Anomalías congénitas de arterias coronarias, estudio de aquellas con Importancia hemodinámica / Evaluation of the hemodynamically significant congenital anomalies of coronary arteries

Resumen: Las anomalías de las arterias coronarias son poco frecuentes, con una prevalencia de 0,21- 5,79%. Su presentación clínica es amplia, pudiendo ser asintomáticas o presentarse como isquemia miocárdica y muerte súbita, la que puede estar ligada o no al ejercicio. Existen varias clasificaciones, siendo las más usadas las que las agrupan desde un punto de vista anatómico en relación con el segmento afectado (origen, curso o terminación) y desde el punto de vista funcional (hemodinámicamente significativa y no significativa). Actualmente la Tomografía Computada Cardiaca se considera el estándar de referencia, siendo de suma importancia su adecuada caracterización ya que, de requerir tratamiento, este generalmente es quirúrgico. El objetivo de este trabajo es identificar, caracterizar y clasificar las anomalías congénitas de las arterias coronarias por su importancia hemodinámica mediante la presentación de casos clínicos y revisión de la literatura.

Abstract: Coronary artery anomalies are rare, with a prevalence ranging from 0.21 to 5.79%. Their clinical presentation is variable; being either asymptomatic or presenting as myocardial ischemia and sudden death, which may or may not be linked to exercise. There are several classifications, the most commonly used being those that sort them from an anatomical point of view in relation to the affected segment (origin, course or termination) and from a functional point of view (hemodynamically significant and not significant). Currently, Cardiac Computed Tomography is considered the reference standard allowing an adequate characterization of the anomaly, which is highly relevant since, if treatment is needed, it usually involves surgery. The purpose of this review is to identify, characterize and classify congenital anomalies of the coronary arteries according to their hemodynamic significance through the presentation of clinical cases and review of the literature.

Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology--a position statement of the development, anatomy, and pathology ESC Working Group.

Congenital coronary artery anomalies are of major significance in clinical cardiology and cardiac surgery due to their association with myocardial ischaemia and sudden death. Such anomalies are detectable by imaging modalities and, according to various definitions, their prevalence ranges from 0.21 to 5.79%. This consensus document from the Development, Anatomy and Pathology Working Group of the European Society of Cardiology aims to provide: (i) a definition of normality that refers to essential anatomical and embryological features of coronary vessels, based on the integrated analysis of studies of normal and abnormal coronary embryogenesis and pathophysiology; (ii) an animal model-based systematic survey of the molecular and cellular mechanisms that regulate coronary blood vessel development; (iii) an organization of the wide spectrum of coronary artery anomalies, according to a comprehensive anatomical and embryological classification scheme; (iv) current knowledge of the pathophysiological mechanisms underlying symptoms and signs of coronary artery anomalies, with diagnostic and therapeutic implications. This document identifies the mosaic-like embryonic development of the coronary vascular system, as coronary cell types differentiate from multiple cell sources through an intricate network of molecular signals and haemodynamic cues, as the necessary framework for understanding the complex spectrum of coronary artery anomalies observed in human patients.

Coronary arterial development: a review of normal and congenitally anomalous patterns.

Coronary artery development is a delicate, complex, and finely tuned process that includes multiple interactions among many pathways, especially in the pericardium and the developing myocardium. There still exists some controversy on the exact origin of certain cellular components. Nevertheless, an understanding of this extremely important developmental process is paramount in identifying some of the causes of anomalous coronary development. There are different patterns of anomalous coronary arteries, with variable risk of myocardial ischemia, malignant arrhythmias, and sudden cardiac death. These anomalies can be broadly categorized into 2 basic anatomic subsets: those with origin of the anomalous coronary artery from the opposite aortic sinus, and those with origin of the anomalous coronary artery from the pulmonary artery. Diagnosis and management of such patterns continues to be challenging. A good knowledge of the normal and abnormal coronary artery development could potentially help us explore new avenues in the treatment of ischemic heart disease as well as anomalous coronary arteries.

Left main coronary atresia in a child with absent pulmonary valve syndrome: early entrapment of an innocent bystander.

Atresia of the left main coronary artery is a rare anomaly that, if left untreated, has an unfavorable outcome. We hereby report left main coronary artery atresia in a child with tetralogy of Fallot with absent pulmonary valve and discuss the possible developmental basis of the association.

Nitric oxide synthase-3 deficiency results in hypoplastic coronary arteries and postnatal myocardial infarction.

AIMS: Hypoplastic coronary artery disease is a rare congenital abnormality that is associated with sudden cardiac death. However, molecular mechanisms responsible for this disease are not clear. The aim of the present study was to assess the role of nitric oxide synthase-3 (NOS3) in the pathogenesis of hypoplastic coronary arteries. METHODS AND RESULTS: Wild-type (WT), NOS3(-/-), and a novel cardiac-specific NOS3 overexpression mouse model were employed. Deficiency in NOS3 resulted in coronary artery hypoplasia in foetal mice and spontaneous myocardial infarction in postnatal hearts. Coronary artery diameters, vessel density, and volume were significantly decreased in NOS3(-/-) mice at postnatal day 0. In addition, NOS3(-/-) mice showed a significant increase in the ventricular wall thickness, myocardial volume, and cardiomyocyte cell size compared with WT mice. Lack of NOS3 also down-regulated the expression of Gata4, Wilms tumour-1, vascular endothelial growth factor, basic fibroblast growth factor and erythropoietin, and inhibited migration of epicardial cells. These abnormalities and hypoplastic coronary arteries in the NOS3(-/-) mice were completely rescued by the cardiac-specific overexpression of NOS3. CONCLUSION: Nitric oxide synthase-3 is required for coronary artery development and deficiency in NOS3 leads to hypoplastic coronary arteries.

Successful surgical treatment of a gigantic congenital coronary artery fistula immediately after birth.

A foetus was prenatally diagnosed with a gigantic (12 mm) coronary artery fistula (CAF) from the left anterior descending (LAD) coronary artery to right ventricular apex at 38 weeks of gestation. LAD was dilated to 10 mm with partial aneurysmal changes. Because of concern for sudden ischaemic cardiogenic shock soon after birth, the child was electively delivered by caesarean section, with surgical fistula closure subsequently performed 1 h after birth. We also highly suspected the presence of a clinically significant accessory diagonal branch just around the fistula, thus direct fistula closure from outside the heart without cardiopulmonary bypass was abandoned and cardiopulmonary bypass was initiated. The terminal end of LAD was carefully opened, and the fistula was directly closed with four pairs of 6-0 polypropylene mattress sutures under cardioplegic arrest, while the opened terminal end of LAD was also repaired with plegetted 6-0 polypropylene mattress and over-and-over sutures. After 4 days of post-surgical extracorporeal life support for over-systemic pulmonary hypertension, the patient recovered without complications. Although postoperative echocardiography 5 months after the operation showed normal cardiac function without ventricular asynergy, the dilated and aneurysmal LAD remained unchanged.

The cytoplasmic domain of TGFßR3 through its interaction with the scaffolding protein, GIPC, directs epicardial cell behavior.

The epicardium is a major contributor of the cells that are required for the formation of coronary vessels. Mice lacking both copies of the gene encoding the Type III Transforming Growth Factor ß Receptor (TGFßR3) fail to form the coronary vasculature, but the molecular mechanism by which TGFßR3 signals coronary vessel formation is unknown. We used intact embryos and epicardial cells from E11.5 mouse embryos to reveal the mechanisms by which TGFßR3 signals and regulates epicardial cell behavior. Analysis of E13.5 embryos reveals a lower rate of epicardial cell proliferation and decreased epicardially derived cell invasion in Tgfbr3(-/-) hearts. Tgfbr3(-/-) epicardial cells in vitro show decreased proliferation and decreased invasion in response to TGFß1 and TGFß2. Unexpectedly, loss of TGFßR3 also decreases responsiveness to two other important regulators of epicardial cell behavior, FGF2 and HMW-HA. Restoring full length TGFßR3 in Tgfbr3(-/-) cells rescued deficits in invasion in vitro in response TGFß1 and TGFß2 as well as FGF2 and HMW-HA. Expression of TGFßR3 missing the 3 C-terminal amino acids that are required to interact with the scaffolding protein GIPC1 did not rescue any of the deficits. Overexpression of GIPC1 alone in Tgfbr3(-/-) cells did not rescue invasion whereas knockdown of GIPC1 in Tgfbr3(+/+) cells decreased invasion in response to TGFß2, FGF2, and HMW-HA. We conclude that TGFßR3 interaction with GIPC1 is critical for regulating invasion and growth factor responsiveness in epicardial cells and that dysregulation of epicardial cell proliferation and invasion contributes to failed coronary vessel development in Tgfbr3(-/-) mice.

Imaging of coronary artery anomalies.

Coronary artery anomalies (CAA) are uncommon congenital variations in coronary anatomy, occurring in 0.2% to 1.2% of the general population, the majority of which are detected incidentally and have little clinical significance. A minority of CAA, primarily due to an interarterial course, is clinically significant, and may present with symptoms of myocardial ischemia, malignant ventricular arrhythmias, and even sudden cardiac death. Until recently, CAA were primarily detected at catheter coronary angiography. With recent advances in multidetector computed tomography (CT) technology and the use of electrocardiographic gating, coronary CT angiography provides an exquisite omnidimensional display of the anomalous coronary arteries and their relation to the adjacent structures noninvasively, and is the diagnostic test of choice. Understanding CAA morphology and clinical significance of CAA is important for establishing a diagnosis, and is essential for appropriate patient management and treatment planning.

[Surgical relevance of some aspects of heart's embriology]. / Importancia quirúirgica de algunos aspectos de la embriología del corazon.

We consider some aspects of cardiac embriology which explain the formation of pericardial cysts, anomalies of venae cavae, types of atrial septal defect (ostium primum, secundum, foramen ovale), anomalies in septal ventricular development by absence of structures to perform the septum (atrio-ventricularis communis, truncus arteriosus), lack of alineation (Taussig-Bing's complex, transposition of the great vessels, Eisenmenger's complex, Fallot's tetralogy) or interruption in their development (isolated ventricular septal defect). Finally the evolution of aortic arcs, ductus, aorta's istmus and anomalies in coronary arteries, are also considered.

Ectopic origin of left coronary ostium from left ventricle, with occlusive membrane: a previously unreported anomaly, with an embryologic interpretation.

Congenital atresia of the left main coronary artery, a condition in which the left main trunk is developed but has been occluded since birth, is a rare coronary anomaly. Herein, we describe this anomaly's association with a subannular location of an obliterated left main ostium in a patient with a bicuspid aortic valve and severe aortic stenosis. The patient underwent successful surgery. We discuss the embryologic implications of congenital atresia of the left main coronary artery, in view of the exceptional anatomic features of this condition. To our knowledge, this is the 1st report of a left coronary artery that was found to arise from the left ventricle.

A new hypothesis of the developmental origin of congenital left anterior descending coronary artery to pulmonary artery fistulas.

The embryologic origin of fistulous communications between a coronary artery and the pulmonary artery has traditionally been explained as the persistence of an immature supernumerary coronary artery with its origin in the pulmonary trunk. Although this hypothesis is consistent with the occurrence of the termination of the fistula in the posterior sinus of the pulmonary artery, it does not completely explain several morphologic and physiologic aspects. In this report, we present a case illustrating the classic anatomic features of left anterior descending artery to pulmonary artery fistulas and develop a new hypothesis of its embryologic origin and re-emergence in adults that fully explains its angiographic appearance and clinical attributes.

Management of sinus venosus defects.

Sinus venosus defects are not atrial septal defects, but are intra-atrial communications outside of the boundaries of the atrial septum. The superior type is located above and separate from the fossal ovalis, usually adjacent to the superior vena cava and the right upper pulmonary vein. The inferior type is located near the orifice of the inferior vena cava and the right lower pulmonary vein. The goal of surgical repair is closure of the defect with unobstructed drainage of the pulmonary veins to the left atrium and of the vena cava to the right atrium. Numerous techniques have been described, particularly for the repair of the superior vena cava type of defect. Mortality and morbidity should be minimal. The risk of either vena cava or pulmonary vein obstruction is low. Sinus node dysfunction can occur postoperatively, particularly when an incision has been made across the superior vena cava/right atrial junction. There is little long-term data on the functional outcomes following repair of these defects.

Coronary artery and orifice development is associated with proper timing of epicardial outgrowth and correlated Fas-ligand-associated apoptosis patterns.

The proepicardial organ provides differentiated cell types to the myocardial wall and facilitates coronary development. Ingrowth of the coronary arteries into the aorta has recently been linked to apoptosis. This study was set up to examine the effect of an inhibition of epicardial outgrowth on apoptotic patterning and coronary development. Epicardial outgrowth was blocked at HH15-17 in quail embryos, which survived until HH25-35 (n=33). Embryos with complete inhibition of outgrowth did not survive after HH29. These embryos presented with thin compact myocardium, devoid of vessels. In embryos with delayed epicardial outgrowth the phenotype was less severe, and surviving embryos were studied up to HH35. In these embryos, myocardial vascularization was poor and apoptosis in the peritruncal region at HH30 was diminished. Embryos at HH35 displayed an abnormal coronary network and absent coronary orifices. In a further set of experiments (n=10), outgrowth was inhibited in chicken embryos at HH15, followed by transplantation of a quail proepicardial organ into the pericardial cavity to rescue cardiac phenotype. These chimeras were studied at HH29 and HH35. Myocardial development was restored; however, in 3 of 4 embryos (HH35), the coronary orifices were absent. Examination of double stainings of quail-chicken chimeras revealed that EPDCs produce Fas ligand as an apoptotic inductor at sites of coronary ingrowth. In the absence of proper timing of epicardial outgrowth, myocardial development and vascularization are disturbed. Also apoptosis in the peritruncal region is diminished. During later development, this leads to defective or absent connections of the coronary system to the systemic circulation.

Role of growth factors in coronary morphogenesis.

This communication briefly reviews the role of angiogenic growth factors in myocardial vessel formation during development. The earliest signs of vascularization are the migration and differentiation of angioblasts from the epicardium and subepicardium into the myocardium. A regulator of this process is vascular endothelial growth factor (VEGF), which is probably triggered by hypoxia. The subsequent formation of vascular tubes is regulated by multiple growth factors: VEGF family members, fibroblast growth factors (FGFs), and angiopoietins and their receptors. Our studies on explanted quail hearts reveal that these growth factors are interdependent. We also have shown that a harmonic interplay of growth factors characterizes early postnatal development in rats. Neutralizing antibodies to either basic FGF (bFGF) or VEGF inhibit capillary formation, whereas arteriolar growth is markedly inhibited by bFGF, but not VEGF, neutralizing antibodies. Arteriolar diameter is also increased when anti-bFGF and anti-VEGF are administered in combination. Thus, the hierarchical development of the arteriolar vasculature depends on both of these growth factors; however, the establishment of arterioles, as reflected by length density, is dependent on bFGF but not on VEG. Finally, stretch of cardiac myocytes and endothelial cells serves as a stimulus for increases in growth factor and receptor proteins. We have shown that cyclic stretch of either cell type increases VEGF, and that endothelial cells respond to stretch by up-regulation of VEGF receptor-2 (VEGFR-2), and Tie-2 receptor. These results indicate that both mechanical and metabolic factors are primary stimuli for coronary angiogenesis.

Coronary arterial and sinusal anatomy in hearts with a common arterial trunk.

Eighty-four specimens of common arterial trunk were studied with special reference to the arrangement of the leaflets in relation to the atrioventricular valves, the origin of the coronary arteries in relation to the arterial sinuses, and the epicardial course of the coronary arteries. Fourteen normal hearts were used for comparison. In the hearts with common arterial trunk, the location and level of the coronary artery orifices (as well as the relationship of the truncal root to the area of fibrous continuity with the mitral valve) are different from those in normal hearts. In none of the hearts with common arterial trunk (particularly the 53 hearts with three leaflets in the truncal valve) did the appearance of the truncal valve approximate that of a normal aortic valve. Among the 22 hearts with four leaflets, there was a high incidence of coronary artery orifices in opposite sinuses (17/22 or 77.3%) and a low incidence of coronary artery orifices in adjacent sinuses (2/22 or 9.1%). These results suggest that the formation of the truncal valve is independent of the formation of the coronary orifices. Its leaflets are not predestined to become part of either the aortic valve or the pulmonary valve.

Pathogenesis of persistent truncus arteriosus in light of observations made in a dog embryo with the anomaly.

Among 36 embryos obtained from a strain of Keeshond dogs in which there is a large incidence of spontaneously occurring conotruncal anomalies, a specimen with persistent truncus arteriosus, type 1 was found. The embryo had a crown-rump length of 20 mm. The specimen was serially sectioned and a wax plate reconstruction was made of the heart and proximal great vessels at a magnification of X100. The truncal valve was quadricuspid and dysplastic; associated anomalies were a right subclavian artery arising anomalously from the descending aorta, a single coronary artery, an absent ductus arteriosus and a small persistent left cranial (superior) vena cava. The truncus cushions were hypoplastic, had failed to fuse and each had simply produced an arterial cusp. The observations made on this embryo support the view that in persistent truncus arteriosus there is failure of septation of the truncus arteriosus. No evidence was found in favor of the concept that persistent truncus arteriosus represents a form of tetralogy of Fallot with atresia of the subpulmonary infundibulum and partial or complete absence of the aorticopulmonary septum.