Single Ventricle 

  • Author: Alvin J Chin, MD; Chief Editor: Stuart Berger, MD   more...
 
Updated: Nov 10, 2011
 

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, 2 (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 2 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 4 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.

Hepatic and biliary dysfunction, protein-losing enteropathy, and disadvantageous ejection efficiency combined with elevated after load[9] characterize Fontan-type circulation.[10] 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.[10] More detailed information about the technical aspects of the modified Fontan operation are available elsewhere.[10, 11]

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Pathophysiology

No circulatory derangement is observed in fetal development because pulmonary circulation and systemic circulation are normally in parallel, with 2 levels of connection: atrial and ductal. However, lack of separation between pulmonary and systemic circulations causes obvious cyanosis postnatally, with severity dependent on the degree of coexistent subpulmonary stenosis. Although cases of single ventricle and arch obstruction are the least cyanotic because they never display subpulmonary stenosis, such patients are vulnerable to poor lower body perfusion upon reduction in ductal diameter.

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Epidemiology

Frequency

United States

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

Mortality/Morbidity

The severity and timing of presentation depend on the extent of coexistent subpulmonary stenosis (or, alternatively, aortic obstruction) and on reduction in caliber of the ductus arteriosus.

Sex

No disparities are known.

Age

Presentation is generally within the first month of life. As the ductus arteriosus reduces in caliber within the first few days of life, those infants with severe subpulmonary stenosis or aortic obstruction present with cyanosis or poor peripheral perfusion, respectively.

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Contributor Information and Disclosures
Author

Alvin J Chin, MD  Professor of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Cardiology Division, Children's Hospital of Philadelphia

Alvin J Chin, MD, is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and Society for Developmental Biology

Disclosure: Nothing to disclose.

Specialty Editor Board

Juan Carlos Alejos, MD  Clinical Professor, Department of Pediatrics, Division of Cardiology, University of California, Los Angeles, David Geffen School of Medicine

Juan Carlos Alejos, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Medical Association, and International Society for Heart and Lung Transplantation

Disclosure: Actelion Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Ameeta Martin, MD  Clinical Associate Professor, Department of Pediatric Cardiology, University of Nebraska College of Medicine

Ameeta Martin, MD is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Gilbert Z Herzberg, MD  Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Consulting Staff, Department of Pediatrics, Sound Shore Medical Center

Gilbert Z Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD  Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin

Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions

Disclosure: Nothing to disclose.

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Cranially angulated frontal angiogram of an L-looped single left ventricle. Abbreviations are as follows: ao=aorta, mpa=main pulmonary artery, oc=outlet chamber (rudimentary right ventricle).
Long axial oblique-equivalent subcostal echocardiogram of single left ventricle (vent) with narrow communication (unlabeled arrow) between left ventricle and outlet chamber (oc). Abbreviations are as follows: L=left, lav=left atrioventricular valve, P=posterior, rav=right atrioventricular valve, S=superior.
Cardiac MRI. Frontal view of a 3-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.
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.
 
 
 
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