Continuing Education Activity

A single ventricle is an uncommon occurrence in embryogenesis, which results in the anatomical or functional loss of a ventricular cavity. These malformations are life-threatening and necessitate quick revision to correct. Prompt identification and goals of care discussions provide optimal outcomes for potential interventions. This activity reviews the evaluation and treatment of a single ventricle and explains the role of the interprofessional team in managing patients with this condition.

Objectives:

• Describe the etiology of a single ventricle.
• Review the common presentation of a patient with a single ventricle.
• Identify treatment considerations for patients with a single ventricle.
• Explain the importance of improving care coordination among the interprofessional team to improve outcomes for patients affected by a single ventricle.

Introduction

A single ventricle or univentricular heart is a broad term covering various cardiac structural abnormalities in which one ventricle is severely underdeveloped, or a ventricular septal wall did not form. Through various mechanisms, the anomalous structure typically results in the mixing of oxygenated and deoxygenated blood. Occurrences are generally caused by genetic factors, though environmental factors are known to promote malformation.

Etiology

The origin of each condition varies by type and is influenced by multiple factors. The development process for each variation is not entirely understood.

Malformation occurs in embryogenesis, during days 30 to 56 of gestation.[1][2] Cardiac structural abnormalities are commonly associated with lateralization disorders, such as situs inversus totalis and heterotaxy.[3] In patients with primary ciliary dyskinesia (PCD), 12% of patients had evidence of heterotaxy.[4] Other genetic causes have also been identified, including Tbx5 and GATA4; the inactivation of both genes has a direct influence on the formation of the ventricular septum.[5][6] Genetic malformations without explicitly known causes have also been postulated, suggestively induced by defects in the formation of endocardial cushions and developmental influence by dynamic blood flow. These other causes are associated with extracardiac structural anomalies, as seen in DiGeorge syndrome.[7]

 Environmental factors also influence cardiac structural formation. Risk factors include:

• Increasing parental age[8]
• Phenylketonuria, pregestational diabetes, febrile illnesses, influenza, maternal rubella, anticonvulsants, ibuprofen, sulfasalazine, thalidomide, trimethoprim-sulfonamide, retinoids, marijuana, and organic solvents[9]
• Lithium is associated with an increased risk of cardiac malformations, specifically at higher doses and with use during the first trimester[10][11]

 Key univentricular variations and typical features:

• Hypoplastic left heart syndrome (HLHS): The left ventricle, mitral valve, aortic valve, and aorta are underdeveloped.
• Tricuspid atresia: The tricuspid valve fails to develop, leading to an underdeveloped right ventricle.
• Ebstein anomaly: Abnormal development of tricuspid valve leaflets causes right ventricular atrialization. The anomaly is associated with various cardiac structural abnormalities, including pulmonary valve pathologies, septal defects, and electrical conduction lesions.
• Double outlet right ventricle: The aorta and the pulmonary artery exit from the right ventricle, leaving the left ventricle underdeveloped.
• Double inlet left ventricle: Both atria connect to the left ventricle, resulting in an underdeveloped right ventricle.
• Atrioventricular canal defect: An atrial or ventricular septal defect forms large enough to make a functionally single ventricle.

Epidemiology

The occurrence of congenital heart disease is between 6 and 13 in 1,000 live births.[12][13][14][15] Hypoplastic left heart syndrome, the most common form of univentricular heart disease, is seen in 2 to 3 per 10,000 births with a higher incidence in males.[12][16][17] Tricuspid atresia occurs in about 1 per 10,000 live births.[18][19] Ebstein anomaly occurs in about 0.5 per 10,000 live births with gender predilection.[20] However, with the maternal use of lithium, the Ebstein anomaly can increase nearly seven-fold.[21] Double outlet right ventricle occurs in 0.009 cases per 10,000 live births.[22] Double inlet left ventricle occurs in up to 0.01 per 10,000 live births.[23] Atrioventricular canal defect occurs in 0.03 to 0.04 per 10,000 live births.[24]

Pathophysiology

With a single ventricle, mixed oxygenated blood circulates throughout the body. Depending on the structural anomaly, a patent ductus arteriosus (PDA), atrial septal defect (ASD), ventricular septal defect (VSD), or communication in the great arteries may be required to maintain pulmonary and systemic circulations. More information about anatomical requirements can be found under each disease's respective chapters.

History and Physical

The presentation of a single ventricle may be identified as early as the 18th week of gestation.[25] Other structural variations may also be seen near this time, including mispositioning of the great arteries and reversal of blood flow through portions of the fetal cardiac system. Ultrasound may also reveal extracardiac structural manifestations, assisting in diagnosis.[26][27]

Post-natal presentations vary depending on underlying structural variations. Typically, a heart murmur, tachypnea, respiratory distress, cyanosis, or hypotension may be present when circulation and oxygenation are not satisfactory.[28][29] Other physical exam findings, such as hepatomegaly or dysmorphic features, may be clues to more underlying abnormalities. A neonate may not present symptoms at birth or before discharge if circulation is adequate at the time of examination.[19] Closure of the patent ductus arteriosus (PDA) or changes in flow to end organs may precipitate these symptoms after discharge.

Evaluation

Prenatal diagnosis is made through routine ultrasound techniques for gestation and fetal echocardiography. Visualization of structural abnormalities or deviations from standard flow patterns may distinguish a single ventricle in utero.

Post-natal diagnosis is made through a variety of techniques. Echocardiography is the best modality for the diagnosis of a single ventricle. Other techniques may aid in the diagnosis of a single ventricle, including electrocardiography, plain chest films, and pulse oximetry.[30][31] Physical exam findings may also support the diagnosis. Computed tomography (CT), cardiac catheterization, magnetic resonance imaging (MRI), and cardiac magnetic resonance imaging might also reveal a single ventricle but are typically reserved for indeterminant investigations or treatment.

Treatment / Management

Treatment options of the univentricular variants depend on the time of discovery, prognosis, and goals of care. Prognosis must be discussed in depth before proceeding with treatment, as an intervention may be futile in some instances.

Univentricular heart syndrome medical management is targeted to the underlying pathology. Supplemental oxygen will help alleviate hypoxemia, and acid-base or metabolic disturbances should have correctable factors mended.[32] Inhaled nitric oxide is beneficial to reduce resistance in the pulmonary vasculature, allowing more blood to be oxygenated by the lungs.[33] In strained hearts, inotropes may assist contraction force, but catecholamines should be avoided due to arrhythmogenesis.[34] When a patent ductus arteriosus (PDA) is needed to maintain collateral flow, prostaglandin E1 prolongs the opening of the ductus arteriosus, providing a bridge to permanent interventions.[32] Non-steroidal anti-inflammatory medications should be avoided to maintain a patent ductus arteriosus.

Catheter-based management is also based on underlying etiology, time of discovery, and prognosis. When discovered in utero, catheter-based structural interventions and valvuloplasty can mitigate sequala by correcting anomalies during the developmental process.[35][36][37] Many interventions can also be performed after delivery, though further development is less influenced. In Ebstein anomaly, associated pulmonary arteriovenous malformations can be occluded using a transcatheter approach.[38]

Surgical intervention can also correct any of the abovementioned anatomical variations, though technique varies by condition. The Fontan procedure, a popular choice for intervention, works by delivering blood to the lungs utilizing central venous pressure, and reduced intrathoracic pressure.[39] Optimal pressure dynamics with low pulmonary flow resistance allows for anterograde circulation.[40] Though reliably successful, the Fontan procedure should not be the only option considered. 

In patients with severe disease, palliative surgery may be the best option and is typically preferred over choosing strict comfort measures.[41] Data is unclear if the Fontan procedure is superior to palliative options.[42] Patients should be referred to tertiary care centers for specialized evaluation and treatment.[42] Cardiac transplantation may be considered, albeit associated with suboptimal outcomes due to comorbidities.[43][44] Cardiac transplantation may also be required despite previous alternative procedures.

Differential Diagnosis

The neonatal presentation may be seen emergently after birth or develop within a few days of delivery, as collateral circulations diminish. Emergent presentations after delivery should consider sepsis, infantile respiratory distress syndrome (IRDS), independent aortic and pulmonary disorders, and transposition of the great arteries.[45]

Less severe cases may present after a few months or years when growth rates are affected; infection, failure to thrive, and malnutrition etiologies should be considered.

Prognosis

Hypoplastic left heart syndrome is almost universally fatal if untreated but improves to 60% to 70% survival with partial revisions.[46][47][48] Patients alive beyond one year of age after surgical correction have a 90% chance of living to 18 years of age.[49] While survival is optimistic, regardless of the intervention performed, there is an increased risk of suboptimal neurodevelopment.[50][51] Consequently, the American Heart Association recommends developmental evaluation for patients, which may be caused by poor nutrition delivery.[52][53]

Patients with tricuspid atresia are typically better with intervention, noting 90% survival at one year of age and 80% survival at ten years.[54][55] Ebstein anomaly has high perinatal mortality, with up to 32% of live births expiring before discharge.[56] One-year and ten-year survival rates are 67% and 59%, respectively.[57] Limited prognostic data is available after ten years.

The prognosis for other causes of single ventricles vary by etiology; nevertheless, more than half survive two years with the average length of up to 30 to 40 years.[58]

Complications

Single ventricle heart syndromes are typically corrected through direct intervention, obfuscating the origin of certain complications. Expected complications of corrected single ventricle hearts are listed below:

• Arrhythmias[59][60][61]
• Esophageal varices[61]
• Heart failure with thrombus formation and increased risk of bleeding from treatment[62][63]
• Increased risk for decompensation with anesthesia[64]
• Long-term cyanosis[65]
• Restrictive and diffusion-limited lung disease.[66][67] Pulmonary diseases may be due in part to subclinical plastic bronchitis and subclinical pulmonary embolisms[68]
• Protein-losing enteropathy[69][70]
• Recurrent laryngeal nerve injury[71]
• Reduced height and somatic development[72]
• Renal dysfunction[65]
• Systemic venous-to-pulmonary venous and systemic artery-to-pulmonary artery collaterals[61]

Consultations

Consultations with interventional specialists and thoracic surgeons should be made when the anomaly is discovered. Prompt referral allows for earlier intervention with optimal informed consent.

Deterrence and Patient Education

Intervention is not always sensible or the best option. In-depth discussions about prognosis and outcomes should be discussed with family members. A specific expression that staged procedures may not be curative should be given, mentioning the possible need for cardiac transplantation in the future. If found in utero, elective termination may be necessary for the discussion of available options. Living conditions should also be discussed with patients. Families residing at altitudes higher than 1700 meters above sea level may impair long-term survival benefits.[73]

Enhancing Healthcare Team Outcomes

The identification of a single ventricle can be made in utero or after birth. When made in utero, healthcare teams must report this finding and begin goal discussions with the mother as soon as possible. When found emergently after delivery, healthcare employees need to work as an interprofessional team to provide an urgent resolution quickly. Overall, general practitioners should understand the severity of single ventricles and the suboptimal prognoses to guide decision-making better.

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

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Disclosure: Joseph Heaton declares no relevant financial relationships with ineligible companies.

Disclosure: Daniel Heller declares no relevant financial relationships with ineligible companies.