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Review
. 2023 Aug 3;10(8):333.
doi: 10.3390/jcdd10080333.

Unique Pulmonary Hypertensive Vascular Diseases Associated with Heart and Lung Developmental Defects

Hidekazu Ishida  1 , Jun Maeda  2 , Keiko Uchida  3   4 , Hiroyuki Yamagishi  3
Affiliations
Review

Unique Pulmonary Hypertensive Vascular Diseases Associated with Heart and Lung Developmental Defects

Hidekazu Ishida et al. J Cardiovasc Dev Dis. .

Abstract

Although pediatric pulmonary hypertension (PH) shares features and mechanisms with adult PH, there are also some significant differences between the two conditions. Segmental PH is a unique pediatric subtype of PH with unclear and/or multifactorial pathophysiological mechanisms, and is often associated with complex congenital heart disease (CHD), pulmonary atresia with ventricular septal defect, and aortopulmonary collateral arteries. Some cases of complex CHD, associated with a single ventricle after Fontan operation, show pathological changes in the small peripheral pulmonary arteries and pulmonary vascular resistance similar to those observed in pulmonary arterial hypertension (PAH). This condition is termed as the pediatric pulmonary hypertensive vascular disease (PPHVD). Recent advances in genetics have identified the genes responsible for PAH associated with developmental defects of the heart and lungs, such as TBX4 and SOX17. Targeted therapies for PAH have been developed; however, their effects on PH associated with developmental heart and lung defects remain to be established. Real-world data analyses on the anatomy, pathophysiology, genetics, and molecular biology of unique PPHVD cases associated with developmental defects of the heart and lungs, using nationwide and/or international registries, should be conducted in order to improve the treatments and prognosis of patients with these types of pediatric PH.

Keywords: Fontan circulation; congenital heart disease; developmental disorders; genetic analysis; major aortopulmonary collateral arteries; pulmonary hypertension; tetralogy of Fallot.

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Conflict of interest statement

H.Y. received research grants from Jansen Pharmaceuticals Japan, Ltd. The sponsors had no role in the design, execution, interpretation, or writing of the study. The authors declare that the research was conducted in the absence of commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Development of the normal pulmonary artery and types of MAPCA [10]. (A) The developing pulmonary vascular system in the early embryonic stage. (B–E) Development of the pulmonary artery and MAPCA. The development of the sixth pharyngeal arch artery, pulmonary blood supply, and frequency of each type are shown in the table below the figure. Ao, aorta; ISA, intersegmental artery; MAPCA, major aorto-pulmonary collateral arteries; PAA, pharyngeal arch artery; PPA, peripheral pulmonary artery; PT, pulmonary trunk.
Figure 2
Figure 2
MDCT imaging and aortogram of MAPCA. (A) MAPCA (arrows) viewed from the back. (B) The central PA (arrowhead) and MAPCA. (C) Aortogram showing the total image of MAPCA. (D–H) Selective angiograms of MAPCA. Ao, descending aorta; MAPCA, major aorto-pulmonary collateral arteries; MDCT, multidetector computed tomography; PA, pulmonary artery.
Figure 3
Figure 3
MDCT imaging of repaired TOF and MAPCA in frontal (A) and back (B) views. The left pulmonary arteries are hypoplastic and tortuous (arrows). MAPCA, major aorto-pulmonary collateral arteries; MDCT, multidetector computed tomography; TOF, tetralogy of Fallot.
See this image and copyright information in PMC

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