Background: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy that is associated with high morbidity and mortality rates. Recently, LVNC was classified into several phenotypes including congenital heart disease (CHD). However, although LVNC and CHD are frequently observed, the role and clinical significance of genetics in these cardiomyopathies has not been fully evaluated. Therefore, we aimed to evaluate the impact on the perioperative outcomes of children with concomitant LVNC and CHD using next-generation sequencing (NGS). Methods: From May 2000 to August 2018, 53 Japanese probands with LVNC (25 males and 28 females) were enrolled and we screened 182 cardiomyopathy-associated genes in these patients using NGS. Results: The age at diagnosis of the enrolled patients ranged from 0 to 14 years (median: 0.3 months). A total of 23 patients (43.4%) were diagnosed with heart failure, 14 with heart murmur (26.4%), and 6 with cyanosis (11.3%). During the observation period, 31 patients (58.5%) experienced heart failure and 13 (24.5%) developed arrhythmias such as ventricular tachycardia, supraventricular tachycardia, and atrioventricular block. Moreover, 29 patients (54.7%) had ventricular septal defects (VSDs), 17 (32.1%) had atrial septal defects, 10 had patent ductus arteriosus (PDA), and 7 (13.2%) had Ebstein’s anomaly and double outlet right ventricle. Among the included patients, 30 underwent surgery, 19 underwent biventricular repair, and 2 underwent pulmonary artery banding, bilateral pulmonary artery banding, and PDA ligation. Overall, 30 genetic variants were identified in 28 patients with LVNC and CHD. Eight variants were detected in MYH7 and two in TPM1. Echocardiography showed lower ejection fractions and more thickened trabeculations in the left ventricle in patients with LVNC and CHD than in age-matched patients with VSDs. During follow-up, 4 patients died and the condition of 8 worsened postoperatively. The multivariable proportional hazards model showed that heart failure, LV ejection fraction of < 24%, LV end-diastolic diameter z-score of > 8.56, and noncompacted-to-compacted ratio of the left ventricular apex of > 8.33 at the last visit were risk factors for survival. Conclusions: LVNC and CHD are frequently associated with genetic abnormalities. Knowledge of the association between CHD and LVNC is important for the awareness of clinical implications during the preoperative and postoperative periods to identify the populations who are at an increased risk of additional morbidity.

The aim of this study was to characterize the kinetics of metabolite formation of the phosphodiesterase type-5 (PDE5) inhibitors sildenafil and tadalafil by CYP3A4, CYP3A5, and CYP3A7 isoforms. The formations of N-desmethyl sildenafil and desmethylene tadalafil were examined using CYP3A supersomes co-expressing human P450 oxidoreductase and cytochrome b5. Both sildenafil N-demethylation and tadalafil demethylenation were catalyzed by CYP3A4, CYP3A5, and to a lesser extent by CYP3A7. The kinetics of desalkyl metabolite formation of the two drugs were well fitted to the Hill equation; however, the Hill coefficients (n) suggested CYP3A-mediated negative cooperativity. Next, we analyzed the kinetics with a two binding sites model assuming two reaction steps: reaction 1 with high-affinity and low-capacity metabolism and reaction 2 with low-affinity and high-capacity metabolism. The kinetics of desalkyl metabolite formation were also fitted to the two binding sites model. The intrinsic clearance (CLint) values of reactions 1 and 2 for sildenafil N-demethylation were 0.733 and 0.033 µL/min/pmol P450 for CYP3A4, 0.788 and 0.019 µL/min/pmol P450 for CYP3A5, and 0.079 and 0.004 µL/min/pmol P450 for CYP3A7, respectively. The CLint values of reactions 1 and 2 for tadalafil demethylenation were 0.187 and 0.014 µL/min/pmol P450 for CYP3A4, 0.050 and <0.001 µL/min/pmol P450 for CYP3A5, and 0.004 and <0.001 µL/min/pmol P450 for CYP3A7, respectively. These results may provide the basis not only for understanding the metabolic properties of the two PDE5 inhibitors, but also for one possible explanation of the mechanisms of CYP3A-mediated negative cooperativity.

Background: Isolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH.Methods: A systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021.Results: Thirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0–15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was −2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death.Conclusions: IRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.

Background: Tachycardia-induced cardiomyopathy (TIC) is caused by prolonged tachycardia, leading to left ventricular dilatation and systolic dysfunction with heart failure. Although TIC is more common in adults, it is rare in early infancy. Methods: Clinical testing was performed as part of medical evaluation and management. Next-generation sequencing (NGS) was conducted for a patient with TIC. A literature review on TIC was also conducted. Results: The case involved a 5-month-old infant referred to the hospital due to symptoms of heart failure lasting at least two months. The infant’s heart rate was 200 beats per minute, the left ventricular ejection fraction fell below 14%, and electrocardiograms showed atrial flutter, suggesting TIC. After cardioversion, there was no recurrence of atrial flutter, and cardiac function improved 98 days after tachycardia arrest. The NGS did not identify any pathogenic variants. The literature review identified eight early infantile cases of TIC. However, no previous reports described a case with such a prolonged duration of TIC as ours. Conclusions: This is the first report of a case of prolonged TIC in a child with the documented time to recover normal cardiac function. The improvement of cardiac function depends on the duration of TIC. Early recognition and intervention in TIC are essential to improve outcomes for infantile patients, as timely treatment offers the potential for recovery.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC. Methods and Results: We recruited children with left ventricular noncompaction from Japanese multi‐institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy‐associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate ( P =0.0009). Conclusions: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease‐causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality‐related cardiac phenotypes.

乳び胸に対する新しい治療戦略としてinterventional radiology （IVR）の有効性が報告されている．成人例では症例が蓄積されつつあるが，小児，特に新生児領域での報告は稀である．症例は完全大血管転位，心室中隔欠損，右側大動脈弓と日齢1に診断した女児．日齢13に肺動脈絞扼術を施行したが，開胸時に乳び胸水を認めた．術後3日目に経管栄養を開始したところ，術後6日目にドレーンより乳び胸水が大量（170 mL/day）に排泄され，内科的治療を開始したが抵抗性であった．そのため，術後11日目にエコーガイド下で鼠径リンパ節からリピオドールを使用したリンパ管造影（intranodal lymphangiography: IL）を施行した．3日後，乳び胸水は改善した．今回，我々は内科的治療に抵抗性であった術後乳び胸の新生児に対して，ILが治療に有効であった症例を経験した．ILは外科的治療と比較して低侵襲なうえ，高い有効率も期待できる手技であり，今後は小児，新生児領域でも症例の蓄積が必要である．