The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome.

Understanding the transcriptomic impact of microgravity and the spaceflight environment is relevant for future missions in space and microgravity-based applications designed to benefit life on Earth. Here, we investigated the transcriptome of adult and neonatal cardiovascular progenitors following culture aboard the International Space Station for 30 days and compared it to the transcriptome of clonally identical cells cultured on Earth. Cardiovascular progenitors acquire a gene expression profile representative of an early-stage, dedifferentiated, stem-like state, regardless of age. Signaling pathways that support cell proliferation and survival were induced by spaceflight along with transcripts related to cell cycle re-entry, cardiovascular development, and oxidative stress. These findings contribute new insight into the multifaceted influence of reduced gravitational environments.

Aortic root valve-sparing repair and dissections in Marfans syndrome during pregnancy: A case series.

INTRODUCTION: Marfan syndrome is a connective tissue disorder caused by mutations in the fibrillar FBN-1 gene. Aortic dissection and rupture are major causes of morbidity and mortality and are of special concern during pregnancy. MATERIALS AND METHODS: The authors report four cases of aortic root repair with preservation of the native aortic valve that have has created a discussion between cardiothoracic surgeons, obstetricians, and gynecologists regarding the best care for Marfan syndrome patients. We present these cases here with a review of the literature. RESULTS: Surgery of the aorta and valves in Marfan syndrome is less risky than in previous eras and surgical management guidelines are generally accepted. Yet, we may be unnecessarily referring women to terminate pregnancies or to avoid pregnancy. We believe there may be alternative options for these patients. CONCLUSIONS: Marfan syndrome during pregnancy can be navigated with preconception counseling, antepartum care, and close postpartum follow-up involving an appropriate multidisciplinary team.

Debranching of Supra-aortic Vessels via Femoral Artery Inflow for Late Ascending Aortic Rupture.

A 56-year-old man with a history of Marfan's syndrome, total arch replacement, descending thoracic endovascular aortic repair, and twice redo sternotomy for pseudoaneurysm repair, presented with a pulsatile chest mass secondary to a contained rupture of the ascending aorta. The patient underwent supra-aortic debranching via the superficial femoral artery and ascending thoracic stent-graft placement under continuous transesophageal echocardiography. Completion angiography demonstrated successful exclusion of the contained rupture. Postoperatively, the patient was neurologically intact, the pulsatile mass resolved, and the bypass grafts remained patent. Chronic respiratory failure and multidrug-resistant pneumonia led to late mortality. This case demonstrates that hybrid repair is effective in the emergent setting of ascending aortic rupture. Debranching of the ascending arch using the superficial femoral artery as inflow is feasible and provides adequate cerebral perfusion despite the length of the bypass. The use of transesophageal echocardiography during stent-graft deployment allows precise device placement in the high-risk area of the ascending aorta proximal to the innominate artery.

Effects of Spaceflight and Simulated Microgravity on YAP1 Expression in Cardiovascular Progenitors: Implications for Cell-Based Repair.

Spaceflight alters many processes of the human body including cardiac function and cardiac progenitor cell behavior. The mechanism behind these changes remains largely unknown; however, simulated microgravity devices are making it easier for researchers to study the effects of microgravity. To study the changes that take place in cardiac progenitor cells in microgravity environments, adult cardiac progenitor cells were cultured aboard the International Space Station (ISS) as well as on a clinostat and examined for changes in Hippo signaling, a pathway known to regulate cardiac development. Cells cultured under microgravity conditions, spaceflight-induced or simulated, displayed upregulation of downstream genes involved in the Hippo pathway such as YAP1 and SOD2. YAP1 is known to play a role in cardiac regeneration which led us to investigate YAP1 expression in a sheep model of cardiovascular repair. Additionally, to mimic the effects of microgravity, drug treatment was used to induce Hippo related genes as well as a regulator of the Hippo pathway, miRNA-302a. These studies provide insight into the changes that occur in space and how the effects of these changes relate to cardiac regeneration studies.

Social framework of pediatric heart recipients who have survived more than 15 post-transplant years: A single-center experience.

To evaluate social development of pediatric heart transplant (tx) recipients who have lived 15 or more years after transplantation. Among 498 pediatric patients, age less than 18 years, who underwent heart transplantation, at a single institution, 337 were performed between 1985 and 1998. We identified all who survived more than 15 years and engaged them in a survey regarding employment, education, marital, and social status. One hundred and eighty-three recipients (54.3%; 183/337) have survived greater than 15 years; of these, 150 (81.9%) subjects are alive with age ranging from 15.04 from 28 years (median, 23.6 years). Forty-two patients (23%) are independent, 127 (69%) were living at home, and 14 (8%) have been lost to follow-up. Ninety-nine survivors (66%) responded to the survey study. Currently, five recipients are married. Seventy-four completed high school, 21 are enrolled in high school, and four did not complete high school. Of the 47 recipients who started college, 27 are currently enrolled, 11 graduated, and nine did not finish college. Ninety-four patients have health insurance, 40 are employed, and 31 receive financial assistance for a disability. The majority of recipients of pediatric heart transplantation are able to reach reasonable academic milestones, achieve social well-being, and professional independence.

Intraperitoneal hemorrhage secondary to ruptured omental artery aneurysm associated with polyarteritis nodosa: a case report.

BACKGROUND: Polyarteritis nodsa (PAN) is a rare disease characterized by acute focal inflammatory damage to small and medium arteries. PAN complicated by ruptured aneurysm is an infrequent presentation with the most affected arteries being the renal and mesenteric arteries. CASE PRESENTATION: A 76-year-old female presented with a low-grade fever, generalized body aches, and abdominal pain. Investigation revealed intraperitoneal bleeding secondary to a ruptured and actively bleeding right omental artery aneurysm. Clinical manifestation, angiography and histology were consistent with PAN. Laparotomy was performed for stabilization and resection of the bleeding aneurysm followed by post operative steroids and cyclophosphamide. Patient was discharged in a stable condition. We reviewed seven cases found in the literature of omental artery aneurysm and rupture. Four cases were proceeded with laparotomy and aneurysm resection while three cases were proceeded with a less invasive approach of arterial embolization. CONCLUSIONS: Omental artery aneurysm is a rare occurrence with even fewer reported cases associated with PAN. Of the seven reported cases, all patients were treated with a surgical intervention. In addition, PAN patients should be treated post-operatively with a course of steroids and cyclophosphamide.

MicroRNA Expression in the Infarcted Heart Following Neonatal Cardiovascular Progenitor Cell Transplantation in a Sheep Model of Stem Cell-Based Repair.

Myocardial infarctions affect approximately 735,000 people annually in the United States and have a substantial impact on quality of life. Neonates have an enhanced capability of repairing cardiovascular damage, while adults do not. The mechanistic basis for this age-dependent difference in regenerative capacity remains unknown. Recent studies have shown that microRNAs (miRNAs) play a significant role in regulating the regenerative ability of cardiovascular cells. This report defines the alterations in miRNA expression within the cardiovascular repair zone of infarcted sheep hearts following intracardiac injection of neonatal islet-1+ cardiovascular progenitor cells. Sheep were infarcted via left anterior descending coronary artery ligation. After 3 to 4 weeks of infarction, sheep neonatal islet-1+ cardiovascular progenitor cells were injected into the infarcted area for repair. Cell-treated sheep were euthanized 2 months following cell injection, and their hearts were harvested for the analysis of miRNA and gene expression within the cardiovascular repair zone. Ten miRNAs were differentially regulated in vivo, including miR-99, miR-100, miR-302a, miR-208a, miR-665, miR-1, miR-499a, miR-34a, miR-133a, and miR-199a. These miRNAs promote stemness, cell division, and survival. Several signaling pathways are regulated by these miRNAs, including Hippo, Wnt, and Erythroblastic Leukemia Viral Oncogene B (ERBB). Transcripts encoding Wnt, ERBB, and Neuregulin 1 (NRG1) were elevated in vivo in the infarct repair zone. Wnt5a signaling and ERBB/NRG1 transcripts contribute to activation of Yes-Associated Protein 1. MiRNAs that impact proliferation, cell survival, and signaling pathways that promote regeneration were induced during cardiovascular repair in the sheep model. This information can be used to design new approaches for the optimization of miRNA-based treatments for the heart.

Intercostal Hernia due to Forceful Coughing With Protrusion of the Lung.

Intercostal herniation is an abnormal protrusion of lung tissue through the boundaries of the thoracic cavity. It is commonly seen after chest trauma or thoracic surgery but rarely occurs spontaneously. We report a male patient who presented with an intercostal herniation after vigorous coughing for over 2 weeks. Treatment of post-coughing intercostal hernias is either conservative management or surgical intervention, which is dictated by the signs, symptoms, site, and presence of strangulation.

Treatment of Chylothorax After Coronary Artery Bypass Grafting.

Chylothorax after coronary artery bypass grafting is a rare complication. The treatment protocol is not well described because of its rarity. The current treatment options for chylothorax include conservative medical treatment or an interventional approach (ie, thoracic duct embolization or surgical ligation of the thoracic duct). With high chest tube output, medical treatment has a high failure rate, and early embolization or surgical ligation of the thoracic duct should be considered to reduce hospital stay cost and morbidity. This report presents 2 cases of chylothorax after coronary artery bypass grafting with different treatment approaches.

Ischemia-reperfusion injury in the lung: quantitation using electron microscopy.

BACKGROUND: The primary objectives of this study were to determine the time course of ischemia-reperfusion injury in an isolated rabbit lung model and to quantify this damage using electron microscopic methodology coupled with statistical analyses. MATERIALS AND METHODS: Eight groups of isolated rabbit lungs (n = 5 per group) were subjected to predetermined periods of ischemia-reperfusion. Two hours of ischemia and 4 hours of reperfusion were concluded to be necessary to induce optimal ischemia-reperfusion injury in this model. Four other groups were subjected to 2 hours of ischemia followed by selected periods of reperfusion. These groups were compared to 4 control groups that were perfused for comparable time periods but without the initial ischemia. New quantitative methods were developed based on the average surface area of the alveoli and average number of alveoli per unit surface area, using scanning electron microscopic examination. RESULTS: Ischemia per se caused substantial damage. Restoration of volume and nutrients reversed this damage at 1 hour of reperfusion, but severe damage was evident at 4 hours of reperfusion, as reported by subjective and blinded examination. By using the new quantitative methods, there was a significant difference between the groups (P < .005) according to the time of post-ischemia-reperfusion, which correlated with the subjective evaluation of damage. CONCLUSIONS: These 2 new quantitative techniques provide an objective assessment of damage in the isolated rabbit lung model, suggesting that they warrant further consideration in similar studies of ischemia reperfusion injury.

Improving outcomes through the use of surgical sealants for anastomotic sealing during cardiovascular surgery.

The continued need to minimize blood product usage both during and after cardiac surgical procedures has been challenged by a changing patient population, and most recently by the withdrawal of the antifibrinolytic aprotinin (Trasylol, Bayer Pharmaceuticals, West Haven, CT, USA) from the market. To meet these challenges, a variety of topical hemostatic tools have continued to emerge in the surgical armamentarium. These include hemostatic agents, adhesives, and sealants designed to control perioperative bleeding and decrease blood product utilization. Optimal application of novel topical adjuncts can be limited due to the lack of clarity on how to differentiate between these adjunctive hemostatic products and their appropriate uses. This paper will review the classes of these products, how and where such products can be used during cardiovascular surgery for achieving hemostasis, and the potential for improved outcomes through the appropriate selection and use of these agents.

Long-term transplant outcomes of donor hearts with left ventricular dysfunction.

OBJECTIVE: Despite small single-center reports demonstrating acceptable outcomes using donor hearts with left ventricular dysfunction, 19% of potential donor hearts are currently unused exclusively because of left ventricular dysfunction. We investigated modern long-term survival of transplanted donor hearts with left ventricular dysfunction using a large, diverse cohort. METHODS: Using the United Network for Organ Sharing database, we reviewed all adult heart transplants between January 2000 and March 2016. Baseline and postoperative characteristics and Kaplan-Meier survival curves were compared. A covariates-adjusted Cox regression model was developed to estimate post-transplant mortality. To address observed variation in patient profile across donor ejection fraction, a propensity score was built using Cox predictors as covariates in a generalized multiple linear regression model. All the variables in the original Cox model were included. For each recipient, a predicted donor ejection fraction was generated and exported as a new balancing score that was used in a subsequent Cox model. Cubic spline analysis suggested that at most 3 and perhaps no ejection fraction categories were appropriate. Therefore, in 1 Cox model we added donor ejection fraction as a grouped variable (using the spline-directed categories) and in the other as a continuous variable. RESULTS: A total of 31,712 donor hearts were transplanted during the study period. A total of 742 donor hearts were excluded for no recorded left ventricular ejection fraction, and 20 donor hearts were excluded for left ventricular ejection fraction less than 20%. Donor hearts with reduced left ventricular ejection fraction were from younger donors, more commonly male donors, and donors with lower body mass index than normal donor hearts. Recipients of donor hearts with reduced left ventricular ejection fraction were more likely to be on mechanical ventilation. Kaplan-Meier curves revealed no significant differences in recipient survival up to 15 years of follow-up (P = .694 log-rank test). Cox regression analysis showed that after adjustment for propensity variation, transplant year, and region, ejection fraction had no statistically significant impact on mortality when analyzed as a categoric or continuous variable. Left ventricular ejection fraction at approximately 1 year after transplantation was normal for all groups. CONCLUSIONS: Carefully selected donor hearts with even markedly diminished left ventricular ejection fraction can be transplanted with long-term survival equivalent to normal donor hearts and therefore should not be excluded from consideration on the basis of depressed left ventricular ejection fraction alone. Functional recovery of even the most impaired donor hearts in this study suggests that studies of left ventricular function in the setting of brain death should be interpreted cautiously.

Atrial natriuretic peptide protects against ischemia-reperfusion injury in rabbit hearts in vivo.

The aim of this study is to investigate whether atrial natriuretic peptide can mimic preconditioning to protect ischemia or reperfusion injury in rabbit hearts. New Zealand white rabbits were randomized into 3 groups: (1) Controls. Hearts received a 60 minute-occlusion of the left anterior descending artery, followed by a 180 minute-reperfusion. (2) Preconditioning. Two 5-minute periods of ischemia separated by a 10-minute reperfusion, followed by a 60-minute ischemia and a 180-minute reperfusion. (3) Atrial natriuretic peptide treatment. Bolus injection of exogenous atrial natriuretic peptide (2.5 microg/kg) given intravenously at 15 minutes prior to 60 minute-ischemia followed by a 180-minute reperfusion. Myocardial necrotic area and area at risk of necrosis were determined by triphenyltetrazolium chloride staining. Ratio of necrotic area to area at risk was 49.95% +/- 1.15%, 7.95% +/- 0.33%, and 8.36% +/- 0.61% in the controls, preconditioning group, and atrial natriuretic peptide group, respectively. Both preconditioning and atrial natriuretic peptide significantly reduced the size of infarct caused by ischemia (preconditioning vs controls, P < .05; atrial natriuretic peptide vs controls, P < .05). Atrial natriuretic peptide can mimic ischemic preconditioning to protect rabbit hearts from prolonged ischemia and reperfusion injury. It may be involved in the cardioprotective mechanisms of preconditioning.

Role of Negative Pressure Wound Care and Hyperbaric Oxygen Therapy for Sternal Wound Infections After Pediatric Cardiac Surgery.

BACKGROUND: Sternal wound infections after pediatric cardiac surgery are uncommon but can be morbid. METHODS: We describe an institutional protocol for complicated sternal wounds utilizing hyperbaric oxygen therapy (HBO) and negative pressure wound therapy (NPWT). PARTICIPANTS: A retrospective chart review (2001-2013) of 4,028 pediatric cardiac operations in 3,264 patients less than 18 years of age. RESULTS: Fifty-three patients (1.62%; 53/3,264) were diagnosed with clinical sternal wound infections. There were 27 (50.9%) males and 26 (49.1%) females. Thirty-seven (69.8%) patients received antibiotics and/or debridement; sixteen (30.2%) patients had more complicated infections requiring NPWT and/or HBO therapy. The time to heal for wounds treated with HBO and HBO + NPWT was a mean of 43.75 (±24.27) days (range: 21-98 days; median: 35 days). Among all infected patients, the time from diagnosis of the infection to resolution of the infection for all survivors was 7 to 98 days (mean: 26.41 days; median: 21 days). Forty-eight (90.6%) patients completely healed their wounds, and 45 (84.9%) patients are currently alive. Thirty-eight patients had a cyanotic cardiac diagnosis and 15 had an acyanotic cardiac diagnosis. The most common bacteria isolated from the blood or wound cultures was Staphylococcus aureus. Six of 53 patients died. Causes of death are as follows: three from respiratory failure, one from sepsis, one from hypoxic ischemic encephalopathy, and one from exsanguination leading to cardiac arrest Conclusions: Complicated sternal wound infections after pediatric cardiac surgery refractory to antibiotic therapy and/or debridement can be successfully treated with NPWT and/or HBO therapy.

Spaceflight Activates Protein Kinase C Alpha Signaling and Modifies the Developmental Stage of Human Neonatal Cardiovascular Progenitor Cells.

Spaceflight impacts cardiovascular function in astronauts; however, its impact on cardiac development and the stem cells that form the basis for cardiac repair is unknown. Accordingly, further research is needed to uncover the potential relevance of such changes to human health. Using simulated microgravity (SMG) generated by two-dimensional clinorotation and culture aboard the International Space Station (ISS), we assessed the effects of mechanical unloading on human neonatal cardiovascular progenitor cell (CPC) developmental properties and signaling. Following 6-7 days of SMG and 12 days of ISS culture, we analyzed changes in gene expression. Both environments induced the expression of genes that are typically associated with an earlier state of cardiovascular development. To understand the mechanism by which such changes occurred, we assessed the expression of mechanosensitive small RhoGTPases in SMG-cultured CPCs and observed decreased levels of RHOA and CDC42. Given the effect of these molecules on intracellular calcium levels, we evaluated changes in noncanonical Wnt/calcium signaling. After 6-7 days under SMG, CPCs exhibited elevated levels of WNT5A and PRKCA. Similarly, ISS-cultured CPCs exhibited elevated levels of calcium handling and signaling genes, which corresponded to protein kinase C alpha (PKCα), a calcium-dependent protein kinase, activation after 30 days. Akt was activated, whereas phosphorylated extracellular signal-regulated kinase levels were unchanged. To explore the effect of calcium induction in neonatal CPCs, we activated PKCα using hWnt5a treatment on Earth. Subsequently, early cardiovascular developmental marker levels were elevated. Transcripts induced by SMG and hWnt5a-treatment are expressed within the sinoatrial node, which may represent embryonic myocardium maintained in its primitive state. Calcium signaling is sensitive to mechanical unloading and directs CPC developmental properties. Further research both in space and on Earth may help refine the use of CPCs in stem cell-based therapies and highlight the molecular events of development.

An Absorbable Hydrogel Spray Reduces Postoperative Mediastinal Adhesions After Congenital Heart Surgery.

BACKGROUND: Adhesions encountered during reoperative cardiac surgery can prolong operative time and increase operative risk. The purpose of this clinical study was to investigate the antiadhesion property of a synthetic bioabsorbable polymer spray after cardiac reoperations in infants. METHODS: A prospective randomized double-blinded study was designed. Forty infants requiring staged cardiac operations were randomly allocated to a study group (n = 20) or a control group (n = 20). The appropriate volume of the polymer was sprayed onto the mediastinal surfaces before chest closure after the first surgical procedure in the study group. At reoperation, adhesions were evaluated by a blinded investigator following a 5-grade scoring system. Five predetermined anatomic areas were scored. Incision to extracorporeal circulation time was also analyzed. RESULTS: In all, 40 subjects were enrolled into the study. Four babies died before the second operation. Three others were missed for reevaluation. The control group (n = 16) had longer incision to extracorporeal circulation time (38 ± 10 minutes) than the study group (n = 17; 23 ± 6 minutes; p < 0.001). The control subjects had significantly more severe adhesions than the study group at all five mediastinal areas: (1) retrosternal (p < 0.001); (2) base of the heart (large vessels [p < 0.05]); (3) right side (p < 0.01); (4) left side (p < 0.02); and (5) diaphragmatic side of the mediastinum (p < 0.001). CONCLUSIONS: The use of synthetic bioabsorbable polymer sealant spray at the end of primary pediatric cardiac surgery reduces the intensity of mediastinal adhesions and the reentry time in infants undergoing repeat median sternotomy.

Effect of left ventricular dysfunction on utilization of donor hearts.

BACKGROUND: In this study we investigated modern, non-utilization rates of potential cardiac donors with left ventricular dysfunction (LVD) to clarify this phenomenon's magnitude and the impact of recent studies suggesting these organs can be safely transplanted. METHODS: Using the United Network for Organ Sharing transplant database, we reviewed all donors evaluated between January 1, 2007 and June 30, 2014. Exclusion criteria included lack of consent and age <13 or >59 years. The number of hearts not transplanted due to non-cardiac causes, structural disease, "other" (previous cardiac surgery, donation after cardiac death, etc.) and isolated LVD was determined and a covariates-adjusted Poisson regression model with robust standard errors was developed to estimate non-utilization relative risk (RR) with 95% confidence interval (CI) for LVD. Heart disposition for potential donor hearts was determined separately for 2 previous eras (1990 to 1999 and 2000 to 2006), and trends were evaluated. RESULTS: There were 60,789 donors assessed. Of the 44,829 organs meeting the inclusion criteria, 15,654 (34.92%) were transplanted and 29,175 (65.08%) were not. Of the non-utilized hearts, 15,512 (34.60%) were declined for non-cardiac reasons, 1,051 (2.34%) for structural disease, 4,073 (9.09%) for "other" and 8,539 (19.05%) exclusively for LVD. Of this last category, 4,950 (11.04%) lacked documented evidence of LVD. Covariates-adjusted RR for non-utilization showed that, for every 10% increase in LV ejection fraction, the risk of non-utilization decreased by 20% (RR = 0.80, 95% CI 0.79 to 0.81). Analysis of era-effect demonstrated significantly decreased overall utilization of donor hearts, with increases in the number of hearts not transplanted across all categories over time (p < 0.001). CONCLUSIONS: Roughly 20% of potential cardiac donors are excluded due to LVD. This figure has not been impacted by recent studies indicating that these hearts may be used safely. More complete data are required to understand why 11.04% of hearts that met inclusion criteria were refused for "poor function" without documented evidence.

Short-term hypoxia improves early cardiac progenitor cell function in vitro.

The use of cardiovascular progenitor cells (CPCs) to repair damaged myocardium has been the focus of intense research. Previous reports have shown that pretreatments, including hypoxia, improve cell function. However, the age-dependent effects of short-term hypoxia on CPCs, and the role of signaling in these effects, are unknown. Cloned neonatal and adult CPCs expressing Isl1, c-Kit, KDR, PDGFRA, and CXCR4, were preconditioned using hypoxia (1% O2 for six hours). Intracellular signaling pathway changes were modeled using Ingenuity Pathway Analysis (IPA), while qRT-PCR, flow cytometry, and immunoblotting were used to measure pathway activation. Cellular function, including survival, cell cycle, and invasion, were evaluated using a TUNEL assay, flow cytometry, and a Transwell® invasion assay, respectively. IPA predicted, and RT-PCR and flow cytometry confirmed, that the PI3K/AKT pathway was activated following short-term hypoxia. Heat shock protein (HSP) 40 expression increased significantly in both age groups, while HSP70 expression increased only in neonatal CPCs. Neonatal CPC invasion and survival improved after hypoxia pre-treatment, while no effect was observed in cell cycling and developmental status. Prostaglandin receptor expression was enhanced in neonatal cells. Prior to transplantation, hypoxic preconditioning enhances CPC function, including invasion ability and pro-survival pathway activation.

Subaortic Stenosis Resection in Children: Emphasis on Recurrence and the Fate of the Aortic Valve.

BACKGROUND: Recurrence after surgical resection of discrete subvalvar aortic stenosis in children often requires repeat operation. Risk factors for recurrence are poorly understood. We sought to determine potential risk factors for recurrence and postoperative comorbidities in the long term. METHODS: Retrospective chart review was performed on all pediatric patients who underwent surgical resection of discrete subaortic stenosis at our institution. Demographics, perioperative findings, and clinical data were analyzed for predisposing factors. RESULTS: From 1991 to 2015, a total of 104 patients underwent primary surgical resection of discrete subaortic stenosis. There were no postoperative deaths. Three (2.9%) patients required pacemaker implantation. Nine (8.4%) patients required repeat resection for recurrence of subaortic membrane over a median follow-up of 8.5 years (interquartile range: 5.9-13.5 years). Actuarial freedom from repeat resection was 100%, 94%, and 82% at one, five, and ten years, respectively. Repeat resection occurred more frequently in patients with genetic disease (37.5% vs 10.7%; P = .033) and preoperative mitral regurgitation (MR; 25% vs 1.2%; P < .001). Postoperative aortic insufficiency (AI) that was moderate or worse was associated with older age at the time of first resection (relative risk [RR]: 1.54, P < .05), moderate or severe preoperative AI (RR: 1.84, P = .002), and repeat resection of subaortic stenosis (RR: 1.90, P < .001). CONCLUSION: The majority of children who undergo surgical resection of subaortic stenosis will not experience recurrence in childhood and those who do require repeat resection may have a higher incidence of genetic disease and preoperative MR. Postoperative AI is associated with repeat resection, older age at the time of surgery, and degree of preoperative AI.