We isolated cardiac stem cells （CSCs）, named CSC-4A, from adult rats that revealed high GATA4 expression levels. When the primary cardiomyocytes from the adult rat heart were co-cultured with CSC-4A with or without inserts （the filter that separates these two types of cells to avoid direct contact）, the cardiomyocytes sustained the contraction compared with the cardiomyocytes cultured alone or those cultured with fibroblasts or GATA4 low CSCs. The medium from the co-cultures of CSC-4A and cardiomyocytes contained higher IGF-1 concentrations. CSC-4A did not release IGF-1 or expressed IGF-1 mRNA. Therefore, CSC-4A may express some soluble factors that enhance IGF-1 expression in co-cultured cardiomyocytes. Identification of such soluble factors would enable us to develop the appropriate drugs or regeneration materials or a combination of both, which are key to the development of more efficient regenerative medical tools in the future.
Information is provided that a medical doctor must know when using an unapproved or off-label drug. News of the death of an infant sedated with propofol, a contraindicated drug for patients under mechanical ventilation in the intensive care unit, has developed into a serious social problem. Although, as a general rule, unapproved or off-label and contraindicated drugs should not be used, they are indispensably used at the discretion of medical doctors, especially when no other treatment has been established. However, this discretion does not legally protect doctors from medical law suits if such unapproved or off-label drugs have harmful effects, even if they obtained the approval of the ethical committee and informed consent from the patients. This is because discretion is considered a legal concept that guides the decision to violate a medical standard, and a serious harmful effect caused by an unapproved or off-label drug would suggest that the violation was a deviation from the discretion of a medical doctor. The drug information sheet is the only official document provided by the Pharmaceutical Affairs Law, and therefore, the standard of medical treatment depends on it. It goes without saying that we must avoid using drugs in contraindicated ways, since previous evidence has demonstrated them unsafe and risky. Medical doctors should read the drug information sheet before using medicines for the first time.
Congenital heart disease （CHD）occurs in nearly 1% of all live births and is the major cause of infant mortality and morbidity. Despite its clinical importance, the underlying genetic etiology of most CHD remains unknown because of the multi-factorial nature. As CHD results usually from abnormal morphogenesis in specific structural regions of the developing heart and vessels, an understanding of the individual modular steps in cardiovascular morphogenesis is particularly relevant to CHD. Transcription factors Nkx2.5/Csx and dHAND/Hand2 are together essential for ventricular morphogenesis. TBX1, a major genetic determinant of 22q11.2 deletion syndrome, regulates second heart field （SHF）cells during outflow tract development. Mutations of GATA6 result in outflow tract defects implicated in the interaction between the SHF and neural crest progenitors. Finally, intracellular calcium signaling redundantly mediated by three subtypes of IP3 receptors may play essential roles in region-specific development of the heart. Through the advance of molecular biology combined with human genetics, basic and clinical understanding of cardiovascular development and diseases have emerged. Elucidation of the mechanisms from gene to morphology would provide targets for prevention or genetic intervention of CHD as suggested in Professor Takao’s will.
Prosthetic materials currently used in pediatric cardiovascular surgery such as expanded polytetrafluoroethylene （ePTFE）, lack growth potential and are prone to thrombosis and infection. We developed a novel tissue-engineered vascular graft （TEVG） using a biodegradable scaffold seeded with bone marrow mononuclear cells. By use of the TEVG, vascular neotissue forms and, a living, biocompatible conduit was created as the scaffold degraded. We performed a pilot clinical study in Japan in 2001 using TEVG as a conduit for extracardiac total cavopulmonary connections in patients with single ventricle cardiac anomalies. Twenty-five TEVGs were implanted with ten-year follow up. The TEVGs were shown to function well without evidence of aneurysmal change or calcification. No graft had to be replaced and there was no graft related mortality. Four patients required catheter intervention for the stenosis. We started a clinical trial under Food and Drug Administration （FDA） approval in the United States in 2011. To develop the second generation of the TEVG, extensive laboratory research is underway to figure out the mechanism of vascular tissue formation and stenosis formation using various genetically engineered mouse models.
Because of the various causes of pediatric heart failure （circulatory failure）, there are few strong evidences regarding drug treatment for pediatric heart failure. Using drugs aimed at improving hemodynamics （catecholamines, diuretics, etc.）, monitoring hemodynamics and clinical conditions enable us to judge the therapeutic value of the drugs. However, it is impossible to judge the effectiveness of the drugs aimed at improving prognosis （blockades of renin-angiotensin-aldosterone system and beta-blockers） from each of the patients. Using the latter drugs, we have to make the therapeutic plans based on a few reports in pediatric patients and many reports in adult patients with heart failure.
Pacemaker is the only effective permanent therapy for bradycardias. There are few cases which have indication of pacemaker implantation in children in comparison with adults. On the grounds that children have small body, grow and need long-term management, there are some different pointes about implantation method and complications. In 2011, guideline of pacemaker implantation has been updated by the study group of Japanese circulation society and others. Pacemaker constricted by battery and leads, pacing methods are temporary and permanent, electrodes are endcardiac and myocardia. Function of pacemaker is expressed by 3-4 characters code display. We call the pacing style which pace atrium preceding and after that ventricle as physiological pacing, and it is advantage of circulate condition. We should select appropriate pacemaker implantation method for each cases and set parameters. In pacemaker clinic, we check 12 lead ECG, chest （and abdominal） radiographs, and parameters check by programmer. And keeps appropriate management of pacemaker by optimization of parameter setting, prediction of generator remaining term, and avoidance of troubles or complication.
Background: Starting in infancy, patients with congenital heart disease （CHD） encounter specific difficulties that they must work to overcome as they age. This study was conducted in order to identify the structure of resilience related to illness experiences, and development of an assessment tool to measure resilience related to illness experiences. Methods: A questionnaire focusing on resilience was distributed to 500 individuals diagnosed with CHD. In total, 178 responses were obtained. The questionnaire was developed based on an interview with a focus group conducted in a prior study. For statistical interpretation and analyses of questionnaire data, factor analysis and Mann-Whitney U-tests and other tests were conducted using IBM SPSS Statistics software （version 22）. Results: Completed questionnaires were received from 178 individuals diagnosed with CHD （95 males and 83 females） aged between 10 and 32 years （mean age 17.2± 5.8 years）. Factor analysis identified the following three factors: a） I can understand my illness; b） I exhibit positive behavior; c） I do not engage in strenuous physical activity. Cronbach’s α values for the three factors ranged from 0.706 to 0.791. With differences or correlation in resilience related to illness experiences due to back-ground, in a）, the score had a weak association with age, in b）, the serious group had a low score and in c）, there were no differences in background. Conclusions: The results of this study can be summarized as follows: 1） It is important that an understanding of illness is promoted amongst children in the early developmental stage; 2） it is important that positive behavior and thinking is promoted amongst the serious group; and 3） in addition to resilience, “I do not engage in strenuous physical activity” is a characteristic trait for a person with CHD.
Background: Recently the outcome of extremely low birth infants （ELBWI）has been improving, whereas the reports of treatment are still limited for those with complications of congenital heart disease. We report four cases of ELBWI who successfully underwent corrective cardiac surgery for congenital heart disease with pulmonary overcirculation. Case: 1）Atrial septal defect: Gestational Age （GA）29 weeks, birth weight （BW）504 g. A female infant developed pulmonary hypertension at 2 months of age, which was treated with oral sildenafil. The defect was closed at 4 months. 2）Complete atrioventricular septal defect: GA 26 weeks, BW 670 g. A Trisomy 21 male infant who underwent pulmonary artery banding at 2 months. Corrective surgery was performed at 4 months. 3）Ventricular septal defect: GA 27 weeks, BW 412 g. A male infant presented with severe pulmonary hypertension at 5 months. He was treated with oxygen and sildenafil, subsequently underwent surgical closure at 10 months of age. 4）Truncus arteriosus: GA 29 weeks, BW 752 g. A girl underwent bilateral pulmonary artery banding at 7 months. After being optimized with oxygen therapy, sildenafil, and beraprost, she underwent corrective surgery at the age of 25 months. Conclusion: Extremely low birth weight patients with congenital heart disease and pulmonary overcirculation can be successfully treated by intensive control of pulmonary blood flow and pulmonary hypertension. Surgery should not be delayed for premature infants with congenital heart disease, who might benefit from early and aggressive treatment.
Background: Outcomes for fetuses with minor abnormal sonographic findings detected by fetal cardiac echocardiography remain unclear. Methods: We retrospectively reviewed the minor abnormal sonographic findings in 1,753 fetuses （26.9 ± 2.2 weeks gestation） whose screening heart scans were performed by an obstetrician （Level I screening） and subsequently performed detailed fetal cardiac scans by a pediatric cardiologist （Level II screening） at our institute between May 2008 and May 2013. In this study, a minor abnormal sonographic finding was defined as slight valvular regurgitation and structural abnormalities with slight rhythm disorders, which could not affect fetal hemodynamic parameters. Results: There were 11 cases of premature atrial contraction, 9 cases of mild tricuspid regurgitation （TR）, 1 cases of mild mitral regurgitation, 4 cases of mild pulmonary regurgitation, 3 cases of ductus arteriosus tortuosity, and 2 cases of mirror image dextrocardia. One case of TR gradually developed into mild to moderate regurgitation with mild cardiomegaly during follow-up and was diagnosed as an Ebstein anomaly without hypoplastic right ventricle after birth. All cases with the other sonographic findings, including the remaining 8 cases with TR, were recognized transiently or unchanged Conclusions: Minor abnormal sonographic findings detected by fetal cardiac screening revealed mostly favorable outcomes, and there were no cases of specialized treatment. However, some may develop and become apparent later in gestation, so repeat follow-up fetal echocardiography should be required in order to confirm definite organic heart defect.
Background: The preoperative strategy is important for successful hybrid therapy （HT）. Purpose: To investigate the impact of the preoperative strategy on HT. Subjects: Seven patients received HT at our hospital. The diagnosis was 1） tricuspid atresia complicated by Cantrell syndrome （1 case）, 2） pulmonary atresia （PA） with ventricular septal defect （VSD） and major aortopulmonary collateral arteries （MAPCAs） （1 case）, 3） total cavopulmonary connection （TCPC） candidates with thromboembolism of the left pulmonary artery （LPA） （4 cases）, and 4） transposition of the great arteries （TGA） with the hypoplastic right ventricle （1 case）. Method: The procedures were 1） TCPC via lateral thoracotomy and coil embolization for a left Blalok-Taussig shunt （BTS） in the patient with Cantrell syndrome, 2） direct stenting for pulmonary stenosis that was inaccessible by catheter intervention, 3） direct stenting for LPA thromboembolism, and 4） trans-right atrial balloon atrial septostomy （BAS） via anterior thoracotomy. In all patients, we investigated the imaging data carefully and simulated treatment with all staff participating, so that everyone understood the processes and procedures. Results: All procedures were performed successfully and less invasively. TCPC for Cantrell syndrome was done via lateral thoracotomy. A palliative Rastelli procedure could be performed for PA with VSD and MAPCAs. The TCPC candidates with thromboembolic LPA avoided the future risk of unilateral pulmonary circulation. BAS could be done safely for TGA. Conclusion: Even if an institution does not have a Hybrid Suite, sufficient preoperative planning for HT and good teamwork among the staff can achieve successful results.
Objective: To assess the current status of deep sedation for diagnostic and interventional cardiac catheterization procedures performed at Japanese Society of Pediatric Cardiology and Cardiac Surgery institutions. Methods: Questionnaires were distributed to institutions belonging to the Japanese Society of Pediatric Cardiology and Cardiac Surgery （JSPCCS） regarding general anesthesia and deep sedation administered for cardiac catheterization procedures. Results: At 60 institutions, 9,942 cases of cardiac catheterizations procedures are performed per year. Among these, 3,694 procedures （37%） are performed under general anesthesia or deep sedation by anesthesiologists and 4,979 （50%） are performed under deep sedation by pediatricians. While in deep sedation by pediatricians, electrocardiographic monitors and pulse oximeters are used in 52/52 （100%） institutions and end-tidal carbon dioxide monitors in 8/52 （15%）. Vital signs are continuously recorded at 5-minute or shorter intervals in 15/37 （41%） institutions. Conclusion: Pediatricians administered deep sedation for 50% of cardiac catheterization procedures in Japan. The use of end-tidal carbon dioxide monitors and the interval for recording vital signs were considered insufficient. Issuing JSPCCS guidelines on administering deep sedation for cardiac catheterization procedures and revising medical fees may improve the current situation.
Background: We aimed to clarify the issues of the percutaneous transconduit puncture and the results of catheter ablation of supraventricular tachycardia with an extracardiac total cavopulmonary connection （eTCPC） Method: Four cases of tachyarrhythmia after the eTCPC undergoing catheter ablation via the transconduit approach were included in this study. We analyzed patient characteristics, issues associated with the transconduit puncture and catheter ablation, and the results. Results: The age at the time of catheter ablation was from 13 to 19. Three had a right isomerism heart and single ventricle and the other had a double outlet of the right ventricle. The targeted arrhythmias were atrioventricular reciprocating tachycardia via the accessory pathway （AVRT via AP） in one, AVRT via AP and a tachycardia involving twin atrioventricular nodes in one, intra-atrial reentrant tachycardia in one, and paroxysmal junctional tachycardia in one. All patients were successfully ablated via the transconduit approach. The interval from the eTCPC to the catheter ablation was three to twelve years. It was difficult to puncture the straight shaped conduit and ringed artificial conduit. We needed to devise a way to advance the long sheath into the atrium and had a hard time treating complicated arrhythmias, such as intra-atrial reentrant tachycardia and junctional tachycardia. Conclusion: We experienced four cases of catheter ablation for tachyarrhythmia using the transconduit approach. This technique will be a useful technique for treating increasing tachycardias after an eTCPC. It is important to clarify the issues and establish the safety of this technique in the future.