Atsuhito Takeda

Aortic pressure wave reflection in children.

Aortic pressure wave reflection is one of the risk factors for developing cardiovascular disease in adults, and the degree of pressure wave reflection increases with aging. However, enhanced pressure wave reflection has also been reported in infants and children. The purpose of this study was to clarify pressure wave reflection during childhood and to determine the reference for the augmentation index, which is one of the most useful parameters used to represent the degree of aortic pressure wave reflection in children. This study enrolled 72 patients with normal aortic circulation. The aortic pressure waveform was recorded using a pressure sensor-mounted catheter, and the augmentation index was thus calculated. The augmentation index tended to decrease with increasing age until around 15 years of age and then increased thereafter. For children below 15 years of age, multiple regression analysis revealed a significant negative correlation between body height and augmentation index. In children, increases in aortic pressure wave reflection are probably attributable to changes in body height.

Eponym: Barth syndrome

UNLABELLED Barth syndrome (OMIM #302060) (BTHS) is an X-linked disorder of lipid metabolism characterized by skeletal myopathy, neutropenia, growth delay, and cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ), which lead to decreased production of an enzyme required to produce cardiolipin, a component of the inner mitochondrial membrane necessary for proper functioning of the electron transport chain. The most common initial presentation of BTHS is significant heart failure due to cardiomyopathy, which is the main cause of death in infancy or childhood. On the other hand, some patients have limited clinical features of BTHS. These patients may be overlooked or misdiagnosed with unclassified congenital myopathy, especially when heart failure is not clinically significant. However, these patients could also develop significant heart failure or life-threatening arrhythmias during or even after childhood. Heart failure in BTHS is often responsive to standard medical therapy, indicating early diagnosis is critical. Diagnostic clues of BTHS in the subclinical stage of heart failure include family histories, findings of lipid storage myopathy in the skeletal muscle biopsy, and elevated plasma brain natriuretic peptide levels. The genetic analysis of TAZ is the only confirmatory method for the diagnosis of BTHS. CONCLUSION physicians should be aware of the possibility of this disease and carry out genetic studies when it is considered.

Aortic pressure wave reflection in patients after successful aortic arch repair in early infancy

Despite the apparently successful surgical repair of aortic coarctation, subsequent cardiovascular complications have sometimes been encountered. Aortic pressure wave reflection is one of the risk factors for developing cardiovascular diseases, and an enhancement of the pressure wave reflection has been reported in patients after aortic arch repair. To clarify this issue, the increase in pressure wave reflection was evaluated in patients <15 years old who underwent aortic arch repair. This study enrolled 35 patients after aortic arch repair in early infancy. All patients underwent cardiac catheterization, and in 20 patients, there was no pressure difference within the repaired aortic arch. The aortic pressure waveforms in patients after successful aortic arch repair were recorded using a pressure sensor-mounted catheter, and the augmentation index in the ascending aorta was calculated. The augmentation index in patients after an aortic arch repair was increased compared with control subjects, although there was no pressure difference between the ascending and descending aorta (P<0.0001). The increase in the augmentation index was correlated with the patient’s age (r=0.8932, P<0.0001) and with the left ventricular posterior wall thickness (r=0.4075, P=0.0373). In patients who undergo aortic arch repair, the pressure wave reflection is accelerated, even when the aortic arch repair is ‘successful’. This increase is one of the possible causes of left ventricular hypertrophy.

Barth syndrome diagnosed in the subclinical stage of heart failure based on the presence of lipid storage myopathy and isolated noncompaction of the ventricular myocardium

Barth syndrome (BTHS) is an X-linked disorder characterized by skeletal myopathy, neutropenia, growth delay, and cardiomyopathy. It is caused by mutations in the tafazzin gene (TAZ). Although early diagnosis is critical to prevent the progression of heart failure, this disease remains unrecognized when heart failure is not clinically significant. Here we report on a 13-year-old boy with no family history of BTHS who was diagnosed with the syndrome in the subclinical stage of heart failure. The clues to the diagnosis of BTHS in this patient were the findings of lipid storage myopathy in the skeletal muscle biopsy, elevated plasma brain natriuretic peptide, and the diagnosis of isolated noncompaction of the ventricular myocardium in echocardiography. Genetic studies of TAZ revealed a disease-causing mutation (p.Gly216Arg) in this patient. Physicians should be aware of the possibility of this disease and carry out genetic studies when it is considered.

Cardiovascular effects of a phosphodiesterase III inhibitor, amrinone, in infants: Non-invasive echocardiographic evaluation

Objective : The inotropic effect of amrinone is still controversial in management of congestive heart failure in pediatric patients, especially in infants. In order to determine the cardiovascular effect of amrinone in pediatric patients, we performed echocardiographic evaluation in 11 infants (mean age of 2 months) after intracardiac surgery.

Primary prevention of sudden cardiac death in a low-risk child with familial hypertrophic cardiomyopathy: the role of cardiac magnetic resonance imaging

Sirs: The incidence of hypertrophic cardiomyopathy (HCM) is 0.2 %, and this condition is considered the most common genetic cardiovascular disease. In addition, HCM is one of the most common causes of sudden cardiac death (SCD) in young people [1]. An implantable cardioverter defibrillator (ICD) is a highly effective device for inhibiting ventricular tachyarrhythmias. It is generally agreed that the indications for an ICD strongly support the secondary prevention of SCD [2]. However, the indications for primary preventive ICD placement for SCD remain controversial. Recently, it has been shown that late gadolinium enhancement magnetic resonance imaging (LGE-MRI) can be used to evaluate myocardial fibrosis as an arrhythmic substrate [3, 4]. Here, we report a familial case of HCM in which we decided to place an ICD as primary prevention for SCD based on the LGE-MRI findings. The cases described are two brothers whose father and grandmother were diagnosed with HCM, and the elder brother of the father had a sudden death. Gene analysis was carried out in the father and the two brothers described here. An Ala63Val mutation in exon 2 of TPM1 gene, which encodes alpha tropomyosin, was found (Fig. 1a). The eldest brother in our two cases was 18 years old. He was diagnosed with HCM following medical screening at age 13. The interventricular septum diameter (IVSd) on echocardiography was 18.2 mm (Z-score was 8.5), which is far from the SCD risk criteria (over 30 mm) at age 18. LGE-MRI demonstrated diffuse contrast enhancement in the left ventricular myocardium. The extent of LGE was 8 % of the LV mass using previously reported methods [1] (Fig. 1b). The patient had been managed with mild limitation of physical activity. At the age of 18, he had syncope due to ventricular tachycardia (Fig. 1c) and was successfully resuscitated without any complications. Then, an ICD was implanted for secondary prevention of SCD. The youngest brother of the above-mentioned case was also diagnosed with HCM following medical screening at age 6. He has been managed by mild mobility limitation and treated by beta-blockers because a left ventricular outflow tract obstruction was detected by echocardiography. Though the extent of myocardial fibrosis using LGE-MRI was only 1 % of the LV mass at age 10, it markedly progressed to 16 % in 2 years (Fig. 1d). In addition, LGEMRI demonstrated a diffuse pattern of enhancement, similar to that observed in the elder brother. Because the presence of LGE was seen more strongly in the younger brother than in the elder brother, the younger brother was scheduled for the placement of a prophylactic ICD. The selection of patients for the primary prevention of SCD with an ICD has been predicated on the assessment of well-known five key risk factors, which were reported previously [2]. Recently, ACCF/AHA guidelines indicated primary prevention with the ICD a class IIa indication, based on the presence of one or more conventional key risk factors [5]. However, it is difficult to determine whether our case represents a form of primary prevention of SCD with an ICD because it was unclear whether the cause of sudden death in a family member was related to hypertrophic cardiomyopathy. In addition, there was no case of sudden death in a first-degree relative [2]. Recently, myocardial fibrosis detected by LGE-MRI was reported as a candidate for a new risk factor that may be able to predict SCD. Green et al. [6] mentioned that H. Yamazawa (&) A. Takeda K. Takei T. Furukawa Department of Pediatrics, Hokkaido University School of Medicine, North 15 West 7, Kitaku, Sapporo, Hokkaido 060-8638, Japan e-mail: h-yamazawa@umin.org

Loss of pulse pressure amplification between the ascending and descending aorta in patients after an aortic arch repair

Introduction: One of the most important problems in patients with an aortic coarctation after an aortic arch repair is future cardiovascular disease. We previously reported the enhancement of the aortic pressure wave reflection in patients and hypothesized that the enhancement was caused by a new pressure wave reflection generated from the repaired site. To prove the hypothesis, we analyzed the pressure waveform in the ascending and descending aorta and examined their pulse pressure (PP) amplification. Methods: Fifteen patients after an aortic arch repair without a recoarctation were enrolled. The ascending and descending aorta pressure waveforms were recorded by a pressure sensor mounted catheter. The pressures were compared with those of age-matched controls. Results: The patients age was 7.3 ± 2.7 years, and they underwent the aortic arch repair at 30.1 ± 29.0 days. The ascending aorta SBP (106.1 ± 12.7 mmHg) was higher than in the control patients (97.9 ± 14.3) (P = 0.015). The PP at the ascending aorta in the patients (41.3 ± 7.8) was wider than that in the controls (36.4 ± 5.0) (P = 0.010). There was no difference concerning the PP at the descending aorta between the patients (41.0 ± 7.7) and controls (40.5 ± 6.5). The difference in the PP between the descending and ascending aorta (PP at the descending aorta – PP at the ascending aorta) in the patients was −0.3 ± 1.7 and 5.1 ± 2.9 in the controls (P < 0.0001). Conclusion: The ascending aortic PP was augmented in the patients after the aortic arch repair. It could be one of the causes of future cardiovascular disease.

Multiple Coronary Stenosis in Infantile Moyamoya Disease

A 3-year-old girl was referred to our institution for evaluation of mitral valve regurgitation. A heart murmur was observed when she visited a pediatrician for treatment of a respiratory infection, and it was diagnosed as mitral valve regurgitation. The regurgitation gradually became worse and she was referred to the hospital. An echocardiographic examination showed moderate mitral valve regurgitation. Because her ECG demonstrated a slight ST depression on the left chest leads, dipyridamole stress thallium imaging was performed. However, it …

Cardiac progenitor cells activated by mitochondrial delivery of resveratrol enhance the survival of a doxorubicin-induced cardiomyopathy mouse model via the mitochondrial activation of a damaged myocardium

Abstract It has been reported that transplanting native cells would lack efficiency without producing artificial cell‐tissue, due to the exaggerated oxidative stress in doxorubicin‐induced cardiomyopathy. We attempted to activate cardiac progenitor cells (CPCs) by delivering resveratrol to mitochondria using a mitochondrial drug delivery system (MITO‐Porter system). We first evaluated the viability of H9c2 cells (a cardio myoblast cell line) after doxorubicin treatment, where H9c2 cells were co‐cultured with or without the mitochondria activated CPCs (referred to herein as MITO cell). We next evaluated the survival rate of doxorubicin treated mice, with or without the injection of MITO cells into the myocardium. Finally, we examined the molecular mechanism of the cell therapy by detecting oxidative stress and the induction of apoptosis in addition to quantification of the mRNA and protein levels about oxidative phosphorylation (OXPHOS). The MITO cell transplanted mice lived significantly longer than the conventional CPC transplanted ones. Oxidative stress and massive cell death were both significantly reduced in the MITO cell transplanted hearts, in which the expression levels of OXPHOS protein and gene were also higher than the control group. In doxorubicin‐induced cardiomyopathy, the transplantation of MITO cells, which possess activated mitochondria, is more efficient compared to conventional CPC transplantation. Graphical abstract Figure. No Caption available.

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

Importance Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants 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. Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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.