Comprehensive guide to anti-arrhythmia medications in ACHD patients. Learn Vaughan Williams classification, drug selection and clinical pearls for managing arrhythmias.

Published: December 17, 2025 | Updated: January 27, 2026

Arrhythmias represent  one of the most significant challenges in adults with congenital heart disease (ACHD),  constituting the leading cause of morbidity, mortality and hospitalization in this population. Understanding the appropriate use of anti-arrhythmia medications is critical for clinicians managing these complex patients. Shelby Mangeot, DNP, APRN, presented “Anti-arrhythmia Medications: A Necessary Evil” during a continuing medical education (CME) program, currently available on demand at NortonCME.com.

Understanding the arrhythmia burden in ACHD

The question is not whether ACHD patients will develop arrhythmias — it’s when. Multiple factors predispose this population to rhythm disturbances, including the underlying congenital anomaly, intracardiac scarring and suture lines from prior repairs, and long-standing hemodynamic changes such as chamber dilation and/or reduced ventricular function.

Arrhythmias in ACHD patients can lead to serious consequences, including syncope, heart failure, thromboembolic events and sudden cardiac death. The spectrum of arrhythmias is broad. It includes atrial arrhythmias — such as focal or triggered atrial tachycardia, atrial flutter,  and atrial fibrillation — as well as other supraventricular tachycardia substrates and ventricular tachyarrhythmias.

Pretreatment priorities

Before initiating anti-arrhythmia medications , clinicians must:

• Identify and treat reversible causes such as residual lesions, electrolyte abnormalities, thyroid dysfunction, obstructive sleep apnea, and so forth.
• Define your goal when initiating anti-arrhythmia medications:
  • Determine whether rate control or rhythm control  is more appropriate
  • Assess whether the arrhythmia is amenable to procedural intervention versus requiring chronic medical therapy.

Rate control versus rhythm control: Making the right choice

• Rate control aims to slow the ventricular rate by reducing atrioventricular (AV) nodal conduction, but likely will not terminate the abnormal rhythm. This strategy prevents symptoms and complications like tachycardia-induced cardiomyopathy. Common agents include esmolol and diltiazem.
• Rhythm control aims to chemically terminate the arrhythmia and restore normal sinus rhythm. Common agents include Procainamide, Flecainide, Amiodarone, or Sotalol.
• The choice between strategies is highly individualized, considering the arrhythmia substrate, patient clinical status, underlying heart disease and symptom burden.

Understanding cardiac action potentials

Anti-arrhythmia medications work by modifying cardiac action potentials. Two types exist:

Fast-response action potentials occur in atrial and ventricular myocytes responsible for muscle contraction. The phases progress from resting membrane potential (Phase 4, -90 mV) through rapid depolarization via sodium influx (Phase 0), early repolarization (Phase 1), plateau phase with calcium-potassium balance (Phase 2), and lastly,  repolarization (Phase 3).

Slow-response action potentials occur in nodal tissue (SA node, AV node). These modified cardiac myocytes lose their ability to induce muscle contraction and alternatively gain the ability to generate spontaneous action potentials. . They feature a gradual Phase 4 depolarization through “funny” sodium channels, calcium-mediated depolarization (Phase 0), and potassium-mediated repolarization (Phase 3).

Vaughan Williams classification: A systematic approach

Class I: Sodium channel blockers

These agents block fast-sodium channels responsible for rapid depolarization during Phase 0 of the “fast-response” action potential, primarily affecting cardiac myocyte depolarization with minimal effects on nodal tissue.

Class 1 agents are further sub-divided into Class 1A, 1B, or 1C depending on their degree of sodium channel blockade.

Class Ia): These agents exhibit a moderate degree of sodium channel blockade, slowing phase 0 depolarization and increasing action potential duration. These agents also block potassium channels during Phase 3, which can prolong QT intervals and be pro-arrhythmic. Agents include Procainamide, Quinidine, and Disopyramide. Procainamide:.

• Indications:
  • First-line agent for Wolff-Parkinson-White syndrome arrhythmias in the acute setting, particularly antidromic reentrant supraventricular tachycardia (SVT) or preexcited atrial fibrillation in stable patients
  • Often the drug choice for ventricular tachycardia with a pulse
  • Can be used for chemical cardioversion of atrial fibrillation/flutter
• Considerations:
  • Requires monitoring of kidney function (renally excreted) and drug levels (procainamide and N-acetylprocainamide metabolite)
  • Risk for torsades de pointes due to increased QT intervals; obtain baseline and serial electrocardiograms (ECGs).
  • Chronic use may cause gastrointestinal effects, agranulocytosis, hypotension, drug-induced lupus.
• Class Ib: These agents exhibit the weakest degree of sodium channel blockade amongst the Class 1 agents. This class does not block potassium channels; therefore, there is no risk for pro-arrhythmia. Agents include Lidocaine and Mexiletine. These block  uncontrolled sodium influx in ischemic cells, increasing electrical threshold.

Lidocaine is highly effective for ventricular arrhythmias with myocardial ischemia

• First-line advanced cardiac life support agent (with amiodarone) for shock-refractory ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT
• Particularly effective for polymorphic VT secondary to prolonged QT
• Not indicated for suppression of chronic VT or SVT

Class Ic These agents exert the strongest sodium-channel blocking effects amongst the Class 1 agents, which can lead to marked QRS widening and prolongation of the PR interval. Agents include Flecainide and propafenone.

• Multiple indications: atrial arrhythmias, SVT substrates, ventricular arrhythmias
• Renally excreted; monitor kidney function.
• Can be proarrhythmic, obtain baseline and serial ECGs.
• Avoid in coronary artery disease, ventricular dysfunction, or AV block without pacemaker.

Class II: beta-blockers

These agents primarily affect “slow-response” action potentials, reducing heart rate, increasing PR interval, decreasing contractility and myocardial oxygen demand. They’re especially effective for catecholamine-sensitive arrhythmias.

Indications:

• Nodal-dependent reentrant arrhythmias (atrioventricular reentrant tachycardia, atrioventricular nodal reentrant tachycardia)
• Rate control for atrial tachycardia, flutter, fibrillation
• Catecholamine-sensitive ventricular arrhythmias

Considerations: Hypotension, bradycardia, bronchospasm. Esmolol is the IV agent of choice.

Class III: Potassium channel blockers

These agents primarily block potassium repolarization during Phase 3 of the “fast-response” action potential, increasing action potential duration and effective refractory period. As a result, they can prolong QT intervals and be pro-arrhythmic.

Amiodarone exhibits Class III properties plus sodium channel, calcium channel and alpha/beta receptor blockade.

• Multiple indications: refractory SVT, atrial arrhythmias, junctional ectopic tachycardia, ventricular arrhythmias.
• Significant long-term side effects can limit use: hepatic injury, thyroid dysfunction, pulmonary fibrosis, vision loss, photosensitivity, gray-blue skin discoloration, and many more.
• Requires extensive baseline and long-term monitoring for side effects.

Sotalol combines Class III effects with Class II beta-blocker properties.

• Indicated for SVT, atrial arrhythmias, atrial fibrillation rhythm control, ventricular arrhythmias.
• Renally excreted; absolutely contraindicated in kidney dysfunction
• Often initiated inpatient with baseline and serial ECG monitoring.
• Absolutely contraindicated in acquired or congenital long QT syndrome
• Highly pro-arrhythmic—  can cause profound QT prolongation, leading to malignant ventricular arrhythmias, if not managed appropriately

 Class IV: Calcium channel blockers

Diltiazem and verapamil block voltage-sensitive calcium channels in Phase 4 of “slow- response” action potentials, decreasing Phase 0 slope and slowing AV nodal conduction.

Diltiazem is primarily used for ventricular rate control of atrial arrhythmias.

Considerations:

• Most common side effect: hypotension
• Can cause peripheral edema and varying degrees of AV block
• Contraindicated in second/third-degree AV block without pacemaker, sick sinus syndrome, severe bradycardia, severe heart failure

Class V: Other agents

Ivabradine selectively blocks pacemaker “funny” sodium channels responsible for Phase 4 depolarization of the “slow-response” action potential, slowing heart rate without affecting myocardial contraction or ventricular depolarization.

Indications:

• Food and Drug Administration approved for heart failure with reduced ejection fraction, inappropriate sinus tachycardia, and postural orthostatic tachycardia syndrome
• Commonly used to manage junctional ectopic tachycardia and atrial arrhythmias with focal automaticity (focal atrial tachycardia, ectopic atrial tachycardia)

Memory aid for drug classes

Class I (sodium channel blockers): Remember: “Double Quarter Pounder with Lettuce, Mayo and Tomato and more Fries, Please”

• 1A: Disopyramide, Quinidine, Procainamide
• 1B: Lidocaine, Mexiletine, Tocainide
• 1C: Moricizine, Flecainide, Propafenone

Class II (beta blockers): LOLs atenolol, metoprolol, carvedilol and propranolol.

Class III: SAD (sotalol, amiodarone, dofetilide)

Class IV: diltiazem, verapamil

The management of arrhythmias in ACHD requires careful consideration of the complex interplay between congenital anatomy, hemodynamics and electrophysiology. By understanding the mechanisms of anti-arrhythmia medications and their appropriate use, clinicians can optimize outcomes in this challenging patient population.

Key takeaways for clinical practice

• Arrhythmias are inevitable in ACHD — early recognition and appropriate management are essential.
• Always address reversible causes before initiating anti-arrhythmia therapy.
• Individualize the choice between rate and rhythm control.
• Understand which action potential each drug class affects to predict ECG changes and side effects.
• Many anti-arrhythmia medications require inpatient initiation with continuous monitoring.
• Monitor organ function (renal, hepatic, thyroid) and drug levels as indicated.
• Be aware of proarrhythmic potential, especially torsades risk with QT-prolonging agents.
• Consider the long-term toxicity profile when selecting chronic therapy.