When does a prolonged QTc (corrected QT interval) become problematic?

From the Guidelines

A prolonged QTc interval becomes problematic when it exceeds 500 milliseconds, as this significantly increases the risk of adverse events, including torsades de pointes and sudden cardiac death, as noted in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.

Key Considerations

• The risk of adverse events increases in patients with long QT syndrome with prolongation of the QTc >500 ms, as stated in the 2017 AHA/ACC/HRS guideline 1.
• QT-prolonging medications should not be used in patients with long QT syndrome unless there is no suitable alternative, and careful monitoring of the QTc during therapy is recommended 1.
• Episodes of torsades de pointes can be precipitated by exposure to a QT prolonging medication, or hypokalemia induced by diuretics or gastrointestinal illness, highlighting the importance of maintaining normal potassium and magnesium balance 1.

Management and Prevention

• Immediate actions for a patient with a prolonged QTc should include correcting electrolyte abnormalities, discontinuing offending medications when possible, and monitoring cardiac rhythm.
• The European Society of Cardiology also suggests that QTc intervals >450 ms in men and >460 ms in women are considered abnormal, with QTc prolongation >500 ms and a change from baseline of >60 ms being of particular concern due to the increased risk of torsades de pointes 1.
• It is crucial to assess cardiac risk before initiating treatment with drugs that can prolong the QT interval and to monitor the QT interval during treatment, especially in elderly patients or those with structural heart disease, as recommended in the European Heart Journal 1.

From the FDA Drug Label

Prolongation of the QT interval is dose related, increasing from baseline an average of 25,40, and 50 msec in the 80,120, and 160 mg groups, respectively, in the clinical dose-response study. In this clinical trial Sotalol AF treatment was not initiated if the QT interval was greater than 450 msec and during therapy the dose was reduced or discontinued if the QT interval was ≥520 msec Table 7 Relationship Between QTc Interval Prolongation and Torsade de Pointes * ( ) Number of patients assessed On-Therapy QTc Interval(msec) Incidence of Torsade dePointes Change in QTc Interval FromBaseline (msec) Incidence of Torsade dePointes less than 5001.3% (1787)less than 651.6% (1516) 500 to 5253.4% (236)65 to 803.2% (158) 525 to 5505.6% (125)80 to 1004.1% (146) >55010. 8% (157)100 to 305.2% (115) >1307. 1% (99)*

A prolonged QTc becomes problematic at ≥ 500 msec, with an increased incidence of Torsade de Pointes, and the risk further increases at ≥ 520 msec and ≥ 550 msec. The dose of Sotalol AF should be reduced or discontinued if the QT interval is ≥ 520 msec. Key factors that increase the risk of Torsade de Pointes include:

• Dose: Higher doses of Sotalol AF increase the risk of Torsade de Pointes.
• QTc interval prolongation: Greater prolongation of the QTc interval increases the risk of Torsade de Pointes.
• Gender: Females have a higher incidence of Torsade de Pointes.
• History of cardiomegaly or congestive heart failure: Patients with a history of cardiomegaly or congestive heart failure are at higher risk for serious proarrhythmia. 2

From the Research

Prolonged QTc Interval

A prolonged QTc interval can be problematic when it increases the risk of life-threatening arrhythmias, such as torsade de pointes [ 3, 4,5,6 ].

Risk Factors for Prolonged QTc Interval

Several factors can contribute to a prolonged QTc interval, including:

• Demographic factors: age, female sex 4
• Comorbidities: thyroid disease, myocardial infarction 4
• Electrolyte imbalances: hypokalemia, hypocalcemia 4, 6
• Medications: anti-arrhythmic drugs, antimicrobial agents, atypical antipsychotic drugs 3, 5, 7
• Other risk factors: history of stroke, hypertension, diabetes 4

QTc Prolongation and Medications

Certain medications can prolong the QTc interval, including:

• Anti-arrhythmic drugs: amiodarone, sotalol, dofetilide, procainamide, quinidine, flecainide 3
• Antimicrobial agents: macrolides, quinolones, azoles, pentamidine, protease inhibitors 5
• Atypical antipsychotic drugs: risperidone, quetiapine, ziprasidone 7

Management of Prolonged QTc Interval

The management of a prolonged QTc interval typically involves:

• Reducing the dosage of or discontinuing the offending medication 3
• Employing selective beta blockers 3
• Close monitoring of the QT interval 3
• Consideration of patient-specific risk factors for QTc prolongation 3, 4, 6