Patients with congenital heart disease (CHD) are surviving into adulthood, due to the major achievements in their diagnosis, medical management, surgical repair, and postoperative treatment (1,2). As more patients with CHD are now encountered in everyday practice, it is therefore timely and appropriate to start addressing the somewhat-neglected issue of myocardial ischemia in this patient population. Although chest pain is common in patients presenting to pediatric cardiology clinics, myocardial ischemia is rarely ever the etiology. The list of etiologies leading to myocardial ischemia is potentially long and each diagnosis for the most part is uncommon. Myocardial ischemia must always be considered in any patient who presents with chest pain, or has a known diagnosis that could lead to ischemia, that is, Kawasaki disease (KD) in childhood.

The consequences of not considering this diagnosis can be devastating. Unfortunately, many patients who suffer an ischemic episode do not present until after myocardial injury or infarction has already happened. These patients often undergo a rapid evaluation leading to definitive therapy. The patient who presents with symptoms of chest pain before an event or in the middle of an event will be the focus of this particular chapter. A detailed history, clinical examination, and appropriate diagnostic testing should lead to the correct diagnosis and offer the ability to include or exclude myocardial ischemia from the differential diagnosis. For the purposes of this chapter we will not review atherosclerotic coronary artery disease, it is covered in Chapter 71.

Myocardial ischemia is an imbalance between myocardial oxygen supply and demand. Left untreated, it results in angina pectoris, myocardial stunning, myocardial hibernation, or under the most severe instances, acute coronary syndromes like myocardial infarctions. Myocardial ischemia can be caused by several mechanisms, including increased myocardial oxygen demand in the presence of a severe fixed stenosis, coronary spasm due to local release of vasoactive mediators, and transient thrombus formation. The determinants of myocardial ischemia are likely to differ in patients with unstable coronary syndromes as the underlying pathologic substrate usually consists of plaque rupture with a varying degree of intracoronary thrombus formation (1,3,4).

In normal conditions, an uninterrupted flow of large quantities of oxygenated blood to the myocardium is critical to its normal function. During systole, this flow can be abolished or even reversed toward the epicardial vessels. The blood must flow from low-to-high intramyocardial pressure in order to meet the metabolic demands of each layer. Flow must be regulated in such a way that areas of high demand can immediately increase their blood supply. The myocardium extracts about 60% to 75% of oxygen from the blood that passes through it. Because of this high level of extraction, coronary sinus blood has low oxygen tension, generally around 25 to 35 mm Hg. This low level of oxygen tension requires that any increase in oxygen demand be met by an increase in blood flow rather than an increase in extraction (5,6).

There are two main mechanisms by which myocardial ischemia can occur: (a) a reduction in myocardial supply of oxygen, and (b) an increase in myocardial oxygen demand. The first situation can occur as a result of reduced coronary blood flow or reduced oxygen content despite normal coronary flow. Reduced coronary blood flow can result from congenital malformations of the coronary arteries, acquired coronary diseases, and also postoperative states, especially after surgical reimplantation of the coronary arteries. Examples of reduced oxygen content in coronary blood include cyanotic heart diseases, severe anemia, and hemoglobinopathies (4,7).

On the demand side, an increase in myocardial oxygen demand, that is, exercise, may lead to ischemia if there is a limitation on supply that under normal or steady state conditions is adequate but not sufficient during times of increased demand. Although this mechanism of ischemia may lead to an acute coronary syndrome, more commonly, patients suffer chronic chest pain during times of increased demand. The second mechanism can also occur in the presence of hypertrophic cardiomyopathy or vigorous exercises (8).

Therefore, in the pediatric population and in adults with CHD, chest pain often stems from a benign etiology, but rarely it may portend an imminent catastrophe.

For the patient who presents with chest pain, a detailed history provides the most important information to include or exclude myocardial ischemia from the differential diagnosis. Myocardial ischemia causing chest pain has typical characteristics that when present requires further investigation. Chest pain is more likely ischemic in nature when it is associated with:

and characterized as:

Other important historical features include how the pain is relieved. If a patient is able to continue to run and play and the pain goes away despite continuing activity, myocardial ischemia is less likely. Excluding atherosclerotic coronary artery disease, where
hypertension, diabetes, tobacco use, hyperlipidemia, and diabetes are important risk factors, prior medical history tends not to be helpful in evaluating other causes except for KD. Patients diagnosed with KD should be extensively interviewed and old records obtained to review history of treatment, echocardiogram results, and follow-up studies. Patients should also be screened for prior febrile illnesses that may have been mistaken for KD. A family history should screen for Marfan syndrome, other aortopathies, and for hypertrophic cardiomyopathy.

A prior surgical history where the coronary arteries were manipulated or reimplanted is important in a patient with typical chest pain or ischemia. The surgical reports pertaining to the procedure and how the coronary arteries were either reimplanted or manipulated may be important to the current care of the patient and future testing that must be done.

The etiologies for nonatherosclerotic coronary artery disease and myocardial ischemia remain rare and for the most part are difficult to diagnose, require a high index of suspicion, and often involve advanced imaging studies. Most of the diagnoses are covered in other areas of this textbook and are detailed in those chapters. This group of diagnoses can be divided into those involving the coronary arteries directly and those that involve the myocardium leading to myocardial ischemia.

The entire blood flow to the myocardium comes from two main coronary arteries that arise from the right and left aortic sinuses of Valsalva. In 69% of the population, the right coronary artery is dominant. Although there are normal variations of the coronary anatomy, a comprehensive discussion of this topic is beyond the scope of this chapter, which will focus only on the clinically significant anomalies. The most common anomaly, accounting for about one-third of all major coronary arterial anomalies, is origin of the left circumflex coronary artery from the right main coronary artery. However, this anomaly is rarely of clinical significance. Less common, the origin of the left coronary artery from the right sinus of Valsalva is of greater significance, and is associated with sudden death in children during or just after vigorous exercise (9).

A single coronary artery may be observed in 5% to 20% of major coronary anomalies. About 40% of these anomalies are associated with other cardiac malformations, including TGA, tetralogy of Fallot, ccTGA, double-inlet left ventricle, double-outlet right ventricle, truncus arteriosus, coronary-cameral fistulas, and bicuspid aortic valve (9). Only a small number of premature deaths have been reported with this anomaly. When the coronary arteries (either right or left) have their origins in inappropriate sinus, the mechanism of ischemia and death involves an increase in myocardial oxygen demand during exercise that, in turn, causes increases in systolic blood pressure and aortic root distension. If part of the anomalous artery runs within (intramural course) or adjacent to the aortic wall, it may be stretched, compressed, or both, leading to insufficient coronary blood flow.

Other rare coronary anomalies include coronary atresia, stenosis or atresia of a coronary ostium, all coronary arteries from pulmonary artery, left anterior descending coronary artery from pulmonary artery, left circumflex coronary artery from the pulmonary artery or branches, right coronary artery from pulmonary artery, myocardial bridges, etc.

In this anomaly the left coronary artery arises from the pulmonary artery. Therefore, after birth, the left ventricle is perfused with desaturated blood. The left ventricle then becomes hypoxic, and collaterals start to develop. The left ventricle vessels then dilate to reduce their resistance and increase flow, but this is often not enough to prevent ischemia with compromise of left ventricular function especially in concert with the physiologic drop in pulmonary vascular resistance. This leads to congestive heart failure that can be worsened by mitral regurgitation. With time, the collaterals between the right and left coronary artery enlarge until the collateral flow tends to reverse in the left coronary and ultimately into the pulmonary artery. The left-to-right shunt is usually not significant. This anomaly is usually isolated but can be associated with patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot, or coarctation of the aorta (7,9).

In this disease, a hypertrophied right ventricle is always present, with a high oxygen demand to overcome the outflow tract obstruction and provide pulmonary blood flow. In face of severe cyanosis and hemodynamic impairment, the oxygen supply may not balance the high requirements of the right ventricle, leading to myocardial ischemia (7).

Children with a large patent ductus arteriosus with left-to-right shunt, those with severe aortic regurgitation, and those with hypoplastic left heart syndrome, among others, are at great risk for myocardial ischemia, especially in the presence of severe hypoxemia or hypotension. A large patent ductus arteriosus with significant left-to-right shunt can decrease the diastolic pressure in the aorta, along with the increased preload increasing the LV end-diastolic pressure, significantly diminishing coronary blood flow. Severe aortic regurgitation can lead to the same deleterious consequences with diastolic pressures. In patients with hypoplastic left heart syndrome, the ascending aorta receives retrograde poorly oxygenated blood that originated from a patent ductus arteriosus. Therefore, these patients are particularly sensitive to hypotension, severe hypoxemia, imbalances between pulmonary and systemic blood flows, and a claudicating ductus arteriosus (7).

In patients with ccTGA, the right ventricle supports the systemic circulation and can become dilated and hypertrophied with time. Once ventricular dilation and hypertrophy settle in, the blood supply through a normal right coronary artery can become insufficient to meet the increased metabolic demands of the systemic right ventricle leading to further ventricular dysfunction (5,10). The latter may also have a deleterious effect on left ventricular perfusion, ultimately leading to left ventricular dysfunction (5,11). Hypertrophy can also develop in many other situations, especially in aortic stenosis and chronic systemic hypertension (7).