Giant coronary aneurysms in children with Kawasaki disease and major cardiac complications and dynamic follow-up

Table 1 Overall clinical features of patients with Kawasaki disease

Parameters	Total group (n = 139)	Without CA lesions (n = 107)	With CA lesions (n = 32)	P value
Onset age (years), median (25%, 75%)	3.0 (1.0, 5.0)	3.0 (1.3, 5.5)	1.0 (0.5, 3.4)	0.004
Number of days of fever (days), median (25%, 75%)	10.0 (5.0, 14.0)	11.0 (7.0, 15.0)	5.5 (3.0, 13.0)	0.068
Male sex	73 (53.0)	49 (46.0)	24 (75.0)	0.003
Complete Kawasaki disease criteria	62 (45.0)	49 (46.0)	13 (41.0)	0.608
Neurological symptoms, including	36 (26.0)	24 (22.0)	12 (37.0)	0.088
Aseptic meningitis	9 (6.5)	5 (5.0)	4 (12.0)	0.116
Shock	49 (35.0)	38 (35.5)	11 (34.0)	0.906
Acute renal failure	7 (5.0)	4 (4.0)	3 (9.0)	0.203
Hematologic abnormalities	7 (5.0)	5 (5.0)	2 (6.0)	0.722
Polyserositis	22 (16.0)	18 (17.0)	4 (12.0)	0.560
Acute respiratory distress syndrome	30 (22.0)	18 (17.0)	12 (38.0)	0.012
Coronary thrombosis	6 (4.3)	0	6 (19.0)
Acute heart failure	9 (6.5)	6 (6.0)	3 (9.0)	0.450

Data are presented as n (%). СA: Coronary artery.

Table 2 Clinical features of patients with Kawasaki disease and giant/medium coronary artery aneurysms

Parameters	Giant1 and medium2 CAA (n = 13)	Moderate CAA dilatation3 (n = 19)	P value
Onset age, years, median (25%, 75%)	2.0 (0.8, 5.0)	0.8 (0.4, 1.7)	0.196
Male sex	10 (77.0)	14 (74.0)	0.841
Number of days of fever, median (25%, 75%)	10 (5, 14)	5 (3, 10)	0.073
Complete Kawasaki disease criteria	7 (54.0)	6 (32.0)	0.220
Neurological symptoms	8 (62.0)	4 (21.0)	0.019
Aseptic meningitis	2 (15.0)	2 (11.0)	0.694
Acute kidney failure	1 (8.0)	2 (11.0)	0.795
Polyserositis	2 (15.0)	2 (11.0)	0.694
Hematologic abnormalities	1 (8.0)	1 (5.0)	0.788
Coronary thrombosis	5 (42.0)	1 (5.0)	0.017
Shock	7 (54.0)	4 (21.0)	0.057
Acute heart failure	2 (17.0)	1 (5.0)	0.350
Myocardial dysfunction (heart failure) 1-4 functional class	10 (77.0)	11 (58.0)	0.280
Pericarditis	5 (38.0)	6 (32.0)	0.698
Hemophagocytic syndrome	1 (8.0)	2 (11.0)	0.795
Left ventricle dilatation	1 (8.0)	2 (11.0)	0.795
Right ventricle dilatation	3 (23.0)	3 (16.0)	0.617
Reduced left ventricle ejection fraction	1 (8.0)	0 (0)	-

¹Giant coronary artery aneurysm (CAA) was defined by a Z-score > 10 standard deviations (SD).

²Medium CAA was defined by a Z-score > 5 SD but < 10 SD.

³Moderate CAA dilatation was defined by Z-score < 5 SD but > 2.5 SD.

CAA: Coronary artery aneurysms.

Table 3 Clinical features of patients with Kawasaki disease and giant coronary artery aneurysms (subgroup 1a)

ID, sex, age	Affected coronary arteries	KD form	Cardiovascular events	Other KD manifestation	Treatment
1, M, 5 months	Bilateral multiple LCA d = 0.60 cm (Z-score = 13.7), RCA d = 0.45 cm (Z-score = 10.79)	Complete	Acute HF: HF 4 FC. Subtotal thrombosis of AIVA, acute anterolateral myocardial infarction, ischemic DCM, apical aneurysm of LV	CNS injury-aseptic meningitis, seizures	IVIG 2 courses, AA + clopidogrel, heparin, and LMWH, therapy of chronic HF, Mammarocoronary AIVA bypass grafting
2, M, 9 months	Bilateral multiple LCA d = 0.51 cm (Z-score = 10.25); RCA d = 0.50-0.51 cm (Z-score = 10.79)	Complete	Acute coronary syndrome, ischemic myocardial damage	CNS injury (stunned consciousness) hemophagocytic syndrome	IVIG + GCS + AA + clopidogrel, heparin/LMWH
3, M, 3 months	Bilateral multiple LCA d = 0.50 cm (Z-score = 10.8); RCA d = 0.35 cm (Z-score = 6.8)	Complete	Acute HF giant extracardiac aneurysms	CNS injury-aseptic meningitis hemophagocytic syndrome	IVIG + GCS + AA + clopidogrel, heparin/LMWH
4, M, 8 years	Bilateral multiple AIVA d = 0.626 cm (Z-score = 11.29), circumflex 0.372 cm (Z-score = 4.25); RCA trunk 0.428 cm (Z-score = 4.77), mid. RCA 0.531 cm (Z-score = 7.83)	Complete	Ischemic DCM, HF 4 FC	CNS injury–stunned consciousness	IVIG + АА + LMWH
5, M, 3 years	LCA aneurysm d = 0.7 cm (Z-score = 11.28)	Incomplete	LCA aneurysm, thrombosis, LV dilatation	KD recurrence after 12 months	IVIG + AA + LMWH
6, M, 3 months	RCA aneurysm d = 1.5 cm (Z-score = 37)	Complete	NA	NA	IVIG + AA
7, F, 5 years	LCA aneurysm d = 0.874 cm (Z-score = 18.00	Complete	Ischemic DCM, aortic valve valvulitis with transient, transvalvular flow, acceleration (blood flow rate = 1.78 m/second, pressure gradient 1733 kPa)	CNS injury-stunned consciousness arthritis with rapid reversal	IVIG + AA
8, F, 8 months	Dilatation of the LCA and descending branch, aneurysm of the circumflex artery d = 0.74 cm (Z-score = 17.66)	Incomplete	NA	CNS injury-cerebral vasculitis	IVIG + AA
9, F, 2 years	LCA aneurysm d = 0.715 cm (Z-score = 14.39)	Incomplete	Near-wall thrombus in LCA aneurysm	NA	IVIG + AA

АА: Acetylsalicylic acid; AIVA: Anterior interventricular artery; CNS: Central nervous system; d: Diameter; DCM: Dilated cardiomyopathy; F: Female; FC: Functional class; GCS: Glucocorticosteroids; HF: Heart failure; IVIG: Intravenous immunoglobulin; KD: Kawasaki disease; LCA: Left coronary artery; LMWH: Low molecular weight heparin; LV: Left ventricle; M: Male; NA: Not available; RCA: Right coronary artery.

Table 4 Clinical features of patients with Kawasaki disease and medium coronary artery aneurysms (subgroup 1b)

ID, sex, age	Affected coronary arteries	KD form	Cardiovascular events	Other KD manifestations	Therapy
10, M, 6 years	LCA aneurysm d = 0.55 cm (Z-score = 8.24)	Complete	NA	NA	IVIG + AA
11, M, 6 years	RCA aneurysm d = 0.65 cm (Z-score = 9.84)	Incomplete	Near-wall thrombus in RCA aneurysm coronary-right atrial fistula	NA	IVIG + AA + heparin and low molecular weight heparin surgical closure of the coronary fistula
12, M, 1.5 years	LCA aneurysm along d = 0.53 cm (Z-score = 9.57)	Complete	NA	NA	IVIG + AA
13, M, 3 years	LCA aneurysm d = 4.6 mm	Complete	NA	NA	IVIG + AA

Numbering continued from Table 3. АА: Acetylsalicylic acid; d: Diameter; IVIG: Intravenous immunoglobulin; KD: Kawasaki disease; LCA: Left coronary artery; M: Male; NA: Not available; RCA: Right coronary artery.

Table 5 Treatment at the onset of Kawasaki disease

Therapy at onset	Children with coronary dilatation (n = 32)	Group 1 (with giant/medium coronary artery aneurysms) (n = 13)	Group 2 (with moderate coronary dilatation) (n = 19)
Intravenous immunoglobulin	30 (94.0)	13 (100)	17 (89.0)
Glucocorticosteroids	3 (9.0)	2 (15.0)	1 (5.0)
Etanercept	1 (3.0)	1 (8.0)	0 (0)
Cyclosporine	2 (6.0)	1 (8.0)	1 (5.0)
Acetylsalicylic acid	31 (97.0)	13 (100)	18 (95.0)
Anticoagulants: LMWH or heparin (intravenous) with subsequent LMWH	12 (38.0)	7 (54.0)	5 (26.0)
Heart failure therapy at the Kawasaki disease onset
Carditonics	2 (6.0)	1 (8.0)	1 (5.0)
Diuretics	22 (69.0)	11 (85.0)	11 (58.0)
Beta-blockers	14 (44.0)	5 (38.0)	9 (47.0)
Angiotensin-converting enzyme inhibitors	7 (22.0)	5 (38.0)	2 (11.0)
Outcomes
Regression of thrombosis	6/6 (100)	6/6 (100)	0 (0)
Ischemic dilated cardiomyopathy	3 (9.4)	3 (23.0)	0 (0)

Data are presented as n (%). LMWH: Low molecular weight heparin.

Table 6 Follow-up of patients with Kawasaki disease and giant coronary aneurysms (9 patients, subgroup 1a)

ID, sex, age at KD onset	CA	CA, Z-score, SD				Clinical events
		At onset	After 3 months	After 6 months	After 1 year
1, M, 5 months	LCA	12.80 multiple aneurysms	9.80	NA	4.80	Giant CA of AIVA and RCA, subtotal thrombosis of AIVA, acute myocardial infarction, coronary bypass grafting. After 1-year complete recanalization of thrombosis. Regression of LCA aneurysm to ectasia, recanalization of AIVA, and shunt thrombosis. After 15 years normal LCA and RCA diameter
	RCA	13.70 multiple aneurysms	4.20	NA	2.90	Regression to ectasia, normal diameter after 15 years
2, M, 9 months	LCA	11.08	8.80	8.51	6.74	Partial regression, complete regression after 3 years
	RCA	10.44	8.39	6.83	5.93	Partial regression, normal diameter after 3 years
3, M, 3 months	LCA	10.80	5.41	6.69	3.56	Slow wave-like regression to ectasia after 5 years
	RCA	6.80	5.73	7.26	4.71	Slow wave-like regression to ectasia after 5 years
4, M, 8 years	LCA	11.20	NA	NA	-0.44	Complete regression after 1 year
	RCA	8.43	NA	NA	3.07	Slow regression to ectasia in 1-year, complete regression after 4 years
5, M, 3 years	LCA	2.12	0.91	0.24	11.59	Moderate dilatation in the first episode of KD with regression and formation of giant CA in the recurrence of KD. Complete regression after 4 years
	RCA	2.22	0.81	0.65	1.29	In the first episode of KD, moderate coronary dilatation with further complete regression
6, M, 3 months	LCA	1.74	NA	6.8	3.59	Coronary dilatation after 6 months with progression to CA and partial regression to ectasia after 1 year
	RCA	26.50	NA	1.70	4.88	Complete regression did not occur after 1 year of partial regression of giant CA to ectasia; complete regression did not occur
7, F, 5 years	LCA	10.90	18.00	NA	0.11	Giant CA with diameter increased after 3 months and complete regression after 1 year from the onset of KD
	RCA	1.37	1.06	NA	0.06	Not involved
8, F, 8 months	LCA	12.90	NA	12.70	12.21	Giant aneurysm after 1 year without change, complete regression after 5 years
	RCA	-0.51	NA	-0.58	-0.36	Not involved
9, F, 2 years	LCA	14.30	NA	NA	16.36	Giant CA with diameter increased after 1-year, partial regression to large aneurysm (Z-score < 10) after 4 years
	RCA	0.50	NA	NA	0.72	Not involved

Numbering corresponds to Table 3. AIVA: Anterior interventricular artery; СA: Coronary artery; F: Female; KD: Kawasaki disease; LCA: Left coronary artery; M: Male; NA: Not available; RCA: Right coronary artery; SD: Standard deviation.

Table 7 Follow-up of patients with Kawasaki disease and medium coronary aneurysms

ID, sex, age	Affected CA	Z-score				Clinical events
		At onset	After 3 months	After 6 months	After 12 months
10, M, 6 years	LCA	8.24	4.10	4.42	3.28	Regression to ectasia, normal diameter after 1 year
	RCA	1.46	1.27	0.04	-0.46	Not involved
11, M, 6 years	LCA	0.86	NA	-0.24	0.65	Not involved
	RCA	8.68	NA	1.57	1.05	Near-wall thrombosis of CA, formation of coronary fistula, ligation of fistula, complete regression of CA
12, M, 1.5 years	LCA	9.57	NA	NA	0.38	Complete regression of CA after 1 year
	RCA	1.56	NA	NA	0.01	Not involved
13, M, 3 years	LCA	6.13	NA	NA	NA	Not seen in follow-up
	RCA	-0.14	NA	NA	NA	Not involved

Numbering of patients corresponds to Table 4 (4 patients, subgroup 1b). СA: Coronary artery; LCA: Left coronary artery; M: Male; NA: Not available; RCA: Right coronary artery.