What is a prolonged QT interval?

Prolonged QT Interval

A prolonged QT interval is a cardiac electrical abnormality defined as a QTc interval >450 ms in males or >470 ms in females, with values >500 ms considered highly abnormal and associated with increased risk of torsades de pointes, a potentially fatal ventricular arrhythmia. 1

Definition and Measurement

The QT interval represents the time from the beginning of ventricular depolarization to the end of ventricular repolarization, measured from the onset of the QRS complex to the end of the T wave on an electrocardiogram (ECG). 1

Key measurement considerations:

• The QT interval must be corrected for heart rate (QTc)
• The Fridericia formula (QT divided by cube root of RR interval) is recommended by the FDA for heart rate correction 1
• Normal QTc values are:
  • <430 ms in males
  • <450 ms in females 1

According to the Common Terminology Criteria for Adverse Events (CTCAE), QTc prolongation is graded as:

• Grade 1: 450-480 ms
• Grade 2: 481-500 ms
• Grade 3: >501 ms
• Grade 4: ≥501 ms or >60 ms change from baseline with torsades de pointes or sudden death 1

Clinical Significance

Prolonged QT interval is clinically significant because:

• QTc >500 ms or an increase >60 ms from baseline is associated with increased risk for torsades de pointes 1
• Torsades de pointes is a polymorphic ventricular tachycardia that can lead to syncope, sudden cardiac arrest, or death 2
• It may be misdiagnosed as a seizure disorder 2

Causes of QT Prolongation

Congenital Causes

• Inherited as autosomal dominant variants (congenital long QT syndrome) 2

Acquired Causes

1. Medications:

   • Class IA antiarrhythmics (quinidine, procainamide, disopyramide)
   • Class III antiarrhythmics (sotalol, dofetilide, ibutilide) 3
   • Antipsychotics (especially thioridazine, pimozide, ziprasidone) 3, 4
   • Antidepressants 4
   • Macrolide antibiotics (clarithromycin, erythromycin) 3
   • Fluoroquinolone antibiotics 3
   • Antihistamines (terfenadine, astemizole) 3
   • Antimalarials (chloroquine, halofantrine) 3
   • Methadone 3
   • Gastrointestinal drugs (cisapride) 3

2. Electrolyte Abnormalities:

   • Hypokalemia
   • Hypomagnesemia
   • Hypocalcemia 1, 5

3. Other Factors:

   • Female sex
   • Advanced age
   • Bradycardia
   • Heart disease
   • Heart failure
   • Hypothyroidism
   • Renal or hepatic dysfunction 3, 5

Risk Assessment

High-risk factors for QT prolongation and torsades de pointes include:

• QTc >500 ms
• Increase in QTc >60 ms from baseline
• Female sex
• Advanced age (>65 years)
• Heart disease (especially left ventricular hypertrophy or low ejection fraction)
• Bradyarrhythmias
• Electrolyte abnormalities
• Concomitant use of multiple QT-prolonging medications 1, 3

Warning Signs of Impending Torsades de Pointes

• Sudden bradycardia or long pauses
• Enhanced U waves
• T wave alternans
• Nonsustained polymorphic ventricular tachycardia 1

Management of QT Prolongation

1. Prevention:

   • Baseline ECG before starting QT-prolonging medications
   • Correction of electrolyte abnormalities (particularly hypokalemia and hypomagnesemia)
   • Identify and avoid drug-drug interactions that prolong QTc 1

2. Monitoring:

   • ECG should be repeated 7 days after initiation of QT-prolonging therapy
   • Follow-up ECGs after any dosing changes 1
   • Use the same ECG lead for consistent QT measurements 1

3. Intervention:

   • Discontinue QT-prolonging medications if QTc >500 ms 1
   • Maintain serum potassium between 4.5-5 mEq/L 1
   • For torsades de pointes:
     • Administer 2g IV magnesium regardless of serum magnesium level
     • Consider overdrive pacing (90-110 bpm) if TdP is precipitated by bradycardia
     • Use IV isoproterenol if temporary pacing is not immediately available
     • Correct all electrolyte abnormalities 1

Common Pitfalls in QT Assessment and Management

• Failing to recognize drug interactions that can prolong QT
• Overlooking electrolyte abnormalities
• Using Bazett's formula at high heart rates (tends to overestimate QTc)
• Administering isoproterenol to patients with familial long QT syndrome 3
• Not accounting for widened QRS when assessing QT prolongation (should subtract increased QRS length from QT interval or measure JT interval instead) 1
• Including U waves in QT measurement when they are discrete and occur after T wave returns to baseline 1

Special Considerations

• In patients with bundle branch block, subtract the difference in QRS widths before and after the block, or measure the JT interval 1
• For QT monitoring, select the ECG lead with the longest T wave and avoid leads with U waves 1
• The same lead should be used consistently for monitoring the same patient 1

Understanding and recognizing prolonged QT interval is critical for preventing potentially fatal arrhythmias, particularly when prescribing medications known to affect cardiac repolarization.