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Objectives: While carotid sinus syndrome (CSS) is traditionally defined by the association of carotid sinus hypersensitivity (CSH) with syncope, uncertainty remains over the role, if any, of complex pacing in patients with CSH and unexplained or recurrent falls. We sought to clarify the role of dual chamber pacing in this patient group in the first placebo-controlled study in CSH. Design: Randomised, double-blind, crossover, placebo-controlled trial. Setting: Specialist falls and syncope facility. Patients: Consecutive subjects aged over 55 years with CSH as the sole attributable cause of three or more unexplained falls in the 6 months preceding enrolment. Intervention: Dual-chamber permanent pacing with rate-drop response programming. The pacemaker was switched on (DDD/RDR) or off (ODO (placebo)) for 6 months, then crossed over to the alternate mode for a further 6 months, in randomised, double-blind fashion. Main outcome measure: The primary outcome measure was number of falls in paced and non-paced modes. Results: Twenty-five of 34 subjects (mean 76.8 years (SD 9.0), 27 (79%) female) recruited completed the study. Pacing intervention had no effect on number of falls (4.04 (9.54) in DDD/RDR mode, 3.48 (7.22) in ODO; relative risk of falling in ODO mode 0.82, 95% CI 0.62 to 1.10). Conclusion: Permanent pacing intervention had no effect on fall rates in older patients with CSH. Further work is urgently needed to clarify the role, if any, of complex pacing in this patient group.

Syncope, or fainting, affects approximately 6.2% of the population, and is associated with significant comorbidity. Many syncopal events occur secondary to excessive venous pooling and capillary filtration in the lower limbs when upright. As such, a common approach to the management of syncope is the use of compression stockings. However, research confirming their efficacy is lacking. We aimed to investigate the effect of graded calf compression stockings on orthostatic tolerance. We evaluated orthostatic tolerance (OT) and haemodynamic control in 15 healthy volunteers wearing graded calf compression stockings compared to two placebo stockings in a randomized, cross-over, double-blind fashion. OT (time to presyncope, min) was determined using combined head-upright tilting and lower body negative pressure applied until presyncope. Throughout testing we continuously monitored beat-to-beat blood pressures, heart rate, stroke volume and cardiac output (finger plethysmography), cerebral and forearm blood flow velocities (Doppler ultrasound) and breath-by-breath end tidal gases. There were no significant differences in OT between compression stocking (26.0±2.3 min) and calf (29.3±2.4 min) or ankle (27.6±3.1 min) placebo conditions. Cardiovascular, cerebral and respiratory responses were similar in all conditions. The efficacy of compression stockings was related to anthropometric parameters, and could be predicted by a model based on the subject's calf circumference and shoe size (r = 0.780, p = 0.004). These data question the use of calf compression stockings for orthostatic intolerance and highlight the need for individualised therapy accounting for anthropometric variables when considering treatment with compression stockings.

BackgroundCardioinhibitory carotid sinus hypersensitivity (CICSH) is highly prevalent among older people with falls.ObjectiveTo assess the efficacy of dual-chamber pacing in older patients with CICSH and unexplained falls.DesignA multicentre, double blind, randomised controlled trial.SettingSelection from emergency room, geriatric medicine and orthopaedic departments.PatientsPatients aged >50 years, with two unexplained falls and/or one syncopal event in the previous 12 months for which no other cause is evident apart from CICSH.InterventionsPatients randomised to either a 700/400 κ, rate responsive pacemaker or implantable loop recorder (Medtronic Reveal thera RDR, Medtronic, Minneapolis, Minnesota, USA).Main outcome measuresThe primary outcome was the number falls after implantation. Secondary outcomes were time to fall event, presyncope, quality of life and cognitive function.Results141 patients were recruited from 22 centres. Mean age was 78 years and mean follow-up 24 months. The overall relative risk of falling after device implantation compared with before was 0.23 (0.15 to 0.32). No significant reduction in falls was seen between paced and loop recorder groups (RR=0.79; 95% CI 0.41 to 1.50). Data were also consistent in both groups for syncope, quality of life and cognitive function.ConclusionsThese results question the use of pacing in CICSH. However, the study was underpowered and also patient characteristics differed from those in Safepace 1—participants were physically and cognitively frailer. Further work is necessary to assess cardiac pacing in this setting.

Objectives Syncope is a cause of significant morbidity in sick sinus syndrome (SSS) which may not be resolved with permanent pacemaker therapy. We aimed to determine the incidence, predictors and prognostic implication of syncope in paced patients with SSS. Methods We studied 1415 patients (mean age 72.9 years, SD 11.1) with SSS who were randomised in the DANPACE study to either rate-responsive single chamber pacing (n=707) or rate-responsive dual chamber pacing (n=708). Main outcome measures were patient-reported syncope after pacemaker implantation and mortality. Results Mean follow-up was 5.4 years (SD 2.6). A total of 247 (17.5%) patients experienced syncope after pacemaker implantation (135 (19%) from the rate-responsive single chamber pacing group, and 112 (15.8%) from the rate-responsive dual chamber pacing group. Predictors of syncope post pacemaker implantation included: age 0–39 years (HR 2.9, 95% CI 1.4 to 6.3, p=0.01; reference range 60–79 years), age ≥80 years (HR 1.4, 95% CI 1.0 to 1.8, p=0.03), syncope prior to pacemaker implant (HR 1.8, 95% CI 1.4 to 2.3, p<0.001), previous myocardial infarction (HR 1.5, 95% CI 1.1 to 2.1, p=0.03), heart failure (HR 1.4, 95% CI 1.0 to 1.9, p=0.046), and high Charlson comorbidity index (HR 1.6, 95% CI 1.1 to 2.2, p=0.01). Patients who experienced syncope post pacemaker implant had higher mortality compared with patients who did not (adjusted HR 1.6, 95% CI 1.3 to 2.1, p<0.001). Conclusions Syncope in paced patients with SSS is common, and is associated with higher mortality. The predictors identified in this study suggest a multifactorial aetiology of syncope.

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.

Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders 1 . The Bezold–Jarisch reflex (BJR), first described 2 , 3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing 4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses—hypotension, bradycardia and suppressed respiration—and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push–pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels. The molecular mechanisms underlying the Bezold–Jarisch reflex and syncope (fainting) involve vagal sensory neurons that express neuropeptide Y receptor Y2, the deletion of which in animal models abolishes the Bezold–Jarisch reflex.

Aortic dissection is a rare but potentially catastrophic condition. Misdiagnosis of aortic dissection is not uncommon as symptoms can overlap with other diagnoses. We conducted a systematic review to better understand the factors contributing to incorrect diagnosis of this condition. We searched MEDLINE and EMBASE for studies that evaluated the misdiagnosis of aortic dissection. The rate of misdiagnosis was pooled and results were narratively synthesized. A total of 12 studies with were included with 1663 patients. The overall rate of misdiagnosis of aortic dissection was 33.8%. The proportion of patients presenting with chest pain, back pain and syncope were 67.5%, 24.8% and 6.8% respectively. The proportion of patients with pre-existing hypertension was 55.4%, 30.5% were smokers while the proportion of patients with coronary artery disease, previous cardiovascular surgery or surgical trauma and Marfan syndrome was 14.7%, 5.8%, and 3.7%, respectively. Factors related to misdiagnosis included the presence of symptoms and features associated with other diseases (such as acute coronary syndrome, stroke and pulmonary embolism), the absence of typical features (such as widened mediastinum on chest X-ray) or concurrent conditions such congestive heart failure. Factors associated with more accurate diagnosis included more comprehensive history taking and increased use of imaging. Misdiagnosis in patients with an eventual diagnosis of aortic dissection affects 1 in 3 patients. Clinicians should consider aortic dissection as differential diagnosis in patients with chest pain, back pain and syncope. Imaging should be used early to make the diagnosis when aortic dissection is suspected.

The widespread use of visual technologies such as Virtual Reality increases the risk of visually induced motion sickness (VIMS). Previously, the 6-item short version of the Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ short form) has been validated for predicting individual variation in VIMS. The aim of the current study was to investigate how the susceptibility to VIMS is correlated with other relevant factors in the general population. A total of 440 participants (201 M, 239F), mean age 33.6 (SD 14.8) years, completed an anonymous online survey of various questionnaires including the VIMSSQ, Motion Sickness Susceptibility Questionnaire (MSSQ), Vertigo in City questionnaire (VIC), Migraine (scale), Social & Work Impact of Dizziness (SWID), Syncope (faintness), and Personality (‘Big Five’ TIPI). The VIMSSQ correlated positively with the MSSQ (r = 0.50), VIC (r = 0.45), Migraine (r = 0.44), SWID (r = 0.28), and Syncope (r = 0.15). The most efficient Multiple Linear Regression model for the VIMSSQ included the predictors MSSQ, Migraine, VIC, and Age and explained 40% of the variance. Factor analysis of strongest correlates with VIMSSQ revealed a single factor loading with VIMSSQ, MSSQ, VIC, Migraine, SWID, and Syncope, suggesting a common latent variable of sensitivity. The set of predictors for the VIMSSQ in the general population has similarity with those often observed in patients with vestibular disorders. Based on these correlational results, we suggest the existence of continuum of underlying risk factors for sensitivity, from healthy population to patients with extreme visual vertigo and perhaps Persistent Postural-Perceptual Dizziness.

Aims: To describe a large series of children with anoxic-epileptic seizures (AES)—that is, epileptic seizures induced by syncopes. Methods: Retrospective case-note review in a tertiary paediatric neurology unit. For all 27 children seen with a definite diagnosis of AES between 1972 and 2002, a review of clinical histories, videotapes, and EEG/ECG studies was undertaken. Main outcome measures were: age of onset, frequency and type of syncopes; age of onset and frequency of AES; type and duration of induced epileptic seizures; effect of treatment of syncopal and epileptic components. Results: Median age of onset of syncopes was 8 months (range 0.2–120), frequency 2 in total to 40/day, median total ∼200. Syncopes were predominantly reflex asystolic (RAS), prolonged expiratory apnoea (cyanotic breath-holding spells), or of mixed or uncertain origin; there was one each of ear piercing and hair grooming vasovagal syncope and one of compulsive Valsalva. Median age of onset of AES was 17 months (range 7–120), frequency from total 1 to 3/day, median total 3. The epileptic component was almost always bilateral clonic; three had additional epilepsy, one each with complex partial seizures, myoclonic absences, and febrile seizures plus. Median duration of epileptic component was 5 minutes (range 0.5–40, mean 11). Cardiac pacing prevented RAS in two patients: most other anti-syncope therapies were ineffective. Diazepam terminated the epileptic component in 6/8. Valproate or carbamazepine abolished AES in 5/7 without influencing syncope frequency. Conclusions: Although uncommon compared with simple syncopes, syncope triggered epileptic seizures (AES) are an important treatable basis of status epilepticus.

Syncope can be caused by serious conditions not evident during initial evaluation, which can lead to serious adverse events, including death, after disposition from the emergency department. We sought to develop a clinical decision tool to identify adult patients with syncope who are at risk of a serious adverse event within 30 days after disposition from the emergency department. We prospectively enrolled adults (age ≥ 16 yr) with syncope who presented within 24 hours after the event to 1 of 6 large emergency departments from Sept. 29, 2010, to Feb. 27, 2014. We collected standardized variables at index presentation from clinical evaluation and investigations. Adjudicated serious adverse events included death, myocardial infarction, arrhythmia, structural heart disease, pulmonary embolism, serious hemorrhage and procedural interventions within 30 days. We enrolled 4030 patients with syncope; the mean age was 53.6 years, 55.5% were women, and 9.5% were admitted to hospital. Serious adverse events occurred in 147 (3.6%) of the patients within 30 days after disposition from the emergency department. Of 43 candidate predictors examined, we included 9 in the final model: predisposition to vasovagal syncope, heart disease, any systolic pressure reading in the emergency department < 90 or > 180 mm Hg, troponin level above 99th percentile for the normal population, abnormal QRS axis (< −30° or > 100°), QRS duration longer than 130 ms, QTc interval longer than 480 ms, emergency department diagnosis of cardiac syncope and emergency department diagnosis of vasovagal syncope (C statistic 0.88, 95% confidence interval [CI] 0.85–0.90; optimism 0.015; goodness-of-fit p = 0.11). The risk of a serious adverse event within 30 days ranged from 0.4% for a score of −3 to 83.6% for a score of 11. The sensitivity was 99.2% (95% CI 95.9%–100%) for a threshold score of −2 or higher and 97.7% (95% CI 93.5%–99.5%) for a threshold score of −1 or higher. The Canadian Syncope Risk Score showed good discrimination and calibration for 30-day risk of serious adverse events after disposition from the emergency department. Once validated, the tool will be able to accurately stratify the risk of serious adverse events among patients presenting with syncope, including those at low risk who can be discharged home quickly.