CONGENITAL HEART DISEASE

BRIEF REVIEW Atrial Septal Defect in the Adult Thomas Ryan, MD, Duke Uniierrity Medical Center, Durham, North Carolina

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A trial septal defect (ASD) is one of the most frequently encountered forms of congenital heart disease. The type of ASD is defined by the location of the defect

within the septum. Secundum ASD, involving the region of the fossa ovalis, is by far the most common and occurs two to three times more often in women than in men. Secundum ASD may be familial and is usually an isolated lesion. Sinus venosus ASD involves the superior portion of the septum ac the junction of the superior vena cava and is often associated with anomalous drainage of the right pulmonary veins. The physiology and clinical features are similar to secundum defects. Primum ASDs involve the most apical portion of the atria1 septum, are frequently associated with other congeni- tal lesions and are most often detected and repaired in childhood. For these reasons, this review will focus on secundum and sinus venosus ASD and their management in adult patients.

Regardless of type, an uncomplicated ASD results in a shunt from the left to the right atrium, the magnitude of which is determined by the size of the defect, the ratio of pulmonary to systemic vascular resistance and the relative compliance of the two ventricles. Because of the relatively small pressure gradient between the atria, a high-velocity jet does not occur and most of the flow takes place in late ventricular systole and early diastole. Because pulmonary resistance decreases soon after birth (and right ventricular compliance increases), left-to-right shunting gradually in- creases. In most patients, the augmented pulmonary flow occurs without an associated increase in arterial pressure. The shunt flow crosses a low-pressure, low-resistance vas- cular bed. As a result, Eisenmenger’s physiology is uncom- mon and is almost never encountered before adulthood (1). Instead, a diastolic right ventricular volume overload is created. The left heart is conspicuously spared until the later stages when stroke volume may diminish. This is usually a reversible mechanical phenomenon in part attributable to leftward displacement of the interventricular septum and to reduced left ventricular preload (2-4). These hemodynamic alterations are generally well tolerated in infants and chil- dren (even when the shunt is large) and symptoms seldom develop until later in life.

Prevalence

With the increasing accuracy and availability of diagnostic modalities, most patients with ASD are identified and re- paired during childhood. Despite this trend, ASD still ac- counts for more than 25% of patients followed in adult

congenital heart disease clinics and the de novo diagnosis of ASD in an adult is a common occurrence. There are several reasons to explain these observations. Physical findings in patients with ASD are often subtle and symptoms frequently do not surface until early adulthood. The symptoms, usually dyspnea or fatigue, are nonspecific and may suggest another etiology. In some patients, for example, associated mitral valve prolapse is blamed. Thus, the diagnosis may be de- layed until a chest x-ray or echocardiogram is obtained, often for an unrelated indication. In fact, the proliferation of echocardiography has “created” a new population of pa- tients with ASD-those with subtle signs and no symptoms.

Diagnosis

If an ASD is suspected from the history or physical exami- nation, an electrocardiogram (ECG), chest x-ray, and echo- cardiogram will provide useful diagnostic information. The ECG typically reveals sinus rhythm with mild prolongation of QRS duration. The frontal plane QRS axis is normal or slightly rightward. Left axis deviation should suggest a pri- mum defect. In the right precordial leads, an rSr’ pattern is characteristic, reflecting right ventricular volume overload. The chest x-ray shows an enlarged right heart with dilation of the pulmonary trunk and increased pulmonary vascular- ity. The aorta and left ventricle are normal. Echocardiogra- phy is diagnostic in most instances and permits the size and location of the ASD to be determined. In addition to direct visualization of the defect, the degree of right ventricular dilation, right ventricular and pulmonary artery pressure and the presence of associated findings (such as mitral regurgitation) can also be assessed. If results are equivocal, transesophageal echocardiography is the most accurate and precise method to visualize the interatrial septum. The di- mensions of the defect can be measured and Doppler can be used co assess shunt flow. This information may be particu- larly useful to identify patients who are candidates for trans- catheter closure of secundum ASD and to help guide the deployment of these devices.

With the use of modem echocardiographic techniques, a complete evaluation of most patients is possible and cardiac catheterization is seldom necessary unless other more com- plex pathology is suspected. Catheterization does permit pulmonary and systemic blood flow to be quantified and the pulmonary pressures can be measured directly. Shunt ratio and pulmonary vascular resistance, both of which may be important factors in the decision making, can then be calcu- lated. In selected patients, such as those with significant pulmonary hypertension, this may be necessary. As a prac- tical matter, however, most of the essential diagnostic infor- mation will be available noninvasively. For example, if a defect is large and the right ventricle is dilated, a significant shunt is likely present and calculating the shunt ratio adds little incremental data. For these reasons, in most experi-

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CONGENITAL HEART DISEASE

enced laboratories the primary indication for invasive study of adults with ASD is to determine coronary anatomy before surgical repair.

Natural History

The natural history and clinical course of patients with ASD have been well studied (5,6). Most children and adolescents are asymptomatic. Exertional dyspnea and fatigue generally have their onset in early adulthood and are present in the majority of patients older than 50 years. By age 40 years, annual mortality approaches 5% and then accelerates rap- idly (6,7). Early studies reported only lOoh survival beyond age 60 (6). The reasons for this clinical deterioration in adults are several. Mild to moderate pulmonary hyperten- sion, which is common after age 40 years, creates a com- bined volume and pressure overload on the right ventricle. Atria1 fibrillation becomes increasingly common and is present in more than 50% of patients by age 60 years. The potential for both pulmonary and paradoxical emboli fur- ther contribute to the morbidity in adult patients.

Surgical Considerations

The relatively poor prognosis for adults with ASD has con- tributed greatly to the enthusiasm for recommending surgi- cal repair in most patients. Before examining the data sup- porting surgical intervention, it is worthwhile to mention an important limitation of these natural history studies. Almost all of what is known about the natural history of ASD was reported before 1970. Because sophisticated diagnostic techniques were not yet available, only the most clinically obvious cases were included in these early series, which serve as historical controls for more recent studies. The mild cases, consisting of small ASDs in asymptomatic patients, were almost certainly excluded because they were not de- tected. In recent years, it has become standard practice to repair most ASDs, regardless of symptom status, provided the left-to-right shunt exceeds 1.5: 1. This approach prevents a reexamination of the natural history of ASD in the modem era. Thus, “historical controls” represent a skewed popula- tion and the dismal prognosis that is quoted in the literature may not be applicable to many patients seen at present.

Despite this note of caution, a sizable body of literature exists demonstrating the value of surgical intervention in adult patients with ASD. The benefits of surgery have been examined in a variety of clinical circumstances. Murphy et al. (8) reviewed the Mayo Clinic experience in 123 patients followed for 27 to 32 years after ASD repair. All patients underwent surgery before 1960 and only those with isolated secundum or sinus venosus defects were included. Symp- toms were present in 75% and pulmonary artery systolic pressure varied over a wide range. Perioperative mortality was 3.3%, much higher than it is now, and 30-year survival was 74%. Among patients who underwent repair before the

age of 25, long-term survival was similar to age-matched control subjects. If surgery was performed after age 25, survival was less than the control population, especially if there was a significant elevation in preoperative pulmonary artery pressure. Late cardiac events, such as stroke, heart failure and atria1 fibrillation, were also more likely to occur when surgery was performed at an older age. After multiva- riate adjustment for the different clinical and hemodynamic variables, age at operation and pulmonary artery systolic pressure were the significant predictors of long-term sur- vival. This study confirms the potential benefits of surgical repair. If performed at a young age in symptomatic patients, surgery is almost certainly associated with improved long- term survival and a reduced risk of late complications. The advantages of surgery in older patients is, however, less clear.

Another review of ASD repair in adult patients is provided by Horvath et al. (9). These investigators reported the out- come of 166 patients who underwent surgery between 1971 and 199 1, The study population covered a wide range of ages, pulmonary artery pressures and clinical status. Symp- toms were absent or mild in 88% of patients. Operative mortality was 1.3% and follow-up ranged from 2 months to 20 years (mean, 7.5 years). Five- and lo-year survival rates were 98% and 94%, respectively, and more than half of the late deaths occurred in patients who were older than 50 years at the time of operation. Event-free survival at IO years was 92% and the most common late complication was atria1 fibrillation, which developed in 7% of patients.

The value of surgical closure of ASD in older patients (aged 250 years) has been examined by several investiga- tors. These studies included predominantly symptomatic patients with a wide range of pulmonary vascular resistance and shunt ratios. In most, symptoms were reduced or elim- inated and functional status was improved after repair. Among patients whose hemodynamics were measured post- operatively, pulmonary artery pressure generally decreased (lo), although the magnitude was quite variable and pulmo- nary vascular resistance was often unchanged (I I). Postop- erative arrhythmias, especially atria1 fibrillation, were very common. Most of these investigators concluded that, even in older patients, surgical repair is associated with a reduction in symptoms and improved survival compared to medically treated patients.

Not represented in these series is the group of patients with significant pulmonary hypertension. Steele et al. (I) reviewed the Mayo Clinic experience in treating adults with ASD complicated by pulmonary vascular disease. They de- scribed 40 patients (representing 6% of the total number of cases of isolated secundum or sinus venosus ASD) with total pulmonary resistance (TPR) >7 U/m’. Thirty-four (85%) of the patients were women. Median follow-up was I2 years and overall mortality was 42%. Surgical repair was per-

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formed in 26 patients and medical therapy was undertaken in 14. This was a retrospective, observational study and the two treatment groups were quite different. For example, TPR was substantially higher and systemic arterial oxygen satu- ration was lower in the medically treated cohort. The best predictor of outcome was TPR. If it was less than 10 U/m’, long-term survival was better in surgically treated patients. If TPR was greater than 15 U/m’, prognosis was generally poor regardless of therapy (although one patient in the surgical group survived 13 years and one in the medical group 9 years). Among patients with a TPR between 10 and 15 U/m’, outcome was variable, although the researchers recom- mended surgery in most instances. This study demonstrated that surgery should be recommended in most patients with mild to moderate pulmonary hypertension. If pulmonary vascular disease was severe, however, surgery is unlikely to be beneficial.

The rationale for enthusiastically recommending surgery for the vast majority of adults with ASD has been questioned recently. Shah et al. (12) compared the results of long-term follow-up of medically versus surgically treated patients at the Hammersmith Hospital in London. Since 1955, all pa- tients with isolated ASD who were at least 25 years of age at presentation and were over 45 years at the time of follow-up were examined. Of the 82 patients in the study, 34 were managed medically and 48 underwent surgical repair. At the time of entry into the study, the two groups were similar with respect to age, functional class and hemodynamic sta- tus. Patients with severe pulmonary hypertension were ex- cluded. It is interesting that more than 70% of patients in both subsets were asymptomatic at presentation and atria1 fibrillation was noted in 24%. Mean follow-up was 25 years and there were no operative or perioperative deaths. Overall survival (more than 90% in both groups) and symptom status at follow-up were similar in the two groups. Likewise, atria1 fibrillation was equally prevalent in medically versus surgically managed patients (56% and 53%, respectively).

Comment

There are several interesting and important aspects to the study cited above (12). Unlike most other reports, the ma- jority of patients were either asymptomatic or minimally symptomatic at presentation. This may explain the favorable outcome of the medically treated patients. Only one cardiac death occurred among the 34 patients despite a mean age at follow-up of 63 years. There was no significant deterioration in New York Heart Association functional class over the course of the study in either group. Clearly, these patients bear little similarity to the historical controls described pre- viously. Their long-term prognosis is substantially better, although certain complications, especially atria1 fibrillation, became increasingly prevalent with aging. Because of this markedly improved outlook for medically treated patients, it

was impossible to demonstrate any advantage to surgical intervention. After 25 years of follow-up, the two subsets were similar in almost every outcome category. The investi- gators stressed the inappropriateness of comparing current surgical results to natural history series from the 1950s and 1960s. They conclude that “. neither survival nor the incidence nor timing of development of atria1 arrhythmias, embolic stroke, pulmonary vascular disease, or heart failure were affected by heart surgery in our patients whose defects had not been detected until adulthood’ (12).

Taken together, these studies help to clarify the proper approach to adults with ASD. Several conclusions can be drawn. Many adult patients will be symptomatic at the time of presentation and these symptoms will diminish after repair. Surgery is safe and the only real contraindication is severe pulmonary vascular disease, which is a rare condition found predominantly in middle aged women. If repair can be accomplished in young adults, long-term survival is im- proved and complications may be avoided. When surgery is delayed, symptoms are progressive and repair at an older age will be less likely to prevent the development of late events, especially atria1 fibrillation and subsequent emboli. At what age surgery should no longer be recommended is still un- known In the rare case complicated by pulmonary vascular disease, surgical therapy may still be beneficial unless the pulmonary arterial resistance is extremely elevated. Thus, most adults with significant symptoms should be offered surgical closure of their ASD.

Recommendations regarding the management of asymp- tomatic patients are less clear. The natural history of this group is poorly defined, but their prognosis is almost cer- tainly brighter than the older literature would suggest. It is not known why some adult patients remain symptom free. If a patient reaches adulthood without significant symptoms, what is the likelihood that problems will eventually develop and, if so, when? It is apparent that these patients are underrepresented in most natural history series, therefore the oft-quoted superiority of surgical therapy may not apply. In fact, in the only modem longitudinal study comprised predominantly of asymptomatic adults (12), no advantages of surgical over medical treatment could be demonstrated. This same argument, however, may not be applicable to younger patients. If a large ASD is detected in a child or adolescent, the opportunity to prevent the development of symptoms and complications and perhaps to restore life expectancy to normal argue in favor of an aggressive surgical approach.

REFERENCES

1. Steele PM, Fuster V, Cohen M. Ritter DG, McGoon DC. Isolated atrial septal defect with pulmonary vascular obstructive dtsease-long-term

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follow-up and predtctton of outcome after surgical correction Ctrculatton 1987;76:1037-42.

2. Bonow RO. BorerJS, Rosmg DR. et al Left ventricular functtonal resetv in adult patients wtth atnal septal defect: pre and post-operative studtes. Circulation 1981;63.1315-22.

3. Carabello BA, Gash A, Mayers D, et al. Normal left ventricular function m adults with atnal septal defect and left heart fatlure Am J Cardiol 1982;49:1968-73.

4. Booth DC, Wtsenbaugh T, Smtth M, DeMana AN. Left ventrtcular dtstenstbility and passwe elasttc stiffness tn atnal septal defect J Am Co11 Cardiol 1988;12:1231-6.

5. Craig RJ. Seizer A. Natural htstory and prognoses of atrial septal defect Cnculation 1968;37:805-15.

6. Campbell M. Natural htstoty of atnal septal defect. Br Heart J 1970;32 820-6.

7. Markman P, Howttt G, Wade EG. Atria1 septal defect m the middle aged and elderly Q J Med 1965;34 409-26

8. Murphy JG, Gersh BJ, McGoon MD, et al. Long-term outcome after

surgtcal repan of isolated atnal septal defect. Follow-up at 27 to 32 years. N Engl J Med 1990:323,1645-50

9. Howath KA, Burke RP, Colhns JJ, Cohn LH Surgical treatment of adult atrial septal defect early and long-term results. J Am Co11 Cardiol 1992;20: 1156-9.

10. Haqula A, Kupan M. Kyosola K, et al Early and late resuks of surgery for atnal septal defect in patients ages over 60 years. J Cardtovasc Surg 1988:29:134-9

11 St John Sutton MG, Tank AJ, McGood DC. Atnal septal defect in patients aged 60 years or older: operawe results and long-term postoper- attve follow-up. Circulatton 1981,64:402-9.

12 Shah D, Azhar M. Oakley CM, Cleland JGF, Nthoyannopoulos P. Natural htstoty of secundum atnal septal defect m adults after medical or surgtcal treatment a historical prospectwe study. Br Heart J 1994;71: 224-8

Address correspondence and reprint requests to Thhomas Ryan, MD, Box

3542, Duke Lrntvers~ty Medical Center, Durham, NC 27710.

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The most common electrocardiographic finding in atrial septal defea, namely, an incomplete right bundle branch block. Courtesy of Charles Fisch, MD, Indianapolis, Indiana

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