affects almost 10% of chronically treated patients The most serious complication in adults is pulmonary toxicity, which can rarely occur early after treatment initiation Amiodarone should be immediately discontinued if the mother develops pulmonary inflammatory changes A nonproductive cough and dyspnea are the main symptoms of affected individuals at presentation Pleuritic pain, weight loss, fever, and malaise can also occur As with other class III agents, there is a risk of torsade de pointes, which can be minimized by avoiding excessive QTc prolongation Adverse fetal effects attributed to the use of amiodarone include transient congenital thyroid dysfunction, growth retardation, and mild neurodevelopmental abnormalities.34,35,42–44 Direct Fetal Treatment Direct fetal treatment should be considered if other less invasive treatment measures have failed or if immediate treatment is required to terminate or slow down a life-threatening SVA In the presence of fetal hydrops, the transplacental transfer of most antiarrhythmic medication is hampered and therapeutic levels of drugs may not be reached even with high maternal doses To overcome this problem, repeated intravenous, intramuscular, and intraperitoneal fetal injections of amiodarone and/or digoxin, in addition to transplacental maternal medication, have been successfully used to deal with treatment-refractory fetal AVRT, although fetal deaths with the use of this strategy have occurred.10,19,36,45,46 Amiodarone seems to be predestined for direct use, both because of its efficiency and long half-life, thus limiting the number of invasive fetal procedures required to maintain therapeutic levels Direct intravenous adenosine may instantly terminate AVRT,47–49 but because of its short duration of action, it should be administered in combination with a longer-acting antiarrhythmic agent Other Antiarrhythmic Agents Other antiarrhythmic agents such as verapamil, procainamide, and quinidine are not recommended for prenatal therapy11 because of the potential risks of severe side effects and/or insufficient antiarrhythmic action Treatment Results Retrospective case series report inconsistent success rates for all antiarrhythmic medication in treating fetal SVA, which may be explained, among other things, by differences in the definition of a treatment success and in disease severity between patient cohorts With this caveat in mind, in studies using oral digoxin as first-line agent, in utero cardioversion has been reported in 50% to 100% of fetuses with SVA without hydrops, but in 40% or less of fetuses with SVA and hydrops.7,9,10,18,28,29,50 Flecainide has resulted in sinus rhythm in 58% to 100% of SVA cases without hydrops and in 43% to 86% of those with hydrops.17,18,26,28–30,34 Sotalol monotherapy has been successful in 40% to 100% of SVA cases without hydrops and in 50% to 67% of those with hydrops.6,21,22,25,27 When used to treat drug-refractory SVT, transplacental amiodarone alone or in combination with digoxin was associated with a 71% rate of in utero cardioversion.34,35 Similar or higher cardioversion rates to amiodarone were obtained with combination treatment of digoxin plus flecainide,23,33 sotalol plus digoxin,21,25 and sotalol plus flecainide.27 Results of direct fetal drug therapy are largely unavailable Although these published data suggest similar treatment results with the currently used antiarrhythmic agents, drug-specific differences in their modes of action and pharmacokinetics likely predetermine the potential of a compound in terminating and, once this has been achieved, suppressing SVA recurrences In the retrospective multicenter study by Jaeggi et al.5 comparing nonrandomized first-line treatment with one of three agents―digoxin, flecainide, or sotalol―the fetal response to antiarrhythmic therapy was significantly influenced by fetal hemodynamics, arrhythmia mechanism, and the choice of drug management Slower cardioversion rates to a normal rhythm were found to be significantly associated with (1) a persistent tachycardia pattern (hazard ratio [HR], 3.1; P < 001) during the initial fetal echocardiogram when compared with intermittent arrhythmia; (2) fetal hydrops (HR, 1.8; P = 04), presumably due to incomplete passage of maternally administered antiarrhythmic drugs across the placenta; (3) AF (HR, 2.0; P = 005) when compared with other forms of SVA; and (4) the choice of first-line therapy (Fig 9.1) Sotalol was associated with higher rates of prenatal AF termination than digoxin (HR, 5.4; P = 05) or flecainide (HR, 7.4; P = 03) The median time to conversion of AF cases was almost 2 weeks with sotalol, whereas this was not achieved with digoxin or flecainide before delivery Flecainide (HR, 2.1; P = 02) or digoxin (HR, 2.9; P = 01) were associated with a higher rate of conversion of fetal SVA other than AF to a normal rhythm compared with sotalol The median time to cardioversion of AVRT, AET, and PJRT was 3 days with digoxin, 4 days with flecainide, but 12 days with sotalol If the SVA persisted, tachycardia rates declined more with flecainide and digoxin Finally, therapy initiation with digoxin, flecainide, or sotalol as monotherapy appeared safe unless fetal hydrops was present, which was associated with 21% perinatal mortality This led to the study's recommendation to consider drug combinations (e.g., flecainide plus digoxin for AVRT; sotalol plus digoxin for AF) as first-line treatment when rapid tachycardia control becomes a matter of urgency