With dramatic advances in the field of molecular genetics, the investigation of the genetic background in pulmonary hypertension has also remarkably improved. In 2018, the 6th World Symposium on Pulmonary Hypertension (6th WSPH) identified 17 genes as causative factors for pulmonary arterial hypertension (PAH). In this review, the author discusses the candidate causative genes of PAH that have been identified consecutively after the 6th WSPH. Furthermore, interesting reports on new modifier and susceptibility genes for PAH and the methods of interpreting these genes are discussed. This review also presents other noteworthy basic studies.

Direct cellular reprogramming provides a new strategy for tissue regeneration, especially to the adult heart. However, endogenous cardiomyocytes have limited regenerative capacity. Since our first report of direct cardiac reprogramming from cardiac fibroblasts with three cardiac developmental transcriptional factors (Gata4, Mef2c, and Tbx5), numerous international studies have been reported to reveal the molecular mechanisms of cardiac reprogramming and improve the efficiency of this nascent technology for cardiac regenerative medicine. These advancements include additional transcriptional factors, microRNAs, epigenetic factors, secreted factors, and cellular microenvironment. Cardiac reprogramming of human fibroblasts has also improved. Although direct cardiac reprogramming may resolve the difficulties in applying induced pluripotent stem cells for cardiac regeneration, numerous challenges remain for future clinical application. In this review, we will provide an update on recent advances in research on direct cardiac reprogramming and discuss the perspectives and challenges of this technology in clinical applications.

Background: Radiation exposure doses during pediatric catheterization may be effectively compared using dose area product per body weight (DAP/BW). Hence, we used DAP/BW to determine the effects of radiation dose reduction caused by era and technology change.

Methods: This study included 2757 patients (＜15 years old) who underwent cardiac catheterization at our institute between 2008 and 2019. The procedure included transcatheter atrial septal defect closure (Group A; n＝107), balloon dilatation for pulmonary stenosis (BAP) (Group B; n＝117), coil embolization for aortopulmonary collateral arteries (Group C; n＝395), diagnostic procedures (Group D; n＝1918), and radiofrequency ablation (Group R; n＝220). We compared the radiation doses during three time periods (period 1, 2008–2011; period 2, 2012–2016; period 3, 2017–2019).

Results: The DAP/BW levels decreased in Groups A and R at time period 3 (Group A: 1, 13.5; 2, 13.5; 3, 9.8; p＜0.05; Group R: 1, 51.6; 2, 33.4; 3, 20.5; p＜0.05). The DAP/BW in Group C remained unchanged. In Groups B and D, the DAP/BW was highest in period 3 (Group B: 1, 76.8; 2, 108.5; 3, 117.0; p＜0.05; Group D: 1, 41.0; 2, 45.1; 3, 46.0; p＜0.05).

Conclusion: In Groups A and R, radiation doses were reduced by changes in technology and experience. In Groups B and D, the radiation doses increased because of the complexity of the lesion or anatomy. Therefore, DAP/BW can be an indicator of radiation dose reduction in pediatric cardiac catheterizations.

Background: The heart-rate–corrected QT interval (QTc) by automatic measurements is longer than that by manual measurements. The reference QTc values used for screening QT prolongation in school cardiac screening are generated by manual measurements; when such values are used in automatic measurements, overscreening occurs.

Methods: We retrospectively analyzed the electrocardiogram records of all first- and seventh-grade students who underwent school cardiac examinations in Kagoshima City from 2009 to 2013. Only students screened using the automated QTc values underwent manual measurements, and those who exceeded the manual reference QTc values were selected. The automated reference values were developed according to the automatically measured QTc values of the extracted students.

Results: Out of 54,586 students, 1233 (2.3％) were screened using manual measurement. Among them, 52 (0.10％) exceeded the reference QTc values. The lowest automated QTc values were 445 and 447 ms for first-, 463 and 451 ms for seventh-grade male and female students, respectively.

Conclusion: The reference values for the automatic screening of QT prolongation were 445 and 450 ms in first- and seventh-grade students, respectively.

A 16-year-old male with complete congenital atrioventricular block since 1 year old was treated by epicardial pacemaker lead implantation. At 9 years old, he was diagnosed with supravalvular pulmonary artery stenosis resulting from epicardial pacemaker leads with cardiac strangulation as the possible cause. Transient ST change was seen only in the exercise tolerance test, with no chest pain, indicating that myocardial ischemia was absent. The deterioration status of supravalvular pulmonary artery stenosis was assessed by catheterization. With his arms raised, he was injected with a small amount of contrast media, suddenly, he lost consciousness. Electrocardiography showed ST segment alterations after frequent premature ventricular contractions, followed by junctional bradycardia that rapidly progressed to asystole. Hence, transient ischemia caused by arm raising or frequent premature ventricular contractions and deterioration of the coronary artery compression was suspected. The leads were then removed in an urgent surgery. In conclusion, contrast-enhanced computed tomography should be conducted in patients with cardiac strangulation, and earlier lead exchange should be performed because of the rapid deterioration of myocardial ischemia.

Hypertrophic cardiomyopathy (HCM) is generally accompanied with left ventricular diastolic dysfunction, leading to a poor prognosis in patients with congenital heart diseases. An atrial septal defect (ASD) rarely needs surgical intervention in infancy. However, we report a case of HCM-complicated ASD that required fenestrated ASD closure in early infancy. A 5-month-old girl with cardiofaciocutaneous syndrome was transferred to our institution because of severe lung congestion triggered by fever and convulsions. Echocardiography revealed right ventricle enlargement secondary to left ventricular diastolic dysfunction and severe pulmonary hypertension. She was intubated and supported with mechanical ventilation, with nitric oxide inhalation. Immediately, her ventricular interdependence and circulatory dynamics improved. On hospitalization day 18, cardiac catheterization showed pulmonary hypertension improvement with high pulmonary blood flow and low cardiac output. However, she had severe lung congestion triggered by a repeat convulsion on day 60. Thus, we performed ASD partial closure with 4 mm fenestration. Postoperative cardiac catheterization showed a good control of pulmonary blood flow, with a Qp/Qs of 1.3. In conclusion, fenestrated ASD closure is a safe and effective treatment option for left ventricular diastolic dysfunction in early infants with ASD and HCM.

Secondary cardiomyopathy related to a systemic disorder should be ruled out when diagnosing idiopathic cardiomyopathy. Nutrient deficiency is a known cause of secondary cardiomyopathy. Herein, we report a case of secondary cardiomyopathy caused by carnitine deficiency with short bowel syndrome. A 6-year-old girl receiving total parenteral nutrition for short bowel syndrome manifested cold symptoms for 5 days that resulted in orthopnea, thereby prompting hospitalization. Chest radiography showed a cardiothoracic ratio of 60％, and echocardiography revealed fraction shortening of 17％. Her operated bowel was bleeding, causing chronic anemia, obtaining a hemoglobin level of 6.7 g/dL. Cardiac function was not improved by blood transfusion and milrinone therapy but improved in merely 3 days by L-carnitine administration. The free carnitine level was found to be low after treatment (17.8 µmol/L); therefore, she was diagnosed with secondary cardiomyopathy caused by carnitine deficiency. In conclusion, carnitine deficiency can cause secondary cardiomyopathy; hence, the serum carnitine level of patients at risk should be examined periodically. Furthermore, the risk of cardiomyopathy must be considered in patients with increased cardiac load, including anemia and infection. Thus, early administration of L-carnitine is necessary for secondary cardiomyopathy caused by carnitine deficiency.

Infective obstruction of a modified Blalock–Taussig shunt (mBTS) has remained poorly investigated. Here, we present six cases of this condition and discuss the therapeutic strategy. The underlying congenital heart diseases were tetralogy of Fallot (n＝2), complete atrioventricular septal defect with pulmonary atresia (n＝1), pulmonary atresia with an intact ventricular septum (n＝1), tricuspid atresia (n＝1), and truncus arteriosus communis persistens (n＝1). Only two cases had infection during the diagnosis of mBTS obstruction. The bacterial pathogens were methicillin-resistant coagulase-negative staphylococci (n＝3), Salmonella spp. (n＝1), Serratia marcescens (n＝1), and Staphylococcus epidermidis (n＝1). Furthermore, three cases had pseudoaneurysm at the proximal anastomotic site of the mBTS. Pulmonary blood flow supply was established by mBTS recanalization through catheterization (n＝1), right ventricular outflow tract reconstruction (n＝1), original BTS utilization (n＝2), and a larger-sized right ventricle-pulmonary artery conduit (n＝1). Only one patient with no alternative therapeutic options was applied with prosthetic materials. Foci of infection, such as artificial shunt graft and pseudoaneurysm, were completely removed, except in one patient who underwent effective catheterization. In conclusion, possible infection must be considered in patients with mBTS obstruction. Pseudoaneurysm at the proximal anastomotic site of the mBTS suggests infective obstruction. Furthermore, the therapeutic strategy includes 1) treatment for hypoxemia, 2) establishment of a new supply of pulmonary blood flow, 3) surgery without using prosthetic materials, and 4) removal of infection foci.

Patients with severe and complex congenital heart diseases frequently require multiple repeat sternotomies. We recently performed cardiac surgery through the fifth sternotomy in a 29-year-old female patient with corrected transposition of the great arteries and pulmonary atresia. Previously, she underwent six cardiac operations, including four sternotomies. She also underwent double-switch operation and mechanical valve replacements for mitral and tricuspid positions. Eventually, she manifested repeated ascites, syncope, palpitation, and fatigue. Echocardiography, computed tomography, and cardiac catheterization detected severe left ventricular outflow tract stenosis, severe pulmonary valve insufficiency, and moderate aortic valve insufficiency. Hence, aortic and pulmonary valve replacement and release of the left ventricular outflow tract stenosis were performed, and all four cardiac valves were replaced with mechanical valves. Consequently, her postoperative course was uneventful, with remarkable attenuation of symptoms.