Modeling of multiple atrial septal defects with inferior vena cava rim deficiency: Three-dimensional visualization of the rim based on transthoracic echocardiographic imaging.

The morphologic features of the multiple atrial septal defects assessed by TTE-based 3D imaging were similar to those by 3D-TEE. TTE-based 3D model had excellent visibility, allowing observation of 3D structure of the rims of the defects. It may be useful method for assessment of the multiple atrial septal defects.

Cardiac features of Noonan syndrome in Japanese patients.

BACKGROUND: Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. METHODS: This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. RESULTS: Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. CONCLUSIONS: These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.

Electrocardiographic Changes with Age in Japanese Patients with Noonan Syndrome.

Little information is available on age-related electrocardiographic changes in patients with Noonan syndrome. This single-center study evaluated the electrocardiograms of patients with Noonan syndrome. We divided the patients (n = 112; electrocardiograms, 256) into four groups according to age: G1 (1 month-1 year), G2 (1-6 years), G3 (6-12 years), and G4 (>12 years). Typical Noonan syndrome-related electrocardiographic features such as left-axis deviation, abnormal Q wave, wide QRS complex, and small R wave in precordial leads were detected. A high percentage of QRS axis abnormalities was found in all groups. Significant differences in right-axis deviation (RAD) were noted among the groups: 56.5% of G1 patients showed RAD compared with 33.3% of G2, 21.1% of G3, and 19.2% of G4 patients. The small R was also significantly different among the groups: 32.6% of G1 patients showed a small R wave compared with 14.9% of G2, 8.5% of G3, and 15.4% of G4 patients. Of the 53 patients with Noonan syndrome aged 1 month to 2 years, 18 had T-positive V1 with a higher prevalence of pulmonary stenosis and cardiac interventions. QRS axis abnormalities, small R in V6, and T-positive V1 could help diagnose Noonan syndrome in infants or young children.

Assessment of the left ventricular volume of tetralogy of Fallot by electrocardiogram.

BACKGROUND: Sufficient left ventricular volume is required for patients with tetralogy of Fallot (TOF) who are going to have biventricular repair. In this study, we investigated the utility of the electrocardiogram to evaluate left ventricular volume in patients with TOF. METHOD: Patients whose left ventricular (LV) end-diastolic volume was lower than 80% of normal were defined as having a small LV. Seven patients with TOF who had to undergo Blalock-Taussig shunt surgery because of a small LV were assigned to group S. Twenty patients with TOF who had sufficient LV volume were assigned to group G. The amplitudes of the Q wave of V5-7 leads (QV5-QV7), the S wave of V1 lead, and the R wave of the II, III, aVf, and V5-7 leads of the electrocardiogram were evaluated. RESULTS: The amplitude of QV5 was 0 mV in all cases in group S, which was significantly smaller than that in group G (0 vs 0.01 mV, P = 0.028). The frequency of absent QV5 was significantly higher in group S than in group G (100% vs 50%, P = 0.026). Absent QV5 showed 100% sensitivity, 50% specificity, and a negative predictive value of 100% for a small LV. CONCLUSIONS: In TOF, the amplitude of the septal Q wave reflects LV volume. In particular, the absence of QV5 suggests a small LV end-diastolic volume, which is lower than 80% of normal.

A retrospective study of perioperative clinical seizures and epilepsy in children after operation for CHD.

This study investigated the incidence and risk factors of perioperative clinical seizure and epilepsy in children after operation for CHD. We included 777 consecutive children who underwent operation from January 2013 to December 2016 at Kanagawa Children's Medical Center, Kanagawa, Japan. Perinatal, perioperative, and follow-up medical data were collected. Elastic net regression and mediation analysis were performed to investigate risk factors of perioperative clinical seizure and epilepsy. Anatomic CHD classification was performed based on the preoperative echocardiograms; cardiac surgery was evaluated using Risk Adjustment in Congenital Heart Surgery 1. Twenty-three (3.0%) and 15 (1.9%) patients experienced perioperative clinical seizure and epilepsy, respectively. Partial regression coefficient with epilepsy as the objective variable for anatomical CHD classification, Risk Adjustment in Congenital Heart Surgery 1, and the number of surgeries was 0.367, 0.014, and 0.142, respectively. The proportion of indirect effects on epilepsy via perioperative clinical seizure was 22.0, 21.0, and 33.0%, respectively. The 15 patients with epilepsy included eight cases with cerebral infarction, two cases with cerebral haemorrhage, and three cases with hypoxic-ischaemic encephalopathy; white matter integrity was not found. Anatomical complexity of CHD, high-risk cardiac surgery, and multiple cardiac surgeries were identified as potential risk factors for developing epilepsy, with a low rate of indirect involvement via perioperative clinical seizure and a high rate of direct involvement independently of perioperative clinical seizure. Unlike white matter integrity, stroke and hypoxic-ischaemic encephalopathy were identified as potential factors for developing epilepsy.

Transient phrenic nerve palsy induced by cardiac catheterisation in an infant.

We report on a 7-month-old male with transient phrenic nerve palsy induced by diagnostic cardiac catheterisation. The phrenic nerve palsy, which is a rare complication, was due to extravascular bleeding from a branch of the internal mammary artery.

Correlation of exercise-induced peripheral venous hypertension with exercise intolerance in patients with Fontan circulation.

Owing to the absence of a sub-pulmonary ventricle, the central venous pressure rises in patients with Fontan circulation. During exercise, central venous pressure may rise further to increase the systemic ventricular preload and cardiac output. We performed a single-centre prospective trial of cardiopulmonary exercise test while monitoring peripheral venous pressure which strongly correlates with central venous pressure. The objective of this study was to test the hypothesis that peripheral venous pressure at peak exercise inversely correlates with exercise capacity in patients with Fontan circulation. Seventeen patients following Fontan operation performed cardiopulmonary exercise test while monitoring peripheral venous pressure. Peak oxygen uptake, heart rate reserve, peak oxygen pulse (divided by body surface area), and peripheral venous pressure at peak exercise were measured. Correlations of peripheral venous pressure at peak exercise with the peak oxygen uptake, heart rate reserve, and peak oxygen pulse were evaluated. The peripheral venous pressure at peak exercise inversely correlated with the peak oxygen uptake (R = -0.66, p < 0.01), heart rate reserve (R = -0.6, p < 0.05), and peak oxygen pulse (R = -0.48, p < 0.05). Exercise-induced peripheral venous hypertension correlates with exercise intolerance in patients with Fontan circulation. Peak oxygen uptake is a useful index for evaluating the status of congestion in the daily life of patients with Fontan circulation.

Fetal case of right atrial isomerism with infracardiac total anomalous pulmonary venous connection and agenesis of the ductus venosus.

After birth, the ductus venosus becomes an important route connecting the pulmonary and systemic venous systems for survival in infracardiac total anomalous pulmonary venous connection. We encountered a fetal case of right atrial isomerism with infracardiac total anomalous pulmonary venous connection and agenesis of ductus venosus. Prenatal echocardiography suggested that the fetus had severe pulmonary venous obstruction; however, no obstructive lesions were detected at the level of the vertical vein that drained into the portal veins. Therefore, we concluded that emergency surgical pulmonary venous obstruction release was the only way for the fetus to survive. However, the saturation level was maintained above 70% due to the abundant communications via the hepatic sinusoid over 1 week after birth. In conclusion, hepatic sinusoids can be a sufficient route for pulmonary venous return and may not cause severe pulmonary venous obstruction in infracardiac total anomalous pulmonary venous connection with agenesis of ductus venosus.

Familial total anomalous pulmonary venous return with 15q11.2 (BP1-BP2) microdeletion.

A 15q11.2 microdeletion (BP1-BP2) is associated with congenital heart diseases (CHDs), developmental delay, and epilepsy. This deletion co-occurs with CHD in 20-30% patients, but a familial case of CHD and a 15q11.2 deletion has not been identified. Here we report the first familial (three siblings) case of total anomalous pulmonary venous return associated with 15q11.2 deletion. Array comparative genomic hybridization identified a ~395 kb deletion at 15q11.2 in patient 1. This deletion was confirmed by fluorescence in situ hybridization in patients 1 and 3 and their asymptomatic father. No deleterious mutation was identified by proband-only exome sequencing of patient 1. One healthy sibling and their mother did not carry the deletion. This deletion is often inherited from asymptomatic parents with an estimated low penetrance of 10.4%. Conversely, we observed high penetrance of this deletion, but secondary copy-number variants or pathogenic variants were not detected in this family.

Nemaline myopathy with dilated cardiomyopathy in childhood.

We present a case of a 9-year-old boy with nemaline myopathy and dilated cardiomyopathy. The combination of nemaline myopathy and cardiomyopathy is rare, and this is the first reported case of dilated cardiomyopathy associated with childhood-onset nemaline myopathy. A novel mutation, p.W358C, in ACTA1 was detected in this patient. An unusual feature of this case was that the patient's cardiac failure developed during early childhood with no delay of gross motor milestones. The use of a ß-blocker did not improve his clinical course, and the patient died 6 months after diagnosis of dilated cardiomyopathy. Congenital nonprogressive nemaline myopathy is not necessarily a benign disorder: deterioration can occur early in the course of dilated cardiomyopathy with neuromuscular disease, and careful clinical evaluation is therefore necessary.

Single-lobe lung transplantation for rapidly deteriorating pulmonary venoocclusive disease.

Pulmonary venoocclusive disease, classified as a subgroup of pulmonary arterial hypertension, is known to show poor prognosis and lung transplantation is the only possible treatment. Single living-donor lobar lung transplantation is a unique method of treatment, mostly for small children, and size matching is the most important factor to conduct single living-donor lobar lung transplantation safely. We report a successful single living-donor lobar lung transplantation for a 6-year-old girl with pulmonary venoocclusive disease who received the graft from her mother. Preoperatively, the recipient was intubated under deep sedation because of repeated episodes of pulmonary edema due to rapidly deteriorating pulmonary venoocclusive disease.

Device closure of atrial septal defect: immediate and mid-term results.

BACKGROUND: Transcatheter closure of atrial septal defects (ASDs) has become an alternative to open surgical procedures. The Amplatzer septal occluder (ASO) has been approved since 2005 in Japan, but there are still many concerns about adverse events, and information about outcomes and complications is limited. The objective of this study was to assess the immediate and mid-term outcomes of device closure of secundum ASDs. METHODS AND RESULTS: From August 2005 to July 2011, 208 consecutive patients with a significant secundum ASD underwent percutaneous closure with the ASO [72 males, 136 females; median age, 7.3 years (range, 3.3-21.9 years)]. Follow-up was available for 206 (99%) patients. Device closure was successful in 203 (98%) patients. Device embolization occurred in 1 case within 1h of device implantation, but the device was surgically retrieved without any neurological sequelae. During the follow-up period, complete closure was observed in 202 of 203 patients. There were no cases of erosions, late embolization, thrombus formation, or death. CONCLUSIONS: Transcatheter closure of ASDs using the ASO is safe and effective, with excellent results during mid-term follow-up. Appropriate patient selection and accurate device selection is mandatory to avoid serious complications.

Intrapericardial and retrocardial implantation of implantable cardioverter-defibrillator lead in a child with type 3 long QT syndrome.

A 6-year-old girl with type 3 long QT syndrome was safely and successfully implanted with an implantable cardioverter-defibrillator (ICD) system. Prior to implantation, she had experienced uncontrollable life-threatening arrhythmia in spite of high-dose administration of mexiletine. An ICD coil lead for transvenous use was placed in the intrapericardial and retrocardial space and was connected to a generator placed in front of the posterior sheath of the right abdominal rectal muscle. Administration of a beta-blocker in addition to atrial pacing almost completely eliminated the patient's life-threatening arrhythmia attacks. Intrapericardial and retrocardial implantation of ICD coil leads might be useful for children.

A symptomatic neonate with tetralogy of Fallot, an absent pulmonary valve, and a single coronary artery with a major fistula.

We present a case with a rare combination of tetralogy of Fallot with an absent pulmonary valve, and a single coronary artery with a major fistula to the main pulmonary artery. Myocardial ischemia developed in response to increasing shunt flow through the coronary fistula, resulting in heart failure. We ligated the coronary fistula and plicated the anterior wall of the dilated pulmonary arteries during the neonatal period. Complete repair through a transatrial-transpulmonary approach was performed at the age of 17 months. The postoperative course was excellent and the patient maintained a stable hemodynamic and respiratory state with no evidence of myocardial ischemia.

Early diagnosis of Kawasaki disease in patients with cervical lymphadenopathy.

BACKGROUND: Among typical patients with Kawasaki disease (KD), a few KD patients present with only fever and cervical lymphadenopathy at admission (KDL). These patients have a significant risk for misdiagnosis, delay in treatment for KD, and development of coronary artery abnormalities. Therefore, the development of an easy tool for early diagnosis in these patients is desirable. METHODS AND RESULTS: Patients who presented with only fever and cervical lymphadenopathy at admission were studied. Of these, 14 patients were eventually diagnosed with KD (KDL) and 24 patients were successfully treated using antibiotics (control). KDL patients were significantly older than control patients (P > 0.022). Among the laboratory findings, neutrophil counts (P > 0.003), C-reactive protein (CRP; P < 0.001), and aspartate aminotransferase (AST; P > 0.018) were significantly different between the groups. To discriminate KDL patients from controls, cut-off points of the aforementioned parameters (KDL indices) were determined using the receiver operating characteristic curves in order to maximize sensitivity and accuracy (age, 5.0 years; neutrophil counts, 10,000 /microL; CRP, 7.0 mg/dL; AST, 30 IU/L). One point was assigned if a subject exceeded the cut-off point in a KDL index. If a patient with three or four KDL indices was considered to have KD, the sensitivity was 78% and the specificity 100%. None of the patients with one or zero KDL index developed KD. CONCLUSIONS: KDL indices may be helpful in discriminating KDL from lymphadenitis at admission. It is important to monitor the symptoms of KD in a patient with three or four KDL indices at admission.

Four cases of Kawasaki syndrome complicated with myocarditis.

BACKGROUND: Myocarditis frequently occurs in the acute phase of Kawasaki syndrome (KS), and a few severe cases have been reported. Four cases of myocarditis in KS required additional catecholamine treatment because of severe left ventricular dysfunction (LVD). CASE REPORTS: Three cases were relatively older children and 2 cases were complicated with encephalopathy. All 4 developed coronary artery abnormalities during convalescence. There was 1 case of LVD because of prolonged severe inflammation prior to administration of intravenous immunoglobulin (IVIG). The remaining 3 patients had normal values for ejection fraction before the administration of IVIG but decreased values (42-51%) and increased C-reactive protein levels after IVIG administration. These cases demonstrate an association between myocarditis in KS and severe or worsened inflammation. CONCLUSIONS: Even with prior normal echocardiography, careful observation of cardiac function may be necessary for patients with KS, especially older children, when inflammation deteriorates after administration of IVIG.

Interval representative of transmural dispersion of repolarization in children and young adolescents with congenital long QT syndrome.

BACKGROUND: It has been shown experimentally that the interval from the nadir of the initial negative T wave to the end of the T wave is representative of transmural dispersion of repolarization (TDR) when complex T waves are present. In the clinical setting, however, the interval representative of TDR in patients with long QT syndrome (LQTS) is a controversial subject. METHODS AND RESULTS: Five symptomatic patients (3 boys, 2 girls; 3 LQT1, 2 LQT2) were evaluated by a face immersion test before and after treatment to compare the configuration of the T wave. When the notch disappeared after treatment, the single peak of the T wave after treatment coincided with the nadir of the notch before treatment. When the notch remained the same after treatment as before treatment and when the QTc decreased, the corrected interval from the nadir of the notch to the end of the T wave was for the most part shortened. CONCLUSIONS: The present study showed that the interval representative of the TDR in the clinical surface electrocardiogram can be obtained from the nadir of the notch to the end of the T wave in children and adolescents with LQTS, as was shown in the experimental study.

Heart rate variability and ambulatory blood pressure monitoring in young patients with hypertrophic cardiomyopathy.

BACKGROUND: Sudden cardiac death commonly occurs in young patients with hypertrophic cardiomyopathy (HCM); however, their heart rate variability (HRV) and blood pressure (BP) response to daily life activities is not well known. METHODS AND RESULTS: HRV and ambulatory BP monitoring were performed in 20 patients (age range: 7-21 years) and 57 age-matched healthy volunteers (age range: 10-22 years). Time domain variables and spectral data were obtained at hourly intervals throughout the day. To determine the BP response to daily life activities, the ratios of the mean BP and pulse pressure in the morning, afternoon, and night to those during sleeping were calculated. The association between the BP level and HRV was also evaluated. The HCM patients showed significantly increased sympathovagal imbalance and decreased parasympathetic activity in the early morning, around noon, and in the early evening. This abnormality was independent of cardiac symptoms. Symptomatic patients showed a significantly lower systolic BP response in the morning, and a higher incidence of dissociation between sympathetic activity and BP response than asymptomatic patients. CONCLUSION: An abnormal BP response in the presence of impaired HRV appears to be predictive for cardiac events in young patients with HCM.