PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

BACKGROUND: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. METHODS: We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. RESULTS: Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. CONCLUSIONS: PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.

Reduced morbidity with early surgical ligation of patent ductus arteriosus in extremely low birth weight infants: a retrospective single-centre study.

INTRODUCTION: Failure of the patent ductus arteriosus to close is common among extremely low birth weight neonates and has been associated with increased morbidities. The objective of this study was to compare outcomes between early and late surgical ligation in extremely low birth weight patients. METHODS: This was a single-centre retrospective cohort study of infants who required surgical closure of patent ductus arteriosus between January 2017 and August 2022. RESULTS: A total of 43 neonates were identified with birth weight less than 1 kg that underwent surgical patent ductus arteriosus ligation. Compared to the late ligation group, the early ligation group experienced fewer total days of mechanical ventilation (43.9 days vs. 97.2 days, p < 0.05) and a shorter length of hospital stay (114.2 days vs. 169.0 days, p < 0.05). CONCLUSION: Early surgical ligation of haemodynamically significant patent ductus arteriosus in extremely low birth weight neonates may improve hospital morbidity, including improved ventilatory outcomes and a shorter length of stay.

Staged unifocalization revisited.

BACKGROUND: A staged thoracotomy unifocalization approach has not been the dominant option over the past 20 years primarily due to the introduction of midline one-stage complete unifocalization. METHODS: In this issue of the Journal of Cardiac Surgery, van de Woestijne et al. publish their experience over the past 30 years in 39 consecutive patients with "consistent" staged unifocalization through a lateral thoracotomy in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries (PA/VSD/MAPCA). RESULTS: They report definitive repair completion in 76.3% of the patients and an overall survival after definitive repair of 96% at 20 years despite the study period ranging from 1989 to the present. CONCLUSION: Given the multiple variations one could have with PA/VSD/MPACA, a midline unifocalization approach may not always be possible. Surgeons should be familiar with the lateral thoracotomy unifocalization staged approach to PA/VSD/MAPCA.

Sinus of Valsalva aneurysm: Defining the optimal approach.

Sinus of Valsalva aneurysm (SVA) is relatively rare, especially in Western countries, and reports on long-term results after surgical SVA repair in a sizable patient cohort are scarce. In this issue of the Journal of Cardiac Surgery, Chaganti and colleagues publish their surgical experience over the past 30 years in 216 patients with SVA. SVAs were closed via a dual approach, with (1) patch closure (80%) or direct closure (20%) of the base of the fistula through aortotomy and (2) direct closure of the ruptured tip through the chamber of rupture. Aortic valve replacement (9.7%) or repair (6.5%) was performed for moderate to severe aortic regurgitation (AR). There was no hospital mortality. During a mean follow-up of 10 years, no patient had residual/recurrent shunting. The actual survival at 10 years was 99%, with only two deaths. Freedom from moderate or severe AR was 98.5% at 10 years. Early and long-term results after surgical repair of SVA were excellent in their 216 patients with a mean follow-up of 10 years. Their dual approach for SVA was effective in preventing residual/recurrent shunting. The need for AVR in 10% of the patients speaks to the importance of follow-up. The current report provides strong support for surgical repair being the preferred management for SVA.

Parameterization, geometric modeling, and isogeometric analysis of tricuspid valves.

Approximately 1.6 million patients in the United States are affected by tricuspid valve regurgitation, which occurs when the tricuspid valve does not close properly to prevent backward blood flow into the right atrium. Despite its critical role in proper cardiac function, the tricuspid valve has received limited research attention compared to the mitral and aortic valves on the left side of the heart. As a result, proper valvular function and the pathologies that may cause dysfunction remain poorly understood. To promote further investigations of the biomechanical behavior and response of the tricuspid valve, this work establishes a parameter-based approach that provides a template for tricuspid valve modeling and simulation. The proposed tricuspid valve parameterization presents a comprehensive description of the leaflets and the complex chordae tendineae for capturing the typical three-cusp structural deformation observed from medical data. This simulation framework develops a practical procedure for modeling tricuspid valves and offers a robust, flexible approach to analyze the performance and effectiveness of various valve configurations using isogeometric analysis. The proposed methods also establish a baseline to examine the tricuspid valve's structural deformation, perform future investigations of native valve configurations under healthy and disease conditions, and optimize prosthetic valve designs.

Serum Monitoring and Phenotype Identification of Stage I Non-Small Cell Lung Cancer Patients.

A stage I non-small cell lung cancer (NSCLC) serum profiling platform is presented which is highly efficient and accurate. Test sensitivity (0.95) for stage I NSCLC is the highest reported so far. Test metrics are reported for discriminating stage I adenocarcinoma vs squamous cell carcinoma subtypes. Blinded analysis identified 23 out of 24 stage I NSCLC and control serum samples. Group-discriminating mass peaks were targeted for tandem mass spectrometry peptide/protein identification, and yielded a lung cancer phenotype. Bioinformatic analysis revealed a novel lymphocyte adhesion pathway involved with early-stage lung cancer.

Robotic Mitral Valve Repair for Simple and Complex Degenerative Disease: Midterm Clinical and Echocardiographic Quality Outcomes.

BACKGROUND: Severe primary (degenerative) mitral regurgitation (MR) is repaired with durable results when simple single-scallop disease is addressed. The midterm quality outcomes of minimally invasive repair for complex disease are unknown, however. METHODS AND RESULTS: From January 2008 to January 2015, 487 patients (56±11 years, 360 men, ejection fraction 65±6%, 98.8% complete follow-up) underwent robotic mitral valve repair for severe nonischemic degenerative MR. Simple pathology was addressed in 289 of 487 (59%) patients, and complex repair (all others) was performed in 198 of 487 (41%). Four patients died during follow-up with a 5-year survival rate 99.5% (99.4% simple; 99.5% complex; hazard ratio, 0.48; 95% confidence interval, 0.05-4.59); and New York Heart Association functional class I/II was documented in 97.9% (477/487). Eight patients had recurrence of moderate-to-severe MR (4 simple, 4 complex), with a 5-year freedom from MR of 94.6% (96.2% simple; 92.7%, complex; P=0.67; hazard ratio, 1.36; 95% confidence interval, 0.34-5.43). Seven patients (2 simple, 5 complex), underwent mitral reoperation, with a 5-year freedom from reoperation of 97.7% (99.1% simple; 95.7% complex; P=0.13; hazard ratio, 3.35; 95% confidence interval, 0.65-17.32). CONCLUSIONS: At a large tertiary care referral center, midterm quality outcomes after robotic correction of degenerative MR are excellent, with very high survival, infrequent complications, and a low likelihood of MR recurrence, regardless of mitral valve repair complexity. Awareness of these improvements in outcome is important to inform contemporary decisions regarding high-quality alternatives to conventional and percutaneous mitral repair.

Perioperative mortality is the Achilles heel for cardiac transplantation in adults with congenital heart disease: Evidence from analysis of the UNOS registry.

BACKGROUND: Adults with congenital heart disease may present with end-stage heart failure necessitating orthotopic heart transplant (OHT). We sought to review the United Network for Organ Sharing (UNOS) experience with this unique cohort focusing on surgical outcomes and survival. METHODS: From the UNOS registry, 737 adult congenital heart disease recipients (ACHDR) out of 26,993 OHT patients (2.7%) who underwent OHT were studied to analyze early and late outcomes and compared to non-congenital recipients (NCR) over a 15-year period (2000-2014). RESULTS: More ACHDR underwent OHT in the recent-era (3.1%; 2010-2014) as compared to the initial-era (2.5%; 2000-2004; p = 0.03). ACHDR were more likely female (40% vs. 24%; p < 0.01), younger (35 vs. 53 years; p < 0.01), less likely to have ventricular assist devices (4.2% vs. 19.3%; p < 0.01), more likely to have class-II panel-reactive antibody >10%; p < 0.01, and were listed for a longer time (249 vs. 181 days; p < 0.01). When compared to the NCR in the same period, the ACHDR cohort had longer postoperative length of stay (27 vs. 20 days; p < 0.01), higher operative mortality (11.5% vs. 4.6% p < 0.001), higher incidence of primary graft dysfunction (4.3% vs. 2.6%; p < 0.01), and higher need for dialysis (20% vs. 9%; p < 0.01). Primary graft dysfunction is the most common cause of death in (5.8%) ACHDR. Although short-term survival is poorer, long-term survival of ACHDR was found to be equivalent or better than NCR in long term. CONCLUSIONS: Perioperative morbidity and mortality adversely affects short-term survival in ACHDR. ACHDR who survive the first post-transplant year have equivalent or better long-term survival than NCR.

Septal myectomy for hypertrophic obstructive cardiomyopathy in Friedreich's ataxia.

Hypertrophic cardiomyopathy associated with Friedreich's ataxia is progressive, and there are few, if any, effective treatments available at present. This case report describes a Friedreich's ataxia patient who had a septal myectomy for the management of hypertrophic cardiomyopathy with improved symptoms over a 7-year period. This suggests that septal myectomy may be a viable option to relieve symptoms and interrupt progression of heart disease in appropriately selected Friedreich's ataxia patients.

Utilization of stem cells to treat congenital heart disease: hype and hope.

PURPOSE OF REVIEW: Surgical advances over the past few decades have transformed the clinical management of congenital heart disease, such as hypoplastic left heart syndrome. Congenital heart disease affects more than 1% of liveborn infants and accounts for more than 2.5 million affected children per year worldwide. The cost and availability of complex medical management for these children becomes bluntly realized when heart failure progresses and only palliative options remain. Cell-based cardiac regeneration has been the focus of intensive efforts in adult heart disease for more than a decade and now has promise for pediatrics. RECENT FINDINGS: Innate cardiac regeneration in the pediatric setting is measurable and potentially modifiable in the early stages of development. Repurposing cell-based manufactured products to promote cardiac regeneration in congenital heart disease has demonstrated significant improvement in cases of dilated cardiomyopathy and structural heart disease in infants. SUMMARY: A focus on preemptive cardiac regeneration in the pediatric setting may offer new insights into the timing of surgery, location of cell-based delivery, and type of cell-based regeneration that could further inform acquired cardiac disease applications. The concept of cell-based pediatric cardiac regenerative surgery could transform the management of congenital heart disease when cost-effective strategies produce a valuable adjunctive solution to improve outcomes of cardiac surgery.

When repair is not feasible: prosthesis selection in children and adults with congenital heart disease.

Congenital heart surgeons face many challenges when dealing with valvular pathology in the pediatric population. Because of the concerns related to growth, repair should be the main goal. However, this is not always feasible and valve replacement becomes the only other alternative. Valve replacement also represents one of the most common procedures performed for adults with congenital heart disease, with several valve options existing including homografts, xenografts, autografts, and other artificial prostheses. The choice sometimes may be difficult because there are advantages and disadvantages to each valve substitute. In this article, we will address the different options of valve replacement in children and adults with congenital heart disease, and review the current literature that supports current practice.

Perioperative management of patients with DiGeorge syndrome undergoing cardiac surgery.

OBJECTIVE: DiGeorge syndrome is a genetic disorder with multisystem involvement resulting in craniofacial and cardiac anomalies and parathyroid and immune system dysfunction. This study describes perioperative management of a large cohort of patients with DiGeorge syndrome undergoing cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Major academic tertiary institution. PARTICIPANTS: The medical records of patients diagnosed with DiGeorge syndrome and undergoing cardiac surgery at this institution, from January 1, 1976, to July 31, 2012, were reviewed for phenotypic characteristics and intraoperative and postoperative complications, with specific attention to hemodynamic instability, perioperative perturbations of plasma calcium homeostasis, and airway difficulty. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients underwent 136 cardiac surgical procedures; 47 patients (76%) had multiple operations. Sternotomies for reoperations often were complex (8 complicated by vascular injury or difficulty achieving hemostasis and 5 requiring bypass before sternotomy). Two patients had persistent hypocalcemia intraoperatively, requiring infusion of calcium chloride, and hypocalcemia developed postoperatively in 8 patients. Prolonged mechanical ventilation (>24 hours) was required after 48 procedures (35%), and 25 (18%) required prolonged inotropic support (>72 hours). Infectious complications occurred after 31 procedures (23%). There was no in-hospital or 30-day mortality. CONCLUSIONS: Patients with DiGeorge syndrome often have complex cardiac anomalies that require surgical repair. The postoperative course is notable for the frequent need for prolonged respiratory and hemodynamic support. Patients can develop hypocalcemia and may require calcium supplementation. Immunodeficiencies may be associated with the increased rate of postoperative infections and may dictate the need for specific transfusion management practices.

Robotic mitral valve repair: a review of anesthetic management of the first 200 patients.

OBJECTIVE: The aim of this study was to describe the evolution in anesthetic technique used for the first 200 patients undergoing robotic mitral valve surgery. DESIGN: A retrospective review. SETTING: A single tertiary referral academic hospital. PARTICIPANTS: Two hundred consecutive patients undergoing robotic mitral valve surgery using the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) at Mayo Clinic Rochester. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After obtaining institutional review board approval, surgical and anesthetic data were recorded. For analysis, patients were placed in 4 groups, each containing 50 consecutive patients, labeled Quartiles 1 to 4. Over time, there were statistically significant decreases in cardiopulmonary bypass and aortic cross-clamp times. Significant differences in the anesthetic management were shown, with a reduction of intraoperative fentanyl and midazolam doses, and the introduction of paravertebral blockade in Quartile 2. There was a reduction of time between incision closure and extubation, and nearly 90% of patients were extubated in the operating room in Quartiles 3 and 4. Despite changes to the intraoperative analgesic management, and focus on earlier extubation, there were no differences seen in visual analog scale (VAS) pain scores over the 4 quartiles. Reductions were seen in total intensive care unit and hospital length of stay during the study period. CONCLUSIONS: Changes to the practice, including efforts to limit intraoperative opioid administration and the addition of preoperative paravertebral blockade, helped facilitate earlier extubation. In the second half of the study period, close to 90% of patients were extubated in the operating room safely and without delaying patient transition to the intensive care unit.

Septum primum atrial septal defect in an infant with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a form of congenital heart disease characterized by severe underdevelopment of the left heart, leading to inadequate systemic blood flow. Several different atrial septal morphologies are observed in HLHS, most commonly a secundum atrial septal defect, patent foramen ovale, intact septum, and leftward displacement of the superior attachment of the septum primum. It has been postulated that atrial septal development is associated with the development of the left heart. We present a case of a newborn infant with HLHS and the unusual finding of a primum ASD.

Bayesian Optimization-Based Inverse Finite Element Analysis for Atrioventricular Heart Valves.

Inverse finite element analysis (iFEA) of the atrioventricular heart valves (AHVs) can provide insights into the in-vivo valvular function, such as in-vivo tissue strains; however, there are several limitations in the current state-of-the-art that iFEA has not been widely employed to predict the in-vivo, patient-specific AHV leaflet mechanical responses. In this exploratory study, we propose the use of Bayesian optimization (BO) to study the AHV functional behaviors in-vivo. We analyzed the efficacy of Bayesian optimization to estimate the isotropic Lee-Sacks material coefficients in three benchmark problems: (i) an inflation test, (ii) a simplified leaflet contact model, and (iii) an idealized AHV model. Then, we applied the developed BO-iFEA framework to predict the leaflet properties for a patient-specific tricuspid valve under a congenital heart defect condition. We found that the BO could accurately construct the objective function surface compared to the one from a [Formula: see text] grid search analysis. Additionally, in all cases the proposed BO-iFEA framework yielded material parameter predictions with average element errors less than 0.02 mm/mm (normalized by the simulation-specific characteristic length). Nonetheless, the solutions were not unique due to the presence of a long-valley minima region in the objective function surfaces. Parameter sets along this valley can yield functionally equivalent outcomes (i.e., closing behavior) and are typically observed in the inverse analysis or parameter estimation for the nonlinear mechanical responses of the AHV. In this study, our key contributions include: (i) a first-of-its-kind demonstration of the BO method used for the AHV iFEA; and (ii) the evaluation of a candidate AHV in-silico modeling approach wherein the chordae could be substituted with equivalent displacement boundary conditions, rendering the better iFEA convergence and a smoother objective surface.

Multiple arterial grafts improve late survival of patients undergoing coronary artery bypass graft surgery: analysis of 8622 patients with multivessel disease.

BACKGROUND: Use of the left internal mammary artery (LIMA) in multivessel coronary artery disease improves survival after coronary artery bypass graft surgery; however, the survival benefit of multiple arterial (MultArt) grafts is debated. METHODS AND RESULTS: We reviewed 8622 Mayo Clinic patients who had isolated primary coronary artery bypass graft surgery for multivessel coronary artery disease from 1993 to 2009. Patients were stratified by number of arterial grafts into the LIMA plus saphenous veins (LIMA/SV) group (n=7435) or the MultArt group (n=1187). Propensity score analysis matched 1153 patients. Operative mortality was 0.8% (n=10) in the MultArt and 2.1% (n=154) in the LIMA/SV (P=0.005) group, which was not statistically different (P=0.996) in multivariate analysis or the propensity-matched analysis (P=0.818). Late survival was greater for MultArt versus LIMA/SV (10- and 15-year survival rates were 84% and 71% versus 61% and 36%, respectively [P<0.001], in unmatched groups and 83% and 70% versus 80% and 60%, respectively [P=0.0025], in matched groups). MultArt subgroups with bilateral internal mammary artery/SV (n=589) and bilateral internal mammary artery only (n=271) had improved 15-year survival (86% and 76%; 82% and 75% at 10 and 15 years [P<0.001]), and patients with bilateral internal mammary artery/radial artery (n=147) and LIMA/radial artery (n=169) had greater 10-year survival (84% and 78%; P<0.001) versus LIMA/SV. In multivariate analysis, MultArt grafts remained a strong independent predictor of survival (hazard ratio, 0.79; 95% confidence interval, 0.66-0.94; P=0.007). CONCLUSIONS: In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery, arterial grafting of the non-left anterior descending vessels conferred a survival advantage at 15 years compared with SV grafting. It is still unproven whether these results apply to higher-risk subgroups of patients.

Outcomes of general anesthesia for noncardiac surgery in a series of patients with Fontan palliation.

OBJECTIVES: To describe the experience of a single, tertiary care institution in the care of patients with Fontan physiology undergoing anesthesia for noncardiac surgery. BACKGROUND: The Fontan procedure was developed in 1971 to palliate patients with univentricular cardiac physiology leading to long-term survival of these patients, who may now present as adults for noncardiac surgery. METHODS: We retrospectively reviewed the medical records of Fontan patients 16 years and older who underwent general anesthesia for noncardiac surgery at Mayo Clinic in Rochester, Minnesota. Preoperative data, perioperative course, intraoperative and postoperative hemodynamic, pulmonary, cardiovascular, and renal complications were described. RESULTS: Thirty-nine general anesthetics were administered to 31 patients for noncardiac surgery after Fontan palliation. Perioperative complications occurred in 12 of the 39 (31%) noncardiac surgeries, and there was one postoperative death that occurred on day 13 after ventral hernia repair. The two patients who had complications that did not resolve (long-term dialysis and death) had ejection fractions well below the mean for the group (22% and 28%). CONCLUSION: It may be more appropriate for Fontan patients to undergo anesthesia for noncardiac surgery in a tertiary institution, particularly patients with an ejection fraction of <30%. Intraoperative arterial blood pressure monitoring and overnight admission are likely appropriate for most cases.

Repair of acute inferior wall myocardial infarction-related basal ventricular septal defect: transatrial versus transventricular approach.

BACKGROUND: We describe our contemporary experience for the management of patients with an acute postinfarction basal ventricle septal defect (VSD) using the transatrial (TA) and transventricular (TV) approaches. METHODS: Retrospective review of all patients diagnosed with an ischemic basal VSD since January 2000. There were 20 patients with a median age of 68 years (39 to 85); 13 (65%) were males. Median time from diagnosis of the ischemic basal VSD to operation was 22 hours (6 to 144). RESULTS: All patients received standard patch closure of the septal defect with exposure of the VSD through the TA approach in eight patients (40%) and the TV approach in 12 (60%). All TA group patients received tricuspid valve replacement, while in the TV group, two had tricuspid valve replacement and two repair. Five patients (25%) had clinically insignificant (<0.5 mm) residual septal defects; three additional patients (15%) experienced patch dehiscence and two (10%) underwent re-exploration. There were five mortalities (25%): one in the TA group (right ventricular heart failure) and four in the TV group (one right ventricular heart failure, three ventriculotomy site hemorrhage or patch dehiscence). Preoperative right atrial pressure (p=0.0003) and right ventricular dysfunction (p=0.04) were predictors of hospital mortality. Follow-up of the hospital survivors was 4.3 years (40 days to 11.5 years) with one death at seven years. CONCLUSION: Operative mortality associated with repair of postinfarction basal ventricular septal defect is high and is related to right ventricular failure and bleeding from the ventriculotomy. The TA approach avoids ventriculotomy-associated bleeding and provides excellent exposure but is associated with an increased incidence of tricuspid valve replacement.

Quadricuspid aortic valve with ruptured sinus of Valsalva.

We present a case of a 24-year-old woman who was diagnosed with quadricuspid aortic valve with ruptured sinus of Valsalva. Quadricuspid aortic valve is a rare congenital cardiac anomaly. The recognition of quadricuspid aortic valve has clinical significance as it causes aortic valve dysfunction, and is often associated with other congenital cardiac abnormalities. We showed the important role of multimodality imaging in diagnosing a quadricuspid aortic valve associated with ruptured sinus of Valsalva.

Plasma-free hemoglobin levels in advanced vs. conventional infant and pediatric extracorporeal life support circuits.

Extracorporeal life support (ECLS) is a reliable method to support pediatric patients with reversible cardiorespiratory failure associated with congenital heart disease, respiratory insufficiency, or after cardiac surgery. In 2010, our institution adopted an infant/pediatric extracorporeal membrane oxygenation (ECMO) circuit that contains a magnetically levitated centrifugal pump, polymethylpentene oxygenator, and shorter tubing length (ECMO II circuit). Our prior circuit contained a nonocclusive roller pump, polypropylene oxygenator, venous compliance chamber, and hemoconcentrator (ECMO I circuit). A retrospective chart review comparing ECMO I and ECMO II daily plasma-free hemoglobin (PFH) values was conducted. We hypothesized that the PFH is similar between the two ECMO circuit groups. We reviewed medical records of children 3 years of age or younger weighing less than 13 kg who required ECLS between January 2008 and February 2012. PFH levels from 18 ECMO II patients were compared with levels in a retrospective group of an equal number of well-matched ECMO I circuit patients. There was no significant difference between ECMO I and ECMO II circuit groups regarding mean time on ECMO, age in days, and weight. There was also no significant difference in the group mean levels of PFH between ECMO I and ECMO II circuits. There was a significant increase in PFH with hours on ECMO (p < .01) within and between both circuit groups (p < .01) and a significantly greater increase in PFH with ECMO hours (p = .0091) in the ECMO I circuit group. Although there was no significant difference in average PFH with the change in ECMO II circuit technology, advancements such as the magnetically levitated blood pump and polymethylpentene gas exchange device has been associated with significantly fewer mechanical component change-outs (p = .0156) and less clots and fibrin build-up in the circuits (p = .0548).