How do you manage a prolonged QT interval?

From the Guidelines

Managing a prolonged QT interval requires prompt identification and addressing of underlying causes, with the primary goal of preventing Torsades de Pointes and sudden cardiac death, as emphasized in the 2020 study published in the Journal of the American College of Cardiology 1. To manage a prolonged QT interval, the following steps should be taken:

• Discontinue any QT-prolonging medications, such as certain antiarrhythmics, antibiotics, antipsychotics, and antiemetics.
• Correct electrolyte abnormalities, particularly hypokalemia (target K+ >4.0 mEq/L), hypomagnesemia (target Mg >2.0 mg/dL), and hypocalcemia, as recommended in the 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.
• For patients with symptomatic Torsades de Pointes (TdP), administer IV magnesium sulfate 1-2g over 5-10 minutes, even if magnesium levels are normal, as suggested in the 2017 update to practice standards for electrocardiographic monitoring in hospital settings: a scientific statement from the American Heart Association 1.
• In emergency situations with recurrent TdP, temporary overdrive pacing at 100-120 beats per minute or isoproterenol infusion (2-10 μg/min) can shorten the QT interval.
• For congenital Long QT Syndrome, beta-blockers (nadolol 40-80 mg daily or propranolol 10-40 mg three times daily) are first-line therapy, as recommended in the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society 1.
• Patients with high-risk features may require an implantable cardioverter-defibrillator.
• Regular ECG monitoring is essential during treatment, with a goal of QTc <470 ms in women and <450 ms in men, as suggested in the 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines 1. The urgency of intervention depends on the degree of QT prolongation, with QTc >500 ms significantly increasing TdP risk, as emphasized in the 2009 study published in Blood 1. Some key points to consider when managing a prolonged QT interval include:
• Avoiding QT-prolonging drugs, especially in patients with a history of QT prolongation or relevant cardiac disease.
• Monitoring patients with a history of QT prolongation, relevant cardiac disease, or those being treated with QT-prolonging drugs.
• Considering treatment discontinuation or alternative regimens if the QTc is >500 ms, QTc prolongation is >60 ms, or dysrhythmias are encountered.
• Minimizing exposure to other QT-prolonging drugs in patients treated with potentially QT-prolonging chemotherapy.

From the FDA Drug Label

Theoretically, therefore, mexiletine may be useful in the treatment of ventricular arrhythmias associated with a prolonged QT interval Mexiletine did not prolong ventricular depolarization (QRS duration) or repolarization (QT intervals) as measured by electrocardiography.

Managing Prolonged QT Interval:

• Mexiletine may be useful in the treatment of ventricular arrhythmias associated with a prolonged QT interval, as it does not prolong QT intervals.
• However, it is essential to note that the FDA drug label for mexiletine does not provide direct guidance on managing prolonged QT intervals.
• In contrast, flecainide can worsen QT intervals, as it slows cardiac conduction and produces dose-related increases in PR, QRS, and QT intervals.
• Therefore, flecainide should be used with caution in patients with prolonged QT intervals, and its use may not be recommended for managing this condition. 2

From the Research

Managing Prolonged QT Interval

To manage a prolonged QT interval, several factors need to be considered, including patient-related risk factors, the potential risk and degree of QT prolongation associated with the proposed drug, and co-prescribed medicines that could increase the risk of QT prolongation 3.

• Patient-related risk factors: These include female sex, age >65 years, and uncorrected electrolyte disturbances 3.
• Drug-related risk factors: Certain medications, particularly anti-arrhythmic drugs such as quinidine, sotalol, and amiodarone, can lead to acquired Long QT syndrome by prolonging the QT interval 4.
• Management strategies:
  • Reducing the medication dosage or discontinuing it altogether 4.
  • Employing selective beta blockers, such as propranolol and nadolol, which have been shown to be effective in managing Long QT syndrome types 1 and 2 5.
  • Using mexiletine, a sodium channel blocker, which has been shown to shorten the QT interval in patients with potassium channel-mediated type 2 Long QT syndrome 6.
  • Close monitoring of the QT interval is recommended for patients receiving anti-arrhythmic therapy, and consideration should be given to patient-specific risk factors for Long QT syndrome, including age, sex, and electrolyte imbalances 4.

Treatment Options

• Beta blockers: Propranolol and nadolol are effective in managing Long QT syndrome types 1 and 2, while metoprolol should not be used for symptomatic LQT1 and LQT2 patients due to its lower efficacy 5.
• Mexiletine: This sodium channel blocker has been shown to shorten the QT interval in patients with potassium channel-mediated type 2 Long QT syndrome, and may provide added therapeutic efficacy to beta-blocker therapy 6.
• Potassium-elevating treatment: Moderate potassium elevation has been investigated as a potential treatment for Long QT syndrome, but its effectiveness is still unclear, and it may not be beneficial for patients with normal-range potassium levels 7.

Monitoring and Prevention

• Close monitoring: Regular monitoring of the QT interval is essential for patients receiving anti-arrhythmic therapy, especially those with risk factors for Long QT syndrome 4.
• Risk assessment: Assessing patient-related risk factors, such as female sex, age, and electrolyte disturbances, can help identify individuals at higher risk of QT prolongation 3.
• Medication selection: Choosing medications with a lower risk of QT prolongation and avoiding co-prescription of medications that can increase this risk can help prevent QT prolongation 3, 4.