Sleep syncope: a prospective cohort study.

PURPOSE: Sleep syncope is defined as a form of vasovagal syncope which interrupts sleep. Long term follow-up has not been reported. METHODS: Between 1999 and 2013 we diagnosed vasovagal syncope in 1105 patients of whom 69 also had sleep syncope. We compared these 69 patients in the sleep syncope group to 118 patients with classical vasovagal syncope consecutively investigated between 1999 and 2003. We compared baseline demography, syncope history, tilt test results and follow-up findings. RESULTS: At baseline, age and gender distribution (mean ± standard deviation) of the classical VVS and sleep synocope groups were similar: 46 ± 21 vs. 47 ± 15 years (p = 0.53), and 55% versus 66% female (p = 0.28), respectively. Abdominal discomfort and vagotonia were more frequent in sleep syncope patients: 80% versus 8% and 33% versus 2% (p < 0.001). Childhood syncope and blood-needle phobia were also more frequent in sleep syncope patients: 58% versus 15% and 69% versus 19% (p < 0.001). Positive tilt test results were similar for the two groups (93% [classical VVS] vs. 91%; p = 0.56). Blood pressure, heart rate and stroke volume changed in a similar manner from baseline to syncope (p = 0.32, 0.34 and 0.18, respectively). Mean duration of follow-up for the classical VVS and sleep syncope groups, as recorded in the electronic records, were 17 (3-21) and 15 (7-27) years, respectively. Rates of mortality and of permanent pacemaker insertion were similar in the two groups: 16.2% (classical VVS) versus 7.6% (p = 0.09) and 3% (classical VVS) versus 3% (p = 0.9). Incidence of sleep episodes decreased from 1.9 ± 3 to 0.1 ± 0.3 episodes per year (p < 0.001). CONCLUSION: Sleep syncope is a subtype of vasovagal syncope with characteristic symptoms. Despite the severity of the sleep episodes, the prognosis is very good. Very few patients require permanent pacing, and nearly all respond to education and reassurance.

Diagnostic criteria for initial orthostatic hypotension: a narrative review.

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response.

Diagnostic accuracy of evaluation of suspected syncope in the emergency department: usual practice vs. ESC guidelines.

BACKGROUND: Syncope is a frequent reason for referral to the emergency department. After excluding a potentially life-threatening condition, the second objective is to find the cause of syncope. The objective of this study was to assess the diagnostic accuracy of the treating physician in usual practice and to compare this to the diagnostic accuracy of a standardised evaluation, consisting of thorough history taking and physical examination by a research physician. METHODS: This prospective cohort study included suspected (pre) syncope patients without an identified serious underlying condition who were assessed in the emergency department. Patients were initially seen by the initial treating physician and the usual evaluation was performed. A research physician, blinded to the findings of the initial treating physician, then performed a standardised evaluation according to the ESC syncope guidelines. Diagnostic accuracy (proportion of correct diagnoses) was determined by expert consensus after long-term follow-up. RESULTS: One hundred and one suspected (pre) syncope patients were included (mean age 59 ± 20 years). The usual practice of the initial treating physicians did not in most cases follow ESC syncope guidelines, with orthostatic blood pressure measurements made in only 40% of the patients. Diagnostic accuracy by the initial treating physicians was 65% (95% CI 56-74%), while standardised evaluation resulted in a diagnostic accuracy of 80% (95% CI 71-87%; p = 0.009). No life-threatening causes were missed. CONCLUSIONS: Usual practice of the initial treating physician resulted in a diagnostic accuracy of 65%, while standardised practice, with an emphasis on thorough history taking, increased diagnostic accuracy to 80%. Results suggest that the availability of additional resources does not result in a higher diagnostic accuracy than standardised evaluation, and that history taking is the most important diagnostic test in suspected syncope patients. Netherlands Trial Registration: NTR5651. Registered 29 January 2016, https://www.trialregister.nl/trial/5532.

Do we need to evaluate diastolic blood pressure in patients with suspected orthostatic hypotension?

PURPOSE: The contribution of diastolic blood pressure measurement to the diagnosis of classical orthostatic hypotension is not known. We aimed to explore the prevalence of isolated systolic and diastolic orthostatic hypotension components in patients with syncope and orthostatic intolerance. METHODS: A total of 1520 patients aged >15 years with suspected syncope and/or symptoms of orthostatic intolerance were investigated in a tertiary center using tilt-table testing and continuous non-invasive blood pressure monitoring. Classical orthostatic hypotension was defined as a decline in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg at 3 min of tilt test. The prevalence of upright systolic blood pressure <90 mmHg and its overlap with isolated diastolic orthostatic hypotension was also assessed. RESULTS: One hundred eighty-six patients (12.2%) met current diagnostic criteria for classical orthostatic hypotension. Of these, 176 patients (94.6%) met the systolic criterion and 102 patients (54.8%) met the diastolic criterion. Ninety-two patients (49.5%) met both systolic and diastolic criteria, whereas ten patients (5.4%) met the diastolic criterion alone. Of these, three had systolic blood pressure <90 mmHg during tilt test and were diagnosed with orthostatic hypotension on the grounds of low standing blood pressure. Based on patient history and ancillary test results, causes of orthostatic intolerance and syncope other than orthostatic hypotension were present in the remaining seven patients. CONCLUSIONS: An abnormal orthostatic fall in diastolic blood pressure without an abnormal fall in systolic blood pressure is rare among patients with syncope and orthostatic intolerance. Approximately 95% of patients with classical orthostatic hypotension can be identified by systolic criterion alone.

The semiology of tilt-induced reflex syncope in relation to electroencephalographic changes.

Syncope is defined as transient loss of consciousness as a result of cerebral hypoperfusion. Electroencephalography during syncope shows either a 'slow-flat-slow' or a 'slow' pattern. The first is believed to denote more severe hypoperfusion. Although the diagnosis of vasovagal syncope relies primarily on history taking, there is limited evidence regarding the relative importance of various clinical features, and none that relate them to the severity of electroencephalographic changes. The aim of this investigation was to study symptoms, signs and electroencephalographic changes with a 1 s resolution using electroencephalography and video data in 69 cases of tilt-induced vasovagal syncope. The main finding was that flattening of the electroencephalograph indicated more profound circulatory changes: the 'slow-flat-slow' group had a lower minimum blood pressure, longer maximum RR-interval, contained more cases with asystole and had a longer duration of loss of consciousness than the 'slow' group. Second, we describe a range of signs, including some that have rarely been reported in syncope, e.g. oral automatisms. Third, signs occurred at different rates depending on electroencephalographic flattening, suggesting a classification of syncopal signs. Type A signs (e.g. loss of consciousness, eye opening and general stiffening) develop during the first slow phase, stay present during flattening and stop in the second slow phase. Type B (particularly myoclonic jerks) occur when the electroencephalograph is slow but not flat: their abolition with electroencephalographic flattening suggests dependence on cortical activity. Type C signs (making sounds, roving eye movements and stertorous breathing) occur only in the flat phase, whereas type D (dropping the jaw and snoring) may occur either in slow or flat phases. In conclusion, our findings provide a detailed assessment of clinical symptoms in relation to electroencephalographic (EEG) changes during tilt-induced syncope.

Priorities for emergency department syncope research.

STUDY OBJECTIVES: There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS: We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS: There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION: We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial.

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.

Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans.

Syncope is a common clinical condition occurring even in healthy people without manifest cardiovascular disease. The purpose of this study was to determine the role of cardiac output and sympathetic vasoconstriction in neurally mediated (pre)syncope. Twenty-five subjects (age 15­51) with no history of recurrent syncope but who had presyncope during 60 deg upright tilt were studied; 10 matched controls who completed 45 min tilting were analysed retrospectively. Beat-to-beat haemodynamics (Modelflow), muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (MSNA­diastolic pressure relation) were measured. MSNA, haemodynamic responses and baroreflex sensitivity during early tilting were not different between presyncopal subjects and controls. Hypotension was mediated by a drop in cardiac output in all presyncopal subjects, accompanied by a decrease in total peripheral resistance in 16 of them (64%, group A). In the other 9 subjects, total peripheral resistance was well maintained even at presyncope (36%, group B). Cardiac output was smaller (3.26 ± 0.34 (SEM) vs. 5.02 ± 0.40 l min(−1), P = 0.01), while total peripheral resistance was greater (1327 ± 117 vs. 903 ± 80 dyn s cm(−5), P < 0.01) in group B than group A at presyncope. The steeper fall in cardiac output in group B was due to a drop in heart rate. MSNA decreased rapidly at presyncope after the onset of hypotension. Thus, a moderate fall in cardiac output with coincident vasodilatation or a marked fall in cardiac output with no changes in peripheral vascular resistance may contribute to (pre)syncope. However, an intrinsic impairment of vasomotor responsiveness and sympathetic baroreflex function is not the cause of neurally mediated (pre)syncope in this population.

Diagnosis and treatment of orthostatic hypotension.

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

Dissection of carotid sinus hypersensitivity: the timing of vagal and vasodepressor effects and the effect of body position.

We assessed the timing of vagal and sympathetic factors that mediate hypotension during CSM (carotid sinus massage) in patients with carotid sinus hypersensitivity. We hypothesized that a fall in cardiac output would precede vasodepression, and that vasodepression would be exaggerated by head-up tilt. We performed pulse contour analyses on blood pressure recordings during CSM in syncope patients during supine rest and head-up tilt. In a subset we simultaneously recorded muscle sympathetic nerve activity supine. During supine rest, systolic blood pressure decreased from 150±7 to 107±7 mmHg (P<0.001) and heart rate from 64±2 to 39±3 beats/min (P<0.01). Cardiac output decreased with heart rate to nadir (66±6% of baseline), 3.1±0.4 s after onset of bradycardia. In contrast, total peripheral resistance reached nadir (77±3% of baseline) after 11±1 s. During head-up-tilt, systolic blood pressure fell from 149±10 to 90±11 mmHg and heart rate decreased from 73±4 to 60±7 beats/min. Compared with supine rest, cardiac output nadir was lower (60±8 compared with 83±4%, P<0.05), whereas total peripheral resistance nadir was similar (81±6 compared with 80±3%). The time to nadir from the onset of bradycardia did not differ from supine rest. At the onset of bradycardia there was an immediate withdrawal of muscle-sympathetic nerve activity while total peripheral resistance decay occurred much later (6-8 s). The haemodynamic changes following CSM have a distinct temporal pattern that is characterized by an initial fall in cardiac output (driven by heart rate), followed by a later fall in total peripheral resistance, even though sympathetic withdrawal is immediate. This pattern is independent of body position.