Definition and Overview
Vasovagal syncope (VVS) is the most representative form of neurally mediated syncope, in which excessive activation of the vagus nerve simultaneously causes bradycardia and vasodilation, temporarily reducing cerebral blood flow and resulting in loss of consciousness. Syncope is a type of transient loss of consciousness caused by global cerebral hypoperfusion, characterized by spontaneous and complete recovery [2].
VVS accounts for approximately 56-66% of all syncope causes, making it the most common type of syncope [2] [3]. According to the 2018 European Society of Cardiology (ESC) syncope guidelines, approximately 40% of the general population experiences at least one syncopal episode in their lifetime, with more than half attributed to the vasovagal mechanism [2]. The annual incidence is approximately 6.2 per 1,000 population and accounts for approximately 1-3% of emergency department visits [2].
VVS can occur at any age but most commonly first presents between ages 10 and 30 [5]. Women have a slightly higher incidence than men, and differentiation from orthostatic hypotension is important in the elderly. VVS itself is a benign condition that does not threaten life; however, recurrent episodes are associated with injury risk and diminished quality of life. In the study by Sheldon et al. (2006), approximately 25% of VVS patients experienced recurrence within 5 years [6].
Pathogenesis
The core mechanism of VVS is the Bezold-Jarisch reflex [5]. This reflex is a process in which normal autonomic responses become excessively activated, paradoxically causing blood pressure to drop and bradycardia to develop.
Normally upon standing, approximately 500-800 mL of blood shifts gravitationally to the lower extremities and splanchnic vessels. In response, baroreceptors activate the sympathetic nervous system, increasing heart rate and peripheral vascular resistance to maintain blood pressure [2]. In VVS, this compensatory mechanism is reversed.
As the upright posture is sustained, venous return decreases and ventricular filling is reduced. The relatively empty ventricles contract vigorously, stimulating ventricular wall mechanoreceptors [5]. When this signal is transmitted through vagal afferent fibers to the vasomotor center in the medulla oblongata, sympathetic activity is suddenly inhibited and parasympathetic (vagal) activity is overactivated.
As a result, heart rate drops sharply (bradycardia) and peripheral vasodilation occurs, causing a sudden decline in blood pressure [5]. When cerebral blood flow falls below the critical threshold, loss of consciousness occurs. Complete cessation of cerebral blood flow for approximately 6-8 seconds leads to syncope [3].
VVS is classified into three types based on the response pattern [2]:
- Vasodepressor type: Hypotension is the predominant mechanism, with minimal heart rate reduction.
- Cardioinhibitory type: Bradycardia or transient asystole is the predominant mechanism. Asystole lasting 3 seconds or more may be observed.
- Mixed type: Both hypotension and bradycardia are prominent. This is the most common type in clinical practice.
Recently, the role of higher central nervous system structures such as the cerebral cortex, insular cortex, and amygdala has also gained attention [5]. Emotional stress or pain triggering syncope is interpreted as descending signals from the cerebral cortex to the autonomic centers in the medulla.
Triggering Factors
VVS is frequently triggered by specific situations or stimuli [2] [5]. The major triggers are as follows.
Orthostatic factors include prolonged standing, standing in hot environments, crowded spaces, and prolonged immobility during church services or school assemblies. Soldiers or students collapsing while standing in formation is a classic example [3].
Emotional and pain-related factors include blood drawing, injections, witnessing surgical procedures, severe pain, fear, and anxiety. Fainting during blood draws is a typical case of VVS [3].
Physical factors include dehydration, excessive sweating, post-alcohol consumption, prolonged fasting, sleep deprivation, and overexertion. Syncope after hot baths or saunas also occurs through the VVS mechanism due to vasodilation [5].
Situational syncope triggered by specific actions such as urination, defecation, coughing, or swallowing is also broadly included in neurally mediated syncope [2]. Syncope due to carotid sinus hypersensitivity occurs when pressure is applied to the neck and is more common in elderly men.
Symptoms
VVS symptoms are divided into three phases: the prodromal phase, the syncopal phase, and the recovery phase [2] [3].
Prodromal Symptoms
These are warning symptoms that appear seconds to minutes before syncope. Prodromal symptoms precede syncope in approximately 70-80% of VVS patients [3]. Common symptoms include lightheadedness, visual changes such as blurring or darkening, nausea, diaphoresis, facial pallor, tinnitus or diminished hearing, extremity tingling, and generalized weakness. As heart rate decreases and blood pressure falls, the extremities become cold and yawning may occur [5].
Early recognition of prodromal symptoms allows syncope prevention by sitting or lying down, making prodromal symptom recognition training a critical element of patient education [1].
Syncopal Phase
Loss of consciousness occurs when cerebral blood flow falls below the critical threshold. Syncope caused by VVS typically recovers spontaneously within seconds to less than 1 minute [3]. During syncope, muscle tone is lost and the patient collapses, sometimes accompanied by brief tonic or myoclonic jerks. These may be confused with epilepsy; however, convulsive movements in VVS are secondary phenomena caused by cerebral hypoperfusion and are fundamentally different from epileptic seizures [3].
Transient bradycardia or asystole lasting 3 seconds or more may be observed during syncope. According to the 2018 ESC guidelines, asystole of 3 seconds or more is recorded during tilt table testing in approximately 40-50% of VVS patients [2].
Recovery Phase
Upon transitioning to a supine position, cerebral blood flow is restored and consciousness returns. Generalized fatigue, headache, and nausea may persist for minutes to hours after recovery [5]. Standing too quickly after regaining consciousness may result in recurrent syncope, so adequate rest is necessary.
Diagnosis
The diagnosis of VVS relies primarily on clinical history, with the tilt table test serving as the standard diagnostic tool [2].
Clinical History
Typical triggering factors (prolonged standing, pain, heat, emotional stress, etc.), the presence of prodromal symptoms, the pattern of syncope, and the recovery process are systematically assessed [2]. Important information includes the posture at onset (standing or sitting), witness accounts, syncope duration, presence of convulsive movements, and post-recovery status. Family history, cardiac disease history, and medication history must also be reviewed.
The 2018 ESC guidelines state that typical VVS can be diagnosed based on history alone [2]. This applies when typical triggers and prodromal symptoms are present, structural heart disease is excluded, and no neurological abnormalities are found.
Tilt Table Test
The patient is placed on the examination table and tilted to a 60-70 degree angle for 20-45 minutes while blood pressure and heart rate changes are continuously measured [1] [2]. A positive result is determined when syncope is reproduced during the test with confirmed hypotension and bradycardia. If no response occurs during the baseline test, pharmacological provocation with sublingual nitroglycerin or intravenous isoproterenol is performed [2].
The sensitivity of the tilt table test is reported at approximately 61-69% with a specificity of approximately 93% [2]. Reproducibility is not perfect, so a negative test does not exclude VVS.
Differential Diagnosis
The most important consideration in the differential diagnosis of syncope is the exclusion of cardiac syncope [2]. Cardiac syncope is caused by arrhythmias, structural heart disease, and aortic stenosis, and unlike VVS, can be life-threatening. Differentiation is performed through 12-lead ECG, echocardiography, and 24-hour Holter monitoring.
Differentiation from epilepsy is also important. Convulsive movements accompanying VVS (convulsive syncope) may be confused with epileptic seizures; however, in VVS, brief convulsions appear after loss of consciousness, and postictal confusion is absent or very brief [3].
Orthostatic hypotension, carotid sinus hypersensitivity, and psychogenic pseudosyncope are also differential considerations [2].
Treatment
First-line treatment for VVS is non-pharmacological therapy, with pharmacotherapy and device therapy considered for recurrent syncope [1] [2].
Patient Education and Trigger Avoidance
Clearly explaining to the patient that VVS is a benign condition that does not threaten life is the starting point of treatment. This education alone reduces anxiety and lowers recurrence rates in many patients [2]. Individual triggers are identified and patients are guided to avoid them, including prolonged standing, hot environments, dehydration, and excessive alcohol consumption.
Physical Counterpressure Maneuvers
These are isometric muscle contraction movements performed when prodromal symptoms are felt [2]. They include leg crossing with tensing, arm tensing with handgrip, and squatting. In the randomized controlled trial by van Dijk et al. (2006), physical counterpressure maneuvers significantly reduced VVS recurrence [3]. The 2018 ESC guidelines recommend physical counterpressure maneuvers as Class I (recommended) for VVS patients with prodromal symptoms [2].
Fluid and Salt Intake
Daily intake of 2-3 liters of fluid and 6-10 g of salt is recommended [1] [2]. Adequate fluid and salt intake increases circulating blood volume and improves venous return upon standing. Rapidly drinking 500 mL of water upon waking in the morning (water bolus) also has a transient blood pressure-raising effect [5].
Tilt Training
This involves standing with the back against a wall twice daily for 20-30 minutes per session [5]. The goal is to progressively build autonomic tolerance to the upright posture, and consistent practice has been reported to reduce syncope recurrence by approximately 40-50% [5]. However, some suggest that long-term effectiveness is limited due to low patient compliance.
Pharmacological Treatment
Pharmacotherapy is considered for recurrent VVS not controlled by non-pharmacological measures [2]. Medications with consistently proven efficacy for VVS remain limited to date.
Midodrine is an alpha-1 adrenergic receptor agonist that constricts peripheral vessels to maintain blood pressure. Some studies have confirmed its effectiveness in reducing syncope recurrence [2].
Fludrocortisone is a mineralocorticoid that promotes sodium and water retention to increase blood volume [1]. The POST 2 study demonstrated that fludrocortisone significantly reduced VVS recurrence.
Beta-blockers were widely prescribed in the past; however, in the POST study (Prevention of Syncope Trial) by Sheldon et al. (2006), metoprolol showed no significant difference compared to placebo in preventing VVS recurrence [6]. A subgroup analysis suggested potential efficacy in patients aged 42 years and older [6].
Cardiac Pacemaker Implantation
Permanent pacemaker implantation may be considered in cardioinhibitory VVS with documented asystole that is unresponsive to pharmacotherapy [2]. The 2018 ESC guidelines recommend dual-chamber pacemaker as Class IIa for patients aged 40 years or older with recurrent syncope and symptom-correlated asystole of 3 seconds or more documented on implantable loop recorder [2].
Clinical Course and Prognosis
VVS generally follows a benign course. Mortality in VVS patients without structural heart disease is no different from the general population [2]. However, recurrence is common, with a recurrence rate of approximately 25-35% within one year after the first syncope [6]. Risk of recurrence is higher with greater numbers of prior syncopal episodes and younger age at first occurrence [1].
Recurrent VVS significantly impacts quality of life. Occupational limitations, driving restrictions, social withdrawal, and anxiety or depression may be present [5]. Secondary injuries from falls during syncope, including head trauma, dental injuries, and fractures, cannot be overlooked. In elderly patients, hip fractures from falls contribute to increased morbidity and mortality.
Long-term follow-up studies show that many VVS patients tend to experience a natural decrease in syncope frequency over time [2]. In particular, VVS occurring during adolescence often undergoes spontaneous remission in adulthood.
Lifestyle Guide
Daily lifestyle management to reduce VVS recurrence is a cornerstone of treatment.
Target fluid intake of 2-3 liters per day, with drinking adequate amounts immediately upon waking and before meals being most effective [2]. Salt intake of 6-10 g per day is recommended, provided there is no hypertension or kidney disease. Excessive caffeine or alcohol intake should be avoided as they can cause dehydration.
In situations requiring prolonged standing, repeatedly cross the legs, shift weight from side to side, or contract the calf muscles [5]. Avoid standing motionless with knees locked straight. Pay particular attention to hydration in hot environments and avoid prolonged exposure.
Avoid standing up abruptly upon waking in the morning. Sit on the edge of the bed for 1-2 minutes before slowly rising. Wearing compression stockings (30-40 mmHg) reduces lower extremity venous pooling and helps maintain blood pressure [2].
Regular aerobic exercise improves cardiovascular function and autonomic regulatory capacity [1]. Moderate-intensity exercise (brisk walking, cycling, swimming, etc.) for 30-45 minutes, 3-5 times per week, is recommended. Stay well hydrated during exercise and avoid vigorous exercise in a dehydrated state.
In situations that may trigger syncope, such as blood draws or dental procedures, inform the healthcare team of your VVS history in advance and request to have the procedure performed in a supine or semi-recumbent position [5].