Continuing Education Activity

A single ventricle is a rare outcome of abnormal embryonic development, resulting in the anatomical or functional absence of one ventricular cavity. This malformation is life-threatening, necessitating quick correction. The exact etiology remains unclear, but genetic mutations and environmental factors may play crucial roles.

Risk factors include maternal diabetes, infections, and the intake of certain medications during pregnancy, to name a few. Symptoms typically manifest early, with cyanosis, difficulty breathing, and failure to thrive being common. Diagnosis relies on echocardiography, magnetic resonance imaging, or cardiac catheterization to assess ventricular structure and function. Management requires staged surgeries, like the Norwood procedure, to support systemic and pulmonary circulation, along with ongoing monitoring and possible heart transplantation in severe cases.

This activity is designed for healthcare professionals to enhance learners' competence in evaluating and managing single ventricles. Participants gain a deeper understanding of the condition's risk factors, pathophysiology, symptomatology, and best diagnostic and therapeutic approaches. Greater proficiency enables healthcare practitioners to collaborate effectively within an interprofessional team caring for patients with this condition.

Objectives:

• Identify the clinical features indicative of a single ventricle.
• Select appropriate diagnostic methods for evaluating suspected single ventricle cases.
• Implement individualized, evidence-based treatments for single ventricle cases.
• Apply effective strategies to improve care coordination among interprofessional team members to facilitate positive outcomes for patients with single ventricles.

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Introduction

A functionally univentricular heart, or single ventricle, as defined by Jacobs and Anderson, refers to a condition where 1 ventricle cannot adequately support either systemic or pulmonary circulation. Various anomalies, including hypoplastic left heart syndrome (HLHS) and tricuspid atresia, fall under this classification. The International Pediatric and Congenital Cardiac Code provides standardized terminology for these conditions. The anomalous structure often leads to the mixing of oxygenated and deoxygenated blood through various mechanisms. The condition is typically attributed to genetic factors, though environmental influences can contribute to malformations.

With congenital cardiothoracic surgery advancements, children born with a single ventricle can now live for decades to reach adulthood and beyond. The surgically created univentricular anatomy and physiology enable an orphan ventricle to support systemic circulation as pulmonary blood flows passively in the lungs, a configuration known as the Fontan circulation.

Etiology

The formation of univentricular hearts is attributed to multiple factors, each producing a different pathological type, though the mechanisms of their development are not entirely understood. Malformation occurs during embryogenesis on 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, 12% have evidence of heterotaxy.[4]

Other genetic causes have also been identified, including Tbx5 and GATA4 anomalies. The inactivation of both genes has a direct influence on the formation of the ventricular septum.[5][6] Genetic malformations without known causes have been linked to defects in endocardial cushion formation and the influence of dynamic blood flow during development. Such malformations are often associated with extracardiac structural abnormalities, as observed in conditions like DiGeorge syndrome.[7]

Parental factors linked to univentricular heart formation include the following:

• Increasing parental age [8]
• Maternal conditions such as phenylketonuria, pregestational diabetes, febrile illnesses, and infections like influenza and rubella
• Use of anticonvulsants, ibuprofen, sulfasalazine, thalidomide, trimethoprim-sulfonamide, retinoids, marijuana, and organic solvents [9]
• Lithium intake

Lithium exposure increases the risk of cardiac malformations, particularly with high doses or exposure during the first trimester.[10][11] Pregnant patients should be closely monitored to balance maternal benefits and fetal risks.

Key univentricular variations and typical features include the following:

• HLHS: The left ventricle, mitral valve, aortic valve, and aorta are underdeveloped.
• Tricuspid atresia: The tricuspid valve fails to form, leading to an underdeveloped right ventricle.
• Ebstein anomaly: Abnormal growth of the tricuspid valve leaflets causes right ventricular atrialization. This anomaly is associated with various cardiac structural abnormalities, including pulmonary valve pathologies, septal defects, and electrical conduction lesions.
• Double outlet right ventricle (DORV): The aorta and the pulmonary artery exit from the right ventricle, leaving the left ventricle underdeveloped.
• Double inlet left ventricle (DILV): 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.

The development of univentricular hearts stems from a complex interplay of genetic, environmental, and embryologic factors. Understanding the diverse etiologies underlying univentricular heart formation is essential for early diagnosis and genetic counseling.

Epidemiology

The occurrence of congenital heart disease is approximately between 8 and 12 in 1,000 live births.[12][13] HLHS, the most common form of univentricular heart disease, is seen in 2.6 per 10,000 births, with a higher incidence in male infants.[14][15] Tricuspid atresia occurs in about 1 per 10,000 live births.[16][17] Ebstein anomaly is observed in about 0.5 per 10,000 live births with a sex predilection.[18] However, with maternal use of lithium, the likelihood of Ebstein anomaly can increase nearly 7 times.[19] Double outlet right ventricle occurs in 0.009 cases per 10,000 live births.[20] Double inlet left ventricle is reported in up to 0.01 per 10,000 live births.[21] Atrioventricular canal defect is found in 0.03 to 0.04 per 10,000 live births.[22]

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, ventricular septal defect, or communication in the great arteries may be required to maintain pulmonary and systemic circulations. More information about the anatomical factors that improve survival for each type can be found in their respective StatPearls educational activities.

The Fontan procedure is a series of staged surgeries designed to manage blood flow in a univentricular heart and reduce ventricular strain. This technique ultimately redirects systemic venous blood to the pulmonary arteries without passing through the heart, creating a passive pulmonary circuit. In the short term, this approach can save lives with minimal impact on homeostasis. However, within 25 years, approximately half of all patients who undergo the Fontan procedure are expected to experience Fontan failure, characterized by circulatory dysfunction, reduced functional capacity [New York Heart Association (NYHA) class III or IV], takedown or conversion of the Fontan circuit, severe complications such as protein-losing enteropathy (PLE) and plastic bronchitis, the need for heart transplantation, or mortality.[23][24]

PLE is a severe and complex sequela of Fontan physiology that remains poorly understood. Development is believed to result from multiple factors, including chronically elevated systemic venous pressure, heightened mesenteric vascular resistance, reduced cardiac output, diastolic dysfunction, increased intestinal permeability, and abnormalities in the lymphatic system.[25]

History and Physical

A single ventricle may be identified as early as 18 to 24 weeks of gestation, although some major defects can be detected as early as 11 to 13 weeks.[26] Other structural abnormalities, such as mispositioning of the great arteries and reversal of blood flow in parts of the fetal cardiac system, may also be observed around this time. Ultrasound can detect extracardiac structural anomalies, aiding in diagnosis.[27][28]

Postnatal presentations vary based on underlying structural abnormalities. Signs such as a heart murmur, tachypnea, respiratory distress, cyanosis, or hypotension typically emerge when circulation and oxygenation become inadequate following closure of the ductus arteriosus.[29] Additional physical examination findings, including hepatomegaly or dysmorphic features, may suggest extracardiac involvement or syndromic associations.[30][31] A neonate may not show symptoms at birth or before discharge if circulation is sufficient at the time of examination. However, closure of the ductus arteriosus or changes in blood flow to vital organs may produce symptoms after discharge.

Evaluation

Prenatal diagnosis is made using routine ultrasound and fetal echocardiography, which can identify structural abnormalities or atypical blood flow patterns indicative of a single ventricle. Postnatal diagnosis relies primarily on echocardiography, the best modality for confirming a single ventricle. Additional diagnostic tools include electrocardiography, chest x-rays, and pulse oximetry, with physical examination findings providing further diagnostic clues.[32][33] Advanced imaging techniques, such as 3-dimensional ultrasound, spatiotemporal image correlation (STIC), and artificial intelligence-assisted methods, are emerging to improve diagnostic accuracy and support interprofessional planning.[34][35]

Treatment / Management

Management depends 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. Home monitoring and comprehensive caregiver understanding of the disease have become integral to standard care, particularly to improve outcomes during the vulnerable period between surgical palliation stages.[36]

Medical management of univentricular heart syndrome focuses on addressing the ramifications of the underlying pathology. Supplemental oxygen may be used to alleviate hypoxemia. Correctable factors contributing to acid-base or metabolic disturbances should be addressed.[37] Inhaled nitric oxide may reduce pulmonary vascular resistance, improving oxygenation by enhancing pulmonary blood flow.[38] Inotropic agents may be used to support ventricular contraction in cases of cardiac strain, though catecholamines should be avoided due to the risk of arrhythmogenesis.[39] When collateral flow depends on a PDA, prostaglandin E1 may be administered to maintain ductal patency as a temporary measure until definitive interventions are performed. Nonsteroidal anti-inflammatory drugs should be avoided to prevent premature PDA closure. 

The decision to render catheter-based management depends on the underlying etiology, timing of diagnosis, and prognosis. When identified in utero, catheter-based structural interventions or valvuloplasty can address anomalies early, potentially mitigating complications during development.[40][41][42] Many procedures may also be performed postnatally, although they have less influence on developmental progression. In conditions like Ebstein anomaly, associated pulmonary arteriovenous malformations may be treated using a transcatheter occlusion approach.[43]

Surgical intervention may also correct associated anatomical anomalies with techniques tailored to specific conditions. The Fontan procedure, a widely used approach, directs blood to the lungs by relying on central venous pressure and intrathoracic pressure reduction.[44] Optimal pressure dynamics and low pulmonary vascular resistance are critical for maintaining effective anterograde circulation.[45] Perioperative management and advances in surgical techniques have improved early and midterm outcomes, with operative mortality now approaching 1% and 10-year transplantation-free survival rates nearing 90% in contemporary series.[46] While the Fontan procedure has shown consistent success, it should not be viewed as the sole option, as other surgical strategies may be more appropriate, depending on the individual case. 

In patients with severe disease, palliative surgery is often the preferred approach over strictly comfort-focused measures.[47] Evidence remains inconclusive regarding the superiority of the Fontan procedure compared to other palliative options. Referral to tertiary care centers is recommended for specialized evaluation and management.[48] Cardiac transplantation may be considered, though it is associated with suboptimal outcomes due to comorbidities.[49][50] Transplantation may also become necessary despite prior surgical interventions.

Differential Diagnosis

Neonatal symptoms may appear immediately after birth or within a few days as the ductus arteriosus closes and collateral circulations diminish. The clinical presentation of congenital heart disease may be delayed, with symptoms such as cyanosis, tachypnea, or cardiovascular collapse appearing after 48 hours of life. Vigilant postnatal monitoring and screening before discharge are crucial. In infants with severe manifestations after delivery, the differential diagnoses should include sepsis, infantile respiratory distress syndrome, aortic or pulmonary disorders, and transposition of the great arteries.[51] Milder cases may not present until months or years later, detected only when growth is impaired. In such cases, infection, failure to thrive, and malnutrition should be investigated as potential causes.

Prognosis

HLHS is almost universally fatal without treatment. Recent population-based and institutional studies report 5- to 10-year survival rates after surgical intervention ranging from 55% to 65%, with some centers noting 10- and 20-year survival rates exceeding 90% in selected cohorts. However, these higher rates may reflect center-specific outcomes and patient selection. Survival to adolescence and young adulthood is increasingly common, with life expectancy beyond 18 years exceeding 90% among patients whose condition remains stable after the 1st year.[52][53][54][55] The American Heart Association recommends developmental evaluation for these patients, as neurodevelopmental issues may result from inadequate nutritional delivery.

Patients with tricuspid atresia generally have a favorable prognosis with intervention, with a 90% survival rate at 1 year and 80% at 10 years.[56][57] However, Ebstein anomaly has a high perinatal mortality, with up to 32% of live births expiring before discharge.[58] One-year and 10-year survival rates for Ebstein anomaly are 67% and 59%, respectively, with limited prognostic data available beyond 10 years.[59]

The prognosis for other causes of single ventricles varies by etiology. Nevertheless, more than half of the patients survive beyond 2 years, with an average lifespan of 30 to 40 years.[60]

After decades of successful single-heart palliative surgeries, specific sets of risk factors have been found to be associated with a bad prognosis. These risk factors include the following:

• Preoperative factors

  • Male sex [61]
  • Common atrioventricular valve [62]
  • HLHS
  • Mean pulmonary artery pressure greater than 16 mm Hg
• Intraoperative factors

  • Atriopulmonary Fontan [63]
  • Lack of septal fenestrations
  • Late intervention
  • Complicated procedure, eg, prolonged cross-clamp time [64]
• Postoperative factors

  • Early:

    • Fontan circulation pressure greater than 20 mm Hg
    • Unsettled chest drainage lasting longer than 3 weeks [65]
    • Ventricular filling pressure greater than 13 mm Hg
  • Late:

    • PLE [66]
    • Plastic bronchitis [67]
    • Reduced exercise capacity, as signified by a decreased peak VO2 [68]
    • Arrhythmias [69]
    • Need for pacing [70]

Notably, HLHS is not directly linked to increased mortality but is associated with a higher risk of late complications and Fontan failure.[71] Meanwhile, the absence of septal fenestrations and delayed intervention have been linked to an increased risk of PLE and plastic bronchitis.[72]

Complications

Single-ventricle heart syndromes are typically managed through direct surgical or interventional procedures, which can obscure the origins of some complications. The expected sequelae following correction of single-ventricle hearts include the following:

• Arrhythmias [73][74]
• Esophageal varices [75]
• Heart failure with thrombus formation and increased risk of bleeding from treatment [76][77]
• Greater risk of decompensation with anesthesia [78]
• Long-term cyanosis
• Restrictive and diffusion-limited lung disease [79][80]
• PLE [81][82]
• Recurrent laryngeal nerve injury [83]
• Reduced height and impaired somatic development [84]
• Renal dysfunction
• Systemic-to-pulmonary venous and systemic-to-pulmonary artery collaterals

Note that pulmonary disease in these patients may be partly attributable to subclinical plastic bronchitis and pulmonary embolism.[85] Such complications can contribute significantly to morbidity.

Recognition of the above sequelae underscores the importance of lifelong follow-up in patients with single-ventricle physiology. Multisystem involvement necessitates a holistic, interprofessional approach to care.

Consultations

Consultations with interventional specialists and thoracic surgeons should be made when the anomaly is discovered. Prompt referral enables timely intervention and ensures that patients and their families are fully informed about their options.

Deterrence and Patient Education

Intervention, whether medical or surgical, is not always the most appropriate or optimal choice. Detailed discussions about prognosis and potential outcomes should be held with family members. Clinicians should clearly explain that staged procedures may not be curative and that cardiac transplantation may be required in the future. If the condition is identified in utero, elective termination may be presented as an option during counseling. Additionally, living conditions should be addressed, especially for families residing at altitudes above 1,700 meters, as such environments may adversely affect long-term survival.[86]

Enhancing Healthcare Team Outcomes

The identification of a single ventricle can be made in utero or after birth. When made before birth, 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 a quick resolution. Overall, general practitioners should understand the severe impact of single ventricles on patients and their families, as well as their suboptimal prognoses, to guide decision-making.

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

Disclosure: Mohamed Alahmadi declares no relevant financial relationships with ineligible companies.

Disclosure: Laith Rhabneh declares no relevant financial relationships with ineligible companies.

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