Factors facilitating and hindering the implementation of the European Society of Cardiology Syncope Guidelines at the Emergency Department: A nationwide qualitative study.

AIMS: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. METHODS AND RESULTS: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. CONCLUSION: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

External prolonged electrocardiogram monitoring in unexplained syncope and palpitations: results of the SYNARR-Flash study.

AIMS: SYNARR-Flash study (Monitoring of SYNcopes and/or sustained palpitations of suspected ARRhythmic origin) is an international, multicentre, observational, prospective trial designed to evaluate the role of external 4-week electrocardiogram (ECG) monitoring in clinical work-up of unexplained syncope and/or sustained palpitations of suspected arrhythmic origin. METHODS AND RESULTS: Consecutive patients were enrolled within 1 month after unexplained syncope or palpitations (index event) after being discharged from emergency room or hospitalization without a conclusive diagnosis. A 4-week ECG monitoring was obtained by external high-capacity loop recorder (SpiderFlash-T(®), Sorin) storing patient-activated and auto-triggered tracings. Diagnostic monitorings included (i) conclusive events with reoccurrence of syncope or palpitation with concomitant ECG recording (with/without arrhythmias) and (ii) events with asymptomatic predefined significant arrhythmias (sustained supraventricular or ventricular tachycardia, advanced atrio-ventricular block, sinus bradycardia <30 b.p.m., pauses >6 s). SYNARR-Flash study enrolled 395 patients (57.7% females, 56.9 ± 18.7 years, 28.1% with syncope, and 71.9% with palpitations) from 10 European centres. For syncope, the 4-week diagnostic yield was 24.5%, and predictors of diagnostic events were early start of recording (0-15 vs. >15 days after index event) (OR 6.2, 95% CI 1.3-29.6, P = 0.021) and previous history of supraventricular arrhythmias (OR 3.6, 95% CI 1.4-9.7, P = 0.018). For palpitations, the 4-week diagnostic yield was 71.6% and predictors of diagnostic events were history of recurrent palpitations (P < 0.001) and early start of recording (P = 0.001). CONCLUSION: The 4-week external ECG monitoring can be considered as first-line tool in the diagnostic work-up of syncope and palpitation. Early recorder use, history of supraventricular arrhythmia, and frequent previous events increased the likelihood of diagnostic events during the 4-week external ECG monitoring.

A2A adenosine receptor function in patients with vasovagal syncope.

AIMS: Adenosine is a possible mediator in vasovagal syncope (VVS) via the activation of its receptors. High expression of adenosine A2A receptors (A2AR) has been reported in VVS. The function of these over-expressed receptors in this population has never been evaluated. METHODS AND RESULTS: We used Adonis, a specific-made antibody with A2AR agonist properties, to evaluate binding parameters (i.e. dissociation constant KD) and cAMP production (i.e. EC50) by peripheral blood mononuclear cells of 16 VVS patients. Eight healthy volunteers served as controls. A2AR expression was higher in patients than controls; mean: 11.5 ± 1.2 vs. 7.7 ± 0.8 AU, P = 0.04. Also, KD values were higher in patients than controls: 2.1 ± 0.02 × 10(-7) vs. 5 ± 1 × 10(-8) M, P < 0.01 In controls, KD values were lower than EC50 (5 ± 1.7 × 10(-8) vs. 2.8 ± 0.4 10(-7) M, P < 0.01), but in patients, KD values did not differ from EC50: 2. ± 0.2 × 10(-7) vs. 2.5 ± 0.4 × 10(-7) M, P > 0.05. However, four patients had lower EC50 (3.5 ± 0.3 × 10(-8) M) than KD (2.9 ± 1.2 × 10(-7) M; KD/EC50 = 9.6), suggesting the presence of spare receptors. CONCLUSION: The function of A2AR of patients with VVS was preserved since their stimulation by Adonis led to cAMP production with an EC50 comparable with those in controls. However, their affinity was lower than those of controls. Our results suggest that A2AR are implicated in the physiopathology of VVS.

At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity.

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well-established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnose CSH are too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitory CSH (asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients with CSH should be thought of as being 'mixed', between cardioinhibition and vasodepression. The proposed stricter set of criteria for CSH should be evaluated in future studies.

Predictors of clinical efficacy of 'Ablate and Pace' therapy in patients with permanent atrial fibrillation.

OBJECTIVE: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design Prospective multicentre observational study. Setting Cardiology departments of 19 general hospitals in Italy, Spain and Greece. PATIENTS: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. RESULTS: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (non-responders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against non-response (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. CONCLUSIONS: In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echo-optimised CRT were the only independent predictor of clinical benefit.

Clinical predictors of cardiac syncope at initial evaluation in patients referred urgently to a general hospital: the EGSYS score.

OBJECTIVE: To develop, in patients referred for syncope to an emergency department (ED), a diagnostic score to identify those patients likely to have a cardiac cause. DESIGN: Prospective cohort study. SETTING: ED of 14 general hospitals. PATIENTS: 516 consecutive patients with unexplained syncope. INTERVENTIONS: Subjects underwent a diagnostic evaluation on adherence to Guidelines of the European Society of Cardiology. The clinical features of syncope were analysed using a standard 52-item form. In a validation cohort of 260 patients the predictive value of symptoms/signs was evaluated, a point score was developed and then validated in a cohort of 256 other patients. MAIN OUTCOME MEASUREMENTS: Diagnosis of cardiac syncope, mortality. RESULTS: Abnormal ECG and/or heart disease, palpitations before syncope, syncope during effort or in supine position, absence of autonomic prodromes and absence of predisposing and/or precipitating factors were found to be predictors of cardiac syncope. To each variable a score from +4 to -1 was assigned to the magnitude of regression coefficient. A score >or=3 identified cardiac syncope with a sensitivity of 95%/92% and a specificity of 61%/69% in the derivation and validation cohorts, respectively. During follow-up (mean (SD) 614 (73) days) patients with score >or=3 had a higher total mortality than patients with a score <3 both in the derivation (17% vs 3%; p<0.001) and in the validation cohort (21% vs 2%; p<0.001). CONCLUSIONS: A simple score derived from clinical history can be usefully employed for the triage and management of patients with syncope in an ED.

Update in the treatment of neurally-mediated syncope.

Syncope is a transient, self-limited loss of consciousness, usually leading to falling. The underlying mechanism is a transient global cerebral hypoperfusion. Since there are many causes of syncope, a specific treatment cannot be administered without knowing of the exact mechanism responsible of loss of consciousness. Drugs are ineffective. The main therapeutic innovations of the most recent years are isometric counter-pressure maneuvres, lower limb compression bandage and therapy guided by implantable loop recorder in patients with recurrent suspected neurally-mediated syncope.

Analysis of rhythm variation during spontaneous cardioinhibitory neurally-mediated syncope. Implications for RDR pacing optimization: an ISSUE 2 substudy.

BACKGROUND: Little is known of the variations of the heart rate during spontaneous cardioinhibitory neurally-mediated syncope. Their knowledge has both academic and practical implications for the optimization of rate drop response (RDR) pacing mode. METHODS AND RESULTS: We describe variations of the rhythm occurring during 48 syncopal episodes documented by implantable loop recorder. The presyncopal phase of 18 s (interquartile range 9-65) was characterized by a fall in heart rate from 83 +/- 20 bpm to maximal bradycardia or (multiple) asystolic pauses which lasted a median of 19 s (10-30). The recovery phase lasted 22 s (7-52). The total duration of the cardioinhibitory reflex was 85 s (47-116). We then calculated the potential increase in benefit that an optimally programmed drop rate detection could provide compared with a reference Lower Rate detection. Compared with Lower Rate detection (defined as two consecutive beats at 40 bpm), drop rate detection (assumed to be drop size = 20 bpm, detection window = 1 min, and drop rate = 50 bpm) would have been able to introduce intervention pacing, a median of 5.7 s (interquartile range -5.1- -10.4) earlier in 28 cases (58%). CONCLUSION: Cardioinhibitory neurally-mediated reflex varies widely from a few seconds to some minutes. In our data the total duration was <2 min. Optimal RDR programming, being potentially able to anticipate the detection of the cardioinhibitory reflex by a few seconds, could provide an increase in benefit for cardiac pacing therapy in prevention of syncope.

Pacing for neurally mediated syncope: is placebo powerless?

BACKGROUND: After two recent controlled trials failed to prove superiority of cardiac pacing over placebo in patients affected by neurally mediated syncope, a widely accepted opinion is that cardiac pacing therapy is not very effective and that a strong placebo effect exists. AIM: To measure the effect of placebo pacing therapy. METHOD AND RESULTS: We compared the recurrence rate of syncope during placebo vs. no treatment in controlled trials of drug or pacing therapy. Syncope recurred in 38% of 252 patients randomized to placebo pooled from five trials vs. 34% of 881 patients randomized to no treatment pooled from eight trials. The corresponding recurrence rate with active cardiac pacing was 15% in 203 patients from six trials. CONCLUSIONS: Placebo is not an effective therapy for neurally mediated syncope. Different selection criteria in patients who are candidates for cardiac pacing-for example, presence, absence, or severity of the cardioinhibitory reflex may separate positive from negative trials.

International study on syncope of uncertain aetiology 3 (ISSUE 3): pacemaker therapy for patients with asystolic neurally-mediated syncope: rationale and study design.

AIM: To assess the effectiveness of pacing therapy for preventing syncope recurrence in patients with a high probability of cardio-inhibitory neurally-mediated syncope (NMS). STUDY DESIGN: Multi-centre, prospective, double-blind, randomized placebo-controlled study. INCLUSION CRITERIA: Eligible patients are at least 40 years of age and have suffered, in the prior 2 years, > or = 3 syncope episodes of suspected NMS (with the exception of carotid sinus syndrome), which is considered by the attending physician to have a severe clinical presentation requiring treatment initiation. Patients with positive and negative tilt testing are included. EXCLUSION CRITERIA: Patients with one or more of the following are excluded: carotid sinus syndrome; suspected or definite heart disease and high likelihood of cardiac syncope; symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement; loss of consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy); subclavian steal syndrome. STUDY PROTOCOL: Eligible patients receive an Implantable Loop Recorder and are followed till the first documented syncopal recurrence or a significant asystolic event. Those patients who have an asystolic pause (sinus arrest or AV block) > 6 s or a syncopal asystolic pause > or = 3 s receive a dual-chamber pacemaker implantation and are randomized to active therapy (Pm ON) or to placebo therapy (Pm OFF). End-points: Primary end-point is the first syncope recurrence after pacemaker implant. Sample size and duration: A maximum of 710 patients are to be enrolled during an anticipated period of 2 years to allow randomization of 60 patients in the Pm ON arm and 60 in the Pm OFF arm (total 120).

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.

Clinical and electrophysiological characteristics in patients with atrioventricular reentrant and atrioventricular nodal reentrant tachycardia.

AIM: To compare clinical, electrophysiological characteristics and transcatheter ablation results between two groups of patients, one with atrioventricular reentrant tachycardia (AVRT) and the other with atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: The study population consisted of 94 consecutive patients who underwent endocavitary electrophysiological study and radiofrequency (RF) ablation: 46 patients had AVRT due to an accessory pathway with only retrograde conduction while 48 patients had AVNRT. RESULTS: In relation to general and clinical characteristics, differences between the two groups emerged regarding the age of symptom onset (25+/-16 vs 37+/-17 years, p=0.001), the prevalence of heart disease (8 vs 31%, p=0.001) and the correct diagnosis on surface ECG (50 vs 79%, p=0.001). Clinical presentation was quite similar apart from a higher prevalence of fatigue and sweating in the AVNRT group. Transcatheter RF ablation therapy results were similar. CONCLUSIONS: Patients with AVRT have a lower mean age at arrhythmia symptom onset compared with those with AVNRT and have fewer associated cardiac abnormalities. Clinical presentation is quite similar as well as their outcome after ablation. A correct diagnosis by standard ECG is more frequent in AVNRT.

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.

The diagnostic value of ATP testing in patients with unexplained syncope.

A minority of patients with unexplained syncope has an increased susceptibility to adenosine triphosphate (ATP) injection. In these 'hypersensitive' patients, owing to its powerful cardiac and hypotensive effects, endogenous adenosine released under physiological and pathological conditions could trigger bradycardia and/or hypotension and cause syncope. This hypothesis still needs to be proven. However, there is some evidence that the ATP test identifies a group of patients with otherwise unexplained syncope with definite clinical features, absence of structural heart disease and benign prognosis. The mechanism of syncope is heterogeneous; indeed, in cases of electrocardiographic documentation of spontaneous syncope, either a long ventricular pause (mainly due to paroxysmal atrioventricular (AV) block) or no rhythm variations or even tachycardia were documented. ATP-positive patients have clinical features and mechanisms of syncope which are different from tilt-positive patients. Owing to its low positive predictive value, the ATP test is of little value in selecting treatment. A favourable outcome suggests a strategy of postponing treatment, in particular pacemaker therapy, until a definite diagnosis can be made by documenting a spontaneous syncopal relapse.

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.