children Review Single Ventricle—A Comprehensive Review P. Syamasundar Rao McGovern Medical School, University of Texas-Houston, Children’s Memorial Hermann Hospital, 6410 Fannin Street, UTPB Suite # 425, Houston, TX 77030, USA; [email protected] or [email protected]; Tel.: +1-713-500-5738; Fax: +1-713-500-5751 Abstract: In this paper, the author enumerates cardiac defects with a functionally single ventricle, summarizes single ventricle physiology, presents a summary of management strategies to address the single ventricle defects, goes over the steps of staged total cavo-pulmonary connection, cites the prevalence of inter-stage mortality, names the causes of inter-stage mortality, discusses strategies to address the inter-stage mortality, reviews post-Fontan issues, and introduces alternative approaches to Fontan circulation. Keywords: single ventricle; double-inlet left ventricle; hypoplastic left heart syndrome; tricuspid atresia; unbalanced atrioventricular septal defect; mitral atresia with normal aortic root; heterotaxy syndromes; Down syndrome; Fontan circulation; biventricular repair 1. Introduction The term “single ventricle” is generally utilized to describe any congenital heart defect (CHD) with one functioning ventricle, and these are: double-inlet left ventricle (DILV), single ventricle, common ventricle, and univentricular atrio-ventricular (AV) connection [1]. Other lesions, namely hypoplastic left heart syndrome (HLHS), tricuspid atresia, unbal- Citation: Rao, P.S. Single anced AV septal defect, mitral atresia with normal aortic root, and heterotaxy syndromes Ventricle—A Comprehensive Review. with one functioning ventricle may now be added to this group. The objectives of this Children 2021, 8, 441. https:// paper are to specify congenital heart defects with one functioning ventricle, describe single doi.org/10.3390/children8060441 ventricle physiology, present management strategies to address the single ventricle defects, cite the prevalence of and name the causes of inter-stage mortality, discuss strategies to Academic Editor: Bibhuti B. Das address the inter-stage mortality, review post-Fontan issues, and to introduce alternative approaches to Fontan palliation. Received: 28 April 2021 Accepted: 21 May 2021 2. Cardiac Defects with Functionally Single Ventricle Published: 24 May 2021 As mentioned above, there are number of cardiac defects that have a functionally single ventricle and are candidates for single ventricle/Fontan repair. These will be described Publisher’s Note: MDPI stays neutral briefly. The order of presentation is arbitrary. with regard to jurisdictional claims in published maps and institutional affil- 2.1. Hypoplastic Left Heart Syndrome iations. The phrase “HLHS” was first suggested by Noonan and Nadas [2] to characterize a very small left ventricle with poorly developed aortic and mitral valves. The left ventricle (LV) is usually a slit-like cavity (Figure1) with thick muscle, especially when mitral atresia co-exists. The aortic valve is atretic or markedly narrowed with annular hypoplasia. Copyright: © 2021 by the author. Similarly, the mitral valve is markedly stenotic, hypoplastic or atretic (Figure1). The LV Licensee MDPI, Basel, Switzerland. is very small when the mitral valve is open. Endocardial fibroelastosis is often present. This article is an open access article Hypoplasia of the ascending aorta is present, and its diameter is usually 2–3 mm (Figure2). distributed under the terms and However, it is adequate to supply ample coronary blood flow retrogradely. The left atrium conditions of the Creative Commons is very small (Figure1). The interatrial septum is usually thickened with a small patent Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ foramen ovale (PFO) and rarely the atrial septum is intact. A patent ductus arteriosus 4.0/). (PDA) is classically present and is necessary for the baby to survive [3–5]. Children 2021, 8, 441. https://doi.org/10.3390/children8060441 https://www.mdpi.com/journal/children Children 2021, 8, x FOR PEER REVIEW 2 of 32 Children 2021, 8, x FOR PEER REVIEW 2 of 32 Children 2021, 8, 441 2 of 31 small patent foramen ovale (PFO) and rarely the atrial septum is intact. A patent ductus small patent foramen ovale (PFO) and rarely the atrial septum is intact. A patent ductus arteriosus (PDA) is classically present and is necessary for the baby to survive [3–5]. arteriosus (PDA) is classically present and is necessary for the baby to survive [3–5]. FigureFigure 1. 1.Echocardiogram Echocardiogram in anin an apical apical 4-chamber 4-chamber view view of a babyof a baby with hypoplasticwith hypoplastic left heart left syn- heart syn- Figure 1. Echocardiogram in an apical 4-chamber view of a baby with hypoplastic left heart syn- drome,drome, showing showing a strikingly a strikingly small, small, slit-like slit- (thicklike (thick arrow) arrow) left ventricle left ventricle (LV), obviously (LV), obviously enlarged andenlarged and drome, showing a strikingly small, slit-like (thick arrow) left ventricle (LV), obviously enlarged and hypertrophiedhypertrophied right right ventricle ventricle (RV), (RV), and and a dilated a dilated right right atrium atrium (RA). The(RA). atretic The atretic mitral valvemitral (MV) valve (MV) hypertrophied right ventricle (RV), and a dilated right atrium (RA). The atretic mitral valve (MV) (thin(thin arrow) arrow) and and hypoplastic hypoplastic left atriumleft atrium (LA) are(LA) also are seen. also seen. (thin arrow) and hypoplastic left atrium (LA) are also seen. Figure 2. Echocardiogram in a parasternal long short axis view of a baby with hypoplastic left heart FiguresyndromeFigure 2. 2.Echocardiogram Echocardiogram illustrates a small in a in parasternal lefta parasternal ventricle long (LV), shortlong axisashort severely view axis of viewhypoplastic a baby of witha baby hypoplasticaorta with (Ao) hypoplastic left(arrow heart), andleft heartan syndromeenlargedsyndrome illustratesright illustrates ventricle a small a small (RV). left left ventricleLA, ventricle left atrium. (LV), (LV), a severely a severely hypoplastic hypoplastic aorta (Ao) aorta (arrow), (Ao) (arrow and an), and an enlargedenlarged right right ventricle ventricle (RV). (RV). LA, leftLA, atrium. left atrium. 2.2. Tricuspid Atresia 2.2.2.2. Tricuspid Tricuspid Atresia Atresia Tricuspid atresia (TA) is a cyanotic CHD and is characterized as a congenital ab- TricuspidTricuspid atresia atresia (TA) (TA) is a cyanotic is a cyanotic CHD and CHD is characterized and is characterized as a congenital as a absence congenital ab- orsence agenesis or agenesis of the morphologic of the morphologic tricuspid valvetricuspid [6,7]. valve The right [6,7]. atrium The right is dilated atrium and is thedilated and sence or agenesis of the morphologic tricuspid valve [6,7]. The right atrium is dilated and tricuspidthe tricuspid valve isvalve atretic is (Figure atretic3). (Figure In the most 3). commonIn the most muscular common variety, muscular atretic tricuspid variety, atretic the tricuspid valve is atretic (Figure 3). In the most common muscular variety, atretic valvetricuspid is seen valve as a localizedis seen as fibrous a localized thickening fibrous or a dimple thickening in the or floor a dimple of the right in the atrium floor of the tricuspid valve is seen as a localized fibrous thickening or a dimple in the floor of the atright the anticipatedatrium at the site anticipated of the tricuspid site valveof the [ 8tricuspid–12]. An atrialvalve septal[8–12]. defect An atrial is necessary septal defect is right atrium at the anticipated site of the tricuspid valve [8–12]. An atrial septal defect is fornecessary survival for and survival is typically and a stretchedis typically PFO. a stretched The mitral PFO. valve The is usually mitral bicuspid valve is and usually bi- morphologicallynecessary for survival a mitral valve. and is The typically LV is evidently a stretched a morphological PFO. The LV,mitral but it valve is enlarged is usually bi- cuspid and morphologically a mitral valve. The LV is evidently a morphological LV, but cuspid and morphologically a mitral valve. The LV is evidently a morphological LV, but it is enlarged and hypertrophied [8–12]. Usually, a ventricular septal defect (VSD) is it is enlarged and hypertrophied [8–12]. Usually, a ventricular septal defect (VSD) is present. The VSD is most commonly in the muscular ventricular septum [13,14]. The present. The VSD is most commonly in the muscular ventricular septum [13,14]. The Children 2021, 8, 441 3 of 31 Children 2021, 8, x FOR PEER REVIEW 3 of 32 and hypertrophied [8–12]. Usually, a ventricular septal defect (VSD) is present. The VSD is most commonly in the muscular ventricular septum [13,14]. The right ventricle (RV) isright hypoplastic ventricle and (RV) is not is hypoplastic sufficiently large and inis not size sufficiently to support pulmonary large in size circulation. to support The pulmo- originnary ofcirculation. great arteries The is origin variable of andgreat on arteries the basis is ofvariable which aand classification on the basis of this of which disease a clas- entitysification was developed of this disease [6]: Type entity I, normally was developed related great [6]: Type arteries; I, normally Type II, d-transposition related great arteries; of theType great II, arteries; d-transposition Type III, malpositions of the great of arteries; the great Type arteries III, other malpositions than d-transposition; of the great and arteries Typeother IV,