The patient is 70-year-old female presenting with an episode of loss of consciousness at home. While eating dinner with her husband, the patient stated, “I don’t feel well,” and subsequently lost consciousness for 15 seconds. Per her husband, she spontaneously returned to baseline and vomited once. The patient denied any preceding symptoms including chest pain, shortness of breath, dizziness, nausea. There was no seizure-like activity. She stated that this has occurred 5-6 times previously, but she has had unremarkable Holter monitoring.
She has stable vital signs with a normal physical exam. Her symptoms are not reproducible upon sitting or standing. Laboratory testing, including CBC, BMP, troponin, D-Dimer, and urinalysis, are all within normal limits. A routine EKG demonstrates normal sinus rhythm with mild PR prolongation and no acute ST changes.
While discussing disposition, the patient states she feels unwell and develops sinus bradycardia on telemetry. Without complete loss of consciousness, she returns to her baseline after 20 seconds. Repeat EKG demonstrates rebound sinus tachycardia without any ischemic or interval changes. She is admitted to cardiology for further monitoring.
While admitted, the patient has an uneventful hospital course. Her echocardiogram demonstrates an ejection fraction of 70% with no underlying structural heart defects. Serial troponins and EKG trending is unremarkable. She tolerates a trial of metoprolol 25mg BID and is discharged home with instructions to follow up for tilt testing.
Diagnosis: Reflex Syncope
Syncope: A transient loss of consciousness with spontaneous return to baseline
Reflex syncope, or neurally-mediated syncope, is thought to present in three ways:
Vasodepressive- primary loss of sympathetic function, presenting as hypotension (1)
Cardioinhibitory- increased parasympathetic function, presenting as bradycardia or asystole (1)
Mixed type- The majority of reflex syncope is mixed (1)
Reflex syncope is thought to result from a trigger causing orthostasis, decreased venous return, thereby decreased cardiac output, and a transient lack of cerebral perfusion inducing transient loss of consciousness. (2)
Syncope can be vasovagal, during high emotional states, or situational, such as post-micturition, while eating, coughing, sneezing, and post-exercise. Carotid sinus syncope and atypical forms, without trigger or prodromes, can also be forms of reflex syncope.(3) It is important to distinguish reflex syncope from other causes of syncope, such as arrhythmogenic or ischemic, orthostatic syncope, and non-syncopal mimics such as stroke, seizure, hemorrhage, etc.(3) Patient history can help guide this differentiation.
Approximately 40% population have had one or more episodes of syncope. Reflex syncope is the most common type of syncope in any age group; it has been suggested that it may follow a bimodal age distribution.(1) Atypical reflex syncope, without trigger or cause, is more common amongst older patients. However, the rate of cardiac syncope also rises with age and elderly patients are more likely to have concomitant cardiovascular disease or orthostasis induced by medication.(4)
Reflex syncope is generally considered benign and portends a low risk of mortality. However, frequent episodes, particularly in the elderly may predispose to trauma and injury. These patients may benefit from treatment. Researchers have concluded that the number of events in the preceding year is a better predictor of recurrent syncope rather than the total number of lifetime events.(5)
The mainstay of treatment is the of avoidance of triggers. Other non-pharmacologic therapies may also help, such as volume support, from increased fluid intake or a high-salt diet, compression shorts or stockings to support venous return, counter-pressure maneuvers, and tilt training.(4) Counter pressure maneuvers are exercises such as muscle tensing, grip squeezing, leg crossing, squatting, bending forward. Patients can try these maneuvers when they feel a prodrome. Ideally this delays symptoms until patients can lay supine, improving venous return and delaying or preventing syncope.(6) The PC trial investigated this in 2006 and showed a lower recurrence of syncope 31.6% compared to 50.9% at 14 months using counter pressure.(7) However, the ISSUE 3 trial demonstrated no difference in syncope prevention between groups.(6) Given the low cost and low risk associated with these maneuvers with the potential for benefit, patients can try these.
A tilt test can be used to reproduce symptoms in patients whom the cause of syncope is less clear. Patients follow a protocol which is dependent upon steep tilting, with additional provocative medications such as isoproterenol or nitroglycerin as needed. Results are interpreted by patient response, vital sign measurements, and timing of symptoms. While there a high sensitivity is reported, it is at the cost of lowered specificity and many false positives. Additionally, patient assignment is important because factors such as home medications and structural heart disease may impact findings. If positive, it may help guide treatment.(8)
Similarly, it has been suggested that patients can perform tilt training as treatment. First discussed in 1998, tilt training consists of in-hospital sessions of suspended tilting, followed by at home training of standing against a wall for several minutes several times per day. While a meta-analysis has suggested benefit to tilt training, this was not sustained when evaluating only randomized studies. Patient noncompliance can also negatively impact outcomes, and lessen efficacy.(6)
Several medications have been proposed to lessen reflex syncope recurrence including: beta blocker, alpha adrenergic, SSRI, fludrocortisone, and theophylline. Many of these have small data sets of evidence or fail to succeed over placebo and are not routinely recommended.(6)
Since our patient was started on metoprolol, we will examine this more specifically. Physiologically, beta blockers are theorized to reduce overall sympathetic response and prevent vagal “overshooting”.(1) While observational data showed promise, many randomized trials have thus far failed to show benefit in decreasing syncope recurrence over placebo.(4)
The data to support beta blockade is largely driven by the POST trial. While initial study results demonstrated no benefit, a subset analysis of adults >42 years old demonstrated improvement with beta blockers in older patients.(9) Two smaller studies by Natale and Leor also showed an age-related distribution of benefit.(9) A randomized prospective trial, POST 5, is currently underway to further examine this conclusion. Results are expected December 2020.(10) As of the 2018 European Society of Cardiology guidelines, beta blockers are not currently routinely supported.(3) Given upcoming trial results these recommendations may change in the future.
Take Away Summary
Reflex syncope, or neurally-mediated syncope can be cardioinhibitory, vasodepressive, or mixed
Nonpharmacologic interventions such as counter pressure or tilt training may be beneficial for some patients
Pharmacologic interventions are broad; beta blockade has shown some initial promise in a subset of older patients, but is not yet routinely recommended across the board
Reflex syncope is in general benign, but patients at high risk of trauma or injury may benefit from further care. Young, healthy patients can be given reassurance of a good prognosis.
Faculty Reviewer: Dr. Kristina McAteer
Aydin, M. A., Salukhe, T. V., Wilke, I., & Willems, S. (2010, October 26). Management and therapy of vasovagal syncope: A review. Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998831/
Brignole, M., MD. (2016, July 5). Finally, A Drug That Proves to Be Effective Against Vasovagal Syncope! But Not in All Patients. Retrieved May 19, 2019, from http://www.onlinejacc.org/content/accj/68/1/10.full.pdf
Brignole, M., Moya, A., De Lange, F. J., Deharo, J. C., Elliot, P. M., Fanciulli, A., . . . Van Dijk, J. (2018, March 19). 2018 ESC Guidelines for the diagnosis and management of syncope. Retrieved May 21, 2019, from https://academic.oup.com/eurheartj/article/39/21/1883/4939241#13420039
Benditt, D. (n.d.). Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation. Retrieved May 21, 2019, from https://www.uptodate.com/contents/reflex-syncope-in-adults-and-adolescents-clinical-presentation-and-diagnostic-evaluation?search=vasodepressor syncope&source=search_result&selectedTitle=1~84&usage_type=default&display_rank=1
Sumner, G. L., Rose, M. S., Koshman, M. L., Ritchie, D., Sheldon, R. S., & Prevention, I. N. (2010, December). Recent history of vasovagal syncope in a young, referral-based population is a stronger predictor of recurrent syncope than lifetime syncope burden. Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pubmed?term=20662990
Ravielle, A. (2017, August 09). Update on treatment strategies for vasovagal syncope. Retrieved May 21, 2019, from https://cardiacrhythmnews.com/update-treatment-strategies-vasovagal-syncope/
Van Dijk, N., Quartieri, F., Blanc, J., Garcia-Civera, R., Brignole, M., Moya, A., & Wieling, W. (2006, October 17). Effectiveness of physical counterpressure maneuvers in preventing vasovagal syncope: The Physical Counterpressure Manoeuvres Trial (PC-Trial). Retrieved May 21, 2019, from https://www.ncbi.nlm.nih.gov/pubmed/17045903
Benditt, D. (n.d.). Upright tilt table testing in the evaluation of syncope. Retrieved May 21, 2019, from https://www.uptodate.com/contents/upright-tilt-table-testing-in-the-evaluation-of-syncope?search=vasodepressor syncope&source=search_result&selectedTitle=4~84&usage_type=default&display_rank=4#H11
Sheldon, R., Morillo, C., Klingenheben, T., Krahn, A., Sheldon, A., & Rose, M. (2012, October 1). Age-Dependent Effect of β-Blockers in Preventing Vasovagal Syncope. Retrieved May 21, 2019, from https://www.ahajournals.org/doi/10.1161/CIRCEP.112.974386
Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects - Full Text View. (n.d.). Retrieved May 21, 2019, from https://clinicaltrials.gov/ct2/show/NCT02123056