Coronary Artery Anomalies and Coronary Artery Disease in Adults with Congenital Cardiac Disease

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Congenital coronary artery abnormalities include various types of anomalies such as anomalous aortic origin, anomalous proximal course, anomalous distal connection, anomalous pulmonary arterial origin and anomalous coronary artery size. In this article I will review the most frequent abnormality and clinically significant anomalies: coronary artery fistulae and anomalous origin of the left coronary artery from the pulmonary trunk in adults. Recently, many patients with congenital heart disease (CHD) have reached adulthood and some of them are already in their mid-50s. I will touch on coronary artery sequelae attributed to antecedent Kawasaki disease observed in adult ischaemic heart disease, as well as the recent topic of coronary circulation in adults with cyanotic congenital heart disease (CCHD).

Coronary Artery Fistulae

Coronary artery fistulae are the most prevalent haemodynamically significant congenital anomalies of the coronary artery. Both coronary arteries arise from their assigned aortic sinus, but a fistulous branch of one or more of these arteries communicates directly with a cardiac chamber, pulmonary trunk, coronary sinus, vena cava or pulmonary vein. Adult survival is expected, but the lifespan may not be normal. The clinical manifestation depends largely on the amount of blood flowing through the fistula. Myocardial ischaemia may develop when the fistulous bypass induces coronary artery steel. In some cases of Kawasaki disease, this coronary artery anomaly is accidentally detected by a coronary angiogram.

Occasionally, a coronary artery fistula closes naturally.1 The long-term results of surgical repair are related to the volume of blood through the fistulous communication, the site of the communication and myocardial ischaemia before surgery. However, the results of late surgery are excellent in most cases. Surgery is usually safe; therefore, surgery or coil occlusion is usually recommended unless there is a single isolated fistula with a trivial shunt. Many coronary artery fistulae are very small (usually originating from the proximal left coronary artery and entering the pulmonary trunk).2

Anomalous Origin of the Left Coronary Artery from the Pulmonary Trunk

This anomaly is the most common and clinically important congenital anomaly of the coronary circulation. Immediately after birth, high pulmonary pressure provides the antegrade perfusion into the anomalous left coronary artery. As neonatal pulmonary resistance falls, usually within one to three months of birth, there is a parallel fall in flow through the anomalous coronary artery. Myocardial ischaemia occurs unless adequate circulation is established from right to left coronary artery via intercoronary collaterals. Retrograde flow through large intercoronary collaterals may have an unfavourable effect on the heart, such as providing an obstacle for left coronary artery flow.

The clinical course of patients with this anomaly is variable, ranging from death during infancy to asymptomatic adult survival. The oldest unoperated patients with this anomaly are in their 60s.3 In adults this anomaly can be discovered with the murmur of mitral regurgitation. The coronary anomaly may be unsuspected until a previously asymptomatic adult develops cardiac failure, angina, shortness of breath on exertion or sudden death.4

Approximately 10–15% of unoperated patients with this anomaly reach adulthood.3 With optional collateralisation, prolonged survival can occur in the setting of heralded myocardial infarction, although there is usually late left ventricular dysfunction, often with anterolateral ventricular aneurysm and mitral regurgitation secondary to previous myocardial infarction. These provide the substrate for later ventricular tachyarrhythmias and sudden death.

After the current operation to establish two coronary artery systems along with resection of left ventricular aneurysm and mitral valvuloplasty when needed, reduced left ventricular size and improved left ventricular function after repair with low operative mortality have been observed in most patients. The long-term outcome of adults with this anomaly after repair depends on the previous function of the left ventricle, the severity of mitral regurgitation, age at surgery and type of surgery.

Long-term survival also largely depends on the post-operative status of mitral regurgitation and left ventricular function. The prognosis of patients with this anomaly after coronary artery repair during adulthood is excellent.5

Coronary Artery Sequelae Attributed to Antecedent Kawasaki Disease Observed in Adult Ischaemic Heart Disease

As paediatricians were not commonly aware of the cardiac complications of Kawasaki disease in the 1960s and 1970s, cardiologists did not follow up most patients. Recently, there have been several reports on patients thought to have a history of Kawasaki disease who were diagnosed after the appearance of symptoms of acute myocardial infarction, ischaemic heart disease or significant arrhythmia or cardiac failure. These symptoms are supposed to be sequelae from Kawasaki disease. There may be patients who were followed by internists or cardiologists to try to establish the identity of an unknown cause of coronary artery aneurysm or ischaemic heart disease.

The possible contribution of antecedent Kawasaki disease to the genesis of cardiovascular disease in adults was investigated by Kato et al.6 A survey of adult cardiologists throughout Japan identified 130 adult patients with coronary artery aneurysm. These aneurysms were detected by angiograms performed to evaluate myocardial infarction or ischaemia. Twenty-one of these patients (with a mean age of 34 years) had a history compatible with Kawasaki disease in childhood. These patients had severe clinical coronary artery disease with acute myocardial infarction, angina pectoris, mitral regurgitation, arrhythmias, a need for coronary artery bypass grafting and cardiac failure.

The investigators suspected that many of the remaining 109 patients may also have had antecedent Kawasaki disease, but information regarding childhood illness was scarce. This was due to the fact that the diagnosis of Kawasaki disease was not common even in Japan over 30 years ago, and because patients are usually unable to recall childhood illnesses that occurred under the age of one year. Many cases of Kawasaki disease may have been misdiagnosed as other childhood infectious diseases. This study indicated that the coronary artery sequelae of Kawasaki disease may be an important cause of ischaemic heart disease in adults.

Burns et al.7 defined coronary artery involvement in teenagers and young adults attributed to antecedent Kawasaki disease in childhood by the retrospective survey of cases reported in the literature on adult coronary artery disease.

Having reviewed the literature they found that the mean age at presentation with cardiac sequelae was 27.4 years for the 74 patients identified with presumed late sequelae of Kawasaki disease. Symptoms identified in these 74 patients were chest pain/acute myocardial infarction (61%), arrhythmia (11%) and sudden death (16%). These symptoms were precipitated by exercise in 82% of cases.

Angiocardiograms revealed that coronary artery aneurysm was identified in 93% of patients and coronary artery occlusion in 66%. Necropsy findings included coronary artery aneurysm in 100% of patients and coronary artery occlusion in 72%. They concluded that Kawasaki disease in childhood could cause permanent coronary artery damage that may remain clinically silent until adulthood. From these reports, a history of Kawasaki disease should be determined for adult patients with coronary artery aneurysm in the absence of generalised atherosclerotic disease, especially in those without risk factors for metabolic disorder.

Coronary Circulation in Adults with Cyanotic Congenital Heart Disease
Low Incidence of Coronary Atherosclerosis

An estimated minimal incidence of atherosclerotic coronary artery disease in an asymptomatic general population is 4.5%, based on angiogram and necropsy data.8 In some types of CHD, such as coarctation of the aorta, especially in non-operated patients or patients operated on in their 20s or later, persistent hypertension and premature coronary artery disease are often observed.9 Coronary artery disease is reportedly the most common cause of late post-operative death.10 Coronary artery disease is important and requires careful observation in CHD, but such an event is fortunately relatively rare in CCHD.11 Coronary arteries in patients with CCHD were angiographically free of coronary atherosclerosis in their 40s.8 The reason for this low incidence of atherosclerosis in CCHD patients will be described.

Coronary Circulation in Cyanotic Congenital Heart Disease

The coronary arteries were tortuous to markedly dilated in 15% of the coronary arteriograms in inherently cyanotic patients with CHD.12,13 Mild to moderate dilatation of the extramural coronary arteries in CCHD is a response to endothelial vasodilator, nitric oxide and prostaglandins, the collaboration of which is provoked by increased endothelial shear stress of various erythrocytotic perfusaes as well as that of the systemic vascular bed.14,15 Striking dilatation of the coronary artery is possibly due to medial structural abnormalities in the coronary artery walls and vasodilatation due to intrinsic vasodilators.12,14,16

Factors Contributing to the Low Incidence of Coronary Atherosclerosis in Cyanotic Congenital Heart Disease

The low incidence of coronary atherosclerosis is thought to be due to several factors. Hypocholesterolaemia12 is a likely contributor, but other independent variables also likely to contribute are hypoxaemia, upregulated nitric oxide, hyperbilirubinaemia and low platelet counts.


Hypoxaemic erythrocytotic people born and raised at high altitude are hypocholesterolaemic, devoid of clinically ischaemic heart disease and free of coronary atherosclerosis.14 CCHD is a previously unrecognised cause of hypocholesterolaemia with reduced levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, the aetiology of which includes cyanosis (systemic arterial hypoxaemia), erythrocytosis and genetic factors.12 Persistence of hypocholesterolaemia after surgical elimination of cyanosis, hypoxemia and erythrocytosis implies the induction of genes that induce hypocholesterolemia.


Hypoxaemia is associated with a decrease in atherogenic oxidised plasma LDL and a decrease in intimal oxidised LDL. Lack of small, dense, oxidation-sensitive LDL in CCHD may act in a similar way. In normal pulmonary circulation, atherosclerosis is common, especially in patients above the age of 40 years, despite hypoxaemia. When oxygen saturation in the pulmonary bed is increased by a left-to-right shunt, the prevalence of atherosclerosis remains the same or increases slightly.16 Except in the presence of hypercholesterolemia, there is no relationship between atherosclerosis in the hypoxaemic normal pulmonary circulation and in the normally oxygenated systemic circulation.

Nitric Oxide

Nitric oxide is antiatherogenic because the paracrine molecule opposes platelet adherence and aggregation, stimulates disaggregation of preformed platelet aggregates, inhibits monocyte adherence and infiltration and inhibits smooth-muscle proliferation.15 Nitric oxide is increased in CCHD because increased endothelial shear stress provoked by erythrocytosis is a major factor in inducing nitric oxide expression.16 In addition, red blood cells are nitric oxide reservoirs and red cell mass is increased in CCHD.17


Hyperbilirubinaemia is a feature of CCHD because bilirubin is formed from the breakdown of heme, a process made excessive by increased red cell mass.14 Bilirubin is an endogenous antioxidant that inhibits LDL oxidation and reduces atherosclerotic risk.17,18 Gilbert’s disease, a benign hereditary disorder of hepatic bilirubin metabolism, is accompanied by elevated levels of unconjugated bilirubin and is resistant to coronary atherosclerosis.17

Low Platelet Counts

Low platelet counts are antiatherogenic, and the platelet counts are typically low or thrombocytopoenic in CCHD because whole megakaryocytes are shunted from the systemic venous circulation into the systemic arterial circulation and cannot shed platelets by cytoplasmic fragmentation in the pulmonary vascular bed.14 The platelet counts are negatively correlated with haematocrit levels and with the magnitude of the right-to-left shunt.19


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