Does flecainide (antiarrhythmic medication) cause QTc (corrected QT interval) prolongation?

Does Flecainide Cause QTc Prolongation?

Flecainide primarily causes QRS widening rather than true QTc prolongation, though it can produce modest QT interval increases that are predominantly due to QRS prolongation, not delayed ventricular repolarization. 1, 2

Understanding Flecainide's Effects on the ECG

The critical distinction is between QT prolongation and QTc prolongation:

• Flecainide increases the QT interval by approximately 8% on average, but 60-90% of this widening is due to QRS prolongation (sodium channel blockade), not true repolarization delay 1, 2
• The JT interval (QT minus QRS) only widens about 4% on average, indicating minimal effect on ventricular repolarization 1
• QRS duration increases on average by 25% (0.02 seconds), with some patients developing QRS complexes ≥0.12 seconds 2
• PR interval increases on average by 25% (0.04 seconds) 2

Official Guideline Statements on QT Effects

Multiple authoritative guidelines explicitly list QT prolongation as a potential adverse effect of flecainide:

• The 2015 ACC/AHA/HRS guidelines list "QT prolongation, torsades de pointes" as potential adverse effects of flecainide 1
• The 2016 ESC guidelines state flecainide can cause "QT prolongation" and recommend avoiding it in patients with QT prolongation 1
• The 2010 ESC guidelines note QT interval >500 ms as a reason for dose reduction or discontinuation 1
• The 2006 and 2011 ACC/AHA/ESC guidelines similarly list QT prolongation as a potential adverse effect 1

Clinical Reality: Rare but Documented Cases

While uncommon, torsades de pointes has been documented with flecainide:

• The FDA label states "There have been rare cases of Torsade de Pointes-type arrhythmia associated with flecainide acetate therapy" 2
• A 2014 case report documented a 32-year-old man with progressive QTc lengthening on flecainide 150 mg twice daily who developed polymorphic ventricular tachycardia and cardiac arrest during exercise 3
• A 1998 case report described QTc interval prolongation in flecainide overdose 4

Important Caveats and Clinical Pitfalls

The proarrhythmic risk is context-dependent:

• Structural heart disease dramatically increases risk - flecainide is contraindicated in patients with coronary artery disease, reduced ejection fraction, or significant structural heart disease 1, 2
• Electrolyte abnormalities amplify risk - hypokalemia and hypomagnesemia should be corrected before initiating flecainide 5, 2
• Drug interactions matter - flecainide is metabolized by CYP2D6, and inhibitors can increase plasma levels significantly 1, 5
• Dose-dependent effects - higher doses (>100 mg twice daily) carry greater risk 3

Monitoring Recommendations

When prescribing flecainide, monitor for:

• Baseline QTc interval - if >500 ms, avoid flecainide or use with extreme caution 1, 5
• QRS widening >25% above baseline warrants dose reduction 1
• Plasma flecainide levels should be kept below 0.7-1.0 mcg/mL when feasible 2
• Periodic ECG monitoring is recommended, particularly after dose increases 3, 6

Special Population: LQT3 Syndrome

Paradoxically, flecainide can shorten QTc in specific genetic mutations:

• In patients with SCN5A:ΔKPQ mutation (LQT3), low-dose flecainide decreased QTc by an average of 104 ms by blocking persistent sodium current 7
• This represents a unique exception where flecainide corrects rather than worsens repolarization abnormalities 7