scholarly journals Effect of left atrial ligation-driven altered inflow hemodynamics on embryonic heart development: clues for prenatal progression of hypoplastic left heart syndrome

2021 ◽  
Author(s):  
Huseyin Enes Salman ◽  
Maha Alser ◽  
Akshay Shekhar ◽  
Russell A. Gould ◽  
Fatiha M. Benslimane ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Hypoplastic Left Heart Syndrome ◽  
Heart Development ◽  
Left Atrial ◽  
Heart Defects ◽  
Systemic Circulation ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
The Right ◽  
Left Heart Syndrome

AbstractCongenital heart defects (CHDs) are abnormalities in the heart structure present at birth. One important condition is hypoplastic left heart syndrome (HLHS) where severely underdeveloped left ventricle (LV) cannot support systemic circulation. HLHS usually initiates as localized tissue malformations with no underlying genetic cause, suggesting that disturbed hemodynamics contribute to the embryonic development of these defects. Left atrial ligation (LAL) is a surgical procedure on embryonic chick resulting in a phenotype resembling clinical HLHS. In this study, we investigated disturbed hemodynamics and deteriorated cardiac growth following LAL to investigate possible mechanobiological mechanisms for the embryonic development of HLHS. We integrated techniques such as echocardiography, micro-CT and computational fluid dynamics (CFD) for these analyses. Specifically, LAL procedure causes an immediate flow disturbance over atrioventricular (AV) cushions. At later stages after the heart septation, it causes hemodynamic disturbances in LV. As a consequence of the LAL procedure, the left-AV canal and LV volume decrease in size, and in the opposite way, the right-AV canal and right ventricle volume increase. According to our CFD analysis, LAL results in an immediate decrease in the left AV canal WSS levels for 3.5-day (HH21) pre-septated hearts. For 7-day post-septated hearts (HH30), LAL leads to further reduction in WSS levels in the left AV canal, and relatively increased WSS levels in the right AV canal. This study demonstrates the critical importance of the disturbed hemodynamics during the heart valve and ventricle development.

scholarly journals Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeanne L Theis ◽  
Georg Vogler ◽  
Maria A Missinato ◽  
Xing Li ◽  
Tanja Nielsen ◽  
...  
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Heart Development ◽  
Heart Diseases ◽  
Heart Defects ◽  
Patient Specific ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Healthy Human ◽  
Altered Expression ◽  
Left Heart Syndrome

Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates. siRNA/RNAi-mediated knockdown in healthy human iPSC-derived cardiomyocytes (hiPSC-CM) and in developing Drosophila and zebrafish hearts revealed that LDL receptor-related protein LRP2 is required for cardiomyocyte proliferation and differentiation. Consistent with hypoplastic heart defects, compared to parents the proband’s iPSC-CMs exhibited reduced proliferation. Interestingly, rare, predicted-damaging LRP2 variants were enriched in a HLHS cohort; however, understanding their contribution to HLHS requires further investigation. Collectively, we have established a multi-species high-throughput platform to rapidly evaluate candidate genes and their interactions during heart development, which are crucial first steps toward deciphering oligogenic underpinnings of CHDs, including hypoplastic left hearts.

scholarly journals Fluid mechanics of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome

2021 ◽  
Author(s):  
Sheldon Ho ◽  
Wei Xuan Chan ◽  
Choon Hwai Yap
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Left Atrial ◽  
Shear Stresses ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Mechanical Environment ◽  
4D Ultrasound ◽  
The Right ◽  
Left Heart Syndrome ◽  
Pharmacological Manipulations

AbstractLeft atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model.

Hypoplastic left heart syndrome: multiprofessional follow-up in the mid-term following palliative procedures

1997 ◽  
Vol 7 (3) ◽  
pp. 248-253 ◽  
Author(s):  
Petter S. Hagemo ◽  
Magnhild Rasmussen ◽  
Grete Bryhn ◽  
Inger Helena Vandvik
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Motor Development ◽  
Autistic Traits ◽  
Attention Problems ◽  
Child Psychiatrist ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Mild Degree ◽  
The Right ◽  
Left Heart Syndrome

AbstractOf the 12 children who represent the complete cohort of Norwegian patients surviving the complete palliative operative programme for hypoplastic left heart syndrome, 10 were studied by a pediatric cardiologist, a pediatric neurologist, a neuropsychologist and a child psychiatrist. We found significant morbidity. Hemodynamic function was relatively uncompromised in eight of the patients, but one had significant cyanosis due to use of an operative technique subsequently abandoned and one had obstruction of the flow of blood from the left to the right atrium. Five children had disturbances of rhythm, with one requiring insertion of a pacemaker. One child had epilepsy. Delayed motor development, most often to mild degree, was found in seven children, while six had attention problems. Mental retardation was found in two children and autistic traits in one. Despite these various problems, the parents were seemingly satisfied with their own lives, and the quality of life of their children.

Hypoplastic Left Heart Syndrome: Natural History in a Geographically Defined Population

PEDIATRICS ◽  
1990 ◽  
Vol 85 (6) ◽  
pp. 977-983
Author(s):  
Cynthia D. Morris ◽  
Jacquelyn Outcalt ◽  
Victor D. Menashe
Keyword(s):  
Natural History ◽  
Hypoplastic Left Heart Syndrome ◽  
Congenital Heart ◽  
Heart Defects ◽  
Norwood Procedure ◽  
Secular Change ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
History Of ◽  
Left Heart Syndrome

Advances in surgical treatment of hypoplastic left heart syndrome with the Norwood procedure and cardiac transplantation have made essential the understanding of the natural history of hypoplastic left heart syndrome. In a geographically defined population, we ascertained the prevalence of hypoplastic left heart syndrome in children born in Oregon from 1971 through 1986. Clinical and anatomic data were extracted from the charts of the 98 affected children and the survival rate was calculated. Hypoplastic left heart syndrome occurred in 0.162 per 1000 live births in Oregon during this period. No syndrome complex was prevalent and 84% were free of other congenital malformations. However, there was an increased occurrence of congenital heart defects in first-degree relatives of probands with hypoplastic left heart syndrome. Of the affected children 15 ± 4% died on the first day of life, 70 ± 5% died within the first week, and 91 ± 3% died within 30 days. No secular change in survival occurred during the study. Palliation with the Norwood procedure was performed in 20 children. Although survival was significantly improved with this surgery (P = .01), the effect was observed principally through 30 days of life and only one of these children remains alive. Hypoplastic left heart syndrome is a lethal congenital heart defect in children and poses management and ethical dilemmas.

The genetics of hypoplastic left heart syndrome

1999 ◽  
Vol 9 (6) ◽  
pp. 627-632 ◽  
Author(s):  
Paul D. Grossfeld
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Heart Defects ◽  
Left Ventricular ◽  
Left Ventricular Cavity ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Term Survival ◽  
Surgical Options ◽  
Systemic Ventricle ◽  
Left Heart Syndrome

Hypoplastic left heart syndrome is one of the most therapeutically challenging congenital cardiac defects. It accounts for as many as 1.5% of all congenital heart defects, but is responsible for up to one quarter of deaths in neonates with heart disease.1The management of hypoplastic left heart syndrome is controversial. Two surgical options exist:2,3the Norwood procedure, is a three stage repair in which the morphologically right ventricle is converted to function as the systemic ventricle. Alternatively, orthotopic transplantation can be performed. Although both surgical options have had improved outcomes, the prognosis for long-term survival is guarded, with a five year survival for either approach reported to be in the region of 50–60%. In this review, I explore the evidence for a genetic etiology for the “classic” hypoplastic left heart syndrome, defined as mitral and/or aortic atresia with hypoplasia of the left ventricular cavity and the other left-sided structures.

Pathological changes and myocardial remodelling related to the mode of shunting following surgical palliation for hypoplastic left heart syndrome

2008 ◽  
Vol 18 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Massimo A. Padalino ◽  
Chiara Castellani ◽  
Silvia Toffoli ◽  
Mila Della Barbera ◽  
Ornella Milanesi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Right Ventricle ◽  
Hypoplastic Left Heart Syndrome ◽  
Pulmonary Arteries ◽  
Left Heart ◽  
Pulmonary Shunt ◽  
Hypoplastic Left Heart ◽  
Surgical Palliation ◽  
The Right ◽  
Left Heart Syndrome

AbstractBackgroundThe modification of placing the shunt from the right ventricle to the pulmonary arteries, also known as Sano procedure, has allegedly improved results over the short term in surgical palliation of hypoplastic left heart syndrome with the Norwood procedure. With this in mind, we reviewed autopsied specimens from neonates and children who did not survive after either a classic arterio-pulmonary shunt, or the modified procedure with the shunt placed from the right ventricle to the pulmonary arteries, so as to evaluate the pathological substrates of the remodelling of the systemic right ventricle, assessing any differences induced by the 2 techniques.MethodsWe obtained the hearts from 11 patients with neonatal diagnosis of hypoplastic left heart syndrome who died after the first or second stages of the Norwood sequence of operations, comparing them with 6 normal hearts matched for age and weight. Macroscopic, microscopic and morphometric analysis were performed on each specimen, evaluating the diameter of the myocytes, extracellular matrix remodelling in terms of fibrosis and type of collagen, and vascularization in terms of capillary density.ResultsHypertrophy of the myocytes was significantly increased in the hearts from patients having either a classic arterio-pulmonary or the ventriculo-pulmonary modification of the shunt compared to controls (p < 0.05). Myocardial fibrosis was increased in those having a shunt placed from the right ventricle to the pulmonary arteries when compared to the other 2 groups. The ratio of collagen I to collagen III was similar in those undergoing a classic arterio-pulmonary shunt compared to controls (0.94), but was lower in those having a shunt placed from the right ventricle to the pulmonary arteries (0.61), with an increase in collagen type III. The density of capillaries was lower in those who had undergone a classic arterial shunt when compared to the others.ConclusionWe have shown greater remodelling of the ventricular myocardial extracellular matrix in patients having a shunt from the right ventricle to the pulmonary arteries when compared to those having a classic arterio-pulmonary shunt, with this remodelling progressing even after the neonatal period. This may influence a later suboptimal ventricular performance.

scholarly journals Umbilical Neutrophil Gelatinase-Associated Lipocalin Level as an Early Predictor of Acute Kidney Injury in Neonates with Hypoplastic Left Heart Syndrome

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Piotr Surmiak ◽  
Małgorzata Baumert ◽  
Małgorzata Fiala ◽  
Zofia Walencka ◽  
Andrzej Więcek
Keyword(s):  
Acute Kidney Injury ◽  
Hypoplastic Left Heart Syndrome ◽  
Heart Defects ◽  
Kidney Injury ◽  
High Sensitivity ◽  
Left Heart ◽  
Acid Base Balance ◽  
Hypoplastic Left Heart ◽  
Umbilical Blood ◽  
Left Heart Syndrome

Acute kidney injury (AKI) is a primarily described complication after unbalanced systemic perfusion in neonates with congenital heart defects, including hypoplastic left heart syndrome (HLHS). The aim of the study was to compare the umbilical NGAL concentrations between neonates born with HLHS and healthy infants, as well as to analyze whether the determination of NGAL level could predict AKI in neonates with prenatally diagnosed HLHS. Twenty-one neonates with prenatally diagnosed HLHS were enrolled as study group and 30 healthy neonates served as controls. Perinatal characteristics and postnatal parameters were extracted from the hospital neonatal database. In umbilical cord blood, we determined plasma NGAL concentrations, acid base balance, and lactate and creatinine levels. In neonates with HLHS, complications (respiratory insufficiency, circulatory failure, NEC, IVH, and AKI) were recorded until the day of cardiosurgery. We observed in neonates with HLHS higher umbilical NGAL levels compared to controls. Among 8 neonates with HLHS and diagnosed AKI stage 1, we observed elevated NGAL levels in comparison to those newborns without AKI. Umbilical NGAL could predict, with high sensitivity and specificity, AKI development in study neonates. We suggest that the umbilical blood NGAL concentration may be an early marker to predict AKI in neonates with HLHS.

Hypoplastic left heart syndrome with anomalous origin of right pulmonary artery

2020 ◽  
pp. 021849232095506
Author(s):  
Ashish Mishra ◽  
Bhavik Champaneri ◽  
Yashpal Rana ◽  
Gaurav Singh ◽  
Senthilraj Thangasami ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Hypoplastic Left Heart Syndrome ◽  
Venous Drainage ◽  
Anomalous Origin ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Right Pulmonary Artery ◽  
Complex Forms ◽  
The Right ◽  
Left Heart Syndrome

Classic hypoplastic left heart syndrome is a rare but fatal congenital heart disease associated with variable underdevelopment of the left side of the heart. Complex forms of hypoplastic left heart syndrome have been reported to coexist with anomalous pulmonary venous drainage, transposition of the great arteries, or pulmonary valve dysplasia. We report a case of hypoplastic left heart syndrome with anomalous origin of the right pulmonary artery from the ascending aorta a rare association not reported in the literature. Preoperative comprehensive echocardiography is essential for diagnosis and accurate recognition of such rare anatomic variations.

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