Amiodarone for AF with HFrEF: choice, monitoring and pulmonary toxicity — case discussion

Presentation

Practice case (not a real patient). A 68-year-old woman has persistent AF and heart failure with reduced ejection fraction (LVEF 30%).^[1][2] After cardioversion she needs long-term antiarrhythmic drug therapy to prevent recurrence and progression of AF; catheter ablation is not planned. She takes digoxin.^[1][2]

Step 1 — Which drug?

Discussion:

• ESC 2024 AF: amiodarone is recommended in patients with AF and HFrEF requiring long-term antiarrhythmic drug therapy to prevent recurrence and progression of AF, with careful consideration and monitoring for extracardiac toxicity (Class I, Level A).^[1]
• ACC/AHA 2023: in AF with HFrEF (LVEF 40% or less), dofetilide or amiodarone is reasonable for long-term maintenance of sinus rhythm (COR 2a; LOE B-NR for the amiodarone data).^[2]
• ACC/AHA 2023 supportive text: most antiarrhythmic agents, except amiodarone and dofetilide, are contraindicated in HFrEF because of worsening heart failure and/or increased mortality.^[2]
• ACC/AHA 2023 supportive text: sotalol is best avoided in HFrEF, because most patients already take a beta blocker and adding sotalol is unlikely to be well tolerated.^[2]

Step 2 — Before the first dose, and the loading regimen

Discussion:

• The FDA label asks for a baseline chest X-ray, pulmonary function tests, thyroid function tests and liver aminotransferases, and for hypokalaemia, hypomagnesaemia and hypocalcaemia to be corrected first.^[8]
• ACC/AHA 2023 Table 23 gives a total loading dose of 6–10 g, as 400–800 mg daily in 2–4 divided doses for 1–4 weeks, then 200 mg once daily; ESC 2024 AF Table 13 gives a long-term dose of 200 mg oral daily.^[2][1]
• ACC/AHA 2023 Table 23 says amiodarone inhibits P-glycoprotein and increases plasma digoxin; the FDA amiodarone label (Table 1, drug interactions) says to reduce digoxin by half or discontinue it, and to monitor for toxicity if it is continued.^[2][8]
• ACC/AHA 2023 says amiodarone can be started in the outpatient setting.^[2]

Step 3 — Four months later: new cough and breathlessness

She reports a cough and breathlessness that has progressively worsened.^[8]

Discussion:

• The amiodarone label says it may cause a syndrome of cough and progressive dyspnoea with functional, radiographic, gallium-scan and pathological data consistent with pulmonary toxicity.^[8]
• ACC/AHA 2023 Table 24 recommends a chest X-ray for unexplained cough or dyspnoea, and CT chest as indicated to follow up ongoing symptoms or chest X-ray findings.^[2]
• The label says to consider alternative antiarrhythmic therapy if signs or symptoms of pulmonary toxicity appear, and that prednisone 40 to 60 mg/day tapered over several weeks may be helpful in treating pulmonary toxicity.^[8]
• The label reports pulmonary toxicity rates as high as 17%, fatal in about 10% of cases.^[8]

Step 4 — Thyroid, liver and eyes

Discussion:

• ACC/AHA 2023 Table 24: TSH (with T4 and T3 if abnormal) and AST/ALT at baseline, at 3–6 months and every 6 months; an ECG at baseline and annually.^[2]
• The label says hyperthyroidism may cause arrhythmia breakthrough, and radioactive iodine is contraindicated in amiodarone-induced hyperthyroidism because of low radioiodine uptake.^[8]
• If transaminases exceed three times normal, or double from an elevated baseline, the label says to discontinue or reduce the dose, repeat the tests and treat appropriately.^[8]
• The label recommends regular ophthalmic examination, including funduscopy and slit-lamp examination, and says asymptomatic corneal microdeposits alone are not a reason to reduce or stop the drug.^[8]

Step 5 — If amiodarone is stopped

Discussion:

• The label gives a half-life of 15 to 142 days (desethylamiodarone 14 to 75 days), so adverse reactions and drug interactions can persist for several weeks after stopping.^[8]
• ESC 2026 HF says antiarrhythmic drugs such as amiodarone and dronedarone reduce ventricular arrhythmias but do not prolong survival and may shorten it.^[5]
• ACC/AHA 2023 says most antiarrhythmic agents, except amiodarone and dofetilide, are contraindicated in HFrEF, which narrows the drug alternatives.^[2]