Cardiopulmonary exercise testing（CPET） is a kind of clinical testing that allows for the analysis of gas exchange during exercise. Maximal oxygen uptake（VO2max）, an index of cardiac, respiratory, and skeletal muscle functions, is one of the most important measurements obtained in CPET. Anaerobic threshold, the exercise intensity at which lactate starts to accumulate in the blood, is widely used, as it represents an exercise level that is not too strenuous, but not too mild. The minute ventilation/carbon dioxide output relationship（VE/VCO2 slope）is an established prognostic marker in cardiac failure. The oxygen uptake efficiency slope（OUES）, a submaximal index of cardiorespiratory functional reserve, correlates strongly with VO2max and is utilized as a prognostic tool for various heart diseases including congenital heart defects.
Syncope is defined as a transient loss of consciousness due to transient global cerebral hypoperfusion characterized by rapid onset, short duration, and spontaneous complete recovery. Pathophysiological classification of syncope is reflex syncope, orthostatic hypotension, and cardiac syncope. Cardiac syncope has a poor prognosis relative to non-cardiac syncope. Historical features of prior occurence, onset, and end of attack are important for the diagnosis of reflex syncope and orthostatic hypotension. Syncope is often a risk factor in cardiac syncope, it is important to diagnose the underlying heart disease and theat it. In cases of transient loss of consciousness, the diagnosis is based on carefully taken medical history, blood pressure, heart rate, and basic examinations as electrocardiogram, chest X-ray. Further examinations including echocardiogram, CT, MRI is selected if necessary. In children, orthostatic dysregulation should be excluded.
Nuclear cardiology has been used and important in the field of pediatric cardiology for evaluations of impairment of myocardial perfusion and contractile function, fatty-acid metabolism, and sympathetic nerve function associated with various congenital or acquired heart diseases. Myocardial perfusion imaging （MPI） has been established to evaluate myocardial ischemia and infarction with various congenital or acquired coronary artery disease, such as Kawasaki disease, anomalous origin of the left coronary artery from the pulmonary artery, and complete transposition of the great arteries after arterial switch operation. MPI can detect myocardial damages in the morphological right ventricle functioning as a systemic pumping chamber in patients with various complex congenital heart diseases after intra-cardiac repair. MPI is also useful to evaluate primary or secondary cardiomyopathy in children. Magnitude of increased right ventricular uptake on MPI is one of the useful noninvasive means to estimate right ventricular pressure-overload due to congenital heart disease or pulmonary disease. Right and left ventricular contractile function can be assessed reproducibly with ECG-gated blood pool imaging, which has been recently performed by tomographic technique. Myocardial fatty-acid metabolic imaging is useful to detect myocardial ischemia in patients with severe congenital or acquired coronary abnormalities without potential risk associated with pharmacological provocation test. This article reviews nuclear cardiology used for children, especially regarding to technical aspects and current clinical roles in pediatric cardiology.
Children under 15 years of age could not donate their hearts after brain death until the Japanese Organ Transplantation Act was revised on 17th July in 2010, because only persons who had a written consent for organ donation after brain death could donate their organs in Japan. Therefore, small children could not undergo heart transplantation （HTx） in Japan and many Japanese children had been abroad to undergo HTx. After revision of the Act, small children could be able to donate organs if their family accepted and, in fact, finally six children （one younger than 6 years, three between 10 and 14 years, and two between 15 and 17 years） donated his or her heart until the end of 2013. In this review, current status and issues of pediatric HTx in Japan and indication of pediatric HTx and management before and after HTx were described. Briefly, most indication of HTx was dilated cardiomyopathy （DCM） and restrictive cardiomyopahty in Japan and many candidates with DCM required left ventricular assist device （LVAS） for bridge to HTx in Japan. Immunosuppressive regimen was calcineurin inhibitor and mycophenolate mofetil and steroid was discontinued within 6 months in most children. Patient survival at 10 years after HTx was 100% in children transplanted in Japan and 87.6% in children transplanted abroad. Post transplant lymphoproliferative disorder and various infections were major morbidity and mortality. Non-adherence should be carefully observed while taking care of adolescent patients.
Important matters allowing medical investigators to adequately perform clinical trials are described. Clinical trials can provide abundant and clinically important information concerning the efficacy, safety, and pharmacokinetics or pharmacodynamics （PK/PD） of drugs, which are essential for adequate medical treatment. However, for subjects, clinical trials occasionally produce adverse events or present ethical problems. Therefore, investigators should be qualified by education, training, and experience to assume responsibility for properly conducting trials. To ensure scientific data reliability and protect subjects from all clinical trial risks, investigators must follow certain regulations, including the GCP or Ethical Guidance for Clinical Research, as well as the Declaration of Helsinki. Furthermore, all investigators, following the Act on the Protection of Personal Information or other ethical guidelines related to research, must protect the personal information of subjects. The independent ethics committee and the institutional review board serve very important roles in the appropriate performance of clinical trials by reviewing protocols and informed consent documents. Last, the investigators are required to understand how a clinical trial should be carried out in terms of the health insurance system. Keep in mind that qualified investigators can accomplish socially appraised and valuable clinical research.
Background: Balloon dilatation for postoperative pulmonary artery stenosis is important to adjust pulmonary circulation. In semi-compliant balloons, pressure imbalance on inflation （“dog bone appearance”） remains a problem. Recently, the use of noncompliant balloons is increasing because of improved catheter tracking. Purpose: To validate the efficacy of noncompliant balloons in the treatment of postoperative pulmonary stenosis by assessing waist release and pulmonary artery expansion. Method: This retrospective study included 136 patients （154 lesions） who underwent balloon dilatation for postoperative pulmonary stenosis at Saitama Medical University International Medical Center between April 2007 and April 2013. Results: The patients were divided into 2 groups: the semi-compliant balloon group （70 patients ［78 lesions］） and the noncompliant balloon group （66 patients ［76 lesions］）. After balloon dilatation, waist release was achieved for 35 of 78 lesions （45%） in the semi-compliant balloon group and 61 of 76 lesions （80%） in the noncompliant balloon group （p < 0.001）. The expansion rates were 121 ± 2.3% in the semi-compliant balloon group and 139 ± 2.1% in the noncompliant balloon group （p < 0.001）. The balloon size ratios for stenotic lesions were 259 ± 6.6% in the semi-compliant balloon group and 214.9 ± 6.1% in the noncompliant balloon group （p < 0.001）. Conclusion: noncompliant balloon resolved postoperative pulmonary stenosis more effectively with a smaller balloon size compared with semi-compliant balloon. The use of noncompliant balloon may increase with appropriate patient selection.
Background: From 2012, the committee for the board certification system of the Japanese Society of Pediatric Cardiology and Cardiac Surgery （JSPCCS） began to collect annual reports of the previous year from board-certified teaching hospitals and hospital groups. Aim: To analyze annual reports of 2011 and 2012. Method: From annual reports of 2011 and 2012, we analyzed data on human resources and clinical activity of each hospital. Results: 1. In 2011, 42/44 （95.5%） hospitals and 35/38 （92.1%） hospital groups that included 81/97 （83.5%） in-group hospitals, while in 2012, 46/47 （97.8%） hospitals and 34/38 （89.4%） hospital groups that included 85/94 （90.4%） in-group hospitals reported their annual reports. 2. Human resources: Both in 2011 and 2012, the median number of board-certified pediatric cardiologists in teaching hospitals, hospital groups, and in-group hospitals was 3, 5, 2, each. The median number of trainees was 3, 4, and 2 in 2011, and in 2012 which was 4, 4, and 2, respectively. 3. Clinical activity: The median number of admission per year in teaching hospitals, hospital groups, and in-group hospitals was 242，252，and 85, in 2011. In 2012, it was 270, 233, and 94. The median number of cardiac catheterizations was 127, 102, and 31, in 2011, and 146, 105, and 22 in 2012, respectively. In 2011 and 2012, 4 （9.5%） and 4 （8.7%） teaching hospitals did not qualify the number of admission, while 9 （11.1%） and 14 （16.5%） in-group hospitals did also not qualify the number of admission. Two （4.8%） and 2 （4.3%） teaching hospitals, and 5 （14.3%） and 3 （8.8%） hospital groups did not qualified the number of cardiac catheterizations. Conclusion: Human resources of certified pediatric cardiologists in teaching hospitals and in hospital groups matched the number of trainees, while a considerable number of hospitals could not qualify clinical data as a teaching hospital. The qualification system for teaching hospitals and hospital groups may need to be revised in the near future.
Background: Pulmonary arterial hypertension （PAH） is recognized as a spectrum of pulmonary vascular remodeling that leads to lumen obstruction induced by a nexus of unregulated proliferative signaling. We hypothesized that mineralocorticoid receptor （MR） signaling plays a significant role in the remodeling, and that antagonizing MR could ameliorate the vascular impairments in PAH. Methods: Male rats were divided into two groups one day after a single subcutaneous injection of monocrotaline （60 mg/kg）: one group received oral eplerenone （EPL, 100 mg/kg per day, N = 6） and the other received vehicle （N = 8）. Animals in another group with saline injection and no medication served as control （N = 8）. After three weeks of treatment, right ventricular （RV） function was assessed and RV pressure was measured. The mRNA levels for the MR, angiotensin II type 1a receptor and transforming growth factor-β1 in the lungs were measured by quantitative RT-PCR. Results: Peak RV pressure was significantly higher in the vehicle group compared to the control but significantly reduced in the EPL group （p < 0.01）. RV function （Tei-index） was significantly reduced in the vehicle group compared to the control but significantly preserved in the EPL group （p < 0.01）. The eplerenone group showed significantly greater reduction in % medial wall thickness of pulmonary arterioles compared to the vehicle group （20.7±7.4 vs. 43.5±7.5, p < 0.01）. All mRNA levels were significantly upregulated in the vehicle group, compared to the control. Eplerenone treatment resulted in significant reduction in these mRNA levels, compared to the vehicle group （p < 0.01）. Conclusions: These results suggest that MR signaling plays at least a partial role in the proliferative vascular remodeling of PAH and that MR blockade may be an effective alternate treatment for PAH.
Background: We studied usefulness and safety of dual source computed tomography （DSCT）angiography examination for the diagnosis of neonates with major aortopulmonary collateral arteries （MAPCA）. Methods: Six neonates with MAPCAs associated with pulmonary atresia were included in this study. Number of MAPCAs detected by DSCT angiography during neonatal period was compared with that detected by DSCT angiography or cardiac catheter examination at the time of unifocalization （UF）. In order to minimize radiation exposure， we also evaluated the estimated effective dose of each DSCT angiography. Result: The median DSCT scan time was 2.7 （0.4-4.7）seconds and the median estimated effective dose was 2.1 （0.6-6.2）mSv. Twenty-one out of 23 MAPCAs （91%）were detected with DSCT. Although the morphological traits of MAPCAs were complicated and tortuous, we were able to evaluate the spatial relationships between MAPCAs, trachea, and bronchus very precisely. There were no significant complications during the DSCT examinations. Because of the early and precise detection of MAPCSs in neonatal period, cardiac catheter examinations were not necessary until 7.1 （6.9-9.2）months after birth. Conclusion: Detection and spatial evaluation of MAPCAs using DSCT angiography was safely and satisfactorily performed in neonates. DSCT angiography in neonatal period is useful in planning and designing the future unifocalization of MAPCAs.
Background: Patients with adult congenital heart disease （ACHD）who do not attend return-to-clinic （RTC）visits may experience, worsening of the condition and require advanced management. Purpose: To review the problems and countermeasures among ACHD who dropout （DO）during treatment. Subjects and Methods: Group A included 26 patients who made 27 RTC visits after DO, and Group B included 34 patients who did not attend 34 RTC visits after DO. We examined the diagnoses, surgical histories, DO age, New York Heart Association （NYHA）classification, DO reason, RTC reason, referral history, post-RTC treatments, and outcomes. Results: In Group A, DO age was < 15 years in 3, 16-19 years in 12, and adults in 12. The most common DO reasons were impossible diagnosis/treatment during childhood, treatment refusal, lack of subjective symptoms, and change of residence during adolescence and adulthood. Development of subjective symptoms was a commonest RTC reason, and symptomatic patients had worse conditions. Elucidating the clinical history was difficult in 18 patients （67%）at the RTC visit. Intervention was required in all cases with RTC visit, and the NYHA classification levels were similar/improved, except for 1 case of mortality. In Group B, 28 NYHA class I patients had minor conditions, but 4 of 6 class II patients had a DO history. Conclusion: Because DO is an important problem in ACHD treatment, pediatric cardiologist should educate patients from childhood to prevent DO during or after transition to adulthood.
Objective: To determine optimal treatment strategies by examining the long-term outcomes and challenges of different surgical procedures for congenitally corrected transposition of the great arteries （ccTGA）. Subjects: Clinical records of 71 patients with ccTGA, who underwent definitive surgery （physiologic: 45; anatomic: 14; and Fontan-type: 12） in our hospital from November 1977 to October 2013, were retrospectively reviewed. Results: During the follow-up period, there were 7 deaths in 71 patients. Late mortality occurred in 6 patients （in 5 of which TVR was performed） after physiologic repair and early mortality occurred in 1 patient after anatomic repair. While there were no significant differences in the postoperative survival and reoperation rates between the groups, those who underwent physiologic repair with TVR showed a low postoperative survival rate （20-year survival rate with and without TVR: 58.6 and 96.3%, respectively）. After anatomic repair, those treated with Jatene-type DS showed the most favorable prognosis, not requiring reoperation or PMI. In contrast, those treated with Rastelli-type DS frequently needed reoperation and PMI. All Fontan group patients survived, although complications （PLE and hepatic tumor） occurred during the long-term follow-up period. Conclusion: When treating ccTGA, it may be important to develop treatment strategies, according to individual pathological conditions, and stratifying risks.
Objective: The aim of this study is to assess the feasibility and reliability in measurements of left atrial volume using real-time 3D echocardiography （RT3DE） in healthy children. Patients and Methods: A total of 52 healthy children （median age: 5.5 years, range: 0 to 14 years, 23 boys） were enrolled. The 3D volume data were acquired using the Philips iE-33 ultrasound system with the X7-2 probe. The 3D LA volume was measured with the QLAB 7.0. We also evaluated LA volume with the Modified-Simpson （MS） method and the Area Length method （AL） from an apical view obtained from 2D and 3D images. The intraobserver, interobserver, and inter-method agreements were assessed with its limit of agreement （LOA） and Bland-Altman analysis. Results: The feasibility for 3D LA volume measurements was 95%. Mean maximum and minimum LA volume indexes （Max LAVI, Min LAVI） were 17.6 ± 3.7 mL/m2 and 5.9 ± 1.5 mL/m2, respectively. The LA ejection fraction was 66.3 ± 5.2%. There were no age dependency and no gender differences. The correlation of intra- and interobserver agreements of Max LAVI with its LOA were good （r = 0.97, LOA = -1.3± 3.0 mL/m2 and r = 0.90, LOA = 0.5 ± 5.2 mL/m2, respectively）. LA volume measured by RT3DE was well correlated to those measured by the 3D-MS and AL methods （r = 0.92, LOA = 1.0 ± 4.4 mL/m2, r = 0.90, LOA = -0.5 ± 5.4 mL/m2）, while LA measurements by the 2D-MS and AL methods were overestimated （r = 0.89, LOA = -3.3 ± 7.0 mL/m2, r = 0.87, LOA = -3.3 ± 6.6 mL/m2）. Conclusions: The assessment of LA volume by RT3DE is feasible and robust, and to provide reference values for the LA volume in children, further studies are required.