Hypoplastic left heart syndrome

Hypoplastic left heart syndrome

Hypoplastic left heart syndrome
Synonyms	Cyanotic heart disease - hypoplastic left heart<ref> Hypoplastic left heart syndrome: MedlinePlus Medical Encyclopedia(link). medlineplus.gov. </ref>
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Field
Symptoms
Complications
Onset
Duration
Types
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Diagnosis
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Treatment
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Prognosis
Frequency
Deaths

Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect in which the left side of the heart is severely underdeveloped. It may affect the left ventricle, aorta, aortic valve, or mitral valve.<ref>,

 The nomenclature, definition and classification of hypoplastic left heart syndrome, 
 Cardiology in the Young, 
 2006,
 Vol. 16(Issue: 4),
 pp. 339–368,
 DOI: 10.1017/s1047951106000291,
 PMID: 16839428,</ref>

Signs and symptoms

Infant with cyanosis due to hypoplastic left heart syndrome

Closing of the ductus arteriosus in a heart that is severely underdeveloped on the left results in cyanosis and respiratory distress which can progress to cardiogenic shock and death. The first symptoms are cyanosis that does not respond to oxygen administration or poor feeding. Peripheral pulses may be weak and extremities cool to the touch.<ref name=":12"> Fulton, David R.. Hypoplastic left heart syndrome(link). Up To Date.

October 26, 2017.

Accessed 2017-11-30.

</ref>

HLHS often co-occurs with low birth weight and premature birth.<ref name=":12" />

In neonates with a small atrial septal defect, termed "restrictive", there is inadequate mixing of oxygenated and deoxygenated blood. These neonates quickly decompensate and develop acidosis and cyanosis.<ref name=":12" />

On EKG, right axis deviation and right ventricular hypertrophy are common, but not indicative of HLHS. Chest x-ray may show a large heart (cardiomegaly) or increased pulmonary vasculature. Neonates with HLHS do not typically have a heart murmur, but in some cases, a pulmonary flow murmur or tricuspid regurgitation murmur may be audible.<ref name=":12" />

Co-occurring tricuspid regurgitation or right ventricular dysfunction can cause hepatomegaly to develop.<ref name=":12" />

Causes

Diagram of a healthy heart and one with hypoplastic left heart syndrome

There is no known cause in the majority of HLHS cases.<ref name="Barron2009">Barron, D. J., Kilby, M. D., Davies, B., Wright, J. G., Jones, T. J., & Brawn, W. J.,

 Hypoplastic left heart syndrome, 
 The Lancet, 
 2009,
 Vol. 374(Issue: 9689),
 pp. 551–564,
 DOI: 10.1016/s0140-6736(09)60563-8,
 PMID: 19683641,</ref> Some cases may have a genetic component, as HLHS has been shown to be heritable and associated with specific gene mutations.<ref>Hinton, R. B., Martin, L. J., Tabangin, M. E., Mazwi, M. L., Cripe, L. H., & Benson, D. W., 
 Hypoplastic left heart syndrome is heritable, 
 Journal of the American College of Cardiology, 
 2007,
 Vol. 50(Issue: 16),
 pp. 1590–1595,
 DOI: 10.1016/j.jacc.2007.07.021,
 PMID: 17936159,</ref><ref name="pmid11470490">, 
 Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE), 
 Mutat. Res., 
 2001,
 Vol. 479(Issue: 1–2),
 pp. 173–86,
 DOI: 10.1016/S0027-5107(01)00160-9,
 PMID: 11470490,</ref>

Not all, but some, cases of aortic stenosis in a fetus can put stress on the left ventricle in utero, that can eventually lead to decreased perfusion and stop the growth of the left ventricle. <ref name=":4">Schidlow, David N.,

 Fetal interventions for structural heart disease, 
 Echocardiography, 
 
 Vol. 34(Issue: 12),
 pp. 1834–1841,
 DOI: 10.1111/echo.13667,
 
 
 
 Full text,</ref>

Environmental causes

In a retrospective analysis of over 1,300 newborns (born between 1996 and 2006) from 24 children’s hospitals in the United States, researchers at Cincinnati Children’s Hospital in Ohio found that babies with HLHS were more likely to be born in summer months, suggesting that seasonality and environmental factors may play a significant role in causation.<ref>,

 Seasonality of hypoplastic left heart syndrome in the United States: a 10-year time-series analysis, 
 J. Thorac. Cardiovasc. Surg., 
 
 Vol. 141(Issue: 2),
 pp. 432–8,
 DOI: 10.1016/j.jtcvs.2010.06.060,
 PMID: 20817208,</ref>

Genetics

Genetic loci associated with HLHS include GJA1 (connexin 43), HAND1, NKX2.5, 10q22, and 6q23.<ref name=":1" /><ref name="HLHS Review 2012 Feinstein">,

 Hypoplastic left heart syndrome: current considerations and expectations, 
 Journal of the American College of Cardiology, 
 
 Vol. 59(Issue: 1 Suppl),
 pp. S1–42,
 DOI: 10.1016/j.jacc.2011.09.022,
 PMID: 22192720,
 PMC: 6110391,</ref><ref>Hinton, R. B., Martin, L. J., Rame-Gowda, S., Tabangin, M. E., Cripe, L. H., & Benson, D. W., 
 Hypoplastic left heart syndrome links to chromosomes 10q and 6q and is genetically related to bicuspid aortic valve, 
 Journal of the American College of Cardiology, 
 2009,
 Vol. 53(Issue: 12),
 pp. 1065–1071,
 DOI: 10.1016/j.jacc.2008.12.023,
 PMID: 19298921,
 PMC: 2703749,</ref> There is a slight risk of recurrence in future pregnancies, estimated to be 2-4%, which increases to 25% in families with two affected children.<ref name="Barron2009"/> This is thought to be mediated by genetic mutations with incomplete penetrance.<ref name=":1" />

HLHS is also associated with several genetic syndromes, including trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), partial trisomy 9, Turner's syndrome (XO), Jacobsen syndrome (11q deletion syndrome), Holt-Oram syndrome, and Smith-Lemli-Opitz syndrome.<ref name=":1" /><ref name="HLHS Review 2012 Feinstein" />

Risk factors

Presence of a cystic hygroma increases the risk of HLHS in a fetus.<ref name=":2">F. Gary,

 Williams Obstetrics, 
 24 edition, 
 New York, NY:McGraw-Hill Education,</ref>

Pathophysiology

At birth, the ductus arteriosus is still open, and there is higher than normal resistance to blood flow in the lungs. This allows for adequate oxygenation via mixing between the atria and a normal appearance at birth. When the ductus begins to close and pulmonary vascular resistance decreases, blood flow through the ductus is restricted and flow to the lungs is increased. <ref name=":12" />

In typical anatomy, the left side of the heart receives oxygen-rich blood from the lungs and pumps it to the rest of the body. In people with HLHS, the aorta and left ventricle are underdeveloped (beginning in utero),<ref>Galindo, A., Nieto, O., Villagrá, S., Grañeras, A., Herraiz, I., & Mendoza, A.,

 Hypoplastic left heart syndrome diagnosed in fetal life: associated findings, pregnancy outcome and results of palliative surgery, 
 Ultrasound in Obstetrics & Gynecology, 
 2009,
 Vol. 33(Issue: 5),
 pp. 560–566,
 DOI: 10.1002/uog.6355,
 PMID: 19367583,</ref> and the aortic and mitral valves are either too small to allow sufficient blood flow or are atretic (closed) altogether.<ref>

Burns, Paul Burns and Jasper. Hypoplastic Left Heart Syndrome | Congenital Heart Disease - Cove Point Foundation | Johns Hopkins Children's Hospital(link). www.pted.org.

Accessed 2017-11-30.

</ref> As blood returns from the lungs to the left atrium, it cannot be pumped to the rest of the body by the left ventricle. The neonate is reliant on blood flowing through an atrial septal defect to mix oxygenated and deoxygenated blood, and on a patent ductus arteriosus to allow blood to reach the aorta and the systemic circulation via the right ventricle. This is what defines HLHS as a "single ventricle" defect.<ref name=":1" />

Due to the underdevelopment of the left side of the heart in utero, the increased afterload causes hypertension of the left atrium, pulmonary edema, and therefore lung damage to the fetus before birth. <ref name=":4" />

Diagnosis

Hypoplastic left heart syndrome can be diagnosed prenatally or after birth via echocardiography. Typical findings include a small left ventricle and aorta, abnormalities of the mitral and aortic valves, retrograde flow in the transverse arch of the aorta, and left-to-right flow between the atria. It is often recognized during the second trimester of pregnancy, between 18 and 24 weeks' gestation.<ref name=":12" />

Management

Medical

Without life-prolonging interventions, HLHS is fatal, but with intervention, an infant may survive. A cardiothoracic surgeon may perform a series of operations or a full heart transplant. While surgical intervention has emerged as the standard of care in the United States, other national health systems, notably in France, approach diagnosis of HLHS in a more conservative manner, with an emphasis on termination of pregnancy or compassionate care after delivery.<ref name="pmid22397767">,

 Hypoplasies sévères du ventricule gauche : soins palliatifs après un diagnostic prénatal, 
 Archives de pediatrie, 
 
 Vol. 19(Issue: 4),
 pp. 374–380,
 DOI: 10.1016/j.arcped.2012.01.022,
 PMID: 22397767,</ref>

Before surgery, the ductus must be kept open to allow blood-flow using medication containing prostaglandin. Air with less oxygen than normal is used for infants with hypoplastic left heart syndrome. These low oxygen levels increases the pulmonary vascular resistance (PVR) and thus improve blood flow to the rest of the body due to the greater pressure difference between the lungs and body. Achieving oxygen levels below atmosphere requires the use of inhaled nitrogen.<ref name="pmid12881932">,

 The physiologic basis for and nursing considerations in the use of subatmospheric concentrations of oxygen in HLHS, 
 Advances in Neonatal Care, 
 
 Vol. 2(Issue: 4),
 pp. 177–86,
 DOI: 10.1053/adnc.2002.33542,
 PMID: 12881932,</ref> Nitric oxide is a potent pulmonary vasodilator, and thus reduces PVR and improves venous return. Any factor that increases PVR will impede right sided flow.<ref>, 
 Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation, 
 Circulation, 
 2003,
 Vol. 107(Issue: 25),
 pp. 3204–3208,
 DOI: 10.1161/01.cir.0000074210.49434.40,
 PMID: 12821557,</ref><ref>Norwood W. I., 
 Hypoplastic left heart syndrome. The, 
 Annals of Thoracic Surgery, 
 1991,
 Vol. 52(Issue: 3),
 pp. 688–695,
 DOI: 10.1016/0003-4975(91)90978-y,
 PMID: 1898174,</ref>

Surgical

Surgical operations to assist with hypoplastic left heart are complex and need to be individualized for each patient. A cardiologist must assess all medical and surgical options on a case-by-case basis.

Currently, infants undergo either the staged reconstructive surgery (Norwood or Sano procedure within a few days of birth, Glenn or Hemi-Fontan procedure at 3 to 6 months of age, and the Fontan procedure at 1 1/2 to 5 years of age) or cardiac transplantation.<ref>Hypoplastic Left Heart Syndrome (HLHS) | The Children's Hospital of Philadelphia</ref> Current expectations are that 70% of those with HLHS may reach adulthood.<ref name="HLHS Review 2012 Feinstein" /> Many studies show that the higher the volume (number of surgeries performed) at a hospital, the lower the mortality (death) rate.<ref name="pmid20136852">McHugh, KE,

 Three-stage palliation of hypoplastic left heart syndrome in the University HealthSystem Consortium, 
 Congenital Heart Disease, 
 
 Vol. 5(Issue: 1),
 pp. 8–15,
 DOI: 10.1111/j.1747-0803.2009.00367.x,
 PMID: 20136852,</ref><ref name="pmid18080151">Hirsch, JC, 
 Hospital mortality for Norwood and arterial switch operations as a function of institutional volume, 
 Pediatric Cardiology, 
 
 Vol. 29(Issue: 4),
 pp. 713–7,
 DOI: 10.1007/s00246-007-9171-2,
 PMID: 18080151,</ref> Factors that increase an infant's risk include lower birth weight, additional congenital anomalies, a genetic syndrome or those with a highly restrictive atrial septum.<ref name=":3">Vojtovič, P., 
 Long-term results of children operated for hypoplastic left heart syndrome in Children's Heart Centre, 
 Cor et Vasa, 
 
 Vol. 56(Issue: 6),
 pp. e449–e455,
 DOI: 10.1016/j.crvasa.2014.07.006,</ref>) For patients without these additional risk factors, 5 year survival now approaches 80%.<ref name=":3" />  Studies show that about 75% of those children who survive surgery show developmental delays in one or more areas, such as motor, cognitive, or language impairments, with about a third of single-ventricle children without a genetic syndrome having significant impairments.<ref>Mussatto, Kathleen A., 
 Risk and prevalence of developmental delay in young children with congenital heart disease, 
 Pediatrics, 
 
 Vol. 133(Issue: 3),
 pp. e570–577,
 DOI: 10.1542/peds.2013-2309,
 PMID: 24488746,
 PMC: 3934337,</ref> Current research focuses on charting the connections between neurodevelopment injuries, surgical and intensive care procedures, and genetic susceptibility with the goal of modifying interventions that impair neurodevelopmental and psychosocial outcomes.<ref>Wernovsky, Gil, 
 Neurodevelopmental Outcomes in Children with Congenital Heart Disease – What can we impact?, 
 Pediatric Critical Care Medicine, 
 
 Vol. 17(Issue: 8 Suppl 1),
 pp. S232–S242,
 DOI: 10.1097/PCC.0000000000000800,
 PMID: 27490605,
 PMC: 4975480,</ref>  An alternative to the traditional Norwood is the Hybrid procedure.<ref>Yabrodi, Mouhammad, 
 Hypoplastic left heart syndrome: from comfort care to long-term survival, 
 Pediatric Research, 
 
 Vol. 81(Issue: 1–2),
 pp. 142–149,
 DOI: 10.1038/pr.2016.194,
 PMID: 27701379,
 PMC: 5313512,</ref>

Some physicians offer "compassionate care", instead of the surgeries, which results in the child's death, usually within 2 weeks of birth. Compassionate care is overseen by a physician, and may be carried out either in the hospital or at home. However, due to the vast improvement of surgical intervention, with many hospitals achieving over 90% survival, there is debate on whether or not "compassionate care" should still be offered to families.<ref name="pmid18762602">Wernovsky, Gil,

 The Paradigm Shift Toward Surgical Intervention for Neonates With Hypoplastic Left Heart Syndrome, 
 Archives of Pediatrics & Adolescent Medicine, 
 
 Vol. 162(Issue: 9),
 pp. 849–54,
 DOI: 10.1001/archpedi.162.9.849,
 PMID: 18762602,</ref> A study in 2003 concluded that a selection of physicians who are experts in the care of children with HLHS were evenly split when asked what they would do if their own children were born with HLHS, with 1/3 stating that they would choose surgery, 1/3 stating that they would choose palliative (compassionate) treatment without surgery, and 1/3 stating that they are uncertain which choice they would make.<ref name="pmid12804748">Kon, Alexander A., 
 Choices physicians would make if they were the parents of a child with hypoplastic left heart syndrome, 
 The American Journal of Cardiology, 
 
 Vol. 91(Issue: 12),
 pp. 1506–1509,
 DOI: 10.1016/S0002-9149(03)00412-0,
 PMID: 12804748,</ref>

The three-stage procedure is a palliative procedure (not a cure), as the child's circulation is made to work with only two of the heart's four chambers.

Norwood procedure

The first step is the Norwood procedure.<ref name=":0">Feinstein, Jeffrey A.,

 Hypoplastic Left Heart Syndrome, 
 Journal of the American College of Cardiology, 
 
 Vol. 59(Issue: 1),
 pp. S1–S42,
 DOI: 10.1016/j.jacc.2011.09.022,
 PMID: 22192720,
 PMC: 6110391,</ref> In this procedure, the right ventricle is used to pump blood into the systemic circulation. Since the right ventricle is no longer directly pumping blood to the lungs, a shunt is required in order to pass deoxygenated blood through the lungs. Either the subclavian artery can be connected to the pulmonary circulation (Blalock-Taussig shunt), or a shunt is made directly from the right ventricle to the pulmonary circulation (Sano shunt). The narrow aorta is enlarged using a patch to improve blood flow to the body.<ref>

new norwood.gif(link). {{{website}}}.

</ref>

During this time the baby may be medically fragile and have feeding problems because the heart is working very hard. There is a considerable degree of venous mixing in the right ventricle, leading to lower oxygenation saturation. In addition, both the Blalock-Taussig and the Sano shunts expose the lungs to systemic arterial pressures, leading to long-term pulmonary hypertension and eventually heart failure.<ref name=":0" />

Hybrid procedure

The Hybrid procedure may be used in place of the Norwood.<ref name=":0" /><ref>Murphy, Michael O.,

 Hybrid Procedure for Neonates With Hypoplastic Left Heart Syndrome at High-Risk for Norwood: Midterm Outcomes, 
 The Annals of Thoracic Surgery, 
 2015,
 Vol. 100(Issue: 6),
 pp. 2286–2292,
 DOI: 10.1016/j.athoracsur.2015.06.098,
 PMID: 26433522,</ref><ref>Chauhan, Monika, 
 Hypoplastic Left Heart Syndrome in the Emergency Department: An Update, 
 The Journal of Emergency Medicine, 
 2014,
 Vol. 46(Issue: 2),
 pp. e51–e54,
 DOI: 10.1016/j.jemermed.2013.08.061,
 PMID: 24188609,</ref>  The Hybrid procedure does not necessitate the use of heart-lung bypass or performing a sternotomy.  Instead of a six-hour surgery, the Hybrid typically takes one to two hours.  In this procedure, a stent is placed in the ductus arteriosus to maintain its patency, and bands are placed over both the left and right pulmonary artery branches to limit pressure and over-circulation to the lungs.<ref>Children's Hospital Boston | Pediatric Views</ref>  Outcomes with the Hybrid approach are comparable to those with the Norwood.<ref>, 
 Hybrid approach for hypoplastic left heart syndrome: intermediate results after the learning curve, 
 Ann. Thorac. Surg., 
 
 Vol. 85(Issue: 6),
 pp. 2063–70; discussion 2070–1,
 DOI: 10.1016/j.athoracsur.2008.02.009,
 PMID: 18498821,</ref>

Glenn procedure

The second stage—the bidirectional Glenn or Hemi-Fontan (see also Kawashima procedure)—relieves some of the problems introduced by Stage I palliation.<ref name=":0" /> In this operation, the superior vena cava is ligated from the heart and connected to the pulmonary circulation. At this time, the Blalock-Taussig or Sano shunt is taken down. The lungs are no longer exposed to systemic arterial pressures, but much lower venous pressures. Although venous blood from the upper half of the body is no longer mixing with oxygenated blood in the right ventricle, there is still venous mixing from the lower half of the body, leading to some degree of oxygen desaturation.<ref name=":0" />

Fontan procedure

The final procedure, the Fontan procedure, completes the repair of the hypoplastic left heart.<ref name=":0" /> Although there are several variations, the functional effect is to redirect venous blood from the lower body (through the inferior vena cava) away from the right atrium to the pulmonary artery. This should eliminate any mixing of oxygenated and deoxygenated blood in the right ventricle. The right ventricle performs the traditional job of the left, supplying the body with oxygenated blood, while the passive systemic venous pressure performs the traditional job of the right, passing deoxygenated blood to the lungs.<ref name=":0" />

Fetal surgery

Interventions performed during fetal development are under investigation. In fetuses with hypoplastic left ventricles and an intact interatrial septum, percutaneous atrial septostomy has been attempted.<ref name=":2" />

Prognosis

95% of untreated infants with HLHS die in the first weeks of life.<ref name=":12" />

Early survival has improved since the introduction of the Norwood procedure.<ref name="HLHS Review 2012 Feinstein" /> Since there are no long-term studies of HLHS adults, statistics are usually derived from post-Fontan patients; it is estimated that 70% of HLHS patients may reach adulthood.<ref name="HLHS Review 2012 Feinstein" />

Prognosis is dependent upon the health of the child, as there is an increased demand on respiratory and heart rate in infants during common childhood illnesses. This fragile population has little cardiac reserve to accommodate these demands and provide hemodynamic stability during illnesses. <ref>Nieves, Jo Ann,

 Interstage Home Monitoring After Newborn First-Stage Palliation for Hypoplastic Left Heart Syndrome: Family Education Strategies, 
 Critical Care Nurse, 
 
 Vol. 37(Issue: 2),
 pp. 72–88,
 DOI: 10.4037/ccn2017763,
 
 
 
 Full text,</ref>

Children with HLHS and other comparable single-ventricle conditions, as a group, have poorer neurodevelopmental outcomes than their healthy peers. Deficits in language, executive functioning, and higher rates of anxiety and depression disorders have been demonstrated.<ref>White, Brian R.,

 Recent advances in our understanding of neurodevelopmental outcomes in congenital heart disease, 
 Current Opinion in Pediatrics, 
 
 Vol. 31(Issue: 6),
 pp. 783–788,
 DOI: 10.1097/MOP.0000000000000829,
 PMID: 31693588,
 PMC: 6852883,</ref> Some of these outcomes may be a consequence of genetic factors associated with HLHS, and others may be modifiable through changes to procedures and to the healthcare environment. There is an emerging clinical consensus around the importance of continuous neurodevelopmental surveillance from the earliest years into adulthood.<ref>Marino, Bradley S., 
 Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation and Management: A Scientific Statement From the American Heart Association, 
 Circulation, 
 
 Vol. 126(Issue: 9),
 pp. 1143–1172,
 DOI: 10.1161/CIR.0b013e318265ee8a,
 PMID: 22851541,</ref><ref>Gurvitz, Michelle, 
 Emerging Research Directions in Adult Congenital Heart Disease: A Report from a National Heart, Lung, and Blood Institute/Adult Congenital Heart Association Working Group, 
 Journal of the American College of Cardiology, 
 
 Vol. 67(Issue: 16),
 pp. 1956–1964,
 DOI: 10.1016/j.jacc.2016.01.062,
 PMID: 27102511,
 PMC: 4846980,</ref>

As is true for patients with other types of heart defects involving malformed valves,<ref>

Endocarditis: Risk factors(link). '. MayoClinic.com.

</ref> HLHS patients run a high risk of endocarditis, and must be monitored by a cardiologist for the rest of their lives to check on their heart function.

Heart transplantation may be indicated, typically after Fontan completion.<ref name="HLHS Review 2012 Feinstein" /> One multi-center study (of patients undergoing the Fontan from 1993-2001) reported a 76% 1-year survival rate in patients who survived to transplant.<ref>Taylor, D. O., Stehlik, J., Edwards, L. B., Aurora, P., Christie, J. D., Dobbels, F., ... & Hertz, M. I.,

 Registry of the International Society for Heart and Lung Transplantation: twenty-sixth official adult heart transplant report—2009, 
 The Journal of Heart and Lung Transplantation, 
 2009,
 Vol. 28(Issue: 10),
 pp. 1007–1022,
 DOI: 10.1016/j.healun.2009.08.014,
 PMID: 19782283,</ref>

Epidemiology

HLHS occurs in an estimated 1 out of 4,300 live births in the United States, or an estimated total of 960 live births per year in that country.<ref> ,

 Hypoplastic Left Heart Syndrome Facts | Congenital Heart Defects Full text, 
 Centers for Disease Control and Prevention, 
  
 2017-10-26, 
  
  
 Accessed on: 2017-11-30.

</ref><ref>Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A; National Birth Defects Prevention Network.,

 Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006, 
 Birth Defects Res a Clin Mol Teratol., 
 2010,
 Vol. 88(Issue: 12),
 pp. 1008–16,
 DOI: 10.1002/bdra.20735,
 PMID: 20878909,</ref> Overall, it is estimated to make up 2-3% of all cases of congenital heart disease, and is the most common single-ventricle defect. It is thought to be more common in male infants, 1.5 times as common as in female infants.<ref name=":1">

Fulton, David R.. Hypoplastic left heart syndrome(link). Up To Date.

October 26, 2017.

Accessed 2017-11-30.

</ref>

External links

• Hypoplastic left heart syndrome information for parents.

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