/min), an increase in heart rate, induced by DDD pacing or oral theophylline, reduced the incidence of overt heart failure. Therefore, sinus bradycardia seems to play a role in the genesis of heart failure. In a post-hoc analysis of the results of this trial it emerged that in the control (not treated) group, the subjects with sinus bradycardia more prone to develop heart failure were those of old age, about 80 years, with organic heart disease and severe chronotropic incompetence. However, this conclusion needs further validation.

Significance of newly acquired negative T waves after interruption of paroxysmal reentrant supraventricular tachycardia with narrow QRS complex.

Sixty-three patients with paroxysmal supraventricular tachycardia were studied and 25 patients (39%) showed newly acquired negative T waves after tachycardia termination. Silent coronary artery disease could not be found in about 90% of these patients; moreover, age, sex, organic heart disease, and tachycardia duration and rate did not predict the appearance of negative T waves.

Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study.

AIMS: This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm. METHODS AND RESULTS: One hundred and fifty patients with atrial fibrillation or flutter (duration range 2 h-6 months) were given 15-min intravenous infusions of 8 microg. kg(-1)of dofetilide (n=48), 5 mg. kg(-1)of amiodarone (n=50), or placebo (n=52) and monitored continuously for 3 h. Sinus rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0.001, dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more effective in atrial flutter than in atrial fibrillation (cardioversion rates 75% and 22%, respectively;P=0.004). The mean time to conversion with dofetilide was 55+/-15 min. Dofetilide prolonged the QTc interval (+16% at 20 min). Amiodarone substantially decreased the ventricular rate in non-converters (-18 beats. min(-1)at 30 min). Two patients given dofetilide (4%) had non-sustained ventricular tachycardias, and four (8%) had torsade de pointes, in one case requiring electrical cardioversion. CONCLUSION: Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter. However, when infused intravenously at this dose and rate, dofetilide causes a significant incidence of torsade de pointes.

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.

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.

[The tilt test enhanced with oral nitroglycerin in patients with unexplained syncope: the Italian Protocol. The Working Group on Syncope of the Associazione Italiana di Aritmologia e Cardiostimolazione--the Arrhythmia Area of the Associazione Nazionale Medici Cardiologi Ospedalieri]. / Tilt test potenziato con nitroglicerina orale nei pazienti con sincope inspiegata: "Il Protocollo Italiano". Gruppo di Lavoro sulla Sincope AIAC--Area Aritmie ANMCO.

The head-up tilt testing potentiated with oral nitroglycerin, devised by an Italian group, is a simple, safe and powerful, but still not a standardized, diagnostic tool. In fact, owing to its rapid diffusion, the original protocol received, often arbitrarily, subsequent modifications. Thus a task force of experienced cardiologists defined the best methodology for the test on strictly evidence-based criteria. Particular attention was reserved to some controversial topics, such as the tilting angle, the duration of the passive and pharmacological stages of the test, the type and dosage of the drug utilized. We hope that the enclosed protocol, named by us as "The Italian Protocol", will be accepted as the standard methodology of the head-up tilt testing potentiated with oral nitrates.