CLINICAL-FEATURES OF AMIODARONE-INDUCED PULMONARY TOXICITY

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7±1.7 versus 57.4±0.5 years,p=0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0±5.5% versus 90.4±1.4%, p=0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517±25 versus 409±6 mg, p<0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34±0.18 versus 1.92±0.04 μg/ml, p=0.009) but not amiodarone concentrations during maintenance therapy. Death due to pulmonary toxicity occurred in three of 33 patients (9.1%). In conclusion: 1) amiodarone pulmonary toxicity occurred in 5.8% of patients and was more common with a higher amiodarone maintenance dose, advanced age, lower pretreatment DLCO, and higher plasma desethylamiodarone concentrations; and 2) pretreatment chest radiographic, spirometric, and lung volume abnormalities were not predictive for development of amiodarone pulmonary toxicity.