an initial higher risk of death in the neonatal period, the hazard for death was similar among all those aged older than 1 year Of the 403 patients aged between 1 and 25 years, 50 (12.4%) died of the disease Half of the deaths were due to cardiac failure, with 20% dying suddenly, presumably due to an arrhythmia In those older than 25 years, 11 of 67 patients (16.4%) died of natural causes, 2 from congestive cardiac failure and 2 suddenly In 1994 Celermajer and colleagues described 220 cases of Ebstein malformation presenting from fetus to adulthood (see Table 33.1).8 The median age at time of presentation had decreased to less than 1 year, emphasizing the role echocardiography now plays in early diagnosis Neonatal mortality was due to cardiac failure and pulmonary hypoplasia, secondary to cardiomegaly Associated cardiac defects were more common in patients who presented early Those newborns with the isolated form of the malformation usually showed spontaneous improvement as the pulmonary vascular resistance decreased Patients diagnosed later in childhood tended to present with a cardiac murmur discovered incidentally Arrhythmias and progressive desaturation due to rightto-left shunting were more common in the older child and adult Women with Ebstein malformation can tolerate pregnancy, particularly when their functional state is good prior to conception.56–58 In general, there is an increased risk of fetal demise and prematurity in mothers who had more significant disease.59–61 In 1994 Connolly and Warnes reported a comprehensive review of pregnancy outcome in patients with Ebstein malformation, analyzing histories of pregnancies in 72 couples in which one member, 44 women and 28 men, had Ebstein malformation.62 Pregnancy seemed well tolerated by the affected mothers but was associated with an increased risk to the offspring The rates of miscarriage and fetal loss were 18%, slightly higher than the expected age-matched rates of 10% to 15% Infants born to cyanotic women were often premature and had significantly lower birth weights than did those born to noncyanotic mothers Congenital cardiac disease was found in 6% of the offspring of the women with Ebstein malformation but was found in only 1 of the 75 children (1.3%) born to couples in whom the man had the malformation The incidence of Ebstein malformation in the offspring was 0.6%, occurring in only 1 of the 158 children born to the couples There were no significant maternal complications or death Maternal arrhythmias and cyanosis, of course, warrant close observation during the pregnancy Medical Therapy Patients with Ebstein malformation display a wide spectrum of hemodynamic abnormalities and arrhythmias that can occur at any age Consequently, no dogmatic recommendations can be applied Rather, it is more practical to assemble general guidelines for treatment At one end of the spectrum are patients with mild anatomic abnormalities, relatively normal hemodynamics, and no symptoms These patients require only serial observation and monitoring For patients in whom the anatomic and hemodynamic abnormalities do cause symptoms and significantly alter lifestyle, surgical therapy is often the most effective treatment Treatment of the critically ill neonate with Ebstein malformation involves use of prostaglandin E1 to maintain ductal patency to provide pulmonary blood flow and the use of pulmonary vasodilators to reduce pulmonary vascular resistance High levels of inspired oxygen, nitric oxide, and occasionally sildenafil, or epoprostenol, may be used to lower pulmonary resistance and promote forward flow Many babies improve spontaneously as the pulmonary vascular resistance falls, with consequent improvement in right ventricular output, and reduced right-to-left shunting at atrial level Intensive support, including ventilation, may be required during the first few days to weeks If cyanosis is caused by associated structural obstruction of the right ventricular outflow tract, palliative surgery is indicated Many older children and adults are asymptomatic and can be managed conservatively Exceptions include those with symptomatic arrhythmias, poor exercise tolerance, significant resting or exertional cyanosis, or symptoms of cardiac failure Arrhythmias are often difficult to treat medically Accurate diagnosis should be obtained by 12-lead or ambulatory electrocardiographic monitoring or home telemetry devices Drug-refractory patients or those with syncope should have detailed electrophysiologic studies More than half the patients require a trial of two or more antiarrhythmic agents to obtain reasonable symptomatic control with medications alone.63 Radiofrequency ablation has proven to be effective for those with accessory atrioventricular connections, although the procedure may be complicated by the presence of multiple pathways, the enlarged right atrium, and the distorted anatomy of the tricuspid valve Oral anticoagulation is advisable for any patient with paroxysmal or chronic atrial fibrillation or flutter, except in those with a bleeding diathesis or other contraindication Many patients in the first or second functional classes, with mild or no cardiomegaly, can be managed without surgery Surgery is generally reserved for those with cardiac enlargement, progressing symptoms, increasing cyanosis, or intractable arrhythmias requiring surgical ablation, or if paradoxical embolism occurs Operation should also be considered if there is objective evidence of decreasing exercise performance by exercise testing, progressive increase heart size on the chest radiograph, progressive right ventricular dilation, or systolic dysfunction (by echocardiography or other techniques), or inadequate control of atrial or ventricular arrhythmias Since the advent of the cone reconstruction, earlier interventions for those with valvar dysfunction and cardiac enlargement have been advocated.64 Once symptoms develop and progress such that the patient is in the third or fourth functional classes, medical management has little to offer and operation then becomes the best chance for improvement Surgery for Ebstein Malformation Palliative operations, such as construction of a systemic-to-pulmonary arterial shunt, a bidirectional Glenn anastomosis, or pulmonary valvotomy, may be required for neonates or infants with persistent cyanosis associated with structural pulmonary stenosis or atresia In general, these procedures can be performed with low risk.65 Open heart surgery for the symptomatic neonate usually consists of either a biventricular repair66 or a functionally univentricular strategy.67 The neonatal biventricular repair typically consists of repair of the tricuspid valve with subtotal closure of the atrial septal defect The functionally univentricular strategy consists of an initial operation to close the tricuspid valve with a fenestrated patch, atrial septectomy, and construction of a systemic-topulmonary arterial shunt The second stage includes construction of a bidirectional Glenn anastomosis at 3 to 6 months of age and conversion to the Fontan circulation at 2 to 4 years of age Occasionally, surgery for repair of associated defects is indicated in isolation, such as closure of an atrial septal defect in the setting of left-to-right shunting, closure of an associated ventricular septal defect, or isolated surgery to treat arrhythmias Indications for comprehensive surgical repair in Ebstein malformation include presence of symptoms—fatigue, cyanosis, decreased exercise tolerance, poor growth, the presence of an atrial septal defect, paradoxical embolism, increasing cardiomegaly, and onset or progression of atrial tachyarrhythmias Operation is considered in asymptomatic patients with at least moderate valvar distortion and