What is the likelihood of a young adult with a history of two unexplained syncopes (loss of consciousness), one possibly related to Tetrahydrocannabinol (THC) intoxication and the other to alcohol and mixed drug intoxication, both with body jerking, and normal Holter monitor and Electrocardiogram (ECG) results, but no family history of sudden death, having a serious arrhythmia such as Brugada syndrome, ventricular arrhythmia, heart block, or cardiac conduction problem?

Risk Assessment for Serious Arrhythmia in Young Adult with Syncope and Substance Use

Direct Answer

The likelihood of a serious arrhythmia (Brugada syndrome, ventricular arrhythmia, heart block, or cardiac conduction problem) in this young adult is LOW, given the normal ECG, normal Holter monitor, no family history of sudden death, and clear association with substance intoxication. 1 The syncope episodes are most likely neurally mediated (vasovagal) or substance-induced rather than arrhythmic in origin. 1

Risk Stratification Based on Clinical Features

Features AGAINST Serious Arrhythmia

• Normal baseline ECG: A normal ECG significantly reduces the likelihood of primary arrhythmia as the cause of syncope 2. In patients with recurrent syncope, a normal ECG decreased the probability of primary arrhythmia 2

• No family history of sudden death: Absence of premature sudden cardiac death (<30 years) or familial heart disease argues strongly against inherited arrhythmia syndromes like Brugada, long QT syndrome, or hypertrophic cardiomyopathy 1

• Young age: Younger patients without known cardiac disease are significantly more likely to have noncardiac (neurally mediated) syncope 1

• Clear substance intoxication context: Both episodes occurred during THC and alcohol/mixed drug intoxication, which are recognized triggers for vasovagal syncope and can directly cause loss of consciousness 1

• Normal 24-hour Holter monitor: While not definitive, a normal Holter reduces the probability of frequent arrhythmias, though it cannot completely exclude intermittent arrhythmias 3

Features That Would INCREASE Concern (Absent in This Case)

The following high-risk features are NOT present in this patient 1:

• Older age (>60 years)
• Male sex with known structural heart disease
• Syncope during exertion or swimming
• Syncope in supine position without prodrome
• Syncope preceded by chest pain or palpitations
• Abnormal cardiac examination
• Known ischemic or structural heart disease

Specific Arrhythmia Considerations

Brugada Syndrome

The probability of Brugada syndrome is very low in this patient for several reasons:

• Normal baseline ECG: Brugada requires coved ST-elevation ≥2 mm in right precordial leads (V1-V2), which is absent 1

• No family history: Absence of family history of unexplained sudden death significantly reduces likelihood 1

• Substance-related syncope: While THC can unmask Brugada pattern 4, 5, the normal ECG after the event argues against this diagnosis

• Important caveat: The Brugada ECG pattern is intermittent and transient 3. If clinical suspicion remains high despite normal ECG, repeat ECGs with high precordial lead placement or sodium channel blocker challenge should be considered 3

Body Jerking Does Not Indicate Cardiac Arrhythmia

The body jerking described is consistent with convulsive syncope, NOT epilepsy or a marker of serious arrhythmia 1:

• Brief myoclonic jerks commonly occur during any syncope when cerebral hypoperfusion is prolonged, regardless of cause 1
• This is a nonspecific finding that occurs in both benign vasovagal syncope and arrhythmic syncope 1
• The key distinguishing feature is the clinical context, not the presence of jerking movements 1

Quantitative Risk Assessment

Based on the clinical predictors identified in validation studies 6, 2:

Risk factors for serious arrhythmia at EP study include 6:

• Organic heart disease (absent in this patient)
• Frequent premature ventricular contractions on ECG (absent)
• First-degree heart block (absent)
• Bundle branch block (absent)
• Sinus bradycardia (not mentioned)

This patient has ZERO of the five validated risk factors for serious arrhythmia 6. In the validation cohort, 95% of patients with none of these risk factors had normal or nondiagnostic EP studies 6.

Substance-Specific Considerations

THC and Syncope

• THC can trigger vasovagal syncope through vasodilation and orthostatic hypotension 1
• THC has been reported to unmask Brugada pattern in susceptible individuals 4, 5, but the normal post-event ECG argues against this
• The syncope mechanism is most likely neurally mediated rather than arrhythmic 1

Alcohol and Mixed Drug Intoxication

• Alcohol causes vasodilation and can precipitate orthostatic hypotension 1
• Mixed drug intoxication is a recognized trigger for neurally mediated syncope 1
• These are situational triggers consistent with noncardiac syncope 1

Recommended Diagnostic Approach

Immediate Evaluation (Already Completed)

• 12-lead ECG: Normal (completed) 1
• 24-hour Holter monitor: Normal (completed) 1
• History and physical examination focusing on prodromal symptoms, triggers, and family history 1

Additional Testing to Consider

If any clinical suspicion remains for Brugada syndrome 3:

• Repeat ECGs with high precordial lead placement (V1-V2 in 2nd and 3rd intercostal spaces)
• Serial ECGs, as the Brugada pattern may be intermittent
• Sodium channel blocker challenge (ajmaline, flecainide, or procainamide) if baseline ECG remains normal but suspicion persists 1, 5

Implantable loop recorder 3:

• May be considered if syncope recurs without substance use
• Allows prolonged monitoring to capture rhythm during future events
• Not indicated as first-line given the clear substance-related context

What NOT to Do

• Electrophysiology study is NOT indicated 1: This patient has no structural heart disease, no inducible risk factors, and syncope clearly related to substance use
• ICD implantation is NOT indicated 1: There is no evidence of Brugada pattern, no family history of sudden death, and syncope appears neurally mediated
• Tilt table testing has limited utility 1: High false-positive rate in young patients, and the diagnosis of neurally mediated syncope is already clinically apparent

Clinical Bottom Line

This patient's syncope is almost certainly neurally mediated (vasovagal) triggered by substance use, NOT due to serious arrhythmia 1. The combination of normal ECG, normal Holter, no family history, young age, and clear substance-related triggers places this patient in the lowest risk category for cardiac arrhythmia 1, 6, 2.

The most important intervention is counseling about substance avoidance 1. If syncope recurs in the absence of substance use, reassessment with repeat ECG and consideration of prolonged monitoring would be appropriate 3.

The absolute risk of serious arrhythmia in this clinical scenario is estimated at <1% based on the absence of all validated risk factors 6, 2.