Amiodarone-associated thyroid dysfunction in adult patients with congenital heart disease: a nationwide health insurance data analysis including &gt;50.000 individuals
Authors: Fischer A.J , Enders D , Baumgartner H , Diller G.P 
Published: November 2020

Abstract

Background
Arrhythmias are common in adult patients with congenital heart disease (ACHD). Amiodarone is widely used as an antiarrhythmic agent. Thyroid dysfunction represents a serious complication of amiodarone treatment. Systematic data on the prevalence of thyroid dysfunction, risk factors for complications and treatment options are lacking.

Purpose
Based on data from one of the largest German Health Insurance Companies (BARMER GEK, approx. 9 million members), we performed a retrospective analysis investigating the rate of thyroid complications under active amiodarone therapy in ACHD patients and a comparison group of cardiac patients without congenital heart disease on amiodarone between 2005 and 2018.

Result
Overall, 910 ACHD (34% female; median age 66 y; CHD complexity mild, moderate, severe in 64.6%, 23.6%,11.8%, respectively) and 49,782 non-ACHD patients (37% female, median age 73.4 y) received prescriptions for amiodarone without documented pre-existing thyroid disease or use of thyroid medication. Over a treatment period of 184,770 patient-years, 10,874 incidents of thyroid dysfunction occurred in the non-ACHD and 201 in the ACHD cohort, corresponding to an event-rate of 6% and 5.3% per patient year, respectively. Overall, 23.5% of the ACHD patients developed thyroid dysfunction (56.71% hypothyroidism, 43.3% hyperthyroidism). Risk factors for developing thyroid dysfunction on time dependent Cox-analysis were female gender (hazard ratio [HR] 1.44, 95% CI: 1.39–1.50; p&lt;0.001), lower patient age (HR: 0.96 per 10 years, 95% CI: 0.94–0.98, p&lt;0.001) renal dysfunction (HR 1.24, 95% CI: 1.19–1.29, p&lt;0.001), history of alcohol abuse (HR 1.17, 95% CI: 1.07–1.27, p,0.001) and smoking (HR 1.12, 95% CI: 1.06–1.19, p&lt;0.001). Congenital heart disease itself was not associated with a higher risk of thyroid dysfunction (HR 0.96, 95% CI: 0.83–1.10, p=0.53). Within the ACHD group, patients with complex disease had a significantly higher risk of thyroid dysfunction (HR 1.5, 95% CI: 1.00–2.25, p=0.049) compared to patients with simple diagnoses. Once thyroid disease occurred, 48.5% of patients were continued on amiodarone therapy, 12.8% of patients underwent an electrophysiologic procedure and only 2.1% of patients received class I antiarrhythmics. Specific thyroid therapy included thyroxine (62.6% of hypothyroid patients) or thiamazole (22.6% of hyperthyroid patients). Only 2.3% of patients required surgery or radiotherapy within 6 months after thyroid dysfunction.

Conclusion
Amiodarone-associated thyroid dysfunction is a frequent complication in ACHD patients. Overall, one in 4 ACHD patients on amiodarone developed thyroid dysfunction in our study. In itself, ACHD does not seem to increase the risk of thyroid dysfunction. However, female gender, complexity of disease, younger age and renal dysfunction emerged as independent risk factors. When amiodarone therapy can not be avoided, close follow-up and regular thyroid function tests are recommended.

Funding Acknowledgement
Type of funding source: None