Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

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.

[Long-term follow-up of psychogenic pseudosyncope]. / Het beloop van psychogene pseudosyncope na meedelen van de diagnose.

BACKGROUND: Patients with psychogenic pseudosyncope (PPS) are frequently seen by neurologists and psychiatrists. As of yet, there has been no follow-up study of patients with PPS after communicating the diagnosis. AIM: To determine the outcome of patients with psychogenic pseudosyncope (PPS) after communicatingthe diagnosis. METHOD: A retrospective cohort study of patients with PPS referred to a tertiary referral center for syncope from 2007 to 2015. We reviewed patient records, studying attack frequency, factors possibly affecting attack frequency, health care use and quality of life using questionnaires. We explored influences on absence of attack and attack frequency in the six months before follow-up for age, sex, level of education, duration until a diagnosis was made, probability of diagnosis, additional syncope and acceptance of diagnosis. RESULTS: 47 out 57 PPS cases could be traced, of these 35 (74%) participated. Twelve (34%) were attack free for at least six months. The median time from diagnosis to follow-up was 50 months (range 6-103 months). Communication and explanation of the diagnosis resulted in immediate reduction of attack frequency (p=0.007) from the month before diagnosis (median one attack, range 0-156) to the month afterwards (median one attack, range 0-16). In the six months before follow-up the number of admissions decreased from 19/35 to 0/35 (p = 0.002). Furthermore, the demand for somatic health care shifted to psychiatric care (p < 0.0001). Quality of life at follow-up (Short Form Health Survey 36; SF-36) showed lower scores for seven of the eight domains compared to matched Dutch control values. The quality of life was not significantly influenced by absence of attack. CONCLUSION: After communicating the diagnosis of PPS, attack frequency decreased and health care use shifted toward mental care. Low quality of life underlines the fact that PPS is a serious condition. Improvement of quality of life probably requires both a longer treatment and longer follow-up.

[Driving status of syncope patients is not part of standard advice]. / Rijgeschiktheid bij syncope niet standaard besproken.

OBJECTIVE: Some medical problems, such as syncope, have direct consequences for fitness to drive. Our objective was to discover if patients had been informed about their driving status after a syncopal episode by their physician, and if this advice was in line with current legislation. DESIGN: Cross-sectional study. METHOD: By means of a structured questionnaire, 150 patients referred to the syncope clinic at the Academic Medical Centre, Amsterdam, were asked about the advice they had received concerning their driving status during previous consultations with their general practitioner or specialists. A syncope expert then assessed the driving status of all patients in the light of the existing and new ruling. RESULTS: In 121 of the 150 patients (81%), a certain or highly-likely cause for their loss of consciousness was determined: 68 patients had reflex syncope, 25 patients orthostatic hypotension, 20 patients psychogenic pseudosyncope, three patients cardiac syncope, three patients had epilepsy and two patients another diagnosis. Seven patients had experienced an episode while driving. Only 26/150 patients (17%) reported that the consequences of their episodes for their driving status had been discussed with them at earlier consultations. If driving was discussed, in only 31% had the current Dutch legislation on driving been followed. Over a third (38%) of the patients felt they should no longer drive. CONCLUSION: Fewer than one in five patients reported that driving status was discussed by a physician after a syncope episode. If advice had been given, it was often not in line with current legislation.

The heart of epilepsy: Current views and future concepts.

Cardiovascular (CV) comorbidities are common in people with epilepsy. Several mechanisms explain why these conditions tend to co-exist including causal associations, shared risk factors and those resulting from epilepsy or its treatment. Various arrhythmias occurring during and after seizures have been described. Ictal asystole is the most common cause. The converse phenomenon, arrhythmias causing seizures, appears extremely rare and has only been reported in children following cardioinihibitory syncope. Arrhythmias in epilepsy may not only result from seizure activity but also from a shared genetic susceptibility. Various cardiac and epilepsy genes could be implicated but firm evidence is still lacking. Several antiepileptic drugs (AEDs) triggering conduction abnormalities can also explain the co-existence of arrhythmias in epilepsy. Epidemiological studies have consistently shown that people with epilepsy have a higher prevalence of structural cardiac disease and a poorer CV risk profile than those without epilepsy. Shared CV risk factors, genetics and etiological factors can account for a significant part of the relationship between epilepsy and structural cardiac disease. Seizure activity may cause transient myocardial ischaemia and the Takotsubo syndrome. Additionally, certain AEDs may themselves negatively affect CV risk profile in epilepsy. Here we discuss the fascinating borderland of epilepsy and cardiovascular conditions. The review focuses on epidemiology, clinical presentations and possible mechanisms for shared pathophysiology. It concludes with a discussion of future developments and a call for validated screening instruments and guidelines aiding the early identification and treatment of CV comorbidity in epilepsy.

The Role of the Suprachiasmatic Nucleus in Cardiac Autonomic Control during Sleep.

BACKGROUND: The suprachiasmatic nucleus (SCN) may play an important role in central autonomic control, since its projections connect to (para)sympathetic relay stations in the brainstem and spinal cord. The cardiac autonomic modifications during nighttime may therefore not only result from direct effects of the sleep-related changes in the central autonomic network, but also from endogenous circadian factors as directed by the SCN. To explore the influence of the SCN on autonomic fluctuations during nighttime, we studied heart rate and its variability (HRV) in a clinical model of SCN damage. METHODS: Fifteen patients in follow-up after surgical treatment for nonfunctioning pituitary macroadenoma (NFMA) compressing the optic chiasm (8 females, 26-65 years old) and fifteen age-matched healthy controls (5 females, 30-63 years) underwent overnight ambulatory polysomnography. Eleven patients had hypopituitarism and received adequate replacement therapy. HRV was calculated for each 30-second epoch and corrected for sleep stage, arousals, and gender using mixed effect regression models. RESULTS: Compared to controls, patients spent more time awake after sleep onset and in NREM1-sleep, and less in REM-sleep. Heart rate, low (LF) and high frequency (HF) power components and the LF/HF ratio across sleep stages were not significantly different between groups. CONCLUSIONS: These findings suggest that the SCN does not play a dominant role in cardiac autonomic control during sleep.

Tilt table testing in neurology and clinical neurophysiology.

Reflex syncope is responsible for 1-6% of hospital admissions and the economic burden of syncope is huge. A considerable part of these high costs is still spent on tests that are not indicated. Till now few neurologists have taken an interest in syncope and tilt table testing (TTT). However, reflex syncope and epilepsy are often in each other's differential diagnosis and require a similar emphasis on history taking and deductive reasoning. A TTT can be helpful for diagnosis and treatment. The pathophysiological rationale behind the TTT is the fact that it uses gravity to provoke a downwards shift of blood that in turn triggers syncope. Various indications and methods of the TTT are discussed in this paper.

Effect of orthostatic hypotension on sustained attention in patients with autonomic failure.

INTRODUCTION: Orthostatic hypotension has been associated with impaired cognitive function, but cognitive function during orthostatic hypotension has hardly been studied. We studied the effect of orthostatic hypotension, induced by head-up tilt (HUT), on sustained attention in patients with autonomic failure. METHODS: We studied the sustained attention to response task (SART) in the supine position and during HUT in 10 patients with autonomic failure and 10 age-matched and sex-matched controls. To avoid syncope, the tilting angle was tailored to patients to reach a stable systolic blood pressure below 100 mm Hg. Controls were all tilted at an angle of 60°. Cerebral blood flow velocity, blood pressure and heart rate were measured continuously. RESULTS: In patients, systolic blood pressure was 61.4 mm Hg lower during HUT than in the supine position (p<0.001). Patients did not make more SART errors during HUT than in the supine position (-1.3 errors, p=0.3). Controls made 2.3 fewer errors during SART in the HUT position compared to the supine position (p=0.020). SART performance led to an increase in systolic blood pressure (+11.8 mm Hg, p=0.018) and diastolic blood pressure (+5.8 mm Hg, p=0.017) during SART in the HUT position, as well as to a trend towards increased cerebral blood flow velocity (+3.8 m/s, p=0.101). DISCUSSION: Orthostatic hypotension in patients with autonomic failure was not associated with impaired sustained attention. This might partly be explained by the observation that SART performance led to a blood pressure increase. Moreover, the upright position was associated with better performance in controls and, to a lesser extent, also in patients.

Increased prevalence of ECG markers for sudden cardiac arrest in refractory epilepsy.

BACKGROUND AND AIM: People with epilepsy are at increased risk of sudden cardiac arrest (SCA) due to ECG-confirmed ventricular tachycardia/fibrillation, as seen in a community-based study. We aimed to determine whether ECG-risk markers of SCA are more prevalent in people with epilepsy. METHODS: In a cross-sectional, retrospective study, we analysed the ECG recordings of 185 people with refractory epilepsy and 178 controls without epilepsy. Data on epilepsy characteristics, cardiac comorbidity, and drug use were collected, and general ECG variables (heart rate (HR), PQ and QRS intervals) assessed. We analysed ECGs for three markers of SCA risk: severe QTc prolongation (male >450 ms, female >470 ms), Brugada ECG pattern, and early repolarisation pattern (ERP). Multivariate regression models were used to analyse differences between groups, and to identify associated clinical and epilepsy-related characteristics. RESULTS: People with epilepsy had higher HR (71 vs 62 bpm, p<0.001) and a longer PQ interval (162.8 vs 152.6 ms, p=0.001). Severe QTc prolongation and ERP were more prevalent in people with epilepsy (QTc prolongation: 5% vs 0%; p=0.002; ERP: 34% vs 13%, p<0.001), while the Brugada ECG pattern was equally frequent in both groups (2% vs 1%, p>0.999). After adjustment for covariates, epilepsy remained associated with ERP (ORadj 2.4, 95% CI 1.1 to 5.5) and severe QTc prolongation (ORadj 9.9, 95% CI 1.1 to 1317.7). CONCLUSIONS: ERP and severe QTc prolongation appear to be more prevalent in people with refractory epilepsy. Future studies must determine whether this contributes to increased SCA risk in people with epilepsy.

Alterations in diurnal rhythmicity in patients treated for nonfunctioning pituitary macroadenoma: a controlled study and literature review.

OBJECTIVE: Patients treated for nonfunctioning pituitary macroadenomas (NFMAs) have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity frequently. As NFMAs often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect indices of SCN functioning are altered in the long term after surgery for NFMAs. METHODS: We studied 17 NFMA patients in long-term remission after transsphenoidal surgery, receiving adequate and stable hormone replacement for hypopituitarism, and 17 control subjects matched for age, gender, and BMI. Indirect indices of SCN function were assessed from 24-h ambulatory recordings of skin and core body temperatures, blood pressure, and salivary melatonin levels. Altered melatonin secretion was defined as an absence of evening rise, considerable irregularity, or daytime values >3 pg/ml. We additionally studied eight patients treated for craniopharyngioma. RESULTS: Distal-proximal skin temperature gradient did not differ between NFMAs and control subjects, but proximal skin temperature was decreased during daytime (P=0.006). Core body temperature and non-dipping of blood pressure did not differ, whereas melatonin secretion was often altered in NFMAs (OR 5.3, 95% CI 0.9-30.6). One or more abnormal parameters (≥2.0 SDS of control subjects) were observed during nighttime in 12 NFMA patients and during daytime in seven NFMA patients. Similar patterns were observed in craniopharyngioma patients. CONCLUSION: Heterogeneous patterns of altered diurnal rhythmicity in skin temperature and melatonin secretion parameters were observed in the majority of patients treated for NFMAs. On a group level, both NFMA and craniopharyngioma patients showed a lower daytime proximal skin temperature than control subjects, but other group averages were not significantly different. The observations suggest altered function of central (or peripheral) clock machinery, possibly by disturbed entrainment or damage of the hypothalamic SCN by the suprasellar macroadenoma or its treatment.

Carotid body tumors are not associated with an increased risk for sleep-disordered breathing.

PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.

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.

Postictal sleep: syncope or seizure?

A 6-year-old boy presented with prolonged periods of unconsciousness (>60 min) following nausea and dizziness while standing. The application of EEG electrodes provoked a similar episode. These apparently long periods of unconsciousness could be explained by sleep. In view of the triggers (pain, distress, and prolonged standing), the prodromal features, and the transient sinus bradycardia during the EEG examination a diagnosis of vasovagal syncope was made. Sleep is an alternative explanation for delayed recovery after syncope in young children. Prompt recognition might avoid unnecessary investigations, distress, and an incorrect diagnosis.

Transient loss of consciousness through the eyes of a witness.

OBJECTIVE: To assess the accuracy of eyewitness observations of transient loss of consciousness. METHODS: Two sequential cohorts of psychology students unexpectedly viewed videos of a generalized tonic-clonic seizure (n = 125) and of reflex syncope (n = 104) during a lecture on an unrelated subject. Directly afterward, the students filled in a multiple-choice questionnaire regarding muscle tone, twitches, head deviation, eye closure, gaze deviation, drooling, and facial color. The consensus of experienced neurologists served as a gold standard. Even though not all items could be ascertained from the videos, the full range of questions was included to simulate clinical practice. RESULTS: Of all responses to the observable items on the syncope video (flaccid limbs, twitches of one shoulder, head deviation), 44% were correct, 28% erroneous, and 29% had "I do not know" responses. The observable items on the epilepsy video (stiff limbs, twitches of all limbs, normal facial color, drooling, no head deviation) yielded 60% correct responses, 18% erroneous responses, and 22% "I do not know" responses. Regarding features that were not visible on the videos, 77% of the responses were accurate ("I do not know"), whereas 23% erroneously provided an observation. Of all items observable on both videos, muscle tone was the most accurately recalled item. CONCLUSIONS: An eyewitness account of a single episode of transient loss of consciousness (TLOC) should be interpreted with caution because salient features are frequently overlooked or inaccurately recalled. However, the accuracy of the eyewitness observations of TLOC differs per item; muscle tone was reported with high accuracy.

Syncope in migraine: the population-based CAMERA study.

OBJECTIVE: To examine the association between migraine and syncope-related autonomic nervous system (ANS) symptoms. METHODS: A population-based study among migraineurs with and without aura (n = 323) and control subjects (n = 153) was conducted. A systematic questionnaire and cardiovascular measurements during rest, while standing, and after venipuncture addressed the prevalence of syncope, orthostatic intolerance, orthostatic hypotension (OH), and the postural tachycardia syndrome (POTS) in migraineurs and control subjects. RESULTS: The lifetime prevalence of syncope in all participants was 41%, more often in women (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p < 0.001). There was no association between ANS symptoms and the severity of migraine or migraine subtype. Cardiovascular measurements and the prevalence of POTS and OH did not differ significantly between migraineurs and control subjects. CONCLUSION: This population-based study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction.

Stress induced hypotension in pure autonomic failure.

A 47 year old woman with pure autonomic failure complained of dizziness during emotional stress. Emotional stimuli have not previously been reported to cause hypotension in patients with autonomic failure. In the patient, ambulatory blood pressure recording revealed severe hypotension (50/30 mm Hg) after a stressful event. During a tilt table test, hyperventilation was shown to cause a significant fall of blood pressure. This suggests that emotional stress can induce hypotension, probably through hyperventilation, in subjects with autonomic failure.