Congenital anomalies of coronary artery misdiagnosed as coronary dilatations in Kawasaki disease: A clinical predicament

Abstract

BACKGROUND

2D-echocardiography (2DE) has been the primary imaging modality in children with Kawasaki disease (KD) to assess coronary arteries.

AIM

To report the presence and implications of incidental congenital coronary artery anomalies that had been misinterpreted as coronary artery abnormalities (CAAs) on 2DE.

METHODS

Records of children diagnosed with KD, who underwent computed tomography coronary angiography (CTCA) at our center between 2013-2023 were reviewed. We identified 3 children with congenital coronary artery anomalies in this cohort on CTCA. Findings of CTCA and 2DE were compared in these 3 children.

RESULTS

Of the 241 patients with KD who underwent CTCA, 3 (1.24%) had congenital coronary artery anomalies on CTCA detected incidentally. In all 3 patients, baseline 2DE had identified CAAs. CTCA was then performed for detailed evaluation as per our unit protocol. One (11-year-boy) amongst the 3 patients had complete KD, while the other two (3.3-year-boy; 4-month-girl) had incomplete KD. CTCA revealed separate origins of left anterior descending artery and left circumflex from left sinus [misinterpreted as dilated left main coronary artery (LCA) on 2DE], single coronary artery (interpreted as dilated LCA on 2DE) and dilated right coronary artery on 2DE in case of anomalous origin of LCA from the main pulmonary artery. The latter one was subsequently operated upon.

CONCLUSION

CTCA is essential for detailed assessment of coronary arteries in children with KD especially in cases where there is suspicion of congenital coronary artery anomalies. Relying solely on 2DE may not be sufficient in such cases, and findings from CTCA can significantly impact therapeutic decision-making.

Key Words: Coronary artery abnormalities; Congenital coronary artery anomalies; Computed tomography coronary angiography; Kawasaki disease; 2-dimensional echocardiography

Core Tip: Congenital coronary artery anomalies are liable to be misinterpreted as coronary artery abnormalities (CAAs) on 2D-echocardiography in children with Kawasaki disease. Computed tomography coronary angiography is essential for the detailed evaluation of coronary arteries.

INTRODUCTION

Kawasaki disease (KD) is the most common childhood vasculitis and has a special predilection for coronary arteries[1]. 2D-echocardiography (2DE) is a convenient, noninvasive, and inexpensive bedside imaging modality to assess coronary arteries and cardiac function in children with KD[1,2]. It can be repeated as often as required. However, the findings on 2DE are operator-dependent and may have poor reproducibility. Limitations of 2DE in assessing coronaries in children with KD include difficulties in (1) Assessment of left circumflex (LCx) coronary artery; (2) Assessment of mid and distal segments of coronary arteries, and (3) In detecting coronary thrombus and stenosis. Further, a poor acoustic window in adolescent children (because of thick chest wall) creates difficulties for the operator[2-4]. In addition, certain anatomical variations in coronary arteries can be misinterpreted as dilated coronaries, resulting in diagnostic difficulties[5].

Computed tomography coronary angiography (CTCA) has emerged as a new modality for assessing coronary arteries along their entire course[3,4,6,7]. It has a high reproducibility and provides explicit details of anatomy. Though high radiation exposure was a concern in the initial days, in the current era, with advancements in dual-source CT Scanners and radiation-optimized protocols, radiation exposure of < 1 millisievert can be achieved[3,4]. The present study aims to report the presence and implications of incidental congenital coronary artery anomalies that had been misinterpreted as CAAs on 2DE.

MATERIALS AND METHODS

This study was conducted at a federally funded not-for-profit tertiary care teaching institute from North-West India. Our unit has over 29 years of experience managing children with KD. We follow the largest single-center cohort of KD in India.

Study population and duration

Between January 1994-June 2023, 1150 patients were diagnosed and treated with KD at our center. Diagnosis of KD was based on the American Heart Association guidelines[8]. Initial Coronary artery assessment in children with KD was performed using 2DE in accordance with standard guidelines. The coronary artery Z-scores were calculated based on body surface area measurements using the method described by Dallaire et al[9], which is widely recognized for its accuracy in pediatric populations. We started using CTCA as a diagnostic imaging modality in KD in October 2013 on a 128-slice dual-source CT scanner and have carried out this investigation in 241 patients till October 2023. Over the last 10 years or so, CTCA has emerged as an important imaging modality in children with KD. We have recently published the suggested indications for CTCA in KD[4-6]. At our center, the indications for performing CTCA are as follows[3,4]: (1) Children with KD who present with coronary artery abnormalities (CAAs) on 2DE at presentation; (2) Children with KD and resistance to intravenous immunoglobulin (IVIg) therapy; (3) Children with KD in infancy; (4) Children with KD and either myocarditis, or KD shock syndrome; and (5) Children with KD with macrophage activation syndrome.

Medical records of children diagnosed with KD who underwent CTCA during this period were reviewed. Patients with KD in whom incidental congenital coronary artery anomalies were identified on CTCA were analyzed, and results correlated with findings of 2DE. The manuscript was approved by the Departmental Review Board.

RESULTS

Of the 241 patients with KD who underwent CTCA for detailed assessment of CAAs, 3 patients were identified to have incidental congenital coronary artery anomalies (1.25%) on CTCA. Details of the three patients are as follows.

Case 1

11-year-old boy who presented with fever, irritability, vomiting, loose stools, vomiting, and mucocutaneous changes in the form of red and cracked lips. Physical examination showed conjunctival injection, erythematous rash over lower limbs, and altered sensorium with poor Glasgow Coma Scale (E2V5M2). Systemic examination was unremarkable. Investigations showed anemia, thrombocytopenia, neutrophilic leucocytosis, hematuria, elevated creatinine, and liver enzymes (Table 1). Work-up for infectious causes (scrub typhus, leptospirosis, Dengue fever, and malaria) was non-contributory. During illness, on day 6 of illness, he developed periungual desquamation. 2DE for coronary artery assessment showed a left main coronary artery (LCA) aneurysm (10 mm; Z = +14.7 Z). He received IVIg 2 g/kg and hemodialysis and showed marked clinical improvement after treatment and laboratory parameters, including renal functions. He was discharged on low-dose aspirin therapy (3-5 mg/kg/day). CTCA done at 3 weeks during convalescence showed separate origins of the left anterior descending artery (LAD) and LCx from the left sinus with no LCA (Figure 1A and B). Aspirin was discontinued on follow-up.

Figure 1 Computed tomography coronary angiography images of patient 1, 2 and 3. A, C and E: Volume rendered; B: Curved reformatted images show separate origins of left anterior descending artery (thick arrows) and left circumflex (thin arrows) from left sinus with absent left main coronary artery. This was misinterpreted as dilated left main coronary artery on two-dimensional echocardiography; D: Axial images show a single coronary artery (thick arrows in C and D) with the normal course and caliber of left anterior descending artery (arrowheads) and left circumflex (thin arrows). Note the origin of right coronary artery from the left main coronary artery (long arrows in C and D) with inter-arterial course and main pulmonary artery- asterisk; F: Axial; G: Curved reformatted images show the origin of left main coronary artery (arrowhead in E; arrow in F) from the main pulmonary artery (asterisk). Note the dilated entire course of right coronary artery in the G and axial inset image.

Table 1 Characteristics of the patients with Kawasaki disease and congenital coronary artery anomalies.

Characteristics	Case 1	Case 2	Case 3
Age of presentation/sex	11 years/male	3.3 years/male	4 months/female
Clinical presentation	Complete KD	Incomplete KD	Incomplete KD
Haemoglobin (g/L)	105	97	102
Total leukocyte counts (× 109/L)	22.4	6	7.6
Differential leukocyte counts	N62L24M08E06	N67L20M7E06	N51L36M10E3
Platelet counts at presentation (× 109/L)	0.49	4.46	6.1
ESR (mm/hour)	54	29
CRP (mg/L) (n < 6 mg/L)	229	45.63	107
NT-proBNP (n < 125 pg/mL)	39000	1318	2649
Serum albumin (g/dL)	1.7	4.1	3.6
ALT (IU/L)	21	17	951
AST (U/L)	39	37	534
Blood urea (mg/dL)	219		32
Serum creatinine (mg/dL)	5.5		0.11
Urine microscopy	10-12 RBCs/hpf, 5-6 WBCs/hpf
Others	Skin biopsy- features of small vessel vasculitis. Cerebrospinal fluid analysis: Cells- nil, Sugar-88 mg/dL, Protein- 31 mg/dL, Gram stain and Indian ink negative, culture sterile
2DE findings	LCA: 10 mm (+ 14.7 z)	LCA: 3.34 mm (+ 3.44 Z); LAD: 1.5 mm (- 0.17 Z); LCx: 1.53 mm (0.09 Z) RCA: 0.99 mm (-2.06 Z)	LCA: Not visible. Proximal LAD: 1.48 mm (+ 1.59 Z). Mid LAD: 2.01 mm (+ 3.42 Z). RCA: 2.15 mm (+ 4.03Z)
Treatment received	IVIg (2 g/kg); aspirin (3-5 mg/kg/day)	IVIg (2 g/kg); aspirin (3-5 mg/kg/day); infliximab (5mg/kg)	IVIg (2 g/kg); aspirin (3-5 mg/kg/day)
CTCA findings	Separate origins of the LAD and LCx from left sinus with no LCA	Single coronary artery arising from left sinus with left dominant circulation. Anomalous origin of RCA from common trunk left sinus with interarterial course. No evidence of any stenosis/ectasia/aneurysm was seen	Anomalous origin of LCA from MPA c/w ALCAPA with dilated LAD and LCX. Diffusely dilated RCA (likely due to ALCAPA). No aneurysm was seen in the coronary arteries

KD: Kawasaki disease; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; NT-proBNP: N-terminal pro-brain-type natriuretic peptide; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; RBC: Red blood cells; WBC: White blood cells; 2DE: 2dimentional echocardiography; CTCA: Computed tomography coronary angiography; LCA: Left coronary artery; RCA: Right coronary artery; LCx: Left circumflex artery; LAD: Left anterior descending; MPA: Main pulmonary artery; ALCAPA: Anomalous origin of left coronary artery from the main pulmonary artery.

Case 2

A 3.3-year-old boy presented with prolonged fever, maculopapular rash, perianal redness, and dorsal edema. Upon history review, the parents noticed periungual peeling on day 6 of the illness. A clinical possibility of incomplete KD was considered. He had anemia, thrombocytosis, and elevated acute phase reactants (Table 1). He had been administered IVIg (2 g/kg) and low-dose aspirin (3-5 mg/kg/day) at a hospital elsewhere and referred to our institute for further management. Coronary artery assessment by 2DE showed LCA aneurysms [LCA: 3.34 mm; +3.44 Z, LAD: 1.5 mm; -0.17 Z, LCx: 1.53 mm; 0.09 Z, and right coronary artery (RCA): 0.99 mm; -2.06 Z] (Figure 2A-C). He also received infliximab (5mg/kg). CTCA revealed a single coronary artery from the left sinus with the left dominant circulation with anomalous origin of RCA from the common trunk left sinus with the inter-arterial course (Figure 1C and D). Given the morphologically normal coronary arteries, oral aspirin was discontinued.

Figure 2 2D echocardiography images in patient 2 and patient 3. A-C: Images show dilated left main coronary artery (thick arrows in A and B) with normal left anterior descending (arrowhead) and left circumflex (thin arrow in B) and normal proximal right coronary artery (thin arrows in C); D: Image shows dilated proximal right coronary artery in patient 3 (thick arrow).

Case 3

A 4-month-old girl presented with acute febrile illness, erythematous rash, respiratory distress, and hypotensive shock. She required mechanical ventilation and inotropic support. Laboratory investigations showed thrombocytosis, elevated transaminases, and raised inflammatory markers (Table 1). During the course of illness, she developed periungual desquamation. A clinical possibility of KD with myocarditis was considered. 2DE showed left ventricular dysfunction with left ventricular ejection fraction of 15%, severe mitral regurgitation, mild pericardial effusion, dilatation of RCA (2.15 mm; +4.03Z), and a small aneurysm in LAD coronary artery (2.01 mm; +3.42Z) (Figure 2D). She was treated with IVIg (2 g/kg) along with low-dose aspirin (3-5 mg/kg/day). CTCA showed the anomalous left coronary artery from the pulmonary artery (ALCAPA) with predominant right circulation (Figure 1E-G). She underwent corrective surgery for ALCAPA and remains well on follow-up.

DISCUSSION

KD is an acute self-limiting medium vessel vasculitis of childhood with a predilection for the coronary arteries. The most important complication of KD, which also results in significant morbidity is the development of CAAs[8]. Delays in diagnosis and treatment of KD can result in the development of CAAs in 15-25% of patients[10]. 2DE is the established modality for the assessment of CAAs of KD. However, 2DE has several limitations. It is operator-dependent and has lower sensitivity for detection of thrombus and stenosis. The distal segments of coronary arteries, the LCx coronary artery, and congenital coronary artery anomalies are difficult to evaluate on 2DE[3-6,11]. Because of these limitations, CTCA is now being increasingly used for the assessment of coronary arteries in children with KD[3-6].

We identified the presence of incidental congenital coronary artery anomalies in 3/241 (1.24%) children. One of these had ALCAPA (patient 3), which is considered to pose a risk of cardiac dysfunction due to chronic ischemia and thus necessitated immediate surgical correction. Because of the right dominant circulation, the RCA appears dilated in 2DE. The other two had minor coronary artery anomalies: One with separate origins of LAD and LCx from the left sinus with an absent left main trunk (patient 1), while the other had a single coronary artery (patient 2). In both these patients, the congenital anomaly had been misinterpreted as CAAs.

About 66 different varieties of coronary artery anomalies are described and classified in the literature[12]. Of these, only a few pose a risk of myocardial injury. Prevalence of congenital coronary artery anomalies has been variably reported in the literature, from 0.17% in autopsy studies[13] to 1.3% in adults evaluated by digital subtraction angiography for cardiac symptoms[14]. Prevalence of congenital coronary artery anomalies has been reported to be 0.17% (4/2388 patients) with the most common being anomalous origins of LCA and RCA[15].

2DE is standard of care imaging in the assessment of coronary arteries and cardiac functions in children with KD as it is a readily available bedside modality but has many inherent limitations. In our cohort of patients with KD, 2DE was performed at admission and then daily during admission. All 3 patients were found to have CAAs on 2DE by different operators. CTCA was performed in these 3 patients after initial stabilization as per our protocol. At our center, we offer radiation-optimized CTCA in the assessment of CAAs of KD. This is a non-invasive day-care examination with minimal radiation exposure (usually < 1 millisievert)[3,4]. The interval between baseline 2DE and CTCA in these 3 patients ranged from 2 days-3 weeks (patient 1:3 weeks; patient 2:2 days; patient 3:3 days).

Magnetic resonance coronary angiography (MRCA) has also been used in the assessment of CAAs. However, it has several drawbacks when compared to CTCA. One of the primary limitations of MRCA is its lower spatial and temporal resolution – this can impact the accuracy of imaging. Additionally, MRCA typically takes much longer (usually 45-60 minutes), and necessitates general anesthesia in infants and younger children to prevent motion artifacts. MRCA is usually a modality of choice for follow-up of thrombotic CAAs[16,17].

CTCA is a safer and non-invasive technique that can demonstrate coronary arteries along their entire course. Though radiation exposure and motion artifacts were shortcomings, recent advances in CTCA imaging have enabled a high resolution with motion-free cardiac images at any heart rate with optimal radiation exposure. These images with high spatial and temporal resolution can delineate coronary artery anatomy with exquisite details of all coronary artery segments, depict changes in luminal caliber, and characterize plaque and other intramural changes. CTCA is rapidly emerging as a non-invasive imaging modality for evaluating CAAs in KD[3,4,17]. Timely diagnosis and findings of CTCA in the 3 patients being reported herein have significantly impacted therapeutic decision-making.

We have recently published the suggested indications for CTCA in KD[3,4]. Based on our experience over the last 10 years we suggest that CTCA should be carried out in the following situations during the acute phase: (1) Children with KD who present with CAAs on 2DE at presentation; (2) Children with KD and resistance to intravenous immunoglobulin therapy; (4) Children with KD in infancy; (5) Children with KD and either myocarditis or KD shock syndrome; and (6) Children with KD with macrophage activation syndrome.

Strengths of this study is that our unit has over 29 years of experience managing children with KD. We follow the largest single-center cohort of KD in India. We have experience with CTCA in 241 patients with KD-this is arguably one of the largest experiences on CTCA in KD. There are certain limitations inherent to the retrospective study design from a single center.

CONCLUSION

To conclude, this study underscores the misinterpretation risk of congenital coronary anomalies as CAAs in KD using 2DE. The incidental discovery of such anomalies in 1.24% of CTCA-scanned KD patients highlights the need for advanced imaging. CTCA remains crucial for coronary artery assessment in children with KD. One patient necessitated immediate intervention due to an anomalous left coronary artery, initially misdiagnosed as a CAA. These findings emphasize CTCA's pivotal role in precise diagnosis and treatment planning in KD, particularly for coronary artery anomalies. Further research is needed to validate these results and enhance clinical guidelines.

ACKNOWLEDGEMENTS

The authors gratefully acknowledge the role of all faculty members, clinical fellows, nursing officers, research, and technical staff who have been involved in the care of these patients.