The effect of body weight in infants undergoing ventricular septal defect closure: A report from the Nationwide Japanese Congenital Surgical Database.

OBJECTIVE: In infants with ventricular septal defect (VSD) who undergo surgical intervention, body weight, along with age, is frequently thought to be the decisive predictor of morbidity and mortality after surgery; however, its information on quantitative risk assessment is limited. METHODS: All infants (<1 year old) with a fundamental diagnosis of VSD who underwent surgical VSD closure or pulmonary artery banding between 2012 and 2016 were identified from the Japan Cardiovascular Surgery Database Congenital Section. The outcome of interest was a composite end point of all-cause death and major complications within 30 days after surgery. We evaluated the association between body weight at surgery and composite end point using logistic regression models. RESULTS: A total of 4947 cases were analyzed (median age, 125; interquartile range [IQR], 79-193 days; median body weight, 4.94 [IQR, 4.00-6.00] kg), including 4310 cases (87.1%) treated with surgical VSD closure and 637 (12.9%) treated with pulmonary artery banding. The surgical course was uncomplicated in 94.2% of cases, 23 (0.5%) died, and 283 (5.7%) experienced major complications. The risk of the composite end point was higher along with lower body weight (adjusted odds ratio, 1.56 for every -1 kg; 95% confidence interval, 1.30-1.88; P < .001) and plateaued at body weight of approximately >4.5 kg via smoothing spline curve. Importantly, cases with approximately <4.5 kg of body weight had higher predicted risk regardless of age. CONCLUSIONS: Surgical intervention for infants with VSD was safely performed in contemporary practice; however, caution is warranted in lower body weight infants, particularly for infants with approximately <4.5 kg.

Successful Total Pericardiectomy for Constrictive Pericarditis in the First Series of Japanese Patients With Mulibrey Nanism.

Patients with Mulibrey nanism (MUL) present with growth failure and multiple organ manifestations, and MUL is caused by mutations in TRIM37. In this article, we report on the first case series of Japanese patients with MUL who developed congestive heart failure due to constrictive pericarditis. Our case series suggests that early diagnosis and total pericardiectomy before adherence of the pericardium might provide clinical benefit and better prognosis for MUL.

Successful management of living donor liver transplantation for biliary atresia with single ventricle physiology-from peri-transplant through total cavopulmonary connection: A case report.

Children with single ventricle physiology have complete mixing of the pulmonary and systemic circulations, requiring staged procedures to achieve a separation of these circulations, or Fontan circulation. The single ventricle physiology significantly increases the risk of mortality in children undergoing non-cardiac surgery. As liver transplantation for patients with single ventricle physiology is particularly challenging, only a few reports have been published. We herein report a case of successful LDLTx for an 8-month-old pediatric patient with biliary atresia, heterotaxy, and complex heart disease of single ventricle physiology. The cardiac anomalies included total anomalous pulmonary venous return type IIb, intermediate atrioventricular septal defect, tricuspid regurgitation grade III, coarctation of aorta, interrupted inferior vena cava, bilateral superior vena cava, and polysplenia syndrome. Following LDLTx, the patient sequentially underwent total cavopulmonary shunt + Damus-Kaye-Stansel at 3 years of age and extracardiac total cavopulmonary connection (EC-TCPC) completion at 5 years of age; 7 years have now passed since LDLTx (2 years post-EC-TCPC). We describe the details of the management of LTx in the presence of cardiac anomalies and report the long-term cardiac and liver function, from peri-LDLTx through EC-TCPC completion.

Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction.

Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expression and are inefficient. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT in reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial infarction. Thus, efficient, non-integrating SeV vectors may serve as a powerful system for cardiac regeneration.

Palliative Mitral Valve Repair During Infancy for Neonatal Marfan Syndrome.

An infant with neonatal Marfan syndrome (nMFS), a condition that is nearly always lethal during infancy, was referred to our hospital with symptoms of congestive heart failure resulting from severe mitral valve insufficiency. During mitral valve repair, the use of an annuloplasty ring was waived until annular dilatation was achieved after 2 palliative mitral valvuloplasty procedures. After the definitive operation, the patient's mitral valve function remained within normal limits until the last follow-up when the patient was 11 years old. To the best of our knowledge, this patient has the longest recorded survival after mitral valve repair.

Heterotopic transplantation of a decellularized and recellularized whole porcine heart.

OBJECTIVES: One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS: A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS: In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS: To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.

Variable severity of cardiovascular phenotypes in patients with an early-onset form of Marfan syndrome harboring FBN1 mutations in exons 24-32.

A subgroup of patients with Marfan syndrome (MFS) who have mutations in exons 24-32 of the FBN1 gene manifests severe atrioventricular valve insufficiency and skeletal problems as early as the neonatal period. These patients usually die in the first 2 years of life, thus a region between exons 24 and 32 of FBN1 is recognized as a critical region for this neonatal form of MFS (nMFS). Here, we report five consecutive patients who manifested a cardiovascular phenotype until infancy with mutations in the critical region for nMFS. Although three of these patients showed severe mitral regurgitation and died before reaching 1 year of age, the remaining two patients survived for over 5 years under medical and/or surgical interventions. Two splicing mutations and one missense mutation were identified in the three deceased patients, whereas two missense mutations were found in the two survivors. Currently, the clinical severity of patients with early-onset MFS harboring mutations in the critical region for nMFS seem to be more variable than ever thought, and intensive treatments are recommended even in this subgroup of patients with MFS.

Positional desaturation due to persistent left superior vena cava draining into the left atrium.

Persistent left superior vena cava (PLSVC) is a rare congenital anomaly whose prevalence is 0.3 % of general population. The majority of PLSVC drain into right atrium (RA) through the coronary sinus without clinical harm. However, in about 10 % of patients with PLSVC, it drains into left atrium (LA) causing right-to-left shunt. Here, we present a 60-year-old male patient with a PLSVC draining into LA, who developed dyspnea and desaturation depending on the body position after trans-catheter coil embolization of coronary to pulmonary artery fistulas. PLSVC draining into LA should be included in the differential diagnosis of positional desaturation.

Fontan completion in a patient with previous liver transplantation.

We present the first case of a successful Fontan completion in a patient with previous liver transplantation. An infant with polysplenia syndrome with a functional single ventricle and biliary atresia had been surgically managed by pulmonary artery banding, Kasai operation and living donor liver transplantation. Subsequently, the patient successfully underwent bidirectional cavopulmonary shunt and total cavopulmonary connection with extracardiac conduit at 3 and 5 years of age, respectively.

MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures.

Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming.

Negative pressure therapy for post-sternotomy wound infections in young children.

OBJECTIVES: Post-sternotomy wound infection remains a significant morbidity in congenital and paediatric cardiac surgery. However, the techniques used for this complication in children are not optimal in terms of mortality, morbidity and the use of medical resources. Negative pressure therapy is an effective modality in the treatment in adults, but reports of its use in children are limited. This study evaluated the use of negative pressure therapy in young children for post-sternotomy wound infections. METHODS: From October 2004 to June 2012, 15 consecutive cases of post-sternotomy wound infections in patients ≤6 years of age were managed with negative pressure therapy, and these patients were followed up for ≥12 months after wound closure. The median Aristotle comprehensive complexity score was 9.9 ± 4.0. The infection was identified at a median of 16 days after surgery, and the procedure was performed within 24 h of diagnosis. No additional surgical procedures were applied. RESULTS: No cases of hospital mortality or second surgery for infection control occurred. The median duration until wound closure was 25 days (range: 5-92 days). Further, no patient showed sternal instability at treatment termination. During the mean follow-up period of 45.8 ± 31.3 months after wound closure, no admission occurred for infection recurrence. According to a multivariable analysis, the infection depth and patient weight significantly lengthened treatment duration (P = 0.008 and 0.046, respectively). CONCLUSIONS: Negative pressure therapy is an effective treatment modality for wound infections in paediatric cardiac surgery and results in low morbidity, mortality and medical resource use.

Induction of human cardiomyocyte-like cells from fibroblasts by defined factors.

Heart disease remains a leading cause of death worldwide. Owing to the limited regenerative capacity of heart tissue, cardiac regenerative therapy has emerged as an attractive approach. Direct reprogramming of human cardiac fibroblasts (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported previously that induced cardiomyocyte-like cells (iCMs) can be directly generated from mouse cardiac fibroblasts in vitro and vivo by transduction of three transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. In the present study, we sought to determine whether human fibroblasts also could be converted to iCMs by defined factors. Our initial finding that GMT was not sufficient for cardiac induction in HCFs prompted us to screen for additional factors to promote cardiac reprogramming by analyzing multiple cardiac-specific gene induction with quantitative RT-PCR. The addition of Mesp1 and Myocd to GMT up-regulated a broader spectrum of cardiac genes in HCFs more efficiently compared with GMT alone. The HCFs and human dermal fibroblasts transduced with GMT, Mesp1, and Myocd (GMTMM) changed the cell morphology from a spindle shape to a rod-like or polygonal shape, expressed multiple cardiac-specific proteins, increased a broad range of cardiac genes and concomitantly suppressed fibroblast genes, and exhibited spontaneous Ca(2+) oscillations. Moreover, the cells matured to exhibit action potentials and contract synchronously in coculture with murine cardiomyocytes. A 5-ethynyl-2'-deoxyuridine assay revealed that the iCMs thus generated do not pass through a mitotic cell state. These findings demonstrate that human fibroblasts can be directly converted to iCMs by defined factors, which may facilitate future applications in regenerative medicine.

Bilateral banding of malpositioned pulmonary artery branches.

This report presents two rare cases of malpositioned pulmonary artery branches managed by bilateral banding. The left-branch pulmonary artery, originating from and directly superior to the right branch, entered the posterior mediastinum before heading toward the left pulmonary hilum. The ostium of the left branch could not be visualized by midline sternotomy. Therefore, a double-subtraction technique was used to pass the banding tape around the left branch from the right side. The tape location was adjusted and confirmed by intraoperative echocardiography.

Bridging annuloplasty for left atrioventricular valve of partial atrioventricular septal defect.

Residual left atrioventricular valve regurgitation after conventional repair technique for partial atrioventricular septal defect most commonly occurs in the central position. We describe here the technique for bridging annuloplasty on the opposing anterior and posterior annuli of the atrioventricular valve in selected patients with short leaflets.

Open anastomosis of extracardiac conduit for total cavopulmonary connection decreases post-operative pleural effusion.

OBJECTIVE: The goal of this study was to see whether the open anastomosis technique using vacuum-assisted venous drainage at the time of the Fontan procedure was associated with decreased post-operative pleural effusion. METHODS: We analysed a subgroup of patients with a functional single ventricle who underwent non-fenestrated total cavopulmonary connection completion with the insertion of an extracardiac conduit as the sole or predominant procedure conducted by a single surgeon at a single institute, using either an open or closed anastomosis technique. RESULTS: Median age and weight were 2.3 years, with a range from 1.3 to 27.6 years and 11.4 kilograms, with a range from 9.7 to 43 kilograms, respectively. The open anastomosis technique was associated with a shorter bypass run (p = 0.015), decreased surgical duration (p = 0.032), fewer pleural effusion days (p = 0.049), and lesser pleural effusion (p = 0.013) than closed anastomosis. Correlation analysis demonstrated a significant relationship between the amount of pleural effusion and surgical duration (correlation efficient, 0.535; p = 0.033). A logistic regression model showed that the open technique was associated with a 20-fold increase in the likelihood of having a total chest tube discharge of less than 300 millilitres (p = 0.027). CONCLUSIONS: The open anastomosis technique shortens operative duration and bypass run, which in turn might contribute to decreased pleural effusion soon after the modified Fontan procedure.

Fenestrated exclusion of the right ventricle for tricuspid atresia and absent pulmonary valve.

The case of a boy who had an absent pulmonary valve, tricuspid atresia, intact ventricular septum, coronary-to-right-ventricular fistula, and dysplasia of the right ventricular free wall is described. At the bidirectional cavopulmonary shunt procedure, the right ventricular free wall was opened and two major fistula orifices to the cavity were closed with sutures. A fenestrated circular patch was placed in the main pulmonary artery and the right ventricular free wall was plicated. The patient then underwent completion for total cavopulmonary connection. Follow-up catheterization showed that the pulmonary artery was partially excluded with minimal pressure wave conduction from the right ventricle, which significantly shrank. This new approach seems to be effective and reproducible in this particular situation.

Multislice computed tomography is useful for evaluating partial anomalous pulmonary venous connection.

Volume-rendered images, derived from multidetector-row computed tomography (MDCT), can facilitate assessment of the morphology of partial anomalous pulmonary venous connection and are thus useful in pre-operative planning to prevent surgical morbidity and assist post-operative evaluations.

Ross-Konno operation for patients with Shone complex.

We report the cases of 2 pediatric patients who had Shone complex. Each child had severe left ventricular outflow tract obstruction and marginal mitral obstruction, and both underwent the Ross-Konno operation. The mitral valve was left alone. Both patients survived the operations, and serial follow-up echocardiography up to 4 years later showed a decreased or decreasing trend in the peak mitral diastolic velocity. The Ross-Konno procedure can be an acceptable approach for a subgroup of patients who have Shone complex.