Takahiro Shindo

Dissipative energy loss within the left ventricle detected by vector flow mapping in children: Normal values and effects of age and heart rate

BACKGROUND Vector flow mapping (VFM) is a novel echocardiographic technology which enables visualization of the intraventricular flow velocity vector. Dissipative energy loss (EL) derived from the velocity vector field of intraventricular blood flow is considered to reflect the efficiency of blood flow, and could be an indicator of left ventricular function. We aimed to determine the reference values of the EL derived from VFM within the left ventricle. METHODS VFM analysis was performed using echocardiography in 64 healthy children. The velocity vector fields of the intra-left ventricular blood flow were obtained from the apical 5-chamber view, and the EL values during systole and diastole were calculated. The measurements were averaged over three cardiac cycles, and indexed to body surface area (BSA). RESULTS The mean subject age was 6.8±4.3 years. The mean EL was 4.10±2.35mW/m/m(2) BSA during systole and 16.24±11.63mW/m/m(2) BSA during diastole. On multivariate analysis, age and heart rate (HR) were independent predictors of systolic EL, whereas age, HR, and E wave peak velocity were independent predictors of diastolic EL. The regression equations used to predict the BSA-indexed systolic and diastolic EL were as follows: log10 (systolic EL)=-0.0332-0.00213×age (months)+0.00789×HR (beats/min) (adjusted R(2), 0.833; p<0.0001); and log10 (diastolic EL)=0.277-0.00346×age (months)+0.00570×HR (beats/min)+0.00564×E wave peak velocity (cm/s) (adjusted R(2), 0.867; p<0.0001). CONCLUSIONS The systolic and diastolic EL were positively correlated with HR and negatively correlated with age. Moreover, the diastolic EL was positively correlated with the E wave peak velocity. The present study provides reference values for the systolic and diastolic EL that can be used in future studies examining patients with heart disease.

Fever pattern and C-reactive protein predict response to rescue therapy in Kawasaki disease

Evidence to guide rescue therapy in refractory Kawasaki disease (KD) is lacking. The aim of this study was to determine the most important variables in predicting non‐response to rescue therapy in refractory KD.

Novel Risk Assessment Tool for Immunoglobulin Resistance in Kawasaki Disease: Application Using a Random Forest Classifier

Background: Resistance to intravenous immunoglobulin (IVIG) therapy is a risk factor for coronary lesions in patients with Kawasaki disease (KD). Risk-adjusted initial therapy may improve coronary outcome in KD, but identification of high risk patients remains a challenge. This study aimed to develop a new risk assessment tool for IVIG resistance using advanced statistical techniques. Methods: Data were retrospectively collected from KD patients receiving IVIG therapy, including demographic characteristics, signs and symptoms of KD and laboratory results. A random forest (RF) classifier, a tree-based machine learning technique, was applied to these data. The correlation between each variable and risk of IVIG resistance was estimated. Results: Data were obtained from 767 patients with KD, including 170 (22.1%) who were refractory to initial IVIG therapy. The predictive tool based on the RF algorithm had an area under the receiver operating characteristic curve of 0.916, a sensitivity of 79.7% and a specificity of 87.3%. Its misclassification rate in the general patient population was estimated to be 15.5%. RF also identified markers related to IVIG resistance such as abnormal liver markers and percentage neutrophils, displaying relationships between these markers and predicted risk. Conclusions: The RF classifier reliably identified KD patients at high risk for IVIG resistance, presenting clinical markers relevant to treatment failure. Evaluation in other patient populations is required to determine whether this risk assessment tool relying on RF has clinical value.

Clinical implications of mitral valve geometric alterations in children with dilated cardiomyopathy.

We aimed to elucidate the relationship between severity of secondary mitral regurgitation and mitral valve geometry in children with dilated cardiomyopathy. The medical records of 16 children with dilated cardiomyopathy (median age, 1.2 years; range, 0.4-12.3 years) were reviewed. Mitral valve geometry was evaluated by measuring coaptation depth using echocardiographic apical four-chamber views at the initial presentation. Patients were dichotomised according to the mitral regurgitation severity: patients with moderate or severe secondary mitral regurgitation (n=6) and those with mild secondary mitral regurgitation (n=10). A total of 58 healthy children were considered as normal controls, and a regression equation to predict coaptation depth by body surface area was derived: coaptation depth [mm]=4.37+1.34×ln (body surface area [m2]) (residual standard error, 0.49; adjusted R2, 0.68; p<0.0001). Compared with patients with mild secondary mitral regurgitation, those with moderate or severe secondary mitral regurgitation had significantly larger coaptation depth z-scores (6.4±2.3 versus 1.9±1.4, p<0.005), larger mitral annulus diameter z-scores (3.6±2.6 versus 0.9±1.8, p<0.05), higher left ventricular sphericity index (0.89±0.07 versus 0.79±0.06, p<0.005), and greater left ventricular fraction shortening (0.15±0.05 versus 0.09±0.05, p<0.05). In conclusion, geometric alteration in the mitral valve and the left ventricle is associated with the severity of secondary mitral regurgitation in paediatric dilated cardiomyopathy, which would provide a theoretical background to surgical intervention for secondary mitral regurgitation in paediatric populations.

Central extracorporeal membrane oxygenation requiring pulmonary arterial venting after near-drowning

Extracorporeal membrane oxygenation (ECMO) is an effective respiratory and circulatory support in patients in refractory cardiogenic shock or cardiac arrest. Peripheral ECMO sometimes requires left heart drainage; however, few reports state that pulmonary arterial (PA) venting is required during ECMO support. We present a case of a 14-year-old boy who required PA venting during ECMO support after resuscitation from near-drowning in freshwater. A biventricular assist device with an oxygenator implantation was intended on day 1; however, we were unable to proceed because of increasing of pulmonary vascular resistance from the acute lung injury. Central ECMO with PA venting was then performed. On day 13, central ECMO was converted to biventricular assist device with an oxygenator, which was removed on day 16. This case suggests that PA venting during ECMO support may be necessary in some cases of respiratory and circulatory failure with high pulmonary vascular resistance after near-drowning.

Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy

LEOPARD syndrome (LS) is a form of RASopathy caused by mutations in the PTPN11 gene an upstream regulator of RAS/MAPK signaling. Although hypertrophic cardiomyopathy (HCM) is a shared cardiac phenotype among RASopathies, HCM complicating patients with LS is characteristic for its unique early-onset and progressive features. We herein report a neonate with LS who presented with an extremely severe form of HCM. Autopsy revealed remarkable evidence of active cardiomyocyte proliferation contributing to the overt cardiomegaly. The case suggests an intriguing association between the observed dramatic increase in cardiomyocyte mitotic activity and the fatal clinical course of LS-associated HCM. The patient was the second daughter born to nonconsanguineous parents with no significant family history. Marked biventricular hypertrophy was noted on fetal echocardiography at the 28th week of gestation. After an uneventful delivery, the patient was immediately admitted to the neonatal intensive care unit. Physical examination at birth revealed multiple dysmorphic features, including a wide forehead, low set ears, hypertelorism, and wide set nipples. No skin lesions, such as cafe-au-lait spots or lentigines, were noticed, whereas mild hearing loss was detected by newborn screening. The findings were suggestive of LS. Imaging studies were remarkable for cardiomegaly (Figure …

Effect of i.v. immunoglobulin in the first 4 days of illness in Kawasaki disease

Although early treatment of Kawasaki disease (KD) with i.v. immunoglobulin (IVIG) is expected to prevent coronary artery abnormalities, the effectiveness of IVIG by day 4 of illness remains to be determined.

Identification of liver fibrosis using the hepatic vein waveform in patients with Fontan circulation: Liver fibrosis in Fontan patients

Liver fibrosis caused by congestive hepatopathy has emerged as an important complication after Fontan procedure. We evaluated the utility of the hepatic vein (HV) waveform using Doppler ultrasound for identification of liver fibrosis in Fontan patients.

Identification of a novel titin variant underlying myocardial involvement in neurofibromatosis type 1

Because of the rare co-occurrence, it remains a question whether cardiomyopathy is a true association of neurofibromatosis type 1. A boy with café-au-lait spots manifested restrictive cardiomyopathy. Whole exome sequencing confirmed the genetic diagnosis of neurofibromatosis and further identified a novel titin (TTN) missense variant. The significance of the variant is supported by its de novo origin, in silico predictions, and evolutionary conservation. Modern genetics raises an intriguing explanation for the unexpected phenotype and adds to the evolving role of TTN variants in cardiomyopathy.

Minimally invasive, pericardial implantable cardioverter-defibrillator placement in a young child

We report the successful minimally invasive placement of a pericardial implantable cardioverter‐defibrillator (ICD) in a 16‐kg child. A transvenous ICD dual coil was advanced through a small subxiphoid incision and screwed into the oblique sinus pericardium under fluoroscopic guidance. An additional sense‐pace lead was sutured onto the right ventricular apex, and the generator was placed in the upper abdominal wall through the same incision. Threshold testing demonstrated successful defibrillation at 15 J. After implantation, the patient had two episodes of appropriate shock for ventricular fibrillation. The ICD system continues to show stable impedance at 6 months of follow‐up.