A 72-year-old woman with a history of recurrent paroxysmal atrial fibrillation and structural heart disease (ejection fraction 35%) presents for long-term rhythm control. She has had two episodes of AF in the past 3 months despite rate-control therapy. Her renal function is normal (eGFR 65 mL/min/1.73 m²), and baseline QTc is 420 ms. Which antiarrhythmic agent is most appropriate for maintenance rhythm control in this patient?

Explanation

## Antiarrhythmic Selection in Structural Heart Disease: The CAST Principle ### Clinical Context This patient has: - Recurrent paroxysmal AF (symptomatic, refractory to rate control) - **Reduced ejection fraction (EF 35%)** — structural heart disease - Normal renal function - Normal baseline QTc The presence of structural heart disease (reduced EF) is the **critical constraint** that eliminates Class I agents (flecainide, propafenone). ### The CAST Trial Legacy **Key Point:** The CAST trial (1989) demonstrated that Class IC antiarrhythmics (flecainide, encainide) increase mortality in patients with prior MI and reduced EF, even though they suppress arrhythmias. This finding fundamentally changed antiarrhythmic selection in structural heart disease. **High-Yield:** In patients with **reduced EF (< 40%) or structural heart disease:** - **Avoid:** Class IA (quinidine, disopyramide) and Class IC (flecainide, propafenone) - **Preferred:** Class III (amiodarone, sotalol, dofetilide) or Class II (beta-blockers) ### Comparison of Options in Reduced EF | Agent | Class | EF < 40%? | Mechanism | Proarrhythmia Risk | First-Line? | |-------|-------|-----------|-----------|-------------------|-------------| | **Flecainide** | IC | **Contraindicated** | Na⁺ channel block | High (CAST) | **No** | | **Sotalol** | III + II | Caution | K⁺ channel + β-block | **QT prolongation** | Relative | | **Amiodarone** | III | **Safe** | Multi-channel | Low (despite QT↑) | **Yes** | | **Propafenone** | IC | **Contraindicated** | Na⁺ channel block | High (CAST) | **No** | ### Why Amiodarone? **Clinical Pearl:** Amiodarone is the only antiarrhythmic proven safe (and effective) in reduced EF because: 1. It does not increase mortality despite QT prolongation (paradoxical safety) 2. It has the broadest spectrum of action (Class I, II, III, IV properties) 3. It suppresses both atrial and ventricular arrhythmias 4. It has negative inotropic effects that are offset by its vasodilatory properties **Mnemonic:** **SIOFA** — Sotalol, Ibutilide, Oral amiodarone, Flecainide, Amiodarone (IV): - **S**otalol: Use with caution in reduced EF (QT risk) - **I**butilide: IV only, for acute cardioversion - **O**ral amiodarone: **Safe in reduced EF** ← **Best choice** - **F**lecainide: **Contraindicated in reduced EF** (CAST) - **A**miodarone (IV): For acute/unstable AF ### Why Not the Other Options? **Flecainide (Class IC):** Directly contraindicated by the CAST trial in patients with reduced EF. Increases mortality despite suppressing arrhythmias. **Sotalol (Class III + II):** While safer than Class IC agents, sotalol carries a significant QT prolongation risk (3–5% torsades de pointes) and is less preferred than amiodarone in reduced EF. It requires careful QTc monitoring. **Propafenone (Class IC):** Like flecainide, it is a Class IC agent contraindicated in reduced EF by CAST principles. Increases mortality in structural heart disease. ### Treatment Algorithm: AF in Reduced EF ```mermaid flowchart TD A["Atrial Fibrillation + EF < 40%"]:::outcome --> B{"Haemodynamically stable?"}:::decision B -->|"No"|C["Electrical cardioversion"]:::urgent B -->|"Yes"|D{"Acute or chronic?"}:::decision D -->|"Acute/unstable"|E["IV Amiodarone 300 mg"]:::action D -->|"Chronic/maintenance"|F["Oral Amiodarone 200 mg daily"]:::action F --> G["Monitor: LFTs, TFTs, QTc, CXR"]:::outcome H["Avoid: Flecainide, Propafenone, Class IA"]:::urgent ``` **High-Yield:** The **AFFIRM trial** (2002) showed that in AF, rhythm control does not improve survival compared to rate control. However, amiodarone is still the safest rhythm-control agent in reduced EF when rhythm control is chosen. [cite:Harrison 21e Ch 226; Robbins 10e Ch 12]