CARDIOLOGY REVIEW
🫀 Long QT Syndrome
Comprehensive Visual Guide — Types, Diagnostic Criteria & Clinical Approach | April 2026
>50%
15-yr mortality untreated
<1%
20-yr mortality treated
1. Classification Overview
🔴 Congenital LQTS
- Romano-Ward (AD) — cardiac only; LQT1-6, 9-17
- Jervell & Lange-Nielsen (AR) — LQTS + deafness; KCNQ1/KCNE1 biallelic
- Andersen-Tawil (AD) — LQT7; periodic paralysis + dysmorphism
- Timothy syndrome (AD) — LQT8; syndactyly, ASD, autism
🟡 Acquired LQTS
- Drugs: Class Ia/III antiarrhythmics, macrolides, fluoroquinolones, antipsychotics, methadone
- Electrolytes: Hypokalemia, hypomagnesemia, hypocalcemia
- Metabolic: Hypothyroidism, hypothermia
- Bradycardia — pauses promote TdP
2. The Big Three Genotypes (≥90% of cases)
| Type | Gene | Channel | Prevalence | Triggers | T-wave Morphology |
|---|
| LQT1 |
KCNQ1 |
IKs ↓ (loss of function) |
30–35% |
Exercise (swimming), emotional stress |
Broad-based, smooth T |
| LQT2 |
KCNH2 (hERG) |
IKr ↓ (loss of function) |
25–30% |
Auditory stimuli, emotional stress, postpartum |
Low-amplitude, notched/bifid T |
| LQT3 |
SCN5A |
Late INa ↑ (gain of function) |
5–10% |
Rest/sleep, bradycardia |
Late-onset T, long ST segment |
⚡ Clinical memory aid: LQT1 = Swimming/Sympathetic → LQT2 = Alarm/Auditory → LQT3 = Rest/sleep → S.A.R.
3. Complete LQT Subtype Reference (LQT1–17)
| LQT | Gene | Protein/Current | Key Feature |
|---|
| 1 | KCNQ1 | IKs α-subunit | Most common; exercise triggers |
| 2 | KCNH2 | IKr (hERG) | Auditory triggers; notched T |
| 3 | SCN5A | Late INa ↑ | Rest/sleep triggers; mexiletine responsive |
| 4 | ANK2 | Ankyrin-B | Sinus dysfunction, AF |
| 5 | KCNE1 | IKs β-subunit (minK) | Biallelic → JLN + deafness |
| 6 | KCNE2 | IKr β-subunit (MiRP1) | Drug-sensitive QT↑ |
| 7 | KCNJ2 | IK1 (Kir2.1) | Andersen-Tawil; periodic paralysis, U waves |
| 8 | CACNA1C | ICa-L (Cav1.2) | Timothy syndrome; syndactyly, autism, QT>500ms |
| 9 | CAV3 | Caveolin-3 | SIDS association |
| 10 | SCN4B | NaV β4 subunit | Late INa ↑ |
| 11 | AKAP9 | Yotiao (IKs regulation) | Rare |
| 12 | SNTA1 | α1-syntrophin | SCN5A targeting |
| 13 | KCNJ5 | IK(ACh) (Kir3.4) | AF association |
| 14 | CALM1 | Calmodulin | Infantile severe LQTS; seizures |
| 15 | CALM2 | Calmodulin | Infantile severe LQTS |
| 16 | CALM3 | Calmodulin | Infantile severe LQTS |
| 17 | TRDN | Triadin | AR; pediatric cardiac arrest |
4. Diagnostic Criteria: Schwartz Score
| Criterion | Points |
|---|
| QTc ≥480 ms | 3 |
| QTc 460–479 ms | 2 |
| QTc 450–459 ms (males) | 1 |
| Torsades de pointes | 2 |
| T-wave alternans | 1 |
| Notched T waves (3 leads) | 1 |
| Low heart rate for age (children) | 0.5 |
| Syncope with stress | 2 |
| Syncope without stress | 1 |
| Congenital deafness | 0.5 |
| Family history of LQTS | 1 |
| Family history of SCD <30 yr | 0.5 |
✅ Score ≥3.5 = Diagnose LQTS. Score 1.5–3 = Intermediate → provocative testing.
≥3.5 points → HIGH PROBABILITY → Diagnose LQTS
1.5–3 points → INTERMEDIATE → Provocative testing needed
5. QTc Diagnostic Thresholds (2023 HRS/ACC/AHA)
| QTc (ms) | Classification | Action |
|---|
| ≥500 | DEFINITE LQTS | Treat regardless of symptoms |
| 480–499 | HIGH PROBABILITY | Treat if symptoms/family hx |
| 460–479 | BORDERLINE | Exercise test, epinephrine challenge |
| <460 | NORMAL RANGE | Does NOT exclude concealed LQTS! |
⚠️ ~25–35% of genotype-positive patients have QTc <460 ms at rest. Never dismiss LQTS based on a single normal ECG.
6. QT Interval Measurement Technique
Measurement method: From QRS onset to T wave end (tangent method for notched T waves).
✅ Measurement tip: Use tangent method for T wave end when T wave is notched (common in LQT2). Draw tangents from both T wave peaks; intersection = T end.
7. T-Wave Morphology by Genotype
LQT1: Broad-Based T
• Smooth, wide T wave
• T wave duration ↑
• Most common type (30-35%)
LQT2: Notched Bifid T
• Low amplitude, 2 peaks
• T wave amplitude ↓, notch ↑
• Characteristic auditory triggers
LQT3: Late-Onset T
• Long ST segment, late T wave
• ST segment prolonged
• Rest/sleep triggers; highest risk at rest
✅ Diagnostic accuracy: LQT1 T pattern 82% specificity, LQT2 T pattern 78% specificity (Zhang et al., Circulation 2011)
8. Provocative Testing
Exercise Stress Test
| Genotype | Exercise Response | Key Finding |
|---|
| LQT1 | Poor QT shortening | Flat QT-HR slope (IKs can't upregulate) |
| LQT2 | Normal during, ↑↑ in recovery | Prominent recovery QTc prolongation |
| LQT3 | Excessive QT shortening | "Normal" response; risk at rest |
✅ Recovery QTc >480 ms at 1–4 min post-exercise is the single most useful ECG metric for concealed LQTS.
| Genotype | Exercise Response | Key Finding |
|---|
| LQT1 | Poor QT shortening | Flat QT-HR slope (IKs can't upregulate) |
| LQT2 | Normal during, ↑↑ in recovery | Prominent recovery QTc prolongation |
| LQT3 | Excessive QT shortening | "Normal" response; risk at rest |
✅ Recovery QTc >480 ms at 1–4 min post-exercise is the single most useful ECG metric for concealed LQTS.
Epinephrine Challenge
| Response | Suggests | Mechanism |
|---|
| Paradoxical QTc↑ ≥30 ms (low-dose) | LQT1 | IKs cannot respond to β-stimulation |
| Transient QTc↑ then normalizes | LQT2 | Transient IKr suppression by PKA |
| Minimal QTc change | LQT3 | Late INa not β-adrenergically mediated |
8. Risk Stratification: 1-2-3-LQTS-Risk
1️⃣ QTc Duration
Every 10 ms ↑ → ~15% ↑ risk
QTc ≥500 = HIGH RISK
2️⃣ Syncope / Cardiac Arrest History
Strongest predictor of future events
Prior CA → highest risk
3️⃣ Genotype
Risk hierarchy: LQT2 ≥ LQT3 > LQT1
(at comparable QTc)
Other Modifiers
Female sex (LQT2), postpartum, compound heterozygosity, BB non-compliance
| Risk | Features | Management |
|---|
| Low | QTc <480, no syncope, LQT1 | Beta-blocker alone |
| Intermediate | QTc 480–500, syncope on BB | BB ± LCSD |
| High | QTc ≥500, CA, recurrent syncope | BB + ICD ± LCSD |
9. Torsades de Pointes & T-Wave Alternans
Torsades de Pointes (TdP):
• Polymorphic VT with QRS axis rotation
• "Twisting" pattern (pointes = points)
• Initiated by pause-early beat
• Self-terminating or degenerates to VF
T-Wave Alternans:
• Beat-to-beat T amplitude variation
• Macroscopic (visible) or microscopic
• TdP precursor sign
• 2:1 or 3:1 alternation pattern
TdP Warning Signs: QTc > 500 ms, new medications, electrolyte disturbances, bradycardia/pauses
✅ T-Wave Alternans = Red flag. Seen in 15-25% of LQTS patients. Warrants immediate beta-blocker and consider MgSO₄ 2 g IV.
TdP Warning Signs:
• QTc > 500 ms
• New medications
• Electrolyte disturbances
• Bradycardia/pauses
T-Wave Alternans = Red Flag:
• 15-25% of LQTS patients
• Strong TdP predictor
• Warrants immediate BB
• Consider magnesium 2 g IV
10. Management Essentials
Beta-Blockers
❌ AVOID METOPROLOL — significantly higher event rates vs nadolol/propranolol (Chockalingam et al., JACC 2012)
| Drug | Rank | Notes |
|---|
| Nadolol | 1st line ★ | Long half-life; best evidence |
| Propranolol | 1st line ★ | Multiple daily doses needed |
| Atenolol | Alternative | Once daily |
| Metoprolol | NOT preferred | Higher recurrence |
Genotype-Specific Therapy
| Genotype | Specific Approach |
|---|
| LQT1 | BB excellent; avoid strenuous exercise (esp. swimming) |
| LQT2 | BB + K⁺ supplementation; avoid sudden loud noises |
| LQT3 | Mexiletine or ranolazine (late INa blockers); ICD more often |
| LQT7 (ATS) | BB for QT; acetazolamide for paralysis |
| LQT8 (TS) | Verapamil; high ICD rate |
✅ LCSD (Left Cardiac Sympathetic Denervation) — for BB-refractory symptoms, ICD storm, or BB intolerance. Removes lower stellate ganglion + T2-T4. Reduces arrhythmic events ~90%.
11. Take-Home Points
- LQTS is the most common inherited cardiac channelopathy. Think of it in any young person with unexplained syncope, seizures, or family SCD.
- Schwartz ≥3.5 = diagnose. But concealed LQTS exists — use provocative testing.
- LQT1/2/3 = 90%+ of cases. Triggers: S.A.R. = Swimming, Alarm, Rest.
- Nadolol/Propranolol > Metoprolol. Not all beta-blockers are equal.
- QTc ≥500 ms = high risk. Every 10 ms adds ~15% arrhythmic risk.
- Genetic testing changes management. Cascade testing saves lives.
- Recovery QTc >480 ms on exercise test = single most useful metric for concealed LQTS.
- Epinephrine paradoxical QTc prolongation = pathognomonic for LQT1.
Key References
- Adler A, et al. Circulation. 2020;141:418–428. doi:10.1161/CIRCULATIONAHA.119.043132
- Giudicessi JR, Ackerman MJ. Curr Probl Cardiol. 2013;38:417–455.
- Mazzanti A, et al. Europace. 2022;24:614–619.
- Chockalingam P, et al. JACC. 2012;60:2092–2099.
- Al-Khatib SM, et al. 2023 HRS/ACC/AHA Guidelines. Heart Rhythm. 2023.
- Priori SG, et al. 2015 ESC Guidelines. Eur Heart J. 2015;36:2793–2867.
- Kutyifa V, et al. Ann Noninvasive Electrocardiol. 2018;23:e12537.
- Bains S, et al. JACC. 2023;81:477–486.
Long QT Syndrome — Visual Guide | Compiled April 2026 | For educational purposes only