Hitoshi Horigome

Sudden fatal cardiac arrest in a child with an unrecognized anterior mediastinal mass

We report a case of sudden fatal cardiac arrest in a 3-year-old boy. The arrest occurred when he was placed in the supine position by force for a venipuncture. Autopsy revealed a large anterior mediastinal mass. The death was attributed to the airway obstruction and cardiac compression by the mass. Postural change to supine position by force was believed to have triggered compression of the cardiopulmonary system by an unrecognized anterior mediastinal mass, resulting in cardiac arrest.

Group B streptococcal endocarditis in infancy with a giant vegetation on the pulmonary valve

Sir: The association of Dandy-Walker malformation, ventricular septal defect, and characteristic craniofacial appearance was first described by Ritscher and Schinzel in 1987 in two sisters [3]. Verloes reported a third case in 1989 [4] proposing the name 3C syndrome as an acronym for cranio-cerebello-cardiac dysplasia. Two more cases were reported 1989 [2] and 1992 [1]. We present a sixth case with additional bilateral colobomata. The 2.5-year old girl is the first child of a healthy mother. A younger brother has a neuroblastoma. The patients birth weight was 3.4 kg, length 52 cm, occipitofrontal circumference 36 cm. Clinical examination at birth and later disclosed a flat and depressed nasal bridge, flat face, prominent forehead, hypertelorism, bilateral colobomata of the iris, low-set and posteriorly rotated ears, large fontanelles, wide cranial sutures, parietal foramina, thin lips, narrow and high palate, narrow and long feet with sandal gap of 1st and 2nd toes, muscular hypotonia, and joint laxity (Fig. 1). CT scan of the cranium revealed aplasia of the cerebellar vermis, enlarged 4th ventricle, moderate dilatation of the 3rd ventricle, the lateral ventricles, and the prepontine cisternes. Ophthalmological examination disclosed a right-sided coloboma of the retina. A large perimembraneous ventricular septal defect was shown on echocardiography and confirmed by cardiac catheterization. The defect was closed with a dacronpatch at the age of 2 years. At the age of 2.5 years psychomotor development was obviously retarded. The girl was able to sit up without help, pull herself to a standing position, and walk with support. Hearing was normal and she Fig. 1 Proposita at age of 2 years showing prominent forehead, small, triangular face, hypertelorism, downslanting palpebral fissures, rounded nasal tip, microgenia

Increased risk of thromboembolic events in adult congenital heart disease patients with atrial tachyarrhythmias

BACKGROUND Atrial tachyarrhythmias are a major morbidity in patients with adult congenital heart disease (ACHD). However, few studies have investigated risk stratification of thromboembolic events in ACHD patients with atrial tachyarrhythmias. METHODS AND RESULTS This retrospective cohort study reviewed the clinical records of 2314 ACHD patients from 1977 to 2014. We found 242 (10.4%) patients with atrial tachyarrhythmias and excluded 84 patients already being treated with anticoagulant therapy. The remaining 158 patients without anticoagulant therapy were retrospectively followed up from the onset of atrial tachyarrhythmia to the incidence of thromboembolic events. Fourteen thromboembolic events and 5 hemorrhagic events occurred. All patients with thromboembolic events had atrial fibrillation (AF). Thromboembolic events occurred even in the patients with low or intermediate risk as indicated by CHADS2 or CHA2DS2-VASc score. Event rates were higher than those in data from the general adult population in previous studies. Univariate analysis revealed that age≥60years (OR 4.54, 95% CI 1.47-14.06, P=0.009), vascular disease (OR 7.83, 95% CI 1.19-51.53, P=0.032), and persistent AF (OR 5.60, 95% CI 1.73-18.11, P=0.004) were the independent risk factors of thromboembolic events. CONCLUSIONS ACHD patients with atrial tachyarrhythmias and even those with low or intermediate risk as indicated by the CHADS2 or CHA2DS2-VASc score had a higher risk of thromboembolic events. Therefore, anticoagulation should be considered earlier than in the general population in patients with risk factors of age≥60years, vascular disease, or persistent AF.

Maternal predictive factors for fetal congenital heart block in pregnant mothers positive for anti-SS-A antibodies.

Abstract Objective: To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. Methods: The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. Results: Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p = 0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at ≥10 mg/day) after conception before 16-week gestation (OR 0.17, p = 0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p = 0.04) and high titer of anti-SS-A antibodies (OR 3.58, p = 0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p = 0.03). Other maternal clinical features did not influence the development of fetal CHB. Conclusion: The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB.

Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction

BACKGROUND Familial sick sinus syndrome (SSS) is often attributable to mutations in genes encoding the cardiac Na channel SCN5A and pacemaker channel HCN4. We previously found that SSS with SCN5A mutations shows early onset of manifestations and male predominance. Despite recent reports on the complications of atrial fibrillation (AF) and left ventricular noncompaction (LVNC) in patients with SSS caused by HCN4 mutations, their overall clinical spectrum remains unknown. OBJECTIVE The purpose of this study was to investigate the clinical and demographic features of SSS patients carrying HCN4 mutations. METHODS We genetically screened 38 unrelated SSS families and functionally analyzed the mutant SCN5A and HCN4 channels by patch clamping. We also evaluated the clinical features of familial SSS by a meta-analysis of 48 SSS probands with mutations in HCN4 (n = 16) and SCN5A (n = 32), including previously reported cases, and 538 sporadic SSS cases. RESULTS We identified two HCN4 and three SCN5A loss-of-function mutations in our familial SSS cohort. Meta-analysis of HCN4 mutation carriers showed a significantly younger age at diagnosis (39.1 ± 21.7 years) than in sporadic SSS (74.3 ± 0.4 years; P <.001), but a significantly older age than in SCN5A mutation carriers (20.0 ± 17.6 years; P = .003). Moreover, HCN4 mutation carriers were more frequently associated with AF (43.8%) and LVNC (50%) and with older age at pacemaker implantation (43.5 ± 22.1 years) than were SCN5A mutation carriers (17.8 ± 16.5 years; P <.001). CONCLUSION SSS with HCN4 mutations may form a distinct SSS subgroup characterized by early clinical manifestation after adolescence and frequent association with AF and LVNC.

Oesophageal lung with systemic arterial blood supply

An adolescent girl with congenital bronchopulmonary-foregut malformation (BPFM) is reported. The patient had a hypoplastic, non-functioning right lung with the main bronchus originating from the oesophagus. The pulmonary artery of the “oesophageal lung” was supplied by systemic circulation from the descending aorta, and the venous flow drained through a hypoplastic right pulmonary artery (RPA) into the large left pulmonary artery (LPA). This case was a rare type of left-to-right shunt and demonstrates that oesophagography, pulmonary angiography and aortography are important in demonstrating the haemodynamics involving this malformation.

Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes

Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed somatic cells from three ATS patients to generate induced pluripotent stem cells (iPSCs). Multi-electrode arrays (MEAs) were used to record extracellular electrograms of iPSC-derived cardiomyocytes, revealing strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Ca2+ imaging of cells loaded with the Ca2+ indicator Fluo-4 enabled us to examine intracellular Ca2+ handling properties, and we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes than in control-iPSC-derived cardiomyocytes. Drug testing using ATS-iPSC-derived cardiomyocytes further revealed that antiarrhythmic agent, flecainide, but not the sodium channel blocker, pilsicainide, significantly suppressed these irregular Ca2+ release and arrhythmic events, suggesting that flecainides effect in these cardiac cells was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig cardiac ventricular myocytes confirmed that flecainide could directly affect the NCX current (INCX). ATS-iPSC-derived cardiomyocytes recapitulate abnormal electrophysiological phenotypes and flecainide suppresses the arrhythmic events through the modulation of INCX.

Right atrial hemangiopericytoma with hemopericardium during infancy

A male infant with benign hemangiopericytoma of the right atrium is reported. His chief complaint was acute respiratory distress secondary to bloody pericardial effusion. Although the entire mass could not be removed surgically, there was no recurrence of cardiac tamponade or growth of the residual mass during a follow-up period of 3 years. This patient is, to our knowledge, the youngest one with primary cardiac hemangiopericytoma so far reported.

Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial

Introduction Several retrospective or single-centre studies demonstrated the efficacy of transplacental treatment of fetal tachyarrhythmias. Our retrospective nationwide survey showed that the fetal therapy will be successful at an overall rate of 90%. For fetuses with hydrops, the treatment success rate will be 80%. However, standard protocol has not been established. The objective of this study is to evaluate the efficacy and safety of the protocol-defined transplacental treatment of fetal tachyarrhythmias. Participant recruitment began in October 2010. Methods and analysis The current study is a multicentre, single-arm interventional study. A total of 50 fetuses will be enrolled from 15 Japanese institutions. The protocol-defined transplacental treatment is performed for singletons with sustained fetal tachyarrhythmia ≥180 bpm, with a diagnosis of supraventricular tachycardia or atrial flutter. Digoxin, sotalol, flecainide or a combination is used for transplacental treatment. The primary endpoint is disappearance of fetal tachyarrhythmias. The secondary endpoints are fetal death related to tachyarrhythmia, proportion of preterm birth, rate of caesarean section attributable to fetal arrhythmia, improvement in fetal hydrops, neonatal arrhythmia, neonatal central nervous system disorders and neonatal survival. Maternal, fetal and neonatal adverse events are evaluated at 1 month after birth. Growth and development are also evaluated at 18 and 36 months of corrected age. Ethics and dissemination The Institutional Review Board of the National Cerebral and Cardiovascular Center of Japan has approved this study. Our findings will be widely disseminated through conference presentations and peer-reviewed publications. Trial registration number UMIN Clinical Trials Registry UMIN000004270.

Pseudocoarctation of the aorta coexistent with coarctation.

Sir: Pseudocoarctation of the aorta is an uncommon congenital anomaly of the aortic arch, usually detected by cardiac murmur or abnormal superior mediastinal mass on the chest radiograph. The criteria for diagnosing this anomaly include the small pressure gradient of the lesion, usually below 25 mmHg, absence of increased collateral circulations and definitive angiogram of an abnormally elongated aortic arch [2]. However, a few cases of pseudocoarctation have been reported in which the arterial pressure gradient between the upper and lower extremities exceeds 25 mm Hg because of coexisting coarctation of the aorta [1, 3-5]. We present here such a rare type of pseudocoarctation. A 9-year-old girl was refened for evaluation of a grade 2/6 continuous heart murmur in the upper area of the chest and back. Physical examination revealed a healthy-appearing girl. Blood pressure was 132/74 m m H g in the right arm, and 80/60 mm Hg in the left arm and lower extremities. An electrocardiogram and echocardiogram showed no hypertrophy of the left ventricle. Radiographs of the chest revealed high aortic knob which reached the clavicle without cardiomegaly. Retrograde cardiac catheterization was performed via the femoral artery. A soft tip catheter barely passed through the kinked portion of the aorta to reach the ascending aorta. Blood pressure in the ascending aorta, aortic arch and descending aorta were 136/86, 98/62 and 88/62 mm Hg, respectively. Intra-arterial digital subtraction angiography showed a normal ascending aorta and coronary arteries. The aortic segment between the left common carotid artery and the left subclavian artery was apparently elongated with localized coarctation distal to the origin of the left common carotid artery [Fig. 1], which yielded most of the pressure gradient. Pseudocoarctation of the aorta has been thought to develop from failure of the normal compression of the third through seventh dorsal aortic arch during fetal development [2]. Although our case did not demonstrate coarctation histologically, it is possible that the ductal tissue or the ligamentum arteriosus play a role in the formation of a localized stenosis of the elongated segment. We emphasize that invasive catheterization and angiography are essential to determine the coexistence of coarctation in cases of pseudocoarctation involving a significant pressure gradient between the extremities. References