What is considered a prolonged QTc (corrected QT) interval?

From the Guidelines

A prolonged QTc interval is generally considered to be greater than 500 milliseconds, as values exceeding this threshold pose a higher risk for dangerous cardiac arrhythmias, particularly Torsades de Pointes. When evaluating QTc prolongation, it's essential to consider both congenital and acquired causes. Common medications that can prolong QTc include certain antiarrhythmics, antibiotics, antipsychotics, and antidepressants. Electrolyte abnormalities, particularly hypokalemia, hypomagnesemia, and hypocalcemia, can also significantly prolong the QTc interval. The QTc represents the heart's electrical repolarization phase, and prolongation indicates delayed ventricular repolarization, which creates vulnerability to early afterdepolarizations that can trigger dangerous arrhythmias.

Key Considerations

• The QT interval should be measured from the beginning of the QRS complex to the end of the T wave, and corrected for heart rate (QTc) to assess trends in a given patient over time 1.
• A normal QTc is typically considered to be less than 450 milliseconds in men and less than 460 milliseconds in women, but values exceeding 500 milliseconds are considered significantly prolonged and pose a higher risk for torsades de pointes 1.
• The most commonly used QT correction formula in clinical practice is the one introduced by Bazett, QTc = QT interval divided by the square root of the R-R interval measured in seconds, although other formulas like Fridericia's may also be used 1.
• Patients with prolonged QTc should be monitored closely, have electrolytes corrected, and potentially have offending medications discontinued or doses adjusted to reduce the risk of sudden cardiac death 1.

Management and Prevention

• The following lifestyle changes are recommended in all patients with a diagnosis of LQTS: avoidance of QT-prolonging drugs, correction of electrolyte abnormalities, and avoidance of genotype-specific triggers for arrhythmias 1.
• Beta-blockers are recommended in patients with a clinical diagnosis of LQTS, and ICD implantation with the use of beta-blockers is recommended in LQTS patients with previous cardiac arrest 1.
• Left cardiac sympathetic denervation should be considered in patients with symptomatic LQTS when beta-blockers are either not effective, not tolerated, or contraindicated 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 below relates the incidence of Torsade de Pointes to on-therapy QTc and change in QTc from baseline. On-Therapy QTc Interval(msec) Incidence of Torsade dePointes less than 5001.3% 500 to 5253.4% 525 to 5505.6%

1. 8%

A prolonged QtC is considered to be ≥ 500 msec, with the risk of Torsade de Pointes increasing significantly at QtC intervals > 550 msec 2 2.

• Key risk factors for Torsade de Pointes include:
  • Dose: Higher doses of sotalol increase the risk of Torsade de Pointes
  • Gender: Females have a higher incidence of Torsade de Pointes
  • Excessive prolongation of the QtC interval: QtC intervals > 550 msec increase the risk of Torsade de Pointes
  • History of cardiomegaly or congestive heart failure: Patients with a history of cardiomegaly or congestive heart failure appear to have a higher risk for serious proarrhythmia
• Monitoring of the QtC interval is essential during sotalol therapy to reduce the risk of Torsade de Pointes.

From the Research

Definition of Prolonged QTc Interval

• A prolonged QTc interval is considered ≥470 milliseconds (ms) for males and ≥480 ms for females, as defined in the study by 3.
• In both genders, a QTc interval >500 ms is considered severe, according to 3.
• Normal QTc intervals are typically <450 ms for men and <460 ms for women, as stated in the study by 4.
• A QTc interval ≥440 ms is also considered prolonged in some studies, such as the one by 5.

Factors Influencing QTc Interval Prolongation

• Patient-related risk factors, such as female sex, age >65 years, and uncorrected electrolyte disturbances, can contribute to QTc interval prolongation, as mentioned in the study by 4.
• Certain drugs can also prolong the QTc interval, and their use should be carefully considered in patients at risk, as discussed in the studies by 3, 4, and 6.
• Comorbidities, hormonal influences, and genetic factors can also affect the QTc interval, as noted in the study by 6.

Clinical Significance of Prolonged QTc Interval

• Prolongation of the QTc interval may increase the risk of total and cardiovascular mortality, as well as sudden death, particularly in patients with prior cardiovascular disease, as reported in the study by 5.
• However, the clinical importance of modest QTc interval prolongation in the general population remains unclear, as stated in the study by 5.
• The risk of arrhythmic events increases by ~5% for every 10 ms increase in the QTc interval, as mentioned in the study by 4.