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Background: In light of the updated lowered threshold for diagnosing pulmonary hypertension (PH), the reversibility of precapillary PH with left ventricular assist device (LVAD) and the associated post-heart transplantation (HT) outcomes remain unclear., Methods: Using data from the United Network for Organ Sharing database, we aimed to investigate predictors of persistent precapillary PH in HT recipients bridged with LVAD and examine the interrelated post-HT survival using the updated pulmonary vascular resistance (PVR) cutoff of >2 Wood units for precapillary PH., Results: Among 2169 HT recipients bridged with LVAD, 1299 had PVR >2 at baseline; 551 (42.4%) of whom normalized their PVR ≤2 and 748 (57.6%) remained with elevated PVR >2 after LVAD implantation. Female sex (adjusted odds ratio [aOR]; 2.22, 95% confidence interval [CI], 1.61-3.07; P < .001) and inotrope treatment at listing (aOR, 1.31; 95% CI, 1.03-1.66; P = .028) were associated with persistently elevated PVR after LVAD. Conversely, longer duration of LVAD support (aOR, 0.74; 95% CI, 0.65-0.84; P < .001) and use of HeartMate II (aOR, 0.74; CI, 0.59-0.93; P = .011) were found to be protective against persistently elevated PVR after LVAD. Persistently elevated PVR >2 after LVAD was associated with increased risk of death compared with those who normalized their PVR (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.01-1.57; P = .037). However, the normalized PVR post-LVAD group had comparable survival with those with PVR ≤2 at baseline (aHR, 0.76; 95% CI, 0.57-1.02; P = .07)., Conclusions: Many recipients of HT bridged with LVAD remain with PVR >2 after LVAD implantation, which is associated with increased risk of death after HT compared with patients with normalized PVR after LVAD., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First)., Methods: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m 2 ) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed., Results: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m 2 ). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77)., Conclusions: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients., Competing Interests: Conflict of Interest Statement D.F.T.: royalties or licenses from McGraw Hill. R.L.K.: payment for expert testimony University of Michigan. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Right ventricular (RV) donor-recipient sizing has been demonstrated to be a sensitive predictor for mortality after heart transplantation. We sought to understand the relationship between donor-recipient RV mass (RVM) ratio and pulmonary vascular resistance (PVR) on outcomes after heart transplantation., Methods: Adult heart transplant recipients from the United Network for Organ Sharing database were included (N = 42,594). The influence of RVM ratio and PVR on 1-year mortality was assessed by logistic regression after multivariable adjustment., Results: Among transplant recipients, median PVR was 2.4 Wood units (WU) (range, 1.7-3.3 WU) and median RVM ratio was 1.2 (1.0-1.3). Without considering PVR, RVM ratio was highly associated with postoperative dialysis (odds ratio [OR], 0.49; P < .001) and 1-year mortality (OR, 0.64; P < .001). Without considering RVM ratio, PVR was highly associated with 1-year mortality (OR, 1.05; P < .001), but not postoperative dialysis (OR, 0.98; P = .156). When considering both RVM ratio and PVR, the risk associated with each remained significant, but PVR did not modify the effect of RVM ratio on 1-year mortality (RVM ratio × PVR: OR, 0.99; P = .858). To maintain a consistent predicted 1-year mortality, RVM ratio would need to increase by 0.12 for each WU increase in PVR. Secondary analyses found that a 1 WU change in PVR was associated with an 11% increase in mortality risk in RVM ratio mismatched patients (RVM ratio < 1; P = .001), but only a 5% increase in RVM ratio matched patients (RVM ratio ≥ 1; P = .003)., Conclusions: RVM ratio and recipient PVR are independent predictors of 1-year mortality. Still, a larger RV mass may be utilized to mediate the effects of an elevated PVR., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Cardiosphere-derived cell (CDC) transplantation has been shown to attenuate right ventricular (RV) dysfunction in patients with hypoplastic left heart syndrome. However, live cell transplantation requires complex handling protocols that may limit its use. Exosomes are protein and nucleic acid-containing nanovesicles secreted by many cell types, including stem cells, which have been shown to exert a cardioprotective effect comparable with whole cells following myocardial injury. We therefore sought to evaluate 3 human CDC-derived exosome preparations in a juvenile porcine model of acute pressure-induced RV dysfunction., Methods: Twenty immunocompetent juvenile Yorkshire pigs (7-10 kg) underwent pulmonary arterial banding followed by intramyocardial test agent administration: control (n = 6), XO-1 (n = 4), XO-2 (n = 5), and XO-3 (n = 5). Animals were monitored for 28 days postoperatively with periodic phlebotomy and echocardiography, followed by extensive postmortem gross and histopathologic analysis., Results: All animals survived the banding operation. One died suddenly on postoperative day 1; another was excluded due to nonstandard response to banding. Of the remaining animals, there were no clinical concerns. RV fractional area change was improved in the XO-1 and XO-2 groups relative to controls at postoperative day 28. On histologic analysis, exosome-treated groups exhibited decreased cardiomyocyte hypertrophy with respect to controls., Conclusions: Human CDC-derived exosome administration was associated with significant preservation of RV systolic function in the setting of acute pressure overload. Such acellular preparations may prove superior to whole cells and may represent a novel therapeutic approach to clinical myocardial injury., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To select a suitable combination of classic angiogenic and vascular stabilization factors to improve the proliferation and maturity of neovascularization of lung tissue in a rat pulmonary arterial hypertension (PAH) model., Methods: PAH rat model was established by intraperitoneal injection of monocrotaline. Proangiogenic factors hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), as well as vascular stabilization factors angiopoietin-1 (Ang-1), platelet-derived growth factor, and transforming growth factor-beta were transfected by pairs into the lung tissue of rats with PAH through lentivirus. Four weeks later, pulmonary artery angiography and hemodynamic parameters were determined to testify the remission of PAH. Immunofluorescence staining and Western blot were performed to investigate the structure and function of neovascularization., Results: The pulmonary artery pressure and weight index of the right ventricle in HGF+Ang-1 and VEGF+Ang-1 groups were significantly decreased compared with vehicle group. The contrast medium filling time and right pulmonary artery root diameter were also significantly decreased. In addition, the maturity and perfusion of neovascularization in HGF+Ang-1 and VEGF+Ang-1 groups were promoted compared to vehicle group, and vascular leakage was reduced. Finally, the adherens junction integrity of vascular endothelial cells in HGF+Ang-1 and VEGF+Ang-1 combinations was upregulated compared with other combinations., Conclusions: HGF+Ang-1 transfection and VEGF+Ang-1 transfection alleviate PAH by promoting maturation and stability of new blood vessels, which may be potential candidates for PAH treatment., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: A subset of patients with corrected transposition of the great arteries (CC-TGA) will require left ventricular (LV) retraining before undergoing a double-switch procedure. LV retraining results in an immediate increase in LV pressure but not in LV mass. The purpose of this study was to evaluate the relationship between LV pressure and mass during LV retraining., Methods: This was a retrospective review of 36 patients with CC-TGA who were enrolled in LV retraining. The median age at enrollment was 12 months. The majority (82%) had an Ebstenoid tricuspid valve or moderate to severe tricuspid valve regurgitation before pulmonary artery banding., Results: Twenty-seven of the 36 patients underwent LV retraining and a double switch, including 14 patients with a single pulmonary artery band (PAB), 12 patients with 2 PABs, and 1 patient with 3 PABs. There was no early or late mortality associated with these procedures. Ninety percent of the patients demonstrated a linear relationship between LV pressure and mass; however, 3 patients (10%) demonstrated a different LV retraining pattern characterized by excess LV mass compared to LV pressure. Two of these 3 patients are LV retraining failures, whereas the third patient did undergo a double switch., Conclusions: The data show that the majority of patients enrolled in LV retraining have a predictable relationship between LV mass and pressure. A minority demonstrate an excess accrual of mass with respect to pressure load. These results suggest there may be an important distinction between normal and pathological hypertrophy during the LV retraining process., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients., Methods: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018., Results: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged., Conclusions: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Fontan circulatory inefficiency can be addressed by replacing the missing subpulmonary power source to reverse the Fontan paradox. An implantable cavopulmonary assist device is described that will simultaneously reduce systemic venous pressure and increase pulmonary arterial pressure, improving preload and cardiac output, in a univentricular Fontan circulation on a long-term basis., Methods: A rotary blood pump that was based on the von Karman viscous pump was designed for implantation into the total cavopulmonary connection (TCPC). It will impart modest pressure energy to augment Fontan flow without risk of obstruction. In the event of rotational failure, it is designed to default to a passive flow diverter. Pressure-flow performance was characterized in vitro in a Fontan mock circulatory loop with blood analog., Results: The pump performed through the fully specified operating range, augmenting flow in all 4 directions of the TCPC. Pressure rise of 6 to 8 mm Hg was readily achieved, ranging to 14 mm Hg at highest speed (5600 rpm). Performance was consistent across a wide range of cardiac outputs. In stalled condition (0 rpm), there was no discernible pressure loss across the TCPC., Conclusions: A blood pump technology is described that can reverse the Fontan paradox and may permit a surgical strategy of long-term biventricular maintenance of a univentricular Fontan circulation. The technology is intended for Fontan failure in which right-sided circulatory inefficiencies predominate and ventricular systolic function is preserved. It may also apply before clinical Fontan failure as health maintenance to preempt the progression of Fontan disease., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Femoral vein homograft can be used be used as valved right ventricle to pulmonary artery conduit in the Norwood operation. We describe the results of this approach, including pulmonary artery growth and ventricular function., Methods: A retrospective chart review of 24 consecutive neonates with hypoplastic left heart syndrome or complex single ventricle undergoing this approach between June 2012 and December 2017 was performed. Conduit valve competency and ventricular function were estimated using transthoracic echocardiogram, and pulmonary artery growth was measured using Nakata's index. Changes in ventricular function pre-Glenn and at latest follow-up were assessed by ordinal logistic regression with a general linear model to account for the correlation within the same patient over time., Results: Median age at surgery was 4 days, and mean weight was 3 kg. There was no interstage mortality. A total of 21 patients have undergone Glenn operation, and 9 patients have completed the Fontan operation. None of the conduits developed thrombosis. Sixty-three percent of conduits remained competent in the first month, and 33% remained competent after 3 months of operation. Catheter interventions on conduits were necessary in 14 patients. Median Nakata index at pre-Glenn catheterization was 228 mm 2 /m 2 (interquartile range, 107-341 mm 2 /m 2 ). Right ventricular function was preserved in 83% of patients at a median follow-up of 34 (interquartile range, 10-46) months., Conclusions: Femoral vein homograft as a right ventricle to pulmonary artery conduit in the Norwood operation is safe and associated with good pulmonary artery growth and preserved ventricular function as assessed by subjective echocardiography. Catheter intervention of the conduit may be necessary., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: A longer length of stay (LOS) in the intensive care unit (ICU) after the total cavopulmonary connection (TCPC) is thought to be a predictive sign of late Fontan failure. This study was performed to determine the clinical risk factors for ICU LOS., Methods: In total, 483 patients who underwent a TCPC between May 1994 and December 2016 were included the study. Patients' main diagnosis, morphologic characteristics, palliative procedures, hemodynamic parameters, and perioperative variables, were analyzed to identify risk factors influencing ICU stay based on Cox regression. Causes of longer ICU LOS and the impact of ICU LOS on late outcomes were evaluated., Results: Age at TCPC, type of TCPC, and fenestration at TCPC did not affect the ICU LOS. With multivariable model, hypoplastic left heart syndrome (P = .001) and anomalous systemic venous drainage (P < .001) were identified as independent morphologic risk factors for prolonged ICU LOS. Of hemodynamic variables, preoperative high transpulmonary gradient (P = .037), and low aortic oxygen saturation (P = .031) were risks for longer ICU LOS. Of postoperative variables, pleural effusion (P < .001), chylothorax (P = .001), ascites (P < .001), and infection (P = .028) were risks for longer ICU LOS. The ICU LOS was found to be significantly associated with late mortality (P < .001) and late cardiac reoperation (P = .007)., Conclusions: Patients with hypoplastic left heart syndrome and anomalous systemic venous drainage had longer ICU LOS. Extended cyanosis and elevated pulmonary artery pressure affect the ICU LOS. Special care should be provided during the initial postoperative phase in patients with such risk factors., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Mortality in acute pulmonary embolism (PE) is believed to be principally due to the subgroup of PEs that are massive. Systemic thrombolysis is the therapeutic mainstay for acute massive PE, despite evidence suggesting limited survival benefits. Both catheter-based therapies (CBT) and surgical pulmonary embolectomy (SE) are well-accepted alternatives to treat acute PE. However, the comparative effectiveness of these approaches is difficult to study. We conducted a systematic review of CBT and SE for acute PE., Methods: The PubMed database was queried for CBT- and SE-related publications between January 1998 and June 2017. A minimum of 10 patients undergoing intervention(s) was required for inclusion, and studies must not have excluded patients with massive PE. End points examined included hospital mortality, and additionally for CBT, procedural success rate., Results: A total of 75 studies (41 of CBT, 34 of SE) were identified, with 1650 patients undergoing CBT and 1101 undergoing SE. Patients undergoing SE were more critically ill than those undergoing CBT (massive PE, 545 out of 975 [55.9%] for SE vs 742 out of 1553 [47.8%] for CBT). Cardiopulmonary resuscitation (CPR) was required in 217 out of 1015 patients undergoing SE (21.4%) versus 38 out of 983 patients undergoing CBT (4.0%). The hospital mortality of SE was 14.0%, versus 5.6% for CBT, in the entire patient group. However, the hospital mortality of SE in patients with pre-SE CPR was 46.3%, whereas it was 6.8% in those patients without pre-SE CPR. Although CPR was associated with an increased risk of mortality both for CBT and SE, it accounted for all of the mortality effect on SE (the adjusted odds ratio for CPR in a random effects model with treatment considered was 9.79 (95% confidence interval, 4.98-19.17; P < .0001). The adjusted odds ratio for mortality for SE relative to CBT was 1.36 (95% confidence interval, 0.80-2.32; P = .84). Moreover, CBT was associated with a procedural failure rate of 8.3%., Conclusions: Both CBT and SE were associated with satisfactory published outcomes. SE is associated with greater absolute postprocedure mortality than CBT, but has been undertaken in more critically ill populations. The markedly higher incidence of CPR in SE accounts for the differential mortality between the patients undergoing SE and those undergoing CBT. Decision making with respect to best therapy must take into account potential needs for periprocedure artificial mechanical right ventricle and lung support, institutional experience and outcomes, anticipated therapeutic efficacy and benefit, and approach-specific risks., (Published by Elsevier Inc.)

Background: Our institutional approach to tetralogy of Fallot (TOF) with major aortopulmonary collaterals (MAPCAs) emphasizes unifocalization and augmentation of the reconstructed pulmonary arterial (PA) circulation and complete intracardiac repair in infancy, usually in a single procedure. This approach yields a high rate of complete repair with excellent survival and low right ventricular (RV) pressure. However, little is known about remodeling of the unifocalized and reconstructed pulmonary circulation or about reinterventions on the reconstructed PAs or the RV outflow tract conduit., Methods: We reviewed patients who underwent complete repair of TOF with MAPCAs at our center at <2 years of age, either as a single-stage procedure or after previous procedures. Outcomes included freedom from conduit or PA intervention after repair, which were assessed by Cox regression and Kaplan-Meier analysis., Results: The study cohort included 272 patients. There were 6 early deaths and a median of follow-up of 3.6 years after complete repair. Reinterventions on the pulmonary circulation were performed in 134 patients, including conduit interventions in 101 patients, branch PA interventions in 101, and closure of residual MAPCAs in 9. The first conduit reintervention consisted of surgical conduit replacement in 77 patients, transcatheter pulmonary valve replacement with a Melody valve in 14, and angioplasty or bare metal stenting in 10. Surgical PA reinterventions were performed in 46 patients and transcatheter reinterventions in 75 (both in 20). Most PA reinterventions involved a single lung, and most transcatheter reinterventions a single vessel. Freedom from conduit replacement or transcatheter pulmonary valve replacement was 70 ± 3% at 5 years and was shorter in patients with smaller initial conduit size. Freedom from any PA reintervention was 64 ± 3% at 5 years, with the greatest rate during the first year. On multivariable analysis, factors associated with longer freedom from any PA reintervention included lower postrepair RV:aortic pressure ratio and larger original conduit size., Conclusions: We were able to obtain follow-up data for the majority of patients, which demonstrated freedom from PA reintervention for two thirds of patients. The time course of and risk factors for conduit reintervention in this cohort appeared similar to previously reported findings in patients who received RV-PA conduits in early childhood for other anomalies. Relative to the severity of baseline pulmonary vascular anatomy in TOF with MAPCAs, reinterventions on the reconstructed PAs were uncommon after repair according to our approach, and major reinterventions were rare. Nevertheless, PA reinterventions are an important aspect of the overall management strategy., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats., Methods: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 μg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology., Results: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1β levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness., Conclusions: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1β and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Despite advances in the Fontan procedure, there is an unmet clinical need for patient-specific graft designs that are optimized for variations in patient anatomy. The objective of this study is to design and produce patient-specific Fontan geometries, with the goal of improving hepatic flow distribution (HFD) and reducing power loss (P loss ), and manufacturing these designs by electrospinning., Methods: Cardiac magnetic resonance imaging data from patients who previously underwent a Fontan procedure (n = 2) was used to create 3-dimensional models of their native Fontan geometry using standard image segmentation and geometry reconstruction software. For each patient, alternative designs were explored in silico, including tube-shaped and bifurcated conduits, and their performance in terms of P loss and HFD probed by computational fluid dynamic (CFD) simulations. The best-performing options were then fabricated using electrospinning., Results: CFD simulations showed that the bifurcated conduit improved HFD between the left and right pulmonary arteries, whereas both types of conduits reduced P loss . In vitro testing with a flow-loop chamber supported the CFD results. The proposed designs were then successfully electrospun into tissue-engineered vascular grafts., Conclusions: Our unique virtual cardiac surgery approach has the potential to improve the quality of surgery by manufacturing patient-specific designs before surgery, that are also optimized with balanced HFD and minimal P loss , based on refinement of commercially available options for image segmentation, computer-aided design, and flow simulations., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling., Methods: This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed., Results: On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn., Conclusions: In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR)., Methods: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m 2 . These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity., Results: Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m 2 , in adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m 2 , and in adults from 2.8 (2.0-4.7) to 2.1 (1.8-2.8)WU*m 2 . In 71% of patients, PVR fell to less than 2 WU*m 2 . Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3) L/min/m 2 , P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m 2 , P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20) mL/kg/min, P = .03; oxygen consumption and VO 2 max increased from 1.3 (1.0-1.6) to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0) L/beat, P = .01., Conclusions: This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Placement of a right ventricle-pulmonary artery shunt to the left or right of the neoaorta may influence reinterventions, pulmonary artery development, and survival after the Norwood procedure because of differences in shunt and pulmonary artery geometry and blood flow., Methods: We analyzed the Pediatric Heart Network Single Ventricle Reconstruction Trial public use dataset. Comparisons were made between patients who received a left- or right-sided right ventricle-pulmonary artery shunt during the Norwood procedure in both the overall (n = 274) and the propensity score-matched (67 pairs) patient cohorts., Results: A left-sided shunt was placed in 168 patients (61%), and a right-sided shunt was placed in 106 patients (39%). At the 12-month follow-up, there were no differences in pulmonary artery measurements, hemodynamic measurements, or pulmonary artery reinterventions between shunt groups. However, the right-sided shunt was associated with fewer surgical shunt revisions in both the overall (8.3 vs 1.9 events per 100 infants, P = .05) and the propensity score-matched (17.9 vs 0 events per 100 infants, P < .001) patient cohorts. In the propensity score-matched cohort only, right-sided shunts were further associated with fewer serious adverse events (84 vs 46 events per 100 infants, P = .01) and improved transplantation-free survival at 3 years follow-up (61% [95% confidence interval, 48-72] vs 80% [95% confidence interval, 69-88], P = .04)., Conclusions: In the Single Ventricle Reconstruction trial, right ventricle-pulmonary artery shunt placement to the right of the neoaorta was associated with fewer shunt revisions and may contribute to improved outcomes in select patients., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess safety and clinical performance of a novel bioabsorbable vascular graft in pediatric patients with univentricular cardiac malformation who received surgical correction via an extracardiac cavopulmonary conduit., Methods: The implanted graft material is designed to attract patient's own cells and proteins, which trigger a cascade of physiological events leading to endogenous tissue restoration. As the graft resorbs progressively after implantation, components of native tissue including collagen, endothelial lining, and capillary blood vessels develop and organize into a natural tissue. Five patients (aged 4-12 years) received this new vascular graft as interposition between the inferior vena cava and the pulmonary artery. They were followed up to 12 months after surgery. The conduit was assessed by echocardiography, computed tomography and magnetic resonance imaging, including 4-dimensional flow., Results: All patients recovered from the procedure without complications. No device-related adverse events were reported. Two patients required interventional occlusion of aortopulmonary collaterals. At 12 months, there was a significant improvement in the patients' general condition. Imaging studies demonstrated anatomical (conduit diameter, length and wall thickness) and functional (blood flow pattern) stability of the bioabsorbable grafts in all patients with no significant changes at 12 months compared with early postoperative data., Conclusions: Initial clinical experience with a novel absorbable graft underlines the potential of this new material to improve cardiac and vascular surgical procedures. In addition, better biocompatibility may reduce permanent implant-related complications. A longer follow-up is needed to assess the long-term effectiveness of biodegradable vascular grafts, including their ability to grow., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Berry syndrome is a combination of distal aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), intact ventricular septum, and interrupted aortic arch. We present here our current experience of primary repair of this syndrome with the goal of optimizing treatment for this rare condition., Methods: From January 2003 through December 2015, 16 infants with Berry syndrome underwent one-stage repair at Shanghai Children's Medical Center. Three different surgical correction techniques were used to repair the APW and aortic origin of the RPA, including intra-aortic baffle in 5, RPA detachment in 6, and RPA angioplasty with aortic cuff in 5 patients., Results: The median age at repair was 90.5 days (range, 8-170 days). The interrupted aortic arch morphology was type A in 14 and type B in 2 patients. The APW morphology was type IIa in 4, type IIb in 10, and type III in 2 patients. Hospital death occurred in 2 patients, and death at follow-up occurred in one other patient. Three patients who previously underwent RPA angioplasty with aortic cuff required reoperation for aortic or RPA stenosis. Freedom from reoperation was 84.8%, 75.4%, and 75.4%, respectively at 1, 5, and 10 years after surgery., Conclusions: One-stage repair of Berry syndrome has achieved acceptable outcomes. Reoperations mainly are related to aortic or RPA stenosis, and the reoperation rate is higher when RPA arterioplasty is performed with an aortic cuff., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesized that mean pulmonary artery pressure (PAP) detected on a pulmonary flow study may predict medium-term survival and right ventricular systolic pressure (RVSP) in patients with pulmonary atresia (PA), ventricular septal defect (VSD), and major aortopulmonary collateral arteries (MAPCAs)., Methods: Fifty patients with PA/VSD/MAPCAs underwent unifocalization between 2000 and 2013, and 40 of these patients had a pulmonary flow study since 2003. Predictability of the mean PAP on VSD status, medium-term survival, reintervention, and RVSP were analyzed., Results: Forty-seven of the 50 patients (94%) had complete unifocalization at a median age of 11 months (range, 1-194 months), and 37 patients (74%) achieved VSD closure. Among the 40 patients who underwent a pulmonary flow study, the VSD was closed in 34 (85%), with salvage VSD fenestration in 4 (10%), and was intentionally left open in 6 (15%). Survival was 85.5% at 1 year and 78.5% at 5 years. A mean PAP ≥25 mm Hg was associated with worse survival (P = .011). Cox regression analysis identified a mean PAP ≥25 mm Hg as the sole predictor for death (P = .037). Patients with an open VSD had an increased risk of reoperation (P = .001) and pulmonary artery reintervention (P = .010), and had a trend toward increased risk of death (P = .059), compared with those with a closed VSD., Conclusions: PAP obtained from the intraoperative pulmonary flow study is associated with medium-term survival and late RVSP in patients with PA/VSD/MAPCAs. VSD closure for patients with a mean PAP ≥25 mm Hg on a flow study is considered high risk, and sensible judgment and a low threshold for VSD fenestration are required., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To provide initial evidence on the management of mitral stenosis and pulmonary hypertension (PH) based on short-term and long-term outcomes following mitral valve surgery., Methods: Consecutive patients with mitral stenosis (n = 317) who had undergone mitral valve surgery between 1992 and 2014 with recorded pulmonary artery pressure (PAP) data were reviewed. PH severity, based on systolic PAP, was categorized as mild (35 to 44 mm Hg), moderate (45 to 59 mm Hg), or severe (>60 mm Hg). Primary outcomes were 30-day mortality and long-term survival., Results: There were no significant between-group differences in age or preoperative comorbidities. Mitral valve surgery included mitral valve replacement (78%) and repair (22%). The severe PH group had more mitral valve replacement (81%; P = .04), severe tricuspid valve regurgitation (31%; P = .003), right heart failure (17%; P = .02), and concomitant tricuspid valve procedures (46%; P < .001). For severe PH, 30-day mortality was 9%, with no significant group differences. Ten- and 12-year survival were significantly worse in the moderate-severe PH group (58% and 51%, respectively) compared with the normal PAP-mild PH group (83% and 79%, respectively) with a hazard ratio of 2.98 (95% confidence interval, 1.55-5.75; P = .001). Ten-year survival after mitral valve surgery for mitral stenosis was inversely associated with preoperative PAP., Conclusions: Mitral valve surgery can be performed with acceptable 30-day mortality for patients with mitral stenosis and moderate to severe PH, but long-term survival is impaired by moderate to severe PH. Patients with mitral stenosis and mild PH (systolic PAP 35-44 mm Hg) should be considered for mitral valve surgery., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: It is unknown whether changes in pulmonary arterial resistance (Rp), pulmonary arterial compliance (Cp), and the product of Rp and Cp (the RC time) in patients with pulmonary arterial hypertension (PAH) are related to an increase in pulmonary blood flow. The aim of this study is to clarify relationships between these parameters before and after corrective surgery among patients with PAH and congenital heart disease., Methods: We performed cardiac catheter examinations and compared Rp, Cp, and the RC time before and after corrective surgery in 100 infants (53 boys) with PAH related to ventricular septal defect., Results: Median age at surgery was 2.9 (0.6-28.5) months. Preoperative values of the ratio of pulmonary to systemic blood flow (Qp/Qs), systolic pulmonary arterial pressure (PAP), Rp, Cp, and the RC time were 3.5 (2.7-4.3), 65 (56-70) mm Hg, 2.18 (1.64-3.19) Wood unit/m(2), 2.67 (2.01-3.38) mL/mm Hg/m(2), and 0.36 (0.31-0.40) seconds, respectively. Postoperative systolic PAP, Cp, and the RC time were significantly decreased to 26 (23-29) mm Hg, 1.96 (1.77-2.26) mL/mm Hg/m(2), and 0.31 (0.26-0.36) seconds, respectively, although Rp remained unchanged at 2.53 (2.06-3.31) Wood unit/m(2). The relationship between Rp and Cp was inversely related before and after surgery, and the Rp-Cp coupling curve was shifted downward after surgery. In addition, lower preoperative Cp (partial regression coefficient = -3.35; P = .001) and preterm delivery (partial regression coefficient = 6.28; P = .02) were independently related to postoperative higher systolic PAP., Conclusions: Rp-Cp coupling depends on both the amount of pulmonary blood flow and the condition of the pulmonary vasculature. Lower preoperative Cp is an independent predictive factor to predict higher postoperative pulmonary systolic pressure leading to an increase in right ventricular workload. It is necessary to assess Rp-Cp coupling before surgery among patients with PAH related to congenital heart disease., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with single ventricle congenital heart disease often form aortopulmonary collateral vessels via an unclear mechanism. To gain insights into the pathogenesis of aortopulmonary collateral vessels, we correlated angiogenic factor levels with in vitro activity and angiographic aortopulmonary collateral assessment and examined whether patients with single ventricle physiology have increased angiogenic factors that can stimulate endothelial cell sprouting in vitro., Methods: In patients with single ventricle physiology (n = 27) and biventricular acyanotic control patients (n = 21), hypoxia-inducible angiogenic factor levels were measured in femoral venous and arterial plasma at cardiac catheterization. To assess plasma angiogenic activity, we used a 3-dimensional in vitro cell sprouting assay that recapitulates angiogenic sprouting. Aortopulmonary collateral angiograms were graded using a 4-point scale., Results: Compared with controls, patients with single ventricle physiology had increased vascular endothelial growth factor (artery: 58.7 ± 1.2 pg/mL vs 35.3 ± 1.1 pg/mL, P < .01; vein: 34.8 ± 1.1 pg/mL vs 21 ± 1.2 pg/mL, P < .03), stromal-derived factor 1-alpha (artery: 1901.6 ± 1.1 pg/mL vs 1542.6 ± 1.1 pg/mL, P < .03; vein: 2092.8 pg/mL ± 1.1 vs 1752.9 ± 1.1 pg/mL, P < .02), and increased arterial soluble fms-like tyrosine kinase-1, a regulatory vascular endothelial growth factor receptor (612.3 ± 1.2 pg/mL vs 243.1 ± 1.2 pg/mL, P < .003). Plasma factors and sprout formation correlated poorly with aortopulmonary collateral severity., Conclusions: We are the first to correlate plasma angiogenic factor levels with angiography and in vitro angiogenic activity in patients with single ventricle disease with aortopulmonary collaterals. Patients with single ventricle disease have increased stromal-derived factor 1-alpha and soluble fms-like tyrosine kinase-1, and their roles in aortopulmonary collateral formation require further investigation. Plasma factors and angiogenic activity correlate poorly with aortopulmonary collateral severity in patients with single ventricles, suggesting complex mechanisms of angiogenesis., (Published by Elsevier Inc.)

Objective: To report our improving institutional experience with the hybrid alternative surgical strategy for the management of hypoplastic left heart syndrome, in which hybrid stage 1 is followed by a comprehensive stage 2 procedure (removal of patent ductus arteriosus stent and pulmonary artery [PA] bands, aorta and PA reconstruction, Damus-Kaye-Stansel, atrial septectomy, Glenn)., Methods: In this Institutional Review Board-approved retrospective review of all patients undergoing a comprehensive stage 2 procedure between January 2002 and December 2014, data were compared between the pre-protocol group (n = 64; January 2002 to March 2010) and the post-protocol group (n = 55; March 2010 to December 2014). These 2 groups flank the implementation of a perioperative management protocol to prevent PA thrombosis., Results: Pre-protocol mortality was 19% (12 of 64), with the most common mode of death involving PA thrombosis in at least 7 patients, with an urgent indication for surgery and age as contributing factors. Care modifications instituted in March 2010 included avoidance of procedures on an emergent basis or in patients aged <3 months, use of a systemic PA shunt in cases of too-small superior vena cava and/or PA, completion angiogram with a low threshold for intraoperative stenting, and postoperative anticoagulation therapy for 6 weeks. There was a significant decrease in mortality (2 of 55; 4%; P = .01), PA thrombosis (0 of 55; 0%; P = .01), and use of extracorporeal membrane oxygenation (0/55 [0%] compared with 7 of 64 [11%]; P = .01) after protocol implementation., Conclusions: Despite the technical challenges of the comprehensive stage 2 procedure, excellent outcomes are attainable. Experience coupled with an internal quality review drove the implementation of a successful perioperative management protocol., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the incidence and risk factors for endocarditis and reintervention in patients undergoing placement of right ventricle-to-pulmonary artery valve conduits., Methods: All right ventricle-to-pulmonary artery valved conduits placed between 1995 and 2014 were included. Freedom from endocarditis, reintervention, and replacement were analyzed using the Kaplan-Meier method and parametric survival regression models., Results: A total of 586 patients underwent placement of a total of 792 valved conduits, including 289 (36%) pulmonary homografts, 121 (15%) aortic homografts, 245 (31%) bovine jugular grafts, and 137 (17%) porcine heterografts. There were 474 (60%) primary placements and 318 (40%) replacements. The median duration of conduit follow-up was 7 years; 23 conduits developed endocarditis at a median of 5 years after surgery. The use of bovine jugular grafts was the sole significant risk factor associated with endocarditis (hazard ratio, 9.05; 95% confidence interval, 2.6-31.8 compared with homografts). The hazard was greater for bovine jugular grafts compared with the other conduit types and increased with time; however, bovine jugular grafts were associated with a lower risk for reintervention (P < .0001) and replacement (P = .0002). Factors associated with greater risk of both reintervention and replacement were younger age and smaller conduit size. In addition, a diagnosis of truncus arteriosus was associated with a greater risk for replacement (P = .03)., Conclusions: Bovine jugular grafts are associated with a significantly greater risk of late endocarditis but with lower reintervention rates compared with other valved conduits. The risk of endocarditis and durability must be balanced during conduit selection. Antibiotic prophylaxis and a high index of suspicion for endocarditis are warranted in patients with bovine jugular grafts., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the association between surgical management of pulmonary blood flow (PBF) at initial and staged procedures with survival to Fontan/Kreutzer operation (Fontan) in patients with tricuspid atresia., Methods: Infants aged <3 months with tricuspid atresia type I (n = 303) were enrolled from 34 institutions (1999-2013). Among those who underwent surgical intervention (n = 302), initial procedures were: systemic to pulmonary artery shunt (SPS; n = 189; 62%); pulmonary artery banding (PAB; n = 50; 17%); and superior cavopulmonary connection (SCPC; n = 63; 21%). Multiphase parametric-hazard models were used to analyze competing outcomes., Results: Risk-adjusted 6-year survival was lower after SPS (85%; P = .04) versus PAB (93%) or SCPC (93%). Survival after SPS when the main pulmonary artery (MPA) was closed (n = 21) or banded (n = 4) was 60%, versus 93% without MPA intervention (P = .02). After SPS, survival before SCPC was lower with an open ductus arteriosus (n = 7; 76% vs 97%; P = .02). Similarly, after SPS, risk-adjusted survival was similar to that for patients who had an initial PAB or SCPC when MPA intervention was avoided and the ductus arteriosus either closed spontaneously before SPS, or was closed during SPS. For all patients reaching SCPC (n = 277), survival to Fontan was not significantly influenced by whether PBF persisted through the MPA., Conclusions: Tricuspid atresia patients with SPS represent a high-risk subgroup. Avoiding an open ductus arteriosus and concomitant MPA intervention during SPS may help mitigate the risk associated with SPS. The presence of antegrade PBF through the MPA, at initial and staged operations, did not significantly influence survival to Fontan operation., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Pulmonary hypertension is often considered a contraindication to orthotopic heart transplantation. Left ventricular assist device support may improve pulmonary hypertension by unloading the left ventricle, making patients eligible for transplantation. We sought to investigate the effect of continuous-flow left ventricular assist device support on pulmonary hypertension and compare post-transplantation outcomes in patients with preexisting pulmonary hypertension., Methods: Between March 2004 and December 2013, 256 potential orthotopic heart transplantation candidates underwent continuous-flow left ventricular assist device implantation at Columbia University. Preimplantation right heart catheterization data were available for 227 patients. Patients were divided into 2 groups on the basis of preimplantation pulmonary vascular resistance: low (<5 Wood units) (n = 182) and high (≥5 Wood units) (n = 45). Postimplantation and post-transplantation outcomes were compared between the groups., Results: Pulmonary vascular resistance in the high resistance group decreased significantly during left ventricular assist device support (P < .001). Post-transplantation in-hospital mortality was significantly higher in patients with high vascular resistance (P < .05). However, 3-year survival after transplantation was similar between groups (85.0% and 79.0% for low and high vascular resistance, respectively; P = .45)., Conclusions: Continuous-flow left ventricular assist device therapy reduced pulmonary vascular resistance. Subsequent orthotopic heart transplantation in patients with significantly elevated pulmonary vascular resistance resulted in higher in-hospital mortality but similar 3-year survival., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite excellent survival in patients after the arterial switch operation, reintervention is frequently required and exercise capacity is decreased in a substantial number of patients. This study relates right-sided imaging features in patients long-term after the arterial switch operation to exercise capacity and ventilatory efficiency to investigate which lesions are functionally important., Methods: Patients operated in the UMC Utrecht, the Netherlands (1976-2001) and healthy controls underwent cardiac magnetic resonance imaging and cardiopulmonary exercise testing within 1 week. We measured main, left, and right pulmonary artery cross-sectional areas, pulmonary blood flow distribution, peak oxygen uptake, and minute ventilation relative to carbon dioxide elimination., Results: A total of 71 patients (median age, 20 [12-35] years, 73% were male) and 21 healthy controls (median age, 26 [21-35] years, 48% were male) were included. Main, left, and right pulmonary artery areas were decreased compared with controls (190 vs 269 mm(2)/m(2), 59 vs 157 mm(2)/m(2), 98 vs 139 mm(2)/m(2), respectively, all P < .001); however, pulmonary blood flow distribution was comparable (P = .722). Peak oxygen uptake and minute ventilation relative to carbon dioxide elimination were 88% ± 20% and 23.7 ± 3.8, respectively, with 42% and 1% of patients demonstrating abnormal results (≤ 84% and ≥ 34, respectively). The main pulmonary artery area significantly correlated with peak oxygen uptake (r = 0.401, P = .001) and pulmonary blood flow distribution with minute ventilation relative to carbon dioxide elimination (r = -0.329, P = .008). Subanalysis (<18, 18-25, >25 years) showed that the main pulmonary artery area was smaller in older age groups. In multivariable analysis, the main pulmonary artery area was independently associated with peak oxygen uptake (P = .032)., Conclusions: In adult patients after the arterial switch operation, narrowing of the main pulmonary artery is a common finding and is the main determinant of limitation in functional capacity, rather than pulmonary branch stenosis., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of sequential and timely transfection of the recombinant human hepatocyte growth factor (hHGF) gene and human monocyte chemotactic protein-1 (hMCP-1) gene on hyperkinetic pulmonary artery hypertension in a rabbit model., Methods: The rabbits with pulmonary artery hypertension were randomly separated into 5 groups: control; hHGF; hMCP-1; hHGF/hMCP-1 simultaneous transfection; and hHGF/hMCP-1 sequential, timely transfection. Two weeks after the transfection, real-time polymerase chain reaction and immunohistochemistry examination were used to detect the expression of hHGF and hMCP-1. Four weeks later, the hemodynamic parameters were measured, and immunohistochemical and immunofluorescence staining were performed, to investigate microvascular density and arterialization., Results: The final adenovirus coding with enhanced green fluorescent protein-hMCP-1 virus was 3 × 10(10) plaque-forming units/mL, and the purity of adenovirus coding with hHGF was 1.31. Three days after the transfection, enhance green fluorescent protein hMCP-1 green fluorescence was detected in the lung tissues and increased to its peak point in 1 week. Two weeks later, hHGF and hMCP-1 were expressed in all transfection groups. By the end of 4 weeks, the mean pulmonary artery pressure in the hHGF/hMCP-1 sequential and timely transfection group was lower than that in the other groups. Confirmed by immunohistochemical and immunofluorescence staining, the microvascular and arteriolar density in the lung tissues of the sequential and timely hHGF/hMCP-1 transfection group were higher than that in the other groups., Conclusions: Expression of hHGF and hMCP-1 were found in rabbit lung after gene transfection via an airway approach. By increasing the pulmonary microvascular density and promoting arterializations, sequential and timely hHGF/hMCP-1 transfection ameliorates the shunt flow-induced pulmonary artery hypertension., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The pathogenesis of pulmonary arterial hypertension (PAH) involves reactive oxygen species and inflammation. Beneficial effects of molecular hydrogen, which exerts both anti-inflammatory and antioxidative effects, have been reported for various pathologic conditions. We therefore hypothesized that molecular hydrogen would improve monocrotaline (MCT)-induced PAH in rats., Methods: Nineteen male Sprague-Dawley rats (body weight: 200-300 g) were divided into groups, receiving: (1) MCT + hydrogen-saturated water (group H); (2) MCT + dehydrogenized water (group M); or (3) saline + dehydrogenized water (group C). Sixteen days after substance administration, we evaluated hemodynamics, harvested the lungs and heart, and performed morphometric analysis of the pulmonary vasculature. Macrophage infiltration, antiproliferating cell nuclear antigen-positive cells, 8-hydroxy-deoxyguanosine (8-OHdG)-positive cells, and expressions of phosphorylated signal transducers and activators of transcription-3 (STAT3) and nuclear factor of activated T-cells (NFAT) were evaluated immunohistochemically. Stromal cell-derived factor-1 and monocyte chemoattractant protein-1 expressions were evaluated by quantitative reverse-transcription polymerase chain reaction., Results: Pulmonary arterial hypertension was significantly exacerbated in group M compared to group C, but was significantly improved in group H. Vascular density was significantly reduced in group M, but not in group H. Adventitial macrophages, antiproliferating cell nuclear antigen - and 8-OHdG-positive cells, and stromal cell-derived factor-1 and monocyte chemoattractant protein-1 expressions were significantly increased in group M, but improved in group H. Expressions of phosphorylated STAT3 and NFAT were up-regulated in group M, but improved in group H., Conclusions: Molecular hydrogen ameliorates MCT-induced PAH in rats by suppressing macrophage accumulation, reducing oxidative stress and modulating the STAT3/NFAT axis., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hyperkinetic pulmonary arterial hypertension (PAH) is a common complication in congenital heart disease, and affects operations, indications, and prognoses for patients. Gene-based stem cell transplantation is an alternative treatment that can attenuate PAH., Methods: Hyperkinetic PAH rabbit models were successfully established, using common carotid artery and jugular vein anastomosis. Endothelial progenitor cells (EPCs) were isolated from the bone marrow, cultured, and transfected with human hypoxia inducible factor-1 alpha (hHIF-1α), using lentiviruses. Two weeks after the transfected EPCs were transplanted into the rabbits, catheterization was applied to collect hemodynamic data. The hypertrophy of the right ventricle and pulmonary vascular remodeling were evaluated by measuring the right ventricle hypertrophy index, the medial wall thickness, and the medial wall area. Western blot and immunohistochemistry analyses were used to detect the expression of hHIF-1α in the pulmonary small arteries., Results: Two weeks after transplantation, systolic pulmonary arterial pressure and mean pulmonary arterial pressure were both attenuated. The hypertrophy of the right ventricle, and pulmonary vascular remodeling were reversed. Expression of hHIF-1α in the hHIF-1α-transfected EPCs that had been transplanted was high, and the number of pulmonary small arteries had increased. In addition, combined HIF-1α and homogeneous EPC therapy was more effective at attenuating PAH and increasing the density of pulmonary small arteries, compared with EPC transplantation alone., Conclusions: Both the therapy with HIF-1α-transfected EPCs, and EPC transplantation, attenuated shunt flow-induced PAH, by means of an angiogenic effect. The former therapeutic method was more effective., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Hybrid palliation for hypoplastic left heart syndrome has been developed as an alternative to neonatal Norwood surgery. At the second stage, a source of pulmonary blood flow has to be established. Options include an arterial modified Blalock-Taussig or a venous superior cavopulmonary shunt., Methods: We retrospectively reviewed patients who received second-stage palliation after the initial hybrid. Patients were stratified according to the source of pulmonary blood supply into the arterial shunt (n = 17 patients) or venous shunt (n = 26 patients)., Results: Age and weight at second stage were lower in the arterial group (85 [45-268] days vs 152.5 [61-496] days, P = .001 and 3.6 [2.7-9.4] kg vs 5.1 [2.97-9.4] kg, P = .001, respectively). All recorded surgical times were shorter in the arterial group. Mechanical ventilation and intensive care stay were shorter in the venous group (5.82 [2.01-14.9] days vs 2.42 [0.56-13.67] days, P = .005 and 8.5 [3.6-23.7] vs 5.75 [0.8-17.6] days, P = .036, respectively) There was no difference in mortality (2/17 vs 5/26; P = .685) or incidence of complications between the 2 groups. There was a tendency toward a higher need for intervention in the immediate postoperative period in the venous group, but this did not reach significance (6/17 vs 13/26, P = .342). The arterial group has shown better development of the branch pulmonary arteries with a higher lower lobe index (158.38 ± 39.43 mm(2)/m(2) vs 113.33 ± 43.96 mm(2)/m(2), respectively, P = .037)., Conclusions: Both arterial and venous shunts are viable options with mortality and morbidity results comparable to those in the literature. The arterial shunt pathway (2-stage Norwood I) may offer better pulmonary arterial growth than the venous shunt (comprehensive/combined Norwood I and II)., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: An almost universal incidence of developing pulmonary arteriovenous fistulas after the Kawashima operation has been reported. Exclusion of the hepatic venous flow from the pulmonary circulation causes the development of these malformations. Redirection of hepatic venous flow to the pulmonary circulation mostly leads to the regression of the arteriovenous fistulas., Methods: We analyzed 11 patients with arteriovenous fistulas that developed after the Kawashima operation. The hepatic-to-azygos shunts were performed with an off-pump technique through a lateral thoracotomy in all but one. Operative and postoperative data were retrospectively collected., Results: No intraoperative complications occurred, and no patient died in the hospital. Up to 10-year follow-up showed a significant postoperative improvement of patients' oxygen saturation and New York Heart Association class. Apart from 2 re-thoracotomies for bleeding in 1 patient, no complications occurred and no patient died during follow-up. Two other patients underwent reoperation for an undiagnosed additional hepatic vein. The improvement of patients' oxygen saturation and New York Heart Association class persisted during the follow-up period., Conclusions: The surgical connection can be performed safely with an off-pump technique that avoids the risks related to extracorporeal circulation and circulatory arrest. The results at 10 years follow-up confirmed the efficacy and safety of the surgical technique described., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Ventricular kinetic energy measurements may provide a novel imaging biomarker of declining ventricular efficiency in patients with repaired tetralogy of Fallot. Our purpose was to assess differences in ventricular kinetic energy with 4-dimensional flow magnetic resonance imaging between patients with repaired tetralogy of Fallot and healthy volunteers., Methods: Cardiac magnetic resonance, including 4-dimensional flow magnetic resonance imaging, was performed at rest in 10 subjects with repaired tetralogy of Fallot and 9 healthy volunteers using clinical 1.5T and 3T magnetic resonance imaging scanners. Right and left ventricular kinetic energy (KERV and KELV), main pulmonary artery flow (QMPA), and aortic flow (QAO) were quantified using 4-dimensional flow magnetic resonance imaging data. Right and left ventricular size and function were measured using standard cardiac magnetic resonance techniques. Differences in peak systolic KERV and KELV in addition to the QMPA/KERV and QAO/KELV ratios between groups were assessed. Kinetic energy indices were compared with conventional cardiac magnetic resonance parameters., Results: Peak systolic KERV and KELV were higher in patients with repaired tetralogy of Fallot (6.06 ± 2.27 mJ and 3.55 ± 2.12 mJ, respectively) than in healthy volunteers (5.47 ± 2.52 mJ and 2.48 ± 0.75 mJ, respectively), but were not statistically significant (P = .65 and P = .47, respectively). The QMPA/KERV and QAO/KELV ratios were lower in patients with repaired tetralogy of Fallot (7.53 ± 5.37 mL/[cycle mJ] and 9.65 ± 6.61 mL/[cycle mJ], respectively) than in healthy volunteers (19.33 ± 18.52 mL/[cycle mJ] and 35.98 ± 7.66 mL/[cycle mJ], respectively; P < .05). QMPA/KERV and QAO/KELV were weakly correlated to ventricular size and function., Conclusions: Greater ventricular kinetic energy is necessary to generate flow in the pulmonary and aortic circulations in repaired tetralogy of Fallot. Quantification of ventricular kinetic energy in patients with repaired tetralogy of Fallot is a new observation. Future studies are needed to determine whether changes in ventricular kinetic energy can provide earlier evidence of ventricular dysfunction and guide future medical and surgical interventions., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of a hybrid approach to staged palliation of single-ventricle anomalies is designed to minimize the trauma of the first stage. However, the second stage is a complex procedure that may negate the advantages of the first stage. We sought to devise a "hybrid" approach to the second stage when aortic outflow is expected to remain unobstructed., Methods: The procedure involves a simple incision into the main pulmonary artery, dilation/stenting of the ductal continuation, formation of a stented baffle between the branch pulmonary arteries' orifices, and a bidirectional Glenn connection. It avoids dissection of the distal arch and ductal continuation and obviates the need for a Damus-Kaye-Stansel connection. We carried out this procedure in 2 patients, one with unbalanced atrioventricular canal and the other with mitral atresia., Results: Both patients underwent an uncomplicated operative procedure. Both patients were successfully weaned from the ventilator, with no clinically evident neurologic injury. The first patient died of complications related to thrombosis of the left pulmonary artery before initiation of anticoagulation. The second patient is alive and well 1 year postoperation with no obstruction to either systemic or pulmonary flow and no baffle leak and good right ventricle function., Conclusions: This hybrid comprehensive stage II operation appears feasible and technically simpler than the conventional comprehensive stage II procedure. It is applicable to a subset of single-ventricle cases in which aortic outflow is anticipated to remain unobstructed. We recommend early postoperative anticoagulation to avoid early left pulmonary artery thrombosis., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This article presents the long-term results of our patients with a diagnosis of hypoplastic left heart syndrome (HLHS), hypoplastic left heart complex (HLHC), and variants who received a biventricular repair following hybrid stage I with ductal stenting and bilateral pulmonary artery banding., Methods: Between June 1998 and June 2013, a total of 154 patients with hypoplastic left heart structures underwent a hybrid stage I procedure. Forty patients were definitely treated by creating a biventricular circulation. Median age and body weight of patients before hybrid stage I were 8.5 days (2-40) and 3.0 kg (1.6-3.8), respectively. The diagnoses were HLHS with mitral and aortic stenosis (n = 7), HLHC (n = 15), HLHC with interrupted aortic arch (n = 9), critical aortic stenosis with hypoplastic aortic arch (n = 4), imbalanced atrioventricular septal defect with hypoplastic aortic arch (n = 2), double-outlet right ventricle with hypoplastic aortic arch (n = 2), and d-transposition of the great arteries with interrupted aortic arch (n = 1). Median age at the time of biventricular correction was 6.7 months (1.6-13.8). The patients were treated with direct biventricular correction, including repair of intracardiac defects (n = 32), Norwood/Rastelli or Yasui (n = 4), arterial switch (n = 2), Rastelli (n = 1), and Ross-Konno (n = 1) operations with ascending aortic/aortic arch reconstruction., Results: All patients survived hybrid stage I. Median survival after biventricular correction is 7.9 years (0.9-14.9). Overall mortality was 10% (4 patients) at 4 weeks, 5 weeks, 6 weeks, and 4 months after biventricular correction, respectively. One patient had to be switched to univentricular circulation and another patient underwent orthotopic heart transplantation 3 and 4 months after biventricular correction, respectively., Conclusions: The Giessen hybrid approach is an alternative to the conventional strategy to treat neonates with HLHS, HLHC, and variants. Biventricular repair after hybrid stage I is feasible and can be performed with satisfactory long-term survival., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Currently, no quantitative guidelines have been established for treatment of left pulmonary artery (LPA) stenosis. This study aims to quantify the effects of LPA stenosis on postoperative hemodynamics for single-ventricle patients undergoing stage II superior cavopulmonary connection (SCPC) surgery, using a multiscale computational approach., Methods: Image data from 6 patients were segmented to produce 3-dimensional models of the pulmonary arteries before stage II surgery. Pressure and flow measurements were used to tune a 0-dimensional model of the entire circulation. Postoperative geometries were generated through stage II virtual surgery; varying degrees of LPA stenosis were applied using mesh morphing and hemodynamics assessed through coupled 0-3-dimensional simulations. To relate metrics of stenosis to clinical classifications, pediatric cardiologists and surgeons ranked the degrees of stenosis in the models. The effects of LPA stenosis were assessed based on left-to-right pulmonary artery flow split ratios, mean pressure drop across the stenosis, cardiac pressure-volume loops, and other clinically relevant parameters., Results: Stenosis of >65% of the vessel diameter was required to produce a right pulmonary artery:LPA flow split <30%, and/or a mean pressure drop of >3.0 mm Hg, defined as clinically significant changes., Conclusions: The effects of <65% stenosis on SCPC hemodynamics and physiology were minor and may not justify the increased complexity of adding LPA arterioplasty to the SCPC operation. However, in the longer term, pulmonary augmentation may affect outcomes of the Fontan completion surgery, as pulmonary artery distortion is a risk factor that may influence stage III physiology., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Pulmonary artery banding is the initial palliative surgery in patients with single ventricle cardiac anomalies presenting with unrestricted pulmonary blood flow. Reported mortality in those receiving pulmonary artery banding is high, and its application in patients with single ventricle anomalies and arch obstruction is controversial. We report current-era results after pulmonary artery banding in patients with single ventricle anomalies, including those with arch obstruction., Methods: Between 2002 and 2012, 73 patients with single ventricle anomalies and unrestricted pulmonary blood flow underwent pulmonary artery banding, including 29 (40%) who received simultaneous arch repair. Competing risk analysis modeled events after pulmonary artery banding (death/transplantation, transition to the Glenn procedure) and subsequently after the Glenn procedure (death/transplantation, transition to the Fontan procedure) and examined risk factors affecting outcomes., Results: Hospital mortality was 3 of 73 patients (4%). Before the Glenn procedure, 16 patients (22%) underwent 18 reoperations, including shunt (n = 7), Damus-Kaye-Stansel connection plus shunt (n = 5), pulmonary artery banding adjustment (n = 5), and transplantation (n = 1). On competing risk analysis, 2 years after pulmonary artery banding, 8% of patients have died or received transplantation, 88% have undergone the Glenn procedure, and 7% were alive without the Glenn procedure. Five years after the Glenn procedure, 9% have died, 71% have undergone the Fontan procedure, and 20% were alive awaiting the Fontan procedure. Overall survival 5 years after pulmonary artery banding was 86%. On multivariable analysis, risk factors for mortality were associated genetic/extracardiac anomalies (hazard ratio, 3.7; 95% confidence interval, 1.1-12.2; P = .03) and high-risk morphology (heterotaxy, unbalanced atrioventricular septal defect, and mitral atresia) (hazard ratio, 4.1; 95% confidence interval, 1.1-15.6; P = .04)., Conclusions: Pulmonary artery banding is an acceptable initial palliative strategy of selected patients with single ventricle cardiac anomalies and unrestricted pulmonary blood flow, including those with concomitant arch obstruction. Short- and long-term outcomes are generally good, although results diverge with the worst outcomes noted in patients with heterotaxy, unbalanced atrioventricular septal defect, or associated extracardiac anomalies., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: In this study, with the use of computational fluid dynamics, we evaluate the postoperative hemodynamic performance of the first cohort of patients undergoing a handcrafted Y-graft Fontan procedure and validate simulation predictions of hepatic blood flow distribution against in vivo clinical data., Methods: An 18-12 × 2-mm handcrafted Y-graft modification of the Fontan procedure was performed in 6 patients. Early (at the time of discharge) and 6-month postoperative 3-dimensional magnetic resonance imaging data were collected. Patient-specific models were constructed for flow simulations., Results: Hepatic blood flow distribution varied among patients. Lung perfusion data (n = 3) showed good agreement with simulations. Postoperative asymmetry in hepatic blood flow distribution was reduced 6 months postoperatively. In 1 patient, low wall shear stress was found in the left limb of the Y-graft, corresponding to the location of subsequent thrombosis in the patient., Conclusions: The credibility and accuracy of simulation-based predictions of postoperative hepatic flow distribution for the Fontan surgery have been validated by in vivo lung perfusion data. The performance of the Y-graft design is highly patient-specific. The anastomosis location is likely the most important factor influencing hepatic blood flow distribution. Although the development of thrombosis is multifactorial, the occurrence in 1 patient suggests that simulations should not solely consider the hepatic blood flow distribution but also aim to avoid low wall shear stress in the limbs., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To demonstrate the technical feasibility and describe intermediate outcomes for the initial patients undergoing handcrafted, area-preserving, Y-graft modification of the Fontan procedure., Methods: A retrospective review of a pilot study was undertaken to describe preoperative, intraoperative, and postoperative results., Results: Six patients underwent successful procedures and remain alive 3 to 4 years later. The median age at operation was 3.3 years, and median weight was 13.2 kg. Five operations were done without cardiopulmonary bypass and no intraoperative pressure gradients were found. Five patients were extubated by postoperative day 1, Fontan pressures were 12 to 14 mm Hg, transpulmonary gradients were 6 to 8 mm Hg, and no renal or hepatic function abnormalities were found. Length of stay was 10 to 64 days. One patient required venovenous extracorporeal membrane oxygenation for previously undiagnosed plastic bronchitis (64-day stay); another required reoperation for an incidentally diagnosed aortic thrombus (44-day stay). One patient had occlusion of a Y-graft limb noted on magnetic resonance imaging follow-up at 3 months. Catheterization showed excellent hemodynamic parameters and no Fontan obstruction. Occlusion was believed to be due to right-sided pulmonary arteriovenous malformations and widely discrepant flow (80%) to the right lung leading to low flow in the left limb., Conclusions: The area-preserving, bifurcated Y-graft Fontan modification is technically feasible and shows excellent intermediate outcomes. Additional study is required to determine whether the advantages seen in the computational models will be realized in patients over the long-term, and to optimize patient selection for each of the various Fontan options now available., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Hybrid palliation is an alternative to Norwood stage 1 for the initial management of hypoplastic left heart syndrome. Contemporary multicenter hybrid use and institutional/patient factors associated with hybrid use relative to the Norwood have not been evaluated. We describe hybrid use in relation to institutional volume, patient factors, and short-term outcomes., Methods: Infants aged 60 days or less listed in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2012) undergoing initial palliation of hypoplastic left heart syndrome were included. Annual institutional hybrid use rates were calculated: [hybrid procedures/(Norwood + hybrid + transplant procedures)]. In-hospital outcomes for primary hybrid and primary Norwood were compared and stratified by high (defined as ≥50%) versus low (defined as ≤10%) institutional hybrid use., Results: Of 1728 patients (100 centers), most (n = 1496, 87%) underwent an index Norwood; 232 patients (13%) underwent an index hybrid procedure. Preoperative patient risk factors were more prevalent in patients undergoing the hybrid procedure. Only 13 of 100 institutions were high hybrid users, and these tended to have lower annual hypoplastic left heart syndrome index case volume. Unadjusted in-hospital mortality was higher for the hybrid compared with the Norwood procedure (30% vs 16%; P < .001). In-hospital mortality for the hybrid procedure was not associated with hybrid use (26% among institutions with low use vs 28% among institutions with high use). However, centers with high hybrid use had higher mortality after the Norwood (43%) compared with centers with low hybrid use (16%)., Conclusions: Few centers currently select the hybrid procedure for most infants with hypoplastic left heart syndrome. Although unadjusted in-hospital hybrid mortality is higher than Norwood mortality, potential risk factors are more prevalent among hybrid cases. Institutions with higher hybrid use have lower hypoplastic left heart syndrome case volume and higher Norwood mortality., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)