As many as 85% of infants born with congenital heart disease can be expected to survive into adulthood. In the United States, the total number of adults with congenital heart disease is increasing at a rate of about 5% per year. In the current era, more adults have congenital heart disease than children. This number includes both unrepaired and surgically corrected patients. The population of patients with congenital heart disease who reach adult life grows each year because of advances in interventional and noninvasive cardiology, cardiothoracic surgery, and intensive care. As such, a growing number of adult patients with congenital heart disease are likely to present to the general cardiologist as opposed to a highly specialized adult congenital heart disease clinic. The American College of Cardiology Task Force 1 on congenital heart disease estimated that at least 10% of patients with congenital heart disease are diagnosed as adults. Furthermore, the consensus opinion of this committee was that the number of adults with undiagnosed congenital heart disease is increasing due to the growing immigrant population. Thus it is important that all cardiologists possess a sound understanding of the hemodynamics associated with the common congenital heart disease lesions as this provides valuable insight into the pathophysiology of these conditions.
Our understanding of the physiology of congenital heart disease in humans was largely theoretical until the 1940s when Dexter et al. published the first manuscript that described the use of right heart catheterization to directly measure intracardiac pressure and oxygenation saturations in patients with congenital heart disease. Since then, the complete assessment of congenital heart disease has evolved to include echocardiography and magnetic resonance imaging, making reliance on diagnostic catheterization data a less frequent occurrence.
This chapter will focus on lesions more commonly seen in an adult cardiologist’s practice, including atrial septal defect (ASD), ventricular septal defect (VSD), coarctation of the aorta, and Ebstein anomaly of the tricuspid valve. It will also focus on the postoperative, surgically palliated patient with tetralogy of Fallot, the patient with peripheral pulmonary artery stenosis, and the patient with Eisenmenger syndrome.
Atrial Septal Defect
ASDs are the second most common congenital heart defect, following VSDs. This communication results in a left-to-right shunt, leading to a volume load to the right atrium, right ventricle, and pulmonary arteries. The volume load leads to distention of the right atrial and right ventricular myocardium, which, in turn, can promote diastolic dysfunction and lead to arrhythmias. Additionally, the increase in pulmonary blood flow can cause shear stress on the pulmonary endothelium and lead to the development of vascular disease with resulting pulmonary and right ventricular hypertension.
During fetal circulation, the interaction of the inferior/leftward primum and superior/rightward secundum septa forms the foramen ovale, which functions as a valve allowing right-to-left shunting of oxygenated placental blood into the left heart to be ejected preferentially to the cerebral and upper extremity circulation. Following birth, a progressive increase in pulmonary blood flow leads to an increase in pulmonary venous return, an increased left atrial pressure, and subsequent closure of the foramen ovale. The overall incidence of a patent foramen ovale has been estimated to be as high as 27% but has been reported to decline with increasing age. A patent foramen ovale rarely results in significant clinical sequelae and is not associated with hemodynamic abnormalities. The notable (and often debated) clinical exception is the case of a paradoxical embolus, presumed to occur via a patent foramen ovale allowing transient right-to-left shunting.
Four types of interatrial communications have important clinical sequelae: (1) primum ASD, (2) secundum ASD, (3) sinus venosus defect, and (4) coronary sinus septal defect. The majority of cases occur spontaneously; however, reports of familial cases exist.
After patent foramen ovale, the secundum ASD is the most common type of interatrial communication. It comprises up to 75% of ASDs. The interatrial communication may be due to a single hole or multiple fenestrations in the septum primum. In rare cases the secundum ASD may result from an incomplete septum secundum. The pathophysiologic manifestation of a secundum ASD is a left-to-right shunt across the atrial septum, with resultant volume overload of the right heart. Campbell’s natural history studies have shown that, with time, right-sided heart failure and pulmonary hypertension develop and lead to early mortality.
A sinus venosus defect occurs when the tissue between either the vena cava, the right atrium, or the pulmonary veins fails to incorporate properly. It comprises up to 10% of ASDs. The most frequently encountered sinus venosus defect involves a communication between the superior vena cava (SVC)/right atrial junction and the right upper pulmonary vein. Less frequently, these defects involve other right-sided pulmonary veins and the inferior vena cava/right atrial junction. Patients with sinus venosus defects frequently have a partial anomalous pulmonary venous return, with the right upper pulmonary vein draining to the SVC.
The primum ASD is the third most common type of interatrial communication after patent foramen ovale and secundum ASD. It comprises up to 15% of ASDs. The defect is due to maldevelopment of the endocardial cushions and is associated with a cleft in the anterior mitral leaflet and mitral regurgitation.
The least frequently encountered ASD is the coronary sinus septal defect. The tissue that constitutes the wall between the coronary sinus and the left atrium is either completely absent or only partially developed. Therefore the left atrium and right atrium are connected via the coronary sinus.
Hemodynamics
The volume of shunt across an interatrial communication is a function of the size of the defect and the relative compliance of the right and left ventricles, which was first suggested by Dexter in 1956. These variables change throughout life with some defects becoming smaller during periods of myocardial growth in addition to dynamic changes in ventricular compliance during development.
As a neonate, right ventricular compliance is low, reflecting its relatively high workload during fetal development. At this stage, there tends to be a relatively small left-to-right shunt for a given defect size. As the neonate progresses to infancy and pulmonary vascular resistance reduces, the pressure load of the right ventricle declines, resulting in a smaller and more compliant chamber. As the right ventricle continues to become more compliant relative to the left ventricle, flow across an atrial defect will increase throughout childhood and early adolescence. This results in a volume load to the right atrium, right ventricle, and pulmonary arteries. With a significant shunt, this will be demonstrated by dilation of those chambers and pulmonary vessels. Given a significant shunt and adequate time (typically decades) endothelial damage of the pulmonary vasculature and myocardial maladaptation ensue, leading to pulmonary hypertension, arrhythmias, and right ventricular systolic and diastolic dysfunction. If right ventricular diastolic function continues to decline, the atrial shunt may reverse direction from right to left, resulting in systemic hypoxemia.
Cardiac catheterization is performed for hemodynamic assessment and potential closure of secundum ASDs. Right-sided heart catheterization demonstrates an increase in saturations from the SVC into the right atrium, with a significant shunt generally having a pulmonary flow (Qp) to systemic flow (Qs) ratio (or Qp/Qs) ≥1.4. Right atrial pressures tend to be normal but may be elevated if there is right ventricular diastolic dysfunction ( Fig. 13.1 ). Additionally, the atrial tracing may demonstrate a dominant v wave if the atrial defect is large. Right ventricular pressures tend to be normal unless pulmonary hypertension or diastolic dysfunction has developed because of a long-standing shunt.
Closure of an ASD when there is left-sided diastolic dysfunction, common in later decades of life or in those with significant coronary artery disease, should be undertaken with care as the atrial defect acts to volume-unload the left ventricle. With closure of the defect, the increased volume load may elevate left ventricular end-diastolic pressure and subsequently elevate left atrial and pulmonary venous pressure, potentially causing pulmonary congestion.
Effects of Treatment
The majority of patients in the United States with ASD undergo either surgical or percutaneous closure during childhood. In a study of 123 patients who underwent closure at the Mayo Clinic (Rochester, Minnesota), Murphy et al. found that two factors correlated with survival after repair: (1) the age of the patient at the time of the operation ( P < .0001) and (2) the pulmonary artery systolic pressure ( P < .0027). Those patients who had a repair prior to age 25 had a long-term survival similar to that of the control population. However, those patients who were older than age 25 and who had a pulmonary artery pressure ≥40 mm Hg had a shorter life expectancy than controls. At the 25-year follow-up, survival was 39% versus 74% ( P < .0001). The increase in mortality was related to the development of congestive heart failure, atrial fibrillation, or cerebrovascular accident. Kobayashi et al. demonstrated that defect closure in patients with Qp/Qs ≤3 and a pulmonary artery pressure ≤50 mm Hg, or with Qp/Qs ≥3 regardless of pulmonary artery pressure, resulted in increased exercise capacity. Gatzoulis et al. found that as many as 60% of patients with ASD and atrial fibrillation continued to experience this arrhythmia after surgical closure of their defect. Murphy et al. reported that of 104 patients in sinus rhythm prior to repair, 80 remained in sinus rhythm 27 to 32 years after the procedure.
Transcatheter closure of secundum ASDs has demonstrated excellent outcomes, with current-era technology having a shorter hospital stay and lower complication rates compared with surgical closure ( Fig. 13.2A and B ).
Ventricular Septal Defect
VSDs are the most common congenital heart lesions, accounting for 20% to 30% of all patients with congenital heart disease. Additionally, this may be an underestimation as small, hemodynamically insignificant VSDs undergo spontaneous closure in the newborn period prior to diagnosis and may be as common as 10% of all pregnancies. This lesion is much less frequently encountered in the adult population given that most undergo spontaneous closure, are surgically repaired, or are hemodynamically insignificant or, if therapy is not undertaken, death occurs in the newborn or childhood period due to cardiac failure. In those who survive to adulthood with significant unrepaired defects, many will have developed pulmonary vascular disease and Eisenmenger syndrome, which is discussed in a later section.
Though intellectually it is easy to simplify the ventricular septum as merely the structure separating the right and left ventricles, it has a complex embryologic origin derived from muscular, endocardial, and conal septal tissues. The intricate development and fusion of each of these tissues during fetal development likely accounts for the high incidence of incomplete separation of the ventricular chambers. Though there are several accepted classification schemes in use for describing the location of these defects, they tend to be generalized into four : (1) perimembranous (approximately 75%), found at the crux of the heart, (2) muscular (10%–20%), found within the muscular septum, (3) inlet (approximately 5%), found beneath the tricuspid valve, and (4) outlet (approximately 5%), found in the outflow tract beneath the semilunar valves. The location of the defect tends to have little impact on hemodynamic effect, though it does have an important influence on interventional approach and the likelihood of spontaneous closure, with muscular defects most likely and outlet defects least likely to resolve spontaneously.
Hemodynamics
The hemodynamic effects of VSDs are dependent on the size of the defect and the relative vascular resistances of the pulmonary and systemic circuits, resulting in a left-to-right shunt. These two factors determine the pressure and volume load transmitted from the left to the right ventricle and then pulmonary vasculature. By nature, this increased pulmonary blood flow then increases pulmonary venous return to the left atrium and left ventricle, resulting in a volume load to each of those chambers. Large defects will transmit both a pressure and volume load, while small defects will be pressure restrictive with minimal volume burden.
Additionally, it is important to appreciate the dynamic changes in vascular resistances during the neonatal transitional period. A developing fetus has minimal pulmonary blood flow and a low systemic vascular resistance in part because of placental circulation. Following delivery, an abrupt increase in systemic vascular resistance occurs with the removal of placental circulation. Concurrently, there is an increase in pulmonary blood flow to the newly aerated lungs with a progressive reduction in pulmonary vascular resistance occurring over the next 4 to 6 months. For these reasons, even large VSDs may have a minimal left-to-right shunt in the immediate newborn period, which then increases as the infant matures.
With the continued improvement in noninvasive imaging for diagnostic purposes, purely diagnostic cardiac catheterization for isolated VSDs has become less common unless there is concern regarding significant pulmonary vascular disease. In the current era, transcatheter closure of VSDs has become an important option for select situations, including muscular location, postmyocardial infarction, and some perimembranous lesions.
In patients with large, unrestrictive defects, there is an elevation in right ventricular ( Fig. 13.3A ) and pulmonary artery systolic pressures equivalent to that of the systemic circulation. Diastolic and mean pressures in the pulmonary arteries will remain lower than systemic until pulmonary vascular disease develops, at which time they will equilibrate. Left atrial and left ventricular end-diastolic pressures will be elevated, reflective of the volume load to those chambers. With a large shunt, there will be a significant increase in oxygen saturations from the right atrium into the right ventricle and pulmonary arteries. The relative ratio of pulmonary to systemic blood flow (Qp:Qs) tends to be >2:1 ( Fig. 13.3B ).
VSDs that are pressure restrictive may still have significant left-to-right shunt flow, as demonstrated in Fig. 13.3C . Right ventricular pressure will be normal, but the pulmonary arteries, the left atrium, and the left ventricle will be dilated from the volume overload.
In patients with smaller, restrictive defects, the right ventricular and pulmonary artery pressures will be proportionately lower, with the left atrial and left ventricular end-diastolic pressure being normal. Additionally, there will be only a modest increase in oxygen saturation from the right atrium into the right ventricle and pulmonary arteries, reflective of minimal volume load. In this situation, Qp:Qs is generally < 1.5:1.
Effect of Treatment
As stated previously, the rate of spontaneous closure is dependent on the anatomic location. There is a small, continued risk of endocarditis with persistence of the shunt. Surgical approach is determined by location of the defect, with attempts to avoid a ventriculotomy as this can lead to arrhythmias and aneurysm formation. Inlet and perimembranous defects tend to be approached from a right atriotomy through the tricuspid valve, while outlet defects are approached via pulmonary artery incision through the pulmonary valve. Muscular defects present a surgical challenge, particularly if there are multiple, as they are difficult to visualize in the heavily trabeculated right ventricle. Options here include primary surgical repair, pulmonary artery banding, transcatheter closure, or a combination of procedures.
Among those with hemodynamically significant defects undergoing surgical intervention, outcomes tend to be excellent with minimal mortality even in small infants. Pulmonary artery pressures normalize, and the patients have an accelerated growth after closure.
Transcatheter closure of muscular VSDs has been utilized since the late 1980s, as described by Lock et al. and has continued to demonstrate good procedural success; however, adverse event rates are higher for this anatomic location. Transcatheter closure of perimembranous VSDs remains an option; however, there is a nontrivial incidence of complete heart block associated with this procedure. Although not due to congenital heart disease, postmyocardial infarction VSDs remain a challenging situation with a grim prognosis. Transcatheter closure has been technically successful in the majority of patients, though procedural mortality or need for emergent surgery occurs in approximately 10%.
Coarctation of the Aorta
Coarctation of the aorta refers to a congenital narrowing of the artery occurring in approximately 4% of patients with congenital heart disease. Although it may occur in the transverse aortic arch, the distal thoracic aorta, or even rarely in the abdominal aorta, it occurs most commonly in the proximal descending aorta near the ligamentum arteriosum, the remnant of the ductus arteriosus. The most frequently observed variety consists of a discrete narrowing distal to the left subclavian artery ( Fig. 13.4 ). Oftentimes there is associated distal displacement of the left subclavian artery. The embryologic etiology of aortic coarctation is hypothesized to be an extension of tissue from the ductus arteriosus into the aortic wall, which then constricts during the regression of the ductus in the neonatal period. Most cases of coarctation are sporadic; however, an association with Turner syndrome exists. The most commonly reported cardiovascular abnormality coexisting with a coarctation is a bicuspid aortic valve, occurring in 85% of patients. Other abnormalities include intracranial aneurysms in 10% of patients, VSD, aortic medial disease, and abnormalities of the innominate and left subclavian arteries.
The majority of severe coarctations are discovered and treated during infancy in the United States. When the ductus arteriosus closes in an infant causing a severe obstruction, shock or heart failure develops rapidly. Rapid recognition and administration of prostaglandin to reopen the aortic ampulla alone or the full ductus arteriosus allows for reperfusion of the subthoracic organ systems and recovery of function. Surgical intervention is then undertaken for definitive treatment. Balloon angioplasty and stenting can be considered as rescue therapy in those unresponsive to prostaglandin E or those not deemed surgical candidates in the immediate period. Catheter-based intervention, although rare in infancy, can be utilized as a bridge to definitive surgical repair after organ recovery.
The presentation of a coarctation in adolescence or adulthood is often more subtle and discovered during the evaluation of hypertension. Symptoms are not often reported, though some may experience lower extremity fatigue with exertion and headaches.
Campbell reported that the majority of symptomatic infants with coarctation who were untreated died during the first year of life. Reifenstein et al. reported that approximately 20% of asymptomatic children with coarctation survive to adulthood. However, of those surviving into adulthood, 23% died from aortic rupture at an average age of 27 years. Eighty percent of these were rupture of the ascending aorta; the remaining 20% experienced rupture distal to the coarctation. Of the remaining patients, 22% died from infection, including aortitis at an average age of 25 years, and 29% died from intracranial hemorrhage or congestive heart failure.
Hemodynamics
The coarctation represents a fixed resistor to aortic flow with the resulting increase in left ventricular impedance, pressure, and wall stress. The hemodynamic hallmark of coarctation is a pressure gradient across the coarctation, resulting in upper extremity, cerebral, and coronary artery hypertension. This measured gradient may be diminished in the presence of a large patent ductus arteriosus (PDA) in a newborn or with the development of significant aortic collateral circulation later in life. Invasively measured gradients ( Fig. 13.5 ) demonstrate a wide pulse pressure proximal to the lesion and a diminished pulse pressure distally. The diminished pulse and the late or delayed pulse wave distal to the coarctation are termed parvus and tardus , respectively, similar to the pulse described in patients with severe aortic stenosis.
Effects of Treatment
Surgical treatment options for aortic coarctation have included (1) coarctation excision with end-to-end anastomosis, (2) interposition graft, (3) patch aortoplasty, (4) extended end-to-end anastomosis, (5) bypass jump grafting, (6) subclavian flap aortoplasty, and (7) aortic arch advancement. Contemporary treatment includes percutaneous balloon angioplasty and stent implantation, with some studies suggesting primary stent implantation has superior results with fewer complications at mid-term follow-up.
Unfortunately, after successful surgical or percutaneous therapy for coarctation, mid-term and late-term complications may still occur. Cohen et al. reported that even after coarctation repair the mortality of these patients is elevated. In an analysis of 571 patients with repaired coarctations, the mean age of death was 38 years, with 37% dying from premature coronary artery disease and earlier repair associated with improved survival. Additionally, certain types of repairs place patients at increased risk for aortic aneurysm formation and rupture. Mendelsohn et al. reported the incidence of aneurysm development at the site of patch repair to be as high as 30%. Persistent systemic hypertension is not uncommon for many patients with repaired coarctation, even without anatomic obstruction. O’Sullivan et al. demonstrated systemic hypertension in 20% to 25% of children and adolescents repaired as infants or young children with no identifiable aortic arch obstruction. Similarly, of those who undergo repair after age 40, 50% will continue to experience hypertension at rest, and a substantial fraction will have exercise-induced hypertension. This persistent hypertension may be due, in part, to impaired aortic distensibility but also to intrinsic abnormalities of the microvasculature, baroreceptors, and neurohumoral regulation.
Ebstein Anomaly
Ebstein anomaly is an eponym used to designate a syndrome in which the tricuspid valve is apically displaced with variable degrees of tricuspid regurgitation. It has an incidence of <1% of all patients with congenital heart disease. Characteristically, the septal and posterolateral leaflets are positioned below the atrioventricular groove and tend to be deformed and variably adherent to the ventricular septum. Coaptation of the tricuspid leaflets is commonly abnormal, resulting in important tricuspid regurgitation. Apical displacement of the tricuspid valve leads to a right ventricle becoming partially “atrialized.” This atrialized portion encroaches on the right ventricle, resulting in a relatively small ventricular chamber with impaired compliance. Pulmonary blood flow may additionally be impaired by true anatomic pulmonary atresia or by functional right ventricular outflow tract obstruction as a result of severe tricuspid insufficiency, leading to the inability of the right ventricle to generate sufficient pressure to open the pulmonary valve.
The majority of patients with Ebstein anomaly have an interatrial communication, typically in the form of a stretched patent foramen ovale or a secundum ASD. As with other atrial communications, flow through this defect is determined by the relative compliance of the right and left ventricles. With Ebstein anomaly, this commonly results in a right-to-left shunt and systemic desaturation. Additionally, atrial arrhythmias are encountered in 10% to 25% of patients with Ebstein anomaly and are frequent causes of morbidity.
Hemodynamics
The variability of hemodynamics in this condition is predicated on the severity of tricuspid regurgitation and the systolic and diastolic function of the right ventricle. In mild cases of Ebstein anomaly, the only hemodynamic observation may be that of tricuspid regurgitation manifested by a dominant v wave in the right atrium, with modest global elevation of right atrial pressures. As in other situations with atrial shunts, flow through the defect is determined by the relative compliance of the right and left ventricles. With mild disease, right ventricular compliance remains below that of the left ventricle, resulting in left-to-right shunting at the atrial level. In more severe cases, right-to-left shunts may occur across the ASD due to the chronic volume overload and loss of compliance of the right ventricle, thus leading to systemic hypoxemia ( Fig. 13.6 ).
