Pharmacological Treatment Practices for Patients With Congenital Heart Disease and Pulmonary Hypertension in Japan: Insights from the Japanese Association of Congenital Heart Disease Registry (JACPHR)

members (JACPHR) Registry Disease Heart Congenital of Association Japanese

Pulmonary hypertension (PH) is a serious complication that impairs the prognosis of congenital heart disease (CHD) patients. The Japanese Association of Congenital Heart Disease with Pulmonary Hypertension Registry (JACPHR) is a nationwide CHD-PH registry in Japan, established in 2021. We aimed to clarify the current status of pharmacological treatment for CHD-PH using JACPHR data. Data from 266 registered CHD-PH cases for JACPHR were analyzed. Patient characteristics revealed a median age of 11.6 years (range: 0.7 to 85 years), with 51.1% having systemic underlying diseases, the most common being Trisomy 21 (27.8%). Pharmacological treatments were used in 69% of cases, with combination therapy in 44%. The use of combination therapy was linked to concurrent PH and a high pulmonary vascular resistance index. Conversely, patients with left heart disease, especially those with total anomalous pulmonary venous return, were less likely to receive combination therapy. Tadalafil and Macitentan were the most commonly used medications in all age groups, according to age-specific analysis. The drug dosages for pediatric patients were either consistent with the guidelines' recommended doses or calculated using adult dosing recommendations. In conclusion, combination therapies for CHD-PH were widely used in Japan, including for pediatric patients, with treatment decisions based on the clinical context and disease severity. This study sheds light on the real-world application of PH-targeted therapies for CHD-PH.


Electromagnetic Interference from a Tablet Inducing Magnet Response in Abdominal Cardiac Implantable Electronic Devices: A Study from Japan

Journal of Pediatric Cardiology and Cardiac Surgery


Characterization of Intracardiac Flow in the Right Ventricle With Pressure and Volume Overload in Children


Analysis of Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease by Aneurysm Severity: Factors Associated With Regression.

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 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the score of their internal diameter in the acute phase: small (<5), medium (5≤<10), and large (≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.

Journal of the American Heart Association


Novel large deletion involving EVC and EVC2 in Ellis-van Creveld syndrome

Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia that is characterized by thoracic hypoplasia, polydactyly, oral abnormalities, and congenital heart disease. It is caused by pathogenic variants in the EVC or EVC2 genes. We report a case of a newborn with a compound heterozygous variant comprising NM_147127.5: c.1991dup:[p.Lys665Glufs*10] in the EVC2 gene and a novel large deletion involving exon 1 in EVC and exons 1-7 in EVC2.


Three-dimensional Imaging of Pulmonary Arterial Vasa Vasorum Using Optical Coherence Tomography in Patients After Bidirectional Glenn and Fontan Procedures

We evaluated pulmonary arterial (PA) vasa vasorum (VV) in Fontan candidate patients with a novel three-dimensional (3D) imaging technique using optical coherence tomography (OCT). This prospective study assessed the development of adventitial VV in the distal PA of 10 patients with bidirectional Glenn circulation (BDG group, 1.6 ± 0.3 years) and Fontan circulation (Fontan group, 3.3 ± 0.3 years), and in 20 children with normal PA haemodynamics and morphology (Control group, 1.5 ± 0.3 years). We assessed the PA VV with two-dimensional (2D) cross-sectional, multi-planar reconstruction (MPR), and volume rendering (VR) imaging. VV development was evaluated by the VV area/volume ratio, defined as the VV area/volume divided by the adventitial area/volume. Compared to the control group, the observed VV number and diameter on 3D images of MPR and VR were significantly higher, and curved and torturous-shaped VV were more frequently observed in the BDG and Fontan groups (P < 0.001, all). The median VV volume ratio was significantly greater in the BDG than in the control group (3.38% vs. 0.61%; P < 0.001). Although the VV volume ratio decreased significantly after the Fontan procedure (2.64%, P = 0.005 vs. BDG), the ratio remained higher than in the control group (P < 0.001 vs. control). 3D OCT imaging is a novel method that can be used to evaluate adventitial PA VV and may provide pathophysiological insight into the role of the PA VV in these patients.

European Heart Journal Cardiovascular Imaging


Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 1.

A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17-/- mEFs) exogenously expressing each of these mutants, phorbol 12-myristate 13-acetate-stimulated shedding was strongly reduced compared with wild-type ADAM17. Thus, in vitro functional assays demonstrated that both missense variants cause the loss-of-function of ADAM17, resulting in the development of NISBD1. Our study further expands the spectrum of genetic pathology underlying ADAM17 in NISBD1 and establishes functional assay systems for its missense variants.


Descending aorta flow pattern in a neonate with patent ductus arteriosus coexisting with liver hemangioma.


Next-generation sequencing for the diagnosis of patients with congenital multiple anomalies and / or intellectual disabilities

Background : In clinical practice, a large proportion of patients with multiple congenital anomalies and/or intellectual disabilities (MCA / ID) lacks a specific diagnosis. Recently, next-generation sequencing (NGS) has become an efficient strategy for genetic diagnosis of patients with MCA/ID. To review the utility of NGS for the diagnosis of patients with MCA / ID. Patients with MCA/ID were recruited between 2013 and 2017. Molecular diagnosis was performed using NGS-based targeted panel sequencing for 4,813 genes. Promising causative variants underwent confirmation by Sanger sequencing or chromosomal microarray. Eighteen patients with MCA/ID were enrolled in this study. Of them, 8 cases (44%) were diagnosed by targeted panel sequencing. Most of diagnosed patients were able to receive better counseling and more appropriate medical management. NGS-based targeted panel sequencing seems to be an effective testing strategy for diagnosis of patients with MCA/ID. J. Med. Invest. 67 : 246-249, August, 2020.

The Journal of Medical Investigation : JMI


Pregnancy and Delivery in Patients With Repaired Congenital Heart Disease - A Retrospective Japanese Multicenter Study

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 of women with repaired CHD. Overall, 131 women with repaired CHD were enrolled and there were 269 gestations. All patients were classified as New York Heart Association (NYHA) Class I or II. The prevalence of cesarean sections was higher in patients with (CyCHD) than without (AcyCHD) a past history of cyanosis (51% vs. 19%, respectively; P<0.01). There were 228 offspring from 269 gestations and the most prevalent neonatal complication was premature birth (10%), which was more frequent in the CyCHD than AcyCHD group (15.7% vs. 5.6%, respectively; P<0.01). Five maternal cardiac complications during delivery were observed only in the CyCHD group (8%); these were classified as NYHA Class II and none was fatal. Delivery was successful in most women with repaired CHD who were classified as NYHA Class I or II, although some with CyCHD and NYHA Class II required more attention. Cesarean sections were more common in the CyCHD than AcyCHD group, and CyCHD may be a potential risk for preterm deliveries.


Successful treatment by stent implantation for systemic-to-pulmonary shunt obstruction due to a Staphylococcus aureus abscess: A case report

A 13-year-old girl with a single ventricle and bilateral systemic-to-pulmonary shunts developed hypoxia due to shunt stenosis, which was caused by a methicillin-sensitive Staphylococcus aureus abscess. Stent implantation associated with appropriate antibiotic administration was crucial to dilate and maintain shunt patency.


Molecular diagnosis of an infant with TSC2/ PKD1 contiguous gene syndrome

A 1-month-old Japanese infant with cardiac rhabdomyoma was diagnosed with / contiguous gene syndrome by targeted panel sequencing with subsequent quantitative polymerase chain reaction that revealed gross monoallelic deletion, including parts of two genes: exons 19-42 of and exons 2-46 of . Early molecular diagnosis can help to detect bilateral renal cyst formation and multidisciplinary follow-up of this multisystem disease.


Assessment of Right Ventricular Function by Isovolumic Acceleration of Pulmonary and Tricuspid Annulus in Surgically Repaired Tetralogy of Fallot

Assessment of right ventricular (RV) function is quite important in patients with surgically corrected tetralogy of Fallot (TOF). However, quantitative assessment of RV function remains challenging, mainly because of the complex RV geometry. This prospective study investigated isovolumic acceleration (IVA), a parameter of myocardial systolic function not influenced by either preload or afterload, using tissue Doppler imaging. We evaluated IVA measured on pulmonary annulus (PA-IVA) and tricuspid annulus (TA-IVA), because we considered that PA-IVA and TA-IVA correspond with systolic function of the RV outflow tract (RVOT) and RV basal function, respectively. Thirty-nine patients with surgically repaired TOF (TOF group) and 40 age-matched healthy children (control group) were enrolled in this study. No significant difference was seen between TA-IVA (2.5 ± 0.8 m/s2) and PA-IVA (2.4 ± 0.8 m/s2) in the control group. In the TOF group, PA-IVA (1.0 ± 0.5 m/s2) was significantly lower than TA-IVA (1.3 ± 0.6 m/s2, p < 0.05). Both TA-IVA and PA-IVA were significantly lower in the TOF group than in the control group (p < 0.05 each). We concluded that PA-IVA offers a useful index to assess RVOT function in TOF patients. J. Med. Invest. 67 : 145-150, February, 2020.


A novel index equivalent to the myocardial performance index for right ventricular functional assessment in children and adolescent patients.

The aims of the present study were to develop and check the utility and feasibility of a novel right ventricular (RV) functional index (RV angular velocity; RVω, s) derived from the angular velocity in harmonic oscillator kinematics obtained from the RV pressure waveform. We hypothesized that RVω reflects the myocardial performance index (MPI), which represents global RV function. A total of 132 consecutive patients, ranging in age from 3 months to 34 years with various cardiac diseases were included in this prospective study. RVω was defined as the difference between the peak derivative of pressure (dP/dt_max - dP/dt_min) divided by the difference between the maximum and minimum pressure (Pmax - Pmin). RVω showed significant negative correlations with the pulsed-wave Doppler-derived myocardial performance index (PWD-MPI) and the tissue Doppler imaging-derived MPI (TDI-MPI) (r = -0.52 and -0.51, respectively; both p < 0.0001). RVω also showed significant positive correlations with RV fractional area change (RVFAC) and RV ejection fraction (RVEF) (r = 0.41 and 0.39, respectively; both p < 0.0001), as well as a significant negative correlation with tricuspid E/e' (r = -0.19, p = 0.0283). The clinical feasibility and utility of RVω for assessing global RV performance, incorporating both systolic and diastolic function, were demonstrated.


Right Ventricular Myocardial Stiffness and Relaxation Components by Kinematic Model-Based Transtricuspid Flow Analysis in Children and Adolescents with Pulmonary Arterial Hypertension.

We hypothesized that the kinematic model-based parameters obtained from the transtricuspid E-wave would be useful for evaluating the right ventricular diastolic property in pediatric pulmonary arterial hypertension (PAH) patients. The model was parametrized by stiffness/elastic recoil k, relaxation/damping c and load x. These parameters were determined as the solution of m⋅d2x/dt2 + c⋅dx/dt + kx = 0, which is based on the theory that the E-wave contour is determined by the interplay of stiffness/restoring force, damping/relaxation force and load. The PAH group had a significantly higher k and c compared with the control group (182.5 ± 72.4 g/s vs. 135.7 ± 49.5 g/s2, p = 0.0232, and 21.9 ± 6.5 g/s vs. 10.6 ± 5.2 g/s, p <0.0001, respectively). These results indicate that in the PAH group, the right ventricle had higher stiffness/elastic recoil and inferior cross-bridge relaxation. The present findings indicate the feasibility and utility of using kinematic model parameters to assess right ventricular diastolic function.


Optical coherence tomography for observing development of pulmonary arterial vasa vasorum after bidirectional cavopulmonary connection in children.

Hypoxia and low pulmonary arterial (PA) blood flow stimulate the development of systemic-to-pulmonary collateral blood vessels, which can be an adverse factor when performing the Fontan operation. The aim of this study was to use optical coherence tomography (OCT) to elucidate the morphological changes in PA vasculature after creation of a bidirectional cavopulmonary connection (BCPC) in children. This prospective study evaluated PA wall thickness and development of PA vasa vasorum (VV) in the distal PA of eight patients (BCPC group, 1.3 ± 0.3 years) and 20 age-matched children with normal pulmonary artery hemodynamics and morphology (Control group, 1.4 ± 0.3 years). VV development was defined by the VV area ratio, defined as the VV area divided by the adventitial area in cross-sectional images. There was no significant difference in PA wall thickness between the BCPC and control groups (0.12 ± 0.03 mm vs. 0.12 ± 0.02 mm, respectively). The VV area ratio was significantly greater in the BCPC group than in the Control group (14.5 ± 3.5% vs. 5.3 ± 1.6%, respectively; p<0.0001). OCT is a promising new tool for evaluating PA pathology, including the development of VV in patients after BCPC.


Development of acquired intrapulmonary venous anastomosis contributing to establishment of Fontan circulation.

Pulmonary venous (PV) obstruction is associated with a poor prognosis, as well as a high risk of recurrence, following surgical treatment. It can also interfere with the successful completion of Fontan circulation in patients with complex congenital heart disease. A case of a patient who had right isomerism (also known as asplenia syndrome), total anomalous pulmonary venous connection (TAPVC), and a single right ventricle is presented. Although bilateral total occlusion of the inferior PVs was identified postoperatively, the formation of the anastomosis and collateral vessels into the superior and middle PVs enabled successful completion of Fontan circulation. Anastomoses and collateral flow of the PVs were found largely in the interlobar pleura and not in the lung parenchyma.


Pulmonary Artery Wall Thickness Assessed by Optical Coherence Tomography Correlates With Pulmonary Hemodynamics in Children With Congenital Heart Disease.

Pulmonary arterial (PA) wall thickening evaluated by optical coherence tomography (OCT) has been reported in adults with PA hypertension. The purpose of this study was to evaluate the feasibility of OCT for preoperative assessment of the PA wall in children with congenital heart disease (CHD). Participants comprised 39 patients with ventricular septal defect, atrial septal defect, or patent ductus arteriosus. Attempts were made to evaluate vessels of various diameters using OCT. Clearly observed vessels that were optimal for evaluation were selected and classified into 4 subgroups by diameter of the lumen. Optimal depiction was obtained in 80 of 156 vessels in total, and 25 (64.1%), 34 (87.1%), 17 (43.6%), and 4 vessels (10.3%) in each of the 1.0-<2.0 mm, 2.0-<3.0 mm, 3.0-<4.0 mm, and 4.0-5.0 mm subgroups, respectively. Arterial walls in the 2.0-<3.0 mm subgroup were the most frequently delineated, and wall thickness correlated significantly with mean PA pressure, pulmonary vascular resistance index, pulmonary-to-systemic flow ratio, and PA capacitance index (r=0.56, 0.52, 0.37, and -0.49, respectively). The 3-layered appearance was delineated in 29 of 80 vessels (36.2%). This feature had no significant correlation with pulmonary hemodynamics. OCT represents a promising tool for evaluating the PA wall in children with CHD.


右室圧負荷は僧帽弁のtethering を増悪させる:内科的加療のみで軽快した重症僧帽弁狭窄兼閉鎖不全の1乳児例の考察

Pediatric Cardiology and Cardiac Surgery


Analysis of Right Ventricular Myocardial Stiffness and Relaxation Components in Children and Adolescents With Pulmonary Arterial Hypertension.

The rate of left ventricular pressure decrease during isovolumic relaxation is traditionally assessed algebraically via 2 empirical indices: the monoexponential and logistic time constants (τE and τL). Since the pattern of right ventricular (RV) pressure decrease is quite different from that of the left ventricular, we hypothesized that novel kinematic model parameters are more appropriate and useful to evaluate RV diastolic dysfunction. Eight patients with pulmonary arterial hypertension (age 12.5±4.8 years) and 20 normal subjects (control group; age 12.3±4.4 years) were enrolled. The kinematic model was parametrized by stiffness/restoring Ek and damping/relaxation μ. The model predicts isovolumic relaxation pressure as a function of time as the solution of d2P/dt2+(1/μ)dP/dt+EkP=0, based on the theory that the pressure decay is determined by the interplay of inertial, stiffness/restoring, and damping/relaxation forces. In the assessment of RV diastolic function, τE and τL did not show significant differences between the pulmonary arterial hypertension and control groups (46.8±15.5 ms versus 32.5±14.6 ms, and 19.6±5.9 ms versus 14.5±7.2 ms, respectively). The pulmonary arterial hypertension group had a significantly higher Ek than the control group (915.9±84.2 s-2 versus 487.0±99.6 s-2, P<0.0001) and a significantly lower μ than the control group (16.5±4.3 ms versus 41.1±10.4 ms, P<0.0001). These results show that the RV has higher stiffness/elastic recoil and lower cross-bridge relaxation in pulmonary arterial hypertension. The present findings indicate the feasibility and utility of kinematic model parameters for assessing RV diastolic function.

Journal of the American Heart Association


Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events

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). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.


Pulmonary annular motion velocity reflects right ventricular outflow tract function in children with surgically repaired congenital heart disease

Right ventricular (RV) dysfunction is generally evaluated using analyses of tricuspid annular motion. However, it represents only one aspect of RV performance. Whether measuring pulmonary annular motion velocity could serve as a novel way to evaluate global RV and/or RV outflow tract (RVOT) performance in pediatric congenital heart disease (CHD) patients with surgically repaired RVOT was evaluated. In this prospective study, tissue Doppler-derived pulmonary annular motion velocity was measured in children (aged 2-5 years) with RVOT reconstruction (RVOTR group, n = 48) and age-matched healthy children (Control, n = 60). The types of RVOTR procedures were as follows: pulmonary valve-sparing procedure (PVS, n = 7); transannular patch with monocusp valve reconstruction (TAP, n = 29); and RV-to-PA conduit reconstruction using a pericardial valve with expanded polytetrafluoroethylene conduit (Rastelli, n = 12). Pulmonary annular motion velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all participants. The peak velocities of s1', s2', e', and a' were significantly lower in the RVOTR group than in the control group (all p < 0.0001). Furthermore, these parameters depended significantly on the type of surgical procedure. The peak velocities of s1', s2', and e' had significant correlations with RVOT ejection fraction (RVOT-EF) (r = 0.56, 0.49, and 0.34, respectively), and RVOT fractional shortening (RVOT-FS) (r = 0.72, 0.55, and 0.41, respectively), although there were no significant correlations between pulmonary annular motion and global RV function, including RV ejection fraction (RVEF) and RV fractional area change (RVFAC) in the assessment of all RVOTR group patients. The pulmonary annular motion parameters in the PVS group had significant correlations with both global RV and RVOT performance. The TAP group showed significant correlations between RVOT function and pulmonary annular motion. The Rastelli group showed almost no significant correlations between RV/RVOT function and tissue Doppler parameters. Pulmonary annular motion velocity is a simple, rapid, reproducible, and useful method of assessing RVOT function in children with surgically repaired CHD.


Early Diastolic Left Ventricular Relaxation in Normal Neonates is Influenced by Ventricular Stiffness and Longitudinal Systolic Function.

Tissue Doppler velocity during early diastole (e') is one of the most feasible and reproducible echocardiographic assessments to reflect active relaxation of the left ventricle. Although several reports have described the mechanisms of temporal diastolic dysfunction in the early neonatal period, factors influencing diastolic function have not been determined. The purpose of this study was to elucidate factors significantly influencing e' in the early neonatal period.A total of 179 consecutive normal neonates underwent echocardiographic studies performed at 0 days and 5-10 days after birth. The statistical relationships between e' and age, body weight, mean blood pressure, heart rate, shortening fraction of the left ventricle, peak systolic motion velocity (s'), early diastolic transmitral flow velocity over annulus velocity, Tei index, and diastolic wall strain (DWS) were analyzed.Between the 0 days and 5-10-days-after birth groups, significant differences were shown in mean blood pressure, shortening fraction of left ventricle, e', and Tei index. Age, body weight, mean blood pressure, s', and DWS showed significant correlations with e'. In multivariate regression analysis within these parameters, s' (β = 0.6119, P < 0.0001) and DWS (β = 0.1216, P = 0.0321) showed positive correlations with e'.Longitudinal systolic motion velocity and ventricular wall stiffness of the left ventricle influence diastolic relaxation in normal neonates. Age, body weight, and circumferential systolic function are not significant factors.


Prenatal three-dimensional color Doppler imaging showing crossover of the inflow streams of two ventricles in a case of criss-cross heart.


Temporal Sequential Pattern of Right Ventricular Free Wall Contraction in Normal Children.

The temporal sequence of right ventricular (RV) deformation is related to RV dysfunction. The sequence of RV free wall contraction was investigated. In this prospective study, strain profiles using speckle-tracking echocardiography and tissue Doppler-derived pulmonary and tricuspid annular motion were assessed in 60 normal children. Circumferential RV free wall strain of 3 individual segments (anterior, lateral, and inferior) was evaluated. Longitudinal strain was assessed in 3 individual segments (RV outflow tract [RVOT], apical, and RV inflow tract [RVIT]). The isovolumetric contraction time (ICT) and the time interval between the onset of the QRS wave to the peak s' wave were measured for pulmonary and tricuspid annular motion velocities. The time to peak circumferential strain was significantly lower in the anterior than in the lateral and inferior segments (339.1±19.5, 358.3±21.8, and 366.6±22.4 ms, respectively; P<0.0001). Longitudinal deformation of the RVOT segment occurred before the apical and RVIT segments (351.8±23.1, 366.3±20.1, and 369.2±21.3 ms, respectively; P<0.0001). The ICT and the time to peak s' were significantly shorter in pulmonary than in tricuspid annular motion (49.4±10.1 vs 58.0±13.2 ms; and 104.7±12.2 vs. 160.5±27.1 ms; P<0.0001 for each). Longitudinal deformation of RVOT precedes RVIT. Circumferential deformation occurs in the anterior segment before the lateral and posterior segments. The presence of mechanical time heterogeneity appears important for RV performance.


A wide and specific spectrum of genetic variants and genotype? Phenotype correlations revealed by next-generation sequencing in patients with left ventricular noncompaction.

Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype-phenotype correlations in LVNC patients. Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients. We identified 43 pathogenic variants in 16 genes in 39 patients (38%); 28 were novel variants. Sarcomere gene variants accounted for 63%, and variants in genes associated with channelopathies accounted for 12%. and pathogenic variants were the most common, and rare variant collapsing analysis showed variants in these genes contributed to the risk of LVNC, although patients carrying and pathogenic variants displayed different phenotypes. Patients with pathogenic variants had early age of onset and more severely decreased left ventricular ejection fractions. Survival analysis showed poorer prognosis in patients with pathogenic variants, especially those with multiple variants: All died before their first birthdays. Adverse events were noted in 17 patients, including 13 deaths, 3 heart transplants, and 1 implantable cardioverter-defibrillator insertion. Congestive heart failure at diagnosis and pathogenic variants were independent risk factors for these adverse events. Next-generation sequencing revealed a wide spectrum of genetic variations and a high incidence of pathogenic variants in LVNC patients. These pathogenic variants were independent risk factors for adverse events. Patients harboring pathogenic variants showed poor prognosis and should be followed closely.


Assessment of pulmonary arterial compliance evaluated using harmonic oscillator kinematics.

We hypothesized that K, a harmonic oscillator kinematics-derived spring constant parameter of the pulmonary artery pressure (PAP) profile, reflects PA compliance in pediatric patients. In this prospective study of 33 children (age range = 0.5-20 years) with various cardiac diseases, we assessed the novel parameter designated as Kcalculated using the pressure phase plane and the equation K = (dP/dt_max)/([Pmax - Pmin])/2), where dP/dt_max is the peak derivative of PAP, and Pmax - Pmin is the difference between the minimum and maximum PAP. PA compliance was also calculated using two conventional methods: systolic PA compliance (sPAC) was expressed as the stroke volume/Pmax - Pmin; and diastolic PA compliance (dPAC) was determined according to a two-element Windkessel model of PA diastolic pressure decay. In addition, data were recorded during abdominal compression to determine the influence of preload on K. A significant correlation was observed between Kand sPAC (r = 0.52, P = 0.0018), but not dPAC. Significant correlations were also seen with the time constant (τ) of diastolic PAP (r = -0.51, P = 0.0026) and the pulmonary vascular resistance index (r = -0.39, P = 0.0242). No significant difference in Kwas seen between before and after abdominal compression. Khad a higher intraclass correlation coefficient than other compliance and resistance parameters for both intra-observer and inter-observer variability (0.998 and 0.997, respectively). These results suggest that Kcan provide insight into the underlying mechanisms and facilitate the quantification of PA compliance.


The Action of Smooth Muscle Cell Potassium Channels in the Pathology of Pulmonary Arterial Hypertension.


Prenatal assessment of coronary artery anatomy using color Doppler in cases of D-transposition of the great arteries: Case reports

Abnormal coronary artery (CA) anatomy is common in cases of D-transposition of the great arteries (TGA) and can be a significant risk factor during the arterial switch operation. Here, we report three cases of TGA in which CA anatomy was assessed prenatally using color Doppler imaging. All CA, except the left circumflex CA in one case, were identified. CA anatomy was completely correctly diagnosed in one of our three cases. In the two remaining cases, the left circumflex CA could not be visualized in one patient, and the origin of the left anterior descending CA was not correctly diagnosed in the other. We found that prenatal assessment of CA anatomy using color Doppler in TGA was feasible, but the diagnostic accuracy was limited. We anticipate that more experience with the advancing technology will improve accuracy.

The Journal of Obstetrics and Gynaecology Research


Long-term results after open mitral commissurotomy for a one-month-old infant with mitral stenosis.

The strategy for an infant with congenital mitral stenosis should be determined by three important factors: left ventricular volume, the degree of the systemic outflow tract obstruction, and the type of mitral valve dysfunction. A successful staged biventricular repair in early infancy for a patient who had congenital mitral stenosis with short chordae, hypoplastic left ventricle and coarctation of the aorta, and the long-term results are described. There were the following important hemodynamic factors that led to the successful biventricular repair in the patient. Total systemic output was barely supplied through the hypoplastic left ventricle after closure of the ductus arteriosus on admission. The neonate underwent repair of coarctation of the aorta alone as the initial stage at 9 days after birth. Also, spontaneous closure of the foramen ovale following repair of coarctation of the aorta accelerated the progressive left ventricular growth. Open mitral commissurotomy with an interatrial fenestration using the modified Brawley's approach was performed for a 40-day-old infant. Good left ventricular growth and good mitral valve function have been observed for 18 years after open mitral commissurotomy. Appropriate early augmentation of left ventricular inflow through the mitral valve might be effective for growth of a hypoplastic left ventricle. J. Med. Invest. 64: 187-191, February, 2017.

The Journal of Medical Investigation : JMI


Coil occlusion of aberrant arteries to pulmonary sequestration in a case with pulmonary atresia with intact ventricular septum: successful treatment of repetitive myocardial ischaemic attacks

In this study, we describe an infant case of pulmonary atresia with intact ventricular septum associated with ventriculo-coronary arterial communication for which a modified Blalock-Taussig shunt operation was performed. He experienced repeated myocardial ischaemic attacks. Further examination revealed pulmonary sequestration in the right lower lobe. He therefore underwent a bidirectional Glenn operation and coil occlusion of the feeding arteries. His myocardial ischaemic attacks subsequently improved.


Mitral annular plane systolic excursion/left ventricular length (MAPSE/L) as a simple index for assessing left ventricular longitudinal function in children.

Assessment of longitudinal left ventricular (LV) function is important for early detection of cardiac dysfunction. Although mitral annular plane systolic excursion (MAPSE) obtained by M-mode echocardiography offers a simple method for assessing longitudinal LV function, normal values of MAPSE for children change according to body size. To minimize the effects of body size, MAPSE was divided by LV long-axis length (MAPSE/L). MAPSE/L was measured in 210 healthy children from birth to 15 years of age and classified into five subgroups. MAPSE/L was then compared with 10 parameters in 136 children (age, heart rate, mean blood pressure, ejection fraction of the LV (EF), peak atrial flow velocity/peak early diastolic flow velocity of mitral flow, tissue Doppler velocity during systole (s') and early diastole (e'), E/e' ratio, Tei index, and global longitudinal strain (GLS) of the LV by the speckle tracking method). MAPSE/L was significantly lower in the neonate group than in the remaining four groups. MAPSE/L then increased with age to peak at 1-5 years and gradually decreased thereafter. In all cases beyond the neonatal period, MAPSE/L was more than 0.17. Among various parameters, GLS, age, EF, Tei index and s' were significantly associated with MAPSE/L in that order. In univariate analysis, GLS was most significantly associated with MAPSE/L (r=.56). We have established normal reference values for MPSE/L in healthy children. MAPSE/L is expected to offer a simple parameter to evaluate LV longitudinal systolic function during daily routine echocardiography in children.


Noninvasive assessment of pulmonary arterial capacitance by pulmonary annular motion velocity in children with ventricular septal defect.

We hypothesized that longitudinal pulmonary arterial deformation during the cardiac cycle reflects pulmonary arterial capacitance. To examine this hypothesis, we assessed whether tissue Doppler-derived pulmonary annular motion could serve as a novel way to evaluate pulmonary arterial capacitance in pediatric patients with ventricular septal defect (VSD). In this prospective study, pulmonary annular velocity was measured in children (age, 6 months-5 years) with a preoperative VSD (VSD group, n = 35) and age-matched healthy children (Control group, n = 23). Pulmonary artery capacitance was calculated by two methods. Systolic pulmonary arterial capacitance (sPAC) was expressed as the stroke volume/pulmonary arterial pulse pressure. Diastolic pulmonary arterial capacitance (dPAC) was determined according to a two-element windkessel model of the pulmonary arterial diastolic pressure profile. Pulmonary annular velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all participants. The peak velocities of s1', s2', and e' were significantly lower in the VSD group than in the Control group. On multiple regression analysis, sPAC was an independent variable affecting the peak velocities of the s1', s2', and e' waves (β = 0.41, 0.62, and 0.35, respectively). The dPAC affected the s1' wave peak velocity (β = 0.34). The time durations of the s1' and e' waves were independently determined by the sPAC (β = 0.49 and 0.27). Pulmonary annular motion velocity evaluated using tissue Doppler is a promising method of assessing pulmonary arterial capacitance in children with VSD.


Detection of 1p36 deletion by clinical exome-first diagnostic approach.

Although chromosome 1p36 deletion syndrome is considered clinically recognizable based on characteristic features, the clinical manifestations of patients during infancy are often not consistent with those observed later in life. We report a 4-month-old girl who showed multiple congenital anomalies and developmental delay, but no clinical signs of syndromic disease caused by a terminal deletion in 1p36.32-p36.33 that was first identified by targeted-exome sequencing for molecular diagnosis.


胎児期から類洞交通を確認できた純型肺動脈閉鎖の一例

胎児期から類洞交通を確認できた純型肺動脈閉鎖の一例

Journal of Japan Society of Perinatal and Neonatal Medicine

日本周産期・新生児医学会雑誌


Pulmonary annular motion velocity assessed using Doppler tissue imaging - Novel echocardiographic evaluation of right ventricular outflow tract function-

We assessed whether measuring pulmonary annular motion velocity could serve as a novel method of evaluating right ventricular outflow tract (RVOT) performance in pediatric patients with heart disease. Tissue Doppler-derived pulmonary annular motion velocity was determined from the parasternal long-axis view of the RVOT. Pulmonary annular velocity was measured in children (age, 5-10 years) with an atrial septal defect (ASD), pulmonary arterial hypertension (PAH), surgically repaired tetralogy of Fallot (TOF) and healthy children (control). Pulmonary annular velocity waveforms comprised systolic bimodal (s1' and s2') and diastolic e' and a' waves in all groups. The peak velocity of s1' and s2' was significantly higher in the ASD group than in the controls (15.0±2.4 vs. 11.2±2.1 and 6.0±0.9 vs. 4.4±1.2 cm/s; P<0.01 and P<0.001, respectively). The s1' and s2' peak velocities were significantly lower in the PAH group (8.5±1.2 and 3.2±0.4 cm/s; P<0.05 for both), and in the group with TOF (5.3±2.2 and 3.4±1.4 cm/s; P<0.001 and P<0.05, respectively). The peak velocity of e' was significantly decreased in the PAH and TOF, compared with the control group (6.8±1.6 and 8.2±2.9 vs. 11.9±1.9 cm/s; P<0.001 for both). Pulmonary annular motion velocity determined using tissue Doppler imaging is a promising method of assessing RVOT function. (Circ J 2016; 80: 168-176).


正常肺組織を犠牲にすることを前提としてコイル塞栓術を施行した両側肺全区域びまん性肺動静脈瘻の1 例

Pediatric Cardiology and Cardiac Surgery


Optical coherence tomography can visualize the pulmonary artery in Williams-Beuren syndrome

European Heart Journal Cardiovascular Imaging


Aortic forward flow in aortic atresia via ventriculo-coronary arterial connections.


Right ventricular myocardial deformation patterns in children with congenital heart disease associated with right ventricular pressure overload.

Longitudinal wall motion of the right ventricle (RV) has been thoroughly studied in patients with RV dysfunction. However, circumferential strain of the RV free wall has yet to be investigated. Therefore, this study was conducted to assess the utility of RV free wall circumferential strain. Strain profile curves were obtained using speckle tracking echocardiography from the subcostal left ventricular (LV) short-axis view in 30 normal children (normal group) and 25 patients with RV pressure overload (RVO group). The time-strain curves of three individual segmental (anterior, lateral, and inferior segments) and global circumferential deformations were evaluated. RV ejection fraction (RVEF), RV systolic pressure (RVSP), and RV fractional area change obtained in the four-chamber view and LV short-axis view [RVFAC (4CH) and RVFAC (SAX), respectively] were measured, and their relationships with RV free wall deformation were assessed. In the normal group, circumferential strain was significantly lower in the anterior segment than in the other segments. The inferior segment had a significantly larger strain than the other segments in the RVO group. Circumferential strain was predominant over longitudinal RV free wall strain in the RVO group (-18.4 ± 3.9 vs. -14.2 ± 3.8%, respectively; P < 0.005), whereas no significant difference between them was observed in the normal group (-23.0 ± 3.9 vs. -22.4 ± 4.7%, respectively). Global circumferential strain had a significantly higher correlation with RVFAC (4CH), RVFAC (SAX), RVEF, and RVSP than global longitudinal strain (P < 0.05 for all). RV free wall circumferential strain provides better information about RV function than longitudinal strain in children with RVO.


Bronchogenic cyst compressing the pulmonary artery and the left atrium.


Assessment of the Helical Ventricular Myocardial Band Using Standard Echocardiography

The purpose of this study was to assess the feasibility of morphological and functional evaluation of the helical ventricular myocardial band using standard echocardiographic images. Echocardiographic data were obtained from 132 normal children. We attempted to identify the echogenic bright line serving as the boundary between the ascending and descending segments in the ventricular septum, and between the left and ascending segments in the left ventricular inferior wall in the helical myocardial band model proposed by Torrent-Guasp. Myocardial deformations on both sides of the bright line were compared using speckle tracking echocardiography. The bright line separating the ascending from descending segment was visible in the mid-ventricular septum in the four-chamber view in all subjects. This echogenic boundary was observed obliquely in the parasternal short-axis view in 116 subjects (87.9%). There was no significant difference in peak longitudinal or circumferential strain between the ascending and descending segments. However, the time from the QRS onset to peak circumferential strain was significantly lower in the descending than ascending segment (394.5 ± 37.0 vs. 432.7 ± 33.1 ms, P < 0.0001), whereas there was no significant difference in the time to peak longitudinal strain (394.4 ± 26.4 vs. 393.2 ± 24.1 ms). The bright line between the left and ascending segment was detected in the short-axis view from the subcostal region in 86 subjects (65.2%). The time to peak circumferential strain was significantly lower in the left than ascending segment (380.1 ± 32.0 vs. 435.7 ± 37.9 ms, P < 0.0001). There is a helical ventricular myocardial band that can be observed in standard echocardiographic images.


Fibromyxoid excrescence of the aortic valve that manifested after catheterisation and required resection.

A 2-year-old boy developed fibromyxoid excrescence of the aortic valve 2 years after balloon dilatation for simple coarctation. Transthoracic echocardiography showed a mobile mass on the non-coronary cusp of the aortic valve. Definitive diagnosis was achieved after operative resection. This pathology was attributed to injury during catheter manipulation. Catheterised patients should be followed up carefully to avoid missing morphological changes.


Developmental changes in the left ventricular diastolic wall strain on M-mode echocardiography

The diastolic wall strain (DWS) of the left ventricle has been proposed as an indicator of left ventricular (LV) wall stiffness. The DWS is calculated as follows using M-mode echocardiography:[Formula: see text]Although this index is simple and clinically useful, normal values for children, including neonates, have not been reported. The DWS was measured in 235 healthy people, ranging from neonates to adults. They were classified into 8 subgroups according to their age. The DWS was compared with conventional echocardiographic parameters for left ventricle function, including shortening fraction of the left ventricle, the Tei index, E/A of mitral flow, mitral annular tissue Doppler velocity during systole (s') and during early diastole (e'), and the E/e' ratio. The DWS in the just after birth group was 0.28 ± 0.11, which was significantly lower than that of the remaining groups (p < 0.05), except for the neonate group at 5-10 days after birth. The DWS was highest in the 1-9 years of age group, and then gradually decreased with age. Stepwise regression of various echocardiographic parameters showed that e' was the most relevant parameter for the DWS (β = 0.64). Normal values for the DWS of the left ventricle change with age. The data reported in this study can be used as normal values for the DWS of the left ventricle determined by M-mode echocardiography.


Continuing medical education activity in echocardiography.


Assessment of Two-Component Ventricular Septum: Functional Differences in Systolic Deformation and Rotation Assessed by Speckle Tracking Imaging.

The purpose of this study was to elucidate functional differences in the right and left components of the ventricular septum (Rt and Lt, respectively). Strain, strain rate, rotation, and rotation rate profile curves of Rt and Lt were obtained using speckle tracking echocardiography in 38 normal children and adolescents. The echogenic bright line serving as the boundary separating Rt from Lt was consistently visible in the middle of the ventricular septum. There was no significant difference in peak strain or peak strain rate during systole between Rt and Lt. However, the time interval from the onset of QRS-wave to peak strain and peak strain rate were significantly lower in Lt than in Rt in terms of radial and circumferential deformation (P < 0.005, all), whereas there was no significant difference in longitudinal deformation in the time to peak strain or peak strain rate between Rt and Lt. Lt showed counterclockwise rotation, whereas Rt showed clockwise rotation (10.4 ± 2.9° vs. -10.2 ± 2.6°, P < 0.0001). Time to peak rotation was significantly lower in Lt than in Rt (201.7 ± 32.7 msec vs. 370.4 ± 31.2 msec, P < 0.0001). Morphologically and functionally the ventricular septum is a two-component structure. Evaluation of deformation and rotation of the 2 components would help in evaluating septal performance.


Assessment of Pulmonary Artery Morphology by Optical Coherence Tomography in a Patient with Idiopathic Pulmonary Arterial Hypertension

光干渉断層像(Optical Coherence Tomography)で肺血管病変を観察した特発性肺動脈性肺高血圧症

Pediatric Cardiology and Cardiac Surgery


Right ventricular thrombosis in two patients with pulmonary atresia with intact ventricular septum


Echocardiographic assessment of anomalous origin of the left coronary artery from the pulmonary artery


Subclavian and pulmonary artery steal phenomenon in a patient with isolated left subclavian artery and right aortic arch.

We describe a patient with an isolated left subclavian artery associated with right aortic arch, patent ductus arteriosus, and ventricular septal defect. As the isolated left subclavian artery is supplied by the left vertebral artery in which blood flows in the retrograde direction, this anomaly is usually responsible for a congenital subclavian steal phenomenon. Atrophy of the left cerebral hemisphere and inverted left vertebral arterial flow were clearly depicted by echoencephalography in this patient, whose subclavian artery was connected to the main pulmonary artery by a patent ductus arteriosus.


Complete but not partial thymectomy in early infancy reduces T-cell-mediated immune response: three-year tracing study after pediatric cardiac surgery.

The results revealed that complete thymectomy in early infancy reduces the number of circulating T cells and T-cell-mediated immune responses for at least 3 years, suggesting that the thymus should be at least partially preserved during surgery in early infancy to maintain protective immunity.

Journal of Thoracic and Cardiovascular Surgery


Left atrial volume change throughout the cardiac cycle in children with congenital heart disease associated with increased pulmonary blood flow: evaluation using a novel left atrium-tracking method.

There is a paucity of data regarding the significance of left atrial (LA) volume and its changes throughout the cardiac cycle in pediatric patients with heart disease. The recently developed LA volume-tracking (LAVT) method can automatically construct the LA volume curve. The study group consisted of 48 pediatric patients with ventricular septal defect (n = 34) or patent ductus arteriosus (n = 14) and age-matched healthy controls. Maximum and minimum LA volumes (LAVmax and LAVmin, respectively) were measured. The total LA emptying volume (LAVtotal) was defined as LAVmax--LAVmin. Volume parameters were standardized by dividing by body surface area (BSA). The total LA emptying fraction (%LAVtotal) was defined as the ratio of LAVtotal to LAVmax. In the patient group, there was a positive correlation between the ratio of pulmonary to systemic blood flow (Qp/Qs) and LAVmax/BSA, LAVmin/BSA, and LAVtotal/BSA (r = 0.42, 0.44, and 0.34, respectively). LAVmin/BSA was positively correlated with the ratio of early mitral inflow velocity to early mitral annular diastolic tissue Doppler velocity (E/E') (r = 0.32). The %LAVtotal had a negative correlation with left-ventricular (LV) end-diastolic pressure (r = -0.32). There were significant correlations between serum B-type natriuretic peptide level and LAVmax/BSA, LAVmin/BSA, and %LAVtotal (r = 0.38, 0.49, and -0.35, respectively). The LAVT method is useful in the evaluation of LV diastolic function in pediatric patients with chronic LV volume overload.


Multidetector-row computed tomography evaluation of bilateral bronchial narrowing associated with increased pulmonary blood flow in children with congenital heart disease.

Quantitative assessment of bilateral bronchial narrowing in children with congenital heart disease (CHD) with a left-to-right shunt has not yet been reported. In the present study, main bronchial size was evaluated bilaterally in normal subjects using multidetector-row computed tomography (MDCT), and the feasibility for diagnosis of bronchial narrowing in children with CHD associated with increased pulmonary blood flow was investigated. The short-axis diameter, long-axis diameter, and the cross-sectional area of the bilateral bronchi were measured immediately proximal to the origin of the superior lobar branch in 86 children aged 1-52 months. Subjects were divided into three groups as follows: group 1 (normal subjects; n = 52), group 2 (asymptomatic left-to-right shunt group; n = 25), and group 3 (symptomatic left-to-right shunt group with respiratory insufficiency; n = 9). Age, height, weight, and body surface area were significantly correlated with short- and long-axis bronchial diameters, and bronchial cross-sectional area in group 1. In group 2, the left bronchial cross-sectional area was significantly lower than group 1 (P < .001), whereas the right bronchial area was not significantly different. In group 3, the right bronchial area was significantly lower than that in groups 1 and 2 (P < .05). Although the left bronchial area in group 3 was significantly lower than in group 1 (P < .001), it was not significantly different from that in group 2. Our study suggests that MDCT can be used to quantify bilateral bronchial narrowing. Left main bronchial obstruction develops during the early stage of heart failure, followed by the development of right bronchial narrowing.


Stent placement in the ductus venosus of a neonate with total anomalous pulmonary venous return.


肝機能障害なくボセンタンが奏功した胆道閉鎖を合併した多脾症候群・両方向性グレン術後症例


Consideration of the Pathological Features of Pediatric Congenital Heart Diseases Which Are Ideally Suitable for Diagnosing With Multidetector-row CT.

A lots of articles published regarding the usefulness of multidetector-row computed tomography (MDCT) in children with congenital heart disease (CHD) mostly describe that it can be an alternative to the invasive catheterization and angiography. The unique diagnostic features of this imaging modality have been largely ignored or disregarded. We described the pathological conditions that cannot be diagnosed by conventional angiography with cardiac catheterization but can be accurately diagnosed by MDCT. We retrospectively reviewed non-ECG-gated MDCT images acquired from 452 children and young adults with CHD between 2005 and 2010 in our institute. In this article, we focused on the diagnostic advantages of MDCT, and indicated five pathological conditions. (1) When Blalock-Taussig shunt total occlusion prevents catheter insertion into the artificial vessel and angiography is ruled out, the peripheral pulmonary artery during the peripheral pulmonary artery can be imaged and diagnosed using MDCT based on blood flow supplied from many small collateral vessels originating from the aorta. (2) The location and protrusion of the device in the vessel after coil embolization to treat patent ductus arteriosus can be accurately visualized by virtual endoscopy using MDCT. (3) Calcification of patches, synthetic blood vessels, and other prostheses that is indistinct on conventional angiograms is clear on MDCT. (4) Simultaneous MDCT observations of the anatomical relationships between arterial and venous systems on the same image can clarify the detail diagnosis for surgical treatment. (5) Compression of the airways by the great vessels and pulmonary segmental emphysematous change can be diagnosed by MDCT. Among patients with CHD, MDCT is useful not only as a non-invasive alternative to conventional angiography, but also as a tool for specific morphological diagnoses. In the future, it will be necessary to accumulate experience in the recognition of cardiovascular conditions under which MDCT is necessary and to perform as the appropriate examination.


A novel bilayer approach to ventricular septal deformation analysis by speckle tracking imaging in children with right ventricular overload

The aim of this study was to evaluate functional differences between the left and right sides of the ventricular septum in children with right ventricular overload. Radial, longitudinal, and circumferential strain on both sides of the ventricular septum were compared using speckle-tracking echocardiography in patients with preoperative atrial septal defects (n = 22), postoperative tetralogy of Fallot (n = 23) and age-matched normal controls (n = 44). The duration between peak strain of the left and right ventricular septum (TLt-Rt) was also evaluated. Radial and circumferential strain in the control group were significantly higher on the left than the right ventricular septum (41.3 ± 12.8% vs 22.6 ± 6.8% and -28.0 ± 5.4% vs -22.5 ± 4.8%, respectively; P < .0001 for both), whereas longitudinal strain did not significantly differ (-22.0 ± 4.9% and -20.7 ± 5.2%, respectively). TLt-Rt was 52.9 ± 35.6, 33.4 ± 29.0, and 38.7 ± 31.0 msec for radial, longitudinal, and circumferential strain, respectively. Longitudinal and circumferential strain on both sides were significantly increased in patients with atrial septal defects compared with controls (P < .05), although radial strain was similar on both sides. Radial strain on the right side was significantly increased in patients with tetralogy of Fallot compared with controls (P < .05), whereas that on the left side was significantly reduced (P < .001). Longitudinal strain on both sides was significantly decreased (P < .01 and P < .001 for the left and right sides, respectively). In addition, TLt-Rt in patients with tetralogy of Fallot was significantly increased with radial and circumferential deformation (P < .05 for both). Deformation of both sides of the ventricular septum functionally differed. Bilayer analysis of the ventricular septum can help in the evaluation of right ventricular performance under volume and pressure overload.

Journal of the American Society of Echocardiography


Multidetector-row computed tomography visualized peripheral pulmonary artery patency in a patient with occluded modified Blalock-Taussig shunt

Multidetector-row computed tomography visualized peripheral pulmonary artery patency in a 19-year-old female with a single ventricle and an occluded Blalock-Taussig shunt whereas conventional invasive angiography did not.


Serum concentration of Heart-type fatty acid-binding protein in children and adolescents with congenital heart disease

Serum heart-type fatty acid-binding protein (H-FABP) is widely applied as a marker of cardiac myocyte injury. Recently, it has been reported that levels of H-FABP are elevated in adult patients with chronic heart failure and thus provide useful prognostic information. The aim of the present study was to examine the relationships between serum H-FABP levels and pathophysiological characteristics in children and adolescents with congenital heart disease (CHD). Serum H-FABP levels were preoperatively and postoperatively measured in 238 consecutive patients with CHD aged 1-31 years. The relationships between H-FABP levels and severity of heart failure, circulatory status and laboratory data were cross-sectionally analyzed. Multivariate regression analysis indicated that serum H-FABP levels are independently affected by age, New York Heart Association functional class, creatine kinase MB, creatinine and arterial oxygen saturation (standard regression coefficients, -0.378, 0.237, 0.422, 0.615, and -0.210, respectively). Neither left ventricular ejection fraction nor B-type natriuretic peptide correlated with H-FABP levels. H-FABP could serve as a new monitoring tool to provide information that will guide the optimal therapy and management of CHD patients.


Minimum-intensity projection of multidetector-row computed tomography for assessment of pulmonary hypertension in children with congenital heart disease

The present study aimed to assess the feasibility of minimum-intensity projection (minIP) images for the evaluation of pulmonary hypertension (PH) in children with congenital heart disease (CHD). A total of 70 consecutive patients (mean age, 4.6 ± 4.4 years; range, 6 months-16 years) underwent multidetector-row computed tomography (MDCT) angiography of the thorax prior to cardiac catheterization and lung perfusion scintigraphy. Contiguous axial, coronal and sagittal minIP images of 5-mm thickness were reconstructed from the contrast-enhanced CT datasets. Two reviewers evaluated the images in consensus and qualitatively graded lung parenchyma attenuation as homogeneous (Class I), slightly heterogeneous lung attenuation that does not conform to the anatomic boundaries of the secondary pulmonary lobule (Class II), and mosaic pattern (Class III). MinIP attenuation grading results were then compared with those of perfusion scintigraphy. Furthermore, the relationships between the results of these modalities and mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were evaluated. In 51 (73%) patients, concordant findings were observed between the modalities, although minIP showed a higher grade for heterogeneous images than did scintigraphy. mPAP and PVR showed significant difference among the minIP attenuation classes (p<0.0001 for both). High-grade heterogeneous minIP images were associated with high mPAP, high PVR, presence of major aortopulmonary collateral artery, and chromosomal abnormality. MinIP is a promising technique for depicting lung perfusion and can be used as superior alternative to scintigraphy in the evaluation of PH.


Cell membrane stretch activates intermediate-conductance Ca2+-activated K+ channels in arterial smooth muscle cells

The aim of this study is to determine the signal transduction of membrane stretch on intermediate-conductance Ca(2+)-activated K(+) (IKca) channels in rat aorta smooth muscle cells using the patch-clamp technique. To stretch the cell membrane, both suction to the rear end of patch pipette and hypotonic shock were used. In cell-attached and inside-out patch configurations, the open probability of IKca channels increased when 20- to 45-mmHg suction was applied. Hyposmotic swelling efficiently increased IKca channel current. When the Ca(2+)-free solution was superfused, the activation of IKca current by the hyposmotic swelling was reduced. Furthermore, gadolinium (Gd(3+)) attenuated the activation of IKca channels induced by hyposmotic swelling, whereas nicardipine did not. In the experiments with Ca(2+)-free bath solution, pretreatment with GF109203X, a protein kinase C (PKC) inhibitor, completely abolished the stretch-induced activation of IKca currents. The stretch-induced activation of IKca channels was strongly inhibited by cytochalasin D, indicating a role for the F-actin in modulation of IKca channels by changes in cell stretching. These data suggest that cell membrane stretch activates IKca channels. In addition, the activation is associated with extracellular Ca(2+) influx through stretch-activated nonselective cation channels, and is also modulated by the F-actin cytoskeleton and the activation of PKC.


Assessment of systemic-pulmonary collateral arteries in children with cyanotic congenital heart disease using multidetector-row computed tomography: Comparison with conventional angiography

The present study aimed to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of systemic-pulmonary collateral (SPC) arteries in children with congenital heart disease associated with reduced pulmonary blood flow. Forty-eight consecutive patients (mean age 9+/-5 months; range, 0-30 months) underwent MDCT angiography of the thorax with a 16-detector row scanner prior to cardiac catheterization and operation. Conventional angiographic findings were used as a gold standard for the detection of SPC vessels. Findings on CT angiograms, including CT scans, maximum intensity projections, and three-dimensional volume-rendered images, were used to evaluate depiction of SPC arteries. Quantification of measurements at the SPC artery diameter was evaluated independently on MDCT and conventional invasive angiography. Among the 48 patients, 115 SPC arteries were identified with conventional angiography, and 94 SPC arteries were identified with MDCT. In 89 (77%) vessels, concordant findings were observed with both modalities, with adequate depiction in 53 vessels and suboptimal depiction in 36 vessels. In 26 (23%) vessels, MDCT was unable to identify SPC arteries. Further, CT angiography resulted in the false-positive identification of vessels in 5 cases. There was an excellent correlation between MDCT- and conventional angiography-based measurement of SPC vessel diameter (R(2)=0.83), although a systematic overestimation was observed with MDCT (bias 0.19+/-0.74 mm). This study demonstrates that MDCT is a potentially useful tool, which may have implications for planning percutaneous interventions and surgical repair in the future.


Increased mid-left ventricular rotation in patients with Duchenne muscular dystrophy using two-dimensional speckle tracking echocardiography


Coronary arteriovenous fistula: Direct connection of the proximal circumflex artery to the coronary sinus


Assessment of modified Blalock-Taussig shunt in children with congenital heart disease using multidetector-row computed tomography

The purpose of this study was to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of modified Blalock-Taussig (B-T) shunt in children with congenital heart disease associated with reduced pulmonary blood flow. A total of 25 consecutive patients (mean age, 2.6 ± 3.6 years; range, 2 months-16 years) underwent MDCT angiography of the thorax with a 16-detector row scanner prior to cardiac catheterization. A total of 39 shunts (right, 22; left, 17) were included in the study. Conventional angiographic findings were used as the gold standard for the detection of B-T shunts. Shunt diameter was measured quantitatively and independently at four sites (the subclavian artery site, the pulmonary artery site, the widest site, and the stenotic site) on MDCT and on conventional invasive angiography. All B-T shunts were depicted on multiplanar reconstruction (MPR), maximum intensity projection (MIP), curved planar reconstruction (CPR), and three-dimensional volume-rendered (VR) images, enabling evaluation in all patients except for one with occluded shunt. There were excellent correlations between MDCT- and conventional angiography-based measurements of shunt diameter at the subclavian artery site, pulmonary artery site, and the widest site (R² = 0.46, 0.74 and 0.64, respectively; p < 0.0001 for each), although systematic overestimation was observed for MDCT (mean percentage of overestimation, 23.1 ± 32.4%). Stenotic site diameter and degree of stenosis showed a mild correlation (R² = 010 and 0.25, respectively; p < 0.01 for each). This study demonstrates that MDCT is a promising tool for the detection of lesions in B-T shunts.


Autonomic function in patients with Duchenne muscular dystrophy

Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 +/- 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R-R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R-R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut-off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.


Tracheal compression due to an elongated aortic arch in patients with congenital heart disease: evaluation using multidetector-row CT

The airway can become obstructed as a result of compression by an elongated aortic arch. In this study we evaluated tracheal compression using multidetector-row CT in patients with congenital heart disease and an elongated aortic arch. The trachea was measured at the level of the aortic arch in 205 children and young adults and then the severity of tracheal compression was determined by measuring the tracheal diameter ratio (short axis diameter/long axis diameter). Patients were divided as follows: group I (normal aortic arch; n=166), group II (transversely running aortic arch; n=22), and group III (elongated aortic arch; n=17). From the viewpoint of the relationship of the great arteries, group II had D-malposition, and group III had L-malposition. Age, height, weight and body surface area were significantly correlated with the short and long axis diameter in group I. There was a negative correlation between tracheal diameter ratio and the physical size parameters. The tracheal diameter ratio in group III was 0.50+/-0.13, which was significantly lower than in groups I and II (P<0.01 and 0.05, respectively). Even apparently asymptomatic patients with an elongated aortic arch can have tracheal compression. An elongated aortic arch may be a useful predictor of tracheal compression.


Stenting of ductus arteriosus in a neonate with truncus arteriosus and interrupted aortic arch associated with a right aortic arch

This report describes a case in which successful stenting of ductus arteriosus (DA) was performed for a 27-day-old boy with truncus arteriosus (TA) and interrupted aortic arch (IAA). The patent DA was associated with a right aortic arch. During the balloon catheter crossing of the ductus, the DA and descending aorta shifted toward the left side, making appropriate stent placement difficult. Additionally, the DA was longer than in previously reported cases with left aortic arch, thus requiring a longer stent. This experience suggests that DA stenting in neonates with TA and IAA averts surgical repair during the early neonatal period.


Insulin-like growth factor-I inhibits rat arterial K(ATP) channels through pI 3-kinase

Since, in addition to its growth-promoting actions, insulin-like growth factor-I (IGF-I) has rapid vasoactive actions, we investigated the effects of IGF-I on whole-cell ATP-sensitive K(+) (K(ATP)) currents of rat mesenteric arterial smooth muscle cells. IGF-I (10 or 30 nM) reduced K(ATP) currents activated by pinacidil or a membrane permeant cAMP analogue. Inhibition of phospholipase C, protein kinase C, protein kinase A, mitogen-activated protein kinase or mammalian target of rapamycin (mTOR) did not prevent the action of IGF-I. However, inhibition of K(ATP) currents by IGF-I was abolished by the tyrosine kinase inhibitor genistein or the phosphoinositide 3-kinase inhibitors, LY 294002 and wortmannin. Intracellular application of either phosphatidylinositol 4,5-bisphosphate (PIP(2)) or phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) increased the K(ATP) current activated by pinacidil and abolished the inhibitory effect of IGF-I. Thus, we show regulation of arterial K(ATP) channels by polyphosphoinositides and report for the first time that IGF-I inhibits these channels via a phosphoinositide 3-kinase-dependent pathway.

Biochemical and Biophysical Research Communications


Segmental Myocardial Strain of the Left Ventricle in Patients With Duchenne Muscular Dystrophy Using Two-Dimensional Speckle Tracking Echocardiography


Rare venous connection causing severe hypoxia after Fontan operation

We describe a rare case of cyanosis following the Fontan operation with right-to-left shunting at the venous level, that is, an azygos venous to pulmonary venous connection. Few cases with partial anomalous pulmonary venous connection to azygos vein have been reported; however, there have been no reports describing the connection from azygos vein to pulmonary vein, which results in desaturation after Fontan operation. Multidetector-row computed tomography (MDCT) was a useful tool to depict this vascular malformation.

Interactive Cardiovascular and Thoracic Surgery


Virtual endoscopy using multidetector-row CT for coil occlusion of patent ductus arteriosus

The objective of this study was to report the clinical value of virtual endoscopy using multidetector-row CT (MDCT) for coil occlusion of patent ductus arteriosus (PDA). We studied 10 consecutive patients with PDA undergoing cardiac catheterization and coil occlusion. All patients had previously undergone MDCT, and subsequently underwent transcatheter closure of ductus. MDCT evaluations were performed again in 1-3 months after occlusion. Virtual endoscopy showed the anatomy of the orifice of the ductus and spatial relations of adjacent structures from both the aortic and pulmonary sides in all patients. We were able to observe the inner space, and fly through the PDA. This approach is the virtual view of the catheter advancing during coil occlusion. Following occlusion, visualization of the coil can also be established by viewing from inside. Coil protrusion into the aortic and pulmonary sides was clearly observed. Virtual endoscopy provides unique information regarding the ductal lumen that is of use for the coil occlusion of PDA.

Catheterization and Cardiovascular Interventions


Polytetrafluoroethylene graft calcification in patients with surgically repaired congenital heart disease:Evaluation using multidetector-row computed tomography

Noninvasive determination of calcified prosthetic polytetrafluoroethylene (PTFE) is important in improving risk stratification. The purpose of this study is to assess the feasibility of multidetector-row computed tomography (MDCT) for the evaluation of PTFE calcification in patients with surgically repaired congenital heart disease and to evaluate the development and characteristics of calcification for specific surgical procedures. Seventy-six implanted PTFE grafts in 47 patients were evaluated by MDCT (Aquillion 16, Toshiba Corporation, Tokyo, Japan). Explanted PTFE grafts were evaluated histologically in 4 patients who underwent reoperation after MDCT scans. Calcification of prosthetic PTFE was detected in 5 of 29 cases (17%) for ventricular septal defect (VSD) patches, 26 of 32 (81%) for right ventricular outflow tract (RVOT) prosthesis, 2 of 8 (25%) for atrial septal patches of the Fontan procedure, and 7 of 7 (100%) for extracardiac conduits of total cavopulmonary connection. The CT attenuation of PTFE revealed significantly different values for VSD patches (114 +/- 61 Hounsfield units [HU]), RVOT prosthesis (243 +/- 132 HU), atrial septal patches (163 +/- 161 HU), and extracardiac conduits (230 +/- 29 HU) (P < .0001). The CT density value of VSD patches was significantly lower than those of RVOT grafts and extracardiac conduits (P < .05). The MDCT findings were consistent with histologic analysis in the evaluation of calcification. This study demonstrates that MDCT enables the evaluation of prosthetic PTFE graft calcification; PTFE grafts in 4 different implantation sites demonstrated distinctive features and the prevalence of calcification.


Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne's progressive muscular dystrophy.

In patients with Duchenne's progressive muscular dystrophy (DMD), myocardial fibrosis begins from the epicardial half of the left ventricular posterior wall. Myocardial strain imaging by tissue Doppler echocardiography is a new method for assessing regional myocardial function. We hypothesized that this method might be useful for the early detection of subclinical myocardial involvement in DMD patients. Myocardial radial strain of the left ventricle was measured in 25 DMD patients (age: 14.8 +/- 3.1 years) with a normal left ventricular shortening fraction and 25 age-matched healthy controls. Peak systolic radial strain of the posterior wall in a short-axis view of the left ventricle was significantly lower in DMD patients compared to control subjects (P < 0.0001). In the interventricular septum, peak systolic radial strain was not significantly different between the two groups. Receiver operating characteristic curve analysis differentiated DMD patients from control patients with 92% sensitivity and 92% specificity, when the cutoff value for systolic peak strain of the posterior wall was 61%. When radial strain was measured separately for the inner and outer halves of the posterior wall, a systolic negative strain was more frequently observed in the outer half than in the inner half of the posterior wall (6/25 vs. 0/25, P < 0.05). Myocardial strain imaging in DMD patients was characterized by decreased peak systolic strain of the posterior wall despite normal standard echocardiographic findings. Strain measurement might be useful for early detection of subtle regional myocardial dysfunction.


多源性心房性頻拍症の2乳児例

多源性心房性頻拍症の2乳児例


Angiotensin II activates intermediate-conductance Ca2+-activated K+ channels in arterial smooth muscle cells.

Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.

Journal of Molecular and Cellular Cardiology


Mean heart rate at noght as a predictor for the evaluation of autonomic function in patietns with Duchenne progressive muscular dystrophy


Myocardial systolic strain in normal children using a tissue tracking system


Caveolae localize protein kinase A signaling to arterial ATP-sensitive potassium channels.

Arterial ATP-sensitive K+ (K(ATP)) channels are critical regulators of vascular tone, forming a focal point for signaling by many vasoactive transmitters that alter smooth muscle contractility and so blood flow. Clinically, these channels form the target of antianginal and antihypertensive drugs, and their genetic disruption leads to hypertension and sudden cardiac death through coronary vasospasm. However, whereas the biochemical basis of K(ATP) channel modulation is well-studied, little is known about the structural or spatial organization of the signaling pathways that converge on these channels. In this study, we use discontinuous sucrose density gradients and Western blot analysis to show that K(ATP) channels localize with an upstream signaling partner, adenylyl cyclase, to smooth muscle membrane fractions containing caveolin, a protein found exclusively in cholesterol and sphingolipid-enriched membrane invaginations known as caveolae. Furthermore, we show that an antibody against the K(ATP) pore-forming subunit, Kir6.1 co-immunoprecipitates caveolin from arterial homogenates, suggesting that Kir6.1 and caveolin exist together in a complex. To assess whether the colocalization of K(ATP) channels and adenylyl cyclase to smooth muscle caveolae has functional significance, we disrupt caveolae with the cholesterol-depleting agent, methyl-beta-cyclodextrin. This reduces the cAMP-dependent protein kinase A-sensitive component of whole-cell K(ATP) current, indicating that the integrity of caveolae is important for adenylyl cyclase-mediated channel modulation. These results suggest that to be susceptible to protein kinase A-dependent activation, arterial K(ATP) channels need to be localized in the same lipid compartment as adenylyl cyclase; the results also provide the first indication of the spatial organization of signaling pathways that regulate K(ATP) channel activity.


Plasma levels of natriuretic peptide and echocardiographic parameters in patients with Duchenne's progressive muscular dystrophy.

We investigated the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and systolic and diastolic cardiac function, determined by echocardiography, in 63 patients with Duchenne's progressive muscular dystrophy (DMD) (age range 8-21 years). The relationship between shortening fraction of the left ventricle and ANP and BNP levels was curvilinear rather than linear: When the shortening fraction was >15%, increases in ANP and BNP levels were minimal. However, if the shortening fraction was <15%, both natriuretic peptide levels increased dramatically. Stepwise regression analysis revealed that only the deceleration time of the early diastolic filling wave predicted plasma BNP concentration among various diastolic echocardiographic parameters determined by mitral flow. Three patients died of cardiac dysfunction during a 2-year follow-up period. These patients had a severely decreased deceleration time (<65% of normal) in association with increases in both natriuretic peptide levels. In conclusion, plasma ANP and BNP levels are not sensitive markers for the early detection of cardiac systolic dysfunction in patients with DMD. However, in patients with systolic dysfunction, an increase in the concentrations of these peptides, associated with a decrease in the deceleration time of early diastolic filling, suggests poor prognosis.


Angiotensin II inhibits and alters kinetics of voltage-gated K(+) channels of rat arterial smooth muscle.

The vasoconstrictor angiotensin II (ANG II) inhibits several types of K(+) channels. We examined the inhibitory mechanism of ANG II on voltage-gated K(+) (K(V)) currents (I(K(V))) recorded from isolated rat arterial smooth muscle using patch-clamp techniques. Application of 100 nM ANG II accelerated the activation of I(K(V)) but also caused inactivation. These effects were abolished by the AT(1) receptor antagonist losartan. The protein kinase A (PKA) inhibitor Rp-cyclic 3',5'-hydrogen phosphothioate adenosine (100 microM) and an analog of diacylglycerol, 1,2-dioctanyoyl-rac-glycerol (2 microM), caused a significant reduction of I(K(V)). Furthermore, the combination of 5 microM PKA inhibitor peptide 5-24 (PKA-IP) and 100 microM protein kinase C (PKC) inhibitor peptide 19-27 (PKC-IP) prevented the inhibition by ANG II, although neither alone was effective. The ANG II effect seen in the presence of PKA-IP remained during addition of the Ca(2+)-dependent PKC inhibitor Gö6976 (1 microM) but was abolished in the presence of 40 microM PKC-epsilon translocation inhibitor peptide. These results demonstrate that ANG II inhibits K(V) channels through both activation of PKC-epsilon and inhibition of PKA.

American Journal of Physiology, Heart and Circulatory Physiology


Evidence for involvement of A-kinase anchoring protein in activation of rat arterial KATP channels by protein kinase A

1. We have investigated the possible role of A-kinase anchoring proteins (AKAPs) in protein kinase A (PKA) signalling to ATP-sensitive K+ (K(ATP)) channels of rat isolated mesenteric arterial smooth muscle cells using whole-cell patch clamp and peptides that inhibit PKA-AKAP binding. 2. Intracellular Ht31 peptide (20 microM), which inhibits the PKA-AKAP interaction, blocked K(ATP) current activation by either dibutyryl cAMP or calcitonin gene-related peptide. Ht31-proline (20 microM), which does not inhibit PKA binding to AKAP, did not block K(ATP) current activation. 3. Ht31 reduced K(ATP) current activated by pinacidil and also prevented its inhibition by Rp-cAMPS, effects consistent with Ht31 blocking steady-state K(ATP) channel activation by PKA. However, Ht31 did not prevent K(ATP) current activation by the catalytic subunit of PKA. 4. An antibody to the RII subunit of PKA showed localization of PKA near to the cell membrane. Our results provide evidence that both steady-state and receptor-driven activation of K(ATP) channels by PKA involve the localization of PKA by an AKAP.


Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells.

Sulphonylureas stimulate insulin secretion by closing ATP-sensitive potassium (KATP) channels in the pancreatic beta-cell membrane. KATP channels are also found in other tissues, including heart and smooth muscle, where they link cellular metabolism to electrical activity. The sulphonylurea gliclazide blocks recombinant beta-cell KATP channels (Kir6.2/SUR1) but not heart (Kir6.2/SUR2A) or smooth muscle (Kir6.2/SUR2B) KATP channels with high potency. In this study, we examined the specificity of gliclazide for the native (as opposed to recombinant) KATP channels in beta cells, heart and smooth muscle. The action of the drug was studied by whole-cell current recordings of native KATP channels in isolated pancreatic beta-cells and myocytes from heart and smooth muscle. Gliclazide blocked whole-cell beta-cell KATP currents with an IC50 of 184 +/- 30 nmol/l (n = 6-10) but was much less effective in cardiac and smooth muscle (IC50s of 19.5 +/- 5.4 micromol/l (n = 6-12) and 37.9 +/- 1.0 micromol/l (n = 5-10), respectively). In all three tissues, the action of the drug on whole-cell KATP currents was rapidly reversible. In inside-out patches on beta-cells, gliclazide (1 micromol/l) produced a maximum of 66 +/- 13 % inhibition (n = 5), compared with more than 98 % block in the whole-cell configuration. Gliclazide is a high-potency sulphonylurea which shows specificity for the pancreatic beta-cell KATP channel over heart and smooth muscle. In this respect, it differs from glibenclamide. The difference in the maximal block observed in the excised patch and whole-cell recordings from beta-cells, may be due to the absence of intracellular Mg-nucleotides in the excised patch experiments.


Myocardial integrated ultrasound backscatter in patients with Duchenne's progressive muscular dystrophy.


稀な左上大静脈走行異常の2例

稀な左上大静脈走行異常の2例


Left ventricular wall motion velocities in healthy children measured by pulsed wave Doppler tissue echocardiography: normal values and relation to age and heart rate

Left ventricular wall motion velocities were measured by pulsed wave Doppler tissue (PWDT) echocardiography in 131 healthy children (mean age 7.5 +/- 5.5 years) at the interventricular septum and the posterior wall in the left ventricular short-axis view, and at the interventricular septum and the lateral wall in the 4-chamber view. The systolic wave (Sw) consisted of 2 components, and the difference between the 2 components was greater in the lateral wall than in the other walls. The peak early diastolic wave (Ew) velocity was also highest in the lateral wall. Most variables during systole correlated with age. The ratio of peak atrial systolic wave (Aw) velocity to peak Ew velocity (Aw/Ew) correlated with heart rate. The Aw/Ew in each wall correlated with the ratio of late (A) to early (E) peak mitral flow, although regression slopes differed among different wall segments. In younger children with increased heart rates, the Aw/Ew ratio increased because the Ew velocity decreased, although the A/E ratio increased because of an increased A velocity. Normal values for the PWDT variables change with heart rate and age in the pediatric population. The data reported in this study can be used as normal values for left ventricular function for PWDT echocardiography.

Journal of the American Society of Echocardiography


Cyclic variation of integrated ultrasound backscatter in the left ventricle during the early neonatal period.

Significant changes in the contractility and histologic structure of the ventricular myocardium occur during the early neonatal period. Cyclic variation (CV) of ultrasonic integrated backscatter (IBS) reflects myocardial contractile performance. The aim of this study was to define normal values of and its serial changes in CV of IBS in the left ventricle of normal neonates. We recorded long-axis IBS images in 169 healthy neonates within 14 days after birth (mean 4.6 +/- 4.2 days) and in 84 infants and children (mean age 8.7 +/- 5.2 years). For each, we obtained CV of IBS in the interventricular septum (CV(IVS)) and the posterior wall (CV(PW)). In neonates, there was a significant linear correlation between CV and date after birth in measurements of both the interventricular septum and the posterior wall (r = 0.57 and 0. 60, respectively). In infants and children, there was no significant relation between age and CV(IVS) or CV(PW). In neonates >4 days after birth, the magnitude of CV(IVS) was not significantly different from that in infants or children. By contrast, the magnitude of CV(PW) was still significantly decreased in neonates >9 days after birth compared with that in infants and children (P <. 005). The ratio of CV(IVS) to CV(PW) (CV(IVS)/CV(PW)) was significantly higher in neonates than in infants and children (0.99 +/- 0.29 vs 0.80 +/- 0.22, P <.001). Both CV(IVS) and CV(PW) in neonates gradually increase after birth, indicating developmental maturation of the left ventricle. High values of CV(IVS)/CV(PW) might reflect the remnant of relatively high contractile performance in the right ventricle during fetal life.


Retrograge holodiastolic flow in the abdominal aorta detected by pulsed Doppler echocardiography in patients with Kawasaki disease

Retrograde holodiastolic flow in the abdominal aorta (retrograde flow) detected by pulsed Doppler echocardiography is usually noted in patients with aortic regurgitation or patent ductus arteriosus. Similar abnormal flow often is present in patients with acute phase Kawasaki Disease (KD). In 21 patients with acute phase KD, 15 had a retrograde flow. Retrograde flow was recognised in only 3 of patients with acute infection (n = 31) and in no healthy controls (n = 10). The ratio of the time velocity integral for diastolic retrograde flow to that for antegrade flow (regurgitant fraction) was significantly greater in patients with KD (median value 23%) than in patients with acute infection (1%) or healthy individuals (1%) (P < 0.001 for both). Four patients with coronary arterial involvement (one with an aneurysm and three with transient dilation of the coronary arteries) had a greater regurgitant fraction than the 17 patients without coronary arterial involvement (median values: 31% versus 18%, P < 0.05). The C-reactive protein was increased for a longer period of time in patients with KD with a greater regurgitant fraction (P < 0.01). Plasma nitric oxide (NO) metabolite concentrations were significantly greater in patients with KD than in those with acute infection or in healthy controls (P < 0.001 for both). There was a positive correlation between plasma NO metabolite concentrations and the regurgitant fraction in patients with KD (r = 0.69). Retrograde flow in the abdominal aorta is increased in patients with Kawasaki disease. Further studies are needed to clarify the causal relationship between the abnormal flow and the overproduction of nitric oxide.


Diagnosis and natural history of isolated congenital pulmonary regurgitation in fetal life

We describe a rare instance of isolated pulmonary regurgitation caused by a dysplastic pulmonary valve which was detected prenatally. Fetal echocardiography demonstrated severe pulmonary regurgitation, and progressive cardiomegaly because of right ventricular volume overload. After birth, conservative therapy was successful in alleviating the pulmonary vascular resistance, and the pulmonary regurgitation gradually decreased.


冠動脈攣縮性狭心症による胸痛を来たした無脾症候群の1例

冠動脈攣縮性狭心症による胸痛を来たした無脾症候群の1例


Plasma concentrations of atrial and brain natriuretic peptides and cyclic guanosine monophosphate in response to dobutamine infusion in patients with surgically repaired tetralogy of fallot

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 microgram/kg/min and increased by 5 microgram/kg/min up to 20 microgram/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r = 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r = 0.71, p < 0.05), mean right atrial pressure (r = 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r = 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r = 0.61, p < 0.05) and systolic pressure (r = 0. 46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.


Age-related endothelium-dependent vascular relazation in rat thoracic aorta in response to colforsin

Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.