Single Ventricle 

Updated: Aug 09, 2018
Author: Alvin J Chin, MD; Chief Editor: Howard S Weber, MD, FSCAI 

Overview

Background

Because hypoplastic left heart syndrome (eg, aortic atresia with mitral hypoplasia), pulmonary atresia with intact ventricular septum, and tricuspid atresia are discussed in other articles, this article considers the term "single ventricle" to apply to a double-inlet ventricle or common-inlet ventricle, two (or more, if a double-outlet atrium is also present) atrioventricular orifices, or a common atrioventricular orifice, opening into one ventricular chamber, respectively.

High-resolution analyses of early human embryonic development from Carnegie stages 13-23 (representing embryonic days 30-56)[1, 2] have confirmed at least two processes that must go awry to create double-inlet left ventricle (LV): failure of the common (unseptated) atrioventricular canal to move rightward from its "starting" alignment over the eventual LV at day 30 and the contemporaneous failure to form a normal ventricular septum. These two processes may be coupled in human heart development and appear to be independent of atrioventricular canal septation itself because newborns with common-inlet LV are exceedingly rare. Common-inlet right ventricle is uncommon and occurs mostly in the setting of heterotaxy syndrome.

In a remarkable set of experiments, the developmental biologist Benoit Bruneau and his colleagues uncovered the molecular basis for ventricular septum formation.[3] In humans and other mammals, expression of the T-box transcription factor Tbx5 correlates with the formation of the ventricular septum (high in the left ventricle and low in the right, with a sharp boundary of expression exactly at the location where the septum forms).[4] The Tbx5 homozygous null mouse dies at embryonic day 10.5 with a severely hypoplastic LV[5] along with many other defects, reflecting the crucial role this protein has in many aspects of embryonic development.

During early development in the turtle, an animal with only one ventricle, Tbx5 is expressed throughout its lone ventricular chamber.[3] To prove that the level of Tbx5 is causal of ventricular septum formation rather than merely correlative, Bruneau’s laboratory genetically engineered mice to express Tbx5 at a moderate level throughout the developing heart, as in turtles, instead of the normal steep left-right gradient. Offspring from these mice had only a "single ventricle;" although left-right differences in the ventricular expression of downstream genes such as Nppa (atrial natriuretic peptide) persisted, no ventricular septum formed.[3]

By mimicking the turtle pattern of Tbx5, these investigators had created mouse hearts that resembled turtle hearts. Therefore, a sharp line delineating an area of high expression of Tbx5 is critical to induce the formation of a ventricular septum, a precursor for the fashioning of two separate, specialized ventricular compartments. A similar single ventricle phenotype was found by Toshihiko Ogura’s laboratory when they misexpressed Tbx5 in the embryonic chick ventricle.[6]

See the image below.

A sharp left-right gradient in Tbx5 expression is A sharp left-right gradient in Tbx5 expression is required for the formation of the ventricular septum. Image from Zina Deretsky, National Science Foundation after Benoit Brueau, the Gladstone Institute of Cardiovascular Disease.

Until the early 1970s, surgical management did not include separating the pulmonary and systemic circulations. Attempts to septate patients with single ventricle[7] were abandoned by the early 1980s because the surgically placed patch did not grow and ventricular performance remained poor. Modifications of the procedure initially proposed in 1971 by Fontan for tricuspid atresia[8] have been widely adopted over the last four decades. These cavopulmonary or atriopulmonary modifications effectively channel the systemic venous blood directly into the pulmonary arteries. Whether the effect on overall quality of life is superior to that of the more limited palliations used before 1971 is still unclear.[9]

Hepatic and biliary dysfunction with possible cirrhosis, protein-losing enteropathy, and disadvantageous ejection efficiency combined with elevated after load[10] characterize Fontan-type circulation.[11] Other important sequelae include atrial tachyarrhythmias, short stature, thromboembolism, systemic venous-to-pulmonary venous collaterals, systemic artery-to-pulmonary artery collaterals, plastic bronchitis, and esophageal varices.[11] More detailed information about the technical aspects of the modified Fontan operation are available elsewhere.[11, 12]

Pathophysiology

No circulatory derangement is observed in fetal development, because pulmonary circulation and systemic circulation are normally in parallel, with two levels of connection: atrial and ductal. However, lack of separation between pulmonary and systemic circulations causes obvious cyanosis postnatally, with the severity dependent on the degree of coexistent pulmonary outflow tract obstruction. Cases of single ventricle with aortic arch obstruction are the least cyanotic because they never display pulmonary stenosis, although these patients develop poor lower body perfusion as the ductus arteriosus becomes constricted.

Etiology

The cause of single ventricle in humans is unknown.

To date, at least 10 targeted single-gene disruptions in mice have produced a right ventricular (RV) hypoplasia phenotype reminiscent of single left ventricle (LV). These disruptions include global nulls in Nkx2.5; Isl1 [13] ; Mef2c [14] ; dHand (also known as Hand2)[15] ; Fog-2 [16] ; Fgf8 hypomorph[17] ; Foxh1 [18] ; TGF β 2 [19] ; Bop [20] ; and Has2. [21]  The Fog -2 null also displays a common atrioventricular orifice situated almost entirely over the future LV (ie, common-inlet ventricle). Whether hypomorphic alleles of the homologous mutations in the human produce a single ventricle phenotype but do not result in embryonic lethality remains to be shown.

Ventricular-specific misexpression of Tbx5 (as discussed in the Background section[3, 6]  ) and myocardial-specific inactivation of GATA4 [22]  cause single ventricle.

Epidemiology

United States data

Single ventricle occurs in approximately 5 of every 100,000 live births.

Sex- and age-related demographics

No sex disparities are known.

Presentation is generally occurs within the first month of life, although this is dependent on the severity of pulmonary vs systemic outflow tract obstruction.

Prognosis

The majority of patients should survive 20 years. Patients with significant atrioventricular valve regurgitation have a demonstrably poorer outcome.

Treatments for single ventricle (which, as stated earlier in this article, does not include the entity of hypoplastic left heart syndrome) have been refined over the last 30 years, with improved outcomes into early adulthood.

Unlike hypoplastic left heart syndrome, in which the staged approach to reach a cavopulmonary circulation is clearly superior to performing only the first stage (Norwood procedure), the vast majority of patients with single ventricle have a morphologic left ventricle (LV), do not present in extremis, and are relatively stable over many years once initial palliation, including a systemic–to–pulmonary arterial shunt or pulmonary artery banding, is completed and balanced pulmonary/systemic flow ratio is achieved.

A retrospective study (2000-2011) comprising 368 infants with single ventricle who underwent a Norwood procedure and 118 who underwent aortopulmonary shunt operation found similar interstage mortality between the groups.[23]  Risk factors for interstage death in infants who underwent the shunt procedure were lower weight at surgery and the presence of arrhythmias compared to the surviving infants.

In another retrospective study (2012-2016) comprising 57 newborns who underwent hybrid stage 1 surgical palliation, interstage remissions were common (75%), with 17% a result of major adverse events.[24]  Interstage mortality was 7%.

Whether the cavopulmonary circulation matches or surpasses this quality of life over a 30-year period is still an open question.[25]  The long-term effect of a mean systemic venous pressure greater than 10 mm Hg is unknown in the pediatric population.

Morbidity/mortality

The severity and timing of presentation depend not only on the extent of coexistent pulmonary outflow tract stenosis (or, alternatively, aortic obstruction) but also on the reduction in caliber of the ductus arteriosus.[26]  The universal utilization of newborn pulse oximetry screening before discharge to home should aid in the identification of those neonates prior to symptom development.

Patients with single ventricles accompanied by genetic and extracardiac anomalies often have additional risk factors (eg, prematurity, low weight) and have a greater risk of prolonged recovery after first-stage palliation, as well as higher hospital and interstage mortality.[27]

Complications

Pleural effusions, pericardial effusions, ascites post Fontan procedure

Long considered the most agonizing early postoperative complication after Fontan completion, thoracic and abdominal effusions often persisted for weeks and frequently impaired cardiac output. Before the early 1990s, these complications threatened to preclude the application of Fontan's principle to the vast majority of patients with single ventricle.

Although the molecular and cellular basis of this complication remains a mystery, surgeons have begun using various less-than-complete Fontan operations as their final stage.[28]  The partial hepatic vein exclusion variation used by Lecompte and then by Norwood has largely been abandoned because more than 80% of patients developed intrahepatic venous collaterals that resulted in increasing right-to-left shunts.

Hence, the complete Fontan operation most widely used since the late 1990s is the fenestrated Fontan operation proposed by Laks. Early postoperative effusive complications are greatly reduced following the fenestrated Fontan (lateral tunnel or extracardiac conduit) likely secondary to a lower central venous pressure. However, arterial oxygen saturation is usually in the high 80s or low 90s, rather than the mid 90s seen after nonfenestrated Fontan. Moreover, whether the long-term outcome is superior if the fenestrations are closed in the first few postoperative years (spontaneous, surgical, or by catheter-delivered device) remains an unsettled issue.

Atrial tachyarrhythmias

This is the most prevalent of the numerous late complications following the various modifications of the Fontan operation and may be the heralding sign of hemodynamic deterioration. The basis for this complication is probably multifactorial,[29]  and its treatment can be complex because of the frequent coexistence of sinus node dysfunction. Surgical therapy appears to be superior to medical therapy.[30]

Current hypotheses for the etiology of the sinus node dysfunction center on surgical trauma to portions of the sinus node region or its blood supply.

As an alternative to the hemi-Fontan operation, use of the so-called bidirectional Glenn operation, followed subsequently by extracardiac conduit[31]  (rather than the lateral tunnel) placement, has failed to reduce the frequency of sinus node dysfunction. This may be because the demarcation of the sinus node region is not macroscopically evident; thus, attempts to avoid it (such as the bidirectional Glenn) may have been unsuccessful.

Cardiac magnetic resonance imaging. Frontal view o Cardiac magnetic resonance imaging. Frontal view of a three-dimensional flow field in a patient who has undergone a lateral tunnel type of modified Fontan operation (A). This surgical palliation for patients with only one functional ventricle redirects venous blood from the superior vena cava (SVC) and inferior vena cava (IVC) directly into the right (RPA) and left (LPA) pulmonary arteries. Flow streamlines are shown in red. (B.) Frontal view of in plane velocity mapping. Right (R jug) and left (L jug) jugular vein flow towards the feet is signal-poor (black). Flow toward the head in the infrahepatic inferior vena cava (IVC) and intracardiac portion of the systemic venous pathway (svp) is signal-intense (white). Images courtesy of Dr. Mark A Fogel, The Children's Hospital of Philadelphia.

Because the onset of atrial tachyarrhythmia episodes is frequently preceded, if not invariably preceded, by months or years of atrial bradycardia, prophylactic atrial pacing may possibly postpone the emergence of these arrhythmias. Because of the technical challenges of atrial pacing in infants, this proposal has not yet been the subject of a randomized clinical trial.

Hepatic and biliary dysfunction[32, 33]

Liver dysfunction may actually be the underlying etiology for several of the complications listed below (eg, thromboembolism, varices and other venous-to-venous collaterals, thrombocytopenia)

Biliary sludge is the most common finding on gallbladder ultrasonography.

Sinusoidal and portal fibrosis are both seen on biopsy.[34]

Elevated factor VIII, prolonged PT, and elevated GGT are the most sensitive indicators, although other biomarker panels are also currently being evaluated.[35]

Thromboembolism

Venous, but not arterial, thrombosis occurs in nearly 10% of survivors of the fenestrated Fontan operation. The cause of this complication is unknown. Sites can include the pulmonary arteries and the cerebral veins.[36]  Subnormal cardiac output, subnormal intracardiac pulsatility of blood flow, and altered hepatic production of components of endogenous thrombolytic pathways have all been proposed as possible etiologies. Hepatic dysfunction, as measured by prothrombin time and galactose elimination half-life, is the rule.

Thrombi have been observed in both the pulmonary venous side of the "lateral tunnel" baffle and the systemic venous side. The presence of a fenestration allows thrombi in the systemic venous circulation to gain access to the systemic arterial circulation.

Aspirin is often prescribed as prophylaxis for venous thrombosis following fenestrated Fontan, and warfarin is gaining acceptance in patients for whom serial measurements of INR are feasible.[37]

Protein-losing enteropathy

Manifesting as diarrhea, poor appetite, or sometimes simply as growth failure, protein-losing enteropathy occurs in at least 10% of long-term survivors of Fontan procedures.

The cause of this usually devastating complication is unknown; however, enteric protein loss starts early after the Fontan operation and is compensated for by increased protein synthesis in the liver so that serum total protein and albumin levels remain in the normal range for a period of time.[38]  In fact, by the time the serum albumin falls out of the normal range, severe liver dysfunction has already occurred.

For those with little or no fenestration, fenestration creation (or dilation and stenting) appears to be the most consistently successful palliation, with the improvement sometimes lasting longer than a decade. Atrial pacing has succeeded in at least two cases. Other proposed remedies, including oral steroids and subcutaneous low molecular weight heparin, have succeeded in individual cases but have more numerous adverse effects such as osteopenia. Reduction of both CD4+ and CD8+ T lymphocytes is observed; disproportionate reduction of the CD4+ subset results in a reversal of the CD4+/CD8+ ratio. Immunoglobulin G (IgG) levels and, to a lesser extent, immunoglobulin A (IgA) levels are diminished.[39]

Not observed in the pre-1980 era (when Fontan-type operations were rarely performed), protein-losing enteropathy is thus a result of surgically created cavopulmonary/atriopulmonary circulatory arrangements and is not merely a result of being born with a single ventricle heart.

Persistent discrete or long-segment narrowing of the pulmonary arteries

In the program of staged surgery to reach a fenestrated Fontan, distortions of the pulmonary arteries are not uncommon and should be alleviated either prior to the final stage in the catheterization laboratory or surgically at the time of the final stage.

The importance of identifying cases of Fontan-to-one-lung circulation[40]  lies in their vulnerability to the hemodynamic consequences of ipsilateral pulmonary insults. Moreover, 50% of patients with Fontan-to-one-lung circulation develop protein-losing enteropathy, arguing strongly that protein-losing enteropathy is a sequela of Fontan hemodynamics.[41]

Formation of venous collaterals and varices

Patients with single ventricle and the coexistence of interrupted inferior vena cava still have hepatic venous blood that drains to the pulmonary venous side of the circulation after a Kawashima variation of the Fontan procedure.

Collaterals can occasionally form, allowing venous blood from the upper part of the body to eventually reach the pulmonary venous side of the circulation in this subset of patients with single ventricle, as well as in others. Microscopic pulmonary arteriovenous fistulas may also develop in this setting, which is felt to be secondary to absent hepatic blood flow into the pulmonary circulation.

The increased right-to-left shunt can be identified by monitoring either pulse oximetry or hemoglobin levels.

Bronchial wall varices have been observed, possibly due to high superior vena cava pressure. Esophageal varices occur in patients with hepatic dysfunction and portal hypertension.

Low exercise capacity [42]

Although individual exceptions have been observed, the exercise capacity of patients who survive the Fontan procedure, even those with fenestrated variants, is subnormal.

The resting cardiac index is about 70%-80% of normal. Disadvantageous ejection efficiency is present, combined with elevated pulsatile and nonpulsatile components of ventricular afterload.[10]

Short stature

This is observed in patients who survive the Fontan operation even in the absence of documented protein-losing enteropathy. The molecular and cellular basis of this complication is unknown; however, low bone-specific alkaline phosphatase appears to increase when cardiac index is augmented. This suggests that reduced osteoblastic function from subnormal bone perfusion may be the culprit.[43]  Whether exogenous growth hormone ameliorates the subnormal growth (but with acceptable incidence of adverse effects) is not known.

Formation of pulmonary arteriovenous malformations

This complication of the hemi-Fontan operation and its variants sometimes resolves after the performance of a less-than-complete Fontan operation (of the lateral tunnel, extracardiac conduit, or hepatic vein exclusion varieties). Contrast echocardiography, which is best performed directly into the pulmonary arteries at the time of cardiac catheterization, appears to be a highly sensitive method of identifying pulmonary arteriovenous malformations.[44]

Plastic bronchitis

This is characterized by the development of mucinous bronchial casts. Palliation by atrial pacing,[45]  fenestration creation,[46]  or heart transplantation[47]  has been reported.

Formation of systemic-to-pulmonary arterial collaterals

Systemic artery-to-pulmonary artery collaterals can carry as much as 40% of the total ventricular output. Whether this is due to the arterial desaturation caused by the prior hemi-Fontan (or bidirectional Glenn) or by the surgically created fenestration is not yet known.[48]

Magnetic resonance imaging is a useful noninvasive diagnostic modality for screening and hemodynamic assessment; however, angiography is usually required for visualization and intervention.

Thrombocytopenia[49]

Whether this is due to deficient thrombopoietin, which is provided by the liver as well as by the kidney, is not yet known.[50]

Patient Education

Because the outcome of various modifications of Fontan operation includes a monotonically increasing prevalence of serious sequelae, discussion with families about prognoses are necessarily lengthy.

Although moderate altitude does not affect early survival after Fontan,[51]  living at an altitude of 1700 meters does impair long-term survival.[52]

If the initial identification of single ventricle is made in utero, then the possibility of pregnancy termination may also be introduced to family members.

Finally, the family should confront the possibility that cardiac transplantation may eventually be needed, even if the staged approach to achieve a fenestrated Fontan is the initial strategy adopted.

 

Presentation

History and Physical Examination

History

Neonates with single ventricle and severe pulmonary outflow tract obstruction become cyanotic but are usually without other symptoms. Neonates with single ventricle and systemic outflow tract or aortic arch obstruction may have rapid breathing, lethargy, and poor feeding.

Physical examination

Note the following:

  • Cyanosis is present in patients with severe pulmonary outflow tract stenosis.

  • Poor peripheral perfusion is evident in patients with single ventricle with severe systemic outflow tract or aortic obstruction.

  • If aortic obstruction involves coarctation or interruption, then a difference in blood pressure is observed between the right arm and a lower extremity, unless the right subclavian artery is aberrant.

  • The first heart sound is normal.

  • The second heart sound is frequently single.

  • A systolic ejection murmur is present in those with pulmonary or systemic outflow tract stenosis.

 

DDx

Diagnostic Considerations

Important considerations

It is important to recognize symptoms and signs of coexistent aortic arch obstruction.

Clinicians should also be able to recognize inadequately relieved subaortic stenosis, aortic stenosis, or both.

Children with single ventricle cardiac physiology often require airway evaluation and intervention, and those with high-risk cardiac procedures are at greater risk for recurrent laryngeal nerve injury.[53] The best predictor for need of a tracheostomy in these patients appears to be the presence of subglottic stenosis.[53]

Other problems to be considered

Also consider the following conditions when evaluating patients with suspected single ventricle:

  • Pulmonary stenosis or complex heart malformation with pulmonary stenosis as a component

  • Arch obstruction or complex heart malformation with aortic stenosis, arch obstruction, or both as a component

  • Neonatal sepsis

Differential Diagnoses

 

Workup

Laboratory Studies

No specific laboratory blood tests are required in the preoperative workup for single ventricle, although, in the near future, affordable whole-genome sequencing will likely be helpful.

Pulse oximetry or an arterial blood gas (ABG) measurement is frequently helpful in distinguishing between cases of single ventricle with severe pulmonary stenosis and those of single ventricle with arch obstruction, aortic stenosis, or both. For example, when prostaglandin E1 has not been administered, a partial pressure of oxygen (PaO2) of greater than 50 mm Hg lessens the likelihood that a newborn with single ventricle has significant pulmonary stenosis. However, this PaO2 is perfectly consistent with the presence of arch obstruction.

Following Fontan operation, fecal alpha1-antitrypsin measurement is crucial in surveillance for the complication of protein-losing enteropathy (PLE). Abnormalities in serum total protein and albumin are relatively late clues to PLE; because the liver is the sole site of endogenous albumin production, a low serum albumin level signifies the liver's inability to compensate for poor protein intake or excessive protein loss. Prolongation in the prothrombin time (a measure of hepatic synthetic function),[54] abnormally elevated gammaglutamyltranspeptidase, and a reduction in alkaline phosphatase levels (largely a reflection of osteoblastic activity in preadolescent children) are likely early clues to hepatic dysfunction, biliary dysfunction, and reduced bone formation, respectively.[43]

Imaging Studies

Two-dimensional echocardiography and Doppler analysis

Two-dimensional echocardiography is diagnostic for single ventricle. The presence or absence of pulmonary outflow tract stenosis, aortic arch obstruction, and aortic stenosis is easily delineated. The particular atrioventricular connection and ventriculoarterial alignment is also revealed in a straightforward manner.

The two most common forms of single ventricle are L-looped single left ventricle (LV) with transposition of the great arteries and subpulmonary stenosis (see the image below) and D-looped single LV with transposition of the great arteries and subpulmonary stenosis. The third most common form is L-looped single LV with transposition of the great arteries and aortic arch hypoplasia. The fourth most common form is D-looped single LV with normally aligned great arteries (ie, aorta from LV and pulmonary artery from outlet chamber), which is sometimes referred to as a Holmes heart.

Cranially angulated frontal angiogram of an L-loop Cranially angulated frontal angiogram of an L-looped single left ventricle (LV). ao = aorta, mpa = main pulmonary artery, oc = outlet chamber (rudimentary right ventricle).

In single LV with transposition of the great arteries and aortic arch obstruction, the (sub)aortic stenosis that frequently coexists is due to a narrowing at the communication between the LV and the rudimentary right ventricle (outlet chamber). See the image below. This orifice is frequently referred to as a bulboventricular foramen or outlet foramen.

Long axial oblique-equivalent subcostal echocardio Long axial oblique-equivalent subcostal echocardiogram of single left ventricle (vent) with narrow communication (unlabeled arrow) between the left ventricle and outlet chamber (oc). L = left, lav = left atrioventricular valve, P = posterior, rav = right atrioventricular valve, S = superior.

Echocardiography prior to initial surgery

This study is used for evaluation of the following:

  • Initial identification of single ventricle

  • Presence or absence of pulmonary outflow tract stenosis

  • Presence or absence of aortic arch obstruction

  • Presence or absence of narrowing of communication between normal-sized ventricle and rudimentary ventricle (bulboventricular foramen or ventricular septal defect)

  • Presence or absence of straddling AV valve (ie, the AV valve closer to the outlet chamber having attachments to the rim of the outlet foramen or actually within the outlet chamber): The presence of such attachments should be an absolute contraindication to surgical enlargement of the outlet foramen which might otherwise be contemplated in cases of late-onset "subaortic stenosis."

  • Presence or absence of atrioventricular valve regurgitation, which would have to be palliated prior to Fontan operation

  • Presence or absence of proximal pulmonary artery distortion

  • Ventricular performance

Echocardiography prior to hemi-Fontan (or bidirectional Glenn) operation

This study is used for evaluation of the following:

  • Presence or absence of proximal pulmonary artery distortion, either congenital or created inadvertently by prior pulmonary artery surgery

  • Presence or absence of bilateral superior vena cavas

  • Ventricular performance

Chest radiography

Chest radiography findings vary. In cases with pulmonary stenosis, the cardiac silhouette is normal to mildly enlarged. Pulmonary vascularity is not increased. In cases with arch obstruction, the cardiac silhouette is usually at least mildly enlarged. Pulmonary vascularity usually is increased.

Electrocardiography

Common findings include septal q wave in the right precordial leads (in cases of L-looped single LV) and a monotonous R/S pattern over the anterior precordium.

Holter monitoring

This is useful after a hemi-Fontan operation (or bidirectional Glenn operation) and is particularly helpful after a Fontan operation for surveillance of supraventricular arrhythmias,[55]  sick sinus syndrome, and conduction block.

Magnetic resonance imaging

This study is used for evaluation of the following:

  • Anatomy: Static, steady-state free precession (SSFP) bright blood images; double-inversion, dark blood images; half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences

  • Physiology: Stack of cines (short axis of ventricle, to analyze ventricular performance), cines of systemic venous pathway and pulmonary arteries

  • Velocity mapping of superior vena cava, inferior vena cava, branch pulmonary arteries, and aorta

  • Post–gadolinium injection, three-dimensional reconstruction, and viability imaging

Procedures

Cardiac catheterization is utilized for evaluating candidacy for Fontan operation, characterizing post-Fontan hemodynamics, and managing supraventricular arrhythmic complications. Interventional correction (balloon angioplasty or endovascular stenting) of pulmonary artery stenosis, recoarctation of the aorta, and embolization of collaterals vessels has become the procedure of choice in most patients. 

Postcatheterization precautions include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.

Complications may include rupture of blood vessels, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.

 

Treatment

Medical Care

Admit patients with single ventricles for testing and surgical intervention. Evaluation as an inpatient in an intensive care setting is advised for patients with single ventricle.

Administration of intravenous prostaglandin E1 soon after birth is indicated in patients with severe pulmonary outflow tract or aortic arch obstruction.

The need for introduction of an arterial line and assisted ventilation can be judged best from the initial arterial blood gas measurement.

Consultations

Consult with a pediatric cardiologist and a cardiothoracic surgeon.

Transfer

Transfer may be required for further diagnostic evaluation and surgical intervention.

Diet and activity

No special diet is required.

No activity restrictions are needed if coexistent subaortic (and/or aortic) hypoplasia has been successfully relieved.[56]

The resting cardiac index of patients prior to the Fontan operation is about 70%-80% of normal. Also, a limited ability to increase cardiac output typically results in decreased exercise capacity.

Surgical Care

Because the pulmonary vascular resistance gradually falls over the first few months of life, conversion to a cavopulmonary or atriopulmonary circulation cannot be safely accomplished in the first few days of life.

Presence of pulmonary outflow tract stenosis or aortic arch obstruction

If pulmonary stenosis is present, its severity dictates whether a systemic-to-pulmonary artery shunt is needed after ductal closure. If aortic arch obstruction is present instead, the most widely adopted approach is to reestablish unobstructed aortic arch flow and to limit pulmonary blood flow. As a way of limiting pulmonary blood flow, banding of the pulmonary artery has given way to other methods because most patients with arch obstruction have a narrow bulboventricular foramen.

Although it may not be initially restrictive, the bulboventricular foramen tends to reduce in diameter over time and may precipitously reduce in caliber following volume-unloading procedures, including pulmonary artery banding (as well as the hemi-Fontan and Fontan operations).

To avoid the possibility of hemodynamically important systemic outflow tract stenosis, a Norwood-type reconstruction (proximal pulmonary artery–to–aorta anastomosis) is currently favored. Enlarging the bulboventricular foramen by resection of muscle is hazardous because of the proximity of the conduction system and the frequent presence of atrioventricular valve attachments to the rim.

Physiologic sensitivity of infants palliated with Norwood-type procedure

The physiology of the infant palliated with a Norwood-type procedure has been widely observed to be relatively fragile, and this appears to be due to the diminutive native aorta, although this is not usually the case in single ventricle patients. Because coronary arterial flow is largely or, in the case of aortic valve atresia, totally dependent on retrograde aortic perfusion, the coexistent modified Blalock-Taussig shunt sets up a "diastolic steal" phenomenon, which is highly sensitive to changes in pulmonary vascular resistance. In fact, the mortality during the time between stage 1 and stage 2 has remained high for decades and is so high that some centers keep patients in the hospital for the entire interstage period.[57]

Creation of a cavopulmonary circulation

Creation of a cavopulmonary circulation is more safely accomplished in stages over 1-2 years because acute volume unloading is associated with an acute increase in ventricular wall thickness. This wall thickness increase markedly alters the diastolic performance of the single ventricle and can limit cardiac output. Because the cardiac output falls by a lesser amount, the hemi-Fontan procedure results in improved systemic blood flow (cardiac output) than the nonfenestrated "complete Fontan" procedure.[58]

The less-than-complete Fontan is currently viewed as the most favorable balance of nearly normal arterial oxygen saturation and the lowest frequency of effusive complications.[59] Thus, even the so-called "final" stage commonly takes the form of a fenestrated Fontan, in which virtually all of the vena caval blood is routed to the pulmonary arteries.

A solitary hole 4 mm in diameter or multiple holes 2-3 mm in diameter are placed in whatever structure separates the systemic venous pathway from the pulmonary venous pathway. In the latter style, eventual spontaneous closure is the rule; however, some of these patients subsequently develop protein-losing enteropathy and return for catheter or surgical creation of a stable fenestration.

An alternative less-than-complete Fontan involves partial hepatic vein exclusion. One hepatic vein, typically the left anterior hepatic vein, can be excluded from the systemic venous pathway when the baffle is placed. This excluded hepatic vein drains into the pulmonary venous pathway. Unfortunately, most patients with partial hepatic vein exclusion eventually return with right hepatic vein–to–left hepatic vein collaterals.

Cardiac transplantation

Cardiac transplantation is considered for patients who have undergone the Fontan operation and have developed serious complications and for patients whose hemodynamics make them poor candidates for Fontan operation.

Outpatient Monitoring

Following each stage of surgical reconstruction, echocardiographic and Doppler evaluation of hemodynamic adequacy should be performed.

After the Fontan operation, monitor for hepatic and biliary dysfunction (ie, measure prothrombin time [PT], gammaglutamyltranspeptidase [GGT], and factor VIII),[32]  supraventricular arrhythmias (Holter monitoring), short stature, and protein-losing enteropathy (monitor fecal alpha1-antitrypsin level). A focus of intensive research is the identification of particularly informative serum biomarkers.[60, 61]

If possible, perform morphologic assessment of the systemic and pulmonary venous pathways and the pulmonary artery architecture, as well as measurement of cardiac index, using MRI or cardiac catheterization.

Should effusive complications, which are common in the early period after a Fontan procedure, recur months or years later, a comprehensive search for a surgically correctable cause should be undertaken. Examples of such correctable etiologies are late-onset pulmonary venous obstruction and thrombosis of the left pulmonary artery.

Only after mechanical obstructions are ruled out should a classic protein-losing enteropathy workup be initiated.

Pulse oximetry that is lower than expected likely indicates the development of decompressing venous collaterals, micropulmonary arteriovenous fistulas, or baffle leaks within the Fontan lateral tunnel.

 

Medication

Medication Summary

Preoperatively, administer alprostadil (ie, intravenous [IV] prostaglandin E1). Early postoperatively, warfarin is largely protective against venous thrombosis; the optimal late postoperative anticoagulation regimen has not yet been determined. Angiotensin-converting enzyme inhibitors, although popularly utilized, have not been shown to improve resting or exercise cardiac index. 

The medical treatment of postoperative patients with supraventricular arrhythmias is frequently complex, because many patients who have undergone a Fontan operation have sinus node dysfunction and can only be safely administered antiarrhythmic agents if a pacemaker is placed first. Catheter versus surgical therapy for atrial tachyarrhythmias appears to be preferred over medical therapy.

Digoxin, furosemide, spironolactone, and sildenafil are all used in long-term survivors. Various "maintenance drug regimens" are empirically used for patients who have undergone a Fontan operation, including the following:

  • No medications

  • Furosemide

  • Spironolactone

  • Angiotensin-converting enzyme (ACE) inhibitor (ACEI)

  • Sildenafil

  • Digoxin

  • Warfarin (for the first 3 months after fenestrated Fontan)

  • Aspirin (although no evidence suggests this helps for prophylaxis of venous thrombosis)

  • Combinations of the above medications

In an analysis of the Pediatric Heart Network Infant Single Ventricle public use dataset to evaluate associations between digoxin and survival, transplant-free survival, and change in weight-for-age Z (WAZ) before superior cavopulmonary connection (SCPC) and at 14 months in a mixed group of infants with single ventricle, investigators did not find an association between digoxin and improved survival during the interstage or at 14 months in the mixed group, but they noted a trend toward improved interstage transplant-free survival in infants who underwent the Norwood procedure.[62] In addition, digoxin was associated with poorer weight gain.

Prostaglandins

Class Summary

Alprostadil (PGE1) is used for treatment of ductal-dependent cyanotic congenital heart disease, which is due to decreased pulmonary blood flow.

Alprostadil IV (Prostin VR)

Used to maintain patency of the ductus arteriosus in neonates with ductal–dependent congenital heart disease until surgery can be performed. Has direct vasodilatation action on the ductus arteriosus and vascular smooth muscle.

Anticoagulants

Class Summary

These agents prevent recurrent or ongoing thromboembolic occlusion.

Warfarin (Coumadin)

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3.

Angiotensin-converting enzyme (ACE) inhibitors

Class Summary

The pharmacologic effects result in a decrease in systemic vascular resistance, reducing blood pressure, preload, and afterload.

Enalapril (Vasotec)

Competitive inhibitor of angiotensin-converting enzyme. Reduces angiotensin II levels, decreasing aldosterone secretion.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Rapidly absorbed, but bioavailability is significantly reduced with food intake. It achieves a peak concentration in an hour and has a short half-life. The drug is cleared by the kidney. Impaired renal function requires reduction of dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min. Can be started at low dose and titrated upward as needed and as patient tolerates.

Lisinopril (Prinivil, Zestril)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Diuretic

Class Summary

These agents are indicated for management of edema.

Spironolactone (Aldactone)

For management of edema and hepatic congestion resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Aldosterone inhibitors help block the renin-angiotensin system and help prevent potassium loss in the distal tubules. The body conserves potassium, and less PO potassium supplementation is needed.

Phosphodiesterase (type 5) Enzyme Inhibitor

Class Summary

These agents decrease pulmonary arterial pressure by causing vasodilation in the pulmonary vasculature.

Sildenafil (Revatio)

Promotes selective smooth muscle relaxation in lung vasculature possibly by inhibiting phosphodiesterase type 5 (PDE5). This results in subsequent reduction of blood pressure in pulmonary arteries and increase in cardiac output.