Syncope in older adults: challenges, approach and treatment.

Syncope can have devastating consequences, resulting in injuries, accidents or even death. In our ageing society, the subsequent healthcare usage, such as emergency room presentations, surgeries and hospital admissions, forms a significant and growing socioeconomic burden. Causes of syncope in the older adult include orthostatic hypotension, carotid sinus syndrome, vasovagal syncope, structural cardiac abnormalities, cardiac arrhythmias and conduction abnormalities. As stated in the recently published World Falls Guidelines, syncope in older adults often presents as falls, which is either due to amnesia for loss of consciousness, or pre-syncope leading to a fall, especially in those prone to falls with several other risk-factors for falls present. This difference in presentation can hinder the recognition of syncope. In patients with unexplained falls, or in whom the history comprises red flags for potential syncope, special attention to (pre)syncope is therefore warranted. When syncope is mistaken for other causes of a transient loss of consciousness, such as epileptic seizures, or when syncope presents as falls, patients are often referred to multiple specialists, which may in turn lead to excessive and unnecessary diagnostic testing and costs. Specialist services that are able to provide a comprehensive assessment can improve diagnostic yield and minimise diagnostic testing, thus improving patient satisfaction. Comprehensive assessment also leads to reduced length of hospital stay. Increasingly, geriatricians are involved in the assessment of syncope in the older patient, especially given the overlap with falls. Therefore, awareness of causes of syncope, as well as state-of-the-art assessment and treatment, is of great importance.

Cardioneuroablation for treatment of carotid sinus syndrome secondary to oropharyngeal squamous cell cancer.

Head and neck tumors can rarely cause carotid sinus syndrome and this often resolves by surgical intervention or palliative chemoradiotherapy. If these modalities are not an option or are ineffective, the most preferred treatment is permanent pacemaker therapy. Here, we present the first case of cardioneuroablation treatment performed in patient with oropharyngeal squamous cell cancer who developed recurrent asystole and syncope attacks due to compression of the carotid sinus on neck movement.

General Morphology of the Mammalian Carotid Body.

The carotid body (CB) is the main peripheral arterial chemoreceptor that registers the levels of pO2, pCO2 and pH in the blood and responds to their changes by regulating breathing. It is strategically located in the bifurcation of each common carotid artery. The organ consists of "glomera" composed of two cell types, glomus and sustentacular cells, interspersed by blood vessels and nerve bundles and separated by connective tissue. The neuron-like glomus or type I cells are considered as the chemosensory cells of the CB. They contain numerous cytoplasmic organelles and dense-cored vesicles that store and release neurotransmitters. They also form both conventional chemical and electrical synapses between each other and are contacted by peripheral nerve endings of petrosal ganglion neurons. The glomus cells are dually innervated by both sensory nerve fibers through the carotid sinus nerve and autonomic fibers of sympathetic origin via the ganglioglomerular nerve. The parasympathetic efferent innervation is relayed by vasomotor fibers of ganglion cells located around or inside the CB. The glial-like sustentacular or type II cells are regarded to be supporting cells although they sustain physiologic neurogenesis in the adult CB and are thus supposed to be progenitor cells as well. The CB is a highly vascularized organ and its intraorgan hemodynamics possibly plays a role in the process of chemoreception.

Peripheral nerve stimulation and immunity: the expanding opportunities for providing mechanistic insight and therapeutic intervention.

Pre-clinical research advances our understanding of the vagus nerve-mediated regulation of immunity and clinical trials successfully utilize electrical vagus nerve stimulation in the treatment of patients with inflammatory disorders. This symbiotic relationship between pre-clinical and clinical research exploring the vagus nerve-based 'inflammatory reflex' has substantially contributed to establishing the field of bioelectronic medicine. Recent studies identify a crosstalk between the vagus nerve and other neural circuitries in controlling inflammation and delineate new neural immunoregulatory pathways. Here we outline current mechanistic insights into the role of vagal and non-vagal neural pathways in neuro-immune communication and inflammatory regulation. We also provide a timely overview of expanding opportunities for bioelectronic neuromodulation in the treatment of various inflammatory disorders.

Syncope as the initial symptom in a patient with nasopharyngeal carcinoma: a case report.

BACKGROUND: A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. CASE PRESENTATION: This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. CONCLUSIONS: This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective.

Novel approaches: targeting sympathetic outflow in the carotid sinus.

Uncontrolled hypertension drives the global burden of increased cardiovascular disease (CVD) morbidity and mortality. Although high blood pressure (BP) is treatable and preventable, only half of the patients with hypertension undergoing treatment have their BP controlled. The failure of polypharmacy to attain adequate BP control may be due to a lack of physiological response, however, medication non-adherence and clinician inertia to increase treatment intensity are critical factors associated with poor hypertension management. The long-time medication titration, lifelong drug therapy, and often multi-drug treatment strategy are frustrating when the BP goal is not achieved, leading to increased CVD risk and a substantial burden on the healthcare system. Growing evidence indicates that neurohumoral activation is critical in initiating and maintaining elevated BP and its adverse consequences. Over the past decades, device-based therapies targeting the mechanisms underlying hypertension pathophysiology have been extensively studied. Among these, robust clinical experience for hypertension management exists for renal denervation (RDN) and baroreflex activation therapy (BAT), carotid body denervation (CBD), central arteriovenous anastomosis, and to a lesser extent, deep brain stimulation. Future studies are warranted to define the role of device-based approaches as an alternative or adjunctive treatment option to treat hypertension.

Systemic hypertension is a growing contributor to global disease burden and premature cause of death worldwide.The percentage of patients achieving target BP levels remains largely inadequate.Hypertension is characterised by activation of the sympathetic nervous system, with the magnitude depending on age and the disease severity.Device-based interventions have been extensively studied to directly target the relevant sympathetic neural pathophysiological mechanisms involved in BP control.Modulation of the chronic sympathetic outflow with CBD or BAT shows promise for the treatment of poorly controlled hypertension in addition to antihypertensive medicines.The BP response to device-based therapies appears variable and cannot be predicted before the procedure.Until more robust evidence related to patient selection, procedural and technical aspects is available, chemoreflex and baroreflex neuromodulation therapy should be restricted to randomised sham-controlled trials performed in experienced centres.

Chronic Metformin Administration Does Not Alter Carotid Sinus Nerve Activity in Control Rats.

Metformin is a glucose-lowering, insulin-sensitizing drug that is commonly used in the treatment of type 2 diabetes (T2D). In the last decade, the carotid body (CB) has been described as a metabolic sensor implicated in the regulation of glucose homeostasis, being CB dysfunction crucial for the development of metabolic diseases, such as T2D. Knowing that metformin could activate AMP-activated protein kinase (AMPK) and that AMPK has been described to have an important role in CB hypoxic chemotransduction, herein we have investigated the effect of chronic metformin administration on carotid sinus nerve (CSN) chemosensory activity in basal and hypoxic and hypercapnic conditions in control animals. Experiments were performed in male Wistar rats subjected to 3 weeks of metformin (200 mg/kg) administration in the drinking water. The effect of chronic metformin administration was tested in spontaneous and hypoxic (0% and 5% O2) and hypercapnic (10% CO2) evoked CSN chemosensory activity. Metformin administration for 3 weeks did not modify the basal CSN chemosensory activity in control animals. Moreover, the CSN chemosensory response to intense and moderate hypoxia and hypercapnia was not altered by the chronic metformin administration. In conclusion, chronic metformin administration did not modify chemosensory activity in control animals.

Predictors of hemodynamic instability during and persistent after carotid artery stenting.

OBJECTIVES: The risk factors for post-carotid artery stenting severe hemodynamic instability remain elusive. This study aimed to identify the predictors of severe hemodynamic instability during and persisted after carotid artery stenting. MATERIALS AND METHODS: Consecutive patients who underwent carotid artery stenting for extracranial carotid artery stenosis at a single-center between September 2018 and July 2021 were retrospectively assessed. The predictive factors of severe hemodynamic instability intraoperation and post-operation were analyzed. RESULTS: Among the 139 patients included, 63 experienced severe hemodynamic instability, with 45 and 18 cases occurring intra and postoperatively, respectively. Persistent was observed in 21 patients. Smoke exposure (odds ratio [OR], 2.38; p=0.039), carotid bifurcation stenosis (OR, 0.91; p=0.018), and large-diameter balloon (>4 mm) dilatation (OR, 11.95; p<0.001) were identified as independent risk factors for hemodynamic instability at any stage of carotid artery stenting. Intraoperatively, large-diameter balloon (>4 mm) dilatation was associated with an increased risk of hemodynamic instability occurrence (OR, 4.67; p=0.01), whereas general anesthesia (OR, 0.19; p=0.001) and a longer distance from the stenosis to the carotid bifurcation (OR, 0.89; p=0.01) were negatively associated with hemodynamic instability. Furthermore, smoking exposure (OR, 3.73; p=0.03), large diameter balloon dilatation (OR, 6.12; p=0.032), distance from stenosis to bifurcation (OR, 0.85; p=0.047) and long-stent (40 mm) implantation (OR, 0.84 [95% confidence interval, 0.74-0.95]; p=0.007) could independently predict persistent hemodynamic instability. CONCLUSION: Patients with a smoking history, lesions near the carotid bulb, or dilatation using a large-diameter balloon were most likely to suffer severe hemodynamic instability. General anesthesia can protect against severe hemodynamic instability only intraoperatively. Long-term stent implantation may reduce persistent hemodynamic instability.

Carotid body stimulation as a potential intervention in sudden death in epilepsy.

OBJECTIVE: To investigate carotid body (CB) mechanisms related to sudden death during seizure. Ictal activation of oxygen-conserving reflexes (OCRs) can trigger fatal cardiorespiratory collapse in seizing rats, which presents like human sudden unexpected death in epilepsy (SUDEP). The CB is strongly implicated in OCR pathways; we hypothesize that modulating CB activity will provide insight into these mechanisms of death. METHODS: Long-Evans rats were anesthetized with urethane. Recordings included: electrocorticography, electrocardiography, respiration via nasal thermocouple, and blood pressure (BP). The mammalian diving reflex (MDR) was activated by cold water delivered through a nasal cannula. Reflex and stimulation trials were repeated up to 16 times (4 pre-intervention, 12 post-intervention) or until death. In some animals, one or both carotid bodies were denervated. In some animals, the CB was electrically stimulated, both with and without MDR. Seizures were induced with kainic acid (KA). RESULTS: Animals without seizure and with no CB modulation survived all reflexes. Non-seizing animals with CB denervation survived 7.1 ± 5.4 reflexes before death, and only 1 of 7 survived past the 12-trial threshold. Electrical CB stimulation without seizure and without reflex caused significant tachypnea and hypotension. Electrical CB stimulation with seizure and without reflex required higher amplitudes to replicate the physiological responses seen outside seizure. Seizing animals without CB intervention survived 3.2 ± 3.6 trials (per-reflex survival rate 42.0% ± 44.4%), and 0 of 7 survived past the 12-trial threshold. Seizing animals with electrical CB stimulation survived 10.5 ± 4.7 ictal trials (per-reflex survival rate 86.3% ± 35.0%), and 6 of 8 survived past the 12-trial threshold. SIGNIFICANCE: These results suggest that, during seizure, the ability of the CB to stimulate a restart of respiration is impaired. The CB and its afferents may be relevant to fatal ictal apnea and SUDEP in humans, and CB stimulation may be a relevant intervention technique in these deaths.

Relationship between annular calcification of plaques in the carotid sinus and perioperative hemodynamic disorder in carotid angioplasty and stenting.

OBJECTIVE: To investigate the correlation between annular plaque calcification in the carotid sinus and perioperative hemodynamic disorder (HD) in carotid angioplasty and stenting (CAS). METHODS: The clinical data of 49 patients undergoing CAS due to narrowing of the carotid sinus were retrospectively analyzed. All patients had preoperative carotid computed tomography angiography (CTA) and were divided into HD and non-HD groups based on the occurrence of HD in the perioperative period of CAS. HD was defined as persistent bradycardia (heart rate < 60 beats per min) or persistent hypotension (systolic blood pressure < 90 mmHg) in the perioperative period and lasting for at least 1 h. The baseline data, including the degree of carotid artery stenosis, plaque length, plaque thickness, calcified plaque morphologies (i.e., plaque circumferential angle: < 90° defined as dotted calcification; 90°-180° defined as arcuate calcification; > 180° defined as annular calcification), contralateral carotid artery conditions, balloon diameter, and stent types, were compared between the two groups. Binary logistic regression was used to analyze the risk factors for the occurrence of HD. RESULTS: Among the 49 patients undergoing CAS, 14 (28.57%) developed perioperative HD, and 35 did not. Annular calcification was more common in the patients in the HD group than in the non-HD group. No significant differences in the probabilities of dotted and arcuate calcifications were found between the two groups (p > 0.05). The duration of continuous dopamine consumption in the HD group was 9-71 h. The average hospital stay of the HD group (10.14 ± 4.17 days) was significantly longer than that of the non-HD group (6.57 ± 1.9 days; p < 0.001). Patients in the HD group had significantly more pronounced lumen stenosis (p = 0.033) and longer plaque length (p = 0.034) than those in the non-HD group. After adjusting for age and sex, multivariate regression analysis showed that the presence of annular plaque calcification was an independent predictor of HD (odds ratio: 7.68, 95% confidence interval: 1.46-40.37, p = 0.016). CONCLUSIONS: The occurrence of annular plaque calcification in the carotid sinus was an independent risk factor for perioperative HD in CAS. Preoperative carotid CTA assists with the early identification of high-risk patients who may develop HD.

Computed tomography-assessed variations of the carotid sinus.

PURPOSE AND BACKGROUND: Previous studies have identified variations regarding the morphology and location of the carotid sinus, a phenomenon still not commonly approached or studied on computed tomography angiography (CTA). Detailed characterization of the carotid sinus was performed on CTAs, determining its position, diameter and length. METHODS: The study group included 43 patients with disease-free carotid trunks subjected to cervical CTA. We measured the terminal caliber of the common carotid artery (CCA), as well as the calibers of the internal (ICA) and external carotid arteries (ECA) at their origin. The diameters were correlated with the location and the shape of the carotid sinus. We also measured the length of the sinus dilatation (carotid bulb), in regard to its location on the terminal branches of the common carotid artery. RESULTS: Mean diameters of the studied arteries were 7.39 ± 1.04 mm for the CCA, 6.71 ± 1.49 mm for the ICA and, respectively, 4.27 ± 0.75 mm for the ECA. The classical position of the carotid sinus was seen in 80% of cases, the rest being considered anatomical variants. The length of the carotid bulb on the ICA was 9.99 ± 2.22 mm, showing variability between genders. CONCLUSIONS: The carotid sinus does not always extend to the ICA, presenting different distribution patterns that might be relevant in sinus pathology from a clinical point of view, respectively from a surgical point of view during invasive or minimally invasive interventions on the carotid axis.

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

OBJECTIVE: Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3). Approach and Results: In 7626 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and RR [time elapsed between two successive R waves] intervals) and mechanical BRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism and nBRS or mechanical BRS were quantified using multivariable linear regression analysis. There were 319 subjects with T2D (61±6 years, 77% male), 1450 subjects with HMR (60±6 years, 72% male), and 5857 subjects with normal glucose metabolism (59±6 years, 57% male). Compared with normal glucose metabolism, nBRS was significantly lower in HMR subjects (ß=-0.07 [95% CI, -0.12 to -0.01]; P=0.029) and in subjects with T2D (ß=-0.18 [95% CI, -0.29 to -0.07]; P=0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mechanical BRS only among HMR patients who had both impaired fasting glucose and metabolic syndrome. CONCLUSIONS: In this community-based study of individuals aged 50 to 75, a graded decrease in nBRS was observed in HMR subjects and patients with overt T2D as compared with normal glucose metabolism subjects.

Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review.

This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP3R/s) regulating the intracellular calcium content [Ca2+]c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca2+]c changes were measured using cellular Ca2+-sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrodes in in vitro perfused-superfused rat carotid body preparations. The cell-permeant, 2-amino-ethoxy-diphenyl-borate (2-APB; 100 µM) and curcumin (50 µM) were used as the inhibitors of IP3R/s. These agents suppressed the [Ca2+]c, and CSN discharge increases in hypoxia but not in hypercapnia, leading to the conclusion that only the hypoxic effects were mediated via modulation of IP3R/s. The ATP-induced Ca2+ release from intracellular stores in a Ca2+-free medium was blocked with 2-APB, supporting this conclusion.

Efficacy of Carotid Artery Stenting Performed under General Anesthesia with Somatosensory Evoked Potential Monitoring.

OBJECTIVES: During carotid artery stenting (CAS), hemodynamics may be affected by the carotid sinus reflex in some cases. Although general anesthesia has been reported to stabilize intraoperative hemodynamics, the patient's neurological condition must be assessed indirectly. Therefore, we investigated the changes in intraoperative hemodynamics and perioperative complications of CAS under general anesthesia and evaluated the efficacy of somatosensory evoked potential (SEP) monitoring in detecting a reduction in perfusion during CAS. MATERIALS AND METHODS: From April 2011 to August 2016,57 consecutive patients who underwent CAS under general anesthesia were evaluated. The follow-up period ranged from 3 to 8 years. During CAS, anesthesiologists monitored and managed the hemodynamics. SEP monitoring was performed during the CAS procedure in all patients. RESULTS: Intraoperative hypotension (systolic blood pressure ≤ 100 mmHg) was evident in 16 patients (28.1%), and 13 patients (22.8%) experienced intraoperative bradycardia; however, all of these cases were promptly managed under general anesthesia. None of the patients showed systolic blood pressure < 50 mmHg from baseline. Regarding perioperative complications, none of the patients exhibited myocardial infarction or postoperative hyperperfusion symptoms, and there was no mortality. Among 21 patients (36.8%) with a decrease in the intraoperative SEP, 3 (5.3%) exhibited transient ischemic symptoms and 1 (1.8%) had postoperative infarction. CONCLUSIONS: CAS under general anesthesia is a safe and effective management option in terms of intraoperative hemodynamic stability. In addition, our findings indicate that SEP monitoring could be helpful in evaluating transient postoperative cerebral ischemia or cerebral infarction after CAS.

Molecular and cellular mechanisms of the organogenesis and development of the mammalian carotid body.

Despite significant advancements in understanding physiological properties of the carotid body, little attention has been paid to its organogenesis. This review addresses the molecular and cellular mechanisms underlying organogenesis of the carotid body in mammals. The carotid body consists of two types of cells, that is, glomus cells and sustentacular cells, that are derived from different origins. Glomus cells are derivatives of neural crest cells which form sympathetic ganglia. Sustentacular cells are derivatives of mesenchymal neural crest cells which colonize the third pharyngeal arch and form the wall of the third arch artery. Gene-targeting studies indicate that three elements are required for carotid body organogenesis: the carotid sinus nerve (CSN), third arch artery, and superior cervical sympathetic ganglion (SCG). The CSN sends sensory fibers and Schwann cells to the wall of the third arch artery. The third arch artery provides mesenchymal cells, which give rise to sustentacular cells. The nerve process from the SCG sends glomus cell progenitors into the carotid body primordium. The presence of stem cells in the adult carotid body was recently highlighted. The origin of stem cells, however, remains controversial. Based on embryonic development of the carotid body, this review proposes the origin of stem cells.

Forensic Progress on Death Following Carotid Sinus Inhibition.

ABSTRACT: Death after carotid sinus trauma is usually attributed to death from inhibition, a type of sudden death. Currently, the number of incidents is scarce, and related studies are few. Therefore, how to determine the involvement of carotid sinus and determine the role of diseases in the cause of death has always been a difficult point in forensic investigation. This article sorts out the research literature on carotid sinus related death at home and abroad in recent years, systematically reviews the anatomic structure of the carotid sinus nerve, the clinical epidemiology of carotid sinus syndrome, and the research on the death mechanism of carotid sinus injury at home and abroad in recent years, in order to provide references for forensic pathology research and prosecution.

Electrostimulation of the carotid sinus nerve in mice attenuates inflammation via glucocorticoid receptor on myeloid immune cells.

BACKGROUND: The carotid bodies and baroreceptors are sensors capable of detecting various physiological parameters that signal to the brain via the afferent carotid sinus nerve for physiological adjustment by efferent pathways. Because receptors for inflammatory mediators are expressed by these sensors, we and others have hypothesised they could detect changes in pro-inflammatory cytokine blood levels and eventually trigger an anti-inflammatory reflex. METHODS: To test this hypothesis, we surgically isolated the carotid sinus nerve and implanted an electrode, which could deliver an electrical stimulation package prior and following a lipopolysaccharide injection. Subsequently, 90 min later, blood was extracted, and cytokine levels were analysed. RESULTS: Here, we found that carotid sinus nerve electrical stimulation inhibited lipopolysaccharide-induced tumour necrosis factor production in both anaesthetised and non-anaesthetised conscious mice. The anti-inflammatory effect of carotid sinus nerve electrical stimulation was so potent that it protected conscious mice from endotoxaemic shock-induced death. In contrast to the mechanisms underlying the well-described vagal anti-inflammatory reflex, this phenomenon does not depend on signalling through the autonomic nervous system. Rather, the inhibition of lipopolysaccharide-induced tumour necrosis factor production by carotid sinus nerve electrical stimulation is abolished by surgical removal of the adrenal glands, by treatment with the glucocorticoid receptor antagonist mifepristone or by genetic inactivation of the glucocorticoid gene in myeloid cells. Further, carotid sinus nerve electrical stimulation increases the spontaneous discharge activity of the hypothalamic paraventricular nucleus leading to enhanced production of corticosterone. CONCLUSION: Carotid sinus nerve electrostimulation attenuates inflammation and protects against lipopolysaccharide-induced endotoxaemic shock via increased corticosterone acting on the glucocorticoid receptor of myeloid immune cells. These results provide a rationale for the use of carotid sinus nerve electrostimulation as a therapeutic approach for immune-mediated inflammatory diseases.

Complementary effectiveness of carotid sinus massage and tilt testing for the diagnosis of reflex syncope in patients older than 40 years: a cohort study.

AIMS: Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under 'real-world' conditions. METHODS AND RESULTS: We analysed all patients who had undergone CSM and TT in the years 2003-2019 for suspected reflex syncope. Carotid sinus massage was performed according to the 'Method of Symptoms'. Tilt testing was performed according to the 'Italian protocol' which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive. CONCLUSION: The overall diagnostic yield of the tests in patients >40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.

Reproducibility of carotid sinus massage.

AIMS: The reproducibility of carotid sinus massage (CSM) is debated. The aim of this study was to assess the reproducibility according to the methodology and diagnostic criteria defined by the guidelines on syncope of the European Society of Cardiology. METHOD: Among 2800 patients with syncope who underwent CSM in the years 2005-2019, 109 patients (62 males; mean age 76 ± 10 years) had performed a second CSM after a median of 28 months. Carotid sinus hypersensitivity (CSH) was diagnosed when CSM elicited a pause of >3 s and/or a fall in systolic blood pressure >50 mm Hg without reproduction of spontaneous symptoms. Carotid sinus syndrome (CSS) was established when spontaneous symptoms were reproduced in the presence of bradycardia and/or hypotension. RESULTS: The reproducibility of CSM was 78% for 18 CSS patients, 41% for 29 CSH patients, and 77% for 62 negative patients. The corresponding interrater agreement was good for CSS (kappa = 0.66), moderate for negative CSM (kappa = 0.42), and poor for CSH (kappa = 0.30). Combining CSH and negative tests, their reproducibility rose to 90% with kappa = 0.66. CONCLUSION: CSS but not CSH has a good reproducibility. About half of patients with CSH had a negative response at the second test, thus suggesting a great overlap between them.

[Syncope]. / Synkope.

Syncope is a frequent disorder, sometimes due to life-threatening causes. The uncertainty in its diagnosis requires a standardized approach. According to the 2018 European Society of Cardiology (ESC) guidelines, new aspects in evaluation and treatment include risk stratification and decision-making strategies during the initial evaluation in the emergency department, a reconsideration of diagnostic tests, algorithms for the treatment of reflex syncope, indications for an implantable cardioverter/defibrillator in high risk patients for sudden cardiac death, and organizational aspects such as interdisciplinary syncope units. The 2018 ESC guideline and the 2019 commentaries of the German Society of Cardiology (DGK) are an excellent and comprehensive instruction for safe, effective and efficient evaluation and therapy. However, some aspects require critical appraisal. The inadequate availability and reimbursement of pivotal diagnostic tests, such as tilt table testing and the implantable loop recorder is emphasized.