Heart failure is conventionally defined as a dynamic clinical syndrome where the cardiovascular system fails to meet the metabolic demand of the peripheral tissues or can only do so at the expense of increased ventricular filling pressure. Emerging new findings in biomedical research have enabled us to recognize the early preclinical myocardial changes at the cellular and molecular levels before ventricular dysfunction becomes visible. These preclinical changes have also become recognizable by advanced medical technology. Here, we introduce two relatively common clinical entities that present with an asymptomatic preclinical stage in pediatrics, cardiomyopathies in Duchenne muscular dystrophy and anthracycline-induced cardiotoxicity. We will discuss underlying pathobiology, early diagnosis by noninvasive imaging studies, and cardioprotective treatment of the preclinical stage of progressive myocardial disease. The early recognition and treatment of the preclinical stage of heart failure may provide us with new perspectives in understanding this devastating disease.

Background: Chylothorax/abdomen can lead to prolonged hospitalization, cause developmental delays, and sometimes become fatal. Therefore, the development of a new therapy for its treatment has been investigated. Owing to the rapidly expanding knowledge regarding central lymphatic disease, chylothorax/abdomen has been found to be recurrent and to leak due to lymphatic stenosis or obstruction. These lymphatic problems are similar to those in peripheral lymphatic disease, for which we analyzed the lymphatic flow and treated it with direct maneuver. Based on this, we have introduced minimally invasive procedures to correct the central lymphatic system.

Methods: We included 12 pediatric patients aged 30 days to 2 years. Five patients were diagnosed with hereditary diseases other than cardiac anomalies. All patients were followed for >6 months after the lymphatic procedures were performed. Medical treatment was preoperatively administered for 4 weeks and with diet/milk restrictions.

Results: Four patients were completely cured of lymphatic leakage, and 3 patients required further treatment. Five patients died during intensive care, mainly because of respiratory distress.

Conclusions: Lymphangiography and lymphatic venous anastomosis are the most commonly performed procedures, which are effective in some patients. This novel treatment remains limited to patients with complications. However, the new therapy that is based on lymphatic flow analysis may become a novel approach for refractory chylothorax/abdomen. Therefore, studies on lymphatic disease are ongoing, and further improvements are expected in the future.

Background: An international multicenter, placebo-controlled, double-blind study (STARTS-1) and its subsequent extension study (STARTS-2) demonstrated that sildenafil monotherapy with medium dose was well tolerated and improved exercise tolerance, functional class, and hemodynamics in patients with pediatric pulmonary arterial hypertension (PAH). However, clinical studies of pediatric PAH had not been performed in Japan at the time. We therefore aimed to investigate the efficacy, safety and pharmacokinetics of sildenafil in Japanese pediatric patients with PAH.

Methods: We conducted an open-label study consisting of both a 16-week treatment period (Part 1) and a long-term treatment period (Part 2). The efficacy endpoints were improvement in the parameters of pulmonary vascular resistance index (PVRI), mean pulmonary arterial pressure (mPAP), World Health Organization functional class, brain natriuretic peptide (BNP) and N-terminal pro-BNP. The patients received sildenafil at 10 mg or 20 mg that was administered 3 times a day based on body weight.

Results: Six children aged 1 to 14 years with PAH were screened, and sildenafil was assigned. Four patients completed Part 1, and one patient completed Part 2. In Part 1, among the 5 patients with available cardiac catheterization data, PVRI and mPAP decreased in 3 and 2 patients, respectively. There were 11 treatment-related adverse events that were already known, but no serious adverse events including death occurred.

Conclusions: This study suggests that oral sildenafil is well tolerated and acceptable as a therapeutic option in Japanese pediatric patients with PAH. (Clinical Trial Registration: NCT01642407)

Down syndrome and cardiac tumor occurring in the same patient is a rare condition. Patients with primary cardiac tumors face an uncertain treatment strategy that ranges from conservative management to aggressive surgical intervention. We report here the case of cardiac fibroma in a newborn with Down syndrome, and we discuss the most appropriate way of making a diagnosis and treatment in patients with cardiac masses. In this case, although the cardiac mass was large, the patient was asymptomatic. We tried to make a definitive diagnosis through the use of magnetic resonance imaging but failed to reveal the diagnosis. Although histologic and immunohistochemical examinations are useful to get a correct diagnosis of the type of tumor and its malignancy, clinicians should keep in mind that open surgical approach can have serious implications that require consideration. Conservative management of cardiac masses in a newborn who is strictly asymptomatic seems to be an acceptable strategy when the risks of surgical intervention outweigh the benefits.

Few studies have examined the coronary arterial calcification (CAC) caused by Kawasaki disease (KD), although it has been shown to increase the risk of acute coronary syndrome. In this study, we present the case of a 38-year-old patient with KD-induced CAC who was operated by acute myocardial infarction. Pathological examination revealed that coronary arterial lesions included atherosclerosis-like lesions and that KD-induced CAC was composed of >98% calcium phosphate with carbonate, like CAC of atherosclerosis. Radiological analysis using dual-energy computed tomography showed that the composition of KD-induced CAC resembled that of atherosclerosis. However, carotid ultrasonography and pulse wave velocity results were normal. These results suggest that KD-induced arterial calcification formed on tissues damaged in the past subsequently to arteriosclerosis. These findings suggest that patients with the past of KD, especially with KD-induced CAC, are easy to develop atherosclerosis and they should take care of the risk factors of atherosclerosis, such as hypertension, hyperlipidemia, smoking, obesity, and diabetes.

We report the case of a 15-year-old girl with isolated right ventricular hypoplasia without interatrial shunt. At 13 years of age, her right ventricular end-diastolic volume was 58% of the normal and the left ventricular end-diastolic volume was within the normal range with (98% of normal) despite the absence of interatrial shunt. Doppler echocardiography showed anterograde diastolic pulmonary arterial flow, coinciding with the A wave of atrial contraction. At 15 years of age, the right ventricular end-diastolic volume remained unchanged, but the left ventricular end-diastolic volume decreased to 65% of normal. The right ventricular pressure wave form showed a clear dip and plateau and the exacerbation of the restrictive change. The fact that the deterioration of the right ventricular diastolic disorder progressed with the decrease of the left ventricular end-diastolic volume suggests that end-diastolic volume of the patient’s left ventricle was maintained with the end-diastolic forward flow to the pulmonary artery.

Most primary pediatric cardiac tumors are rhabdomyomas, which are generally associated with tuberous sclerosis complex. Large tumors can sometimes cause heart failure, and surgery might be required for patient survival. Everolimus, an oral mammalian target of rapamycin inhibitor, has been recently studied for its antineoplastic effect. Here, we describe a case involving successful everolimus treatment for cardiac rhabdomyomas in a neonate.