Effectiveness of BNT162b2 vaccine against symptomatic SARS-CoV-2 infection in children aged 5-11 years in Japan during Omicron variant predominate periods.

BACKGROUND: Although the effectiveness of BNT162b2 messenger RNA vaccines against the Omicron variant has been reported in several countries, data are limited in children living in Asian countries. Therefore, this study aimed to estimate the effectiveness of the pediatric primary two-dose monovalent mRNA vaccine series in preventing symptomatic coronavirus disease 2019 (COVID-19) in Japan. METHODS: We conducted a test-negative case-control study (262 test-positive cases and 259 test-negative controls) in patients aged 5-11 years who presented with COVID-19-like symptoms during the Omicron BA.2- and BA.5-predominant periods. Vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, living environment, and PCR test results were obtained using parent-administered questionnaires and clinical records. Vaccine effectiveness (VE) against symptomatic COVID-19 was calculated using a multivariate logistic regression analysis. RESULTS: Of the test-positive cases and test-negative controls, 9.2% (n=24) and 12.7% (n=33) received two vaccine doses, respectively. Having siblings and a BA.5-dominant period were significantly associated with symptomatic COVID-19. After adjusting for age, siblings, study period, and duration after the last vaccination, the overall VE of two-dose vaccination was 50.0% (95% confidence interval [CI], 5%-74%). VE was 72% (95%CI: 24%-89%) within 3 months after the two-dose vaccination, while it decreased to 24% (95%CI: -80% to 68%) after 3 months. CONCLUSION: Two BNT162b messenger RNA vaccine doses provided moderate protection against symptomatic COVID-19 during the Omicron variant period. A time-dependent decrease in VE was noted after the second dose; thus, a booster dose 3 months after the second dose is warranted.

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.

Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports.

Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for.

Management of congenital diaphragmatic hernia with transposition of the great arteries.

Congenital diaphragmatic hernia (CDH) is a relatively rare malformation, but it has a high mortality rate. Its association with congenital heart disease lowers survival rate due to severe acidosis and desaturation caused by persistent pulmonary hypertension of the neonate. We describe herein a case of CDH with transposition of the great arteries and intact ventricular septum, in a patient who was prenatally diagnosed, managed with extracorporeal oxygenation (ECMO) support and successfully treated with both CDH repair and Jatene procedure, with no respiratory or circulatory sequelae. In conclusion, precise prenatal estimation is essential, and ECMO is a useful therapeutic option in these complex cases.

Results of extracardiac conduit total cavopulmonary connection in 500 patients.

OBJECTIVES: This single-institution study aimed to evaluate the early to mid-term outcomes of extracardiac conduit total cavopulmonary connection (EC-TCPC). METHODS: Between March 1994 and March 2014, 500 patients (median age, 3.4 years) underwent EC-TCPC at our hospital. One hundred and twenty-three patients (24.6%) showed heterotaxy, and fenestration was created in 6 patients (1.2%). The standard institutional treatment policy included postoperative anticoagulation and individualized cardiovascular medication. The mortality and morbidity rates, haemodynamic status, cardiopulmonary exercise capacity and liver examination results during the follow-up period (median, 6.7 years) were retrospectively reviewed. RESULTS: There were 2 early and 17 late deaths. The Kaplan-Meier estimated survival rate was 96.2% at 10 years and 92.8% at 15 years. Bradyarrhythmia and tachyarrhythmia occurred in 19 and 13 patients, respectively. Other late-occurring morbidities included protein-losing enteropathy in 8, thromboembolism in 5, bleeding complications in 6 and liver cirrhosis in 1 patient. The rate of freedom from late-occurring morbidities was 82.1% at 15 years. In the multivariate analysis, heterotaxy was found to be a predictor for mortality (P = 0.02), whereas age at operation was a predictor for new-onset arrhythmias (P = 0.048). In the cardiopulmonary exercise test (n = 312), the peak VO2 was 84.9 ± 17.3% of the predicted value, which tended to decrease with age (R(2) = 0.32) and elapsed time since operation (R(2) = 0.21). Postoperative cardiac catheterization (n = 468; time from surgery, 3.6 ± 4.3 years) showed central venous pressure of 9.9 ± 2.4 mmHg, ventricular end-diastolic pressure of 5.2 ± 3.3 mmHg, cardiac index of 3.4 ± 0.8 l/min/m(2) and arterial oxygen saturation of 94.2 ± 4.8%. In 101 patients who were followed up for ≥10 years, amino-terminal type III procollagen peptide and collagen type IV levels exceeded the normal ranges in 52.9 and 75.2% of patients, respectively, and liver ultrasonography revealed hyper-echoic spots in 43.3% of patients. CONCLUSIONS: The early to mid-term outcomes of post-EC-TCPC patients managed with individualized pharmacotherapy were excellent, with low mortality and morbidity rates; however, development of late-occurring morbidities specific to Fontan physiology, including exercise intolerance and liver disease, must be carefully monitored during the long-term follow-up.

Aortic regurgitation associated with critical aortic stenosis in a fetus.

Aortic regurgitation in association with aortic stenosis is rare in the fetus. Findings have shown that severe aortic regurgitation is worsened by the increase in systemic vascular resistance after birth, resulting in low cardiac output, hypoxemia, and neonatal death. This report describes a unique case of aortic regurgitation with aortic stenosis, severe mitral regurgitation, retrograde flow in the aortic arch, and an enormous left atrium with a restrictive foramen ovale in a fetus. In this case, aortic regurgitation was diminished immediately after birth, indicating that spontaneous improvement in aortic regurgitation after birth should be taken into account when the final prognosis is predicted.

Twenty-eight years' experience of arterial switch operation for transposition of the great arteries in a single institution.

OBJECTIVES: We reviewed our 28 years of experience of arterial switch operation (ASO) for transposition of the great arteries to investigate late sequelae of this procedure. METHODS: 387 patients who underwent ASO from 1984 to 2010 were included in this retrospective study. The longitudinal data were estimated by the Kaplan-Meier method and compared using a log-rank test. Risk factors for late sequelae were analysed by the multivariable Cox proportional hazards model. RESULTS: The mean follow-up time was 10.0 years. There were 13 early deaths and 17 late deaths. All late deaths were within 1 year, except for three patients. Actuarial survival was 92.2 and 91.6% at 10 and 20 years, respectively. Sixty-six patients (17.1%) had developed pulmonary stenosis (PS) and 29 patients (7.5%) had developed moderate or more aortic insufficiency (AI) during follow-up. Selective coronary angiography was performed in 210 patients (54.3%) at 9.6 ± 5.1 years after ASO. Left main tract occlusion was found in 2 patients (2/210; 1.0%) and hypoplastic left coronary artery was found in 10 patients (10/210; 4.8%). Among these 12 patients, 8 patients were asymptomatic. Re-operation was performed in 76 patients (19.6%), pulmonary artery plasty for PS in 58 patients (15.0%), aortic valve replacement for AI including two Bentall operations in 9 patients (2.3%) and others. Freedom from re-operation was 78.2 and 62.8% at 10 and 20 years, respectively. The risk factor for PS was the use of equine pericardium for reconstruction (P < 0.0001). Factors associated with moderate or more AI was the presence of left ventricular outflow tract obstruction (P = 0.004). There were no risk factors for late coronary lesions. Three hundred and forty surviving patients (340/357; 95.2%) were in NYHA functional class I. Treadmill test, which was performed on 217 patients (56.1%) at 14.3 ± 5.4 years after ASO, revealed that the maximum heart rate was 97.5 ± 7.6% of normal and peak oxygen consumption was 105.2 ± 20.5% of normal. CONCLUSIONS: ASO was performed with satisfactory results in the overall survival and functional status. PS was the main reason for re-operation. Coronary lesions can appear late without any symptoms. Benefits of ASO can be achieved by long-term follow-ups of PS, AI and coronary lesions.

Critical Ebstein anomaly in a fetus successfully managed by elective preterm delivery and surgical intervention without delay after birth.

This report describes a case of Ebstein anomaly in a fetus with cardiomegaly, severe tricuspid regurgitation, pulmonary regurgitation, and retrograde ductal flow that showed a marked increase in the size of the right atrium with advancing gestational age. Elective preterm delivery was performed at 35 weeks gestation. The prostaglandin E1 infusion resulted in more pronounced systemic hypotension and acidosis secondary to circular shunt across the patent ductus arteriosus as well as pulmonary regurgitation and tricuspid regurgitation. Emergency surgical intervention consisting of main pulmonary artery ligation, ductus arteriosus ligation, central shunt creation, and plication of the right atrium without cardiopulmonary bypass was performed 4 h after birth. At the age of 16 days, the Starnes procedure was performed. The infant's postoperative course was uneventful. A fetus that has Ebstein anomaly associated with pulmonary regurgitation is at risk for circular shunt across the patent ductus arteriosus after delivery. Planned delivery and surgical intervention without delay after birth are useful for the treatment of such cases.

Four-year experience with prenatal diagnosis of congenital heart defects at a single referral center in Japan with focus on inaccurately diagnosed cases.

PURPOSE: To evaluate the accuracy of prenatal diagnosis of congenital heart defect at the referral level in our institution. METHODS: One hundred and thirty-two cases were referred for prenatal diagnosis of congenital heart defect (CHD). Cases having CHDs were divided into isolated and complex CHDs, and the prenatal and postnatal diagnoses were compared. RESULTS: Thirty-nine cases were diagnosed with CHDs. The remaining 93 cases were diagnosed as normal. Postnatal diagnosis confirmed that 39 cases had CHDs; there were 19 cases of isolated CHD and 20 cases of complex CHD. Among the 19 cases of isolated CHD, all four cases with a false negative diagnosis had ventricular septal defects of an outlet or muscular type with a small defect. Cases with a false positive diagnosis had coarctation of the aorta (3 cases) or total anomalous pulmonary venous connection (1 case). Among the 20 cases of complex CHD, the prenatal diagnoses in two cases were not the same as the postnatal diagnosis and the prognosis was worse than expected. In one case with a single ventricle, pulmonary stenosis, and pulmonary venous atresia, the prenatal diagnosis was hypoplastic left heart syndrome with a suboptimal study at 38 weeks' gestation. In the other case, the diagnosis of corrected transposition of the great arteries had been missed because of misinterpretation of the anatomically right and left ventricles in utero. CONCLUSIONS: There were three possible causes of misdiagnosis or overdiagnosis of CHD: disease orientation, timing of diagnosis, and skill of the examiners. This information may be helpful for the improvement of diagnosis.

Impact and issues of detecting fetal congenital heart defects in Kyushu, Japan.

AIM: To determine the current status of fetal CHD screening in our region and to establish a CHD screening system in Japan. MATERIAL AND METHODS: Subjects were 168 fetuses prenatally-diagnosed with CHD at four referral centers in Japan from 2003 to 2007. Subjects were divided into two groups: group A (n = 84) included cases without extracardiac sonographic abnormalities and known risk factors for CHD and group B (n = 84) included those with extracardiac sonographic abnormalities or risk factors. The diagnostics and outcomes between the groups were analyzed. RESULTS: There were more cases of single ventricle and restrictive ductus arteriosus and fewer cases of ventricular septal defect and double outlet right ventricle in group A than in group B (P < 0.05). In group A, the most frequent referral reason was an abnormal four-chamber view. In group B, 37 cases had chromosomal anomalies. The mortality rates in group B were higher than those in group A (P < 0.05). There were no differences in mortality rates between fetuses without chromosomal anomalies in group B and group A. CONCLUSION: Prenatally-diagnosed CHD were mostly limited to those cases with obvious abnormalities in the four-chamber view or those with chromosomal anomalies. Prenatal detection of CHD is useful for the prediction of outcomes.

Midterm ventricular performance after Norwood procedure with right ventricular-pulmonary artery conduit.

BACKGROUND: Midterm and long-term results of patients who underwent a Norwood procedure with a right ventricular-pulmonary artery conduit remain unclear. This study aimed to compare the midterm ventricular performance of the Norwood procedure with right ventricular-pulmonary artery conduit and the Norwood procedure with systemic-pulmonary shunt. METHODS: Twenty-one patients who underwent both a bidirectional Glenn procedure and a total cavopulmonary connection after Norwood palliation at Fukuoka Children's Hospital Medical Center were divided into two groups: the systemic-pulmonary shunt group (n = 11) and the right ventricular-pulmonary artery conduit group (n = 10). End-systolic elastance (contractility), effective arterial elastance (afterload), and ventriculoarterial coupling and the ratio of stroke work and pressure-volume area (ventricular efficiency) were measured on the basis of cardiac catheterization data before the bidirectional Glenn procedure, before and after the total cavopulmonary connection, and at approximately 1 year after total cavopulmonary connection. RESULTS: After bidirectional Glenn procedure and total cavopulmonary connection, end-systolic elastance of the right ventricular-pulmonary artery conduit group was lower than that of the systemic-pulmonary shunt group, whereas effective arterial elastance of the right ventricular-pulmonary artery conduit group was lower than that of the systemic-pulmonary shunt group. Consequently, there was no difference in ventricular efficiency in both groups 1 year after total cavopulmonary connection. CONCLUSIONS: The midterm ventricular performance of the right ventricular-pulmonary artery conduit group was comparable with the systemic-pulmonary shunt group in terms of ventricular efficiency. However, after bidirectional Glenn procedure and total cavopulmonary connection, contractility in patients who underwent a Norwood procedure with a right ventricular-pulmonary artery conduit was inferior to that of patients who underwent a Norwood procedure with a systemic-pulmonary shunt.

Left ventricular performance of pulmonary atresia with intact ventricular septum after right heart bypass surgery.

OBJECTIVE: The left ventricular performance in patients with pulmonary atresia with intact ventricular septum who were Fontan candidates before and after the bidirectional Glenn procedure and a staged total cavopulmonary connection was compared with that in patients with tricuspid atresia. METHODS: Contractility (end-systolic elastance), afterload (effective arterial elastance), and ventricular efficiency (ventriculoarterial coupling, arterial elastance/end-systolic elastance ratio), and the ratio of stroke work and pressure-volume area were approximated on the basis of cardiac catheterization data before the bidirectional Glenn procedure, before and after staged total cavopulmonary connection, and approximately 1 year after the completion of total cavopulmonary connection in 20 patients with pulmonary atresia with intact ventricular septum and 21 patients with tricuspid atresia. RESULTS: The end-systolic elastance of the pulmonary atresia with intact ventricular septum group was significantly inferior to that of the tricuspid atresia group after bidirectional Glenn procedure and total cavopulmonary connection (1 year after total cavopulmonary connection 1.85 +/- 0.51 mm Hg . m 2 . mL -1 vs 2.84 +/- 0.96 mm Hg . m 2 . mL -1 , P < .01). The arterial elastance was not different between groups throughout the assessment period and tended to increase in a stepwise fashion after bidirectional Glenn procedure and total cavopulmonary connection. The arterial elastance/end-systolic elastance ratio and ratio of stroke work and pressure-volume area of the pulmonary atresia with intact ventricular septum group tended to worsen, whereas those of the tricuspid atresia group tended to improve. The difference reached statistical significance 1 year after total cavopulmonary connection (1.15 +/- 0.35 vs 0.82 +/- 0.23 and 64.2% +/- 6.7% vs 71.3% +/- 5.7%, respectively, P < .05 and P < .05, respectively). CONCLUSION: The contractility and ventricular efficiency of patients with pulmonary atresia with intact ventricular septum are inferior to those of patients with tricuspid atresia after bidirectional Glenn procedure and total cavopulmonary connection. A high-pressure residual right ventricle may impair the left ventricular performance of patients with pulmonary atresia with intact ventricular septum after bidirectional Glenn procedure and total cavopulmonary connection.

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.

The low resistance strategy for the perioperative management of the Norwood procedure.

BACKGROUND: Postoperative course of the Norwood procedure is fragile because of an unstable pulmonary to systemic blood flow ratio caused by fluctuation of systemic and pulmonary vascular resistance. METHODS: Twenty-seven patients with hypoplastic left heart syndrome who underwent the Norwood procedure from June 1998 to February 2002 were managed with the following low-resistance strategy. Intraoperative high-flow and low-resistance cardiopulmonary bypass was achieved with total avoidance of circulatory arrest and a large dose of chlorpromazine. In weaning from the bypass, pulmonary vascular resistance was maximally decreased by inspired oxygen fraction (100%), inhaled nitric oxide (20 ppm), and nitroglycerin (2 to 4 microg/kg/min). Then pulmonary blood flow was determined by adjusting the systemic to pulmonary shunt. Postoperatively, with continuous infusion of chlorpromazine and nitroglycerin as a systemic and pulmonary vasodilator, the inspired oxygen fraction and inhaled nitric oxide were tapered as the arterial oxygen saturation improved. RESULTS: In most patients, inhaled nitrous oxide and inspired oxygen fraction were weaned within 3 days. The postoperative course was stable with minimum changes in circulatory and respiratory status for the survivors. Patients were extubated on a median of 6 postoperative days. Early mortality was 11.1% (3 of 27), and none of the patients died of hemodynamic deterioration. CONCLUSIONS: The low resistance strategy is a simple and useful method for perioperative management of the Norwood procedure, minimizing fluctuation in both pulmonary and systemic vascular resistance and maintaining stable circulatory and respiratory status.

Midterm surgical results of total cavopulmonary connection: clinical advantages of the extracardiac conduit method.

OBJECTIVE: We evaluated the midterm surgical outcomes of intra-atrial lateral tunnel and extracardiac conduit total cavopulmonary connection to clarify the clinical superiority. METHODS: Patients (n = 167) underwent total cavopulmonary connection (88 with lateral tunnel and 79 with extracardiac conduit) from November 1991 to March 1999. Survival, incidence of reoperation and late complications, exercise tolerance, hemodynamic variables, and plasma concentration of natriuretic peptide type A were compared. In the lateral tunnel group, time-related change in lateral tunnel size was investigated for its relationship to postoperative arrhythmias. RESULTS: The 8-year survival was 93.2% in the lateral tunnel group and 94.9% in the extracardiac conduit group. Seven reoperations were performed in the lateral tunnel group but none in the extracardiac conduit group. Supraventricular arrhythmias developed in 14 patients (15.9%) in the lateral tunnel group and in 4 patients (5.1%) in the extracardiac conduit group (P =.003). Freedom from cardiac-related events was 72.5% in the lateral tunnel group and 89.8% in the extracardiac conduit group at 8 years (P =.0098). Hemodynamic variables and exercise tolerance were similar in both groups but plasma natriuretic peptide type A concentration, a parameter of atrial wall tension, was higher in the lateral tunnel group. In the lateral tunnel group, intra-atrial tunnel size increased by 19.4% during the 44.2-month interval and the percent increase in tunnel size was an independent predictor of supraventricular arrhythmias. CONCLUSIONS: The midterm survival, hemodynamic variables, and exercise tolerance were similar and satisfactory in both lateral tunnel and extracardiac conduit groups; however, the incidence of cardiac-related events was significantly less frequent in the extracardiac conduit group. In the lateral tunnel group, careful observation is required to monitor the relationship of the dilating tendency of the intra-atrial tunnel and the development of late complications.

Total cavopulmonary connection with an extracardiac conduit: experience with 100 patients.

BACKGROUND: In the Fontan procedures total cavopulmonary connection with an extracardiac conduit is a concern. The potential benefits of an extracardiac conduit may be the avoidance of postoperative supraventricular arrhythmias over the long-term, hemodynamic benefits due to laminar flow, possibility of completion without anoxic arrest, and applicability to anomalous systemic or pulmonary venous return, or both anomalous systemic and pulmonary venous return. We demonstrate early to midterm results of total cavopulmonary connection with an extracardiac conduit. METHODS: Between March 1994 and February 2000, a total of 100 patients underwent total cavopulmonary connection with an extracardiac conduit. In 27 patients, who underwent a single stage total cavopulmonary connection operation, 7 were done without palliation. Seventy-three patients had undergone a bidirectional Glenn shunt before completion of the total cavopulmonary connection. We used an expanded polytetrafluoroethylene tube graft as the extracardiac conduit. RESULTS: Cardiopulmonary bypass time was 133.2+/-55.2 minutes. Myocardial ischemic time was 38.5+/-23.2 minutes in 40 patients who needed cardioplegic cardiac arrest for intracardiac procedures. Intraoperative fenestration was done in only 1 patient. There were no operative deaths. During follow-up of 37.3 months, there were 5 late deaths. When compared with the patients treated by the lateral tunnel technique in our institute, there was no significant difference in actuarial survival rate, but the event free rate of the extracardiac conduit group was significantly superior to the lateral tunnel group. CONCLUSIONS: Total cavopulmonary connection with the extracardiac conduit produced good results in short to midterm follow-up.