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OBJECTIVE: The study evaluated the positivity rate, hemodynamic responses, and prognosis in terms of syncopal recurrence among patients with situational syncope (SS) stratified according to the underlying situational triggers. METHODS: We retrospectively evaluated all consecutive patients with SS who underwent nitroglycerin (NTG)-potentiated HUTT at Syncope Unit of the University of Campania "Luigi Vanvitelli" - Monaldi Hospital from March 1st, 2017, to May 1st, 2023. All patients were followed for at least one year. The study population was divided according to the underlying triggers (micturition, swallow, defecation, cough/sneeze, post-exercise). RESULTS: 236 SS patients (mean age 50± 19.3 years; male 63.1%) were enrolled; among them, the situational trigger was micturition in 109 patients (46.2%); swallow in 32 (13.6%) patients; defecation in 35 (14.8%) patients; post-exercise in 41 (17.4%) patients and cough/sneeze in 17 (7.2%) patients. There were no significant differences in baseline clinical characteristics and HUTT responses between different situational triggers. The Kaplan-Meier analysis did not show a statistically different rate of syncope recurrence across patients stratified by baseline situational triggers (log-rank p=0.21). CONCLUSIONS: SS appears to be a homogenous syndrome and different triggers do not impact the HUTT response or syncope recurrence at 1 year.
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INTRODUCTION: The aim of our study was to evaluate the prevalence and clinical predictors of vasodepressor (VD) response during head-up tilt test (HUTT) in patients with history of syncope admitted to a tertiary referral syncope unit. MATERIAL AND METHODS: We retrospectively evaluated all consecutive patients who underwent HUTT for suspected or established reflex syncope at our institution from March 1st, 2017, to June 1st, 2023. VD response was defined when syncope occurred during hypotension along with no or slight (< 10% bpm) decrease of heart rate. Univariate and multivariate analyses were performed to test the association of VD response to HUTT with a set of clinical covariates. RESULTS: 1780 patients (40 ± 19.9 years; 49.3% male) were included; among them, 1132 (63 %) showed a positive response to HUTT and 124 (7.0%) had a VD response. The prevalence of VD response showed a peak after 69 years (11.52% vs 6.18%; P = 0.0016), mainly driven by male patients (13.7% vs 4.9%; P < 0.0001). At multivariate analysis, age (OR: 1.15; P = 0.0026) was independently associated to HUTT-induced VD syncope; in contrast, smoking (OR: 0.33: P = 0.0009) and non-classical presentation of syncope (OR: 0.55; P = 0.0029) inversely correlated with VD syncope. CONCLUSIONS: VD response represents the less frequent responses among those induced by HUTT, accounting up to 7% of overall responses. A gender and age-related distribution has been shown. Advanced age was the only independent predictor of VD syncope; conversely, smoking and non-classical presentation of syncope reduced the probability of VD response to HUTT.
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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.
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BACKGROUND: We aimed to identify the target of deprescribing, i.e. the 24-hour SBP increase needed to achieve the greatest reduction of SBP drops. METHOD: Forty hypertensive patients (mean age 73.6 ± 9.3 years, 26 females) with reflex syncope and SBP drops on a screening ABPM were advised to withdraw or to reduce their therapy. The study objective was the reduction of SBP drops <90 mmHg and <100 mmHg on a second ABPM performed within 3 months. RESULTS: Out of a total of 98 drugs taken during ABPM 1, 44 were withdrawn, 16 had a dose reduction and 38 remained unchanged at the time of ABPM 2. 24-hour SBP increased from 119.7 ± 10.1 mmHg to 129.4 ± 13.2 mmHg during ABPM2. Total disappearance of daytime SBP drops <100 mmHg was achieved in 20 (50 %) patients who had 24-hour SBP of 134±13 mmHg and an increase from ABPM 1 of 12 (IQR 5-20) mmHg. Compared with the 20 patients who had persistence of drops, these patients had a greater reduction of the number of hypotensive drugs (67 % versus 19 %, p = 0.002) and a greater rate of withdrawals (62 % versus 29 %, p = 0.003). CONCLUSION: In hypertensive patients with reflex syncope, an increase of 12 mmHg and an absolute value of 24-hour SBP of 134 mmHg appear to represent the optimal goals aimed to prevent SBP drops. Drugs withdrawal, rather than simply dose reduction, is mostly required to achieve the above target.
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The term non-cardiac syncope includes all forms of syncope, in which primary intrinsic cardiac mechanism and non-syncopal transient loss of consciousness can be ruled out. Reflex syncope and orthostatic hypotension are the most frequent aetiologies of non-cardiac syncope. As no specific therapy is effective for all types of non-cardiac syncope, identifying the underlying haemodynamic mechanism is the essential prerequisite for an effective personalized therapy and prevention of syncope recurrences. Indeed, choice of appropriate therapy and its efficacy are largely determined by the syncope mechanism rather than its aetiology and clinical presentation. The two main haemodynamic phenomena leading to non-cardiac syncope include either profound hypotension or extrinsic asystole/pronounced bradycardia, corresponding to two different haemodynamic syncope phenotypes, the hypotensive and bradycardic phenotypes. The choice of therapy-aimed at counteracting hypotension or bradycardia-depends on the given phenotype. Discontinuation of blood pressure-lowering drugs, elastic garments, and blood pressure-elevating agents such as fludrocortisone and midodrine are the most effective therapies in patients with hypotensive phenotype. Cardiac pacing, cardioneuroablation, and drugs preventing bradycardia such as theophylline are the most effective therapies in patients with bradycardic phenotype of extrinsic cause.
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Hipotensión Ortostática , Hipotensión , Síncope Vasovagal , Humanos , Bradicardia/diagnóstico , Bradicardia/terapia , Bradicardia/complicaciones , Síncope/diagnóstico , Síncope/etiología , Síncope/terapia , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/terapia , Hipotensión Ortostática/complicacionesRESUMEN
BACKGROUND: Approximately 50% of patients with unexplained syncope and negative head-up tilt test (HUTT) who have an electrocardiogram (ECG) documentation of spontaneous syncope during implantable loop recorder (ILR) show an asystolic pause at the time of the event. OBJECTIVE: The aim of the study was to evaluate the age distribution and clinical predictors of asystolic syncope detected by ILR in patients with unexplained syncope and negative HUTT. METHODS: This research employed a retrospective, single-center study of consecutive patients. The ILR-documented spontaneous syncope was classified according to the International Study on Syncope of Uncertain Etiology (ISSUE) classification. RESULTS: Among 113 patients (54.0 ± 19.6 years; 46% male), 49 had an ECG-documented recurrence of syncope during the observation period and 28 of these later (24.8%, corresponding to 57.1% of the patients with a diagnostic event) had a diagnosis of asystolic syncope at ILR: type 1A was present in 24 (85.7%), type 1B in 1 (3.6%), and type 1C in 3 (10.7%) patients. The age distribution of asystolic syncope was bimodal, with a peak at age < 19 years and a second peak at the age of 60-79 years. At Cox multivariable analysis, syncope without prodromes (OR 3.7; p = 0.0008) and use of beta blockers (OR 3.2; p = 0.002) were independently associated to ILR-detected asystole. CONCLUSIONS: In patients with unexplained syncope and negative HUTT, the age distribution of asystolic syncope detected by ILR is bimodal, suggesting a different mechanism responsible for asystole in both younger and older patients. The absence of prodromes and the use of beta blockers are independent predictors of ILR-detected asystole.
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Paro Cardíaco , Síncope , Humanos , Masculino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Estudios Retrospectivos , Distribución por Edad , Síncope/diagnóstico , Síncope/etiología , Paro Cardíaco/complicaciones , Electrocardiografía , Electrocardiografía Ambulatoria/efectos adversosRESUMEN
AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12â b.p.m. and systolic blood pressure (SBP) was 108 ± 19â mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14â b.p.m. within a median of 0.1â min [inter-quartile range (IQR), 0.1-0.7â min] when the SBP was 99 ± 21â mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17â mmHg and the CLS rate was 95 ± 13â b.p.m. The onset of CLS pacing was 1.7â min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0â min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22â mmHg at baseline to 69 ± 4â mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1â b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.
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Marcapaso Artificial , Síncope Vasovagal , Humanos , Estimulación Cardíaca Artificial/métodos , Hemodinámica , Marcapaso Artificial/efectos adversos , Reproducibilidad de los Resultados , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/prevención & control , Pruebas de Mesa Inclinada/métodosRESUMEN
AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5â mmHg (P < 0.0001). The number of SBP drops <90 and <100â mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around â¼15â mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13â mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.
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Hipertensión , Hipotensión , Intolerancia Ortostática , Síncope Vasovagal , Humanos , Antihipertensivos/uso terapéutico , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Intolerancia Ortostática/diagnóstico , Intolerancia Ortostática/tratamiento farmacológico , Reflejo , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/prevención & control , Prueba de Estudio ConceptualRESUMEN
BACKGROUND: The head-up tilt test (HUT) and other evidence suggest that the vagal effect on the heart decreases with age. OBJECTIVES: The main aim of the study was to assess whether this age effect also affects the rate of asystole in spontaneous reflex syncope (RS). METHOD: We performed an analysis of pooled individual data from 4 studies that recruited patients ≥40 years of age affected by certain or suspected RS who received an implantable loop recorder (ILR) and reported follow-up data on syncope recurrence. We assessed the presence of asystolic syncope of >3 seconds or nonsyncopal asystole of >6 seconds recorded by ILR and compared the findings to tilt test results on the same patients. RESULTS: A total of 1,046 patients received ILR because of unexplained syncope. Of these, 201 (19.2%) had a documentation of an asystolic event of 10-second (Q1-Q3: 6- to 15-second) duration. They were subdivided in 3 age tertiles: ≤60 years (n = 64), 61 to 72 years (n = 72), and ≥73 years (n = 65). The rate of asystolic events was similar in the 3 subgroups (50.1%, 50.1%, and 49.2%, respectively; P = 0.99). Conversely, the rate of asystolic syncope induced during HUT (performed in 169 of 201) was greatly age dependent (31.0%, 12.1%, and 11.1% in increasing age tertiles, respectively; P = 0.009). CONCLUSIONS: The rate of the spontaneous asystolic form of RS documented by ILR is constant at any age >40 years. Conversely, the rate of asystolic syncope induced by HUT is higher in younger patients and decreases with age. The contrasting results between spontaneous and tilt-induced events cast doubt on the concept that asystole in RS is less common in older patients.
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Paro Cardíaco , Síncope Vasovagal , Humanos , Anciano , Persona de Mediana Edad , Adulto , Síncope Vasovagal/diagnóstico , Síncope/diagnóstico , Síncope/epidemiología , Síncope/etiología , Pruebas de Mesa Inclinada/efectos adversos , Paro Cardíaco/complicaciones , ReflejoRESUMEN
Although very common, the precise mechanisms that explain the symptomatology of neuroendocrine syncope (NES) remain poorly understood. This disease, which can be very incapacitating, manifests itself as a drop in blood pressure secondary to vasodilation and/or extreme slowing of heart rate. As studies continue, the involvement of the adenosinergic system is becoming increasingly evident. Adenosine, which is an ATP derivative, may be involved in a large number of cases. Adenosine acts on G protein-coupled receptors with seven transmembrane domains. A1 and A2A adenosine receptor dysfunction seem to be particularly implicated since the activation leads to severe bradycardia or vasodilation, respectively, two cardinal symptoms of NES. This mini-review aims to shed light on the links between dysfunction of the adenosinergic system and NHS. In particular, signal transduction pathways through the modulation of cAMP production and ion channels in relation to effects on the cardiovascular system are addressed. A better understanding of these mechanisms could guide the pharmacological development of new therapeutic approaches.
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Adenosina , Síncope , Animales , Anuros , Presión Sanguínea , Frecuencia CardíacaRESUMEN
OBJECTIVE: The study compared clinical characteristics and response at head-up tilt test (HUTT) between situational (SS) and vasovagal syncope (VVS). METHODS: Consecutive patients who underwent nitroglycerin-potentiated HUTT were retrospectively dichotomised into two groups: those with a history of SS and those with a history of VVS. The patients with SS were further subdivided into patients with SS alone and with SS and at least one episode of VVS. RESULTS: 1285 patients were enrolled: 246 (19.1%) had SS (SS alone in 121 and SS+VVS in 125). Patients with SS were older (48.8±20.0 vs 44.4±19.1, p=0.007) and more frequently male (57.3% vs 47.7%, p=0.001). At multivariable analysis, smoking habit (OR 2.28; p<0.0001), history of traumatic syncope (OR 2.29; p=0.0001) and ACE inhibitors/angiotensin II receptor blockers (OR 4.74; p<0.0001) were independently associated with SS. HUTT was positive in 175 (71.1%) patients with SS and in 737 (70.9%) patients with VVS (p=0.9). Patients with SS showed more mixed (42.3% vs 32.0%, p=0.002) and vasodepressor forms (10.6% vs 6.1%, p=0.01) and less cardioinhibitory responses compared with others (18.3% vs 32.8%, p<0.0001). CONCLUSIONS: Compared with VVS, patients with SS have different clinical characteristics and a higher prevalence of hypotensive drugs leading to hypotensive susceptibility. The positivity rate of HUTT is high and similar to that of VVS, although patients with SS show a higher prevalence of hypotensive responses.
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Síncope Vasovagal , Síncope , Humanos , Masculino , Estudios Retrospectivos , Síncope/diagnóstico , Síncope/etiología , Síncope Vasovagal/diagnóstico , Pruebas de Mesa Inclinada , NitroglicerinaRESUMEN
Over the last 25 years, the Europace journal has greatly contributed to dissemination of research and knowledge in the field of syncope. More than 400 manuscripts have been published in the journal. They undoubtedly improved our understanding of syncope. This symptom is now clearly differentiated from other forms of transient loss of consciousness. The critical role of vasodepression and/or cardioinhibition as final mechanisms of reflex syncope is emphasized. Current diagnostic approach sharply separates between cardiac and autonomic pathways. Physiologic insights have been translated, through rigorously designed clinical trials, into non-pharmacological or pharmacological interventions and interventional therapies. The following manuscript is intended to give the reader the current state of the art of knowledge of syncope by highlighting landmark contributions of the Europace journal.
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Síncope Vasovagal , Síncope , Humanos , Síncope/diagnóstico , Síncope/etiología , Síncope/terapia , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/terapia , CorazónRESUMEN
AIMS: Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. METHODS AND RESULTS: Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. CONCLUSION: A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Síncope Vasovagal , Humanos , Femenino , Persona de Mediana Edad , Masculino , Síncope/diagnóstico , Síncope/etiología , Causalidad , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/etiologíaRESUMEN
BACKGROUND: The traditional nitroglycerin (NTG) head-up tilt test (HUTT) is time-consuming and the test duration is a barrier to widespread utilization in clinical practice. It was hypothesized that a short-duration protocol is not inferior to the traditional protocol regarding the positivity rate and has a similar distribution of hemodynamic response. METHODS AND RESULTS: Patients undergoing HUTT were randomized 1:1 to a 10 min passive phase plus a 10 min 0.3 mg NTG if the passive phase was negative (Fast) or to a 20 min passive phase plus a 15 min 0.3 mg NTG if the passive phase was negative (Traditional). A sample size of 277 patients for each group achieved 80% power to detect an expected difference of 0% with a non-inferiority margin of -10% using a one-sided t-test and assuming a significant level alpha of 0.025. A total of 554 consecutive patients (mean age 46.6 ± 19.3 years, 47.6% males) undergoing HUTT for suspected vasovagal syncope were randomly assigned to the Fast (n = 277) or Traditional (n = 277) protocol. A positive response was defined as the induction of syncope in presence of hypotension/bradycardia, and was observed in 167 (60.3%) patients with Fast and in 162 (58.5%) patients with the Traditional protocol. There was a trend of lesser vasodepressor response (14.8% Fast vs. 20.6% Traditional) which was significant during the passive phase (P = 0.01). CONCLUSION: The diagnostic value of the Fast HUTT protocol is similar to that of the Traditional protocol and therefore the Fast protocol can be used instead of the Traditional protocol.
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Nitroglicerina , Síncope Vasovagal , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Síncope Vasovagal/diagnóstico , Vasodilatadores , Síncope/diagnóstico , Pruebas de Mesa Inclinada/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.