The First Case in Japan of Fulminant Myocarditis Due to Multisystem Inflammatory Syndrome in Children (MIS-C) That Required Mechanical Circulatory Support.

Multisystem inflammatory syndrome in children (MIS-C) is a novel hyperinflammatory syndrome that is associated with severe acute respiratory syndrome coronavirus 2 infections. Reports describing the mechanical circulatory support (MCS) and myocardial biopsy for fulminant myocarditis due to MIS-C are limited.A 13-year-old male patient with MIS-C underwent treatment, including immunosuppressive therapy and MCS devices, and managed to recover from pulseless electrical activity cardiac arrest.This is the first patient in Japan with MIS-C who required MCS devices in Japan. Appropriate and immediate treatment with immunosuppressive therapy and MCS devices is important.

Assessment of Platelet Thrombus Formation under Flow Conditions in Patients with Acute Kawasaki Disease.

OBJECTIVE: To assess platelet thrombus formation (PTF) under flow conditions in patients with Kawasaki disease. Previously available platelet activation data were limited for nonphysiological shear stress condition. The total thrombus-formation analysis system (T-TAS) was developed for quantitative PTF analysis. STUDY DESIGN: In total, 33 patients with acute Kawasaki disease were assessed. Whole blood samples, obtained immediately before treatment and 1 week and 1 month after treatment, were assessed using the T-TAS with a collagen-coated platelet chip under high shear values (1000 s-1 [PL12] and 2000 s-1 [PL24]). Measures, such as time to reach 5 kPa above the base pressure (T5+α) and area under the curve for flow pressure curve for 10 minutes (AUC10) were analyzed to quantify PTF. RESULTS: Immediately before treatment, the median PL12-T5+α and PL24-T5+α were 3.3 minutes (IQR 2.0-4.5) and 1.3 minutes (0.9-1.9), respectively, and both values were significantly lower in adult controls (3.5 minutes [2.9-6.4] and 2.8 minutes [1.8-4.8]; P = .015 and P < .001, respectively). In addition, the PL12-AUC10 (151.7 U [94.5-279.9]) significantly decreased in adult controls (234.1 U [110.5-306.5], P = .007). By contrast, at 1 week and 1 month after the start of treatment, the T5+α was longer, and the PL12-AUC10 and PL24-AUC10 decreased. CONCLUSIONS: In patients with acute Kawasaki disease, the PTF had an early onset and weak stability.

Involvement of the ADAMTS13-VWF axis in acute Kawasaki disease and effects of intravenous immunoglobulin.

INTRODUCTION: ADAMTS13 modulates shear-dependent platelet thrombus formation (PTF) by limited proteolysis of von Willebrand factor (VWF). A high-plasma-ratio of VWF antigen to ADAMTS13 activity (VWF:Ag/ADAMTS13:AC) promotes PTF and aggravates shear-induced inflammation mediated by VWF. A role of ADAMTS13 in Kawasaki disease (KD) remains unknown, however. We investigated the involvement of ADAMTS13-VWF axis in the acute-phase of KD (acute-KD). METHODS: VWF:Ag and ADAMTS13:AC in 77 KD infants were measured at three time-points; immediately before (Pre), one-week (1 W) and one-month (1 M) after intravenous-immunoglobulin (IVIG) treatment. VWF multimer (VWFM) distribution and ADAMTS13-isoelectrofocusing (IEF) patterns were compared between the responders and non-responders to IVIG. RESULTS: A high VWF:Ag (195.7 ±â€¯85.6%, p < 0.05), low ADAMTS13:AC (60.3 ±â€¯23.8%, p < 0.05) and high VWF:Ag/ADAMTS13:AC ratio (3.70 ±â€¯2.12, p < 0.05) at Pre were seen compared to control plasmas. These parameters returned to normal levels time-dependently after IVIG treatment. Non-responders to IVIG demonstrated high VWF:Ag and low ADAMTS13:AC at Pre, and high VWF:Ag/ADAMTS13:AC ratio at 1 W compared to responders, but there were no significant differences in VWFM distribution between both groups. IEF analyses revealed the decreased free form of ADAMTS13 and increased complex form with ADAMTS13 and high-molecular-weight-VWFM at Pre in non-responders. A high VWF:Ag/ADAMTS13:AC ratio was associated with increased white blood cell counts, together with decreased serum albumin and sodium at Pre and 1 W. CONCLUSIONS: A high VWF:Ag/ADAMTS13:AC ratio in acute-KD persisted after primary treatment in non-responders, and unbalanced substrate-to-enzyme ratio appeared to associate with vascular endothelial damage. Analysis of existing mode of ADAMTS13 may help to clarify pathogenesis of IVIG resistance in acute-KD.

Dynamic evaluation of hemostasis in the acute phase of Kawasaki disease using comprehensive coagulation functional assays.

INTRODUCTION: Kawasaki disease (KD) is a systemic vasculitis involving coronary arteries, sometimes resulting in aneurysms and myocardial infarction. Hyper-coagulability in the acute-phase of KD is indicated in some circumstances based on changes of individual clotting factors. Comprehensive coagulation assays, clot waveform analysis (CWA) and thrombin/plasmin generation assay (T/P-GA), have been developed to assess physiological hemostasis, but these techniques have not been applied in KD. METHODS: We utilized both assays to analyze coagulation function in KD children (n = 42) prior to intravenous-immunoglobulin (IVIG) treatment (Pre), 1-week (1W) and 1-month (1M) post-IVIG. RESULTS: In CWA, the clot time (CT) pre-treatment was prolonged, and was significantly shortened at 1W and 1M. However, the maximum coagulation velocity (|min1|) and acceleration (|min2|) were ~2-fold greater relative to controls, indicating an overall hypercoagulable tendency. These parameters were related to fibrinogen concentration, and were decreased at 1W and declined to normal at 1M. In T/P-GA, the endogenous potentials of thrombin and plasmin were greater relative to control at each of three time-points, and measurements at 1W were greater than those Pre-treatment. The ratios of TG and PG relative to control were similar, however, suggesting well-balanced dynamic coagulation and fibrinolysis. In non-responders to IVIG, the |min1| and |min2| measurements were greater than those in responders at 1W and 1M, suggesting that non-responders remained hypercoagulable after primary treatment. CONCLUSION: The coagulation data observed in KD were consistent with hypercoagulability, although fibrinolytic function appeared to be well-balanced. Comprehensive assays of this nature could provide valuable information on coagulation potential in KD.

Clinical and Echocardiographic Impact of Tafazzin Variants on Dilated Cardiomyopathy Phenotype in Left Ventricular Non-Compaction Patients in Early Infancy.

BACKGROUND: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood. Methods and Results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar. CONCLUSIONS: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

Stenotic Lesions and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVES: To determine the prevalence of subsequent stenotic lesions based on the maximum diameter of the largest coronary artery aneurysm in patients with Kawasaki disease and the threshold value of coronary artery diameter associated with risk of developing stenotic lesion. STUDY DESIGN: There were 214 patients (160 males) who had at least 1 aneurysm in a selective coronary angiogram (CAG) done <100 days after the onset of Kawasaki disease were studied. We measured the maximal coronary artery aneurysm diameter in 3 major branches in the initial CAGs. Branches were classified into 3 groups according to their maximal coronary artery aneurysm diameter: large, ≥8.0 mm; medium, ≥6.0 mm but <8.0 mm; and small, <6.0 mm. Subsequent CAGs were performed in the late follow-up period. We investigated the stenotic lesion in the follow-up CAGs, and evaluated the prevalence of stenotic lesion in each group based on body surface area (BSA) by the Kaplan-Meier method. Localized stenosis of ≥25% and complete occlusion were included as stenotic lesion in this study. We also determined the cutoff point for stenotic lesion. RESULTS: The median interval from the initial CAGs to the latest CAG was 8 years, with a maximum of 32 years. For a BSA of <0.50 m2, the 20-year prevalence of large and medium stenotic lesions was 78% (n = 62; 95% CI, 63-89) and 81% (n = 40; 95% CI, 63-89), respectively. For a BSA of ≥0.50 m2, large and medium stenotic lesions were 82% (n = 75; 95% CI, 67-91) and 40% (n = 56; 95% CI, 20-64), respectively (P < .0001). CONCLUSION: The cutoff points of the coronary artery diameter within the first 100 days after the onset of Kawasaki disease leading to a stenotic lesion in the late period, were a diameter of ≥6.1 mm with a BSA of <0.50 m2 and a diameter of ≥8.0 mm with a BSA of ≥0.50 m2. Those cutoff points would have corresponded with a Z score of at least 10 on 2-dimensional echocardiography. Careful follow-up and antithrombotic therapy should be provided to patients who meet these criteria.

Cardiac Events and the Maximum Diameter of Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVES: To clarify the occurrence of cardiac events based on the maximal diameter of the maximal coronary artery aneurysm (CAA) in Kawasaki disease (KD). STUDY DESIGN: Two hundred fourteen patients (160 male and 54 female) who had had at least 1 CAA in the selective coronary angiogram less than 100 days after the onset of KD were studied. We measured the maximal CAA diameters in the major branches of the initial coronary angiograms. Death, myocardial infarction and coronary artery revascularization were included as cardiac events in this study. We divided the patients into three groups based on the maximal CAA diameter (large ≥8.0 mm; medium ≥6.0 mm and <8.0 mm; small <6.0 mm). Further, we also analyzed the cardiac events based on laterality of maximal CAA (bilateral, unilateral) and body surface area (BSA). RESULTS: Cardiac events occurred in 44 patients (21%). For BSA < 0.50 m2, the 30-year cardiac event-free survival in the large and medium groups was 66% (n = 38, 95% CI, 49-80) and 62% (n = 27, 95% CI, 38-81), respectively. For BSA ≥ 0.50 m2, that in large group was 54% (n = 58, 95% CI, 40-67). There were no cardiac events in the medium group for BSA ≥0.50 m2 (n = 36) and the small group (n = 56). In the large analyzed group, the 30-year cardiac event-free survival in the bilateral and unilateral groups was 40% (n = 48, 95% CI, 27-55) and 78% (n = 48, 95% CI, 63-89), respectively (P < .0001). CONCLUSIONS: The group with the highest risk of cardiac events was the patient group with the maximal CAA diameter ≥6.0 mm with BSA < 0.50 m2 and the maximal CAA diameter ≥8.0 mm with BSA ≥ 0.50 m2. At 30 years after the onset of KD, cardiac event-free survival was about 60%. Given the high rate of cardiac events in this patient population, life-long cardiovascular surveillance is advised.

Distribution of Kawasaki Disease Coronary Artery Aneurysms and the Relationship to Coronary Artery Diameter.

We investigated how the diameter of coronary artery aneurysm (CAA) relates to the distribution immediately after Kawasaki disease (KD). Two hundred and four pts (155 males and 49 females) who had undergone selective coronary angiography (CAGs) less than 100 days after the onset of KD were studied. We measured the maximum diameter of each artery segment in the initial CAGs. We analyzed the relationship between the maximum diameters and the distribution of CAA. We divided the patients into four groups based on the maximum CAA diameter in each patient (large(L) ≥8 mm, medium(M) ≥6 and <8 mm, small(S) ≥4 and <6 mm, very small(VS) <4 mm) and counted the affected segments. There were 87, 61, 36, and 20 patients in groups L, M, S, VS, respectively. The number of segments with CAA in each group was L 6 ± 2, M 4 ± 2, S 2 ± 2, VS 2 ± 1. The number of affected segments in L was significantly more than M, and a large value for L indicated that involvement was significantly more likely to be bilateral. The larger the maximum diameter of CAA, the more extensive disease involvement and the more likely to be bilateral. A large maximum CAA can also indicate coronary involvement in the longitudinal directions. It is an important charcteristic in distribution of CAA caused by KD vasculitis.

Late Wall Thickening and Calcification in Patients After Kawasaki Disease.

OBJECTIVES: To evaluate the relationship between the initial diameters of the coronary arteries immediately after the onset of Kawasaki disease (KD) and late increased coronary wall thickening/coronary artery calcification (CAC). STUDY DESIGN: Sixty-five patients (50 males and 15 females) who had undergone selective coronary angiography (CAG) <100 days after the onset of KD were studied late in disease by dual-source computed tomography (DSCT). The maximum diameters of each segment were measured in the initial CAGs, and the relationship between the maximum diameters and the appearance of increased wall thickening/CAC was analyzed. The study cohort was divided into 2 groups: the branches group (BG) and bifurcation at the left coronary artery (LCA) group. The cutoff point of acute coronary artery dilatation for increased wall thickening/CAC was calculated for each group. Risk factors for the appearance of CAC in each group were investigated, as was the sex difference related to the prevalence of CAC in coronary artery lesions (CALs) of the initial CAGs. RESULTS: The cutoff points of acute coronary dilatation for increased wall thickening were 4.8 mm in the BG (n = 344; area under the curve [AUC], 0.89; P < .001) and 5.3 mm in the LCA group (n = 65; AUC, 0.87; P < .001). The interval from the onset of KD (P < .0001) and sex (P = .0084) were also related to the appearance of CAC in the BG. CONCLUSION: Acute coronary dilatation of exceeding ~5.0 mm can lead to late abnormalities of the coronary artery wall. The prevalence of CAC increases with age. There was a sex-based difference in the late incidence of CAC in the CALs.

Severe Hemolysis and Pulmonary Hypertension in a Neonate With Upshaw-Schulman Syndrome.

Pulmonary involvement is extremely rare in thrombotic thrombocytopenic purpura. In this report, we present a girl patient with congenital thrombotic thrombocytopenic purpura, known as Upshaw-Schulman syndrome (USS), complicated with severe hemolysis and pulmonary hypertension (PH). The assay results of a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13) activity measured by FRETS-VWF73 and ADAMTS13-act-ELISA were different. Hyperbilirubinemia (total bilirubin, 25.3 mg/dL) interfered strongly with the FRETS-VWF73 assay. Plasma levels of ADAMTS13 activity by act-ELISA were <0.5% of normal. The diagnosis of USS was confirmed by ADAMTS13 gene analysis, which showed compound heterozygous mutations of p.G139Vfs*17 and p.I673F. The p.G139Vfs*17 mutation was previously unreported, and its effect in splicing was confirmed by reverse transcription polymerase chain reaction. The patient received oxygen therapy for PH and exchange blood transfusion for severe hemolysis. The PH resolved without specific treatment. Based on these findings, the PH may have been caused by free hemoglobin that scavenged nitrogen oxide or platelet thrombi in the lungs caused by ADAMTS13 deficiency. Thus, severe PH can occur in neonatal patients with USS, and severe hemolysis might result in overestimation of ADAMTS 13 activity. Both possibilities are important for the diagnosis and management of USS.

Influenza-associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S-deficient boy.

Influenza infections often cause pneumonia, but there is limited information on thrombotic microangiopathy (TMA) in these circumstances. We report the case of an 11-year-old boy who developed TMA during the acute phase of H1N1 influenza. Plasma von Willebrand factor (VWF) was elevated, whereas a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was mildly reduced in the absence of ADAMTS13-neutralizing autoantibody, resulting in low ratio of ADAMTS13 to VWF. The patient was treated intensively, including plasma exchange, and he recovered from the TMA. He developed pulmonary embolism (PE), however, after removal of the central venous catheter. The findings suggested that influenza-associated cytokines enhanced the release of unusually large VWF multimers from vascular endothelial cells and promoted the formation of platelet thrombi and TMA. Subsequent analysis further indicated the presence of familial protein S deficiency, and it seemed likely that the PE was more related to this heterozygous protein S defect.

Displacement of the anterior leaflet of the tricuspid valve: Rare variant of Ebstein's anomaly.

In Ebstein's anomaly, the points of attachment, or hinges, of the septal and mural leaflets in the right ventricle are displaced away from the atrioventricular junction. In contrast, the junctional hinge of the anterior leaflet usually retains a normal position. Here, we report a case of giant right atrial aneurysm due to isolated displacement of the anterior leaflet of the tricuspid valve in an infant, a rare variant of Ebstein's anomaly. Enlargement of the right atrium, which was initially diagnosed during the fetal period, progressively and markedly dilated after birth and was successfully treated with surgical resection. Isolated displacement of the anterior leaflet should be recognized as a variant of Ebstein's anomaly.

High Incidence of Dilated Cardiomyopathy After Right Ventricular Inlet Pacing in Patients With Congenital Complete Atrioventricular Block.

BACKGROUND: Some patients with congenital complete atrioventricular block (CCAVB) develop dilated cardiomyopathy (DCM) after pacemaker implantation (PMI). We evaluated the relationship between pacing site and DCM incidence. METHODS AND RESULTS: We retrospectively evaluated 38 patients with CCAVB; 8 (25%) of 32 patients who had PMI developed DCM/heart failure death (HFD) after PMI, although none of the 6 patients without PMI showed DCM/HFD. All DCM/HFD occurred within 50 months of PMI. Among the 32 patients with PMI, the DCM/HFD incidence was 55% (6/11) for right ventricular inlet (RVI), 18% (2/11) for RV apex (RVA), and 0% for left ventricle (LV) (P=0.013). At the endpoint, the LV ejection fraction and septal-to-posterior wall motion delay of patients with LV pacing were better than those for patients with other pacing sites. Among the 8 DCM/HFD patients, 2 in whom the pacing site was changed from RVI to LV apex or in whom therapy was upgraded to cardiac resynchronization remained alive with no heart failure symptoms, whereas the other 6 died of heart failure. CONCLUSIONS: A total of 25% of the patients who underwent PMI because of CCAVB, but none in the non-PMI group, developed DCM/HFD. DCM/HFD incidence was higher in patients with RVI pacing. Ventricular dyssynchrony related to pacing site may be one cause of DCM in patients with CCAVB. (Circ J 2016; 80: 1251-1258).

Usefulness of Percutaneous Transluminal Coronary Balloon Angioplasty for the Left Coronary Artery Stenosis 10 Years More Than After Arterial Switch Operation.

Proximal stenosis adjacent to the orifice of one or both coronary arteries may occur after the arterial switch operation (ASO) for d-transposition of the great arteries (d-TGA). Coronary artery stenosis (CAS) often progresses within the first 6 months postoperatively and may result in myocardial ischemia and infarction. Although percutaneous transluminal coronary balloon angioplasty (PCBA) for CAS within 15 months after ASO for d-TGA has been reported, there is no report of PCBA for CAS in the late period after ASO. We present the results of PCBA for CAS of the left coronary artery performed more than 10 years after ASO in an 11-year-old boy and a 14-year-old boy without complication. The stenosis degree improved in both patients from 81 to 45 and 80 to 54 %, respectively. Restenosis did not occur, and the stenosis degree improved to about 25 % late after PCBA. Although the initial effect of PCBA may not be dramatic, it can improve late after PCBA. It was considered that the optimal balloon-reference vessel ratio was about 1.0, to obtain the minimal effective lumen diameter. PCBA for CAS even if performed many years after ASO is feasible without complication. PCBA can also provide delayed improvement late after the procedure.

Measurements of Coronary Artery Aneurysms Due to Kawasaki Disease by Dual-Source Computed Tomography (DSCT).

Diameters of coronary artery aneurysms (CAAs) complicating acute phase KD can strongly predict the long-term prognosis of coronary artery lesions (CAL). Recently, computed tomographic angiography (CTA) has been used to detect CAL, and the purpose of this study was to determine whether coronary artery diameters measurements by CTA using dual-source computed tomography (DSCT) can be used instead of coronary angiogram (CAG) measurements. Twenty-five patients (22 males and three females) with CAL due to KD, who had undergone both CTA and CAG within one year, were retrospectively evaluated between 2007 and 2013. A prospective electrocardiogram-triggered CTA was performed on a DSCT (SOMATOM(®) Definition, Siemens Healthcare, Germany). Two pediatric cardiologists independently measured the diameters of CAAs twice in each maximum intensity projection (MIP), curved multiplaner reconstruction (MPR) and CAG. We measured 161 segments in total (segment 1-3, 5-7, 11, 13). Diagnostic accuracy was expressed as κ coefficient. A Bland-Altman analysis was also used to assess the intra-observer, inter-observer and inter-modality agreement. The diagnostic quality of CTA was excellent (κ = 0.93). Excellent inter-observer agreement for the diameters of CAAs was obtained for MIP, MPR and CAG and for the intra-observer agreement. The inter-modality agreement was also excellent in measurements of CAA (MPR-CAG: y = 0.9x + 0.40, r = 0.97, p < 0.0001 MIP-CAG: y = x + 0.1, r = 0.94, p < 0.0001). These values in normal coronary arteries were also obtained. We found a significant correlation between CTA and CAG in measuring the coronary arteries. We conclude that measuring coronary artery diameters by CTA is reliable and useful.

Optimal pacing sites for cardiac resynchronization therapy for patients with a systemic right ventricle with or without a rudimentary left ventricle.

AIMS: This study aims to assess the impact of pacing sites on the effectiveness of cardiac resynchronization therapy (CRT) in systemic right ventricle (sRV) patients with/without a rudimentary left ventricle (rLV). METHODS AND RESULTS: We evaluated 13 procedures in 11 sRV patients with a wide QRS (>150 ms). Based on the digitalization results of ventriculography, long-axis dyssynchrony (LD) was defined as extremely delayed right ventricular (RV) outflow tract movement: ≥100 ms delay from the RV apical contraction, and short-axis dyssynchrony (SD) was defined as a paradoxical contraction between the rLV and sRV caused by a conduction delay between the two ventricles. During the follow-up period (2.1 ± 1.9 years), the response rates were 71% (5/7) and 33% (2/6) in the sRV patients with and without an rLV, respectively (P = ns). Following the CRT, the QRS duration remained similar between the responders and nonresponders. Among five responders with an rLV, the leads were placed in the longitudinal RV direction in two with LD, longitudinal RV direction with fusion of the intrinsic QRS in two with LD + SD, and laterally on opposite sides of both ventricles in one with SD. Among two responders without an rLV, the leads were placed in the longitudinal RV direction in those two with LD. CONCLUSIONS: In sRV patients with LD with/without an rLV, the leads should be placed at furthest sites in the longitudinal RV direction. In patients with an rLV and SD, the leads should be placed laterally on opposite sides of both ventricles.

Comorbid Epilepsy and Developmental Disorders in Congenital Long QT Syndrome With Life-Threatening Perinatal Arrhythmias.

OBJECTIVES: Given the association of long QT syndrome (LQTS) and neurological disorders, we speculated that the more severe LQTS phenotype, perinatal LQTS, would exhibit more frequent comorbid neurodevelopmental anomalies than LQTS without perinatal arrhythmias (nonperinatal LQTS). BACKGROUND: Congenital LQTS with life-threatening perinatal arrhythmias (perinatal LQTS) has a poor life prognosis. METHODS: Twenty-one consecutive LQTS patients diagnosed before 1 year of age at our institution and 3 previously reported perinatal LQTS patients with neurological seizures were enrolled. In total, the clinical course was evaluated in 24 patients. RESULTS: Among 21 infantile LQTS patients, 5 of 6 with perinatal LQTS (83%) were diagnosed with epilepsy and 4 (67%) with developmental disorders, but none with nonperinatal LQTS were. The total development quotient by Kinder Infant Development Scale scores was 17 to 72 (median 67) in 5 epileptic perinatal LQTS. In the 8 perinatal LQTS patients with neurological disorders, including 3 previously reported cases, epileptic seizures occurred at 2 days to 2.5 years of age and 5 had developmental disorders. Mutations in these 8 patients were located in the transmembrane loop of KCNH2, and D3/S4-S5 linker, D4/S4, or the D4/S6 segment of SCN5A. CONCLUSIONS: A high comorbidity of neurodevelopmental anomalies was observed in perinatal LQTS. Mutations in patients with neurological comorbidities were in loci linked to LQTS with a severe cardiac phenotype. These observations indicate the possibility that neurological disorders in perinatal LQTS are manifested as neurological phenotypes associated with severe cardiac phenotypes, while we could not completely exclude another possibility that those were caused by a brain perfusion injury.

The clinical characteristics of sudden cardiac arrest in asymptomatic patients with congenital heart disease.

Sudden cardiac arrest (SCA) is a major cause of death in patients with congenital heart disease (CHD). Systemic ventricular dysfunction is a reported risk factor for SCA. We retrospectively analyzed the medical records of 46 patients (age >6 years) who experienced SCA. The following underlying cardiac defects were observed: biventricular repair with affected subpulmonary right ventricle (n = 18, 39 %), biventricular repair with systemic right ventricle and Eisenmenger syndrome (n = 6 each, 13 %), Fontan circulation and unrepaired CHD (n = 5 each, 11 %), and others (n = 6, 13 %). Twenty-one patients (46 %) had no history of arrhythmias, and 21 of 43 (49 %) showed systemic ventricular ejection fraction >55 %. According to the New York Heart Association classification, 18 patients (39 %) were class I and 28 (61 %) were class II/III. SCA occurred at a younger age in class I (16 ± 5 years) than in the other classes (23 ± 10 years; P = 0.004). QRS duration was similar between the groups (136 ± 38 vs. 141 ± 50 ms; P not significant). Seven patients in class I (15 % of all SCAs) had no history of arrhythmias or features of hemodynamic abnormalities. The proportion of patients with biventricular repair and affected subpulmonary right ventricle was higher than that of patients with other defects, and the majority of SCA patients had more complicated defects than a simple repaired ventricular septal defect or an atrial septal defect. No symptoms of heart failure, history of arrhythmias, or features of hemodynamic abnormalities were observed in 15 % of the patients who experienced SCA. Prolonged QRS duration might be a predictor of SCA even in asymptomatic CHD patients. Prevention of SCA in CHD patients may require more detailed evaluation than is typically considered necessary.