-
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 -
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