Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?

Figures

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  Figure 1. The images, all photographed by Diane E. Spicer and reproduced with her permission, show the phenotypic variants of hypoplastic left heart syndrome as seen in the clinical setting. The upper left panel shows the variant with mitral stenosis and aortic atresia. The heart in the upper right-hand panel has mitral and aortic stenosis. In the lower panels, to the left is seen the variant with mitral atresia, and to the right is the rarest variant with left ventricular hypoplasia with the small aortic and mitral valves, their size in keeping with that of the left ventricle although the aortic valve is not seen in the four-chamber section through the heart.

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  Figure 2. Wildtype (A) and ETS-1 Drosophila loss-of-function mutant (B) demonstrating increased cardiac myocytes causing the obliteration of the chamber (Reproduced with permission from Alvarez AD, et al., Development. 2003;130:3015-26).

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  Figure 3. The ETS-1 knockdown (KD) in a frog. (A) Wildtype (B) neural crest KD, and (C) heartfield KD. SS = spiral septum; OFT = outflow tract; and V = ventricle. The knockdown of ETS-1 only in the neural crest results in outflow tract defects, but a normal ventricle indicates that additional factors are required for the development of the “hypoplastic” ventricle. The knockdown of ETS-1 in the cardiac mesoderm causing the “hypoplastic” left ventricle indicates a mesodermally derived factor contributes to the development of the “hypoplastic” left ventricle (Reproduced with permission from Nie S and Bronner S, 2015).

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  Figure 4. The panels show the result of the knockdown of the cardiac mesoderm-specific ETS-1 knockdown in the frog. The upper left panel (A) shows a control heart, while the upper right (B) and lower (C) show knockdown hearts. The lower panel is particularly significant, with the arrows showing a mixed ventricular phenotype, with differential thinning and thickening of the wall. Abbreviation: V: ventricle.

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  Figure 5. The Drosophila NOTCH mutant heart: (A) a normal heart and (B) a mutant heart. Similar to ETS1 mutants, there is a loss of pericardial cells (pc) and a gain of cardiac myocytes (cb). (Reproduced with permission from Hartenstein A., et al., 1992).

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  Figure 6. The transgenic overexpression of BMP10 in the developing murine left ventricle (A) results in a hypertrabeculated LV in which the chamber volume is severely diminished. The wildtype control is shown in B. (Reproduced with permission from Pashmforoush M., et al., 2004).

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  Figure 7. A fetal echo of a 22-week fetus with hypoplastic left heart syndrome here shown with a dilated, apex-forming, poorly functioning left ventricle. Abbreviations: LV: left ventricle; RV: right ventricle; LA: left atrium; and RA: right atrium (Reproduced with permission from Feinstein J., et al., JACC, 2011).

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  Figure 8. Endocardial-specific genetic ablation in E9.5 mouse embryo. Control: left in each panel; endocadial-deficient embryo: right in each panel (Reproduced with permission from Snider P, et al. J Cardiovasc. Dev. Dis. 2014 Dec;1(3):214-236).