Overview

Definition:
-Prolonged QT syndrome (LQTS) is a disorder of cardiac repolarization, characterized by a prolonged QT interval on the electrocardiogram
-This can lead to life-threatening ventricular arrhythmias, such as Torsades de Pointes, which may manifest with symptoms mimicking seizures, including syncope and generalized tonic-clonic movements
-Differentiating these from true epileptic seizures is crucial for appropriate management.
Epidemiology:
-Congenital LQTS affects approximately 1 in 2,000 to 1 in 30,000 individuals
-Acquired LQTS is more common and can be caused by medications, electrolyte imbalances, or cardiac conditions
-Pediatric syncope is a common presentation, with seizures being a significant differential diagnosis
-Identifying LQTS as a cause of syncope-like episodes is vital for preventing sudden cardiac death.
Clinical Significance:
-Misdiagnosis can lead to delayed or incorrect treatment
-Unrecognized LQTS can result in recurrent syncope, neurological injury from falls, and importantly, sudden cardiac death
-Prompt and accurate differentiation is essential for initiating life-saving cardiac management and preventing neurological sequelae.

Clinical Presentation

Symptoms:
-Syncope, often precipitated by emotional stress, exercise, or auditory stimuli
-Seizure-like activity, including tonic-clonic movements, eye deviation, and altered consciousness
-Palpitations
-Family history of sudden unexplained death or syncope
-Absence of post-ictal confusion typically seen in seizures
-Prodromal symptoms may be absent or minimal.
Signs:
-Bradycardia or irregular heart rhythm
-Hypotension
-Neurological examination may be normal or show transient focal deficits if related to hypoperfusion
-Physical findings during a witnessed event may include opisthotonos, myoclonus, or apnea, mimicking an epileptic seizure
-Documenting the event with video-EEG and ECG is invaluable.
Diagnostic Criteria:
-Prolonged QT interval on ECG (corrected QT [QTc] > 450-460 ms in males, > 470-480 ms in females)
-Presence of Torsades de Pointes
-Clinical criteria including syncope or seizures, congenital LQTS gene mutations, or family history
-Absence of a clear epileptic origin on EEG is supportive of a cardiac cause.

Diagnostic Approach

History Taking:
-Detailed history of the event: precipitating factors, duration, specific movements, witness accounts of any cyanosis or irregular breathing
-Past medical history, especially cardiac or neurological conditions
-Family history of syncope, seizures, arrhythmias, or sudden unexplained death
-Review of all medications, including new prescriptions or over-the-counter drugs known to prolong the QT interval
-Electrolyte balance history.
Physical Examination:
-Comprehensive cardiovascular examination, assessing for murmurs, gallops, and peripheral pulses
-Neurological examination to assess for focal deficits, cranial nerve palsies, and reflexes
-Careful examination for any dysmorphic features suggestive of congenital syndromes (e.g., Romano-Ward, Jervell and Lange-Nielsen syndromes).
Investigations:
-Electrocardiogram (ECG): Essential for measuring QT interval and detecting arrhythmias
-Serial ECGs may be needed
-Holter monitoring: To capture intermittent arrhythmias
-Cardiac MRI: To rule out structural heart disease
-Echocardiogram: To assess cardiac function and rule out structural abnormalities
-Electroencephalogram (EEG): Crucial to differentiate from true seizures
-normal EEG during or between events is highly suggestive of a non-epileptic origin
-Genetic testing: For confirmation of specific LQTS subtypes and genetic counseling.
Differential Diagnosis:
-Epileptic seizures: Differentiated by EEG findings and typical post-ictal state
-Vasovagal syncope: Usually characterized by prodromal symptoms and less frequent seizure-like activity
-Orthostatic hypotension: Less likely to present with typical LQTS-related movements
-Other channelopathies or arrhythmias
-Psychogenic non-epileptic seizures (PNES): May mimic both syncope and seizures but often lack ECG abnormalities and have distinct behavioral patterns.

Management

Initial Management:
-Immediate resuscitation if cardiorespiratory arrest occurs
-Continuous ECG and vital sign monitoring
-Withdrawal of offending medications known to prolong QT
-Correction of electrolyte imbalances (hypokalemia, hypomagnesemia, hypocalcemia).
Medical Management:
-Beta-blockers: Propranolol or nadolol are first-line agents for most LQTS types to reduce adrenergic stimulation and catecholamine-induced arrhythmias
-Specific drug dosages vary by LQTS type and patient age
-e.g., Propranolol 2-4 mg/kg/day divided q6-8h
-Sodium channel blockers (e.g., flecainide) may be considered for specific LQTS types
-Avoid QT-prolonging medications
-Magnesium sulfate infusion for Torsades de Pointes.
Surgical Management:
-Implantable cardioverter-defibrillator (ICD): Indicated for patients with recurrent syncope or documented life-threatening ventricular arrhythmias despite optimal medical therapy
-Left cardiac sympathetic denervation (LCSD): A surgical option for refractory LQTS, particularly in symptomatic individuals who are not candidates for ICD or have failed medical therapy.
Supportive Care:
-Patient and family education on LQTS, triggers to avoid, and emergency management
-Regular follow-up with a pediatric cardiologist and neurologist
-Development of an emergency action plan
-Counseling regarding genetic implications for family members.

Complications

Early Complications:
-Sudden cardiac death (SCD)
-Recurrent syncope or near-syncope
-Neurological injury secondary to syncope (e.g., falls, head trauma).
Late Complications:
-Chronic arrhythmias
-Malfunction or inappropriate shocks from ICD
-Post-denervation syndrome following LCSD
-Psychological impact of living with a life-threatening condition.
Prevention Strategies:
-Strict adherence to beta-blocker therapy
-Regular ECG and clinical monitoring
-Genetic counseling and screening of at-risk family members
-Avoidance of known QT-prolonging drugs and triggers
-Prompt treatment of electrolyte imbalances.

Prognosis

Factors Affecting Prognosis:
-Specific LQTS genotype
-Severity of QT prolongation
-History of syncope or aborted SCD
-Adherence to medical therapy
-Presence of trigger factors
-Family history of SCD.
Outcomes:
-With appropriate management, including beta-blockers and avoidance of triggers, many individuals with LQTS can live normal or near-normal lives
-Patients with high-risk genotypes or a history of SCD have a poorer prognosis and often require ICD implantation
-Risk of SCD is significantly reduced with effective treatment.
Follow Up:
-Regular cardiology and neurology follow-up is essential
-Annual or biannual ECGs and clinical assessments
-Holter monitoring as indicated
-ICD checks if applicable
-Education for patients and families on recognizing warning signs and seeking immediate medical attention.

Key Points

Exam Focus:
-Differentiating cardiac syncope from epileptic seizures is critical
-LQTS predisposes to Torsades de Pointes, a polymorphic VT
-Beta-blockers are the mainstay of medical therapy for most LQTS types
-Avoidance of QT-prolonging drugs is paramount
-ICD implantation for high-risk patients.
Clinical Pearls:
-Always consider LQTS in a child with recurrent syncope or seizure-like activity, especially if triggered by exercise, stress, or auditory stimuli
-A family history of unexplained sudden death in young individuals should raise suspicion for LQTS
-Video-EEG and ECG correlation are key for diagnosis
-Drug-induced LQTS is a common and preventable cause.
Common Mistakes:
-Treating LQTS-induced seizure-like activity with antiepileptic drugs without ruling out a cardiac cause
-Failing to recognize QT prolongation on ECG
-Prescribing QT-prolonging medications in patients with known or suspected LQTS
-Inadequate follow-up and monitoring of patients with LQTS.