What is the cause of a prolonged QTc interval in a patient with a ventricular paced (V paced) rhythm?

From the Guidelines

Ventricular pacing can indeed cause prolonged QTc intervals, and it is crucial to monitor the QTc interval in patients with ventricular pacemakers, especially when starting QT-prolonging medications, as stated in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. When the ventricles are paced artificially, the electrical activation sequence differs from the normal physiological pattern, leading to altered ventricular depolarization and repolarization. This altered electrical pathway typically manifests as a widened QRS complex followed by T-wave changes, which together can prolong the QTc interval. The extent of QTc prolongation depends on several factors including pacing site, underlying cardiac disease, and percentage of ventricular pacing. Some key points to consider include:

• Right ventricular apical pacing particularly tends to cause more significant QTc prolongation compared to other pacing sites because it creates a more dyssynchronous ventricular activation pattern.
• Patients with pre-existing QTc prolongation or those taking QT-prolonging medications, such as those listed in the acc/aha/esc 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, including disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, and others 2, may experience more pronounced effects.
• If problematic QTc prolongation occurs, strategies such as reducing the percentage of ventricular pacing (using algorithms that promote intrinsic conduction), considering alternative pacing sites like the His bundle or left ventricular septum, or adjusting concurrent medications may help mitigate this effect. It is essential to evaluate patients with known or suspected ventricular arrhythmias, considering their history, family history, and physical examination, as outlined in the 2017 AHA/ACC/HRS guideline 1, to assess their risk for QTc prolongation and torsades de pointes.

From the FDA Drug Label

WARNINGS Ventricular Arrhythmia Sotalol AF can cause serious ventricular arrhythmias, primarily Torsade de Pointes (TdP) type ventricular tachycardia, a polymorphic ventricular tachycardia associated with QT interval prolongation. QT interval prolongation is directly related to the dose of Sotalol AF 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.

Ventricular Pacing (V Paced) and Prolonged QTc:

• The FDA drug label does mention that Sotalol AF can cause QT interval prolongation, which is directly related to the dose of the drug.
• However, it does not directly address whether V paced causes prolonged QTc.
• Therefore, based on the available information, no conclusion can be drawn about the relationship between V paced and prolonged QTc in the context of Sotalol AF treatment 3.

From the Research

V Paced Cause Prolonged QTc

• V paced can cause prolonged QTc interval due to abnormal ventricular activation and repolarization [(4, 5)].
• The prolonged QTc interval in V paced patients may not represent true repolarization abnormalities and is not associated with an increased risk of fatal arrhythmia 5.
• However, it is still important to assess the QTc interval in V paced patients, especially when prescribing medications that can prolong the QTc interval [(6, 7, 8)].
• The measurement of the QTc interval in V paced patients can be challenging due to the wide QRS complex, and various correction formulas have been proposed to account for this 8.
• The use of medications with known potential to prolong ventricular repolarization in V paced patients should be considered safe, but requires careful assessment and monitoring of the QTc interval 5.

Risk Factors for Prolonged QTc Interval

• Congenital long QT syndrome, female gender, hypokalemia, and use of sympathomimetics can increase the risk of torsades de pointes 6.
• Certain medications, such as antiarrhythmics, macrolide and fluoroquinolone antibiotics, antipsychotic and antidepressant drugs, can also prolong the QTc interval and increase the risk of torsades de pointes [(6, 7)].
• Ventricular conduction delay and pacing can also affect the QTc interval and increase the risk of torsades de pointes [(4, 8)].

Assessment and Management of Prolonged QTc Interval

• Accurate measurement and interpretation of the QTc interval is essential to assess the risk of torsades de pointes [(7, 8)].
• Various correction formulas can be used to adjust the QTc interval for heart rate and QRS duration 8.
• A step-by-step approach to measuring and correcting the QTc interval, as well as managing patients with prolonged QTc interval, is necessary to prevent torsades de pointes 7.