Prolonged QTc Interval Definition
A prolonged QTc interval is defined as ≥450 ms in men and ≥460 ms in women, with values >500 ms considered highly abnormal and associated with significantly increased risk of life-threatening arrhythmias. 1
Gender-Specific Thresholds
The American Heart Association and American College of Cardiology Foundation provide clear gender-specific cutoffs for clinical practice:
- Men: QTc ≥450 ms is prolonged 1
- Women: QTc ≥460 ms is prolonged 1
- Both sexes: QTc >500 ms is highly abnormal 1, 2
These thresholds represent practical clinical limits based on large community-based population studies using appropriate linear regression functions for QT-rate adjustment. 1
Alternative Percentile-Based Definition
The American Heart Association recommends an alternative approach using the 99th percentile as the threshold for abnormally prolonged QTc:
This percentile-based approach may be more conservative but identifies patients at the highest risk for torsades de pointes. 1
FDA Risk Stratification Levels
For drug safety monitoring and clinical risk assessment, the FDA recommends reporting three severity levels:
These graduated thresholds help stratify arrhythmia risk, with QTc >500 ms carrying the highest risk for torsades de pointes. 1, 2, 3
Pediatric Considerations
In children younger than 12 years, the 98th percentile limit is approximately 450 ms without gender differentiation. 1 The gender difference of approximately 8 ms emerges during the 12-16 year age group as testosterone shortens the QTc in boys. 1
Critical Measurement Caveats
Correction Formula Matters
Bazett's formula (QTc = QT/√RR) tends to overcorrect at heart rates >85 bpm, which is common in hospitalized patients, potentially leading to false-positive prolongation. 1 The Fridericia formula (QTc = QT/∛RR) provides more accurate rate correction, especially at higher heart rates. 1, 2
Bundle Branch Block Adjustment
When bundle branch block or other intraventricular conduction delays are present, the QT interval prolongs due to delayed depolarization, not repolarization abnormality. 1 Two adjustment methods exist:
- Subtract the difference in QRS width before and after the block 1
- Measure the JT interval (from end of QRS to end of T wave) instead, eliminating QRS duration from the measurement 1
Failure to adjust for bundle branch block will falsely suggest repolarization abnormalities when none exist. 1
Clinical Significance for Risk Stratification
Absolute QTc Values and Risk
The risk of torsades de pointes increases progressively with QTc prolongation, as demonstrated in FDA drug safety data:
- QTc <500 ms: 1.3% incidence of torsades de pointes 3
- QTc 500-525 ms: 3.4% incidence 3
- QTc 525-550 ms: 5.6% incidence 3
- QTc >550 ms: 10.8% incidence 3
Changes from Baseline
Serial QTc monitoring is critical when initiating QT-prolonging medications:
- Increase >30 ms from baseline warrants monitoring 1, 2
- Increase >60 ms from baseline is clinically significant and associated with increased torsades de pointes risk 1, 2, 3
Additional Risk Factors
Beyond absolute QTc values, other factors amplify arrhythmia risk:
- Female gender (higher incidence of torsades de pointes) 3
- Reduced creatinine clearance 3
- History of cardiomegaly or congestive heart failure 3
- Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) 4
Patients with sustained ventricular tachycardia and congestive heart failure have the highest risk (7%) for serious proarrhythmia. 3
Common Pitfalls to Avoid
- Not accounting for gender differences when interpreting QTc values leads to overdiagnosis in men and underdiagnosis in women 1
- Using Bazett's formula at heart rates >85 bpm produces falsely elevated QTc values 1
- Failing to adjust for bundle branch block misattributes depolarization delay to repolarization abnormality 1
- Measuring QT in different leads over time introduces variability; always use the same lead with well-defined T-wave end (amplitude ≥2 mm) 1
- Ignoring time of day effects when comparing sequential tracings, as QT intervals vary diurnally 1