Evaluation of Coronary Circulation by 13N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease.

BACKGROUND: Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention. METHODS: Using adenosine-stress 13N-ammonia myocardial perfusion positron emission tomography, we evaluated coronary circulation in 14 patients (12 males) with RCA occlusion to identify ischemia (myocardial flow ratio < 2.0) in the RCA region and examined hemodynamics, cardiac function, and coronary aneurysm diameter. These variables were also compared in patients with/without RCA segmental stenosis (SS). RESULTS: There were five cases of ischemia in the RCA region. RCA myocardial blood flow (MBF) at rest was higher in patients with ischemia than in those without ischemia, but the difference was not significant (1.27 ± 0.21 vs. 0.82 ± 0.16 mL/min/g, p = 0.2053). Nine patients presented with RCA SS, and age at onset of Kawasaki disease tended to be lower in those with SS. The maximum aneurysm diameter of RCA was significantly smaller in patients with SS (10.0 ± 2.8 vs. 14.7 ± 1.6, p = 0.0239). No significant differences in other variables were observed between patients with/without ischemia and SS. CONCLUSIONS: At rest, MBF in the RCA region was relatively well preserved, even in patients with RCA occlusion, and there was no progressive deterioration in cardiac function. Adenosine stress showed microcirculatory disturbances in only half of the patients, indicating that it is reversible in children with Kawasaki disease.

Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease.

GOAL: Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. METHOD: This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13-30 months, and > 30 months) and fever duration (≤5 days, 6-7 days, 8-9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. RESULTS: Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%-1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13-0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13-30 months. CONCLUSION: There are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.

Microvascular changes on nailfold capillaroscopy in acute stage of Kawasaki disease: a new diagnostic paradigm for an enigmatic condition.

OBJECTIVES: Kawasaki disease (KD) is a medium vessel vasculitis with a predilection to involve coronary arteries. However, there is a paucity of literature on microvascular changes in patients with KD. METHODS: Children diagnosed with KD based on American Heart Association guidelines 2017 were enrolled prospectively. Demographic details and echocardiographic changes in coronaries were recorded. Nailfold capillaries were assessed using Optilia Video capillaroscopy and data were analysed using Optilia Optiflix Capillaroscopy software at acute (prior to IVIG administration) and subacute/convalescent phase. RESULTS: We enrolled 32 children with KD (17 boys) with a median age of 3 years. Nailfold capillaroscopy (NFC) was performed in 32 patients in the acute phase (compared with 32 controls) and in 17 during the subacute/convalescent phase at a median follow-up of 15 (15-90) days after IVIG treatment. The following findings were seen in NFC in the acute phase of KD: reduced capillary density (n = 12, 38.6%), dilated capillaries (n = 3, 9.3%), ramifications (n = 3, 9.3%) and capillary haemorrhages (n = 2, 6.2%). Capillary density was reduced significantly in the acute phase of KD (38.6%) as compared with the subacute/convalescent phase (25.4%) (P-value <0.001) and controls (0%) (P-value = 0.03). We observed no correlation between coronary artery involvement and mean capillary density (P = 0.870). CONCLUSION: Results show that patients with KD have significant nailfold capillary changes in the acute phase. These findings may provide a new diagnostic paradigm for KD and a window to predict coronary artery abnormalities.

A Deep Learning Framework for Image-Based Screening of Kawasaki Disease.

Kawasaki disease (KD) is a leading cause of acquired heart disease in children and is characterized by the presence of a combination of five clinical signs assessed during the physical examination. Timely treatment of intravenous immunoglobin is needed to prevent coronary artery aneurysm formation, but KD is usually diagnosed when pediatric patients are evaluated by a clinician in the emergency department days after onset. One or more of the five clinical signs usually manifests in pediatric patients prior to ED admission, presenting an opportunity for earlier intervention if families receive guidance to seek medical care as soon as clinical signs are observed along with a fever for at least five days. We present a deep learning framework for a novel screening tool to calculate the relative risk of KD by analyzing images of the five clinical signs. The framework consists of convolutional neural networks to separately calculate the risk for each clinical sign, and a new algorithm to determine what clinical sign is in an image. We achieved a mean accuracy of 90% during 10-fold cross-validation and 88% during external validation for the new algorithm. These results demonstrate the algorithms in the proposed screening tool can be utilized by families to determine if their child should be evaluated by a clinician based on the number of clinical signs consistent with KD.Clinical Relevance- This screening framework has the potential for earlier clinical evaluation and detection of KD to reduce the risk of coronary artery complications.

Non-contrast magnetic resonance angiography for systemic artery evaluation in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis; systemic arteries other than the coronary arteries should therefore also be evaluated. This study investigated the feasibility of evaluating coronary aneurysms, systemic artery aneurysms (SAAs), and cerebrovascular diseases in patients with KD using non-contrast magnetic resonance angiography (NC-MRA). METHODS: Coronary artery protocols, including coronary magnetic resonance angiography (MRA) and vessel wall imaging, were performed in 57 examinations of 28 patients. Systemic artery protocol, including SAA scans and head MRA, along with coronary artery protocol, were performed in 42 examinations of 42 patients. The image quality of the SAAs was evaluated on a 4-point scale. Examination time and sedation dosage were compared between the protocols. The presence of SAAs and cerebrovascular disease was also evaluated. RESULTS: The image quality score of SAAs was 4 (interquartile range [IQR]: 4-4) for the aorta, 4 (IQR: 3-4) for the subclavian artery, 4 (IQR: 3-4) for the renal artery, and 3 (IQR: 3-4) for the iliac artery. No differences were found between examination time (47.0 [IQR: 43.0-61.0] min vs. 51.0 [IQR: 45.0-60.0] min, p = 0.48) and sedative dose (4.63 [IQR: 3.93-5.79] mg/kg vs. 4.21 [IQR: 3.56-5.71] mg/kg, p = 0.37) between the protocols. Systemic artery protocol detected SAAs in three patients (7.1%), and cerebrovascular disease was not detected. CONCLUSIONS: Evaluating the coronary and systemic arteries in patients with KD using NC-MRA on a single examination was possible without compromising examination time or sedation dose. The systemic artery protocol was useful in finding SAAs.

The role of nailfold capillaroscopy in pediatric patients with Kawasaki disease.

BACKGROUND: Nailfold capillaroscopy has been used as a non-invasive diagnostic method for microvasculature evaluation in various rheumatological disorders. The present study aimed to determine the utility of nailfold capillaroscopy in the diagnosis of Kawasaki Disease (KD). METHOD: In this case-control study nailfold capillaroscopy was performed in 31 patients with KD and 30 healthy controls. All nailfold images were evaluated for capillary distribution and capillary morphology such as enlargement, tortuosity, and dilatation of the capillaries. RESULT: Abnormal capillaroscopic diameter was identified in 21 patients from the KD group and 4 patients in the control group. The most common abnormality in capillary diameter was irregular dilatation in 11 (35.4%) KD patients and in 4 people (13.3%) in the control group. Distortions of the normal capillary architecture was commonly seen in the KD group (n=8). A positive correlation was observed between coronary involvement and abnormal capillaroscopic results (r=.65, P<.03). The sensitivity and specificity of capillaroscopy for the diagnosis of KD were 84.0% (95%CI: 63.9-95.5%) and 72.2% (95%CI: 54.8-85.8%), respectively. The PPV and NPV of capillaroscopy for KD were 67.7% (95%CI: 48.6-83.3) and 86.7% (95% CI: 69.3-96.2), respectively. CONCLUSION: Capillary alterations are more common in KD patients compared to control group. Thus, nailfold capillaroscopy can be useful in detecting these alterations. Capillaroscopy is a sensitive test for detecting capillary alternations in KD patients. It could be used as a feasible diagnostic modality for evaluating microvascular damage in KD.

Left atrial subclinical dysfunction in children with Kawasaki disease: a two-dimensional speckle-tracking echocardiography study.

BACKGROUND: Left atrial (LA) function is a very important prognostic indicator for many cardiovascular diseases. In this study, we aimed to determine whether LA function is impaired in children with Kawasaki disease (KD) and to analyze the relationships between LA deformation and conventional echocardiographic parameters and laboratory markers. METHODS: A total of 50 KD patients during different disease phases and 50 age- and sex-matched controls were retrospectively analyzed. Patients in the acute phase based on coronary artery dilation (CAD) were subdivided into Group I (with CAD) and Group II (without CAD) and compared. RESULTS: During the acute phase, KD patients had a lower peak LA longitudinal strain (PLALS), a lower LA strain peak during LA contraction (LASct), and a lower LA strain rate peak during LA contraction (LASRct) than the controls. The PLALS, LASct and LASRct began to increase during the subacute phase, and during the convalescent phase, all LA strains in patients had recovered to normal compared with the control subjects. Subgroup analysis revealed that, compared with Group II, Group I had higher C-reactive protein (CRP) and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; however, there were no significant differences in LA strains. Only the PLALS during the acute phase was negatively correlated with left ventricular mass index, CRP and NT-proBNP. CONCLUSIONS: In patients with KD, LA function is impaired during the acute phase, and this impairment is transient. Two-dimensional speckled tracking echocardiography is a useful tool for detecting subclinical LA dysfunction.

Z-score regression model for coronary artery diameter in healthy Chinese Han children.

BACKGROUND: Coronary artery distension and aneurysm are complications of Kawasaki disease in children. PURPOSE: To develop a Z-score regression model for coronary artery diameter in children that could be used as reference. MATERIAL AND METHODS: This retrospective analysis included children with normal heart structure between March 2013 and April 2017. Body surface area (BSA) was calculated. The diameters of the right coronary, left main coronary, left anterior descending, and circumflex arteries were measured by echocardiography. Pearson correlation analysis was used to establish linear, exponential, logarithmic, power, and square root regression models. RESULTS: The analysis included 509 children (280 boys) aged 1 day to 15.2 years. Coronary artery diameters were significantly correlated with age, height, body mass, BSA, and BSA (r = 0.663-0.826; P < 0.05), with a stronger correlation for BSA than BSA (P < 0.05). The adjusted determination coefficients (Ra2) were higher for the exponential and square root models than for the other models (P < 0.05). The random error term variance was constant for the exponential model (P > 0.05), and processing with the weighted least-square methods eliminated heteroscedasticity in the other models. The Z-scores were normally distributed for the exponential and square root models (P > 0.05). CONCLUSION: Overall, the square root model was the optimal equation for the calculation of coronary artery Z-score in Chinese Han children. This model could be used to facilitate the diagnosis of coronary artery distension in children with suspected Kawasaki disease.

Distal coronary artery abnormalities in Kawasaki disease: experience on CT coronary angiography in 176 children.

OBJECTIVE: Precise evaluation of coronary artery abnormalities (CAAs) in Kawasaki disease (KD) is essential. The aim of this study is to determine role of CT coronary angiography (CTCA) for detection of CAAs in distal segments of coronary arteries in patients with KD. METHODS: CTCA findings of KD patients with distal coronary artery involvement were compared with those on transthoracic echocardiography (TTE) during the period 2013-21. RESULTS: Among 176 patients with KD who underwent CTCA (128-Slice Dual Source scanner), 23 (13.06%) had distal CAAs (right coronary-15/23; left anterior descending-14/23; left circumflex-4/23 patients). CTCA identified 60 aneurysms-37 proximal (36 fusiform; 1 saccular) and 23 distal (17 fusiform; 6 saccular); 11 patients with proximal aneurysms had distal contiguous extension; 9 patients showed non-contiguous aneurysms in both proximal and distal segments; 4 patients showed distal segment aneurysms in absence of proximal involvement of same coronary artery; 4 patients had isolated distal CAAs. On TTE, only 40 aneurysms could be identified. Further, distal CAAs could not be identified on TTE. CTCA also identified complications (thrombosis, mural calcification and stenosis) that were missed on TTE. CONCLUSIONS: CAAs can, at times, occur in distal segments in isolation and also in association with, or extension of, proximal CAAs. CTCA demonstrates CAAs in distal segments of coronary arteries, including branches, in a significant number of children with KD-these cannot be detected on TTE. CTCA may therefore be considered as a complimentary imaging modality in children with KD who have CAAs on TTE.

Usefulness of Cervical Computed Tomography Hounsfield Units to Differentiate Kawasaki Disease From a Deep-neck Abscess.

We measured the Hounsfield units (HUs) value of cervical plain computed tomography images to differentiate between Kawasaki disease (KD) and a deep-neck abscess (DNA). The HUs value was significantly lower in KD than in DNA, making it a useful marker for differentiating between these 2 diseases.

Ultrasound evaluation of endothelial dysfunction in immunoglobulin-resistant children with acute Kawasaki disease.

INTRODUCTION: Given the evidence that brachial artery flow-mediated dilation (FMD) is declined in children later after the onset of Kawasaki disease (KD), we hypothesized that indicators that detect the situation of the endothelium are useful parameters that can accurately reflect subclinical dysfunction in resistant patients and assist in differentiating patients with KD at a higher risk of IVIG resistance, which may be valuable in better understanding how to protect patients from endothelial and thrombotic complications. METHODS: Fifty IVIG-resistant KD children, 120 IVIG-responsive KD children, 35 febrile children with acute upper respiratory infection, and 50 healthy controls were recruited, and indicators reflecting endothelial inflammation, including flow-mediated dilation (FMD), were measured. Receiver operating characteristic (ROC) curve analysis was utilized to determine the threshold values of these indicators of IVIG resistance. Multiple logistic regression analysis was performed to determine whether FMD was an independent predictor of IVIG-resistant patients. RESULTS: In comparison with the lab data, PCT, Na + , and FMD exhibited AUCs of 0.727, 0.653, and 0.698 (P < 0.05), respectively, in predicting IVIG resistance in KD through ROC analysis. PCT > 1.69 ng/ml, Na + < 133.2 mmol/l, and FMD < 5.79% were independent predictors of IVIG resistance in KD (OR 4.257, 3.516, 3.563, 95% CI 1.549 ~ 11.700, 1.277 ~ 9.680, 1.299 ~ 9.772, P < 0.05). CONCLUSION: More severe endothelial dysfunction, especially lower FMD, was present in IVIG-resistant patients than in IVIG-responsive patients. It is a helpful diagnostic tool that provides supportive criteria to detect KD patients at a higher risk of IVIG resistance when FMD < 5.79% in children. Key Points • IVIG-resistant KD patients have more severe endothelial dysfunction than IVIG-sensitive patients. • FMD < 5.79% may indicate an increased risk of IVIG resistance in children with Kawasaki disease.

Imaging Evaluation of Kawasaki Disease.

PURPOSE OF REVIEW: This review provides the summary of the appropriate use of these modalities when caring for patients with Kawasaki disease at diagnosis and for long-term management. RECENT FINDINGS: Kawasaki disease is an inflammatory syndrome of unknown etiology that can result in coronary artery dilations or aneurysms if left untreated in 25% of the patients and 3-5% in treated patients. In addition to coronary artery aneurysms, patients can have ventricular dysfunction, valvular regurgitation, aortic root dilation, and pericardial effusion due to inflammation of the myocardium. Noninvasive imaging modalities are important to these assessments. Echocardiography is the first-line noninvasive evaluation of coronaries and function. Cardiac magnetic resonance imaging is useful for functional assessment in long-term follow-up. Distal coronaries, thromboses, and stenoses are best evaluated by cardiac computed tomography. Future research should demonstrate the effectiveness of advanced functional imaging in patients with Kawasaki disease and decreased radiation from cardiac computed tomography.

[Analysis of 2 diagnostic criteria of echocardiography for coronary artery aneurysm in Kawasaki disease].

Objective: To analyze the difference between Z score and previous criteria in the diagnosis characteristics of coronary artery aneurysm (CAA) in Kawasaki disease, and to investigate the clinical distribution of Kawasaki disease CAA in the Z score group. Methods: This study retrospectively analyzed the clinical and echocardiographic data of 2 419 children with Kawasaki disease in Shenzhen Children's Hospital from January 2009 to December 2019. The traditional criteria and Z score criteria were used to diagnose CAA, and the differences of diagnostic efficiency between the 2 diagnostic methods were analyzed. The clinical distribution characteristics of CAA in children with Kawasaki disease were analyzed by grouping their sex, clinical classification (complete Kawasaki disease, incomplete Kawasaki disease) the sensitivity to intravenous immunoglobulin (IVIG) (IVIG-sensitive Kawasaki disease,IVIG-unresponsive Kawasaki disease). And the course of the disease (≤6 weeks, >6-8 weeks, >8 weeks to 6 months) etc. The χ² test or Kruskal-Wallis test was used for comparison between the groups, and the Kappa test was used for consistency evaluation. Results: Among the 2 419 children with Kawasaki disease, 1 558 were males and 861 were females. The age of onset was 1.8 (1.0, 3.2) years. The rate of CAA by Z score criteria was higher than that by traditional method (21.9% (529/2 419) vs. 13.9% (336/2 419), χ2=1 074.94, P<0.001). Compared to the traditional method, the Z score criteria found higher rate of CAA in male patients, patients with incomplete Kawasaki disease, and IVIG-unresponsive patients (25.2% (392/1 558) vs. 16.0% (249/1 558), (32.7% (166/507) vs. 19.5% (99/507), 30.5% (95/312) vs. 24.0% (75/312), χ2=694.05, 216.19, 184.37, all P<0.001). The Z score criteria was consistent with the traditional method in diagnosing CAA (κ=0.642,P<0.001). Moreover, in the Z score criteria, the rate of CAA in males (25.2%, 392/1 558) was higher than that in females (15.9%, 137/861), higher in incomplete Kawasaki cases (32.7%, 166/507) than that in complete Kawasaki case (19.0%, 363/1 912), and higher in IVIG-unresponsive cases (30.4%, 95/312) than that in IVIG-sensitive cases (20.6%, 434/2 107), with statistically significant differences (χ2=27.76, 44.38, 15.43, all P<0.001). Coronary Z score of course ≤ 6 weeks was greater than that of course between>6-8 weeks and >8 weeks to 6 months (1.3 (0.7, 2.3) vs. 0.7 (0.3, 1.4), 0.7 (0.3, 1.3), Z=20.65, 13.70, both P<0.001). Conclusions: The rate of CAA in Kawasaki disease by Z score criteria is higher than that by traditional method. In the Z score group, most CAA occur within 6 weeks of the course of the disease, and the rate of CAA in male, incomplete Kawasaki disease, and IVIG-unresponsive is higher.

Explainable deep learning algorithm for distinguishing incomplete Kawasaki disease by coronary artery lesions on echocardiographic imaging.

BACKGROUND AND OBJECTIVE: Incomplete Kawasaki disease (KD) has often been misdiagnosed due to a lack of the clinical manifestations of classic KD. However, it is associated with a markedly higher prevalence of coronary artery lesions. Identifying coronary artery lesions by echocardiography is important for the timely diagnosis of and favorable outcomes in KD. Moreover, similar to KD, coronavirus disease 2019, currently causing a worldwide pandemic, also manifests with fever; therefore, it is crucial at this moment that KD should be distinguished clearly among the febrile diseases in children. In this study, we aimed to validate a deep learning algorithm for classification of KD and other acute febrile diseases. METHODS: We obtained coronary artery images by echocardiography of children (n = 138 for KD; n = 65 for pneumonia). We trained six deep learning networks (VGG19, Xception, ResNet50, ResNext50, SE-ResNet50, and SE-ResNext50) using the collected data. RESULTS: SE-ResNext50 showed the best performance in terms of accuracy, specificity, and precision in the classification. SE-ResNext50 offered a precision of 81.12%, a sensitivity of 84.06%, and a specificity of 58.46%. CONCLUSIONS: The results of our study suggested that deep learning algorithms have similar performance to an experienced cardiologist in detecting coronary artery lesions to facilitate the diagnosis of KD.