Vasovagal Syncope: Diagnosis, Tilt Testing and Treatment

Definition and Pathophysiology

Vasovagal syncope represents the most common form of neurally mediated syncope (NMS), a disorder of autonomic reflexes. It typically occurs after attaining an upright posture or following painful stimuli and emotional stress. By the age of 60, vasovagal syncope is reported to occur in over 40% of females and 30% of males due to a lack of effective reflex response to posture, venous pooling, or external stimuli.

The underlying pathophysiology is rooted in autonomic dysregulation within a structurally normal heart. During an episode, decreased cardiac output and a potential paradoxical vasodilation with hypotension occur, often accompanied by bradycardia. Most cases involve a mixed response of both hypotension and bradycardia. However, some patients exhibit a primary cardioinhibitory response with pronounced bradycardia. Most cardioinhibitory events are due to sinus bradycardia, though transient atrioventricular (AV) block can also occur.

The physiologic response to orthostatic stress is incompletely understood, but redistribution of blood volume and increased ventricular contractility occur consistently. Exaggerated activation of a central reflex produces a stereotypic response: an initial increase in heart rate, followed by a drop in blood pressure, and finally a reduction in heart rate. This sequence is characteristic of neurally mediated hypotension.

Clinical Presentation and Symptoms

Vasovagal syncope is frequently preceded by prodromal symptoms, including diaphoresis, a "warm sensation," and nausea. Patients may also experience lightheadedness and palpitations upon assuming an upright posture.

Specific triggers are well-recognized and include:

• Provoked fear, pain, anxiety, intense emotion, the sight of blood, unpleasant sights and odors, and orthostatic stress.

• Situational triggers such as acute hemorrhage, cough, defecation, laugh, micturition, sneeze, swallow, and postprandial states.

In some instances, patients may present with adenosine-sensitive syncope, a subtype of reflex syncope that manifests without a prodrome and usually features a nonrevealing cardiac workup.

Evaluation and Physical Examination

The initial evaluation of a patient with suspected syncope aims to determine whether the transient loss of consciousness was due to syncope, identify the cause, and assess the risk for future episodes and serious harm. This evaluation should include a detailed history, thorough questioning of eyewitnesses, and a complete physical and neurologic examination. Blood pressure and heart rate should be measured in the supine position and after 3 minutes of standing to determine if orthostatic hypotension is present.

High-risk features on history include:

• New onset of chest discomfort, abdominal pain, shortness of breath, or headache

• Syncope during exertion or while supine

• Sudden onset of palpitations followed by syncope

• Severe coronary artery or structural heart disease

High-risk features on examination include:

• Unexplained systolic blood pressure < 90 mmHg

• Suggestion of gastrointestinal hemorrhage

• Persistent bradycardia (< 40 beats/min)

• Undiagnosed systolic murmur

Carotid sinus massage should be considered in patients with symptoms suggestive of carotid sinus syncope and in patients older than 40 years with recurrent syncope of unknown etiology. This test should be performed under continuous ECG and blood pressure monitoring and must be avoided in patients with carotid bruits, possible or known plaques, or stenosis.

Diagnostics

Electrocardiogram and Cardiac Monitoring

An ECG should be performed if there is suspicion of syncope due to an arrhythmia or underlying cardiac disease. Relevant abnormalities include bradyarrhythmias or tachyarrhythmias, AV block, acute myocardial ischemia, old myocardial infarction, long QT, and bundle branch block.

Cardiac monitoring is indicated for patients with a high pretest probability of arrhythmia causing syncope. In-hospital monitoring is reserved for those with a high likelihood of life-threatening arrhythmia (e.g., severe coronary artery or structural heart disease, nonsustained ventricular tachycardia, trifascicular heart block, Brugada syndrome ECG pattern, syncope during exertion, or family history of sudden cardiac death). Continuous ambulatory ECG monitoring is recommended for frequent syncopal episodes (e.g., daily), whereas external loop recorders are indicated for episodes occurring more than once a month. Implantable loop recorders (ILR) are recommended for infrequent (less than once a month) unexplained syncope suspected to be caused by bradycardia when a comprehensive evaluation has not demonstrated a cause. The monitoring duration should ideally be at least twice the interspell duration.

Imaging and Electrophysiology

Echocardiography should be performed in patients with a history of cardiac disease or if abnormalities are found on physical examination or the ECG. It can identify diagnoses responsible for syncope such as aortic stenosis, hypertrophic cardiomyopathy, cardiac tumors, aortic dissection, and pericardial tamponade, and aids in risk stratification based on left ventricular ejection fraction. Treadmill exercise testing with ECG and blood pressure monitoring is indicated for patients who experience syncope during or shortly after exercise to identify exercise-induced arrhythmias or exaggerated vasodilation. Invasive electrophysiologic studies have low sensitivity and specificity and should only be performed when a high pretest probability exists and noninvasive investigations have failed.

Tilt-Table Testing

Tilt-table testing (TTT) is a valuable diagnostic tool for evaluating patients with syncope, particularly to confirm a diagnosis of NMS when the initial evaluation was insufficient. The test is also of value in diagnosing psychogenic pseudosyncope, as it may trigger loss of consciousness (LOC) in association with a normal blood pressure and heart rate. TTT has no value in assessing the efficacy of treatment for NMS.

Methodology Patients are placed on a tilt table in the supine position. After a 20-minute horizontal pretilt stabilization phase, the table is tilted upright to an angle between 60 and 80 degrees (70 degrees being most common) for 30 to 45 minutes or longer.

Provocation Pharmacologic provocation may be considered after the initial observation period to increase sensitivity, though it decreases specificity. Sublingual nitroglycerin is preferred due to ease of administration. Isoproterenol is an alternative.

Interpretation Without pharmacologic provocation, the specificity of TTT is estimated at 90%; specificity decreases significantly with provocative agents. TTT results are positive in two-thirds to three-fourths of patients susceptible to neurally mediated syncope. Results are reproducible in approximately 80% of patients, with a 10% to 15% false-positive response rate. A positive test result is more meaningful when it reproduces the patient's spontaneous symptoms.

Positive responses are categorized into three types:

• Cardioinhibitory: A positive cardioinhibitory response predicts, with high probability, asystolic spontaneous syncope.

• Vasodepressor: The presence of a positive vasodepressor response does not exclude asystole during spontaneous syncope.

• Mixed

Induction of reflex hypotension/bradycardia without reproduction of syncope points toward NMS but is a less specific response. Induction of LOC with no change in vital signs strongly points toward psychogenic pseudosyncope.

Contraindications TTT is relatively contraindicated in the presence of:

• Severe coronary artery disease with proximal coronary stenoses

• Known severe cerebrovascular disease

• Severe mitral stenosis

• Obstruction to left ventricular outflow (e.g., aortic stenosis, hypertrophic cardiomyopathy)

Biomarkers and Laboratory Findings

Baseline laboratory blood tests are rarely helpful in identifying the cause of syncope. Blood tests should be performed only when specific disorders are suspected, such as myocardial infarction, anemia, or secondary autonomic failure. Specific laboratory tests are recommended in patients with clinical suspicion for potential causes of bradycardia, including thyroid function tests, Lyme titre, digitalis level, potassium, calcium, and pH.

Treatment and Management

Acute and Lifestyle Strategies

The foundation of management for vasovagal syncope involves patient education, reassurance, and trigger avoidance. For patients with a prolonged prodrome, physical counter-pressure maneuvers are recommended. Tilt training may be considered for recurrent vasovagal syncope, particularly in young patients. Increased salt and fluid intake is recommended by US guidelines unless contraindicated. A structured exercise program starting with recumbent exercises is often useful before considering pharmacologic therapies.

Pharmacologic Therapy

When episodes are frequent and lifestyle modifications are insufficient, pharmacologic therapy may be considered. However, no single treatment is reliably effective in most patients.

Cardiac Pacing

Cardiac pacing is indicated in highly selected patients, primarily those with a dominant cardioinhibatory component. Dual-chamber cardiac pacing is indicated to reduce recurrent syncope in patients aged > 40 years with severe, unpredictable, recurrent syncope who have:

• Spontaneous documented symptomatic asystolic pause/s > 3 s or asymptomatic pause/s > 6 s due to sinus arrest or AV block

• Cardioinhibitory carotid sinus syndrome

• Asystolic syncope during tilt testing

Dual-chamber pacing may also be considered to reduce syncope recurrences in patients with the clinical features of adenosine-sensitive syncope.

Regarding pacing mode selection, DDD pacing is widely preferred over single-chamber RV pacing to counteract blood pressure fall and prevent symptom recurrences. DDD pacing with a rate-drop response feature and DDD with closed-loop stimulation have been studied. Small crossover studies showed fewer syncope recurrences with closed-loop stimulation during repeated tilt testing and 18-month follow-up. However, no formal recommendation can be given regarding the selection of the pacing mode until a formal parallel trial is performed.

Guideline Recommendations

Both the 2017 ACC/AHA/HRS and 2018 ESC guidelines emphasize a structured care pathway beginning with history, physical examination, and ECG (Class I). If the initial evaluation suggests reflex syncope, tilt-table testing should be considered in a select group of patients based on clinical judgment (Class IIa).

Prognosis and Follow-up

Vasovagal syncope and related autonomic disorders are not life-threatening but can significantly impair quality of life. The initial evaluation allows for the stratification of patients at risk for cardiac mortality. In the absence of structural heart disease, the prognosis is generally benign. Follow-up should be tailored to symptom recurrence and the initiation of pharmacologic or device-based therapies. For patients with recurrent unexplained falls, the same assessment as for unexplained syncope should be considered.