Published online August 1, 2007
PEDIATRICS Vol. 120 No. 2 August 2007, pp. e424-e427 (doi:10.1542/peds.2006-3181)

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EXPERIENCE & REASON

Myocardial Infarction in an Adolescent: Anomalous Origin of the Left Main Coronary Artery From the Right Coronary Sinus in Association With Combined Prothrombotic Defects

Martin Koestenberger, MD^a, Bert Nagel, MD^a, Andreas Gamillscheg, MD^a, Werner Temmel, MD^b, Gerhard Cvirn, PhD^c and Albrecht Beitzke, MD^a

^a Division of Pediatric Cardiology, Department of Pediatrics
^b Division of Pediatric Radiology, Department of Radiology
^c Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University Graz, Graz, Austria

ABSTRACT

We present the case of a 15-year-old boy with clinical features of an acute myocardial infarction. Angiography revealed a complete obstruction of the left main coronary artery. A coronary-aorto-bypass graft was undertaken immediately. Cardiac computed tomography demonstrated an anomalous origin of the left main coronary artery from the right coronary sinus of the aorta. A thrombophilic state with a heterozygote genotype for prothrombin G20210 mutation, a C677T methylenetetrahydrofolate reductase gene mutation, and a protein C type 1 deficiency was detected. No other embolic source could be identified. The patient recovered with persistent left ventricular dysfunction. He is now taking the anticoagulant warfarin. Combined prothrombotic defects in combination with additional risk factors such as coronary anomalies can lead to myocardial infarction even in children and adolescents.

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Key Words: myocardial infarction • adolescent • coronary anomaly • prothrombotic defects

Abbreviations: MI, myocardial infarction • MTHFR, methylenetetrahydrofolate reductase • LMT, left main trunk • RCA, right coronary artery • CT, computed tomography

Myocardial infarction (MI) is uncommon in previously asymptomatic adolescents.¹ In this age group, various case reports have described sudden cardiac events such as MI secondary to coronary anomalies,² drug use,³ and heritable thrombophilia.⁴ A patent foramen ovale associated with heritable thrombophilia has also been discussed as a triggering mechanism.⁵ Anomalous origin of the left coronary artery from the right coronary sinus is known to be a cause of sudden death in adolescents.⁶ Rarely, combination of a heterozygote genotype for prothrombin G20210 mutation, a heterozygote genotype for C677T methylenetetrahydrofolate reductase (MTHFR) gene mutation, and a protein C type 1 deficiency can be an important risk factor for spontaneous thrombosis in childhood and adolescence.^{7, 8} Although infrequent, a combination of MTHFR gene mutation and prothrombin G20210 mutation as a cause of MI has been reported.⁴ However, only rare data exist about an association of protein C deficiency and the development of MI.⁹ To our knowledge, no data exist about the combination of risk factors given in our case.

CASE REPORT

A 15-year-old boy without any previous cardiac history experienced acute chest pain and dyspnea while playing football. On admission he still suffered from pain but with decreased intensity. An electrocardiogram showed sinus rhythm with ST elevation in lead I, aVL, and V2–V6. His myocardial enzyme levels were significantly increased: troponin T was 11.90 ng/mL (reference: 0.00–0.05 ng/mL), myoglobin was 2014 ng/mL (reference: 0–80 ng/mL), and creatine kinase-myocardial band was 1376 U/L (reference: 0–13 U/L). Additional laboratory results included a creatine phosphokinase level of 17600 U/L (reference: 0–160 U/L) and an aspartate transaminase level of 1832 U/L (reference: 0–43 U/L), and his red blood cells, white blood cells, hemoglobin, renal function, standard coagulation markers, and N-terminal fragment pro–brain natriuretic peptide were within the reference limits. Urine drug screen results were negative. Echocardiography showed a markedly decreased left ventricular function, and the left main trunk (LMT) could not be visualized.

Emergency cardiac catheterization revealed a normal right coronary artery (RCA), but the LMT was completely obstructed, as shown in Fig 1, and stenting by cardiac catheterization was not possible. Clinically, the patient showed signs of a cardiogenic shock and loss of consciousness. In an emergency operation, the proximal part of the left coronary system was found to be completely occluded, and the initial attempted mechanical recanalization and rapid restoration of coronary flow failed. Therefore, coronary-aorto-bypass graft was performed to both the left anterior descending artery and left circumflex coronary artery. His postoperative course was uncomplicated. Postoperative treatment consisted of a combination of diuretics, ß blockers, and angiotensin-converting enzyme inhibitors, as well as anticoagulant treatment with unfractionated heparin and aspirin. Thrombophilia studies established a heterozygote genotype for prothrombin G20210 mutation and a heterozygote genotype for C677T MTHFR gene mutation. Protein C activity and antigen were reduced to 36% and 45%, respectively. Protein S activity was normal. Factor V Leiden mutation was absent, as was lupus anticoagulant and anticardiolipin anticoagulants. Results of a Doppler evaluation of the abdominal and lower-limb veins and arteries were normal. Contrast transesophageal echocardiography excluded a paradoxical embolic event via a patent foramen ovale. The mother was a heterozygote for prothrombin G20210 mutation and heterozygote for factor V Leiden but has not experienced venous thrombosis to date.

View larger version (80K): [in this window] [in a new window]   FIGURE 1 Coronary angiography. A, Hand injection into the right coronary sinus only showed the RCA but not the LMT. B, Hand injection into the left coronary sinus without visualization of the LMT.

 
Postoperative computed tomography (CT) angiography using the 64-slice CT technology demonstrated an anomalous origin of the hypoplastic LMT from the right coronary sinus. It followed a short interarterial course between the aorta and the main pulmonary artery supplying the anterior descending and circumflex coronary arteries, as shown in Fig 2. Serial echocardiography demonstrated persistent impaired left ventricular function. Electrocardiography 2 weeks after the MI exhibited pathologic deep Q waves in aVL and V1–V6 and negative T waves in V3–V6. Because of the coronary-aorto-bypass graft and the combined prothrombotic defects, anticoagulant treatment with warfarin was started.

View larger version (61K): [in this window] [in a new window]   FIGURE 2 A, Axial scan at the level of the left main coronary artery, the hypoplastic left main coronary artery arising from the right coronary sinus with an abnormal course between the aorta, and the main pulmonary trunk. B, Axial scan at the level of the RCA, regular origin of the RCA, the hypoplastic left anterior descending artery, and left circumflex coronary artery.

 

DISCUSSION

Possible causes of MI in children and adolescents are Kawasaki disease, known atherosclerotic disease, drug abuse, sickle cell disease, or myocarditis; therefore, these etiologies have to be excluded.¹ In addition, spontaneous, iatrogenic, or paradoxical coronary artery embolism can result in MI in adolescents.⁵ However, the most common cause of an acute MI in children and adolescents is an anomaly of the coronary arteries. The left coronary artery arising from the right coronary sinus is a rare but dangerous congenital coronary anomaly that can lead to sudden death in adolescents and young adults.⁶ The course of the LMT between the aorta and the main pulmonary trunk in combination with physical exercise is known to be associated with sudden cardiac death.¹⁰ In children and adolescents who present with an acute MI, immediate cardiac catheterization is mandatory. If coronary abnormalities are detected, 64-slice CT, a method that was recently shown to accurately detect obstructive coronary artery disease,¹¹ is helpful in the diagnosis of an abnormal coronary artery course such as that in our patient. In our opinion, the diagnostic workup should also include a complete thrombophilia screening. As shown in various studies, the prothrombin G20210 and C677T MTHFR gene mutations and deficiencies of protein C are important risk factors for thrombosis in childhood and adolescence.^{8, 12} The prevalence of the prothrombin G20210 and C677T MTHFR gene mutations in the general population is 1.3% and 10.4% respectively.^{7, 8} Prevalence of the combined prothrombotic defects shown in our case has not been reported in the literature thus far. Although the results of Doggen et al¹³ in adults indicate that the importance of the prothrombin G20210A mutation is restricted to individuals who have additional cardiovascular risk factors, it was recently shown for adolescents that this gene mutation seems to be the only prothrombotic risk factor associated with the risk of developing MI in that age group.⁹

In our case, MI occurred in a young patient who is heterozygous for the prothrombin G20210 and C677T MTHFR gene mutations and has also a protein C type 1 deficiency. Therefore, we assume that coronary occlusion in our patient occurred as a result of the combination of physical activity, multiple heritable prothrombotic defects, and the hypoplastic anomalous origin of the LMT from the right coronary sinus with an abnormal course between the aorta and the main pulmonary trunk.

CONCLUSIONS

MI in children and adolescents is rare and continues to be a diagnostic challenge. Combined prothrombotic defects in combination with additional risk factors such as coronary anomalies can lead to MI even in this group of patients. Thus, heritable thrombophilia should always be investigated thoroughly in young patients who present with MI even if a coronary anomaly is present.

ACKNOWLEDGMENTS

This study was supported by grants from the Franz-Lanyar-Stiftung.

FOOTNOTES

Accepted Jan 25, 2007.

Address correspondence to Martin Koestenberger, MD, Department of Pediatrics, Medical University Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. E-mail: koestenbergerm{at}gmx.at or martin.koestenberger{at}klinikum-graz.at

The authors have indicated they have no financial relationships relevant to this article to disclose.

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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