Hiroyuki Yamagishi

Fujikura · Department of Production Engineering

Three-dimensional (3D) printing is an advanced technology for accurately understanding anatomy and supporting the successful surgical management of complex congenital heart disease (CHD). We aimed to evaluate whether our super-flexible 3D heart models could facilitate preoperative decision-making and surgical simulation for complex CHD. The super-f...

Background Premature constriction of the ductus arteriosus (PCDA) makes management difficult in neonates with congenital heart defects, particularly those with ductal-dependent pulmonary circulation. This report highlights the challenges and management of a neonate diagnosed with tricuspid atresia and severe right ventricular outflow tract obstruct...

The purpose of this study is to determine whether adding intravenous methylprednisolone pulse (IVMP) to primary adjunctive prednisolone with intravenous immunoglobulin (IVIG) improves treatment resistance and coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) with a high risk of treatment resistance. This multicenter, prospectiv...

We report an infant case after superior vena cava-to-right pulmonary artery anastomosis with antegrade pulmonary flow in which computational fluid dynamics analysis showed that restriction of antegrade blood flow by the remaining right pulmonary stenosis resulted in reduced shear stress and energy loss in the superior vena cava.

Although the molecular mechanisms underlying congenital heart disease (CHD) remain poorly understood, recent advances in genetic analysis have facilitated the exploration of causative genes for CHD. We reported that the pathogenic variant c.1617del of TMEM260 , which encodes a transmembrane protein, is highly associated with CHD, specifically persi...

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions...

Aims Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categorie...

Objective Congenital heart disease (CHD) is caused by cardiovascular developmental defects and has a global prevalence of ∼1%. The etiology of CHD is multifactorial and remains generally unknown, despite advances in analytical techniques based on next-generation sequencing (NGS). The aim of our study was to elucidate the multi-genetic origin and pa...

Introduction: Kawasaki disease (KD) patients with a high risk of coronary artery aneurysm (CAA) development are well characterized and targeted for intensified primary intravenous immunoglobulin (IVIG) treatment. However, the characteristics of KD patients with a low CAA risk are less well-known. Methods: The present study was a secondary analys...

Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z‐Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving...

The existence of a coronary-to-pulmonary artery fistula (CPF) in pulmonary atresia with ventricular septal defect (PAVSD) potentially affects treatment; however, its clinical features have not been comprehensively described due to the disease's rarity. We reviewed 69 cases from 42 studies to reveal the clinical overview of patients with CPF and PAV...

Although the treadmill and cycle ergometer are commonly used for exercise stress electrocardiography (ECG) testing, they are often difficult to perform with children. We herein evaluated the utility and safety of the 2-minute jump test (2MJT) as a simple, alternative exercise test. One hundred patients, including 60 male patients, with an average a...

Background Pulmonary arterial hypertension (PAH) is a fatal disease, with approximately 10% of cases associated with genetic variants. Recent genetic studies have reported pathogenic variants in the TBX4 gene in patients with PAH, especially in patients with childhood-onset of the disease, but the pathogenesis of PAH caused by TBX4 variant has not...

Long-term complications after the Fontan procedure are important concerns for patients with pediatric and adult congenital heart disease. Although thrombocytopenia due to portal hypertension and hypersplenism is a well-known complication of the Fontan circulation, few studies have reported on its management. Herein we describe a young adult Fontan...

Although the treadmill and cycle ergometer are commonly used for exercise stress electrocardiography (ECG) testing, they are often difficult to perform with children. We herein evaluated the utility and safety of the two-minute jump test (2MJT) as a simple, alternative exercise test. One hundred patients, including 60 male patients, with an average...

A female newborn with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries (MAPCAs) showed an echocardiographic finding of a MAPCA originating from the left coronary cusp (LCC) to the right lung; however, the left coronary artery (LCA) branching was ill-defined. At 3 months of age, synthetic electrocardiogram-g...

Background:The correlation between the Z-score of the left ventricular (LV) diameter and the LV volume-overload due to pulmonary over-circulation in children with ventricular septal defect (VSD) or patent ductus arteriosus (PDA) remains unclear. Methods and Results:The present, retrospective study enrolled 70 children (aged 0.3–16.8 years; 33 males...

Objective To detect risk factors of coronary artery aneurysm (CAA) development in patients with Kawasaki disease determined to have a low risk for resistance to primary IVIG treatment based on Kobayashi score. Study design This study included 1757 predicted IVIG responders from Post RAISE, a large- scale, multicenter, prospective cohort study of K...

A correction to this paper has been published: https://doi.org/10.1007/s00380-021-01882-3

Objectives To test the performance of the Son risk score which was created to predict coronary artery abnormalities from baseline variables in North American patients with Kawasaki disease. Study design The dataset from Post RAISE, the largest prospective cohort study of Japanese patients with Kawasaki disease to date, was used for the present stu...

Recently, targeted therapy has been developed for idiopathic pulmonary arterial hypertension (IPAH). Studies evaluating the prognosis of IPAH have been conducted in adults. However, there is no nationwide survey of pediatric patients with IPAH regarding the long-term prognosis in Japan. Therefore, we investigated the clinical outcomes of Japanese p...

Congenital heart disease (CHD) is the most common life-threatening congenital anomaly. CHD occurs due to defects in cardiovascular development, and the majority of CHDs are caused by a multifactorial inheritance mechanism, which refers to the interaction between genetic and environmental factors. During embryogenesis, the cardiovascular system is d...

Background: Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroi...

Background:Although advances in cardiac surgery have led to an increased number of survivors with congenital heart disease (CHD), epidemiological data regarding the pregnancies and deliveries of patients with repaired CHD are scarce. Methods and Results:In this study, we retrospectively reviewed the clinical outcomes of pregnancies and deliveries o...

Background Although Kawasaki disease (KD) is known to cause anemia, the relationship between its prognosis and hemoglobin level is less well known.Methods We herein performed a secondary analysis of data from a previous study (Post-RAISE). Children aged 6 months to 2 years at the time of KD diagnosis were enrolled. Decreased hemoglobin was defined...

Purpose In lung transplantation, ischemia-reperfusion injury (IRI) plays a critical role in the development of primary graft dysfunction. Among cell deaths induced by IRI, regulated necrosis has been garnering much attention. Above all, necroptosis is well known, and there are some reports on necroptosis inhibition attenuated IRI improvement in sol...

Pulmonary vasculature in mice develops through two main mechanisms, namely angiogenesis and vasculogenesis. At embryonic day (E) 9.5, vascular endothelial marker Tie2-driven LacZ expression in whole-mount transgenic lungs showed continuity between the primitive lung vasculature and the aortic sac [1]. Scanning electron microscopic study of vascular...

There is growing evidence that resident progenitor cell populations exist in murine lung tissues and differentiate into a mesenchymal cell lineage [1, 2]. Stem cell antigen-1 (Sca-1) is a cell surface glycoprotein, initially found in murine bone marrow–derived stem cell subtypes, such as hematopoietic stem cells. Some studies showed Sca-1 expressio...

The two cardiac progenitor cell lineages, cardiac neural crest cells (cNCCs) and the second heart field (SHF), play key roles in the development of the cardiac outflow tract (OFT). Both cardiac progenitor cells interact with each other and contribute to OFT formation cooperatively. The neurovascular guiding molecule, semaphorin 3c (Sema3c), is thou...

The T-box family genes are evolutionarily conserved transcription factors. In particular, Tbx4 and Tbx5 are closely conserved and play crucial roles in development and organogenesis. Tbx4 is essential for hindlimb and allantoic vessel formation [1]. It is also highly expressed in the lung mesenchyme (Fig. 8.1), initially expressed at embryonic day...

Inositol triphosphate receptor (IP3R) is an intracellular Ca2+ release channel located on the membrane of the sarco/endoplasmic reticulum (SR/ER), a major intracellular storage site for Ca2+. There are three subtypes of IP3R (IP3R1, 2, and 3), each of which is known to have versatile roles in the pathophysiology of many organs [1].

Pulmonary hypertension (PH) is a frequent complication in patients with congenital heart disease (CHD), before or after cardiac surgery. According to the recent clinical classification, PH associated with CHD is categorized into subclasses depending on the pathogenesis: (1) Eisenmenger syndrome, (2) left-to-right shunts, (3) PH with coincidental CH...

Pulmonary arterial hypertension (PAH) is a lethal disease [1]. Although mutations in BMPR2 and other genes have been reported, the genetic causes in large numbers of patients, especially with sporadic PAH, remain unknown. In 2013, Kerstjens-Frederikse et al. first reported TBX4 mutations in patients with PAH [2]. TBX4 is an essential transcription...

Cardiac neural crest (CNC) cells are pluripotent cells derived from the dorsal neural tube that migrate and contribute to the remodeling of pharyngeal arch arteries and septation of the cardiac outflow tract (OFT). Numerous molecular cascades regulate the induction, specification, delamination, and migration of the CNC. Extensive analyses of the CN...

This open access book focuses on the molecular mechanism of congenital heart disease and pulmonary hypertension, offering new insights into the development of pulmonary circulation and the ductus arteriosus. It describes in detail the molecular mechanisms involved in the development and morphogenesis of the heart, lungs and ductus arteriosus, cover...

Congenital heart diseases (CHDs) involving the outflow tract (OFT), such as persistent truncus arteriosus (PTA), lead to mortality and morbidity with implications not only in the heart, but also in the pulmonary vasculature. The mechanisms of pulmonary artery (PA) development and the etiologies underlying PA disorders associated with CHD remain poo...

A 7-month-old boy with pulmonary atresia and an intact ventricular septum underwent a bidirectional Glenn operation. Perioperative intubation lasted for 8 hours, and immediately after extubation, the boy presented with severe inspiratory stridor and chest retraction. Diagnosis of bilateral vocal cord paralysis was made based on the findings of flex...

Purpose Molecular hydrogen (H2) has been reported as having protective effects on ischemia-reperfusion injury (IRI) in various organs. However, most of the reports are on inhalation of H2. Our group has previously reported the protective effects of H2-rich solution on lung IRI in a rat hilar-clamp model (Takahashi M, et al. Eur J Cardiothorac Surg...

Purpose To evaluate the effects of pathogenic bacteria (PB) in the respiratory tract, we investigated perioperative airway pathogens of recipients and donors in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT). Methods Between Jun. 2008 and Sep. 2018, 193 lung transplants (LTxs) were performed at our institu...

Purpose Lung transplantation is indicated in patients with severe pulmonary arterial hypertension (PAH). Living donor lobar lung transplantation (LDLLT) may be considered in patients who might not survive the longer waiting duration for cadaveric lung transplantation (CLT). This study compared the outcomes of LDLLT and CLT in patients with PAH. Me...

Purpose Lung transplantation is an effective therapy for end-stage patients with chronic respiratory failure due to various benign lung diseases. The organ shortage crisis is a serious problem, so it is required to develop alternative therapies. There have been reports of organ organoids ameliorating organ function but there have been few reports o...

Background: Recent progress in surgical and intensive care has improved the prognosis of congenital heart disease (CHD) associated with heterotaxy syndrome. Less is known, however, about pulmonary vascular complications in these patients. Methods and Results: We reviewed medical records of 236 patients who were diagnosed with polysplenia syndrome a...

Pulmonary arterial hypertension (PAH) is a progressive disease associated with vasoconstriction and remodeling. Intracellular Ca²⁺ signaling regulates the contraction of pulmonary arteries and the proliferation of pulmonary arterial smooth muscle cells (PASMCs); however, it is not clear which molecules related to Ca²⁺ signaling contribute to the pr...

Resting bradycardia is an important symptom for early diagnosis of anorexia nervosa (AN) during weight loss, and it improves with body-weight recovery. However, chronotropic incompetence (CI) in exercise is observed in some patients with AN despite amelioration of resting bradycardia in the recovery phase. We examined the relationship between CI in...

Background: The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVI...

Background: Mortality rates may be high in adult Fontan patients; however, the clinical determinants remain unclear. Purpose: We conducted a prospective multicenter study of adult Fontan survivors to determine the 5-year mortality rate and clarify the determinants. Method and results: We followed 600 adult Fontan survivors from 40 Japanese ins...

Pediatric pulmonary hypertension after surgery for congenital heart disease is a significant complication. We present a case of living-donor lung transplantation for a 12-year-old girl with pulmonary hypertension after surgical repair of transposition of great arteries. Despite repairing the transposition of great arteries, her growth was severely...

A 1-year-old infant with asplenia syndrome and congenital heart disease consisting of common atrium, common inlet left ventricle with a common atrio-ventricular (AV) valve, pulmonary atresia, and total anomalous pulmonary venous connection was admitted to our hospital for radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT)...

Importance Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective To clarify the association of the z score with time-dependent CE occurrence in patients with K...

Children with single ventricle physiology have complete mixing of the pulmonary and systemic circulations, requiring staged procedures to achieve a separation of these circulations, or Fontan circulation. The single ventricle physiology significantly increases the risk of mortality in children undergoing non-cardiac surgery. As liver transplantatio...

Mulibrey nanism (MUL) presents with growth failure and multiple organ manifestations and is caused by mutations in TRIM37. Here, we report on the first case series of Japanese patients with MUL who developed congestive heart failure due to constrictive pericarditis. Our case series suggests that early diagnosis and total pericardiectomy before adhe...

The cardiac neural crest cells (cNCCs) and the second heart field (SHF) play key roles in development of the cardiac outflow tract (OFT) for establishment of completely separated pulmonary and systemic circulations in vertebrates. A neurovascular guiding factor, Semaphorin 3c (Sema3c), is required for the development of the OFT, however, its regula...

Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expressio...

Timothy syndrome (TS) is a congenital long QT syndrome that is associated with syndactyly and mutations in CACNA1C, encoding an L-type voltage-dependent calcium channel, Cav1.2. Recently, TS has been associated with autism and other psychological disorders. This case indicated bradycardia by prenatal screening and was diagnosed as TS by the occurre...

The embryonic-maternal interface of the placental labyrinth, allantois, and yolk sac are vital during embryogenesis; however, the precise mechanism underlying the vascularization of these structures remains unknown. Herein we focus on the role of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular Ca2+ release channels, in...

The placental circulation is crucial for the development of mammalian embryos [1]. The labyrinth layer in the placenta is created by extensive villous branching of the trophoblast and vascularization arising from the embryonic mesoderm. In the labyrinth, materials are exchanged between the maternal and embryonic circulation. Recently, we have found...

Progenitor cells, derived from the cardiac neural crest (CNC) and the second heart field (SHF), play key roles in development of the cardiac outflow tract (OFT), and their interaction is essential for establishment of the separate pulmonary and systemic circulation in vertebrates. 22q11.2 deletion syndrome (22q11DS) or Takao syndrome is the most co...

Congenital heart disease is still the leading cause of death within the first year of life. Our lab forces on understanding the morphology of congenital heart disease. Outflow tract anomalies, including abnormal alignment or septation, account for 30 % of all congenital heart disease. To solve the developmental problem of these defects, we are inte...

Early progressive pulmonary arterial hypertension (PAH) is often observed in patients with heterotaxy/polysplenia especially who have an intracardiac systemic-to-pulmonary shunt. However, its etiology is uncertain and its management is not well established. There was only a Japanese report about PAH in consecutive patients with heterotaxy/polysplen...

Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 fro...

Regional plot for R wave in V5 focused to TBX3. (DOCX)

Multiple linear regression analysis to estimate clinical factors accounting for individual variation in LVH parameters. (DOCX)

We used the multiple linear regression analysis to estimate clinical factors accounting for individual variation in LVH parameters, after removing outliers defined as the values that are either higher or lower than 4*SD from the mean. (DOCX)