A 34-year-old woman was seen in the outpatient clinic for a 1-year history of worsening dyspnea on exertion (New York Heart Association class III), 2-pillow orthopnea, bilateral pedal edema, and occasional episodes of palpitations. Her transthoracic echocardiogram revealed an ostium secundum atrial septal defect (ASD), significant enlargement of the right ventricle, evidence of left-­to-right shunt with a pulmonary to systemic flow (Qp/Qs) ratio of 2.3, and normal left ventricular ejection fraction (Figure 26-1). Transesophageal echocardiogram confirmed an ostium secundum ASD of 18-mm diameter with sufficient tissue rims and ruled out additional congenital defects (Figure 26-2). She underwent successful percutaneous closure of her ostium secundum ASD with a 22-mm atrial septal occluder device using intracardiac echocardiography guidance. After 6 months, she remains asymptomatic and a repeat transthoracic echocardiogram revealed no residual shunt across the interatrial septum and significant reduction in right ­ventricular volume.

Atrial septal defects (ASDs), a congenital deficiency of the interatrial septum, allow intracardiac shunting and account for nearly one third of congenital heart defects in adults.^1,2 Excluding bicuspid aortic valve and mitral valve prolapse, ASDs are the most frequently diagnosed congenital abnormalities in the adult population and encompass 4 distinct types of defects of the interatrial septum (­Figure 26-3). Ostium secundum ASDs are the most common type, accounting for approximately 75% of all ASDs, and are generally the result of an underdeveloped septum secundum and/or excessive reabsorption of septum primum tissue. Ostium secundum defects are therefore found in the central portion of the interatrial septum (Figures 26-1, 26-2, 26-3). Ostium primum ASDs, also known as a partial or transitional atrioventricular canal defects, account for 15% to 20% of all ASDs and are located between the anteroinferior aspect of the fossa ovalis and the atrioventricular valves (Figures 26-3 and 26-4). Because the defect affects the ­endocardial cushion portion of the developing heart, atrioventricular valve abnormalities are nearly universal, particularly a cleft in the anterior leaflet of the mitral valve. Conduction abnormalities are also common with primum ASDs. Sinus venosus ASDs, which make up 5% to 10% of all ASDs, are caused by deficient tissue between 1 or more pulmonary veins and the superior or inferior vena cava and are found near the entry of the superior or inferior vena cava into the right atrium (Figures 26-3 and 26-5). Coronary sinus ASDs are very uncommon (<1% of all ASDs), are caused by deficiencies of the tissue between the coronary sinus and the left atrium,^1–3 and are most often associated with anomalous connections of the right-sided pulmonary veins. Patent foramen ovale (PFO) is another defect of the interatrial septum resulting from incomplete closure of the foramen ovale after birth. However, it is difficult to consider a PFO a true congenital defect of the heart because it is present in all newborns and persists in up to 25% of the general adult population.⁴

Although, most ASDs are sporadic, the Holt-Oram syndrome, an autosomal dominant mutation, has been noted in families with ASDs. Other mutations in genes involved with cardiac septation have also been implicated.^5,6 In addition, several maternal risk factors and substance exposures, including advanced age, diabetes, alcohol, smoking, and antidepressants, have been associated with ASDs.^7–9

Ostium secundum ASDs may range from a few millimeters to virtual absence of the inter-atrial septum, and occasionally, multiple defects are seen (“Swiss cheese septum”).³ Although many small defects close spontaneously in infancy or remain asymptomatic through childhood, the left-to-right shunt associated with larger ASDs tends to increase in size over time, leading to right ventricular volume overload and increased pulmonary blood flow.^1,3 This is in part due to reduction in left ventricular compliance, a natural process in aging, as well as the potential superimposition of hypertensive, ischemic, or valvular heart disease. In this setting, left atrial pressures will rise, forcing more blood across the defect. Most often, when undiscovered in childhood, patients with ASDs are diagnosed in their third or fourth decade of life when symptoms of dyspnea or palpitations develop. A proportion of asymptomatic patients are incidentally diagnosed during echocardiographic evaluation done for an abnormal electrocardiogram or chest x-ray. Symptoms of frank right-sided heart failure are rare, but significant left-to-right shunts and increased pulmonary flow in patients with large ASDs may produce symptoms of fatigue, decreased exercise capacity, dyspnea, palpitations, peripheral edema, syncope, and atrial arrhythmias. Pulmonary arterial hypertension with pulmonary vascular obstructive disease is an unusual complication of an ASD, but may occur in 5% to 10% of patients. Interestingly, the size of the defect and the size of the resulting shunt do not correlate with the presence or absence of pulmonary hypertension, leading some authors to suggest that the 2 conditions are not causally related. Atrial arrhythmias, such as atrial fibrillation or flutter, are seen in up to 20% of adult patients with ASD and develop due to the long-standing right-sided volume overload. Compared with the general population, the initial presentation of atrial fibrillation occurs at a much younger age, typically in the fifth or sixth decade. In addition, paradoxical embolization from the lower extremity or pelvic veins can occur.^1–3

Ostium primum defects are more often diagnosed in childhood because of the concurrent mitral valve dysfunction. Children have murmurs of mitral regurgitation, which are far more audible than those associated with the ASD. In addition, heart failure symptoms may occur, as in any other patient with mitral valve disease. These ASDs need to be surgically corrected. Sinus venosus ASD can also be missed in childhood, but symptoms may occur sooner with anomalous pulmonary venous return adding to the right ventricular volume load.

On physical examination, patients with ostium secundum ASDs may have signs of right-sided volume overload and increased pulmonary blood flow, including a precordial lift, a soft pulmonary flow murmur, and a wide splitting of the second heart sound without respiratory variations. In patients with large shunts and in those with pulmonary hypertension, a diastolic flow rumble across the tricuspid valve and increased intensity of the pulmonary component of the second heart sound may be heard. An ostium primum ASD should be suspected in the presence of a mitral regurgitation murmur.

Electrocardiogram may reveal right atrial enlargement, incomplete right bundle branch block, right-axis deviation, atrial arrhythmias, and, in cases with pulmonary hypertension, right ventricular hypertrophy. Left-axis deviation may be seen in patients with ostium primum ASDs. Right atrial, right ventricular, and pulmonary artery enlargement and prominent pulmonary vasculature are seen in chest x-rays of patients with significant shunts.

Transthoracic echocardiography is the primary tool for the diagnosis of ASDs in children, whereas transesophageal echocardiography is the most effective method of diagnosing an ASD in adults. Two-dimensional imaging of the interatrial septum accurately assesses the defect’s location, number, shape, size, rim characteristics, and hemodynamic consequences (see Figure 26-1). Multiple views are needed to visualize the entire interatrial septum, including parasternal, apical, and subcostal views. Color Doppler assessment helps locate the defect and estimate the degree and direction of the shunt across the septum (see Figure 26-1). Spectral Doppler readily determines flow velocities across the defect, as well as across the tricuspid and pulmonic valves to estimate pulmonary artery pressures. The hemodynamic consequences of large defects include right atrial and ventricular enlargement and other signs of right ventricular volume and pressure overload. In patients with poor transthoracic windows or in those with inconclusive studies, contrast or transesophageal echocardiography (TEE) may be used (see Figure 26-2). With the improvement in ultrasound technology and the introduction of real-time 3-dimensional (3D) TEE, other diagnostic tools such as magnetic resonance imaging (MRI) and diagnostic cardiac catheterization are now rarely required for the assessment of the secundum ASD.

MRI can be used for the diagnosis of ASDs when echocardiography is nondiagnostic or in the case of a sinus venosus ASD, where tomographic imaging enhances the ability to identify anomalous pulmonary venous connections. MRI also allows accurate quantification of right ventricular volumes and shunt fractions to estimate the hemodynamic consequences of ASDs.

Diagnostic cardiac catheterization provides detailed hemodynamic information, including right-sided pressures, vascular resistances, and flow ratios. However, cardiac catheterization is not needed for most cases and should not be done in patients with uncomplicated defects in whom the noninvasive imaging is adequate.¹ Patients with pulmonary arterial hypertension should undergo cardiac catheterization for the assessment of pulmonary vascular reactivity. Coronary angiography should be performed in older adults undergoing surgical repair of the defect to exclude obstructive coronary artery disease requiring treatment.¹

The management of patients with ASDs depends on the defect’s type, associated symptoms, and hemodynamic significance. The definitive treatment of all types of ASDs is either surgical or percutaneous repair. Surgical repair, which is usually done during childhood, is the preferred treatment option for ostium primum, sinus venosus, and coronary sinus ASDs. Transcatheter closure or surgical repair can be used for patients with ostium secundum ASD. Patients with small ostium secundum defects (<5 mm) and no right-sided chamber enlargement may not require defect closure and are typically followed clinically and with echocardiography at least every 2 years. Defect closure is indicated for patients with hemodynamically significant shunts as evidenced by right atrial or ventricular enlargement irrespective of their symptom status (Class I, Level of Evidence [LOE] B) or for patients with defects of any size and hemodynamic significance in the presence of paradoxical embolization (Class IIa, LOE C) or documented orthodeoxia-platypnea (Class IIa, LOE B).¹ Although the presence of pulmonary hypertension was formerly viewed as a contraindication for closure, it may be performed in individuals with net left-­to-right shunt, pulmonary vascular resistance of less than two thirds of the systemic vascular resistance, or pulmonary arterial pressure of less than two thirds of the systemic arterial pressure, or in those who respond to vasoreactivity testing or balloon occlusion of the defect (Class IIb, LOE C). Patients complicated by severe irreversible pulmonary hypertension (typically defined as a pulmonary vascular resistance >8 Woods units) and/or net right-to-left shunt (ie, Eisenmenger syndrome) should not undergo defect closure (Class III, LOE B). Surgical closure of ostium secundum defects should be done when there are anatomic limitations for percutaneous closure or in those undergoing tricuspid valve surgery (Class IIa, LOE C).

MEDICAL THERAPY

Medical management is not a therapeutic option for ASDs per se, but is used for the treatment of its long-term complications. Antiarrhythmics and/or direct current cardioversion with appropriate anticoagulation may be required to maintain sinus rhythm should atrial arrhythmias develop. Medical therapy for pulmonary arterial hypertension is only recommended for patients with irreversible disease and Eisenmenger syndrome in whom defect closure is contraindicated. Oxygen supplementation is controversial and may be only beneficial for patients with oxygen-responsive disease.^10,11 Diuretics are empirically given to manage volume overload in patients with heart failure. Calcium channel blockers can theoretically worsen right-to-left shunting if the systemic vascular resistance falls below the pulmonary vascular resistance.¹² Although there are insufficient data to recommend the use of calcium channel blockers in this setting, nifedipine has been shown to improve oxygen saturation and exercise capacity in small studies in patients with ventricular septal defects and patent ductus arteriosus.^13,14 Despite their potential to worsen right-to-left shunt, pulmonary vasodilators, including prostanoid analogues, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists, have a proven clinical benefit in these patients.¹⁵ Such agents have improved symptoms, exercise capacity, hemodynamic parameters, and even survival in observational studies and randomized trials.^15–18 Heart-lung or lung transplant is an alternative for selected patients with advanced disease.¹⁹