Experimental production of hypoplastic left heart syndrome in the chick embryo

The hypothesis is examined that hemodynamic alterations at the site of the primordial mitral valve may induce malformations that simulate the clinical findings of hypoplastic left heart syndrome. Surgical placement of a nylon device, approximately 90 μ in diameter, into the region of the left atrioventricular (A-V) canal was accomplished in 192 embryos (Hamburger-Hamilton stages 23 to 25). Thirty-nine pairs of experimental and control embryos survived more than 12 days. Twenty-six experimental embryos exhibited various malformations: hypoplastic left atrium and ventricle, mitral valvular atresia, aortic valvular stenosis and tubular hypoplasia of the aorta and brachlocephalic vessels. These findings reemphasize the probable morphogenetic role of blood flow pathways. The findings further implicate involvement of the left A-V canal as well as premature closing of foramen ovale and aortic valvular abnormalities in the hypoplastic left heart syndrome.     

A case of PAGOD syndrome with hypoplastic left heart syndrome

PAGOD syndrome is an extremely rare congenital malformation complex involving multiple organs. These include pulmonary artery and lung hypoplasia, diaphragm defects, omphalocele, sex reversal or ambiguous genitalia, and complex cardiac defects. Eight cases have been reported to date. We report a case of PAGOD syndrome that is manifested by right diaphragm eventration, horseshoe lung with right lung hypoplasia, hypoplastic left heart syndrome (mitral atresia, aortic atresia), scimitar syndrome, agonadism with ambiguous genitalia. A karyotype revealed normal 46-XY. This patient received a modified Norwood procedure for hypoplastic left heart syndrome as an initial palliation and bidirectional cavopulmonary anastomosis as a second stage of operation. The postoperative courses were uneventful. This patient is waiting for Fontan operation.     

Coronary artery abnormalities and right ventricular histology in hypoplastic left heart syndrome.

OBJECTIVES. To determine whether right ventricular preservation is compromised in any anatomic subgroup of hypoplastic left heart syndrome, we assessed the coronary artery anatomy and myocardial histologic features of 151 postmortem specimens with hypoplastic left heart syndrome. BACKGROUND. Although previous studies have shown that coronary artery abnormalities are more prominent in the subgroup of patients who have a patent mitral valve and obstructed aortic valve, it has not been established that these abnormalities compromise right ventricular perfusion. METHODS. Eighty-nine specimens with a patent mitral valve and aortic atresia, 52 with mitral and aortic atresia and 10 with patent mitral and aortic valves were examined. Histologic sections of the right ventricle, left ventricle and coronary arteries were obtained from 64 study hearts and 5 control hearts. RESULTS. Gross coronary anomalies included coronary-cameral communications (n = 29), single left coronary artery (n = 2), single right coronary artery (n = 1) and tortuosity (n = 19). Coronary-cameral communications and tortuosity were significantly associated with the subgroup that had mitral hypoplasia and aortic atresia. Coronary artery wall thickness relative to lumen diameter was not different among the subgroups. No areas of coronary artery stenosis or interruption were discovered. Although endocardial fibroelastosis of the left ventricle was strongly associated with the mitral hypoplasia and aortic atresia group, the right ventricular histologic findings were similar in all subgroups and were not differentially affected by older age. CONCLUSIONS. Although the incidence of coronary abnormalities is greater in patients with mitral hypoplasia and aortic atresia, in this study there was no apparent difference in perfusion of the right ventricle among the anatomic subgroups of hearts with hypoplastic left heart syndrome.     

An infant with hypoplastic left heart syndrome and spinal muscular atrophy

We report an infant with hypoplastic left heart syndrome consisting of mitral valvar atresia, aortic valvar atresia, hypoplasia of the aortic arch and coarctation of the aorta, who demonstrated respiratory failure and global hypotonia, and who was eventually diagnosed with spinal muscular atrophy.     

Fistulous communications with the coronary arteries in the setting of hypoplastic ventricles

Neonates born with hypoplastic left heart syndrome now have a remarkably improved prognosis compared with the situation existing before the development of the Norwood sequence of operative procedures. Some of those born with hypoplastic right ventricles in the setting of pulmonary atresia with an intact ventricular septum, however, still have a relatively poor prognosis. In part this reflects the presence of fistulous communication between the cavity of the right hypoplastic right ventricle and the coronary arterial tree. Such fistulous communications are now increasingly recognised as being important in the setting of hypoplastic left heart syndrome. In this brief review, we describe the anatomy of the communications. Those found with hypoplastic right ventricles are seen most frequently when the cavity of the ventricle effectively represents only the inlet, this in turn reflecting mural overgrowth of the apical trabecular and outlet components during foetal development. This almost certainly reflects an earlier appearance of the pulmonary valvar lesion that promotes the cavitary hypoplasia. In those with hypoplastic left ventricles, the key feature differentiating those with fistulous communications is the presence of a patent mitral valve, since the left ventricle is typically no more than a virtual slit in postero-inferior ventricular wall in the setting of mitral valvar atresia or absence of the left atrioventricular connection.     

Selective aortic root angiography in the hypoplastic left heart syndrome.

Selective aortic root angiography was performed in 18 patients with the clinical diagnosis of hypoplastic left heart syndrome in order to allow more precise correlation with echocardiography. Aortic valve atresia and severe hypoplasia of the left heart chambers subsequently were substaniated at necropsy in each instance. Wide variation in the size and shape of the aortic root and ascending aorta was demonstrated angiographically in these patients. In some patients, despite aortic valve atresia, the dimensions of the aortic root and sinuses of Valsalva at angiography were almost normal. In addition, this technique allowed the demonstration of primitive vascular communications between the coronary artery and left ventricular cavity in 1 patient (coronary-cameral fistula). The realization that the aortic root may approach nearly normal size in some patients with the hypoplastic left heart syndrome is essential to the echocardiographic diagnosis of this disease and to the differential diagnosis from other cardiac and noncardiac causes of severe neonatal congestive heart failure.     

Hypoplastic left heart syndrome: report of a unique survivor

A remarkable patient is described, a child who has survived until the age of 7 years with hypoplastic left heart syndrome (mitral and aortic atresia) without surgical intervention. The child has led an active, normal life and, aside from minimal cyanosis, has remained asymptomatic. The unique clinical course for this patient is the result of a number of favorable hemodynamic factors that have not been previously reported in an individual patient with hypoplastic left heart syndrome and intact ventricular septum widely patent ductus arteriosus, adequate retrograde coronary flow, unrestricted pulmonary venous return, and absence of significant vascular obstructive disease. This documentation of long-term survival in a child without surgical treatment for mitral and aortic atresia suggests that successful early palliative treatment for infants with this syndrome could also result in a favorable prognosis.     

The nomenclature, definition and classification of hypoplastic left heart syndrome

The hypoplastic left heart syndrome encompasses a spectrum of cardiac malformations that are characterized by significant underdevelopment of the components of the left heart and the aorta, including the left ventricular cavity and mass. At the severe end of the spectrum is found the combination of aortic and mitral atresia, when the left ventricle can be close to non-existent. At the mild end are the patients with hypoplasia of the aortic and mitral valves, but without intrinsic valvar stenosis or atresia, and milder degrees of left ventricular hypoplasia. Although the majority of the patients are suitable only for functionally univentricular repair, a small minority may be candidates for biventricular repair. The nature of the syndrome was a topic for discussion at the second meeting of the International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, the Nomenclature Working Group, held in Montreal, Canada, over the period January 17 through 19, 2003. Subsequent to these discussions, the Nomenclature Working Group was able to create a bidirectional crossmap between the nomenclature initially produced jointly on behalf of the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons, and the alternative nomenclature developed on behalf of the Association for European Paediatric Cardiology. This process is a part of the overall efforts of the Nomenclature Working Group to create a comprehensive and all-inclusive international system of nomenclature for paediatric and congenital cardiac disease, the International Paediatric and Congenital Cardiac Code. In this review, we discuss the evolution of nomenclature and surgical treatment for the spectrum of lesions making up the hypoplastic left heart syndrome and its related malformations. We also present the crossmap of the associated terms for diagnoses and procedures, as recently completed by the Nomenclature Working Group.     

Left ventricular dysfunction in the fetus: relation to aortic valve anomalies and endocardial fibroelastosis.

OBJECTIVE--To examine the relation between a characteristic form of left ventricular dysfunction in the fetus and abnormalities of the aortic valve and endocardial fibroelastosis of the left ventricle. DESIGN--A retrospective study to examine the correlation between echocardiographic findings in the fetus and postnatal or necropsy findings. SETTING--Tertiary referral centre for fetal echocardiography. PATIENTS--Thirty fetuses showing a characteristic echocardiographic picture of left ventricular dysfunction. MAIN OUTCOME MEASURES--The relation between the prenatal echocardiographic features and the postnatal and necropsy findings. RESULTS--At presentation the size of the left ventricular cavity was normal or enlarged in all cases. The measurements of the orifice of the aortic root and mitral valve were either normal or small for the gestational age. The echocardiographic diagnosis made at presentation was critical aortic stenosis in all cases. At necropsy or postnatal examination the aortic valve was dysplastic and stenotic in 15 cases and the left ventricle had become hypoplastic in one of these. Aortic atresia was present in seven patients, three of whom had a hypoplastic left ventricle. In six patients the aortic valve was bicuspid although not obstructive. One of these patients had hypoplasia of the aortic arch and one had a hypoplastic left ventricle but in the remaining four patients endocardial fibroelastosis of the left ventricle was the only abnormality found. No follow up information was available in two. Of 26 patients for whom there was postmortem information, 24 had evidence of some degree of endocardial fibroelastosis of the left ventricle. Sequential observations showed that five cases developed into the hypoplastic left heart syndrome. CONCLUSIONS--This type of left ventricular dysfunction in the fetus is the result of an overlap of diseases, including primary left ventricular endocardial fibroelastosis, critical aortic stenosis, and the hypoplastic left heart syndrome.     

Left ventricular dysfunction in the fetus: relation to aortic valve anomalies and endocardial fibroelastosis.

OBJECTIVE--To examine the relation between a characteristic form of left ventricular dysfunction in the fetus and abnormalities of the aortic valve and endocardial fibroelastosis of the left ventricle. DESIGN--A retrospective study to examine the correlation between echocardiographic findings in the fetus and postnatal or necropsy findings. SETTING--Tertiary referral centre for fetal echocardiography. PATIENTS--Thirty fetuses showing a characteristic echocardiographic picture of left ventricular dysfunction. MAIN OUTCOME MEASURES--The relation between the prenatal echocardiographic features and the postnatal and necropsy findings. RESULTS--At presentation the size of the left ventricular cavity was normal or enlarged in all cases. The measurements of the orifice of the aortic root and mitral valve were either normal or small for the gestational age. The echocardiographic diagnosis made at presentation was critical aortic stenosis in all cases. At necropsy or postnatal examination the aortic valve was dysplastic and stenotic in 15 cases and the left ventricle had become hypoplastic in one of these. Aortic atresia was present in seven patients, three of whom had a hypoplastic left ventricle. In six patients the aortic valve was bicuspid although not obstructive. One of these patients had hypoplasia of the aortic arch and one had a hypoplastic left ventricle but in the remaining four patients endocardial fibroelastosis of the left ventricle was the only abnormality found. No follow up information was available in two. Of 26 patients for whom there was postmortem information, 24 had evidence of some degree of endocardial fibroelastosis of the left ventricle. Sequential observations showed that five cases developed into the hypoplastic left heart syndrome. CONCLUSIONS--This type of left ventricular dysfunction in the fetus is the result of an overlap of diseases, including primary left ventricular endocardial fibroelastosis, critical aortic stenosis, and the hypoplastic left heart syndrome.     

Echocardiographic diagnosis of atrial septal aneurysm in an infant with hypoplastic right heart syndrome

Echocardiographic findings are described in a patient with hypoplastic right heart syndrome (pulmonary atresia type with intact ventricular septum and small right ventricular cavity) who had an associated atrial septal aneurysm. An unusual appearance of echoes behind the aorta bulging into the left atrium in diastole on both the M-mode and cross-sectional echo suggested this diagnosis prior to cardiac catheterization. The angiographic findings confirmed the diagnosis of right ventricular hypoplasia, pulmonary atresia and the large atrial septal aneurysm. The infant died after surgery and the atrial septal aneurysm was observed at autopsy. The importance of the diagnosis of the atrial septal aneurysm and its association with restriction of right-to-left atrial shunting prompts this report.     

Fetal hydrops in a newborn with hypoplastic left heart syndrome: tricuspid valve "stopper"

Fetal hydrops in a newborn infant with hypoplastic left heart syndrome led to the discovery of tricuspid stenosis and insufficiency from an unusual malformation of the right venous valve of the embryonic sinus venosus. This unfortunate combination of lesions precluded surgical palliation for the hypoplastic left heart.     

Freedom from Neoaortic Insufficiency: A Comparison of Classic Norwood and Norwood–Sano Procedures

Objectives. To investigate the incidence of neoaortic insufficiency in patients with hypoplastic left heart syndrome treated with the Norwood–Sano palliation and to compare it with that occurring after the classic Norwood procedure. Design, Setting, Patients, Interventions. This was a retrospective review of all echocardiograms of patients diagnosed with hypoplastic left heart syndrome (concomitant presence of left ventricular and aortic and mitral severe hypoplasia or atresia) who underwent staged palliation of the Norwood or Norwood–Sano type at a single academic institution between September 1999 and February 2005 and who survived a minimum of 3 months. Outcome Measures. Neoaortic insufficiency was categorized as absent or mild <1 mm jet width, moderate 1–3 mm jet width, or severe >3 mm jet width. The patients were grouped according to initial palliation, that is, classic Norwood and Norwood–Sano operation. Results. Fifty‐nine consecutive patients (median age of 20 months with a range from 3 to 66 months) satisfied inclusion criteria. Neoaortic insufficiency was absent or mild in 55 of 59 (93.22%) of the patients. There were 4 cases of significant neoaortic insufficiency at late follow‐up: 2 moderate following the classic Norwood and 1 moderate and 1 severe following the Norwood–Sano procedure, one of whom required valve replacement. Conclusions. In this series of patients with hypoplastic left heart syndrome, the Sano modification was not associated with an increased incidence of significant neoaortic insufficiency. When present, moderate/severe neoaortic insufficiency appeared late after initial palliation and was associated with recurrent ascending aortic or aortic arch pathology in every case.     

Echocardiographic spectrum of the hypoplastic left heart syndrome: A clinicopathologic correlation in 19 newborns

Ultrasonic studies were performed in 19 neonates with the hypoplastic left heart syndrome whose diagnosis was confirmed at angiography or autopsy, or both. The patients were classified in two echocardiographic groups: Group I, 10 infants whose ventricular septum could be recorded, and Group II, 9 infants whose septum could not be recorded. The findings in these groups were compared with those in 60 neonates without congenital heart disease also studied with ultrasound. Two additional neonates who presented with signs of shock were also studied.The diagnostic echocardiographic features of hypoplastic left heart syndrome were: (1) a left ventricular end-diastolic dimension of less than 9 mm; (2) an aortic root diameter of less than 6 mm; (3) a ratio of left ventricular end-diastolic to right ventricular end-diastolic dimension of less than 0.6; and (4) a mitral valve echo that is absent or greatly distorted and of small amplitude. These echocardiographic criteria differed significantly from findings in the normal group (P < 0.01). Echocardiography proved valuable in neonates with shock. It is a safe, reliable technique that can be used to delineate the intracardiac anatomy in sick neonates with the hypoplastic left heart syndrome.     

Impact of placing a conduit from the right ventricle to the pulmonary arteries as the first stage of further palliation in the Norwood sequence for hypoplasia of the left heart

OBJECTIVE: We describe the experience from a single institution with the Norwood sequence of palliation for hypoplasia of the left heart, emphasizing complications related to placement of a conduit from the right ventricle to the pulmonary arteries and their management. METHODS: Between November, 2002 and January, 2006, we palliated 32 patients with hypoplastic left heart syndrome or its variants by placing a conduit from the right ventricle to the pulmonary arteries. We reviewed retrospectively the charts and angiograms from these patients. RESULTS: Hospital survival after construction of the conduit was 90.6%. There were 3 interstage deaths, of which 2 were likely due severe obstruction of the conduit. Stents were implanted into the proximal or medial portions of the conduits of 3 patients. Early revision of the distal anastomosis, and shortening the conduit, was performed early postoperatively in 2 patients. So far, 24 out 26 survivors of the first stage underwent a bi-directional cavopulmonary anastomosis after a mean interval of 4.3 plus or minus 1.4 months. Of these, 3 required a semi-urgent second stage of palliation because of worsening cyanosis, with one patient dying after the second stage. Completion of the Fontan circulation by insertion of an extracardiac conduit was performed in 8 patients at the mean age of 19.8 plus or minus 2.2 months. We were able to achieve biventricular repair in 1 patient, with aortic atresia, hypoplastic arch and ventricular septal defect, 4.3 months after the initial palliative procedure. Overall survival of the whole cohort of 32 patients was 78.9%, plus or minus 7.8%, at 5 months, and 74.3%, plus or minus 8.6%, up to 25 months. CONCLUSIONS: The introduction of the conduit placed from the right ventricle to the pulmonary arteries has led to an improved outcome in the complex entity of hypoplastic left heart syndrome and its variants. Stenosis of the conduit, nonetheless, may account for significant interstage morbidity, and often requires intervention or early installation of the second stage of palliation.     

Fetal interventions for structural heart disease

Fetal cardiac intervention (FCI) offers the potential to alter in utero anatomy and physiology. For aortic stenosis with evolving hypoplastic left heart syndrome and pulmonary atresia with intact ventricular septum with evolving hypoplastic right heart syndrome, FCI may result in maintenance of a biventricular circulation, thus avoiding single‐ventricle palliation and its attendant complications. In the case of hypoplastic left heart syndrome with intact atrial septum, FCI may ameliorate in utero pathophysiology and portend a more favorable postnatal prognosis. In all cases, a detailed fetal echocardiographic assessment to identify the appropriate FCI candidate is essential. This article reviews the three aforementioned lesions for which FCI can be considered. The pathophysiology and rationale for intervention, echocardiographic assessment, patient selection criteria, and outcomes for each lesion will be reviewed. A primary focus will be the echocardiographic evaluation of each lesion.     

Hypoplastic left heart with complete transposition of the great arteries

A male newborn infant with hypoplastic left heart and transposition of the great arteries died on the second day of life. The haemodynamic consequences of this malformation are considerably different from those of ordinary hypoplastic left heart syndrome because of pulmonary rather than aortic atresia. In the absence of cross sectional echocardiographic equipment, cardiac catheterisation with angiography is necessary to delineate the anatomical picture. These two conditions have not apparently been reported before in association.     

Hypoplastic left heart with complete transposition of the great arteries.

A male newborn infant with hypoplastic left heart and transposition of the great arteries died on the second day of life. The haemodynamic consequences of this malformation are considerably different from those of ordinary hypoplastic left heart syndrome because of pulmonary rather than aortic atresia. In the absence of cross sectional echocardiographic equipment, cardiac catheterisation with angiography is necessary to delineate the anatomical picture. These two conditions have not apparently been reported before in association.     

Relation of the echocardiographic estimate of left ventricular size to mortality in infants with severe left ventricular outflow obstruction

The relation of left ventricular size, as estimated with echocardiography, to mortality was evaluated in three groups of infants with severe left ventricular outflow obstruction. Group I consisted of 17 patients with combined aortic and mitral stenosis or atresia associated with definite hypoplasia of the left ventricle. Group II consisted of eight patients with the primary diagnosis of severe aortic stenosis. Group III consisted of 12 patients with severe coarctation of the aorta. The left ventricular enddiastolic dimension measured with M mode echocardiography and the cross-sectional area of the left ventricular cavity as seen in the parasternal long axis view of the two dimensional echocardiogram were used as indexes of left ventricular volume.All patients with symptomatic outflow obstruction and a left ventricular end-diastolic dimension of less than 13 mm died in infancy. However, five patients with a hypoplastic left ventricle proved at angiography or at autopsy, or both, were found to have a ventricular end-diastolic dimension of 13 mm or greater. Two dimensional echocardiography showed that the left ventricle in these patients was foreshortened and spherical in shape. The cross-sectional area of the left ventricle of each patient in group I was less than 1.6 cm². This was below the range of cross-sectional areas found in a group of normal infants (1.8 to 3.5 cm² ± 2 standard deviations about the mean). Three patients in groups II and III had a slightly reduced left ventricular area (1.7 cm²) and none of these patients survived infancy.Measurement of the cross-sectional area of the left ventricle is a useful method of determining left ventricular size in infants suspected of having the hypoplastic left ventricle syndrome. Patients who have reduced left ventricular volume as assessed by this technique are at very great risk even if surgical relief of the outflow obstruction is attempted.     

Aortic atresia with a solitary and indeterminate ventricle

A male infant having aortic atresia and double inlet to a solitary and indeterminate ventricle, presented a clinical picture of "hypoplastic left heart syndrome". Haemodynamic consequences are described and comparison made to other types of aortic atresia. Cross-sectional echocardiography was found to be reliable in determining both atrioventricular and ventriculo-arterial connections in the presence of aortic atresia and a solitary ventricle.