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CLINICAL STATEMENTS AND GUIDELINES

January 2, 2024 Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 e82

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

Amiodarone Recommendations for follow-up monitoring for patients taking oral amiodarone are provided in Table 24. Amiodarone contains 37% iodine by weight and is therefore associated with thyroid abnormalities in 2% to 24% of patients.1 In 1 study, the median time to onset of amiodarone-induced hypothyroidism was 183 days, with a median onset of hyperthyroidism of 720 days.2 Oral amiodarone may also provoke elevations in hepatic transaminases and, rarely, hepatotoxicity.3 Amiodarone may cause pulmonary toxicity, most commonly in the form of interstitial lung disease or hypersensitivity syndrome,4 in 1% to 2% of patients and is fatal in approximately 10% of cases. Consequently, a chest x-ray is recommended at baseline and when there is a clinical suspicion for pulmonary toxicity.4,5 Pulmonary function testing, including diffusing capacity for carbon monoxide, can reveal relatively early changes in pulmonary function that may be attributable to amiodarone-associated pulmonary toxicity; however, the sensitivity of the test for routine screening of drug-induced lung toxicity in general is uncertain.4–7 In patients who develop unexplained cough and dyspnea while taking amiodarone, a chest CT scan can be helpful for diagnosis.5 Corneal microdeposits (epithelial keratopathy) are common, but visual abnormalities and light sensitivity are rare.8 Therefore, an ophthalmologic examination is reasonable only if visual abnormalities develop. Amiodarone has also been associated with neurological toxicity, particularly peripheral neuropathy. Although less common than class III antiarrhythmic agents, oral amiodarone may cause torsades de pointes9; 1 analysis estimated the incidence to be 0.7%.10 Other Antiarrhythmic Drugs Recommendations for follow-up of other antiarrhythmic agents used for management of AF are provided in Table 25. Dofetilide Dofetilide is a potent inhibitor of IKr, augments INa-L, and is associated with torsades de pointes.9 The incidence of torsades de pointes associated with dofetilide ranges from 0.9% to 3.3%.11,12 However, the incidence can be substantially higher if the dofetilide dose is not properly adjusted for kidney function. Patients undergoing initiation or reloading of dofetilide are generally admitted for at least 3 days to a health care facility that can provide calculations of CrCl, continuous electrocardiographic monitoring, and cardiac resuscitation. After discharge on a stable dose of these drugs, a 12-lead ECG, and levels for serum magnesium, potassium, and creatinine are recommended every 3 to 6 months for assessment of QTc interval duration, electrolyte balance, and renal function, and more frequently for patients concomitantly taking other QT interval-prolonging drugs or with changing kidney function, to minimize the risk of drug-associated torsades de pointes.

Dronedarone Rare cases of severe liver injury have been reported in association with dronedarone. These cases have occurred 4.5 to 6 months after initiation of dronedarone therapy, although 1 case of hepatotoxicity was reported as early as 2 days after initiation of dronedarone (and was ultimately fatal a few days later),13 although a severe case of dronedarone-associated toxic hepatitis occurred 9 months after initiation of therapy.14 Ibutilide Ibutilide may prolong the QT interval and cause torsades de pointes15–22 and therefore continuous electrocardiographic monitoring is recommended during infusion and for 4 hours after completion of ibutilide infusion. Ibutilide is associated with nonsustained ventricular tachycardia (VT), QT interval prolongation, and torsades de pointes. The incidence of nonsustained VT has been reported to be as high as 8.3%.23 Torsades de pointes occurs in approximately 2% to 7% of patients,15–22 but the

Table 24.  Recommended Monitoring for Patients Taking Oral Amiodarone Adverse Effect Baseline Testing Initial Follow-Up Testing Additional Follow-Up Testing Hypo- or hyperthyroidism TSH (T4 and T3 if TSH abnormal) 3-6 mo Every 6 mo Hepatotoxicity AST, ALT 3-6 mo Every 6 mo QT interval prolongation ECG Annually – Interstitial lung disease Chest x-ray: Recommended CT chest: Not recommended Chest x-ray: Unexplained cough or dyspnea or other signs/symptoms suspicious for interstitial lung disease CT chest: As indicated to follow-up ongoing symptoms or chest x-ray findings Corneal microdeposits (epithelial keratopathy) Not recommended Development of visual abnormalities, which may indicate optic neuropathy – Dermatologic (blue-gray skin discoloration), photosensitivity Not recommended Physical examination annually Development of skin discoloration, severe sunburn Neurological Not recommended Physical examination annually Development of peripheral neuropathy or other neurological abnormalities ALT indicates alanine transaminase; AST, aspartate transaminase; CT, computed tomography; ECG, electrocardiogram; TSH, thyroid-stimulating hormone; and TdP, torsades de pointes.

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