Successful oral midodrine therapy for treatment of refractory postoperative chylothorax in an infant.

Refractory chylothorax, a postoperative complication of CHD, is difficult to manage and sometimes fatal. Herein, we report the case of a 10-month-old infant with 22-mosaic trisomy and a coarctation complex, who developed refractory chylothorax after cardiac repairs and was successfully treated with midodrine, an oral alpha-1-adrenoreceptor agonist. Midodrine may be used as adjunctive therapy for postoperative refractory chylothorax.

Analysis of Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease by Aneurysm Severity: Factors Associated With Regression.

Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z-Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the z score of their internal diameter in the acute phase: small (z<5), medium (5≤z<10), and large (z≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.

A registry study of Kawasaki disease patients with coronary artery aneurysms (KIDCAR): a report on a multicenter prospective registry study three years after commencement.

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA. CONCLUSION: Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable. WHAT IS KNOWN: • Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. • In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events. WHAT IS NEW: • Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms.

Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

BACKGROUND: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity. CONCLUSIONS: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

The Spectrum of Cardiovascular Lesions Requiring Intervention in Adults After Kawasaki Disease.

OBJECTIVES: The aim of this study was to characterize the range of management issues raised by adults with cardiovascular sequelae from Kawasaki disease (KD) in childhood. BACKGROUND: Aneurysms resulting from vascular inflammation associated with KD in childhood may remain clinically silent until adulthood. Adults with large aneurysms, unstable angina, or myocardial infarction following KD in childhood present unique challenges to interventional cardiologists and cardiothoracic surgeons. METHODS: In an observational study of adults with histories of KD in childhood, data were collected regarding the medical histories and outcomes of 154 adult KD patients, of whom 21 underwent either percutaneous interventions or surgery. RESULTS: Of the 21 subjects with interventions, 11 had been diagnosed with KD in childhood, and 10 had histories of KD-compatible illnesses. Seventeen subjects were asymptomatic until experiencing acute cardiovascular symptoms: acute myocardial infarction (n = 12), angina (n = 2), end-stage congestive heart failure requiring cardiac transplantation (n = 1), and claudication (n = 2). CONCLUSIONS: Cardiovascular complications in these subjects illustrate the following points: 1) even small to moderate-sized aneurysms that "normalize" on echocardiography in childhood can lead to stenosis and thrombosis decades after the acute illness; 2) coronary interventions without intravascular ultrasound may result in clinically significant underestimation of vessel luminal diameter; 3) failure to assess the extent of calcification may lead to suboptimal procedural outcomes; and 4) patients with symptomatic peripheral aneurysms may benefit from endarterectomy or resection. Interventional cardiologists should be aware of the potential challenges in treating this growing population of adults.

Soluble LR11 is a novel biomarker for vascular lesions late after Kawasaki disease.

OBJECTIVE: Coronary artery lesions (CALs) and a risk for early onset of atherosclerosis are major concerns following Kawasaki disease (KD). Intimal smooth muscle cells (SMCs) have an important role in vascular lesions in KD. It is known that soluble LR11 (sLR11) is a novel biomarker for vascular lesions and LR11 is markedly expressed in intimal SMCs in atherosclerotic lesions. In this study, we hypothesized that sLR11 reflects the presence of vascular lesions late after KD. METHODS: Twenty-three age-matched controls (group 1) and 59 patients with a history of KD were enrolled; 36 with KD had normal coronary arteries or regressed aneurysms (group 2), and 23 had CALs (group 3). RESULTS: Serum sLR11 levels in group 3 (median, interquartile range (IQR): 11.1 ng/mL, 9.3-13.9 ng/mL) were significantly higher than those in groups 1 (8.4 ng/mL, 7.1-10.2 ng/mL, p < 0.001) and 2 (9.0 ng/mL, 7.7-10.1 ng/mL, p < 0.01). Levels of sLR11 were positively correlated with levels of high-sensitivity C-reactive protein (r = 0.480, p < 0.01) and lipoprotein (a) (r = 0.486, p < 0.01). CONCLUSION: These findings suggest that sLR11 reflects the development of vascular lesions in patients with serious CALs.

Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease.

Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center. Clinical, laboratory, and echocardiographic data from 143 acute KD subjects were analyzed. PA dilation was documented in 23 subjects (16.1 %); these subjects had higher median right ventricle myocardial performance index (RV MPI), higher ratio of early tricuspid inflow velocity to tricuspid annular early diastolic velocity (TV E/e'), and lower median TV e' velocity compared to the non-PA dilation group (0.50 vs 0.38 p < 0.01, 4.2 vs 3.6 p < 0.05, and 13.5 vs 15.2 cm/s p < 0.01, respectively). Almost all subjects with PA dilation had improved PA Z-score, RV MPI, and TV E/e' in the subacute phase (p < 0.01). There were no significant differences in indices of left ventricle function between PA dilation group and non-PA dilation group. In summary, PA dilation was documented in 16 % of acute KD subjects. These subjects were more likely to have echocardiographic indices consistent with isolated RV dysfunction that improved in the subacute phase. The long-term consequence of these findings will require longitudinal studies of this patient population.

Galectin-3 is a marker of myocardial and vascular fibrosis in Kawasaki disease patients with giant aneurysms.

BACKGROUNDS: Galectin-3 (Gal-3) is a multifunctional matricellular protein associated with heart failure and cardiovascular events. Gal-3 is required for transforming growth factor-ß pathway-mediated myofibroblast activation that is a key process in coronary artery aneurysm formation in Kawasaki Disease (KD). Autopsies from young adults late after KD onset (AKD) have demonstrated bridging fibrosis throughout the myocardium and arteries. In this study, we postulated that Gal-3 may participate in the pathogenesis of myocardial and vascular fibrosis and the remodeling of coronary artery aneurysms following acute KD. METHODS AND RESULTS: We measured plasma Gal-3 levels in 63 pediatric KD (PKD) and 81 AKD subjects. AKD subjects with giant aneurysms had significantly higher Gal-3 levels compared to the other adult groups (all p<0.05). All PKD groups had significantly higher Gal-3 levels than pediatric healthy controls (HC) (all p<0.05). Histological and immunohistochemical staining was performed on tissues from 10 KD autopsies and one explanted heart. Gal-3 positive staining was detected associated with acute inflammation and in spindle-shaped cells in the myocardium and arterial wall in KD subjects with giant aneurysms. CONCLUSIONS: AKD subjects with giant aneurysms and PKD subjects had significantly higher plasma Gal-3 levels than HC and Gal-3 expression was increased in the myocardium of KD subjects who died with either acute inflammation or marked myocardial fibrosis. Gal-3 may be a clinically useful biomarker that identifies a subset of KD patients at highest risk of myocardial and vascular fibrosis, and may be an attractive therapeutic target to prevent myocardial dysfunction in this subset.

Successful balloon dilatation for postoperative caval stenosis caused by primary venorrhaphy for traumatic retro-hepatic caval injury in a three-year-old child: Report of a case.

Inferior vena cava injuries are highly lethal. We experienced a case of retrohepatic inferior vena cava injury as a result of blunt trauma in a three-year-old female. Because the site of bleeding of the IVC was identified, we repaired it with running sutures. An attempt at primary repair resulted in postoperative narrowing of the vena cava. There was pressure gradient of the right atrium and inferior vena cava, and collateral circulation developed. Since it was also found that the haemodynamics was unstable, the child underwent another intervention before the stenosis of the IVC was fixed. To the best of our knowledge, there have been no previous reports of therapeutic radiological intervention for stenosis that developed after treatment of a traumatic IVC injury. The IVC in the present case recovered enough patency so that the collateral venous flow could be decreased after balloon dilatation angioplasty.

Intestinal neuronal dysplasia-like histopathology in infancy.

The present patient was delivered at a gestational age of 27 weeks. She had abdominal bloating with symptoms of respiratory distress. We suspected Hirschsprung disease (HD) or small intestinal stricture, but examinations were not definitive. Exploratory laparotomy was performed at 97 days of age. Intraoperative findings showed no evidence of small intestinal stricture or changes in intestinal caliber. A transanal drainage tube was inserted, and decompression therapy and intestinal lavage were started. Rectal mucosal biopsy was performed at 184 days of age, and HE and acetylcholinesterase staining showed intestinal neuronal dysplasia (IND)-like pathological findings. At 15 months, giant ganglia were no longer present on follow-up rectal mucosal biopsy, and the pathological diagnosis was normoganglionosis. It should be recognized that while the enteric nervous system is developing, IND-like pathological findings may be seen as a pathological condition during the maturation process.

Two cases of new coronary aneurysms that developed in the late period after Kawasaki disease.

Two cases of coronary aneurysm developed in the late period after Kawasaki disease (KD). Case 1 involved a 13-year-old boy who had aneurysms develop after a diagnosis of complete regression. Case 2 involved a 29-year-old man who had a new aneurysm develop after he was older than 20 years. Physicians need to be aware that coronary aneurysms can develop in patients with antecedent KD even after regression or in adulthood.

Long QT syndrome with nocturnal cardiac events caused by a KCNH2 missense mutation (G604S).

An 8-year-old boy suffered from an unconsciousness attack and torsade de pointes arrhythmia during sleep or at rest. His electrocardiogram showed prolonged QT intervals, but the T wave morphology was atypical for type 1, 2 or 3 congenital long-QT syndrome (LQTS). Intravenous epinephrine slightly prolonged the QT interval whereas mexiletine infusion shortened the QT interval. Although these clinical characteristics might suggest type 3 LQTS, a genetic analysis identified the G604S-KCNH2 mutation (type 2 LQTS). Because mismatches between the genotype and phenotype of LQTS are possible, genetic analysis of LQTS is important to identify the most appropriate therapeutic option and risk stratification.

Characteristic alteration in the second derivative of photoplethysmogram in children.

BACKGROUND: The second derivative of the photoplethysmogram (SDPTG) has been verified as a useful method for analyzing pulse wave form in adults; however, there have been few studies on the SDPTG in children. METHODS: We examined age-related alteration of SDPTG (study 1) and the SDPTG response to a vasodilator (study 2). The subjects in study 1 were 36 healthy children aged 0.9-16.0 years. The subjects in study 2 were 13 children aged 5.4-18.9 years with a history of Kawasaki disease. Subjects received an i.v. infusion of 0.568 mg/kg dipyridamole. We assessed the SDPTG by d/a ratio, b/a ratio and aging index (AGI). RESULTS: The d/a ratio increased with advance of age (r= 0.636, P < 0.001), and the b/a ratio and AGI decreased with advance of age (r=-0.343, P < 0.05 and r=-0.678, P < 0.001, respectively). The d/a ratio and AGI were correlated with height (r= 0.523, P < 0.01 and r=-0.623, P < 0.001, respectively), but the b/a ratio was not significantly correlated with height. In study 2, the d/a ratio increased significantly (P≤ 0.05), but the b/a ratio and AGI did not alter. CONCLUSIONS: The SDPTG indices in children show characteristic alterations with advance of age and react to a vasodilator.