Attilio Del Rosso

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.

Shortened head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope ☆ ☆☆ ★

BACKGROUND Head-up tilt testing is extensively used to determine the vasovagal origin of syncope in patients with otherwise unexplained loss of consciousness, although issues remain regarding the method of the test. The diagnostic value of a shortened head-up tilt test potentiated with sublingual nitroglycerin was assessed in patients with unexplained syncope. METHODS Two hundred two patients (mean age 49+/-19 years) with syncope of unknown origin and 34 subjects in a control group (mean age 45+/-17 years) were studied. The patients and the subjects in the control group were tilted upright to 60 degrees for 20 minutes. If syncope did not occur, sublingual nitroglycerin (400 microg) was administered, and observation was continued for 25 more minutes. RESULTS During the unmedicated phase syncope occurred in 22 (11%) patients and in one member of the control group. After nitroglycerin was administered, syncope occurred in 119 (59%) patients and in 1 (3%) member of the control group. False-positive response (exaggerated response) was observed in eight (4%) patients and in four (12%) subjects in the control group. The total positivity rate of the test was 70% with a specificity rate of 94%. CONCLUSIONS Short-duration head-up tilt test potentiated with sublingual nitroglycerin provides an adequate specificity and positivity rate in patients with unexplained syncope.

Adenosine-Induced Atrioventricular Block in Patients With Unexplained Syncope The Diagnostic Value of ATP Testing

BACKGROUND ATP and its related nucleoside, adenosine, are ubiquitous biological compounds with potent depressant activity on the atrioventricular node. We hypothesized that an increased susceptibility of the atrioventricular node to adenosine may, in some cases, play a role in the genesis of syncope. METHODS AND RESULTS The study was performed in two parts. In part 1, we evaluated the effects of a bolus injection of 20 mg ATP in a group of 60 patients (57+/-19 years, 31 men) with syncope of unexplained origin and in 90 control subjects without syncope (55+/-17 years, 46 men). In control subjects, the upper 95th percentile of the maximum RR interval distribution, during ATP-induced atrioventricular block (AVB), was 6000 ms. In the syncope group, 28% of patients had a maximum RR interval above this limit (P=.000). The distribution of the maximum RR interval below the 95th percentile was similar in the two groups. In part 2, we validated the ATP test in 24 patients who had the fortuitous ECG recording of a spontaneous syncope caused by a transient asystolic pause (AVB in 15 and sinus arrest in 9). The ATP test caused AVB with an asystolic pause of > or = 6000 ms in 53% of the patients with documented AVB but in none (0%) of the patients with documented sinus arrest (P=.01). Among the patients with spontaneous AVB, the ATP test was abnormal in 6 of the 7 patients (86%) in whom all conventional investigations for syncope had been negative and in 2 of the 8 patients (25%) who had shown positivity (P=.03). CONCLUSIONS An increased susceptibility to ATP testing is present in patients with SUO and patients with syncope due to paroxysmal AVB. Thus, a logical inference is that ATP testing can be used to identify patients with syncope due to paroxysmal AVB. The results of this study form the necessary background for future prospective studies with an aim to validate this assumption.

Diagnosis and Characteristics of Syncope in Older Patients Referred to Geriatric Departments

OBJECTIVES: To test the applicability and safety of a standardized diagnostic algorithm in geriatric departments and to define the prevalence of different causes of syncope in older patients.

Prospective multicentre systematic guideline-based management of patients referred to the Syncope Units of general hospitals

AIMS Although an organizational model for syncope management facilities was proposed in the 2004 guidelines of the European Society of Cardiology (ESC), its implementation in clinical practice and its effectiveness are largely unknown. METHODS AND RESULTS This prospective study enrolled 941 consecutive patients referred to the Syncope Units of nine general hospitals from 15 March 2008 to 15 September 2008. A median of 15 patients per month were examined in each unit, but the five older units had a two-fold higher volume of activity than the four newer ones (instituted <1 year before): 23 vs. 12, P = 0.02. These figures give an estimated volume of 163 and 60 patients per 100,000 inhabitants per year, respectively. Referrals: 60% from out-of-hospital services, 11% immediate and 13% delayed referrals from the Emergency Department, and 16% hospitalized patients. A diagnosis was established on initial evaluation in 191 (21%) patients and early by means of 2.9 +/- 1.6 tests in 541 (61%) patients. A likely reflex cause was established in 67%, orthostatic hypotension in 4%, cardiac in 6% and non-syncopal in 5% of the cases. The cause of syncope remained unexplained in 159 (18%) patients, despite a mean of 3.5 +/- 1.8 tests per patient. These latter patients were older, more frequently had structural heart disease or electrocardiographic abnormalities, unpredictable onset of syncope due to the lack of prodromes, and higher OESIL and EGSIS risk scores than the other groups of patients. The mean costs of diagnostic evaluation was 209 euro per outpatient and 1073 euro per inpatient. The median cost of hospital stay was 2990 euro per patient. CONCLUSION We documented the current practice of syncope management in specialized facilities that have adopted the management model proposed by the ESC. The results are useful for those who wish to replicate this model in other hospitals. Syncope remains unexplained during in-hospital evaluation in more complex cases at higher risk.

Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study

AIMS We evaluated the early (1 month) and late (2 years) death rate and syncopal relapses of patients referred for syncope to 11 general hospitals emergency departments. Patients were enrolled in the Evaluation of Guidelines in SYncope Study 2 (EGSYS 2) study. The guidelines of the European Society of Cardiology were strictly followed in the management of patients. METHODS AND RESULTS Out of the 465 patients enrolled in the EGSYS 2 study, 398 (86%) underwent a complete follow-up. We excluded 18 patients with non-syncopal attacks. Among the remaining 380 patients, death of any cause occurred in 35 (9.2%). The mean follow-up was 614 +/- 73 days. Six deaths (17% of total) occurred during the first month of follow-up. Patients who died were older, had a higher incidence of structural heart disease and/or abnormal ECG, had injuries related to syncope and higher EGSYS score. Syncope recurred in 63 (16.5%) patients. Syncopal relapses occurred in only one patient during the first month of follow-up. The incidence of syncopal recurrences was unrelated to the mechanism of syncope. No clinical differences were found between patients with or without syncopal recurrence and in patients with EGSYS score < or >or=3. CONCLUSION A peak of cardiovascular mortality but not of syncopal recurrences was observed in patients attending to the emergency department for syncope within the first month. Late unfavourable outcomes were caused by associated cardiovascular diseases rather than by the mechanism of syncope. The causes of syncope did not determine the recurrence rate.

Mechanism of syncope in patients with positive adenosine triphosphate tests

OBJECTIVES We prospectively evaluated the mechanism of syncope in patients with positive adenosine triphosphate (ATP) tests (defined as the induction of atrioventricular [AV] block with a ventricular pause >/=6 s after an intravenous bolus of 20 mg ATP). BACKGROUND Patients with unexplained syncope tend to have more positive ATP tests results than those without syncope. METHODS An implantable loop recorder (ILR) was inserted in 36 ATP-positive patients (69 +/- 10 years; 22 women; median of 6 syncopal episodes); 15 of them also had a positive response to tilt testing. RESULTS During the follow-up of 18 +/- 9 months, 18 patients (50%) had syncopal recurrence and 16 (44%) had an electrocardiographically documented episode: AV block (n = 3: paroxysmal in 2 and permanent in 1), AV block followed by sinus arrest (n = 1), sinus arrest (n = 5), sinus bradycardia <40 beats/min (n = 2), normal sinus rhythm (n = 2), sinus tachycardia (n = 1), rapid atrial fibrillation (n = 1), and ectopic atrial tachycardia (n = 1). Bradycardia was documented in a total of 11 cases (69%), and a long ventricular pause (4 to 29 s) was present in eight cases (50%). All three patients with ILR-documented AV block had previously had a negative tilt test, whereas seven of eight with ILR-documented sinus bradycardia or sinus arrest had previously had a positive tilt test. CONCLUSIONS In patients with adenosine-sensitive syncope, the mechanism of syncope is heterogeneous, although bradycardia is the most frequent finding. Adenosine triphosphate-induced AV block predicts AV block as the mechanism of spontaneous syncope in only a few tilt-negative patients.

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.

Diagnosis, management, and outcomes of patients with syncope and bundle branch block

Aims Although patients with syncope and bundle branch block (BBB) are at high risk of developing atrio-ventricular block, syncope may be due to other aetiologies. We performed a prospective, observational study of the clinical outcomes of patients with syncope and BBB following a systematic diagnostic approach. Methods and results Patients with ≥1 syncope in the last 6 months, with QRS duration ≥120 ms, were prospectively studied following a three-phase diagnostic strategy: Phase I, initial evaluation; Phase II, electrophysiological study (EPS); and Phase III, insertion of an implantable loop recorder (ILR). Overall, 323 patients (left ventricular ejection fraction 56 ± 12%) were studied. The aetiological diagnosis was established in 267 (82.7%) patients (102 at initial evaluation, 113 upon EPS, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia–tachycardia (1), and non-arrhythmic (7). A pacemaker was implanted in 220 (68.1%), an implantable cardioverter defibrillator in 19 (5.8%), and radiofrequency catheter ablation was performed in 3 patients. Twenty patients (6%) had died at an average follow-up of 19.2 ± 8.2 months. Conclusion In patients with syncope, BBB, and mean left ventricular ejection fraction of 56 ± 12%, a systematic diagnostic approach achieves a high rate of aetiological diagnosis and allows to select specific treatment.

Syncope risk stratification tools vs clinical judgment: An individual patient data meta-analysis

BACKGROUND There have been several attempts to derive syncope prediction tools to guide clinician decision-making. However, they have not been largely adopted, possibly because of their lack of sensitivity and specificity. We sought to externally validate the existing tools and to compare them with clinical judgment, using an individual patient data meta-analysis approach. METHODS Electronic databases, bibliographies, and experts in the field were screened to find all prospective studies enrolling consecutive subjects presenting with syncope to the emergency department. Prediction tools and clinical judgment were applied to all patients in each dataset. Serious outcomes and death were considered separately during emergency department stay and at 10 and 30 days after presenting syncope. Pooled sensitivities, specificities, likelihood ratios, and diagnostic odds ratios, with 95% confidence intervals, were calculated. RESULTS Thirteen potentially relevant papers were retrieved (11 authors). Six authors agreed to share individual patient data. In total, 3681 patients were included. Three prediction tools (Osservatorio Epidemiologico sulla Sincope del Lazio [OESIL], San Francisco Syncope Rule [SFSR], Evaluation of Guidelines in Syncope Study [EGSYS]) could be assessed by the available datasets. None of the evaluated prediction tools performed better than clinical judgment in identifying serious outcomes during emergency department stay, and at 10 and 30 days after syncope. CONCLUSIONS Despite the use of an individual patient data approach to reduce heterogeneity among studies, a large variability was still present. Current prediction tools did not show better sensitivity, specificity, or prognostic yield compared with clinical judgment in predicting short-term serious outcome after syncope. Our systematic review strengthens the evidence that current prediction tools should not be strictly used in clinical practice.