Cardiology

Background 

Long QT Syndrome (LQTS) is a cardiac channelopathy characterized by delayed ventricular repolarization, resulting in a prolonged QT interval on electrocardiogram (ECG). This prolongation predisposes to life-threatening arrhythmias, especially torsades de pointes (TdP), and sudden cardiac death. It can be congenital or acquired and is typically due to mutations in genes affecting cardiac ion channels.

II) Classification/Types

By Etiology: 

• Congenital LQTS 

• Romano-Ward Syndrome: Autosomal dominant; isolated cardiac phenotype. 

• Jervell and Lange-Nielsen Syndrome: Autosomal recessive; associated with congenital sensorineural deafness. 

• Acquired LQTS 

• Caused by drugs, electrolyte imbalances, bradycardia, or structural heart disease. 

By Genetic Subtypes (Congenital): 

• LQT1: KCNQ1 gene mutation – affects IKs current (slow delayed rectifier K⁺ current) 

• LQT2: KCNH2/HERG mutation – affects IKr current (rapid delayed rectifier K⁺ current) 

• LQT3: SCN5A gene mutation – affects INa current (sodium channels) 

Each type has characteristic triggers (e.g., exercise in LQT1, auditory stimuli in LQT2, rest/sleep in LQT3). 

Pathophysiology 

LQTS results from dysfunctional ion channels that prolong the ventricular action potential, especially phase 3 (repolarization). This increases the QT interval and creates electrical instability, predisposing the myocardium to early afterdepolarizations (EADs), which can trigger torsades de pointes. 

Epidemiology 

• Prevalence: ~1 in 2,000 individuals for congenital LQTS 

• Female predominance in acquired LQTS 

• Congenital forms often manifest in childhood or adolescence 

• Acquired forms more common in adults due to polypharmacy or comorbidities 

Etiology 

I) Causes

• Congenital: Mutations in ion channel genes (e.g., KCNQ1, KCNH2, SCN5A) 

• Acquired: 

• Medications (antiarrhythmics, macrolides, fluoroquinolones, antipsychotics, methadone) 

• Electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia) 

• Bradyarrhythmias 

• Hypothyroidism 

• Intracranial events (e.g., stroke, subarachnoid hemorrhage) 

II) Risk Factors

• Family history of SCD or LQTS 

• Female sex (especially for acquired LQTS) 

• Use of QT-prolonging drugs 

• Electrolyte imbalance 

• Structural or ischemic heart disease 

Clinical Presentation 

I) History (Symptoms)

• Syncope (often exertional or emotional) 

• Seizure-like episodes 

• Palpitations 

• Sudden cardiac arrest (especially during stress, sleep, or auditory stimulation) 

• Asymptomatic (in 25–30% of cases) 

II) Physical Exam (Signs)

• Often normal between episodes 

• Bradycardia may be present 

• Seizure-like activity without neurologic findings during events 

Differential Diagnosis (DDx) 

• Seizure disorders 

• Vasovagal syncope 

• Brugada syndrome 

• Catecholaminergic polymorphic VT (CPVT) 

• Short QT syndrome 

• Structural heart disease 

• AV block or sick sinus syndrome 

Diagnostic Tests 

Initial Work-Up 

• 12-lead ECG: 

• Prolonged QT interval (>460 ms in females, >440 ms in males) 

• T-wave abnormalities: notched, broad, or low amplitude 

• TdP episodes: polymorphic VT with twisting QRS complexes 

• Electrolyte panel: Identify and correct hypokalemia, hypomagnesemia, hypocalcemia 

• Medication review: Identify QT-prolonging drugs 

Advanced Testing 

• Genetic Testing: Confirms congenital LQTS subtype; helps guide therapy and family screening 

• Exercise Stress Test: QT response may differ by genotype (e.g., paradoxical QT prolongation in LQT1) 

• Holter/Event Monitor: Detects intermittent arrhythmias or TdP episodes 

Treatment 

1. I) Acute Management

• Torsades de Pointes: 

• IV magnesium sulfate (even if normal serum magnesium) 

• Temporary pacing or isoproterenol for bradycardia-induced TdP 

• Electrical cardioversion if hemodynamically unstable 

• Discontinue offending drugs and correct electrolytes 

II) Chronic Management

• Beta-blockers (e.g., nadolol, propranolol): First-line for congenital LQTS, especially LQT1 and LQT2 

• ICD (Implantable Cardioverter-Defibrillator): 

• Indicated for secondary prevention (after cardiac arrest or sustained VT/VF) 

• Consider for primary prevention in high-risk patients (e.g., syncope despite beta-blockers) 

• Left cardiac sympathetic denervation (LCSD): For refractory cases or ICD-intolerant patients 

Medications 

Device Therapy 

• ICD: Life-saving for high-risk or post-arrest patients 

• Pacing: Overdrive pacing can suppress TdP in bradycardia-induced LQTS 

• LCSD: Surgical option for patients with recurrent arrhythmias despite optimal therapy 

Patient Education, Screening, Vaccines 

Education: 

• Avoid QT-prolonging medications  

• Importance of medication adherence (especially beta-blockers) 

• Recognize prodromes (dizziness, palpitations) 

• Seek immediate help if syncopal episodes occur 

Screening/Prevention: 

• ECG and genetic screening in first-degree relatives 

• Avoid competitive sports in some subtypes (e.g., LQT1) 

• Monitor electrolytes in at-risk patients (e.g., diuretic users) 

Vaccinations: 

• Routine immunizations encouraged 

• Monitor for fever-related dehydration and electrolyte imbalance 

Consults/Referrals 

• Cardiology/Electrophysiology: For diagnostic work-up and ICD evaluation 

• Genetics: For testing and counseling 

• Neurology: If episodes are misinterpreted as seizures 

• Pharmacy: For QT-prolonging drug review and education 

Follow-Up 

Short-Term: 

• Monitor QT interval after correcting causes or medication changes 

• Repeat ECG after acute events or medication changes 

Long-Term: 

• Annual ECG and Holter monitoring 

• Regular ICD checks (if implanted) 

• Family member follow-up and cascade testing 

Prognosis 

• Excellent with early diagnosis and treatment, especially with beta-blockers and/or ICD 

• High risk of sudden cardiac death if left untreated or misdiagnosed 

• Risk varies by genotype (LQT3 has higher risk of lethal arrhythmias at rest)