Severe Anomaly of Coronary-Artery Development
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《新英格兰医药杂志》
To the Editor: A three-week-old boy was admitted to the hospital because of cardiac failure with diffuse ventricular hypocontractility and normal cardiac anatomy on echocardiography. Coronary and ventricular angiography failed to show any coronary arteries from the aortic root, the pulmonary arteries, or the ventricular cavities (Figure 1A). No coronary artery was visible on the surface of the heart at the time of exploratory sternotomy. The baby died suddenly afterward.
Figure 1. Angiography and Postmortem Examination of the Heart of the Three-Week-Old Patient.
Aortography shows no coronary arteries visible from the aorta (Panel A). In an external view of the anterior face of the heart specimen, no coronary arteries are visible, only coronary veins (Panel B, arrows). With the sole segment of the coronary artery opened, one branch can be seen directed toward the left atrium (Panel C, white arrows) and one branch descending a few centimeters toward the left ventricular apex (black arrows), with the coronary veins visible (arrowheads). Histologic analysis of a section of the left ventricular wall shows the intramyocardial arteries (Panel D, arrows). Ao denotes aorta, LV left ventricle, PA pulmonary arteries, and RV right ventricle.
Postmortem examination revealed a dense network of coronary veins (Figure 1B) and a very short coronary arterial segment in the posterior atrioventricular sulcus (Figure 1C). The right ventricle, tricuspid valve, and pulmonary valve were of normal size and anatomy and had a subpulmonary conus. The left ventricle was dilated with uniformly thin walls. There were fibrous zones on the left ventricular surface and on the papillary muscles, which suggested the presence of antenatal chronic ischemia. The superior part of the inlet septum was paperlike. There were no coronary ostia within the aortic root or the pulmonary trunk or its branches. No communication was found between the cardiac chambers or the coronary veins and the small coronary arterial segment, even after the injection of contrast medium. Histologic analysis revealed a normally developed epicardium containing no coronary vessels. Several large arterial vessels were identified within the myocardium (Figure 1D). There was no communication between these vessels and the lumen of the ventricles on histologic analysis.
During embryogenesis, after cardiac-tube formation, cells that are derived from the proepicardial organ cover the myocardium to form the epicardium.1 After epithelial–mesenchymal cell transformation mediated by the friend of GATA-binding protein 2 (FOG-2) protein,2 proepicardial cells that are destined to contribute to the formation of the coronary vessels migrate to the myocardium.3 There, the cells differentiate into smooth-muscle cells, fibroblasts, and endothelial cells and form a primitive vascular network within the myocardium (called vasculogenesis, mediated by vascular endothelial growth factor and fibroblast growth factor).4 Angiogenesis and vascular remodeling lead to the formation of definitive, mature coronary arteries connected to the aorta.4
Our patient had one small coronary arterial segment, which was located at the point of emergence of definitive coronary arteries and associated with large intramyocardial arteries. This finding suggests a disruption of coronary-artery development at the remodeling stage, before the penetration of the coronary arteries into the aorta. Further genetic analysis will be needed to elucidate this unique human phenotype.
Antoine Legendre, M.D.
Lucile Houyel, M.D.
Alain Serraf, M.D.
Marie-Lannelongue Hospital
92350 Le Plessis-Robinson, France
houyel@ccml.com
References
Viragh S, Gittenberger-de Groot AC, Poelmann RE, Kalman F. Early development of quail heart epicardium and associated vascular and glandular structures. Anat Embryol (Berl) 1993;188:381-393.
Tevosian SG, Deconinck AE, Tanaka M, et al. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell 2000;101:729-739.
Reese DE, Mikawa T, Bader DM. Development of the coronary vessel system. Circ Res 2002;91:761-768.
Vrancken Peeters M-PFM, Gittenberger-de Groot AC, Mentink MMT, Hungerford JE, Little CD, Poelmann RE. The development of the coronary vessels and their differentiation into arteries and veins in the embryonic quail heart. Dev Dyn 1997;208:338-348.
Figure 1. Angiography and Postmortem Examination of the Heart of the Three-Week-Old Patient.
Aortography shows no coronary arteries visible from the aorta (Panel A). In an external view of the anterior face of the heart specimen, no coronary arteries are visible, only coronary veins (Panel B, arrows). With the sole segment of the coronary artery opened, one branch can be seen directed toward the left atrium (Panel C, white arrows) and one branch descending a few centimeters toward the left ventricular apex (black arrows), with the coronary veins visible (arrowheads). Histologic analysis of a section of the left ventricular wall shows the intramyocardial arteries (Panel D, arrows). Ao denotes aorta, LV left ventricle, PA pulmonary arteries, and RV right ventricle.
Postmortem examination revealed a dense network of coronary veins (Figure 1B) and a very short coronary arterial segment in the posterior atrioventricular sulcus (Figure 1C). The right ventricle, tricuspid valve, and pulmonary valve were of normal size and anatomy and had a subpulmonary conus. The left ventricle was dilated with uniformly thin walls. There were fibrous zones on the left ventricular surface and on the papillary muscles, which suggested the presence of antenatal chronic ischemia. The superior part of the inlet septum was paperlike. There were no coronary ostia within the aortic root or the pulmonary trunk or its branches. No communication was found between the cardiac chambers or the coronary veins and the small coronary arterial segment, even after the injection of contrast medium. Histologic analysis revealed a normally developed epicardium containing no coronary vessels. Several large arterial vessels were identified within the myocardium (Figure 1D). There was no communication between these vessels and the lumen of the ventricles on histologic analysis.
During embryogenesis, after cardiac-tube formation, cells that are derived from the proepicardial organ cover the myocardium to form the epicardium.1 After epithelial–mesenchymal cell transformation mediated by the friend of GATA-binding protein 2 (FOG-2) protein,2 proepicardial cells that are destined to contribute to the formation of the coronary vessels migrate to the myocardium.3 There, the cells differentiate into smooth-muscle cells, fibroblasts, and endothelial cells and form a primitive vascular network within the myocardium (called vasculogenesis, mediated by vascular endothelial growth factor and fibroblast growth factor).4 Angiogenesis and vascular remodeling lead to the formation of definitive, mature coronary arteries connected to the aorta.4
Our patient had one small coronary arterial segment, which was located at the point of emergence of definitive coronary arteries and associated with large intramyocardial arteries. This finding suggests a disruption of coronary-artery development at the remodeling stage, before the penetration of the coronary arteries into the aorta. Further genetic analysis will be needed to elucidate this unique human phenotype.
Antoine Legendre, M.D.
Lucile Houyel, M.D.
Alain Serraf, M.D.
Marie-Lannelongue Hospital
92350 Le Plessis-Robinson, France
houyel@ccml.com
References
Viragh S, Gittenberger-de Groot AC, Poelmann RE, Kalman F. Early development of quail heart epicardium and associated vascular and glandular structures. Anat Embryol (Berl) 1993;188:381-393.
Tevosian SG, Deconinck AE, Tanaka M, et al. FOG-2, a cofactor for GATA transcription factors, is essential for heart morphogenesis and development of coronary vessels from epicardium. Cell 2000;101:729-739.
Reese DE, Mikawa T, Bader DM. Development of the coronary vessel system. Circ Res 2002;91:761-768.
Vrancken Peeters M-PFM, Gittenberger-de Groot AC, Mentink MMT, Hungerford JE, Little CD, Poelmann RE. The development of the coronary vessels and their differentiation into arteries and veins in the embryonic quail heart. Dev Dyn 1997;208:338-348.