Rudolph's Pediatrics, 22nd Ed.

CHAPTER 498. The Patient with Single Ventricle

Jacqueline Kreutzer

Single ventricle or univentricular heart refers to a limited number of congenital heart lesions from a strict anatomic perspective. Anatomically, single ventricle lesions can be either a single left ventricle, due to agenesis of the right ventricular inlet (there is often a small component of the right ventricular outlet present), or a single right ventricle, secondary to agenesis of the left ventricle.1,2 In both, the atria drain through one or two atrioventricular valves into the only ventricular chamber (Fig. 498-1). These lesions are rare, and do not include common lesions such as tricuspid atresia and hypoplastic left-heart syndrome.

In practice the concept of “single ventricle” expands beyond the strict anatomic definition, and refers to all congenital heart lesions that share a single ventricle physiology, regardless of the underlying structural variant.3,4 This expanded functional definition includes all those lesions in which the patient lacks a second ventricle that can independently support the pulmonary circulation. In most such lesions, components of a second ventricle exist.

Thus, the single ventricle from a physiologic perspective includes patients with

• single right ventricle

• single left ventricle

• unbalanced complete atrioventricular (AV) canal (a common AV valve is more aligned to one ventricle than the other, typically associated with asymmetry in the development of the two ventricular chambers)

• tricuspid atresia (eFig. 498.1 )

• hypoplastic tricsupid valve and right ventricle, frequently with intact ventricular septum and pulmonary atresia

• mitral atresia

• hypoplastic left heart syndrome and its variants (eFig. 498.2 )

PATHOPHYSIOLOGY

Overall, patients with single ventricle preoperatively tend to have complete mixing of pulmonary and systemic venous returns within the heart (Fig. 498-2). Blood leaving the heart goes both to the pulmonary and systemic circulations; therefore, the aortic and pulmonary oxygen saturations are usually equal but sometimes streaming of blood within the heart causes differences in aortic and pulmonary oxygen saturations. The single ventricle is volume overloaded, as it supplies both circulations. This parallel circulation is relatively inefficient because some previously oxygenated blood from the lungs returns to the pulmonary circulation and some systemic venous blood is shunted into the systemic arterial circulation (Fig. 498-2, eFig. 498.4 ).3

The balance between the systemic and the pulmonary circulations depends on multiple factors, including anatomic obstruction as well as relative vascular resistances and perfusion pressure. Ideally, the relationship between the pulmonary and systemic blood flows (Qp/Qs) should be kept at least at 1:1, which typically is achieved in the presence of complete mixing when the systemic arterial oxygen saturation is around 75%, in the absence of lung disease and with a normal cardiac output. Some cardiologists recommend maintaining aortic oxygen saturation over 85% with a QP/QS of 1.5 to 2, to improve growth potential.

FIGURE 498-1. Diagram illustrates anatomy of double inlet single ventricle (A) and common inlet single ventricle (B). (Source: Modified from Schultz AH, Kreutzer J. Cyanotic heart disease. In: Vetter VL, ed. Pediatric Cardiology. The Requisites in Pediatrics. Philadelphia, PA: Mosby Elsevier; 2006:51-78.)

In the absence of obstruction at any level, the relationship between pulmonary and systemic blood flow depends on the relative resistances of the two vascular beds. At birth, Qp/Qs is only modestly increased as pulmonary vascular resistance falls from in utero levels, so that systemic arterial oxygen saturation is generally in the mid 70s. As pulmonary vascular resistance decreases in the first few weeks of life, pulmonary blood flow and systemic arterial oxgyen saturation increase greatly because the vascular resistance of the pulmonary vascular bed is much lower than that of the systemic bed. Saturations greater than 85% are associated with such high pulmonary blood flow and in some of these patients heart failure may develop, with respiratory distress, diaphoresis, and failure to thrive. Providing supplemental oxygen to infants with single ventricle to increase saturations when the oxygen levels are above 80% can be detrimental, as oxygen acts as a pulmonary vasodilator, decreasing pulmonary vascular resistance, increasing the pulmonary blood flow, altering the Qp/Qs relationship such that the systemic output decreases.3

However, many patients with single ventricle physiology have various levels of obstruction within the heart and great vessels, so that Qp/Qs depends on factors other than relative vascular resistances. The levels of obstruction include

• Pulmonary or subpulmonary stenosis or atresia: This may lead to a marked decrease in systemic arterial oxygen saturation, as the ductus arteriosus closes over the first hours of life. The degree of cyanosis is determined by the severity of the obstruction. In patients with severe pulmonary stenosis or pulmonary atresia, severe cyanosis can occur rapidly, and is a life-threatening event. In that situation, the infant is considered to be “ductal dependent.” Prostaglandin E1 is started immediately to reverse the problem. The typical hemodynamic status once the PDA is opened is illustrated in eFigure 498.6 .

• Systemic (aortic) obstruction: This can be below the aortic valve (subaortic stenosis), at the valve, in the aortic arch (hypoplasia or aortic arch interruption), or in the aortic isthmus between the left subclavian artery and ductus arteriosus (coarctation of the aorta). When the obstruction is critical, newborns are ductal dependent, meaning that patency of the ductus arteriosus is necessary to maintain adequate systemic blood flow.

• Atrioventricular obstruction: With a stenotic or atretic atrioventricular valve, restriction of flow between the two atria can be very deleterious. In the hypoplastic left heart syndrome, for example, restriction at the foramen ovale causes severe left atrial and pulmonary venous hypertension.

NATURAL HISTORY

The vast majority of the patients with single ventricle variants develop symptoms in the newborn period and early infancy. Patients with ductal dependent lesions need emergency intervention. Those with increased pulmonary blood flow may show signs of heart failure as the pulmonary vascular resistance drops, whereas those with decreased pulmonary blood flow have severe cyanosis. If not treated, death occurs in infancy in more than 50% of patients,12-14more than half occurring during the neonatal period.

Patients with increased pulmonary blood flow may develop irreversible pulmonary vascular changes after the first year of life, leading to a decrease in the Qp/Qs. As pulmonary blood flow decreases the symptoms of heart failure resolve, but progressively severe cyanosis appears. Typical complicating features related to cyanosis and polycythemia include stroke, renal dysfunction, scoliosis, and endocarditis. Patients eventually develop progressive ventricular dysfunction, arrhythmias, and worsening heart failure.

PHYSICAL EXAMINATION

Patients with single ventricle have variable physical examinations, depending on the presence or absence of associated pathology, particularly pulmonary or systemic obstruction.15

Pulmonary stenosis (decreased pulmonary blood flow): Variable cyanosis is present. On auscultation, there is a systolic ejection murmur of intensity and duration directly correlating with the amount of pulmonary blood flow, and inversely correlated with the severity of the pulmonary stenosis and level of cyanosis. The absence of a systolic ejection murmur may suggest pulmonary stenosis. A continuous murmur from a patent ductus or aortopulmonary collateral vessels may be present.

No pulmonary stenosis (increased pulmonary blood flow): With no pulmonary stenosis, patients tend to present with heart failure due to increased pulmonary blood flow, manifested by respiratory distress, diaphoresis, and poor weight gain.

FIGURE 498-2. Color diagram of hypoplastic left heart syndrome. The pulmonary venous return (red) mixes at the right atrial level with the systemic venous return (blue), to enter the right ventricle or main systemic pump, from which the blood will circulate to the pulmonary arteries and through the patent ductus arteriosus into the descending and in a retrograde fashion, into the ascending aorta. The arrows indicated the direction of the blood flow. (Reprinted from PedHeart Resource, 2010. Scientific Software Solutions. www.HeartPassport.com, with permission.)

Systemic outflow or aortic obstruction: In newborns, systemic obstruction presents typically with signs of hypoperfusion, including decreased peripheral pulses, duskiness, and, eventually, cardiovascular collapse. Findings specific to the level of obstruction may be found, particularly in the older infant with adequate systemic output.

Following surgical palliation cardiac examination depends on the procedure performed and the underlying anatomy. An aortopulmo-nary shunt is associated with a continuous murmur at the site of the shunt. The second heart sound is single after a modified Norwood procedure.16 Murmurs are frequently absent after the bidirectional Glenn and modified Fontan procedures, A blowing systolic murmur occurs in the setting of systemic atrioventricular valve regurgitation, whereas a systolic ejection murmur may indicate subvalvar or valvar aortic stenosis.

DIAGNOSTIC EVALUATION

During evaluation and follow-up, patients with single ventricle variants regularly undergo an electrocardiogram, echocardiogram, chest x-ray, and pulse oximetry. The results vary depending on the underlying anatomic variant. Some electrocardiographic and radiographic findings are pathognomonic of the condition. When children are over 7 years of age, cardio-pulmonary stress testing is also performed. Holter monitors are obtained every other year to evaluate the presence of silent arrhythmias. Cardiac magnetic resonance is ordered more and more often to evaluate anatomic and functional features in these patients. Cardiac catheterization continues to be generally performed prior to surgical procedures, and it is especially indicated when complications arise during follow-up with possible interventional transcatheter therapy to address specific abnormalities encountered (Table 498-1).

Diagnostic evaluation will help identify risk factors for surgical palliation (Table 498-2).

MANAGEMENT

MEDICAL MANAGEMENT

Prior to surgical intervention, newborns with ductal-dependent lesions are placed on prostaglandin E1 until surgery is performed. Newborns who do not have a ductal-dependent lesion but have pulmonary stenosis may have a good balance between systemic and pulmonary blood flow once the ductus arteriosus closes, and may be discharged without an initial surgical intervention. In the absence of an adequate degree of pulmonary stenosis, heart failure may develop, as discussed above. These patients may be managed with diuretics and afterload reduction, or pulmonary artery banding, particularly those patients without any pulmonary outflow obstruction.35,36

In order to balance pulmonary and systemic blood flow in the intensive care unit, the intensivist typically manipulates pulmonary vascular resistance, increasing it to minimize pulmonary blood flow and maintain systemic perfusion.12,37 This may be achieved either by using a closed hood to increase inspired and pulmonary vascular resistance, or by using a hypoxic or hypercarbic mixture, or by hypoventilation utilizing mechanical ventilation, sedation and paralysis. Supplemental oxygen and hyperventilation should be avoided, as well as any other factor that could lower the pulmonary vascular resistance. Additional medical management in the intensive care unit prior to surgery depends upon the patient’s condition. Common drugs used for inotropic support in the perioperative period include milrinone, low-dose dopamine, and epinephrine.12

Following Surgical Intervention

Significant alteration in physiology may occur with the surgical intervention, although the initial neonatal palliative procedures typically retains the same physiologic model of complete mixing and circulations in parallel. After stage II, the circulation is in series for the upper half of the body, but will not be completely in series until after stage III, the modified Fontan procedure. If the stage I palliation includes an aortopulmonary shunt, the patient is placed on low dose aspirin (3–5 mg/kg/day) as antiplatelet agent.15,16 Because a volume load persists after stage I palliation, the patient commonly receives diuretics, occasionally an afterload reducing agent (such as captopril), and occasionally digoxin to maximize ventricular function. Infants at this stage are typically in need of high-calorie formula, with very careful monitoring of weight gain.16 Respiratory syncytial virus (RSV) vaccination is warranted.

After stage II (bidirectional Glenn procedure) and stage III (Fontan procedure) patients are typically continued on afterload reduction and sometimes digoxin, but diuretics are often discontinued. Following stage II patients typically improve in growth parameters, and can be weaned from high-calorie feeds because of a more stable and efficient circulation—the single ventricle is volume downloaded because pulmonary blood flow is directly provided to the lungs, passively. However, other medical problems can present. For example, chronic hypertension of the upper-body venous circulation may cause pleural effusions and upper-body edema.

INTERVENTIONAL CARDIAC CATHETERIZATION

Interventions during cardiac catheterization are common in patients with single ventricle and these include coil embolization of venous anomalies24 or aortopulmonary collaterals,25 balloon dilation and/or stenting of branch pulmonary artery stenosis, pulmonary valvotomy or balloon dilation of coarctation of the aorta, closure of a prior surgical shunt, transcatheter closure of residual anterograde flow through the pulmonary valve, transcatheter closure of fenestration or baffle leaks, and so on (Table 498-1).

Table 498-1. “Abnormalities” in the Single Ventricle Circulation Obstructions

Table 498-2. Significant Risk Factors for a Fontan Procedure

Age < 1.5 years

Pulmonary vascular resistance > 3 indexed units

Mean pulmonary artery pressure > 18 mm Hg

Pulmonary artery hypoplasia or distortion

Moderate to severe systemic ventricular dysfunction

Ventricular end diastolic pressure > 12 mm Hg

Heterotaxy

Atrioventricular valve moderate or severe insufficiency

Lack of normal sinus rhythm (ie, sinus node dysfunction)

Subaortic stenosis

Arch obstruction

Pulmonary vein stenosis

Noncardiac issues that lead to an increase in pulmonary vascular resistance: living at high altitude, chronic airway obstruction, obesity

There are patients with single ventricle variants who still may not be candidates for single ventricle palliation, and for whom the only option is transplantation.

SURGICAL MANAGEMENT

Staged Surgical Palliation

The goals in the management of patients with single ventricle variants include protection of the pulmonary vasculature by avoiding elevation in pulmonary arterial blood flow and pressure, and preservation of ventricular function by minimizing volume and pressure overload.

First-Stage Palliation The early operative mortality in the newborn with single ventricle ranges from 8% to 25%, and depends on the specific lesion, the presence of hemodynamic compromise or organ dysfunction prior to surgery, and associated cardiac malformations.33 It is highest in patients who require complex surgery, such as aortic arch reconstruction or resection of subaortic stenosis, and in those with complex lesions such as patients with heterotaxy and associated anomalous pulmonary venous connections. Over the years the surgical mortality for stage I palliation in the form of Norwood procedure has continued to improve, as low as 12% for some centers and patient populations.42 However, there is a significant interstage mortality of up to 15%, mostly represented by sudden death.12

Patients with hypoplastic left heart syndrome undergo a modified Norwood procedure, which includes ascending aortic enlargement via modification of the Damus-Kaye-Stansel procedure, aortic arch augmentation, atrial septectomy, and either a Blalock-Taussig shunt or a right ventricle-to-pulmonary artery conduit (eFig. 498.16 ).3,46 The latter is a recent modification and is commonly referred to as the Sano modification34 (eFig. 498.25 ). It is thought to minimize the risk of interstage death because aortic diastolic pressure is higher, putatively decreasing the risk of coronary ischemia.

Second Stage Palliation: The Bidirectional Glenn Procedure Around 4 to 6 months of age, a bidirectional cavopulmonary anastomosis, or Glenn procedure, is performed.3,49 There is an immediate change in ventricular geometry following a bidirectional Glenn because of the decrease in ventricular volume and increase in the ventricular mass/volume ratio). This can lead to subaortic stenosis in certain single ventricle variants.47,48 Currently the surgical mortality following bidirectional Glenn procedure is less than 5%.

Third Stage Palliative Surgery: Fontan Procedure Complete separation of systemic venous return from the heart (total cavopulmonary bypass) is commonly called a modified Fontan procedure. Many modifications of the initial Fontan procedure have been proposed and performed. Originally, the anastomosis was created between the atrial appendage and the pulmonary artery, directly or by interposition of a conduit43,44 (Fig. 498-3). Later, the anastomosis was made at the roof of the right atrium medial to the entry point of the superior vena cava.50 Subsequently, the entry point of the superior vena cava was used at the site of anastomosis to the pulmonary artery and a baffle was used to direct blood within the right atrium to the superior vena cava and the pulmonary arteries (lateral tunnel).3,51 Currently, the extracardiac conduit is the preferred technique used in most centers3,52 (eFig. 498.19  and Fig. 498-3). Many surgeons prefer to add a fenestration or small hole (4 mm) within the Fontan pathway allowing right-to-left shunting to serve as a pop-off, lowering postoperative venous pressures.30 Patients with a fenestrated Fontan circulation typically have oxygen saturation in the high 80s to low 90s range. If the Fontan is unfenestrated, then the oxygen saturations are almost normal (the only source of desaturation comes from coronary venous return). Generally the Fontan procedure is performed in patients between ages 2 and 5 years, depending on the preference of the center.49

The surgical mortality of the Fontan procedure has improved significantly over the past 2 decades, to less than 5% currently.3,42,52-55 Unfortunately, recent reports suggest that a total cavopulmonary bypass, or the Fontan circulation, is not without long-term consequences.54,55 Estimated freedom from Fontan failure at 5 and 10 years has been reported in the order of 90% and 87%, respectively,42,53 with a continued risk of death of about 1% to 3% per year.

MORBIDITY AFTER SINGLE VENTRICLE PALLIATION

The total right heart bypass, or Fontan circulation, may become dysfunctional for various reasons:

a. Increase in the transpulmonary gradient: The difference between pulmonary arterial and pulmonary venous pressure is the transpulmonary pressure gradient and it should not exceed about 8 mmHg. Over time, it tends to increase in the Fontan patient due to deficient pulmonary arterial growth, pulmonary artery branch stenosis,60 chronic pulmonary micro or macro thromboembolism,61 or a progressive increase in pulmonary vascular resistance. This typically translates into increase in pulmonary arterial and systemic venous pressures. In these patients, oral anticoagulants should be routinely prescribed. The clinical manifestations of elevated systemic venous pressures are described below.

b. Myocardial failure: An increase in the systemic ventricular end diastolic pressure due to myocardial failure leads to an elevation in pulmonary venous pressure and subsequently in pulmonary arterial and systemic venous pressure. This can occur in hand with atrioventricular valve insufficiency.

c. Pulmonary venous obstruction: Pulmonary venous stenosis or extrinsic compression, or obstruction between the left and right atrium (in patients with hypo-plastic left heart syndrome) can also lead to elevated pulmonary venous and, subsequently, pulmonary arterial and systemic venous pressures.

d. Systemic venous pathway obstruction: If there is obstruction within the Fontan baffle or conduit, systemic venous hypertension will occur proximal to the obstruction.

Clinical manifestations of Fontan failure include peripheral edema, chronic pleural effusions, protein-losing enteropathy,62 decreased exercise tolerance, chronic atrial arrhythmias, and chronic cyanosis.

FIGURE 498-3. Color diagram of the hemodynamics after a Fontan procedure. There is no right to left shunting other than the small amount of coronary venous return). (Reprinted from PedHeart Resource, 2010. Scientific Software Solutions. www.HeartPassport.com, with permission.)

Cardiac catheterization may be indicated to evaluate hemodynamics with a particular focus on a possible, intervention to relieve right- or left-sided obstruction. Protein losing enteropathy occurs in up to 11% of the patients.62 They present with chronic diarrhea, hypoproteinemia, hypoalbuminemia, chronic edema, pleural effusions, ascites, pericardial effusions, and increase of the fecal alpha-1 antitrypsin. This problem is thought to be related to venous hypertension, although hemodynamic correlation is not always present. Medical management includes maximization of anticongestive therapy, and use of anticoagulation, steroids, all with limited success. The prognosis is poor, and thus, intervention is required. Creation of a Fontan fenestration is an option, to lower venous pressures. Heart transplantation may be indicated, but it is of increased risk.

Following staged surgical palliation sinus node dysfunction is reported to be as high as 37%.64

Supraventricular tachycardia in the form of atrial flutter is a serious problem following the Fontan procedure.65 Management includes antiarrhythmic drugs, pacemakers, and radiofrequency ablation, as well as Fontan redo.66

Patients with a Fontan circulation have mildly diminished functional capacity by ergometry to about 70% of the estimated functional capacity in association with mild desaturation and subnormal chronotropic response.59

Although limited reported experience demonstrated feasibility of a successful pregnancy in single ventricle mothers, there is significant morbidity and potential mortality related to it. Forty-five percent of pregnancies resulted in live births in a study of 33 pregnancies.67