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Heart Rhythm Jul 2020Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasovagal syncope (VVS) significantly reduces quality of life, yet lacks effective medical therapies. Pharmacological norepinephrine transporter (NET) inhibition increases synaptic norepinephrine reuptake, which may be able to prevent hypotension, bradycardia, and syncope.
OBJECTIVE
The objective of this systematic review was to evaluate the ability of 3 NET inhibitors-reboxetine, sibutramine, and atomoxetine-to prevent head-up tilt-induced vasovagal outcomes in healthy participants and patients with VVS.
METHODS
Relevant studies were identified from Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature without language restriction from database inception to August 2019. All randomized controlled trials comparing the benefit of a NET inhibitor vs placebo in adult populations were selected for review and meta-analysis.
RESULTS
Four studies (101 participants) met inclusion criteria. The mean study size was 25 (range 11-56) participants. NET inhibition reduced the likelihood of vasovagal reactions marked by hypotension and bradycardia in healthy participants during head-up tilt testing (relative risk 0.15; 95% confidence interval 0.04-0.52; P = .003). This relative risk reduction also occurred in patients with VVS during head-up tilt when given atomoxetine (relative risk 0.49; 95% confidence interval 0.28-0.86; P = .01). This was achieved through heart rate compensation with NET inhibition toward the end of tilt testing (106 ± 32 beats/min vs 60 ± 22 beats/min; P < .001), which in turn preserved cardiac output and mean arterial pressure (71 ± 20 mm Hg vs 43 ± 13 mm Hg; P < .001) in the absence of significantly increased systemic vascular resistance.
CONCLUSION
NET inhibition prevents severe vasovagal reactions and syncope induced by head-up tilt testing in both healthy participants and patients with VVS. Pharmacological NET inhibition is a promising potential treatment of recurrent syncope.
Topics: Adult; Cardiac Output; Heart Rate; Humans; Norepinephrine Plasma Membrane Transport Proteins; Quality of Life; Reboxetine; Syncope, Vasovagal; Young Adult
PubMed: 32151742
DOI: 10.1016/j.hrthm.2020.02.033 -
Pacing and Clinical Electrophysiology :... Oct 2019Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied...
Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied in recurrent vasovagal syncope (VVS), with conflicting results. We aim to investigate the role of pacemaker therapy and anti-syncope pacing mode in cardioinhibitory recurrent VVS. MEDLINE, Cochrane Library and registered clinical trials were searched for single or double-blind randomized controlled trials on pacing as a treatment for recurrent VVS. Five studies were eligible, overall enrolling 228 patients. After pooling data from all trials, pacemaker therapy showed a 63% reduction in syncope recurrence compared to control [Risk Ratio (RR): 0.37; 95% CI: 0.14-0.98; I = 67%)]. Subgroup analyses suggested that the effect was greater in single-blind studies (RR: 0.07; 95% CI: 0.01-0.52, I = 0%). When comparing pacing algorithms, the results from RDR versus no pacing trials (n = 2) did not show a significant reduction in syncope recurrence (RR: 0.73; 95% CI: 0.25-2.16, I 60 = 75%). In contrast, the data from the CLS versus standard pacing trials (n = 3) evidenced a statistically meaningful reduction in syncopal burden (RR: 0.18; 95% CI: 0.07-0.47, I = 0%). It is unclear whether pacemaker therapy reduces syncopal burden in cardioinhibitory recurrent VVS. However, our results suggest effectiveness of CLS pacing mode.
Topics: Algorithms; Cardiac Pacing, Artificial; Humans; Randomized Controlled Trials as Topic; Recurrence; Syncope, Vasovagal
PubMed: 31433493
DOI: 10.1111/pace.13790 -
JAMA Jun 2019Syncope can result from a reduction in cardiac output from serious cardiac conditions, such as arrhythmias or structural heart disease (cardiac syncope), or other...
IMPORTANCE
Syncope can result from a reduction in cardiac output from serious cardiac conditions, such as arrhythmias or structural heart disease (cardiac syncope), or other causes, such as vasovagal syncope or orthostatic hypotension.
OBJECTIVE
To perform a systematic review of studies of the accuracy of the clinical examination for identifying patients with cardiac syncope.
STUDY SELECTION
Studies of adults presenting to primary care, emergency departments, or referred to specialty clinics.
DATA EXTRACTION AND SYNTHESIS
Relevant data were abstracted from articles in databases through April 9, 2019, and methodologic quality was assessed. Included studies had an independent comparison to a reference standard.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, and likelihood ratios (LRs).
RESULTS
Eleven studies of cardiac syncope (N = 4317) were included. Age at first syncope of at least 35 years was associated with greater likelihood of cardiac syncope (n = 323; sensitivity, 91% [95% CI, 85%-97%]; specificity, 72% [95% CI, 66%-78%]; LR, 3.3 [95% CI, 2.6-4.1]), while age younger than 35 years was associated with a lower likelihood (LR, 0.13 [95% CI, 0.06-0.25]). A history of atrial fibrillation or flutter (n = 323; sensitivity, 13% [95% CI, 6%-20%]; specificity, 98% [95% CI, 96%-100%]; LR, 7.3 [95% CI, 2.4-22]), or known severe structural heart disease (n = 222; range of sensitivity, 35%-51%, range of specificity, 84%-93%; range of LR, 3.3-4.8; 2 studies) were associated with greater likelihood of cardiac syncope. Symptoms prior to syncope that were associated with lower likelihood of cardiac syncope were mood change or prodromal preoccupation with details (n = 323; sensitivity, 2% [95% CI, 0%-5%]; specificity, 76% [95% CI, 71%-81%]; LR, 0.09 [95% CI, 0.02-0.38]), feeling cold (n = 412; sensitivity, 2% [95% CI, 0%-5%]; specificity, 89% [95% CI, 85%-93%]; LR, 0.16 [95% CI, 0.06-0.64]), or headache (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 80% [95% CI, 75%-85%]; LR, 0.17 [95% CI, 0.06-0.55]). Cyanosis witnessed during the episode was associated with higher likelihood of cardiac syncope (n = 323; sensitivity, 8% [95% CI, 2%-14%]; specificity, 99% [95% CI, 98%-100%]; LR, 6.2 [95% CI, 1.6-24]). Mood changes after syncope (n = 323; sensitivity, 3% [95% CI, 0%-7%]; specificity, 83% [95% CI, 78%-88%]; LR, 0.21 [95% CI, 0.06-0.65]) and inability to remember behavior prior to syncope (n = 323; sensitivity, 5% [95% CI, 0%-9%]; specificity, 82% [95% CI, 77%-87%]; LR, 0.25, [95% CI, 0.09-0.69]) were associated with lower likelihood of cardiac syncope. Two studies prospectively validated the accuracy of the multivariable Evaluation of Guidelines in Syncope Study (EGSYS) score, which is based on 6 clinical variables. An EGSYS score of less than 3 was associated with lower likelihood of cardiac syncope (n = 456; range of sensitivity, 89%-91%, range of specificity, 69%-73%; range of LR, 0.12-0.17; 2 studies). Cardiac biomarkers show promising diagnostic accuracy for cardiac syncope, but diagnostic thresholds require validation.
CONCLUSIONS AND RELEVANCE
The clinical examination, including the electrocardiogram as part of multivariable scores, can accurately identify patients with and without cardiac syncope.
Topics: Age Factors; Aged; Biomarkers; Diagnosis, Differential; Electrocardiography; Female; Heart Diseases; Humans; Risk Factors; Sensitivity and Specificity; Syncope
PubMed: 31237649
DOI: 10.1001/jama.2019.8001 -
Prehospital Emergency Care 2020Syncope is a common condition that may be prevented. There are non-pharmacological interventions that may be of benefit during the acute episode preceding syncope...
Syncope is a common condition that may be prevented. There are non-pharmacological interventions that may be of benefit during the acute episode preceding syncope (presyncope), including physical counter-pressure maneuvers (PCM) or change of body position. We performed a systematic review of interventions that may be applied during presyncope as an immediate, first aid tactic. We searched Medline, Embase, and CINAHL and used the Grading of Recommendations Assessment, Development and Evaluation methods, and risk of bias assessments to determine the certainty of the evidence. We included randomized controlled trials (RCTs), non-randomized studies, and case series investigating adults and children with signs and symptoms of presyncope of suspected vasovagal or orthostatic origin who applied any intervention that could be used as an immediate, first aid intervention. We examined the following outcomes: prevention of syncope, adverse events, symptom improvement, and vital signs. We conducted a sub-group analysis based on the etiology of vasovagal or orthostatic presyncope. We screened 5,160 titles and abstracts followed by 81 full text articles. We identified 8 studies meeting inclusion criteria, including 2 RCTs and 6 observational studies. All studies used PCM in adults and all were judged to be of low and very low certainty of evidence. For prevention of syncope, one RCT demonstrated benefit with the use of PCM (RR = 1.80 [1.26-1.89]), while observational studies failed to show benefit (RR = 1.31 [0.98 - 1.75]). Two RCTs showed benefit in symptom improvement (RR = 6.00 [2.21 - 8.61] and (RR = 1.57 [1.06 - 1.93]). Blood pressure (BP) improved with the use of PCM: systolic BP mean difference (MD) 21 mmHg higher (95% CI: 18.25 to 23.41 BPM) and diastolic BP MD 11 mmHg higher (95% CI: 9.39 to 13.10 mmHg higher). No adverse events were reported. While there is a minimal amount of evidence available and the findings were mixed, PCM may provide benefit for prevention of syncope during acute episodes of presyncope and may be tried in the first aid setting. No evidence was found for other non-pharmacologic interventions or for the use of PCM in children.
Topics: Adolescent; Adult; Aged; Blood Pressure; Child; Emergency Medical Services; Humans; Middle Aged; Syncope; Young Adult
PubMed: 30957664
DOI: 10.1080/10903127.2019.1605431 -
Frontiers in Physiology 2019The paper presents a meta-analysis of studies comparing hemodynamic parameters: heart rate (HR), systolic blood pressure (sBP), diastolic blood pressure (dBP), and...
The paper presents a meta-analysis of studies comparing hemodynamic parameters: heart rate (HR), systolic blood pressure (sBP), diastolic blood pressure (dBP), and stroke volume (SV) measured during head-up tilt table test (HUTT) in patients with positive and negative HUT test outcome. Pubmed and Clinical Key databases were searched for English-only articles presenting results of biosignals measurements during tilt test in patients suffering from syncope. From 3,289 articles 13 articles published between 1997 and 2015 investigating 892 patients (467 with positive HUTT outcome and 401 with negative one) were selected. There were not statistically significant differences observed between the parameters measured in supine position in patients with positive and negative test outcome [HR ( = 0.86), sBP ( = 0.32), dBP ( = 0.21), SV ( = 0.71)]. In tilt position the parameters HR and SV were significantly different when compared between the two groups of patients [HR ( = 0.02), sBP ( = 0.10), dBP ( = 0.59), SV ( = 0.0004)]. Changes in HR and SV parameters in response to tilt test turned out to be statistically significant. In supine position the differences between patients with positive and negative test outcome were not significant, hence tilt test can be considered as necessary in the diagnosis of vasovagal syndrome.
PubMed: 30899228
DOI: 10.3389/fphys.2019.00184 -
Journal of Interventional Cardiac... Jun 2019A proportion of patients with vasovagal syncope (VVS) experience recurrence despite appropriate management. Closed loop stimulation (CLS) pacing is a promising treatment... (Meta-Analysis)
Meta-Analysis
PURPOSE
A proportion of patients with vasovagal syncope (VVS) experience recurrence despite appropriate management. Closed loop stimulation (CLS) pacing is a promising treatment for a subgroup of patients with cardioinhibitory response on head-up tilt table test (HUTT). Nonetheless, its efficacy remains uncertain. We sought to assess the efficacy of CLS pacing in patients with cardioinhibitory VVS.
METHODS
We searched PubMed, Google Scholar, and the Cochrane Central Register of controlled trials for relevant studies (last search date April 23, 2018). Data were pooled using the Mantel-Haenszel fixed-effects model. For cohort studies, we used a Freeman-Tukey transformation to calculate the weighted summary proportion. Primary outcomes are syncope and presyncope.
RESULTS
Eight studies were included in the final analyses (two single-blinded and one double-blinded RCT, two prospective observational studies, and three retrospective observational studies). Two hundred ninety-one patients included, with an average age of 57 years. Quality of evidence is moderate. Use of CLS pacing was associated with reduced risk of syncope (OR 0.08; 95% CI 0.03-0.18; I 32%) and presyncope (OR 0.34; 95% CI 0.18-0.63; I 0.00%). Using proportion meta-analysis, the summary estimate of the proportion of cases that developed syncope during CLS pacing was similar between RCTs and prospective studies (3.2% and 3.1%), respectively. This is much lower than the rate of recurrence in the control arm of RCTs at 33.7%. Sensitivity analyses yielded similar results.
CONCLUSION
CLS pacing is beneficial for patients with recurrent vasovagal syncope who demonstrate a cardioinhibitory response on HUTT.
Topics: Cardiac Pacing, Artificial; Humans; Recurrence; Syncope, Vasovagal; Tilt-Table Test
PubMed: 30863907
DOI: 10.1007/s10840-019-00531-0 -
PloS One 2019To summarize the best available evidence on the effectiveness of physical counterpressure manoeuvers (PCM) for vasovagal syncope management compared to a control... (Meta-Analysis)
Meta-Analysis
AIMS
To summarize the best available evidence on the effectiveness of physical counterpressure manoeuvers (PCM) for vasovagal syncope management compared to a control intervention. Control interventions included either a PCM, no intervention, or other interventions feasible in a lay setting.
METHODS
A systematic literature search (March 21st 2018) was performed in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. PCM were subdivided into 1) PCM decreasing orthostatic load (PCMOL), 2) PCM shortening the hydrostatic column between heart and brain (PCMHC), 3) PCM using mechanical compression of the veins (PCMMC). The primary outcome was syncope, secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR). When possible, a random effects meta-analysis was performed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes, and mean differences (MD) or standardized mean differences (SMD) were calculated for continuous outcomes. Heterogeneity was assessed by means of the I2 statistic. The total body of evidence was evaluated by means of the GRADE methodology.
RESULTS
Eleven trials involving 688 people with vasovagal syncope were included. Risk of bias was high in all included studies. The total body of evidence (GRADE) was considered to be low or very low. PCM were found to improve syncope as compared to control (OR: 0.52, 95% CI [0.33;0.81], p = 0.004). Similarly, before-and-after studies without a control group showed a significant reduction in syncope following PCM (OR: 0.01, 95%CI [0.00;0.01], p<0.001). No studies investigated PCMOL. PCMHC increased SBP, DBP, MAP, SV, and CO, and decreased HR. PCMMC increased SBP, DBP, and MAP.
CONCLUSION
PCM may reduce syncope and increase SBP, DBP, and MAP. The effects on other outcomes are less clear. Additional high-quality studies are needed.
Topics: Bias; Blood Pressure; Female; Humans; Male; Motor Activity; Non-Randomized Controlled Trials as Topic; Randomized Controlled Trials as Topic; Syncope, Vasovagal; Treatment Outcome
PubMed: 30818337
DOI: 10.1371/journal.pone.0212012 -
Journal of Arrhythmia Oct 2018Vasovagal syncope (VVS) is defined by transient loss of consciousness with spontaneous rapid recovery. Recently, a closed-loop stimulation pacing system (CLS) has shown...
BACKGROUND
Vasovagal syncope (VVS) is defined by transient loss of consciousness with spontaneous rapid recovery. Recently, a closed-loop stimulation pacing system (CLS) has shown superior effectiveness to conventional pacing in refractory VVS. However, systematic review and meta-analysis has not been performed. We assessed the impact of CLS implantation and reduction in recurrent VVS events by a systematic review and a meta-analysis.
METHODS
We comprehensively searched the databases of MEDLINE and EMBASE from inception to September 2017. Included studies were published prospective or retrospective cohort, randomized controlled trial, and case-control studies that compared VVS events between recurrent, severe, or refractory cardioinhibitory VVS patient implanted with CLS and conventional pacing. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odds ratios and 95% confidence intervals.
RESULTS
Six studies from November 2004 to October 2017 were included in this meta-analysis involving 224 recurrent, severe, or refractory cardioinhibitory VVS patients implanted with CLS and 163 recurrent, severe, or refractory VVS patients implanted with conventional pacing. CLS significantly reduced recurrent VVS events compared to conventional pacing (pooled odds ratio = 0.23, 95% confidence interval: 0.13-0.39, = 0.000, = 36.5%) as well as subgroup of four randomized controlled trial studies (pooled odds ratio = 0.28, 95% confidence interval: 0.17-0.44, = 0.000, = 39.2%).
CONCLUSION
Closed-loop stimulation significantly reduced recurrent VVS events up to 80% when compared to conventional pacing. Our study suggests that CLS is an effective tool for preventing syncope recurrences in patients with recurrent, severe, or refractory cardioinhibitory VVS.
PubMed: 30327702
DOI: 10.1002/joa3.12102 -
JACC. Clinical Electrophysiology Apr 2017The aims of this study were to quantify the degree of improvement in vasovagal syncope after assessment and to identify predictive factors. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aims of this study were to quantify the degree of improvement in vasovagal syncope after assessment and to identify predictive factors.
BACKGROUND
No treatments for vasovagal syncope have been proved effective, but patients in all prospective studies appear to show a reduction in the likelihood of fainting.
METHODS
A systematic review and meta-analysis was performed of studies published from 1993 through 2013. Inclusion criteria were: 1) vasovagal syncope frequency in the preceding 1 to 2 years; and 2) the proportion of subjects with syncope in at least the first follow-up year. Random-effects methods were used.
RESULTS
Of 338 screened studies, 17 were analyzed, with a mean of 112 subjects (range 9 to 511 subjects). In the preceding epoch, 97% of subjects fainted, with 2.6 ± 1.0 syncopal spells per year. In the follow-up year, the proportion of patients with ≥1 syncope recurrence was 677 of 1,912 (35.4%), and in the meta-analysis, the proportion of subjects fainting was only 0.44 (95% confidence interval: 0.41 to 0.46; p < 0.001). Subjects in larger studies were less likely to faint than those in randomized trials (relative risk: 0.35 vs. 0.55; p = 0.004). The probabilities of ≥1 syncope recurrence in the observational versus randomized studies were 0.30 (95% confidence interval: 0.24 to 0.37) and 0.54 (95% confidence interval: 0.46 to 0.62), respectively (p < 0.001). None of the degree of blinding, type of intervention, age, sex, and number of recent faints predicted the probability of syncope recurrence. Heterogeneity was very high in all analyses (I = 60% to 96%).
CONCLUSIONS
The spontaneous remission rate in highly symptomatic syncope patients is high, and remission occurs in all types of studies. Improvement was more likely in larger and observational studies.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Remission, Spontaneous; Syncope, Vasovagal
PubMed: 29759452
DOI: 10.1016/j.jacep.2016.10.012 -
Heart Rhythm Aug 2017To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients... (Review)
Review
Pacing as a treatment for reflex-mediated (vasovagal, situational, or carotid sinus hypersensitivity) syncope: A systematic review for the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association...
OBJECTIVES
To determine, using systematic review of the biomedical literature, whether pacing reduces risk of recurrent syncope and relevant clinical outcomes among adult patients with reflex-mediated syncope.
METHODS
MEDLINE (through PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (through October 7, 2015) were searched for randomized trials and observational studies examining pacing and syncope, and the bibliographies of known systematic reviews were also examined. Studies were rejected for poor-quality study methods and for the lack of the population, intervention, comparator, or outcome(s) of interest.
RESULTS
Of 3,188 citations reviewed, 10 studies met the inclusion criteria for systematic review, including a total of 676 patients. These included 9 randomized trials and 1 observational study. Of the 10 studies, 4 addressed patients with carotid sinus hypersensitivity, and the remaining 6 addressed vasovagal syncope. Among the 6 open-label (unblinded) studies, we found that pacing was associated with a 70% reduction in recurrent syncope (relative risk [RR]: 0.30; 95% confidence interval [CI]: 0.15-0.60). When the 2 analyzable studies with double-blinded methodology were considered separately, there was no clear benefit (RR: 0.73; 95% CI: 0.25-2.1), but confidence intervals were wide. The strongest evidence was from the randomized, double-blinded ISSUE-3 (Third International Study on Syncope of Uncertain Etiology) trial, which demonstrated a benefit of pacing among patients with recurrent syncope and asystole documented by implantable loop recorder.
CONCLUSIONS
There are limited data with substantive evidence of outcome ascertainment bias, and only 2 studies with a double-blinded study design have been conducted. The evidence does not support the use of pacing for reflex-mediated syncope beyond patients with recurrent vasovagal syncope and asystole documented by implantable loop recorder.
Topics: American Heart Association; Cardiac Pacing, Artificial; Cardiology; Disease Management; Humans; Practice Guidelines as Topic; Societies, Medical; Syncope; United States
PubMed: 28286245
DOI: 10.1016/j.hrthm.2017.03.006