Hypoplastic left heart syndrome

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Hypoplastic left heart syndrome
Other namesCyanotic heart disease - hypoplastic left heart [1]
Hlhs-web.jpg
Illustration of heart with hypoplastic left heart syndrome
Specialty Cardiology   OOjs UI icon edit-ltr-progressive.svg

Hypoplastic left heart syndrome (HLHS) is a rare congenital heart defect in which the left side of the heart is severely underdeveloped and incapable of supporting the systemic circulation. [2] It is estimated to account for 2-3% of all congenital heart disease. [3] Early signs and symptoms include poor feeding, cyanosis, and diminished pulse in the extremities. [4] The etiology is believed to be multifactorial resulting from a combination of genetic mutations and defects resulting in altered blood flow in the heart. [5] [6] [7] Several structures can be affected including the left ventricle, aorta, aortic valve, or mitral valve all resulting in decreased systemic blood flow. [8]

Contents

Diagnosis can occur prenatally via ultrasound or shortly after birth via echocardiography. [5] Initial management is geared to maintaining patency of the ductus arteriosus - a connection between the pulmonary artery and the aorta that closes shortly after birth. [9] Thereafter, a patient subsequently undergoes a three-stage palliative repair over the next few years of life. [10] The Norwood procedure is typically done within a few days of birth. [10] The Glenn procedure is typically performed at three to six months of age. [10] Finally the Fontan procedure is done sometime between the age of two and five years of age. [10]

If left untreated, patients with HLHS die within the first weeks of life while 70% of those that undergo three-staged palliative surgery reach adulthood. After surgery, children with HLHS typically experience neurodevelopmental as well as motor delay and are at an increased risk of heart failure as adults. [11] [12]

Epidemiology

HLHS occurs in an estimated 1 out of 3,841 live births in the United States, or an estimated total of 1,025 live births per year in the US. [13] [14] Overall, it is estimated to make up 2-3% of all cases of congenital heart disease, and is the most common single-ventricle defect. [3] It is thought to be more common in male infants, 1.5 times as common as in female infants. [15] A recent systematic review found a slight decrease in prevalence of HLHS from 0.689/1000 in 1995 -1999, to 0.475/1000 in 2010 - 2017. [3] This is thought to be due to improvements in prenatal detection and prenatal counseling and subsequent pregnancy.

Signs and symptoms

Infant with cyanosis due to hypoplastic left heart syndrome HLHS.jpg
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. Early symptoms might include poor feeding or cyanosis that does not respond to oxygen administration. Peripheral pulses may be weak and extremities cool to the touch. [5]

HLHS often co-occurs with low birth weight and premature birth. [5]

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. [5]

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. [5]

Co-occurring tricuspid regurgitation or right ventricular dysfunction can cause hepatomegaly to develop. [5]

Pathogenesis

The majority of HLHS cases are sporadic meaning they arise in patients with no family history of HLHS. [4] Some cases may have a genetic component, as HLHS has been shown to be heritable and associated with specific gene mutations. [16] [17] Possible contributing factors may include intrauterine infarction, infectious changes, and a selective left ventricular cardiomyopathy.

Genetics

Genetic loci associated with HLHS include GJA1 (connexin 43), HAND1, NKX2.5, 10q22, and 6q23. [15] [18] [6] 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. [4] This is thought to be mediated by genetic mutations with incomplete penetrance. [15]

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. [15] [18]

Altered Blood Flow

A popular theory termed the "no flow, no grow" hypothesis suggest that primary anatomic defects of the aortic and mitral valves lead to malformations of the left ventricle and its outflow tract. [9] These primary defects can be divided into those that lead to outflow tract obstruction or reduced left ventricular filling. [7] Outflow tract obstruction leads to left ventricular hypertrophy and reduction in the left ventricular lumen. One example of this would be in the case of aortic stenosis. Aortic stenosis that occurs during fetal development results in added stress on the left ventricle in utero. This can eventually lead to decreased perfusion through the left ventricle which is believed to inhibit ventricular growth. [19]

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. [5]

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. Patients with HLHS can have a number of cardiac malformations that ultimately lead to a diminutive left ventricle that is unable to supply sufficient blood flow to the rest of the body. [20] There are three main anatomic variants of the disease differentiated by either stenosis or atresia of the aortic and mitral valve. [20]

Mitral atresia and aortic atresia (MA-AA) subtype is the most severe form of HLHS resulting in no blood flow entering the left ventricle at all resulting in no possibility of left ventricular output. [20] In the mitral stenosis and aortic atresia (MS-AA) subtype blood is able to fill the left ventricle, however it is unable to be supplied to the systemic circulation via the hypoplastic ascending aorta. [20] Lastly, the mildest form is the mitral stenosis and aortic stenosis (MS-AS) subtype. [20] In these patients although the left ventricle is able to supply some blood flow to the rest of the body the overall left ventricular systemic output remains inadequate. [20]

In all of these cases blood is unable to 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. [15]

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. [19]

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. [5]

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. [8]

Before surgery, the ductus must be kept open to allow blood-flow using medication containing prostaglandin. [9] 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. [21] 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. [22] [23]

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.[ citation needed ]

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. [10] Current expectations are that 70% of those with HLHS may reach adulthood. [18] Many studies show that the higher the volume (number of surgeries performed) at a hospital, the lower the mortality (death) rate. [24] [25] 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. [26] For patients without these additional risk factors, 5 year survival now approaches 80%. [26] 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. [27] 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. [28] An alternative to the traditional Norwood is the Hybrid procedure. [29]

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. [30] 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. [31]

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.[ citation needed ]

Norwood procedure Norwood Surgical Correction.png
Norwood procedure

Norwood procedure

The first step is the Norwood procedure. [32] 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. [33]

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. [32]

Hybrid procedure

The Hybrid procedure may be used in place of the Norwood. [32] [34] [35] 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. [36] Outcomes with the Hybrid approach are comparable to those with the Norwood. [37]

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. [32] 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. [32]

Fontan procedure

Fontan procedure.svg

The final procedure, the Fontan procedure, completes the repair of the hypoplastic left heart. [32] 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. [32]

Fetal surgery

Interventions performed during fetal development are under investigation. When signs of HLHS are detected prenatally via ultrasound, a percutaneous procedure involving the insertion of a balloon catheter can open the atrial septal defect to prevent left atrial hypertension and promote improved heart development. [38] [39]

Prognosis

95% of untreated infants with HLHS die in the first weeks of life. [5]

Early survival has improved since the introduction of the Norwood procedure. [18] 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. [18]

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. [40]

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. [41] 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. [11] [42] Additionally, a recent meta-analysis comparing twenty-two studies showed that 64.7% of the studies reported delayed motor development in children with single ventricle physiologies, such as hypoplastic left heart syndrome. [12]

As is true for patients with other types of heart defects involving malformed valves, [43] 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.[ citation needed ]

Heart transplantation may be indicated, typically after Fontan completion. [18] One multi-center study (of patients undergoing the Fontan from 1993 to 2001) reported a 76% 1-year survival rate in patients who survived to transplant. [44]

Future of stem cell therapies

A systematic review found 23 articles, published since 2010, as well as nine relevant clinical trials related to congenital heart disease and recent advances in stem cell therapies. [45] Pre-clinical research has focused on several types of stem cells including: mesenchymal stem cells (MSCs), autologous umbilical cord blood cells, c-kit+ cardiac stem cells, and neonatal thymus mesenchymal stem cells. [45] These cell types have shown the ability to differentiate into cardiac tissue making them ideal for cardiac regenerative therapy.  The first use of autologous umbilical cord blood cells was done at the Mayo Clinic in 2015 and was found to increase right ventricular function in the patient after their procedure. [45] The first use of cardiac progenitor cells occurred in the Transcoronary Infusion of Cardiac Progenitor Cells in Patients with Single-Ventricle Physiology (TICAP) Trail of 2011. [45]

Ongoing trials

There are several ongoing studies testing the feasibility and efficacy of stem cell therapies for single ventricle diseases such as HLHS. [45] These trials focus on what are the most effective stem cells, what is the best timing in the 3-stage repair, and what is the optimal delivery method.

It is important to keep in mind that patients with HLHS are at increased risk of developing heart failure as adults. It remains unknown if these potential therapies would reduce the future risk of heart failure in these patients.

Related Research Articles

<span class="mw-page-title-main">Tetralogy of Fallot</span> Type of congenital heart defect

Tetralogy of Fallot (TOF), formerly known as Steno-Fallot tetralogy, is a congenital heart defect characterized by four specific cardiac defects. Classically, the four defects are:

<span class="mw-page-title-main">Congenital heart defect</span> Defect in the structure of the heart that is present at birth

A congenital heart defect (CHD), also known as a congenital heart anomaly, congenital cardiovascular malformation, and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular disease. Signs and symptoms depend on the specific type of defect. Symptoms can vary from none to life-threatening. When present, symptoms are variable and may include rapid breathing, bluish skin (cyanosis), poor weight gain, and feeling tired. CHD does not cause chest pain. Most congenital heart defects are not associated with other diseases. A complication of CHD is heart failure.

A cyanotic heart defect is any congenital heart defect (CHD) that occurs due to deoxygenated blood bypassing the lungs and entering the systemic circulation, or a mixture of oxygenated and unoxygenated blood entering the systemic circulation. It is caused by structural defects of the heart such as right-to-left or bidirectional shunting, malposition of the great arteries, or any condition which increases pulmonary vascular resistance. The result may be the development of collateral circulation.

<span class="mw-page-title-main">Ventricular septal defect</span> Medical condition

A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one common ventricle. The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.

<span class="mw-page-title-main">Fontan procedure</span> Surgical procedure used in children with univentricular hearts

The Fontan procedure or Fontan–Kreutzer procedure is a palliative surgical procedure used in children with univentricular hearts. It involves diverting the venous blood from the inferior vena cava (IVC) and superior vena cava (SVC) to the pulmonary arteries. The procedure varies for differing congenital heart pathologies. For example in tricuspid atresia, the procedure can be done where the blood does not pass through the morphologic right ventricle; i.e., the systemic and pulmonary circulations are placed in series with the functional single ventricle. Whereas in hypoplastic left heart syndrome, the heart is more reliant on the more functional right ventricle to provide blood flow to the systemic circulation. The procedure was initially performed in 1968 by Francis Fontan and Eugene Baudet from Bordeaux, France, published in 1971, simultaneously described in 1971 by Guillermo Kreutzer from Buenos Aires, Argentina, and finally published in 1973.

Situs ambiguus is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen. Clinically heterotaxy spectrum generally refers to any defect of Left-right asymmetry and arrangement of the visceral organs; however, classical heterotaxy requires multiple organs to be affected. This does not include the congenital defect situs inversus, which results when arrangement of all the organs in the abdomen and chest are mirrored, so the positions are opposite the normal placement. Situs inversus is the mirror image of situs solitus, which is normal asymmetric distribution of the abdominothoracic visceral organs. Situs ambiguus can also be subdivided into left-isomerism and right isomerism based on the defects observed in the spleen, lungs and atria of the heart.

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<span class="mw-page-title-main">Pulmonary atresia</span> Medical condition

Pulmonary atresia is a congenital malformation of the pulmonary valve in which the valve orifice fails to develop. The valve is completely closed thereby obstructing the outflow of blood from the heart to the lungs. The pulmonary valve is located on the right side of the heart between the right ventricle and pulmonary artery. In a normal functioning heart, the opening to the pulmonary valve has three flaps that open and close.

<span class="mw-page-title-main">Tricuspid atresia</span> Medical condition

Tricuspid atresia is a form of congenital heart disease whereby there is a complete absence of the tricuspid valve. Therefore, there is an absence of right atrioventricular connection. This leads to a hypoplastic (undersized) or absent right ventricle. This defect is contracted during prenatal development, when the heart does not finish developing. It causes the systemic circulation to be filled with relatively deoxygenated blood. The causes of tricuspid atresia are unknown.

<span class="mw-page-title-main">Atrioventricular septal defect</span> Medical condition

Atrioventricular septal defect (AVSD) or atrioventricular canal defect (AVCD), also known as "common atrioventricular canal" or "endocardial cushion defect" (ECD), is characterized by a deficiency of the atrioventricular septum of the heart that creates connections between all four of its chambers. It is a very specific combination of 3 defects:

<span class="mw-page-title-main">Norwood procedure</span> Surgery performed on the heart

The Norwood procedure is the first of three surgeries intended to create a new functional systemic circuit in patients with hypoplastic left heart syndrome (HLHS) and other complex heart defects with single ventricle physiology. The first successful Norwood procedure involving the use of a cardiopulmonary bypass was reported by Dr. William Imon Norwood, Jr. and colleagues in 1981.

<span class="mw-page-title-main">Bidirectional Glenn procedure</span>

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<span class="mw-page-title-main">Hypoplastic right heart syndrome</span> Type of congenital heart disease

Hypoplastic right heart syndrome or HRHS is a congenital heart defect in which the structures on the right side of the heart, particularly the right ventricle, are underdeveloped. This defect causes inadequate blood flow to the lungs, and thus a cyanotic infant.

<span class="mw-page-title-main">Ventricular outflow tract obstruction</span> Medical condition

A ventricular outflow tract obstruction is a heart condition in which either the right or left ventricular outflow tract is blocked or obstructed. These obstructions represent a spectrum of disorders. Majority of these cases are congenital, but some are acquired throughout life.

Fetal aortic stenosis is a disorder that occurs when the fetus’ aortic valve does not fully open during development. The aortic valve is a one way valve that is located between the left ventricle and the aorta, keeping blood from leaking back into the ventricle. It has three leaflets that separate when the ventricle contracts to allow blood to move from the ventricle to the aorta. These leaflets come together when the ventricle relaxes.

The Damus–Kaye–Stansel (DKS) procedure is a cardiovascular surgical procedure used as part of the repair of some congenital heart defects. This procedure joins the pulmonary artery and the aorta in situations where the systemic circulation is obstructed. It is commonly used when a patient has the combination of a small left ventricle and a transposition of the great arteries (TGA); in this case, the procedure allows blood to flow from the left ventricle to the aorta.

The Yasui procedure is a pediatric heart operation used to bypass the left ventricular outflow tract (LVOT) that combines the aortic repair of the Norwood procedure and a shunt similar to that used in the Rastelli procedure in a single operation. It is used to repair defects that result in the physiology of hypoplastic left heart syndrome even though both ventricles are functioning normally. These defects are common in DiGeorge syndrome and include interrupted aortic arch and LVOT obstruction (IAA/LVOTO); aortic atresia-severe stenosis with ventricular septal defect (AA/VSD); and aortic atresia with interrupted aortic arch and aortopulmonary window. This procedure allows the surgeon to keep the left ventricle connected to the systemic circulation while using the pulmonary valve as its outflow valve, by connecting them through the ventricular septal defect. The Yasui procedure includes a modified Damus–Kaye–Stansel procedure to connect the aortic and pulmonary roots, allowing the coronary arteries to remain perfused. It was first described in 1987.

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Single ventricle is a rare congenital heart defect, which constitutes just over 1% of congenital cardiovascular diseases. The single functional ventricle could be morphologically right or left with the second ventricle usually hypoplastic and/or insufficiently functional. Therefore, there are several subtypes of the disease, depending on which ventricle is underdeveloped.

References

  1. ↑ "Hypoplastic left heart syndrome: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 28 May 2019.
  2. ↑ Tchervenkov, C. I; Jacobs, J. P; Weinberg, P. M; Aiello, V. D; Béland, M. J; Colan, S. D; Elliott, M. J; Franklin, R. C; Gaynor, J. W; Krogmann, O. N; Kurosawa, H; Maruszewski, B; Stellin, G (2006). "The nomenclature, definition and classification of hypoplastic left heart syndrome". Cardiology in the Young. 16 (4): 339–368. doi: 10.1017/s1047951106000291 . PMID   16839428.
  3. 1 2 3 Liu, Yingjuan; Chen, Sen; Zühlke, Liesl; Black, Graeme C.; Choy, Mun-Kit; Li, Ningxiu; Keavney, Bernard D. (2019-04-01). "Global birth prevalence of congenital heart defects 1970-2017: updated systematic review and meta-analysis of 260 studies". International Journal of Epidemiology. 48 (2): 455–463. doi:10.1093/ije/dyz009. ISSN   1464-3685. PMC   6469300 . PMID   30783674.
  4. 1 2 3 Barron, D. J., Kilby, M. D., Davies, B., Wright, J. G., Jones, T. J., & Brawn, W. J. (2009). "Hypoplastic left heart syndrome". The Lancet. 374 (9689): 551–564. doi:10.1016/s0140-6736(09)60563-8. PMID   19683641. S2CID   3285769.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. 1 2 3 4 5 6 7 8 9 10 Fulton, David R. (October 26, 2017). "Hypoplastic left heart syndrome". Up To Date. Retrieved 2017-11-30.
  6. 1 2 Hinton, R. B., Martin, L. J., Rame-Gowda, S., Tabangin, M. E., Cripe, L. H., & Benson, D. W. (2009). "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. 53 (12): 1065–1071. doi:10.1016/j.jacc.2008.12.023. PMC   2703749 . PMID   19298921.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 Kritzmire, Stacy M.; Cossu, Anne E. (2021), "Hypoplastic Left Heart Syndrome", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   32119463 , retrieved 2021-11-12
  8. 1 2 Noseda C, Mialet-Marty T, Basquin A (April 2012). "Hypoplasies sévères du ventricule gauche : soins palliatifs après un diagnostic prénatal". Archives de Pédiatrie . 19 (4): 374–380. doi:10.1016/j.arcped.2012.01.022. PMID   22397767.
  9. 1 2 3 Crucean, A.; Alqahtani, A.; Barron, D. J.; Brawn, W. J.; Richardson, R. V.; O’Sullivan, J.; Anderson, R. H.; Henderson, D. J.; Chaudhry, B. (2017-08-10). "Re-evaluation of hypoplastic left heart syndrome from a developmental and morphological perspective". Orphanet Journal of Rare Diseases. 12 (1): 138. doi: 10.1186/s13023-017-0683-4 . ISSN   1750-1172. PMC   5551014 . PMID   28793912.
  10. 1 2 3 4 5 Hypoplastic Left Heart Syndrome (HLHS) | The Children's Hospital of Philadelphia
  11. 1 2 Marino, Bradley S.; Lipkin, Paul H.; Newburger, Jane W.; Peacock, Georgina; Gerdes, Marsha; Gaynor, J. William; Mussatto, Kathleen A.; Uzark, Karen; Goldberg, Caren S. (2012-08-28). "Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation and Management: A Scientific Statement From the American Heart Association". Circulation. 126 (9): 1143–1172. doi: 10.1161/CIR.0b013e318265ee8a . ISSN   0009-7322. PMID   22851541.
  12. 1 2 Sprong, Maaike C. A.; Broeders, Willem; van der Net, Janjaap; Breur, Johannes M. P. J.; de Vries, Linda S.; Slieker, Martijn G.; van Brussel, Marco (2021-10-01). "Motor Developmental Delay After Cardiac Surgery in Children With a Critical Congenital Heart Defect: A Systematic Literature Review and Meta-analysis". Pediatric Physical Therapy. 33 (4): 186–197. doi: 10.1097/PEP.0000000000000827 . ISSN   1538-005X. PMID   34618742. S2CID   238255373.
  13. ↑ "Hypoplastic Left Heart Syndrome Facts | Congenital Heart Defects". Centers for Disease Control and Prevention. 2017-10-26. Retrieved 2017-11-30.
  14. ↑ 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. (2010). "Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006". Birth Defects Research Part A: Clinical and Molecular Teratology. 88 (12): 1008–16. doi:10.1002/bdra.20735. PMID   20878909.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. 1 2 3 4 5 Fulton, David R. (October 26, 2017). "Hypoplastic left heart syndrome". Up To Date. Retrieved 2017-11-30.
  16. ↑ Hinton, R. B., Martin, L. J., Tabangin, M. E., Mazwi, M. L., Cripe, L. H., & Benson, D. W. (2007). "Hypoplastic left heart syndrome is heritable". Journal of the American College of Cardiology. 50 (16): 1590–1595. doi: 10.1016/j.jacc.2007.07.021 . PMID   17936159.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ↑ Dasgupta C, Martinez AM, Zuppan CW, Shah MM, Bailey LL, Fletcher WH (2001). "Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE)". Mutat. Res. 479 (1–2): 173–86. doi:10.1016/S0027-5107(01)00160-9. PMID   11470490.
  18. 1 2 3 4 5 6 Feinstein, JA; Benson, DW; Dubin, AM; Cohen, MS; Maxey, DM; Mahle, WT; Pahl, E; Villafañe, J; Bhatt, AB; Peng, LF; Johnson, BA; Marsden, AL; Daniels, CJ; Rudd, NA; Caldarone, CA; Mussatto, KA; Morales, DL; Ivy, DD; Gaynor, JW; Tweddell, JS; Deal, BJ; Furck, AK; Rosenthal, GL; Ohye, RG; Ghanayem, NS; Cheatham, JP; Tworetzky, W; Martin, GR (3 January 2012). "Hypoplastic left heart syndrome: current considerations and expectations". Journal of the American College of Cardiology. 59 (1 Suppl): S1–42. doi:10.1016/j.jacc.2011.09.022. PMC   6110391 . PMID   22192720.
  19. 1 2 Schidlow, David N.; Freud, Lindsay; Friedman, Kevin; Tworetzky, Wayne (2017). "Fetal interventions for structural heart disease". Echocardiography. 34 (12): 1834–1841. doi:10.1111/echo.13667. ISSN   1540-8175. PMID   29287139. S2CID   12087225.
  20. 1 2 3 4 5 6 Tchervenkov, C. I.; Jacobs, M. L.; Tahta, S. A. (April 2000). "Congenital Heart Surgery Nomenclature and Database Project: hypoplastic left heart syndrome". The Annals of Thoracic Surgery. 69 (4 Suppl): S170–179. doi:10.1016/s0003-4975(99)01283-7. ISSN   0003-4975. PMID   10798427.
  21. ↑ Green A, Pye S, Yetman AT (August 2002). "The physiologic basis for and nursing considerations in the use of subatmospheric concentrations of oxygen in HLHS". Advances in Neonatal Care . 2 (4): 177–86. doi:10.1053/adnc.2002.33542. PMID   12881932.
  22. ↑ Khambadkone S.; Li J.; De Leval M. R.; Cullen S.; Deanfield J. E.; Redington A. N. (2003). "Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation". Circulation. 107 (25): 3204–3208. doi: 10.1161/01.cir.0000074210.49434.40 . PMID   12821557.
  23. ↑ Norwood W. I. (1991). "Hypoplastic left heart syndrome. The". Annals of Thoracic Surgery. 52 (3): 688–695. doi: 10.1016/0003-4975(91)90978-y . PMID   1898174.
  24. ↑ McHugh, KE; Hillman, DG; Gurka, MJ; Gutgesell, HP (Jan–Feb 2010). "Three-stage palliation of hypoplastic left heart syndrome in the University HealthSystem Consortium". Congenital Heart Disease. 5 (1): 8–15. doi:10.1111/j.1747-0803.2009.00367.x. PMID   20136852.
  25. ↑ Hirsch, JC; Gurney, JG; Donohue, JE; Gebremariam, A; Bove, EL; Ohye, RG (July 2008). "Hospital mortality for Norwood and arterial switch operations as a function of institutional volume". Pediatric Cardiology. 29 (4): 713–7. doi:10.1007/s00246-007-9171-2. PMID   18080151. S2CID   23456242.
  26. 1 2 Vojtovič, P.; Tláskal, T.; Gebauer, R.; Reich, O.; Chaloupecký, V.; Tomek, V.; Krupičková, S.; Matějka, T.; Hecht, P. (December 2014). "Long-term results of children operated for hypoplastic left heart syndrome in Children's Heart Centre". Cor et Vasa. 56 (6): e449–e455. doi: 10.1016/j.crvasa.2014.07.006 . ISSN   0010-8650.
  27. ↑ Mussatto, Kathleen A.; Hoffmann, Raymond G.; Hoffman, George M.; Tweddell, James S.; Bear, Laurel; Cao, Yumei; Brosig, Cheryl (2014). "Risk and prevalence of developmental delay in young children with congenital heart disease". Pediatrics. 133 (3): e570–577. doi:10.1542/peds.2013-2309. ISSN   1098-4275. PMC   3934337 . PMID   24488746.
  28. ↑ Wernovsky, Gil; Licht, Daniel J. (2016). "Neurodevelopmental Outcomes in Children with Congenital Heart Disease – What can we impact?". Pediatric Critical Care Medicine. 17 (8 Suppl 1): S232–S242. doi:10.1097/PCC.0000000000000800. ISSN   1529-7535. PMC   4975480 . PMID   27490605.
  29. ↑ Yabrodi, Mouhammad; Mastropietro, Christopher W. (2016-10-04). "Hypoplastic left heart syndrome: from comfort care to long-term survival". Pediatric Research. 81 (1–2): 142–149. doi:10.1038/pr.2016.194. ISSN   0031-3998. PMC   5313512 . PMID   27701379.
  30. ↑ Wernovsky, Gil (1 September 2008). "The Paradigm Shift Toward Surgical Intervention for Neonates With Hypoplastic Left Heart Syndrome". Archives of Pediatrics & Adolescent Medicine. 162 (9): 849–54. doi:10.1001/archpedi.162.9.849. PMID   18762602.
  31. ↑ Kon, Alexander A.; Ackerson, Lynn; Lo, Bernard (31 May 2003). "Choices physicians would make if they were the parents of a child with hypoplastic left heart syndrome". The American Journal of Cardiology. 91 (12): 1506–1509. doi:10.1016/S0002-9149(03)00412-0. PMID   12804748.
  32. 1 2 3 4 5 6 7 Feinstein, Jeffrey A.; Benson, D. Woodrow; Dubin, Anne M.; Cohen, Meryl S.; Maxey, Dawn M.; Mahle, William T.; Pahl, Elfriede; Villafañe, Juan; Bhatt, Ami B. (Jan 2012). "Hypoplastic Left Heart Syndrome". Journal of the American College of Cardiology. 59 (1): S1–S42. doi:10.1016/j.jacc.2011.09.022. PMC   6110391 . PMID   22192720.
  33. ↑ "new norwood.gif". Archived from the original on November 24, 2010.
  34. ↑ Murphy, Michael O.; Bellsham-Revell, Hannah; Morgan, Gareth J.; Krasemann, Thomas; Rosenthal, Eric; Qureshi, Shakeel A.; Salih, Caner; Austin, Conal B.; Anderson, David R. (2015). "Hybrid Procedure for Neonates With Hypoplastic Left Heart Syndrome at High-Risk for Norwood: Midterm Outcomes". The Annals of Thoracic Surgery. 100 (6): 2286–2292. doi: 10.1016/j.athoracsur.2015.06.098 . PMID   26433522.
  35. ↑ Chauhan, Monika; Mastropietro, Christopher W. (2014). "Hypoplastic Left Heart Syndrome in the Emergency Department: An Update". The Journal of Emergency Medicine. 46 (2): e51–e54. doi:10.1016/j.jemermed.2013.08.061. PMID   24188609.
  36. ↑ "Children's Hospital Boston | Pediatric Views". Archived from the original on 2012-02-29. Retrieved 2010-05-14.
  37. ↑ Galantowicz M, Cheatham JP, Phillips A, et al. (June 2008). "Hybrid approach for hypoplastic left heart syndrome: intermediate results after the learning curve". Ann. Thorac. Surg. 85 (6): 2063–70, discussion 2070–1. doi:10.1016/j.athoracsur.2008.02.009. PMID   18498821.
  38. ↑ Sood, Vikram; Zampi, Jeffrey D.; Romano, Jennifer C. (6 April 2020). "Hypoplastic left heart syndrome with an intact atrial septum". JTCVS Open. 1: 51–56. doi:10.1016/j.xjon.2020.03.001. PMC   9390260 . PMID   36003193.
  39. ↑ Cunningham, F. Gary; Leveno, Kenneth J.; Bloom, Steven L.; Spong, Catherine Y.; Dashe, Jodi S.; Hoffman, Barbara L.; Casey, Brian M.; Sheffield, Jeanne S. (2013). "Fetal Imaging". Williams Obstetrics (24 ed.). New York, NY: McGraw-Hill Education.
  40. ↑ Nieves, Jo Ann; Uzark, Karen; Rudd, Nancy A.; Strawn, Jennifer; Schmelzer, Anne; Dobrolet, Nancy (2017-04-01). "Interstage Home Monitoring After Newborn First-Stage Palliation for Hypoplastic Left Heart Syndrome: Family Education Strategies". Critical Care Nurse. 37 (2): 72–88. doi:10.4037/ccn2017763. ISSN   0279-5442. PMID   28365652. S2CID   39147698.
  41. ↑ White, Brian R.; Rogers, Lindsay S.; Kirschen, Matthew P. (2019). "Recent advances in our understanding of neurodevelopmental outcomes in congenital heart disease". Current Opinion in Pediatrics. 31 (6): 783–788. doi:10.1097/MOP.0000000000000829. ISSN   1040-8703. PMC   6852883 . PMID   31693588.
  42. ↑ Gurvitz, Michelle; Burns, Kristin M.; Brindis, Ralph; Broberg, Craig S.; Daniels, Curt J.; Fuller, Stephanie M.P.N.; Honein, Margaret A.; Khairy, Paul; Kuehl, Karen S. (2016-04-26). "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. 67 (16): 1956–1964. doi:10.1016/j.jacc.2016.01.062. ISSN   0735-1097. PMC   4846980 . PMID   27102511.
  43. ↑ "Endocarditis: Risk factors". MayoClinic.com. Retrieved 2007-10-23.
  44. ↑ Taylor, D. O., Stehlik, J., Edwards, L. B., Aurora, P., Christie, J. D., Dobbels, F., ... & Hertz, M. I. (2009). "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. 28 (10): 1007–1022. doi:10.1016/j.healun.2009.08.014. PMID   19782283.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. 1 2 3 4 5 Brown, Matthew A.; Rajamarthandan, Siva; Francis, Berline; O'Leary-Kelly, Meghan K.; Sinha, Pranava (January 2020). "Update on stem cell technologies in congenital heart disease". Journal of Cardiac Surgery. 35 (1): 174–179. doi: 10.1111/jocs.14312 . ISSN   1540-8191. PMID   31705822. S2CID   207963021.
  46. ↑ Timothy J. Nelson (2021-05-12). "Phase IIb Study of Intramyocardial Injection of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Stage II Surgical Repair of Right Ventricular Dependent Variants of Hypoplastic Left Heart Syndrome (AutoCell-S2)".{{cite journal}}: Cite journal requires |journal= (help)
  47. ↑ Pepe, Salvatore (2020-08-31). "Safety Study of Autologous Cord Blood Stem Cell Treatment in Hypoplastic Left Heart Syndrome Patients Undergoing the Norwood Heart Operation". Murdoch Childrens Research Institute.{{cite journal}}: Cite journal requires |journal= (help)
  48. ↑ Longeveron Inc. (2021-09-24). "Lomecel-B Injection in Patients With Hypoplastic Left Heart Syndrome: A Phase I/II Study (ELPIS)".{{cite journal}}: Cite journal requires |journal= (help)
  49. ↑ Timothy J. Nelson (2021-03-08). "Phase I Safety Study of Autologous Umbilical Cord Blood Derived Mononuclear Cells During Surgical Stage II Palliation of Hypoplastic Left Heart Syndrome".{{cite journal}}: Cite journal requires |journal= (help)
  50. ↑ Oh, Hidemasa (2017-01-03). "Phase 2 Study of Intracoronary Infusion of Cardiac Progenitor Cells in Patients With Univentricular Heart Disease". Okayama University, Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan.{{cite journal}}: Cite journal requires |journal= (help)
  51. ↑ Japan Regenerative Medicine Co., Ltd. (2020-11-15). "Efficacy and Safety Study of Autologous Cardiac Stem Cells (JRM-001) Treated After Reconstructive Surgery in Pediatric Patients With Congenital Heart Disease: A Multicenter Randomized Single-blind Parallel-group Study".{{cite journal}}: Cite journal requires |journal= (help)
  52. ↑ University of Miami (2021-10-05). "Autologous Cardiac Stem Cell Injection in Patients With Hypoplastic Left Heart Syndrome: An Open Label Pilot Study".{{cite journal}}: Cite journal requires |journal= (help)
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