Everything You Need to Know About Long QT syndrome for Step 1

Long QT syndrome (LQTS) is one of those Step 1 “ECG + genetics + lethal arrhythmia” topics that shows up everywhere: on question stems about syncope after swimming, on pharm questions about macrolides, and on sudden death vignettes that end with torsades de pointes. If you can recognize a prolonged QT, understand why it happens, and know what it predisposes to + what to do, you’ll pick up a lot of easy points.

---

What “Long QT” Actually Means (Definition + Core Concept)

QT interval basics

• The QT interval represents ventricular depolarization + repolarization (action potential duration).
• It varies with heart rate, so we use QTc (corrected QT).

A common correction on exams is Bazett’s formula:

$QTc = \frac{QT}{\sqrt{RR}}$

Where QT and RR are in seconds.

Diagnostic thresholds (high yield)

• Prolonged QTc (typical board cutoffs):
  • > 440 ms in men
  • > 460 ms in women
• Marked risk often emphasized when QTc ≥ 500 ms (torsades risk rises).

Key Step concept: Prolonged QT = delayed ventricular repolarization → “electrical instability” → polymorphic VT (torsades).

---

Pathophysiology: Why Does QT Prolong?

Think ion channels and action potential phases.

Ventricular action potential tie-in (HY physiology)

• Phase 0: fast Na⁺ influx
• Phase 2 plateau: Ca²⁺ influx balanced by K⁺ efflux
• Phase 3 repolarization: K⁺ efflux dominates (delayed rectifier K⁺ currents are key)

Long QT typically results from:

• Decreased outward K⁺ current (slower repolarization), and/or
• Increased inward Na⁺ current (persistent depolarizing current)

This prolongs the action potential → increases risk of early afterdepolarizations (EADs), which can trigger torsades.

The big mechanism sentence (worth memorizing)

Prolonged QT predisposes to torsades because delayed repolarization promotes EADs during phases 2–3, leading to triggered activity and polymorphic VT.

---

Congenital vs Acquired LQTS (The Two Buckets You Must Separate)

Quick comparison table

---

Congenital Long QT: High-Yield Genetics + Triggers

The “classic” congenital types you’ll see on Step

Most common inheritance is autosomal dominant (Romano-Ward). There’s also Jervell and Lange-Nielsen (autosomal recessive + congenital deafness).

Romano-Ward syndrome (AD)

• Pure cardiac phenotype (no deafness)
• Mutations often involve:
  • KCNQ1 (LQT1): ↓ K⁺ current
  • KCNH2 / hERG (LQT2): ↓ K⁺ current
  • SCN5A (LQT3): ↑ late Na⁺ current

Jervell and Lange-Nielsen syndrome (AR)

• Congenital sensorineural deafness + long QT
• Classically due to K⁺ channel mutations

Trigger patterns (frequent testable associations)

• LQT1 (KCNQ1): events triggered by exercise, classically swimming
• LQT2 (hERG/KCNH2): events triggered by sudden loud noises (alarm clock)
• LQT3 (SCN5A): events during rest/sleep (bradycardia can worsen QT)

You don’t need to be a cardiologist—just match trigger + channel.

---

Acquired Long QT: The “Don’t Miss” Causes

1) Drugs (the Step 1 favorites)

Remember the big classes that prolong QT and can cause torsades:

• Antiarrhythmics class IA (quinidine, procainamide, disopyramide)
• Antiarrhythmics class III (amiodarone, sotalol, dofetilide, ibutilide)
• Macrolides (erythromycin, clarithromycin, azithromycin)
• Fluoroquinolones (levofloxacin, moxifloxacin)
• Antipsychotics (especially haloperidol, ziprasidone; also others)
• TCAs
• Methadone
• Ondansetron (commonly tested)

First Aid cross-reference: Look at the antiarrhythmic drugs table (QT prolongation + torsades warning) and the antipsychotic adverse effects section.

2) Electrolytes (most tested triad)

• Hypokalemia
• Hypomagnesemia
• Hypocalcemia (classically prolongs QT by prolonging ST segment)

Clinical pearl: HypoK and hypoMg are the most torsades-associated in practice and on exams.

3) Bradycardia

Slower heart rates can increase QT and torsades risk—often relevant when a stem mentions:

• AV block
• Sinus bradycardia
• Overdose of AV nodal blockers (context-dependent)

---

Clinical Presentation: How It Shows Up in Vignettes

Core symptoms

• Syncope (often exertional or sudden)
• Palpitations
• Seizure-like activity (actually cerebral hypoperfusion)
• Sudden cardiac death

The classic exam vignette styles

• Teen collapses while swimming → congenital LQTS (often LQT1)
• Patient started on erythromycin + antipsychotic → acquired QT prolongation → torsades
• Recurrent syncope + family history of sudden death → congenital LQTS
• Prolonged QT + sensorineural deafness → Jervell and Lange-Nielsen

---

ECG Interpretation: What You’re Looking For (Step-Friendly)

What “prolonged QT” looks like

• QT interval measured from start of QRS to end of T wave
• QTc prolonged beyond normal thresholds
• T waves may look broad, notched, or abnormal depending on subtype (nice-to-know, not required)

What it can lead to: Torsades de pointes

Torsades is a form of polymorphic ventricular tachycardia with:

• “Twisting” QRS complexes around the baseline
• Often initiated by a premature ventricular beat in the setting of prolonged QT

High-yield phrase: “Polymorphic VT in the setting of prolonged QT” = torsades until proven otherwise.

---

Diagnosis: How Questions Want You to Confirm It

First step: Identify prolonged QTc

• Compute/estimate QTc if needed (often they’ll just tell you QTc)

Consider underlying cause

• Medication review
• Electrolytes (K, Mg, Ca)
• Family history, triggers, congenital deafness

Tests you might see mentioned

• Genetic testing (more real-world than Step, but may appear)
• Holter/event monitor (for intermittent arrhythmias)
• Schwartz score (rare on Step; don’t over-focus)

---

Management: Acute vs Long-Term (Very Testable)

If the patient has torsades (acute management)

1. IV magnesium sulfate (even if Mg level is normal)
2. Stop QT-prolonging drugs
3. Correct electrolytes (replete K⁺, Mg²⁺; address Ca²⁺ if low)
4. If unstable: cardioversion/defibrillation as appropriate
5. If recurrent torsades with bradycardia: increase heart rate
   • Overdrive pacing or IV isoproterenol (classically discussed for acquired torsades)

First Aid cross-reference: Ventricular arrhythmias section—torsades treatment is a classic FA bullet.

Long-term management (especially congenital LQTS)

• Beta-blockers (mainstay; reduce sympathetic triggers)
  • Particularly emphasized for LQT1/LQT2
• Avoid QT-prolonging medications (patient counseling is a big deal)
• ICD for high-risk patients (history of cardiac arrest, recurrent syncope despite therapy)
• Sometimes left cardiac sympathetic denervation (specialized; low-yield)

Nuance that can show up: LQT3 is sodium-channel related and events at rest; beta-blockers still used, but management can be more individualized. For Step purposes: beta-blocker = cornerstone.

---

High-Yield Associations & “Gotcha” Facts (USMLE Favorites)

Long QT → torsades → VF risk

• Torsades can degenerate into ventricular fibrillation → sudden death.

The “EAD” connection

• Prolonged QT is associated with early afterdepolarizations (EADs)
• EADs occur in phases 2 and 3
• Hypokalemia increases EAD risk (less K⁺ conductance → slower repolarization)

Electrolyte distinctions (easy points)

• Hypocalcemia prolongs QT (prolonged ST)
• Hypercalcemia shortens QT
  (These are common ECG electrolyte questions.)

Drug interaction trap

• Two QT-prolonging meds together (e.g., macrolide + antipsychotic) or QT-prolonger + electrolyte derangement (e.g., diuretic-induced hypoK) is a classic setup.

---

Rapid Review Checklist (What You Should Recall in 15 Seconds)

• Definition: Prolonged QTc → delayed ventricular repolarization
• Main danger: torsades de pointes (polymorphic VT)
• Mechanism: prolonged AP → EADs
• Congenital: channelopathies (Romano-Ward AD; Jervell-Lange-Nielsen AR + deafness)
• Acquired causes: drugs (IA, III, macrolides, FQs, antipsychotics, TCAs, methadone, ondansetron), hypoK/hypoMg/hypoCa, bradycardia
• Acute torsades treatment: IV magnesium
• Long-term congenital treatment: beta-blocker, avoid triggers/drugs, consider ICD