Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

Ex Vivo Evaluation of Mechanical Anisotropic Tissues with High-Frequency Ultrasound Shear Wave Elastography.

The use of imaging devices to assess directional mechanics of tissues is highly desirable. This is because the directional mechanics depend on fiber orientation, and altered directional mechanics are closely related to the pathological status of tissues. However, measuring directional mechanics in tissues with high-stiffness is challenging due to the difficulty of generating localized displacement in these tissues using acoustic radiation force, a general method for generating displacement in ultrasound-based elastography. In addition, common ultrasound probes do not provide rotational function, which makes the measurement of directional mechanics inaccurate and unreliable. Therefore, we developed a high-frequency ultrasound mechanical wave elastography system that can accommodate a wide range of tissue stiffness and is also equipped with a motorized rotation stage for precise imaging of directional mechanics. A mechanical shaker was applied to the elastography system to measure tissues with high-stiffness. Phantom and ex vivo experiments were performed. In the phantom experiments, the lateral and axial resolution of the system were determined to be 144 µm and 168 µm, respectively. In the ex vivo experiments, we used swine heart and cartilage, both of which are considered stiff. The elastography system allows us to acquire the directional mechanics with high angular resolution in the heart and cartilage. The results demonstrate that the developed elastography system is capable of imaging a wide range of tissues and has high angular resolution. Therefore, this system might be useful for the diagnostics of mechanically anisotropic tissues via ex vivo tests.

Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

Utilization of Coronary Artery to Aorta for the Early Detection of Kawasaki Disease.

Timely diagnosis of coronary involvement is paramount in Kawasaki disease (KD) as it can be associated with long-term morbidity. However, echocardiographic measurements of coronary artery dilation in KD are inconsistent and not proficient for all abnormal arteries. The purpose of this study was to investigate more valuable indices and determine their sensitivity and specificity for early diagnosis of coronary involvement in KD. We performed this retrospective study in 218 children. All patients underwent laboratory and echocardiographic evaluations upon admission. We measured the size of the left main coronary artery (LMA), left anterior descending coronary artery (LAD), right coronary artery (RCA), and aorta (Ao), and calculated the LMA/Ao, LAD/Ao, and RCA/Ao ratios. We also calculated the cut-off values of each index using receiver operating characteristic curves. LMA, LAD, and RCA measurements did not correlate with white blood cell count, platelet count, erythrocyte sedimentation rate, C-reactive protein level, or brain natriuretic peptide level. The LMA measurement was associated with hemoglobin, hematocrit, and iron saturation. LAD/Ao was correlated with white blood cell and platelet counts (P < 0.05), whereas RCA/Ao was correlated with ferritin level (P < 0.05). The cut-off value of LMA/Ao was 0.2, with a sensitivity of 85% and specificity of 70%. Individual coronary artery/Ao ratios might provide helpful insight for detection of coronary abnormality in KD in the acute phase. Further investigation is essential to clarify prompt early diagnosis of coronary involvement in KD.

Incomplete Kawasaki disease in a 12-month-old girl presenting with cardiac murmur and iron deficiency anemia.

Kawasaki disease (KD) is an acute necrotizing vasculitis that occurs in children <5 years of age. The cause of KD remains unknown, but various complications, including dilatation of the coronary arteries, can occur. Coronary artery aneurysm or ectasia are the most important complications of KD. Children with suspected KD who do not fulfill the diagnostic criteria may have incomplete KD. Given that incomplete KD is associated with delayed diagnosis and treatment, children with incomplete KD have a high risk of cardiovascular complications. Meanwhile, iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies in the world. Children with IDA are prone to infection and inflammation. We report the case of a 12-month-old girl with incomplete KD who presented with cardiac murmur and severe IDA.

Myocardial Layers Specific Strain Analysis for the Acute Phase of Infant Kawasaki Disease.

Recently, the prevalence of infant Kawasaki disease (KD) has increased. However, the myocardial functional analysis of infant KD can be difficult and rarely reported. The purpose of this study was to investigate layer specific myocardial strain analysis for better assessment of the acute period in infant KD. The study retrospectively reviewed the echocardiographic data of 25 infant patients with KD at the acute phase. With advanced imaging, pulsed tissue Doppler velocity data, myocardial strain with three layers specific analysis was performed. Then the data were compared with 25 age-matched healthy control infants. The measures of longitudinal strain and radial strain were decreased in infant KD compared to healthy controls. The circumferential strain was significantly decreased in infant KD at all three myocardial layers, especially in the endocardial layer (KD: -20.5 ± 6.4 % vs. CONTROL: -25.6 ± 7.6 %, endocardium, p = 0.00001; -14.6 ± 4.4 % vs. -18.1 ± 4.0 %; middle myocardium, p = 0.01; -9.7 ± 3.3 % vs. -11.4 ± 3.8 %; epicardium, p = 0.04). The acute phase of infant KD demonstrated decreased myocardial strain measurement. Circumferential strain was the lowest in the endocardial layer. Further continuous long-term follow up for myocardial assessment should be recommended even after recovery with appropriate treatment.

Life-threatening acute gastric dilatation with aorta compression in a 3-year-old child.

We report a fatal case of acute gastric dilatation in a 3-year old boy who presented with severe abdominal pain and massive gastric distension in the emergency room. On physical examination the patient was in shock due to acute abdomen and lower limb ischemia. Initial laboratory findings showed multi-organ failure with acute renal failure and pancreatitis. Abdominal computed tomography (CT) showed marked dilatation of the stomach resulting in compression of the abdominal aorta. The left kidney, spleen and pancreas were not visible on CT due to the necrotic changes. The patient was quickly stabilized by initial volume resuscitation, but suddenly deteriorated immediately after gastric decompression via nasogastric tube, and died from multi-organ failure 3 h after initial presentation.

Erythromelalgia with a linear pattern in a 12-year-old girl.

Erythromelalgia is a rare clinical syndrome characterized by erythema, increased temperature, and severe burning pain that can be aggravated by warmth or relieved by cold. Erythromelalgia occurs either as a primary, idiopathic form, or secondary to a number of diseases and conditions. Although fairly well studied in adults, the characteristics, pathogenesis, and natural history are poorly characterized in the pediatric age group. Different therapeutic options have been tried, but no optimal treatment has been suggested for erythromelalgia. We report a rare case of linear erythromelalgia in a 12-year-old girl involving her central body from the peripheral extremities, which seemed to be secondary due to vasculitis. Clinical progress waxed and waned on maintenance aspirin and propranolol.

Do predictors of incomplete Kawasaki disease exist for infants?

Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in infants and young children. However, the diagnosis of infantile KD can be difficult or delayed due to vague clinical manifestations. This current study aimed to assess the clinical characteristics and cardiac complications of infantile KD. The study retrospectively reviewed the data of 242 patients with KD. The clinical, laboratory, and echocardiographic data between infants and older children were analyzed. The patients were divided into two groups: infants 12 months old or younger and children older than 12 months. The rate of incomplete KD was much more frequent in infants. During all phases, prohormone brain natriuretic peptide (Pro-BNP) levels were higher in infants, as was thrombocytosis. The coronary artery z-score was higher in infants at all phases of KD. On tissue Doppler imaging, the E/E' ratio (ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity) was higher at the septal and lateral annulus in infants. Infant patients with KD are at increased risk for the development of coronary abnormalities and diastolic dysfunction. Higher levels of Pro-BNP and thrombocytosis with diastolic echo parameters of a higher E/E' ratio can help to identify incomplete KD in infants.

Characteristics of Teenagers Presenting with Chest Pain after COVID-19 mRNA Vaccination.

In this study, we evaluated the clinical and radiological manifestations of teenagers presenting with chest pain after coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination. We retrospectively enrolled 61 teenage patients, aged 13 to 19 years, who underwent echocardiography and cardiac magnetic resonance imaging (CMR) for chest pain after COVID-19 mRNA vaccination, from November 2021 to April 2022. Medical records, laboratory results, echocardiographic, and CMR findings were analyzed. The mean age of the participants was 14.4 ± 1.9 years, with a male:female ratio of 28:33. Among the sixty-one patients with chest pain after COVID-19 vaccination, only two (3.3%) were diagnosed as confirmed myocarditis, and almost all of them recovered with conservative treatments. However, on CMR, 24 (39.3%) presented with mild myocardial abnormalities; 22 (36.1%) showed myocardial edema, and 19 (31.1%) were found to have a myocardial injury. Multivariate logistic analyses revealed that older age and female sex were significantly associated with myocardial abnormalities. In teenagers who present with chest pain after COVID-19 mRNA vaccination, confirmed myocarditis is uncommon. However, myocardial abnormalities on CMR might occur frequently, and females in their late teens might be more vulnerable to myocardial abnormalities.

New Metric to Evaluate Cardiac Anisotropic Mechanics by Directional High-Frequency Ultrasound-Based Transverse Wave Elastography.

The evaluation of cardiac anisotropic mechanics is important in the diagnosis of heart disease. However, other representative ultrasound imaging-based metrics, which are capable of quantitatively evaluating anisotropic cardiac mechanics, are insufficient for accurately diagnosing heart disease due to the influence of viscosity and geometry of cardiac tissues. In this study, we propose a new ultrasound imaging-based metric, maximum cosine similarity (MaxCosim), for quantifying anisotropic mechanics of cardiac tissues by evaluating the periodicity of the transverse wave speeds depending on the measurement directions using ultrasound imaging. We developed a high-frequency ultrasound-based directional transverse wave imaging system to measure the transverse wave speed in multiple directions. The ultrasound imaging-based metric was validated by performing experiments on 40 rats randomly assigned to four groups; three doxorubicin (DOX) treatment groups received 10, 15, or 20 mg/kg DOX, while the control group received 0.2 mL/kg saline. In each heart sample, the developed ultrasound imaging system allowed measuring transverse wave speeds in multiple directions, and the new metric was then calculated from 3-D ultrasound transverse wave images to evaluate the degree of anisotropic mechanics of the heart sample. The results of the metric were compared with histopathological changes for validation. A decrease in the MaxCosim value was observed in the DOX treatment groups, with the degree of decrease depending on the dose. These results are consistent with the histopathological features, suggesting that our ultrasound imaging-based metric can quantify the anisotropic mechanics of cardiac tissues and potentially be used for the early diagnosis of heart disease.

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.

Assessment of cardiac function in syncopal children without organic causes.

BACKGROUND: Syncope is a common problem in children and adolescents. However, a large proportion of syncope cases have no underlying cause. PURPOSE: This study aimed to identify the factors affecting the severity of syncope using tissue Doppler imaging (TDI). METHODS: This retrospective study included 61 children and adolescents with syncope who underwent echocardiography. The head-up-tilt test (HUT) was performed when there was a more severe syncopal event. We compared the echocardiographic findings between the execute HUT and nonexecute HUT, negative HUT result and positive HUT result, and normal electrocardiogram (ECG) and abnormal ECG groups. Data were analyzed using an unpaired t test post hoc analysis. RESULTS: In the execute and nonexecute HUT groups, the odds ratios were 0.55 for medial E/E' (P=0.040) and 0.64 for lateral E/E' (P=0.049). Comparison of the results of the decreased, normal, and increased groups for lateral E/E' revealed a significant difference in the execution HUT and nonexecute HUT groups (overall, P=0.004; decreased vs. increased, P= 0.003; normal vs. increased, P=0.050). CONCLUSION: Medial E/E' and lateral E/E' were decreased in patients with severe syncopal events. These findings suggest that the presence of left ventricular diastolic deterioration may cause hypoperfusion even in the absence of organic causes and, consequently, increase syncope severity and frequency. The TDI measured by echocardiography can be used as an index to predict syncope recurrence and/or severity.

Overexpression of phosphoinositide-3-kinase class II alpha enhances mesenchymal stem cell survival in infarcted myocardium.

The efficacy of mesenchymal stem cell (MSC) therapy for myocardial regeneration is limited by the poor survival of stem cells after transplantation into the infarcted heart. To improve the cell survival of MSCs in the infarcted heart, MSCs were genetically engineered to overexpress phosphoinositide-3-kinase class II alpha (PI3K-C2α). PI3K-C2α overexpression increased PI3K expression and the cell viability of MSCs. Furthermore, levels of survival-related phosphorylation were elevated in PI3K-C2α-MSCs. But, the level of apoptotic proteins downregulated and the number of PI-positive cells decreased in PI3K-C2α-MSCs compared to hypoxic MSCs. Nine rats per group had 1×10(6) cells (20 µl PBS) transplanted after myocardial infarction. One week after transplantation, infarct size and area of fibrosis were reduced in the PI3K-C2α-MSC-transplanted group. The number of TUNEL positive cells declined, while the mean microvessel count per field was higher in the PI3K-C2α-MSC group than the MSC-injected group. Heart function was improved in the PI3K-C2α-MSCs group as assessed using a Millar catheter at 3weeks after transplantation. These findings suggest that overexpression of PI3K-C2α in MSCs can assist cell survival and enhance myocardial regeneration.

Comparison of the Change in Diastolic Dysfunction after Transcatheter Atrial Septal Defect Closure between Asymptomatic Younger and Older Age Groups.

Transcatheter device closure of a secundum atrial septal defect (ASD) is followed by a noticeable change in the left atrium (LA) and left ventricle (LV) over a long-term follow-up. This study aimed to assess the remodeling of the atrial and ventricular myocardium with respect to diastolic function in adult ASD patients. Around 38 asymptomatic patients (age: 48.6 ± 17.1 years, range: 23-69 years) diagnosed with ASD during routine health check-up and who underwent ASD device closure with the Amplatzer septal occluder were included in this retrospective study, and their medical records (containing echocardiographic data) were reviewed. The defect size was 21.77 + 6.79 mm, while the balloon measurement of the defect was 24.29 ± 6.64 mm. The patients were divided into two groups, namely, Group I (with 18 patients aged <50 years [mean: 33.06 ± 9.43 years] and Group II (with 20 patients aged ≥50 years [mean: 62.55 ± 7.54 years]). Comparison of echocardiographic data collected before closure and at a follow-up 2 years later revealed significant differences between pre-closure and post-closure states in the left ventricular end-diastolic dimension (40.76 ± 3.28 vs. 43.39 ± 3.52), left ventricular mass (99.64 ± 28.81 vs. 116.57 ± 32.03), and right ventricular pressure (36.88 ± 12.20 vs. 31.81 ± 11.11). Tissue Doppler measurements were significantly decreased 2 years after closure, while the post-closure E/E' was higher than the pre-closure E/E' (11.58 ± 4.80 vs. 8.79 + 3.19, p < 0.005). In both groups, mitral A and tissue Doppler E', A', and S' values decreased post-closure, while the E/E' was higher in Group II than in Group I at both pre-closure and long-term follow-up measurements (pre-closure: 9.60 ± 5.15 vs. 7.41 ± 1.42, p < 0.003; post-closure: 13.03 + 4.05 vs. 10.49 ± 3.95, p < 0.02). The LA size and LV function exhibited recognizable remodeling after transcatheter ASD closure. Because the LV preload elevation (i.e., E/E') after ASD closure can be pronounced in older patients, caution should be provided more in older patients than in younger patients. Hence, it may be beneficial to close the ASD at an earlier age in adults even after a late diagnosis; a relatively younger age may be more suited for adaptation to the remodeling process to protect the myocardial function. Careful consideration should be given to the previous underloaded left heart after long-term closure.

Is It Possible for Children in Duchenne Muscular Dystrophy to Preserve Cardiac Function with Medical Assistance?

In patients with Duchenne muscular dystrophy (DMD), death secondary to cardiac or respiratory failure typically occurs in the second or third decade without treatment. Although cardiac dysfunction is treated with standard heart-failure strategies, it remains insufficient in DMD children. The purpose of this study was to evaluate the efficiency of cardiac medication and noninvasive ventilator support in DMD cardiomyopathy children with analyzing echocardiographic data. Forty-eight DMD children patients were included and divided into 2 groups by left ventricular (LV) ejection fraction (EF) at the time of initial treatment. Group 1: LV EF ≥ 45% and Group 2: LV EF < 45%. p-values were calculated using a Linear mixed model to estimate the association between cardiac medications and echocardiographic measurements. Before and after cardiac medications, the change values were significantly different in interventricular septal thickness at end diastole (IVSd), interventricular septal thickness at end systole (IVSs), left ventricular internal diameter end systole (LVIDs), left ventricular posterior wall thickness end diastole (LVPWd), ejection fraction (EF), fractional shortening (FS), deceleration time (DT), DT slope, Lat A' and Lat E/E' (p < 0.05). Group 2 patients revealed to take more kinds of cardiac medications than Group 1 (p < 0.05) including ACEIs, beta-blocker, and inotropics, then LV EF was better preserved in Group 2 than Group 1. It is certainly helpful to take individualized medical combination therapy including inotropic agents for cardiomyopathy in DMD children patients with EF < 45%.

Early Outcomes of Percutaneous Pulmonary Valve Implantation with Pulsta and Melody Valves: The First Report from Korea.

Percutaneous pulmonary valve implantation (PPVI) is used to treat pulmonary stenosis (PS) or pulmonary regurgitation (PR). We described our experience with PPVI, specifically valve-in-valve transcatheter pulmonary valve replacement using the Melody valve and novel self-expandable systems using the Pulsta valve. We reviewed data from 42 patients undergoing PPVI. Twenty-nine patients had Melody valves in mostly bioprosthetic valves, valved conduits, and homografts in the pulmonary position. Following Melody valve implantation, the peak right ventricle-to-pulmonary artery gradient decreased from 51.3 ± 11.5 to 16.7 ± 3.3 mmHg and right ventricular systolic pressure fell from 70.0 ± 16.8 to 41.3 ± 17.8 mmHg. Thirteen patients with native right ventricular outflow tract (RVOT) lesions and homograft underwent PPVI with the new self-expandable Pulsta valve-a nitinol wire stent mounted with a trileaflet porcine pericardial valve. Following Pulsta valve implantation, cardiac magnetic resonance imaging showed a decreased PR fraction and that the right ventricular end-diastolic volume index decreased from 166.1 ± 11.9 to 123.6 ± 12.4 mL/m2. There were no mortality, severe procedural morbidity, or valve-related complications. At the mean 14.2 month (4-57 months) follow-up, no patients had more than mild PR. PPVI using Melody and Pulsta valves was first shown to provide excellent early outcomes without serious adverse event in most patients with RVOT dysfunction in Korea.

Epidemiology of Kawasaki Disease in South Korea: A Nationwide Survey 2015-2017.

BACKGROUND: This study aimed to investigate recent epidemiologic features of Kawasaki disease (KD) in South Korea. METHODS: The ninth triennial nationwide questionnaire survey collected data on the demographic findings, symptoms and signs, treatment patterns and coronary artery complications of acute-phase KD occurred in 2015-2017 from 98 hospitals with pediatric residency programs and 108 community hospitals without residency programs. RESULTS: We received data from 93 of the 98 hospitals (response rate: 94.9%) with residency programs and 75 of the 108 community-based children's hospitals (response rate: 69.4%) without residency programs. In the 3-year survey period, a total of 15,378 (5449 in 2015, 5171 in 2016 and 4758 in 2017) cases of KD were reported. The mean age at diagnosis was 33.0 ± 24.8 months (range: 0-205 months), and the male-to-female ratio was 1.41:1. The overall KD incidence was 196.9 (202.2 in 2015, 197.1 in 2016 and 191.0 in 2017) per 100,000 younger than 5 years population. Recurrent cases were 4.85%. KD occurred more frequently during winter (December-January) and late spring (May-June). Intravenous immunoglobulin (IVIG) was administered to 95% of the patients; nonresponder rate for the first IVIG was 14.8%. Coronary artery aneurysms and giant coronary artery aneurysms (internal diameter >8 mm) occurred in 1.7% and 19 patients, respectively. Two patients died due to multiorgan failure and hepatic encephalopathy. CONCLUSION: Peak incidence of KD in South Korea was 202.2 per 100,000 younger than 5 years population (2015), and the incidence of giant coronary artery aneurysm decreased to 0.09% (2017).