Akiko Komori

Factors affecting N-terminal pro-brain natriuretic peptide elevation in the acute phase of Kawasaki disease.

The aim of this study was to investigate the clinical significance and factors that affect N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications.

Idiopathic pulmonary hemosiderosis complicated by Down syndrome

We report the case of a 9‐year‐old girl with Down syndrome (DS) diagnosed with idiopathic pulmonary hemosiderosis (IPH). Although acute pneumonia complicated by hemolytic anemia was suspected, IPH was finally diagnosed on bronchoscopy. Treatment with prednisolone achieved good clinical response. An association between IPH and DS was not able to be identified, but immunological issues in DS may contribute to the onset of IPH. Recurrent and intractable respiratory symptoms with marked infiltrative shadows in the bilateral lungs and complicated by severe anemia in patients with DS should suggest IPH.

Cardiac function on 3‐D speckle tracking imaging and cytokines in Kawasaki disease

Serum N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) tends to rise in acute phase Kawasaki disease (KD), but the cause of NT‐proBNP elevation has not been clarified. In a previous study, cardiac function evaluated on 2‐D echocardiography (2D‐E) such as ejection fraction was normal, but this does not reflect subtle changes in cardiac dysfunction, and hence the association between cardiac function and NT‐proBNP elevation is still controversial. The aim of this study was therefore to elucidate the influence of cardiac function on NT‐proBNP elevation, by evaluating cardiac function via strain on 3‐D speckle tracking imaging (3D‐STI), in acute and subacute KD patients. Given that cytokines are also thought to induce NT‐proBNP in acute phase KD, serum cytokines and cytokine receptors were measured at the same time.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

Importance Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1–15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7–4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4–3.6) were significantly associated with CE. Conclusions and Relevance Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Recent updates on echocardiography and ultrasound for Kawasaki disease: beyond the coronary artery

Kawasaki disease (KD) is a systemic vasculitis with a predilection for damage to the coronary arteries. In the acute phase, clinical decision making for KD relies on the measurements of the coronary z-score obtained by 2-dimensional echocardiography (2DE). In the convalescent phase, KD patients with coronary artery abnormalities (CAAs) eventually show arteriosclerotic vascular remodeling characterized by marked intimal proliferation and neoangiogenesis after KD vasculitis, which often induces myocardial ischemia. To date, several well-established surrogate markers including dobutamine stress echocardiography (DSE), the carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD), have been made available for risk assessment and the prediction of cardiovascular disease (CVD) in KD patients. Additionally, the use of carotid contrast-enhanced ultrasonography (CEUS), has enabled the visualization and quantification of the adventitial vasa vasorum (VV) network, assessing active vascular remodeling at remote arterial sites in KD patients with CAAs. However, there was no evidence of major vascular structural changes in KD patients in whom CAAs had never been detected. Thus, assessment of multiple modalities using 2DE may provide direct information not only on the vascular health but also on the stratification of the risk of CVD in KD patients with CAAs.

Congenital complete atrioventricular block with pulmonary hypertension

Congenital complete atrioventricular block (CCAVB) is difficult to manage in the neonatal period. Approximately half of the patients need pacemaker implantation in the neonatal period. Dilated cardiomyopathy (DCM) is a well-known and occasionally fatal complication. The prevalence of DCM ranges between 5% and 30%, but no case of pulmonary hypertension (PH) with CCAVB has been reported previously. We encountered a patient with CCAVB who was stable until 1 month, after which severe (but reversible) PH developed. The infant was born at 37 weeks of gestation to a 23year-old mother by cesarean section. SSA/Ro antibody was positive in the mother’s blood. The infant was diagnosed with 2:1 atrioventricular block in utero. He was born at 2,370 g without asphyxia. The infant was admitted to a neonatal intensive care unit. Immediately electrocardiogram showed isolated CCAVB after birth. Respiration, peripheral perfusion and blood pressure were stable, even though the heart rate was 70–90 beats/min. Given that signs of heart failure and other arrhythmias were not apparent, pacemaker implantation was not carried out. Milk intake and weight gain were satisfactory after discharge. At 1 month of age, he was seen in the hospital for routine examination. Vital signs were as follows: temperature, 37.2°C; pulse rate, 83 beats/min; respiration, regular at 42 breaths/ min; systemic blood pressure, 86 mmHg; and SpO2, 95% (room air). Chest auscultation indicated bradycardia and accentuated second pulmonary sound with no murmur. Laboratory tests indicated anemia (hemoglobin [Hb], 9.9 g/dL; and 14.0 g/dL 6 weeks earlier), and a rise in brain natriuretic peptide to 173 pg/mL. Rapid antigen test for human metapneumovirus was positive. Twelve-lead electrocardiogram demonstrated CAVB with an atrial rate of 185 beats/min and a ventricular rate of 88 beats/min, and right ventricular pressure overload. Chest computed tomography showed cardiomegaly, pulmonary artery dilation, atelectasis, and pulmonary hyperinflation (Fig. S1). Echocardiogram showed normal ejection fraction (61%) and a normal structure, despite tricuspid and pulmonary regurgitation. Intraventricular septum was markedly compressed into the left ventricular cavity in the systolic phase, and right ventricular pressure was assumed as >90 mmHg because the pressure gradient estimated on tricuspid regurgitation flow velocity was 87 mmHg (Fig. 1). He had significant PH on echocardiography, but pulmonary perfusion scintigram did not suggest pulmonary embolism. After improvement on fluid transfusion and oxygen supply, pulmonary artery pressure (systolic/diastolic/ mean) was 40/14/27 mmHg, and pulmonary wedge pressure (systolic/diastolic/mean) was 6/7/6 mmHg on cardiac catheterization, and pulmonary resistance was calculated as 8.1 Wood/m. Simultaneous systemic arterial pressure was 75/33/49 mmHg and resistance was 17.4 Wood/m (Rp/Rs, 0.47). The pulmonary vein was not obstructed. Cardiac index was 2.61/min/m, but venous oxygen saturation was 42.8% at Hb 8.8 g/dL. The infant was treated with red blood cell transfusion, sildenafil against PH, and theophylline and b2stimulator for bradycardia. The tricuspid regurgitation pressure gradient decreased to 19 mmHg after initiation of the aforementioned treatment. Congenital complete atrioventricular block is a passively acquired autoimmune disease in utero. It is thought to be a consequence of inflammatory injury, fibrosis, and scarring of the conduction system. CCAVB can develop into DCM, which can be fatal. There have been no reports, however, of PH with CCAVB. In the present case, PH might not have been due only to CCAVB. PH was not caused by left heart disease because the pulmonary wedge pressure was low according to the cardiac catheterization data. The present patient did not have serious cyanotic crisis such as persistence of PH during the neonatal period, but it is possible that CCAVB caused slower adaptation of pulmonary vascular relaxation after the neonatal period. Additionally, respiratory infection, induced anemia, and mild–moderate hypercapnea probably contributed to the additional worsening of PH (Table S1). Given that treatment with novel pulmonary vasodilator such as sildenafil was effective, the pulmonary vascular reaction was able to be reversed. In conclusion, we encountered a case of PH complicating CCAVB. If CCAVB patients develop other complications such as anemia, hypoxia and hypercapnea due to respiratory infection, this may worsen PH. Novel pulmonary vasodilator is effective for improvement of neonatal PH. Correspondence: Mamoru Ayusawa, MD PhD, Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1, Ooyaguchikamichou, Itabashi-ku, Tokyo 173-8610, Japan. Email: ayusawa.mamoru@nihon-u.ac.jp Received 11 April 2017; revised 13 June 2017; accepted 14 June 2017. doi: 10.1111/ped.13347