Cyclophosphamide exposure factors in family caregivers for pediatric cancer patients.

The exposure of family caregivers to anticancer drugs for pediatric patients with malignancy is a potential health risk that needs to be minimized. We monitored the amount of cyclophosphamide (CPM) that had adhered to the undershirts of patients and the personal protective equipment (PPE) of family caregivers as well as the caregivers' urine levels of CPM within the first three days after the first and second courses of high-dose CPM therapy. Liquid chromatography/mass spectrometry (LC/MS/MS) detected >0.03 ng/ml of CPM in 26% (23/88) of urine samples from 8 of 11 (72.7%) patients' family caregivers, with a peak of 0.7 ng/ml from 24 to 48 h after administration. Since urine CPM concentrations in family caregivers varied after the first and second courses, the exposure risk factors were analyzed by scoring the PPE-wearing time index (caring minutes × PPE points from wearing masks, gloves, and/or gowns) and CPM adhesion of PPE items with the caring patterns of diaper change, washing body care, oral care, eating assistance, emotional support, and co-sleeping. The closest association was observed for CPM adhesion between oral care gloves and undershirts (correlation coefficient 0.67, p = 0.001). The mixed-effect model analysis indicated only a significant correlation between the PPE-wearing time index and emotional care (playing, cuddling, and physical contact) (p = 0.016). These results suggest that prolonged emotional support results in poor PPE protection, which increases the risk of exposure in family caregivers. Strict PPE care within 48 h after high-dose CPM controls the exposure to high-risk anticancer drugs in caregivers of pediatric patients.

Long-Term Renal Involvement in Association with Fontan Circulation.

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15-37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26-194) vs. 56 (8-292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49-6.35) vs. 2.71 (1.40-4.95) L/min/m2, p = 0.02], central venous pressure [12 (7-19) vs. 9 (5-19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44-65) vs. 65 (45-102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12-3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR.

Usefulness of a Radiofrequency Transseptal Needle in the Second Puncture of Fontan Extracardiac Conduit.

We performed a second puncture of the extracardiac conduit in an 11-year-old Fontan patient to assess the patency of the stent previously deployed in the left pulmonary vein. For the first puncture, a mechanical Brockenbrough needle was selected to puncture the Gore-Tex conduit, an electrical insulator. For the second puncture, the location of that previous hole was detected as an indentation covered with atrial tissue, which is an electrical conductor. The second puncture was performed safely using a radiofrequency transseptal needle.

Paroxysmal sympathetic hyperactivity and the later development of epilepsy in a chemotherapy-associated brain damage.

BACKGROUND: Chemotherapy in childhood leukemia potentially induces brain lesions and neurological sequelae. Paroxysmal sympathetic hyperactivity (PSH) is known as a treatment-associated complication; however, the full clinical spectra of PSH remain to be elusive. CASE REPORT: A 5-year-old girl was diagnosed of acute myeloid leukemia (AML) M5. After the intensification therapy, she developed recurrent symptoms of episodic tachycardia, hypertension and perspiration lasting for several hours per day. The low-frequency-high-frequency ratio on Holter electrocardiography was rapidly increased from 0.84 to 2.24 at the onset of the paroxysmal event, whereas the video-monitoring electroencephalography (EEG) never identified ictal patterns of epileptiform discharges during the episodes. Thus, the diagnosis of PSH was given at 7 years of age. Myoclonic and generalized tonic-clonic seizures frequently appeared from 10 years of age, which poorly responded to anticonvulsants. EEG showed diffuse slow-wave bursts with multifocal spikes. Serial head magnetic resonance imaging (MRI) revealed diffuse cerebral and hippocampal atrophy, but not inflammatory lesions in the limbic system. CONCLUSION: We first demonstrate a pediatric case with PSH who developed drug-resistant epilepsy 3 years after the onset of PSH. Our data suggest the pathophysiological link of persistent PSH with chemotherapy-associated brain damage.

Percutaneous major aortopulmonary collateral artery banding using a covered stent in an infant.

We report a 6-month-old infant with pulmonary atresia with ventricular septal defect who was successfully treated with a novel technique of percutaneous major aortopulmonary collateral artery (MAPCA) banding with a covered stent. He suffered from heart failure due to a residual MAPCA of 4.5 mm in diameter. A covered stent tied with 2 5-0 size nylon threads was successfully deployed into the MAPCA in a dumbbell shape with a banding diameter of 2.8 mm. Banding covered stent implantation is a useful method to reduce the pulmonary blood flow in patients with MAPCA, which could be a less-invasive alternative to surgery.

The impact of pulmonary valve replacement on pregnancy outcomes in women with tetralogy of Fallot.

BACKGROUND: Pregnant women with repaired tetralogy of Fallot (rTOF) are at increased risk of adverse outcomes. Although pre-pregnancy pulmonary valve replacement (PVR) may be considered in some women to attenuate risk, published data to support this practice are lacking. Our objective was to explore the impact of pre-pregnancy PVR on pregnancy outcomes in rTOF. METHODS: Women with rTOF and cardiovascular magnetic resonance imaging (CMR) before and after pregnancy were included if CMR studies were completed within 3 years of pregnancy. Subjects were compared according to presence (+) or absence (-) of PVR at pre-pregnancy CMR. Pregnancy outcomes (cardiovascular, obstetric, and fetal/neonatal) were documented. RESULTS: Of the 29 study women identified, 7 were PVR+ and 22 were PVR-. Post-pregnancy, the PVR- group demonstrated interval increase in indexed right ventricular end-diastolic volumes (RVEDVi) (157 ± 28 versus 166 ± 33 ml/m2, p = 0.003) and end-systolic volumes (RVESVi) (82 ± 17 versus 89 ± 20 ml/m2, p = 0.003) as compared with pre-pregnancy, but no significant change in RV ejection fraction, RV mass, or left ventricular measurements. In the PVR+ group, there were no interval changes in RV measurements pre-versus post pregnancy. Interval rate of change in RVESVi of PVR- exceeded PVR+ women (+3.7 ± 5.0 versus -2.2 ± 5.0 ml/m2/year, p = 0.03). Pregnancy outcomes did not differ in PVR+ versus PVR- women. CONCLUSIONS: Pregnancy outcomes did not differ according to PVR status in our cohort. While RV volumes remained unchanged in PVR+ women, interval RV dilation was observed in PVR- women. Additional study of a larger population with longer follow-up may further inform clinical practice regarding pre-pregnancy PVR.

Augmentation of pulmonary blood flow and cardiac output by non-invasive external ventilation late after Fontan palliation.

OBJECTIVES: Although a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the impact of non-invasive, external, thoraco-abdominal ventilation on pulmonary blood flow (PBF) and cardiac output (CO) as measured by cardiovascular magnetic resonance (CMR) imaging in adult Fontan subjects. METHODS: Adults with a dominant left ventricle post-Fontan palliation (lateral tunnel or extracardiac connections) and healthy controls matched by sex and age were studied. We evaluated vascular flows using phase-contrast CMR imaging during unassisted breathing, negative pressure ventilation (NPV) and biphasic ventilation (BPV). Measurements were made within target vessels (aorta, pulmonary arteries, vena cavae and Fontan circuit) at baseline and during each ventilation mode. RESULTS: Ten Fontan subjects (50% male, 24.5 years (IQR 20.8-34.0)) and 10 matched controls were studied. Changes in PBF and CO, respectively, were greater following BPV as compared with NPV. In subjects during NPV, PBF increased by 8% (Δ0.20 L/min/m2 (0.10-0.53), p=0.011) while CO did not change significantly (Δ0.17 L/min/m2 (-0.11-0.23), p=0.432); during BPV, PBF increased by 25% (Δ0.61 L/min/m2 (0.20-0.84), p=0.002) and CO increased by 16% (Δ0.47 L/min/m2 (0.21-0.71), p=0.010). Following BPV, change in PBF and CO were both significantly higher in subjects versus controls (0.61 L/min/m2 (0.2-0.84) vs -0.27 L/min/m2 (-0.55-0.13), p=0.001; and 0.47 L/min/m2 (0.21-0.71) vs 0.07 L/min/m2 (-0.47-0.33), p=0.034, respectively). CONCLUSION: External ventilation acutely augments PBF and CO in adult Fontan subjects. Confirmation of these findings in larger populations with longer duration of ventilation and extended follow-up will be required to determine sustainability of haemodynamic effects.

[Diagnosis and management of early-onset thrombophilia/thrombosis: a review].

Evidence of the molecular epidemiology of thrombophilia is growing, and the clinical management of adult thromboembolism patients has recently made significant progress. On the other hand, there is little or no evidence concerning the genetic variation, treatment, and prophylaxis of thromboembolism development in the early life stage. The clinical presentation of early-onset thrombosis/thrombophilia, which mostly occurs in newborns and adolescents, differs from that in cases of adult-onset. Recurrent purpura fulminans and/or intracranial hemorrhage/infarction leads to dangerous lifelong complications. As in the setting of cancer genomic medicine, germline variants require determination for the individualized control of early-onset thrombophilia. The genetic predisposition to thrombosis varies among ethnicities. In the Japanese population, the protein S variant (PS-Tokushima, K196E) has attracted attention as the cause of a common and low-risk prothrombotic predisposition in adults, while protein C deficiency greatly impacts the onset of pediatric thrombosis. In 2020, 3 years after the registration of idiopathic thrombosis as a designated intractable disease, genetic tests have been promulgated for health insurance portability. Disease-specific therapy for early-onset thrombophilia is crucial. Here, we review the genetic heterogeneity, prophylaxis, and treatment strategy of the rare subgroups of severe heritable thrombosis conditions in Japan.

Elevated non-invasive liver fibrosis markers and risk of liver carcinoma in adult patients after repair of tetralogy of Fallot.

BACKGROUND: Congestive hepatopathy and hepatocellular carcinoma is a serious complication after Fontan procedure. Liver fibrosis due to hepatic congestion could occur also in adult patients after repair of tetralogy of Fallot (rTOF). However, the incidence and severity remain unclear. METHODS: A total of 111 patients with adult congenital heart disease between 2009 and 2016 were enrolled. Liver fibrosis markers and hemodynamic parameters assessed by cardiac magnetic resonance imaging and catheterization were analyzed in 50 rTOF patients having significant pulmonary regurgitation and/or stenosis, 50 Fontan patients and 11 controls. RESULTS: Liver fibrosis markers in patients with rTOF were significantly higher than controls, and tended to be lower than Fontan patients (median, hyaluronic acid: 25.8 vs. 15.9 vs. 40.8, type IV collagen: 129 vs. 113 vs. 166, ng/mL, p < 0.05, respectively). Patients with rTOF showed abnormal hyaluronic acid levels more frequently than controls, and less frequently than Fontan patients (22% vs. 0% vs. 38%, respectively, p < 0.05). Multivariate analyses indicated a positive association of right atrial pressure with type IV-collagen or hyaluronic acid levels (each, p < 0.001, p = 0.003). Abdominal ultrasonography revealed hepatic congestion in 50% of rTOF patients tested. Liver biopsy of the two rTOF patients with highest hyaluronic acid levels showed pathological evidence of moderate and severe (F2 and F3) liver fibrosis and one had combined hepatocellular and cholangiocarcinoma. CONCLUSIONS: We first demonstrated elevated liver fibrosis markers in adult patients with rTOF. These levels may help to predict the progressive liver disease as well as consider the timing of pulmonary valve replacement.

Slow component apparent diffusion coefficient for prostate cancer: Comparison and correlation with pharmacokinetic evaluation from dynamic contrast-enhanced MR imaging.

PURPOSE: Dynamic contrast enhancement (DCE)-MRI has high diagnostic performance of prostate cancer. However, it is preferable to avoid the use of MRI contrast media. A study reported that the diagnosability of the wash-in index of DCE-MRI was equivalent to the intravoxel incoherent motion of the diffusion weighted image. The purpose of this study was to examine the correlation between the slow component apparent diffusion coefficient (ADC) and the wash-out index of the DCE. MATERIALS AND METHODS: Thirty-eight patients diagnosed with prostate cancer by biopsy were enrolled in this study. The fast and slow component ADCs of the DWI were calculated for 76 points of the tumor and the contralateral normal parts. Furthermore, the wash-in and wash-out indices of the DCE-MRI were calculated. The correlations for each calculated index were compared. RESULTS: There was a significant difference between the tumor and the contralateral normal parts for both fast (p = 0.03) and slow component (p < 0.01) ADCs. In addition, the slow component ADC was correlated with the wash-out index (r = 0.64). CONCLUSION: The slow component ADC was correlated with the wash-out index, and may, therefore, be a suitable substitute for DCE-MRI.

Analysis of MRI Values and Hemoglobin and Total Protein Concentrations of Cystic Ovarian Tumors.

BACKGROUND: Endometrioma generally shows higher intracystic signal intensity (SI) than mucinous cystadenoma (MCA) on T1 -weighted imaging (T1 WI). Nonendometrioma-associated malignant ovarian epithelial tumors (nonendometrioma group) often show higher intracystic SI than benign tumors on T1 WI, while the converse is true for endometrioma and endometrioma-associated malignant tumors (endometrioma group). However, it is sometimes difficult to differentiate between hemorrhagic and mucinous content based on SI on T1 WI. Hemoglobin (Hb) and protein are both speculated to shorten T1 . PURPOSE: To examine MRI values and Hb and total protein (TP) concentrations in ovarian tumors. STUDY TYPE: Prospective. SPECIMEN: In all, 182 samples from 167 cystic ovarian tumors. FIELD STRENGTH: 1.5T, spin-echo T1 WI, fast spin-echo T2 WI. ASSESSMENT: The in vivo intracystic/psoas major muscle SI ratios were determined as references for intracystic SI. T1 and T2 values, cystic content inversion times (TIs), and Hb and TP concentrations were determined to evaluate differences between 1) endometrioma and MCA; 2) benign, borderline, and malignant tumors in the nonendometrioma group; and 3) those in the endometrioma group. STATISTICAL TESTS: Wilcoxon's rank-sum test, Kruskal-Wallis test. RESULTS: In endometriomas (n = 43) and MCAs (n = 27), mean T1 and T2 (TP, Hb concentrations) were 428 and 162 msec (52.7, 12.00 g/dl) and 1639 and 600 msec (7.1, 0.06 g/dl), respectively (all, P < 0.0001). In the nonendometrioma group (epithelial benign, n = 56; borderline, n = 20; malignant, n = 25), these values were 1657 and 696 msec (6.4, 0.35 g/dl), 1235 and 400 msec (13.5, 0.83 g/dl), and 1184 and 311 msec (19.7, 0.84 g/dl), respectively (all, P < 0.0001). In the endometrioma group (endometrioma, n = 43; borderline, n = 3; malignant, n = 8), these values were 428 and 162 msec (52.7, 12.00 g/dl), 427 and 108 msec (16.6, 3.07 g/dl), and 1010 and 268 msec (24.2, 1.56 g/dl), respectively (all, P < 0.05). DATA CONCLUSION: TP and Hb concentrations were higher in the contents of endometriomas than MCAs, leading to lower T1 and T2 values. In the nonendometrioma group, TP and Hb concentrations were higher in the cystic contents of borderline and malignant tumors than benign tumors, leading to lower T1 and T2 values. Conversely, the cystic contents of borderline and malignant tumors in the endometrioma group showed lower TP and Hb concentrations compared to endometriomas, leading to higher T1 and T2 values. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1133-1140.

Mode of death and predictors of mortality in adult Fontan survivors: A Japanese multicenter observational study.

BACKGROUND: Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear. PURPOSE: We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants. METHOD AND RESULTS: We followed 600 adult Fontan survivors from 40 Japanese institutions (307 men, 28 ±â€¯7 years old, follow-up: 18 ±â€¯6 years). The New York Heart Association (NYHA) functional class I and II was 51% and 42%, respectively. During the follow-up period of 4.1 ±â€¯1.6 years, 33 patients died, and the 5-year survival rate was 93.5%. The mode of death was heart failure in 11 patients (34%), arrhythmia or sudden death in 8 (24%), cancer in 5 (15%), perioperative problems and hemostatic problems in 4 each (12% for each), and infection in 1 (3%). Left isomerism, prior hospitalization, protein losing enteropathy (PLE), pulmonary arteriovenous fistulae, NYHA functional class, impaired hemodynamics, hyponatremia, hepatorenal dysfunction, and use of diuretics were associated with a high mortality rate (p < 0.05-0.0001). Further, PLE (hazard ratio [HR]: 14.4), left isomerism (HR: 3.5), and NYHA (HR: 2.4) independently predicted a high 5-year high mortality (p < 0.05 for all). The incidence of cancer-related mortality increased markedly with age >40 years. CONCLUSIONS: Majority of the Japanese adult Fontan survivors had good functional status, with an acceptable 5-year survival rate. However, the significant prevalence of non-cardiac mortality highlights Fontan pathophysiology as a multi-organ disease that requires a multidisciplinary management strategy to improve the long-term outcome.

Right ventricular fibrosis is associated with cardiac remodelling after pulmonary valve replacement.

OBJECTIVE: The relationship between right ventricular (RV) fibrosis and right heart reverse remodelling following pulmonary valve replacement (PVR) has not been well studied in adults with repaired tetralogy of Fallot (rTOF). Our aims were to histologically quantify RV fibrosis and to explore the relationship between fibrosis severity and cardiac remodelling post-PVR. METHODS: Adults with rTOF and pre-PVR cardiovascular (CMR) imaging were consented to procurement of RV muscle during PVR. Samples were stained with picrosirius red to quantify collagen volume fraction. Clinical data at baseline and at last follow-up were reviewed. Adverse cardiovascular outcomes included death, sustained arrhythmia and heart failure. RESULTS: Fifty-three patients (male 58%, 38±11 years) were studied. Those with severe fibrosis (collagen volume fraction >11.0%, n=13) had longer aortic cross-clamp times at initial repair compared with the remainder of the population (50 vs 33 min, p=0.018) and increased RV mass:volume ratio pre-PVR (0.20 vs 0.18 g/mL, p=0.028). Post-PVR, the severe fibrosis group had increased indexed RV end-systolic volume index (RVESVi) (74 vs 66 mL/m2, p=0.044), decreased RVESVi change (Δ29 vs Δ45 mL/m2, p=0.005), increased RV mass (34 vs 25 g/m2, p=0.023) and larger right atrial (RA) area (21 vs 17 cm2, p=0.021). A trend towards increased heart failure events was observed in the severe fibrosis group (15% vs 0%, p=0.057). CONCLUSIONS: Severe RV fibrosis was associated with increased RVESVi, RV mass and RA area post-PVR in rTOF. Further study is required to define the impact of fibrosis and persistent right heart enlargement on clinical outcomes.

Procalcitonin levels predicting the infliximab response of immunoglobulin resistant Kawasaki disease.

OBJECTIVE: To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. STUDY DESIGN: Twenty-seven patients with KD who received infliximab after 4-5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. RESULTS: Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00-5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32-1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. CONCLUSION: Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment.

Effective infliximab therapy for the early regression of coronary artery aneurysm in Kawasaki disease.

BACKGROUND: There is limited information available regarding the role of infliximab (IFX) following the acute phase of Kawasaki disease (KD). We aimed to evaluate whether IFX is associated with coronary artery aneurysm (CAA) regression. METHODS: Between 2005 and 2016, we identified 971 consecutive patients with KD from 3 tertiary institutions, and 49 (5%) with CAAs were enrolled in our study. Patients were divided into 2 groups: 27 who received IFX and 22 who did not. The persistence rate of CAAs was compared between the groups. RESULTS: Age, sex, and duration of the febrile period did not significantly differ between the groups. The maximum value of C-reactive protein was higher in the IFX- than in the non-IFX group. The maximum z-score of CAAs did not differ between the groups. The 2-, 4- and 6-year cumulative persistence rate of CAA was 24%, 24% and 24% in IFX-group, whereas 67%, 52% and 33% in non-IFX group, respectively (P = 0.03). The median duration of CAA regression was 1.1 vs. 4.6 years. Among those who developed medium- or large-sized CAAs, the 2-, 4- and 6-year cumulative persistence rate of CAA was 33%, 33% and 33% in IFX group, whereas 77%, 51% and 48% in non-IFX group, respectively (P = 0.047). Multivariate logistic regression analysis indicated that the maximum z-score (hazard ratio 0.72, p < 0.001) and response to IFX (hazard ratio 4.56, p = 0.017) were independently related to regression. CONCLUSION: IFX therapy was observed to be effective for the early improvement of CAAs in patients with intravenous immunoglobulin-resistant KD.

Thrombotic microangiopathy in a very young infant with mitral valvuloplasty.

BACKGROUND: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. CASE PRESENTATION: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle. ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) activity was sustained (64%) with the undetectable inhibitor. Von Willebrand factor (VWF) multimer analyses showed absent high-molecular weight multimers. Echocardiography disclosed severe mitral regurgitation. The mitral valve repair 32 days after the initial valvuloplasty led to prompt resolution of TMA. These suggested that TMA occurred in association with valvulopathy-triggered turbulent shear flow, mechanical hemolysis and endothelial damage. The consumption of large VWF multimers might account for the vascular high shear stress shown in Heyde syndrome. CONCLUSION: The youngest case of post-operative TMA underscores the critical coagulopathy after the first surgical intervention for congenital heart disease.

Prolonged PR Interval at Birth Predicting the High Occurrence of Fatal Atrioventricular Block in Hypoplastic Left Heart Syndrome.

Infants with hypoplastic left heart syndrome (HLHS) are at high mortality especially when they are associated with bradyarrhythmias. However, the risk factor of developing high-grade atrioventricular block (HAVB) is still unclear. Seventy-three patients with HLHS in our institutions from 2002 to 2011 were enrolled. The survival rate was assessed by the anatomical types, treatments, occurrence of HAVB, severe tricuspid regurgitation (TR), and restrictive atrial septal defect (ASD) along with electrocardiogram findings at birth. There were 23 (32%) cardiogenic and 7 (10%) non-cardiogenic deaths. The occurrence rate of HAVB but not severe TR or restrictive ASD was higher in 30 deceased patients than in 43 survived patients [7 (23%) vs. 1 (2.3%), p = 0.0038]. The overall mortality rate was higher in patients with HAVB than in those without it (p = 0.0002). Of 7 deceased patients with HAVB, 6 HAVB occurred within 10 days post-surgery, and 3 HAVB led to the early death. The mortality rate of patients with prolonged PR (≥ 0.15 s) but not wide QRS (> 0.08 s) or prolonged QTc (> 0.43 s) at birth was higher than each without it (p = 0.0106). Multivariate analysis indicated that prolonged PR but no other variables was independently associated with the mortality (hazard ratio: 2.948, p = 0.0104). Prolonged PR at birth in HLHS infants predicts the development of fatal HAVB.

Surgical strategy according to the anatomical types of congenital portosystemic shunts in children.

BACKGROUND: Congenital portosystemic shunts (CPSS) with intrahepatic portal vein (IHPV) hypoplasia or absence cause encephalopathy or pulmonary hypertension (PH). Acute shunt closure may result in postoperative portal hypertension. The aim of this study was to propose a surgical strategy according to the anatomical types of CPSS and IHPV. METHODS: Twenty-three CPSS patients were diagnosed from1990 to 2015. All patients were evaluated by computed tomography, angiography, and PV pressure monitoring under a shunt occlusion test. CPSS were categorized into 5 types according to the anatomical shunt location. RESULTS: The median age at diagnosis was 34months. Three of 23 total patients, who had an extrahepatic portosystemic shunt with a hypoplastic IHPV, died before treatment initiation because of severe PH. Fourteen cases received surgical or interventional treatment at the median age of 5years. A total of 6 cases received surgical therapy, including liver transplants for 2 absent IHPV cases. The remaining 8 cases received interventional coiling. All shunt ligations were successfully accomplished in 1-stage ligation without any complications. After the treatment, the hypoplastic IHPV gradually enlarged with an efficient portal inflow. CONCLUSION: A precise pretreatment anatomical evaluation of CPSS and IHPV types is mandatory for the selection of surgical treatment. LEVEL OF EVIDENCE: Diagnostic study - level II and treatment study - level III.

Is cardiac and hepatic iron status assessed by MRI T2* associated with left ventricular function in patients with idiopathic cardiomyopathy?

Excess accumulation of iron in the heart is known to aggravate cardiac function in some cases of genetic and acquired iron overload. We investigated the possible association between cardiac function and iron content in the heart and liver, estimated non-invasively by T2 star (T2*)-weighted magnetic resonance (MR) imaging among patients with cardiomyopathy. MR images were acquired on a 3.0 T MR imaging system using an 8-channel phased-array cardiac coil. Average T2* values of the heart were estimated at regions of interest that were located on short axis mid-ventricular slices positioned at the cardiac septum. In total, 82 patients were enrolled: 48 patients with dilated cardiomyopathy (DCM), 16 patients with hypertrophic cardiomyopathy (HCM), and 18 patients without apparent cardiovascular abnormalities. Cardiac T2* values were lower in the DCM group (median 18.6 ms) than in the HCM (22.0 ms) and control (21.4 ms) groups, although hepatic T2* values did not differ significantly across the groups. Among the whole population, the highest cardiac T2* tertile (≥21.2 ms) was significantly negatively associated with a low left ventricular ejection fraction (LVEF) of <50 %, and this association retained statistical significance after adjustment for sex, age, renal function, hemoglobin and hepatic T2*. Among DCM patients, both hemoglobin and cardiac T2* were selected as parameters that were, respectively, negatively and positively, associated with LVEF (P < 0.05). DCM patients with lower cardiac T2*, and thus higher iron content, were found to have lower LVEF. The possibility that cardiac iron overload may have a role in reducing the systolic cardiac function in DCM patients who do not have systemic iron overload requires further investigation in the future.