Orthostatic intolerance (OI) is defined as the development of characteristic symptoms while standing, which significantly improve by recumbency. The most common forms are vasovagal syncope (VVS), orthostatic hypotension, and postural orthostatic tachycardia syndrome (POTS). Lately, there has been a growing body of evidence that autoimmunity may play a role in the pathophysiology of orthostatic intolerance syndromes. The aim was to compare the presence and levels of autoimmune autoantibodies in patients with POTS, VVS syncope, and the control group. Altogether, 61 patients with symptoms of orthostatic intolerance were evaluated in this study - 19 POTS patients and 42 VVS patients. The control group contained 22 patients with no signs of orthostatic intolerance. We evaluated levels of autoantibodies against three subtypes of G-protein coupled adrenergic receptor (alpha-1 and beta-1,2 adrenergic receptors), type 4 of muscarinic acetylcholine receptor, and angiotensin II type 1 receptor. We compared the levels between the three patient groups. Significantly higher levels of angiotensin II type 1 receptor (AT1R) autoantibodies were found in the POTS group compared with controls (0.67± 0.35 ng/ml vs. 0.38±0.32 ng/ml, p=0.008). There was no significant difference in AT1R antibodies between the VVS and control groups (0.46±0.34 ng/ml vs 0.38±0.32 ng/ml, p= 0.38). Autoantibody concentration against ADRA1, ADRB1, ADRB2, and M4R were not significantly different between the groups. Autoimmune mechanisms may lead to abnormal regulation of the renin-angiotensin-aldosterone system and may contribute to the pathophysiology of POTS.
- MeSH
- autoimunita * MeSH
- autoprotilátky * krev MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ortostatická intolerance * krev imunologie diagnóza MeSH
- receptor angiotensinu typ 1 imunologie MeSH
- syndrom posturální ortostatické tachykardie * imunologie krev diagnóza MeSH
- vazovagální synkopa * imunologie krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- autoprotilátky * MeSH
- biologické markery MeSH
- receptor angiotensinu typ 1 MeSH
Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.
- Klíčová slova
- Atrioventricular block, Autonomic nervous system, Reflex syncope, Sinus bradycardia, Vasovagal syncope,
- MeSH
- ablace MeSH
- bradykardie * terapie patofyziologie chirurgie diagnóza MeSH
- katetrizační ablace metody MeSH
- konsensus MeSH
- lidé MeSH
- srdeční frekvence MeSH
- vazovagální synkopa * chirurgie diagnóza patofyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- směrnice pro lékařskou praxi MeSH
- Klíčová slova
- autonomic nervous system, cardioneuroablation, catheter ablation, extracardiac vagal stimulation, functional bradycardia, ganglionic plexi, syncope,
- MeSH
- bradykardie chirurgie MeSH
- katetrizační ablace * škodlivé účinky MeSH
- lidé MeSH
- vazovagální synkopa * chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
BACKGROUND AND IMPORTANCE: In 2018, the European Society of Cardiology (ESC) produced syncope guidelines that for the first-time incorporated Emergency Department (ED) management. However, very little is known about the characteristics and management of this patient group across Europe. OBJECTIVES: To examine the prevalence, clinical presentation, assessment, investigation (ECG and laboratory testing), management and ESC and Canadian Syncope Risk Score (CSRS) categories of adult European ED patients presenting with transient loss of consciousness (TLOC, undifferentiated or suspected syncope). DESIGN: Prospective, multicentre, observational cohort study. SETTINGS AND PARTICIPANTS: Adults (≥18 years) presenting to European EDs with TLOC, either undifferentiated or thought to be of syncopal origin. MAIN RESULTS: Between 00:01 Monday, September 12th to 23:59 Sunday 25 September 2022, 952 patients presenting to 41 EDs in 14 European countries were enrolled from 98 301 ED presentations (n = 40 sites). Mean age (SD) was 60.7 (21.7) years and 487 participants were male (51.2%). In total, 379 (39.8%) were admitted to hospital and 573 (60.2%) were discharged. 271 (28.5%) were admitted to an observation unit first with 143 (52.8%) of these being admitted from this. 717 (75.3%) participants were high-risk according to ESC guidelines (and not suitable for discharge from ED) and 235 (24.7%) were low risk. Admission rate increased with increasing ESC high-risk factors; 1 ESC high-risk factor; n = 259 (27.2%, admission rate=34.7%), 2; 189 (19.9%; 38.6%), 3; 106 (11.1%, 54.7%, 4; 62 (6.5%, 60.4%), 5; 48 (5.0%, 67.9%, 6+; 53 (5.6%, 67.9%). Furthermore, 660 (69.3%), 250 (26.3%), 34 (3.5%) and 8 (0.8%) participants had a low, medium, high, and very high CSRS respectively with respective admission rates of 31.4%, 56.0%, 76.5% and 75.0%. Admission rates (19.3-88.9%), use of an observation/decision unit (0-100%), and percentage high-risk (64.8-88.9%) varies widely between countries. CONCLUSION: This European prospective cohort study reported a 1% prevalence of syncope in the ED. 4 in 10 patients are admitted to hospital although there is wide variation between country in syncope management. Three-quarters of patients have ESC high-risk characteristics with admission percentage rising with increasing ESC high-risk factors.
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- synkopa * diagnóza epidemiologie terapie MeSH
- urgentní služby nemocnice * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Kanada MeSH
Orthostatic intolerance (OI) is defined as a group of diseases which symptoms are typically manifested in a standing position. These symptoms result from cerebral hypoperfusion and disappear in the supine position. We include postural orthostatic intolerance syndrome (POTS), orthostatic hypotension (OH) and vasovagal orthostatic syncope in this group of diseases. Each of them have similar clinical presentation (blurred vision, weakness, dizziness, nausea, headaches, fatigue). However, they vary from each other in biochemical, autonomic and hemodynamic characteristics. The aim of the work is to provide an overview of humoral and non-human markers that are involved in the etiopathogenesis of orthostatic intolerance.
- Klíčová slova
- POTS, biomarker, biomarkers, orthostatic intolerance, vasovagal syncope,
- MeSH
- biologické markery MeSH
- lidé MeSH
- ortostatická intolerance * diagnóza MeSH
- syndrom posturální ortostatické tachykardie * diagnóza MeSH
- synkopa diagnóza MeSH
- vazovagální synkopa * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
[Figure: see text]
- Klíčová slova
- Catheter ablation, Methods, Neurally mediated syncope, Reflex syncope, Syncope, Vasovagal syncope,
- MeSH
- bradykardie MeSH
- lidé MeSH
- reflex MeSH
- vazovagální synkopa * diagnóza chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The endothelin system may play a role in the pathogenesis of vasovagal syncope (VVS) because it is implicated in blood pressure regulation. We hypothesized that endothelin-related genetic polymorphisms might modulate susceptibility to VVS. This study aimed to evaluate the possible influence of endothelin-1 (EDN1) and endothelin receptor A (EDNRA) gene variants on the occurrence of tilt-induced VVS and autonomic nervous system activity during the head-up tilt test (HUT). Results were expressed as mean +/- SEM. In 254 patients with recurrent syncope (age 45.33+/-1.22 years, 94 males, 160 females), heart rate variability (HRV) was measured during HUT. EDN1 rs5370 G>T and EDNRA rs5333 T>C gene polymorphisms were assessed using high-resolution melting analysis. There was no statistically significant association between polymorphisms EDN1 rs5370 and EDNRA rs5333 and positivity of HUT or hemodynamic types of VVS. Patients with GT or TT genotypes at the rs5370 locus of the EDN1 had significantly higher values of high-frequency (HF) and the standard deviation of the average NN intervals at the time of the syncope, and they tended to have lower low-frequency (LF) and LF/HF ratio when compared to homozygotes (GG). No statistically significant differences were found in HRV parameters concerning the EDNRA rs5333 genotypes. Our findings suggest the potential role of EDN1 rs5370 variants in regulating autonomic nervous activity and pathogenesis of VVS.
- MeSH
- dospělí MeSH
- endotelin-1 * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický genetika MeSH
- receptor endotelinu A genetika MeSH
- srdeční frekvence genetika MeSH
- test na nakloněné rovině MeSH
- vazovagální synkopa * diagnóza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- EDNRA protein, human MeSH Prohlížeč
- endotelin-1 * MeSH
- receptor endotelinu A MeSH
BACKGROUND: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. OBJECTIVES: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. METHODS: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. RESULTS: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). CONCLUSIONS: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.
- Klíčová slova
- KCNJ2, genetics, inherited arrhythmias, life-threatening arrhythmic events, sudden cardiac death,
- MeSH
- amiodaron aplikace a dávkování škodlivé účinky MeSH
- Andersenův syndrom komplikace genetika terapie MeSH
- antiarytmika aplikace a dávkování škodlivé účinky MeSH
- beta blokátory terapeutické užití MeSH
- databáze faktografické MeSH
- defibrilátory implantabilní MeSH
- dítě MeSH
- dospělí MeSH
- draslíkové kanály dovnitř usměrňující genetika MeSH
- elektrokardiografie MeSH
- genetické testování MeSH
- hodnocení rizik * MeSH
- kojenec MeSH
- komorová tachykardie etiologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- náhlá srdeční smrt epidemiologie MeSH
- předškolní dítě MeSH
- srdeční arytmie etiologie terapie MeSH
- svalová slabost etiologie MeSH
- synkopa etiologie terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amiodaron MeSH
- antiarytmika MeSH
- beta blokátory MeSH
- draslíkové kanály dovnitř usměrňující MeSH
- KCNJ2 protein, human MeSH Prohlížeč
BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. RESULTS: In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. CONCLUSIONS: Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. TRIAL REGISTRATION: ClinicalTrials.org NCT01784562 . Registered February 4, 2013.
- Klíčová slova
- Chronic thromboembolic pulmonary hypertension, Early access study, Riociguat,
- MeSH
- antihypertenziva aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chronická nemoc MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní hypertenze farmakoterapie patofyziologie MeSH
- pyrazoly aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- pyrimidiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- synkopa chemicky indukované MeSH
- tromboembolie komplikace MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- Názvy látek
- antihypertenziva MeSH
- pyrazoly MeSH
- pyrimidiny MeSH
- riociguat MeSH Prohlížeč
