Congenital and pediatric coronary artery abnormalities

INTRODUCTION — Coronary artery abnormalities in the pediatric population may be acquired or congenital. Coronary artery embryological development is not completely understood. However, abnormal coronary embryogenesis may result in abnormalities in coronary artery origin (either from the aorta or the pulmonary artery) or incomplete development, resulting in coronary artery fistulae or coronary sinusoids (see 'Persistent sinusoids' below). This review covers the physiology and management of these abnormalities, the resultant findings on history and physical examination, and the laboratory diagnosis.

VARIATIONS OF CORONARY ARTERY ORIGIN FROM THE AORTA — In otherwise normal patients, there may be variations in the number, shape, and location of the ostia or origins of the coronary arteries. Most of these variations appear to be of no clinical significance [1], although a high origin of the ostia may reduce diastolic coronary artery blood flow [2].

Separate origins of the right coronary artery (RCA) and its conal branch occur in 50 percent of the population and separate origins of the left circumflex coronary artery (LCx) and left anterior descending artery (LAD) in 1 percent.

More important lesions include origin of the left main coronary artery or LAD from the right sinus of Valsalva or RCA, referred to as anomalous aortic origin of a coronary artery (AAOCA). This can further be grouped into interarterial (with or without an intramural course), prepulmonic, subpulmonic, retroaortic, and retrocardiac [3]. The subsequent course between the aorta and pulmonary artery to the left ventricle may result in compression of the vessel, myocardial ischemia, and sudden death in both adults and teenagers [4,5]. Alternatively, it may be the intramural course and acute angle of takeoff that may predispose to obstruction to blood flow [6]. In one study, the length of the intramural course was found to correlate with symptoms [7]. This was not found in a subsequent study at the same institution [8].

Although rare, complications commonly occur during or immediately after exercise, though sudden death may occur without prior symptoms. It has been proposed that exercise leads to expansion of the aortic root and pulmonary trunk, which, in addition to external coronary artery compression, may increase the pre-existing angulation of the coronary artery takeoff, reducing the luminal diameter in the proximal portion of the coronary artery [4].

Similarly, a single coronary artery originating from the right sinus of Valsalva may result in compression of the LAD or its branches via the same mechanism. Origin of the RCA from the left sinus of Valsalva or LAD also can lead to myocardial ischemia and sudden death [9].

In contrast, origin of the LCx from the RCA is generally felt to be of no clinical significance due to its posterior course to the left ventricle. However, it is possible that vascular compression can occur.

Incidence — The incidence of abnormal aortic origin of the coronary arteries is low with reported values of approximately 0.64 percent of births [10] and 0.17 percent in asymptomatic children and adolescents who were referred for and underwent echocardiography [11]. The most common anomaly is the left circumflex from the right sinus of Valsalva, followed by a single coronary artery from the left sinus of Valsalva, both coronary arteries from the right sinus of Valsalva, and the LAD from the right sinus of Valsalva. The prevalence of either the RCA arising from the left sinus of Valsalva or the left main coronary artery arising from the right sinus of Valsalva is between 0.1 and 0.3 percent [12]. The prevalence of the RCA arising from the left sinus of Valsalva is greater than the left coronary artery from the right sinus of Valsalva (0.17 versus 0.047 percent), though both are uncommon [13].

Clinical presentation — The clinical presentation of a patient with the above mentioned abnormalities may be anginal chest pain, or syncope, especially with exercise. Unfortunately, the first clinical symptom may be sudden death, particularly in young athletes and military recruits [14-16]. In a registry of sudden death in 286 competitive athletes under age 35 in whom cardiovascular disease was shown to be the cause at autopsy, an anomalous coronary artery of wrong sinus origin was responsible for 13 percent of cases, being second in frequency to hypertrophic cardiomyopathy [15]. In a series of autopsies in military recruits, an anomalous coronary artery was the most frequent cause of sudden cardiac death [16] (see "Athletes: Overview of sudden cardiac death risk and sport participation"). Overall, the incidence of sudden death in patients with AAOCA is low, though higher for patients with AAOCA of the left coronary artery than with AAOCA of the RCA, especially in the absence of symptoms [17]. There has been an excellent and extensive AAOCA review of the anatomy, incidence, risk of sudden death, diagnosis, and management [3].

Diagnosis — Physical examination and diagnostic studies are usually unrevealing in the absence of myocardial infarction or symptoms of ongoing ischemia [4,18]. When anomalous origin of a coronary artery is suspected, echocardiography may establish the diagnosis [19]. However, even using established echocardiographic protocols to diagnose coronary artery abnormalities, there remains significant variation amongst institutions and suboptimal reliability of established detailed anatomy [20]. With improvement of cardiac magnetic resonance angiography and coronary cardiac computed angiography (CCTA), reliable anatomic description of the coronary artery origins and the proximal course is possible. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

In an extensive review, there is a comparison of different imaging modalities to characterize coronary artery anatomy [3]. Although echocardiography is the most widely used as a screen due to availability, relatively low cost, and noninvasive nature, it is limited by the ability to visualize surrounding structures, spatial resolution (though better than magnetic resonance imaging, it is less than CCTA), and confounding factors such as body habitus and sonographer experience and technique. CCTA has high resolution and is able to visualize surrounding structures but may be less available and requires radiation and contrast. Cardiac magnetic resonance angiography (CMRA) does not require radiation or contrast, but does not have the spatial resolution of CCTA that may be important in decision making. Traditional angiography has excellent spatial resolution (of the coronary artery course), though is more invasive and uses both contrast and radiation. It also has limited visualization of the coronary ostia, proximal course, and structures surrounding the coronary arteries. Intraluminal ultrasound has the benefit of demonstrating dynamic coronary artery compression and perhaps the highest intraluminal spatial resolution of the imaging modalities but is invasive and may have a higher cost and difficulty engaging the coronary artery in question.

Other imaging studies may be of some benefit. Stress studies (echocardiography or radionuclide myocardial perfusion imaging) may aid in the management of coronary artery variations, including a superior location of the coronary ostia, if it is unclear whether there is a risk of ischemia [21].

Treatment — The indications for intervention in asymptomatic patients with AAOCA with an intramural course are debated, especially with AAOCA RCA from the left sinus of Valsalva [12,17]. There has been considerable variation in practice management [21], establishing a need for a more standardized approach. More recently, a working group provided the first written consensus statement for practice guidelines on this topic [22].

In this consensus statement, surgical intervention is recommended for those with signs or symptoms of myocardial ischemia (eg, true angina, findings on provocative testing, aborted sudden cardiac death or arrest, or non-vagally-mediated arrhythmia). In asymptomatic patients with AAOCA, intervention in those with an interarterial/intramural left coronary artery from the right sinus of Valsalva (AAOLCA) is recommended due to the higher calculated risk of sudden cardiac death. In asymptomatic patients with an intramural RCA from the left sinus of Valsalva (AAORCA), provocative testing is recommended.

The prevalence of AAOCA without an intramural course is not known, in part due to the lack of study of this issue using high resolution imaging techniques. Based on anecdotal information, an intramural course of the coronary artery is likely in all cases of AAOCA, but the length of the intramural course may vary.

Surgical interventions can consist of coronary artery bypass grafting (CABG; which is generally not satisfactory [22]) or unroofing (marsupialization) of the coronary artery [23] to prevent compression from a change in the angulation. The "hinge-twist" procedure has been described for AAOCA without an intramural course [24], and a pulmonary artery translocation technique has been described for a single coronary ostium without an intramural course [25]. Intracoronary stents have also been used as an alternative to CABG in symptomatic patients with ischemia; their structural rigidity may protect the vessel against compression [26]. Stenting has not been advised in children due to growth. Ostial revision has also been employed, though is described as the most technically challenging [22].

Exercise guidelines have also been reconsidered, and the newer consensus states that the asymptomatic patient with AAORCA and no evidence of ischemia clinically or with provocative testing should be allowed to participate in competitive athletics. However, appropriate informed consent/counseling of the affected individual with the known risks (eg, sudden cardiac death) is necessary. Preparedness for cardiac events (eg, having an automated external defibrillator [AED] available with individuals who can use it) is recommended. Individuals with untreated AAOLCA should be restricted from competitive sports.

Based on consensus, following intervention for AAOCA, those with a history of aborted sudden cardiac death may return to competitive athletics after 12 months, provided they are free of symptoms suggesting ischemia or arrhythmia and have no evidence of myocardial ischemia on provocative testing or concerning arrhythmia. Individuals with AAOCA and no aborted sudden cardiac death may be allowed to return to competitive sports three months post-surgery, provided they have had no symptoms suggesting ischemia or arrhythmia and have no evidence of myocardial ischemia on provocative testing or concerning arrhythmia. An AED should available for all of these patients with personnel trained in their use.

VARIANT CORONARY ORIGIN ASSOCIATED WITH OTHER CONGENITAL HEART DISEASES — Variations in origin of the coronary arteries from the aorta are commonly seen with congenital heart diseases such as tetralogy of Fallot, transposition of the great arteries, double outlet right ventricle, univentricular hearts, and truncus arteriosus.

Tetralogy of Fallot — Anomalous origin of the coronary arteries occurs in approximately 9 percent of patients with tetralogy of Fallot [27,28]. The most common variations are an enlarged conal artery, an anomalous left anterior descending artery (LAD) arising from the right coronary artery (RCA) or right sinus of Valsalva, and a single coronary artery. These variations are important to recognize for surgical repair, as the coronary arteries may be vulnerable to injury during right ventricular outflow tract reconstruction. (See "Tetralogy of Fallot (TOF): Management and outcome".)

Transposition of the great arteries — A variety of coronary anomalies are seen in patients with D-transposition of the great arteries [29,30]:

●The most common, occurring in about 60 percent of patients, is origin of the RCA from the posterior aspect of the right-facing sinus of Valsalva and the left main coronary artery from the posterior aspect of the left-facing sinus.

●The next most common abnormality, seen in about 20 percent, is a left circumflex artery (LCx) arising from the RCA.

●Other lesions, each occurring in 3 to 9 percent of patients, include coronary artery inversion (ie, the RCA arising from the left posterior sinus of Valsalva and the left main coronary artery arising from the right posterior sinus of Valsalva), inversion of the coronary arteries with the LCx artery arising from the RCA, and single coronary artery, arising from either the right or left sinus of Valsalva.

An intramural rather than epicardial course of any of the coronary arteries may be seen in D-transposition. Since coronary artery reimplantation is part of the repair of D-transposition of the great arteries, knowledge of the coronary artery pattern is important.

In L-transposition of the great arteries, there is confusion in the nomenclature of the coronary arteries, since they may be named for the sinus of Valsalva from which they originate or the ventricle that they supply [1,30-33]. Using the convention of naming from the sinus of origin, the RCA supplies the right-sided left ventricle and branches into an LCx and LAD branch the way a left coronary artery usually does. The left coronary artery takes a course similar to the usual RCA in the interventricular groove.

Truncus arteriosus — In truncus arteriosus, the usual coronary artery pattern is present unless more than three cusps are present. In this setting, variations can occur, which may lead to injury during surgical procedures, including coronary arteries that course over the anterior surface of the right ventricle (predisposing to coronary artery injury during surgical procedures), a single coronary artery, or displacement of the coronary ostia [33-35].

Other congenital heart defects — Other congenital heart defects, such as a univentricular heart, have coronary artery patterns similar to those described above depending upon the relationship of the great arteries to each other and the outflow chambers. The coronary artery variations may be diagnosed prior to surgery with echocardiography or ultrafast computed tomography in some centers, although angiography remains the gold standard.

Treatment — Treatment of the above variations depends upon the exact nature of the lesion. Many of the variations, especially if the origin is from the aorta, do not require surgical correction if there is no evidence of ongoing or predicted development of myocardial ischemia.

VARIATIONS OF CORONARY ARTERY ORIGIN FROM THE PULMONARY ARTERY — An anomalous origin of one or more coronary arteries from the pulmonary artery is usually an isolated abnormality, occurring in 0.4 percent of patients with congenital cardiac abnormalities (image 1). Unlike variations of the coronary artery from the aorta, a coronary artery origin from the pulmonary artery is governed by different hemodynamics, as noted below. The latter will result in myocardial ischemia that may be progressive and lead to ischemic cardiomyopathy. The following mechanisms may be involved:

●The myocardium is perfused by the abnormally arising coronary artery, which has a relatively low perfusion pressure and carries blood with a low oxygen saturation, reflecting the pulmonary artery source.

●In the presence of collateral circulation from a normally arising coronary artery, there will be coronary artery steal, as flow will be directed from the normal coronary artery to the pulmonary artery (ie, a left-to-right shunt) via the collateral vessels [36,37].

The most common defect of this type is origin of the left coronary artery from the pulmonary artery, sometimes known as Bland-White-Garland syndrome [38-40]. In some cases, the left anterior descending and left circumflex coronary arteries have individual origins from the pulmonary artery, with similar pathophysiologic and clinical sequelae [41,42]. The origin of the right coronary artery from the pulmonary artery has been thought to be benign; however, clinical sequelae have been described [43].

Clinical presentation — The clinical presentation varies with the coronary artery involved and its myocardial distribution, the pulmonary vascular resistance, and the number and size of collateral vessels.

●Without significant collateral blood supply, myocardial ischemia in the region supplied by the abnormal coronary artery will occur in infancy when the neonatal elevated pulmonary vascular resistance normalizes. With the onset of ischemia, myocardial function deteriorates with the associated signs and symptoms of heart failure (see "Heart failure: Clinical manifestations and diagnosis in adults"). In neonates, angina may manifest as irritability, pallor, and diaphoresis, with progression to signs and symptoms of shock. These findings usually become apparent at four to six weeks of age when the pulmonary vascular resistance has decreased, though the presentation may be delayed.

●With good collateral blood flow, the presentation of this abnormality may be delayed to later childhood, teen, or even adult age [1] (see "Coronary collateral circulation"). Older children and adults may present with findings of a dilated cardiomyopathy or sudden death.

Physical examination — With good collateral coronary artery circulation, or a pulmonary origin of the right coronary artery from the pulmonary artery, there may be few if any physical findings. Other than physical signs of shock, important physical findings include a gallop or a murmur of mitral regurgitation, reflecting papillary muscle dysfunction due to ischemia (see "Auscultation of cardiac murmurs in adults"). A continuous murmur resembling a patent ductus arteriosus, with flow from the aorta to the pulmonary circulation, may be noted, reflecting flow through collaterals. (See "Clinical manifestations and diagnosis of patent ductus arteriosus (PDA) in term infants, children, and adults".)

Chest radiograph and electrocardiogram — The chest radiograph may show cardiomegaly and/or pulmonary edema. The electrocardiogram of an infant with an anomalous left coronary artery from the pulmonary artery shows evidence for anterolateral ischemia or infarction, including transient or chronic ST-segment changes in the anterolateral leads or Q waves in leads I aVL, V5, and V6 [44]. However, 20 to 45 percent of patients do not have abnormal Q waves. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Anterior MI on the ECG'.)

Noninvasive imaging — Echocardiography typically demonstrates a dilated heart with global myocardial dysfunction and associated mitral regurgitation. Echogenic papillary muscles and endocardial borders are frequently noted. The abnormal coronary artery origins and associated dilation due to shunting or runoff should be apparent with two-dimensional imaging, although color Doppler may provide additional evidence of this diagnosis by showing the abnormal direction of coronary blood flow. Noninvasive imaging with either cardiac computed tomography angiography (CCTA) or cardiac magnetic resonance angiography (CMRA) may provide additional information, and in many cases may be diagnostic [45].

Diagnosis — The diagnosis of an anomalous coronary artery (usually the left anterior descending) originating from the pulmonary artery is made in a patient (often a young child) in whom it is suspected based on the findings described above with a diagnostic imaging modality (either CCTA or CMRA), which may vary among institutions. Coronary angiography, which is the gold standard, may be necessary in some cases, and cardiac catheterization may provide additional hemodynamic information.

Treatment — All anomalously arising coronary arteries from the pulmonary artery require surgical correction, which consists of reimplantation of the coronary artery to the aorta or tunneling of the coronary artery to the aorta (Takeuchi procedure) so that unimpeded normally saturated blood will reach the heart. Older therapies, such as ligation of the abnormally arising coronary artery, have been largely abandoned in favor of the establishment of a normal two coronary artery system [46]. At this time, there are no percutaneous treatment options for abnormalities of coronary artery origin.

ABNORMALITIES IN THE CALIBER OF THE CORONARY ARTERIES — Abnormalities in the caliber of the coronary arteries include narrowing due to stenosis or hypoplasia or enlargement, including ectasia or aneurysmal dilation. Enlargement is mainly seen in accompanying inflammatory disease. (See "Kawasaki disease: Clinical features and diagnosis".)

Coronary artery narrowing — Stenosis of the coronary arteries can occur at the ostium or throughout the coronary artery. These lesions can be congenital or acquired. The pathophysiology is similar for all of the above causes with the common denominators of coronary blood flow insufficiency and myocardial ischemia, and their resultant signs and symptoms. (See "Approach to the patient with suspected angina pectoris".)

Causes — Causes of coronary artery narrowing can be subdivided into congenital and acquired causes [47,48]. The narrowing may be ostial or within the coronary artery.

Congenital causes:

●A congenital abnormality, such as an acute takeoff of the coronary artery from the sinus of Valsalva, which may become compressed with aortic root dilation [2], or formation of a nonatheromatous ridge.

Coronary artery involvement in Williams syndrome [49]. The location of the coronary arteries proximal to the area of supravalvular aortic stenosis may predispose the development of intimal hyperplasia due to the associated hypertension [50]. (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults" and "Williams syndrome".)

●Abnormal aortic origin of the coronary artery from the opposite side of the sinus of Valsalva (see prior discussion).

●Congenital ostial atresia or stenosis [51].

●Congenital tunneling of the coronary arteries into the myocardium, known as myocardial bridges [52,53] or arterial loops [54], can cause localized narrowing of the coronary arteries. Though myocardial bridges are typically described in adults, they can be seen in children, and a familial clustering has been reported [55], thus they are considered a congenital abnormality.(See "Myocardial bridging of the coronary arteries".)

●Congenital hypoplasia associated with long segment narrowing may involve one or both coronary arteries [56]. There may be a remnant fibrous cord in the area usually occupied by a coronary artery, most often the left.

Noncongenital/acquired causes of coronary artery stenosis in the pediatric population:

●Many of the acquired causes of coronary artery stenosis described in adults (eg, methysergide or syphilitic-associated coronary artery diseases [47]) are not described in children, although are theoretically possible in older children.

●Familial hypercholesterolemia can result in coronary artery lesions similar to adults. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

●Takayasu arteritis or other inflammatory diseases such as the thrombosis or intimal hyperplasia of coronary artery aneurysms seen in Kawasaki disease. (See "Clinical features and diagnosis of Takayasu arteritis".).

●Surgical manipulation (eg, aortic valve surgery, coronary artery cannulation) near or directly involving the coronary arteries (eg, arterial switch procedure or Ross procedure for infective endocarditis [57]) or trauma.

●Transplant-related coronary artery vasculopathy.

Screening and risk stratification — The predisposition to or suspicion of coronary artery narrowing as noted above may be found in the history (risk factors). In individuals with risk factors (eg, underlying diseases, prior surgeries, and those who are known to have coronary abnormalities) for coronary narrowing and inducible myocardial ischemia, long-term surveillance is indicated to determine whether or not intervention is needed. Surveillance usually consists of imaging (eg, noninvasive echocardiography, computed tomography, magnetic resonance imaging, or invasive angiography), as well as an assessment for underlying ischemia (eg, stress testing, exercise or pharmacologic stress with noninvasive imaging). The frequency and type of surveillance vary among institutions and individual patients. Based on the surveillance findings, a risk for myocardial infarction and sudden death is estimated.

Treatment — Treatment of coronary artery narrowing, whether congenital or acquired, is similar in children and adults [58]. Depending upon the degree of narrowing and expected future risks of untreated narrowing, intervention may be indicated. Treatment can consist of one or more of the following:

●Risk factor reduction (eg, hyperlipidemia, hypertension, inflammation).

●Surgical intervention, including coronary artery bypass graft surgery or epicardial laser revascularization. (See "Chronic coronary syndrome: Indications for revascularization" and "Transmyocardial laser revascularization for management of refractory angina".)

●Percutaneous coronary intervention with or without stent placement. Covered stents may be less prone to intimal hyperplasia in this setting [59]. (See "Percutaneous coronary intervention with intracoronary stents: Overview".)

Heart transplantation — In the pediatric population, coronary artery stent placement may not be feasible due to size. If coronary artery bypass graft surgery is not possible either (for diffuse disease), the only interventional option is for stabilization and transplantation. (See "Cardiovascular sequelae of Kawasaki disease: Management and prognosis", section on 'Cardiac transplantation'.)

CORONARY ARTERY FISTULAE — Communications between the coronary arteries and the cardiac chambers (coronary-cameral fistulae) or other vessels (coronary artery arteriovenous malformations) are often due to deviations from normal embryological development (image 2). They may also be acquired from trauma (stab, gunshot, or projectile injuries), or from invasive cardiac procedures such as pacemaker implantation, endomyocardial biopsy, or coronary angiography [60].

The resultant physiologic derangement depends upon the site of origin and termination of the abnormal connection and the size of the connection [61]. The major sites of origin are the right coronary artery (55 percent), the left coronary artery (35 percent), and both coronary arteries (5 percent). The major termination sites with right and left coronary artery origins are the right ventricle (40 percent) (image 3), right atrium (26 percent) (image 4), and pulmonary arteries (17 percent). The fistulae less frequently drain into the superior vena cava or coronary sinus, and least often to the left atrium or left ventricle.

The outcome with these connections depends upon the termination site:

●There is a left-to-right shunt if termination is to the systemic venous side, or proximal to the tricuspid valve (pre-tricuspid valve left-to-right shunt).

●There is left-sided volume overloading if the termination is distal to the tricuspid valve (post-tricuspid valve left-to-right shunt).

The volume of the shunt varies with the size of the fistula and differences between the systemic resistance and the resistance in the terminating vessel/chamber; flow moves from the coronary arteries to the lower pressure chambers or vessels.

Symptoms and complications — Most coronary artery fistulae are small, myocardial blood flow is not compromised, and the patient is asymptomatic. However, there may be coronary artery steal, with resultant ischemia of the segment of myocardium perfused by the coronary artery distal to the fistula; the coronary artery proximal to the fistula enlarges in a compensatory fashion.

If untreated, hemodynamically significant fistulae may result in clinical symptoms or sequelae in approximately 19 percent of patients under the age of 20 and 63 percent of those over the age of 20 [62]. Symptoms and sequelae include:

●Chronic myocardial ischemia and angina

●Heart failure and a cardiomyopathy

●Myocardial infarction

●Pulmonary hypertension

●Endocarditis

●Rhythm abnormalities

●Thrombosis of the fistula or an associated aneurysm

●Rupture of the fistula, which is rare

Spontaneous closure has been reported in children [63], and less frequently in adults. Spontaneous closure may be a more common occurrence in biopsy-related coronary-cameral fistulae.

Diagnosis — Many patients with a coronary artery fistula are identified and referred because of the associated murmur, which is loud, superficial, and continuous at the lower or midsternal border, depending upon the site of drainage (see "Auscultation of cardiac murmurs in adults", section on 'Continuous murmurs'). The chest radiograph and electrocardiogram are normal if the shunt through the fistula is small, but may show evidence of chamber enlargement or ischemia with a larger shunt and coronary artery steal.

Significantly enlarged coronary arteries can be detected by two-dimensional echocardiography. The actual diagnosis of a coronary artery fistula can often be made with transthoracic two-dimensional and color Doppler echocardiography in children. However, in adults, two-dimensional transesophageal echocardiography may be more sensitive for detection of the entrance and termination site of the shunt, which is characterized by a continuous turbulent systolic and diastolic flow pattern [64]. In one report of 21 coronary artery fistulas detected by the transesophageal approach in 17 adults and four adolescents, transthoracic echocardiography was suggestive of a fistula in only 6 of 18 patients in whom the test was performed.

Coronary fistulae have also been detected noninvasively using 64-slice multi-detector computed tomography [65].

The size and anatomical features of the fistula can be reliably established during coronary angiography or with retrograde thoracic and aortic root aortography.

Treatment — The approach to the elimination of coronary artery fistula (surgical versus transcatheter) depends on the expertise of the physicians involved in the management of the patient. The decision process in managing fistulae depends on site of origin of the fistula (proximal versus distal) [66], size of the fistula, patient's symptoms, presence of any complication caused by the fistula (eg, angina, heart failure, endocarditis, rupture, etc), age of the patient, the anatomy of the fistula, and presence of other indications to undergo an invasive procedure. The class 1 recommendations by the American Heart Association/American College of Cardiology (AHA/ACC) [67] include:

●Patients with continuous murmur should undergo exact delineation of the origin and termination of the fistula by either echocardiography or computed tomography/magnetic resonance imaging.

●Patients with large fistulae should undergo closure (surgical or percutaneous) after delineation of the exact anatomy.

●Patients with small to moderate fistulae with complications (eg, ischemia, arrhythmias, or ventricular dysfunction of unexplained etiology) should undergo fistulae closure.

Of note is that the approach of elimination of the fistula (surgical versus transcatheter) depends on the expertise of the physicians involved in the management of the patient. In general, a small fistula in an asymptomatic patient should be observed with no closure or medical therapy recommended. Intermediate (moderate to large) fistulae without symptoms are managed slightly different depending on the location. Large fistulae should be closed.

●Proximal fistulae: Closure is recommended (surgical versus transcatheter) followed by antiplatelet therapy for at least one year.

●Distal fistulae: Two treatment options are suggested: closure followed by antiplatelet therapy for one year or observation while receiving antiplatelet therapy indefinitely.

Post-closure management:

After transcatheter closure of a large symptomatic fistula, heparin should be started six hours after the procedure and adjusted to keep the partial thromboplastin time at 1.5 times normal while warfarin is started. Patients should be discharged home on warfarin and be adjusted to keep the international normalized ratio (INR) around 2.5 for a period of 6 to 12 months [66]. Also, these patients should receive antiplatelets indefinitely. If the fistula is large with no symptoms, one has two options: either observation while receiving antiplatelets indefinitely or closure. If fistula is closed, one should treat as large fistula with symptoms.

Another important factor in the decision-making process is the size of the patient.

●Fistulae in small patients: If small to moderate in size, fistulae can be left untreated until the patient is larger. Spontaneous regression of fistulae has been reported [68]; however, if the fistula is large and associated with cardiac symptoms, closure is recommended. Elective closure of moderate to large sized fistulae that are not causing symptoms is reasonable and can be performed once the child is an appropriate weight (approximately >15 kg). If fistula is associated with other cardiac lesions (most commonly tetralogy of Fallot, patent ductus arteriosus, or atrial septal defect), the fistula can be closed at the time of repair of the primary cardiac lesion.

Surgical methods of closure are associated with low mortality and morbidity; long-term outcome is excellent and most patients remain asymptomatic [69,70]. Despite the good results with surgery, closure during cardiac catheterization has become the method of choice. Various percutaneous catheter techniques have been employed, including Gianturco coils (image 3), interlocking detachable coils, detachable balloons, polyvinyl alcohol foam, double umbrellas, the Amplatzer duct occluder (image 4), and the Amplatzer vascular plug [60,71-77]. Risks of fistula closure with these devices include myocardial infarction and migration of coils or discs to extracoronary vascular structures or within the coronary artery branches [78].

The potential efficacy and safety of transcatheter closure was illustrated in a review of 35 procedures (coil in 28, umbrella device in 6, and vascular occlusion device in 1) [71]. Post-deployment, there was complete occlusion in 19, trace flow in 11, and small residual flow in 5. At a median follow-up of two years in 27 patients, there was no flow in 22 and small residual flow in five. Early complications include transient ST and T changes in five, transient arrhythmia in five, and single cases of fistula dissection and coil embolization. Device placement was not attempted in patients with multiple fistula drainage sites.

The risk of endocarditis is unclear, but endocarditis prophylaxis is not indicated [76]. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Persistent sinusoids — Direct communication between the cardiac chambers and the coronary arteries result from sinusoids that persist during development of the heart. (See 'Introduction' above.)

These are usually seen with congenital heart defects such as pulmonary or aortic atresia with an intact ventricular septum. The coronary artery perfusion in these patients may be dependent on flow from the ventricles to coronary arteries via the sinusoids. Thus, ventricular pressure must be maintained; the sinusoids should not be occluded nor should the ventricular pressure be lowered with valvuloplasty in these patients.

Diagnosis — The diagnosis of persistent sinusoids can be made with color Doppler echocardiography if there is a large enough amount of blood flow [79]. Depending on the relative resistance, flow may be to or from the ventricular cavity to the epicardium and to the coronary arteries. However, the diagnosis is more frequently made during angiography, which is part of the usual diagnostic evaluation of patients in whom sinusoids are likely to exist (eg, pulmonary atresia with intact septum).

Treatment of sinusoids — In general, no treatment of sinusoids is required or it is contraindicated as noted above.

RECOMMENDATIONS OF OTHERS — A discussion of coronary artery abnormalities can be found in the 2008 American College of Cardiology/American Heart Association guidelines for the management of adults with congenital heart disease [67].

A guideline on the indications for cardiac catheterization and intervention in pediatric cardiac disease is also available [80].

SUMMARY AND RECOMMENDATIONS

●Introduction – Congenital anomalies of the coronary circulation include variations in origin, abnormalities in caliber, and coronary artery fistulae.

●Incidence – The incidence of abnormal aortic origin of the coronary arteries is low. The most common anomaly is the left circumflex from the right sinus of Valsalva. (See 'Variations of coronary artery origin from the aorta' above.)

●Disease associations – Variations in origin of the coronary arteries from the aorta are commonly seen with congenital heart diseases such as tetralogy of Fallot, transposition of the great arteries, double outlet right ventricle, univentricular hearts, and truncus arteriosus. (See 'Variant coronary origin associated with other congenital heart diseases' above.)

●Aortic origin from the opposite sinus of Valsalva (AAOCA) – This may result in ischemia and sudden death. AAOCA right coronary artery arising from the left sinus of Valsalva is more common than the left from right sinus of Valsalva, with the latter being at greater risk for sudden cardiac death. Consensus guidelines for the diagnosis and management of these abnormalities have recently been published. (See 'Variations of coronary artery origin from the aorta' above.)

●Pulmonary origin – An anomalous origin of one or more coronary arteries from the pulmonary artery is usually an isolated abnormality (image 1). Such lesions are hemodynamically significant and produce myocardial ischemia that may be progressive and lead to ischemic cardiomyopathy. (See 'Variations of coronary artery origin from the pulmonary artery' above.)

●Abnormalities in the caliber of the coronary arteries – These include narrowing due to stenosis or hypoplasia or enlargement, including ectasia or aneurysmal dilatation. (See 'Abnormalities in the caliber of the coronary arteries' above.)

●Communications between the coronary arteries and the cardiac chambers – This includes coronary-cameral fistulae or other vessels (coronary artery arteriovenous malformations); they are often due to deviations from normal embryological development (see 'Introduction' above).

They may also be acquired from trauma (stab, gunshot, or projectile injuries), or from invasive cardiac procedures such as pacemaker implantation, endomyocardial biopsy, or coronary angiography. (See 'Coronary artery fistulae' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Thomas P. Graham for his past contributions as a section editor to this topic review.