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Model of Human Fetal Growth in Hypoplastic Left Heart Syndrome: Reduced Ventricular Growth Due to Decreased
Sukriti Dewan1, Adarsh Krishnamurthy2, Devleena Kole1
1Department of Bioengineering, University of California at San Diego , La Jolla, CA , USA.
Insights
Reduced fetal heart filling in utero may cause hypoplastic left heart syndrome (HLHS) by decreasing myocardial strains. This study developed a fetal heart model to predict LV size and shape at birth using mid-gestation data.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Fetal Development
Background:
- Hypoplastic left heart syndrome (HLHS) is a congenital defect characterized by an underdeveloped left ventricle (LV), leading to insufficient systemic blood flow.
- Altered biomechanical stimuli during gestation are hypothesized to contribute to HLHS development.
- Predicting LV size at birth via mid-gestation fetal echocardiography is crucial for prognostic counseling.
Purpose of the Study:
- To investigate the hypothesis that decreased in utero ventricular filling, specifically due to mitral stenosis, reduces fetal left ventricular (LV) growth through mechanical growth signaling.
- To develop and validate a computational model for predicting fetal LV growth and remodeling.
Main Methods:
- A novel finite element model of the human fetal heart was developed, incorporating cardiac myocyte growth rates dependent on fiber and cross-fiber strains.
- The model simulates alterations in LV growth and remodeling influenced by changes in ventricular filling.
- Model results were validated against echocardiogram measurements from normal and HLHS fetal hearts.
Main Results:
- A strain-based fetal growth model accurately replicated published measurements of LV volume and dimensions from mid-gestation to birth in normal fetuses.
- Simulating a 25% reduction in mid-gestation volumetric load (emulating mitral stenosis) predicted a 65% reduction in LV end-diastolic volume and a 46% reduction in LV wall volume at birth.
- The model successfully predicted borderline and severe hypoplastic LV in retrospective HLHS case studies, with predictions validated by LV shape changes.
Conclusions:
- Reduced ventricular filling and altered shape in utero may impede LV growth by decreasing myocardial strains, which are essential myocyte growth stimuli.
- The developed human fetal growth model shows potential as a clinical tool for predicting fetal LV size and shape at birth using mid-gestation echocardiographic data.
Introduction:
Hypoplastic left heart syndrome (HLHS) is a congenital condition with an underdeveloped left ventricle (LV) that provides inadequate systemic blood flow postnatally. The development of HLHS is postulated to be due to altered biomechanical stimuli during gestation. Predicting LV size at birth using mid-gestation fetal echocardiography is a clinical challenge critical to prognostic counseling.
Hypothesis:
We hypothesized that decreased ventricular filling in utero due to mitral stenosis may reduce LV growth in the fetal heart via mechanical growth signaling.
Methods:
We developed a novel finite element model of the human fetal heart in which cardiac myocyte growth rates are a function of fiber and cross-fiber strains, which is affected by altered ventricular filling, to simulate alterations in LV growth and remodeling. Model results were tested with echocardiogram measurements from normal and HLHS fetal hearts.
Results:
A strain-based fetal growth model with a normal 22-week ventricular filling (1.04 mL) was able to replicate published measurements of changes between mid-gestation to birth of mean LV end-diastolic volume (EDV) (1.1-8.3 mL) and dimensions (long-axis, 18-35 mm; short-axis, 9-18 mm) within 15% root mean squared deviation error. By decreasing volumetric load (-25%) at mid-gestation in the model, which emulates mitral stenosis in utero, a 65% reduction in LV EDV and a 46% reduction in LV wall volume were predicted at birth, similar to observations in HLHS patients. In retrospective blinded case studies for HLHS, using mid-gestation echocardiographic data, the model predicted a borderline and severe hypoplastic LV, consistent with the patients' late-gestation data in both cases. Notably, the model prediction was validated by testing for changes in LV shape in the model against clinical data for each HLHS case study.
Conclusion:
Reduced ventricular filling and altered shape may lead to reduced LV growth and a hypoplastic phenotype by reducing myocardial strains that serve as a myocyte growth stimulus. The human fetal growth model presented here may lead to a clinical tool that can help predict LV size and shape at birth based on mid-gestation LV echocardiographic measurements.
