Why partial heart transplantation could be regulated as organ transplantation.

Partial heart transplant (PHT) is a recent clinical innovation involving the transplantation of a segment of the heart (valves) directly from the deceased donor into the recipient patient. This procedure holds out the possibility of significant benefit, especially for pediatric patients because these grafts show growth potential after transplant, reducing or eliminating the current need for repeat procedures. The clinical process for donation and transplant of partial heart (PH) grafts generally follows an organ clinical pathway; however, the Food and Drug Administration has recently stated its intent to regulate PH as tissues, raising a host of regulatory considerations. PHT requires donor testing and eligibility determinations within a short, clinically viable timeframe and, similar to organ transplant, involves donor-recipient matching. Waitlist allocation policies that are a regulatory focus of the Organ Procurement and Transplantation Network including equity and efficiency may become relevant. Oversight of PHT by the Organ Procurement and Transplantation Network could be accomplished through interpretation of the vascular composite allograft definition or through designation by the US Department of Health and Human Services of PH grafts as organs. While some clinical questions remain unanswered, it is important to carefully address these regulatory considerations to support the emergence of this innovation and ensure the continued trust of the donating public and the patients who may benefit from PHT.

Mitral valve orifice area predicts outcome after biventricular repair in patients with hypoplastic left ventricles.

BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

Endocardial Fibroelastosis Resection: When it Works and When it Does Not.

Endocardial fibroelastosis (EFE) is a thickening of the endocardial layer by accumulation of collagen and elastic fibers. Endothelial to mesenchymal transformation is proposed to be the underlying mechanism of formation. Although EFE can occur in both right and left ventricles, this article will focus on management of left ventricular EFE. Through its fibrous, nonelastic manifestation EFE restricts the myocardium leading to diastolic and systolic ventricular dysfunction and prevents ventricular growth in neonates and infants. The presence of EFE may be a marker for underlying myocardial fibrosis as well. The extent of EFE within the left ventricular cavity can be variable ranging from patchy to confluent distribution. Similarly the depth of penetration and degree of infiltration into myocardium can be variable. The management of EFE is controversial, although resection of EFE has been reported as part of the staged ventricular recruitment therapy. Following resection, EFE recurs and infiltrates the myocardium after primary resection. Herein we review the current experience with EFE resection.

Perioperative Hyper-coagulation and Thrombosis: Cost Analysis After Congenital Heart Surgery.

Thrombosis, a major adverse event of congenital heart surgery, has been associated with poor outcomes. We hypothesized that in CHD patients undergoing cardiac surgery, increased perioperative use of pro-coagulant products may be associated with postoperative thrombosis in the setting of hyperfibrinogenemia, leading to greater hospital and blood product costs. Single-center retrospective study. Data from Boston Children's Hospital's electronic health record database was used in this study. All patients undergoing congenital heart surgery between 2015 and 2018 with postoperative fibrinogen levels above 400 mg/dl were reviewed. Of 334 patients with high plasma fibrinogen levels, 28 (8.4%) developed postoperative thrombosis (median age: one year, 59% male). In our cohort, 25 (7%) demonstrated evidence of baseline hypercoagulability by one or more panel test results. Thrombosis was associated with greater hospital and blood product costs, longer ventilation times, and longer hospital and ICU length of stays. Preoperative hypercoagulable state (odds ratio: 2.58, 95% CI [1.07, 9.99], p = 0.002), postoperative red blood cell transfusion (odds ratio: 1.007, 95% CI [1.000, 1.015], p = 0.04), and single ventricle physiology (univariate odds ratio: 2.94, 95% CI [1.09, 7.89], p = 0.03) were predictors of postoperative thrombosis. Preoperative hypercoagulable state and intraoperative platelet transfusion were predictors of hospital cost. Thrombosis was associated with worse in-hospital outcomes and higher costs. Preoperative hypercoagulable state and postoperative red blood cell transfusion were significant predictors of thrombosis. Risk prediction models that can guide thrombosis prevention are needed to improve outcomes of patients undergoing congenital heart surgery.

Cardiac magnetic resonance parameters associated with successful conversion from a single ventricular to a one-and-a-half or biventricular circulation in patients with a hypoplastic right ventricle.

BACKGROUND: Some patients with pulmonary atresia with an intact ventricular septum (PA/IVS) or a left ventricle dominant atrioventricular canal defect (LDAVC) with a hypoplastic right ventricle (RV) and univentricular (1 V) circulation may be candidates for conversion to either a complete biventricular (2 V) repair or a one-and-a-half ventricle repair (1.5 V). We sought to identify pre-operative cardiovascular magnetic resonance (CMR) findings associated with successful conversion from 1V to 1.5V or 2V circulation. METHODS: In this single center retrospective study, subjects with PA/IVS or LDAVC and no conotruncal abnormalities were included if they had a 1 V circulation at the time of CMR followed by a surgical intervention intended to convert them to a 1.5 V or 2 V circulation. Conversion failure was defined as any of the following: (1) oxygen saturation < 90% at the most recent follow-up, (2) conversion back to a 1.5 V or 1 V circulation, or (3) death. RESULTS: In the PA/IVS cohort (n = 15, median age 1.32 years), 10 patients underwent surgical conversion to a 1.5 V circulation and 5 to a 2 V circulation. In the attempted 1.5 V group, there were 2 failures, and these cases had a lower RV mass (p = 0.04). In the attempted 2 V group, there was 1 failure, and no CMR parameters were significantly different compared to the successes. Among the successful 2 V group patients, the minimum RV end-diastolic volume (EDV) was 27 ml/m2. In the LDAVC cohort (n = 15, median age 1.0 years), 1 patient underwent surgical conversion to a 1.5 V circulation and 14 patients to a 2 V circulation. In the attempted 1.5 V group, the 1 conversion was a failure and had an RV EDV of 15 ml/m2. In the attempted 2 V group, there were 2 failures, and these cases had a smaller RV:LV stroke volume ratio (p = 0.05) and a lower RV ejection fraction (p = 0.05) compared to the successes. Among the successful 2 V group patients, the minimum RV EDV was 22 ml/m2. CONCLUSIONS: We identified multiple CMR parameters associated with successful conversion from 1 V circulation to 1.5 V or 2 V circulation in patients with PA/IVS and LDAVC. This information may improve patient selection for conversion procedures and encourage larger studies to better define the role of CMR.

Implications of Transfusion in Adults with Congenital Heart Disease Undergoing Cardiac Surgery.

The number of adults with congenital heart disease (CHD) requiring cardiovascular (CV) surgery is increasing rapidly in today's era. We hypothesized that exposure to perioperative blood products is associated with worse outcomes in adults. All adults (≥ 18 years old) undergoing CV surgery with Cardio-Pulmonary Bypass (CPB) between 2015 and 2020 were reviewed retrospectively. Associations between transfusion and outcomes were studied by univariable logistic regression and Wilcoxon rank sum tests. Cox/ logistic regression was used to assess (a) postoperative ventilation time and length of stay, and (b) major complications, respectively. Of 323 patients, 170 (53%) received blood products perioperatively. The median age was 27 (interquartile range [IQR]: 22-36) years, there were 181 (46%) males, and 16 (5%) patients had single ventricle anatomy. Patients receiving products experienced more complications (OR: 6.6, 95% CI: [2.9, 14.7], p < 0.001) specifically, cardiac arrest (OR: 8.8, 95% CI: [1.1, 71.9], p = 0.04). Transfusion was associated with greater frequency of thrombosis ((OR: 7.8, 95% CI: [1.8, 34.7], p = 0.01)), longer ventilation time (HR: 3.0, 95% CI: [2.4, 3.9], p < 0.001), and longer hospital length of stay (HR: 2.7, 95% CI: [2.1, 3.4], p < 0.001). Longer CPB time (OR: 1.0, 95% CI: [1.0, 1.1], p < 0.001) and prior cardiac surgery (OR: 1.6, 95% CI: [1.3, 2.1], p < 0.001) were independent predictors of perioperative blood product transfusion. Adults who received perioperative blood products experienced more complications and worse in-hospital outcomes. Future research on optimizing blood product transfusion based on risk prediction is needed to optimize outcomes in adults with CHD.

Double Aortic Arch with Atresia of the Left Aortic Arch Proximal to the Left Common Carotid Artery: First Report of Documentation by Surgical Observation.

Double aortic arch associated with atresia of the left arch proximal to the left common carotid artery has been considered a theoretical possibility. To our knowledge, we report the first patient with this anatomy confirmed by surgical observation.

Clinical implications of acute shunt thrombosis in paediatric patients with systemic-to-pulmonary shunt re-interventions.

PURPOSE: Systemic-to-pulmonary shunts are used as a source of pulmonary blood flow in palliated Congenital Heart Disease in neonates and young infants. Shunt thrombosis, often requiring shunt interventions during index hospitalisation, is associated with poor outcomes. We hypothesised that extensive use of perioperative pro-coagulant products may be associated with shunt thrombosis. METHODS: Children (≤18 years) undergoing systemic-to-pulmonary shunts with in-hospital shunt reinterventions between 2016 and 2020 were reviewed retrospectively. Perioperative associations to shunt thrombosis were examined by univariate logistic regression and Wilcoxon rank sum tests as appropriate. Cox and log transformed linear regression were used to analyse postoperative ventilation duration, length of stay, and cost. RESULTS: Of 71 patients requiring in-hospital shunt intervention after systemic-to-pulmonary shunts, 10 (14%) had acute shunt thrombosis, and among them five (50%) died. The median age was four (interquartile range: 0-15) months. There were 40 (56%) males, 41 (58%) had single ventricle anatomy, and 29 (40%) were on preoperative anticoagulants. Patients with acute shunt thrombosis received greater volume of platelets (p = 0.04), cryoprecipitate (p = 0.02), and plasma (p = 0.04) postoperatively in the ICU; experienced more complications (p = 0.01) including re-exploration for bleeding (p = 0.008) and death (p = 0.02), had longer hospital length of stays (p = 0.004), greater frequency of other arterial/venous thrombosis (p = 0.02), and greater hospital costs (p = 0.002). CONCLUSIONS: Patients who develop acute shunt thrombosis receive more blood products perioperatively and experience worse hospital outcomes and higher hospital costs. Future research on prevention/early detection of shunt thrombosis is needed to improve outcomes in infants after systemic-to-pulmonary shunt surgery.

Exploratory Use of Glycoprotein IIb/IIIa Inhibition in Prevention of Blalock-Taussig Shunt Thrombosis.

OBJECTIVES: Morbidity and mortality related to modified Blalock-Taussig shunt (mBTTS) thrombosis remain a significant risk. Platelet inhibition following mBTTS may reduce this risk. However, oral antiplatelet agents have variable absorption following surgery. We determine risk factors for mBTTS thrombosis and hypothesize that IV glycoprotein IIb/IIIa inhibitor (tirofiban) as a bridge to oral aspirin reduces the rate of shunt thrombosis in the immediate postoperative period. End points within the 14-day follow-up period include mBTTS thrombosis, overall thrombosis, bleeding, length of stay, and mortality. DESIGN: Retrospective, Institutional Review Board-approved cohort study. SETTING: Single-center cardiac ICU. PATIENTS: Patients under the age of 18 who had an mBTTS placed within the study period of January 2008 to December 2018 were included. INTERVENTIONS: Patients were divided into two groups: standard of care (SOC) anticoagulation alone and SOC with tirofiban as a bridge to oral aspirin. MEASUREMENTS AND MAIN RESULTS: Freedom from mBTTS thrombosis was estimated using the Kaplan-Meier method. A multivariable predictive model using the four most significant risk factors was developed using logistic regression. A total of 272 patients were included: 36 subjects in the SOC/tirofiban group and 236 in the SOC group. Shunt thrombosis occurred in 26 (11%) SOC group with zero in SOC/tirofiban group ( p = 0.03). The median time to thrombosis was 0 days (range, 0-12 d). The area under the curve for the predictive model (anticoagulation group, history of coagulopathy, intraoperative shunt clipping, and shunt size/weight ratio) is 0.790 ( p < 0.001). Prevalence of bleeding and mortality was not significantly different between the groups. CONCLUSIONS: Highest risk for shunt thrombosis following mBTTS occurs within the first few days after surgical procedure. Tirofiban is a safe addition to SOC and may be an effective strategy to prevent early mBTTS thrombosis.

Plasma and Platelet Transfusions Strategies in Neonates and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass or Neonates and Children Supported by Extracorporeal Membrane Oxygenation: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.

OBJECTIVES: To present the recommendations and consensus statements with supporting literature for plasma and platelet transfusions in critically ill neonates and children undergoing cardiac surgery with cardiopulmonary bypass or supported by extracorporeal membrane oxygenation from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. DESIGN: Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children. SETTING: Not applicable. PATIENTS: Critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of nine experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill neonates and children following cardiopulmonary bypass or supported by extracorporeal membrane oxygenation. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed one good practice statement, two recommendations, and three expert consensus statements. CONCLUSIONS: Whereas viscoelastic testing and transfusion algorithms may be considered, in general, evidence informing indications for plasma and platelet transfusions in neonatal and pediatric patients undergoing cardiac surgery with cardiopulmonary bypass or those requiring extracorporeal membrane oxygenation support is lacking.

Executive Summary of Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB).

OBJECTIVES: Critically ill children frequently receive plasma and platelet transfusions. We sought to determine evidence-based recommendations, and when evidence was insufficient, we developed expert-based consensus statements about decision-making for plasma and platelet transfusions in critically ill pediatric patients. DESIGN: Systematic review and consensus conference series involving multidisciplinary international experts in hemostasis, and plasma/platelet transfusion in critically ill infants and children (Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding [TAXI-CAB]). SETTING: Not applicable. PATIENTS: Children admitted to a PICU at risk of bleeding and receipt of plasma and/or platelet transfusions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A panel of 29 experts in methodology, transfusion, and implementation science from five countries and nine pediatric subspecialties completed a systematic review and participated in a virtual consensus conference series to develop recommendations. The search included MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020, using a combination of subject heading terms and text words for concepts of plasma and platelet transfusion in critically ill children. Four graded recommendations and 49 consensus expert statements were developed using modified Research and Development/UCLA and Grading of Recommendations, Assessment, Development, and Evaluation methodology. We focused on eight subpopulations of critical illness (1, severe trauma, intracranial hemorrhage, or traumatic brain injury; 2, cardiopulmonary bypass surgery; 3, extracorporeal membrane oxygenation; 4, oncologic diagnosis or hematopoietic stem cell transplantation; 5, acute liver failure or liver transplantation; 6, noncardiac surgery; 7, invasive procedures outside the operating room; 8, sepsis and/or disseminated intravascular coagulation) as well as laboratory assays and selection/processing of plasma and platelet components. In total, we came to consensus on four recommendations, five good practice statements, and 44 consensus-based statements. These results were further developed into consensus-based clinical decision trees for plasma and platelet transfusion in critically ill pediatric patients. CONCLUSIONS: The TAXI-CAB program provides expert-based consensus for pediatric intensivists for the administration of plasma and/or platelet transfusions in critically ill pediatric patients. There is a pressing need for primary research to provide more evidence to guide practitioners.

Comparison of Thromboelastography Devices TEG®6S Point of Care Device vs. TEG®5000 in Pediatric Patients Undergoing Cardiac Surgery.

Thromboelastography (TEG) can predict bleeding in pediatric patients undergoing cardiac surgery. We hypothesized that results obtained from TEG®5000 correlate with the new point-of-care TEG®6S system and that TEG®6S rewarming maximum amplitude (MA) is associated with surrogate endpoints for perioperative bleeding in pediatric patients who underwent complex cardiac surgery. We describe a retrospective study of pediatric (≤18 years) patients who underwent complex cardiac surgery on cardiopulmonary bypass. Citrate whole-blood samples were used to compared TEG®5000 vs.TEG®6S and TEG®6S-FLEV (with fibrinogen measurement) vs. Clauss-fibrinogen methods. TEG®6S parameters obtained during rewarming were compared to the surrogate endpoints for perioperative bleeding using linear regression analysis. Among 100 patients, 225 TEG®5000 vs.TEG®6S comparisons and 54 TEG®6S-FLEV were analyzed. Good correlation was observed for all parameters comparing TEG®5000 to TEG®6S and TEG®6S-FLEV to the Clauss-fibrinogen method (Pearson r ≥ .7). Similar to rewarming TEG®5000 MA, rewarming TEG®6S MA was the only parameter independently associated with risk for perioperative bleeding (median [interquartile range {IQR}] in bleeding vs. nonbleeding patients: 35 [29, 48] vs. 37 [32, 55]; p = .02). A platelet transfusion calculator was developed based on TEG®6S results by determining the relationship between platelet transfusion volume (mL/kg) and percent change in MA using linear regression analysis. TEG®6S is a good alternative point-of-care method to analyze a patient's coagulation profile and it is comparable to TEG®5000 in pediatric patients undergoing cardiac surgery on cardiopulmonary bypass. Lower TEG®6S MA during rewarming is associated with increased risk for perioperative bleeding. TEG analysis during rewarming may be useful in customizing platelet transfusion therapy by reducing the risk of bleeding while minimizing excessive blood product transfusions.

Human endothelial colony-forming cells provide trophic support for pluripotent stem cell-derived cardiomyocytes via distinctively high expression of neuregulin-1.

The search for a source of endothelial cells (ECs) with translational therapeutic potential remains crucial in regenerative medicine. Human blood-derived endothelial colony-forming cells (ECFCs) represent a promising source of autologous ECs due to their robust capacity to form vascular networks in vivo and their easy accessibility from peripheral blood. However, whether ECFCs have distinct characteristics with translational value compared to other ECs remains unclear. Here, we show that vascular networks generated with human ECFCs exhibited robust paracrine support for human pluripotent stem cell-derived cardiomyocytes (iCMs), significantly improving protection against drug-induced cardiac injury and enhancing engraftment at ectopic (subcutaneous) and orthotopic (cardiac) sites. In contrast, iCM support was notably absent in grafts with vessels lined by mature-ECs. This differential trophic ability was due to a unique high constitutive expression of the cardioprotective growth factor neuregulin-1 (NRG1). ECFCs, but not mature-ECs, were capable of actively releasing NRG1, which, in turn, reduced apoptosis and increased the proliferation of iCMs via the PI3K/Akt signaling pathway. Transcriptional silencing of NRG1 abrogated these cardioprotective effects. Our study suggests that ECFCs are uniquely suited to support human iCMs, making these progenitor cells ideal for cardiovascular regenerative medicine.

Stratification of Bleeding Risk Using Thromboelastography in Children on Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Patients undergoing extracorporeal membrane oxygenation are at high risk for bleeding and thrombotic complications. Current laboratory methods for assessing the coagulation system may be imprecise and complicate clinical decision-making. We hypothesize that thromboelastography may be more strongly associated with bleeding events than traditional methods and can aid extracorporeal membrane oxygenation coagulation management. DESIGN: In a retrospective study, 40 patients with congenital heart disease requiring extracorporeal membrane oxygenation support yielded a total of 159 patient days of data for thromboelastography analysis. SETTING: Pediatric cardiac ICU at a single institution. SUBJECTS: Pediatric patients (≤ 18 yr) with congenital heart disease requiring extracorporeal membrane oxygenation support. INTERVENTIONS: None. METHODS: Thromboelastography was performed on whole blood samples collected 6-12 hours following extracorporeal membrane oxygenation initiation and daily for the duration of extracorporeal membrane oxygenation. Bleeding during each 24-hour period was defined as need for re-exploration or need for blood transfusion. Associations between thromboelastography variables and bleeding over each 24-hour period (bleeding vs nonbleeding days) were assessed using mixed effects logistic regression and classification and regression tree analysis. MEASUREMENTS AND MAIN RESULTS: Bleeding occurred in 25 patients (63%), contributing 87 bleeding days (55% extracorporeal membrane oxygenation days) for analysis. The probability of bleeding within the 24-hour period was not associated with activated partial thromboplastin time (p = 0.6) or anti-Xa levels (p = 0.3) on that day. The strongest correlate of bleeding was a maximum amplitude less than 55.4 mm on thromboelastography (odds ratio, 3.28; 95% CI, 1.63-6.60; p < 0.001). Bleeding occurred on 73% versus 35% of extracorporeal membrane oxygenation days for maximum amplitude less than 55.4 mm versus greater than or equal to 55.4 mm, respectively. Bleeding occurred on all days when a combination of maximum amplitude less than 55.4 mm and a reaction time greater than 12.9 minutes was present. The lowest risk of bleeding (28% of patient days) was associated with maximum amplitude greater than or equal to 55.4 mm and plasma fibrinogen greater than 345 mg/dL. CONCLUSIONS: Thromboelastography-derived variables maximum amplitude and reaction time, along with plasma fibrinogen levels, can help predict bleeding events in children on extracorporeal membrane oxygenation support. Research based on larger patient samples is needed to confirm the specific thresholds identified for bleeding risk stratification for extracorporeal membrane oxygenation anticoagulation management.

Left Ventricular Recruitment in Patients With Hypoplastic Left Heart Syndrome.

Hypoplastic left heart complex with "borderline left ventricle" and intact ventricular septum is a clinical conundrum for the congenital heart surgeon. The choice between neonatal biventricular repair and single ventricle palliation can be challenging, and the current tools to aid in the decision-making process fail to account for the morbidity associated with intermediate and late diastolic dysfunction. Staged ventricular recruitment, consisting of valvular repair techniques, resection of endocardial fibroelastosis, atrial septal restriction, and augmentation of pulmonary blood flow, has been shown to improve left ventricular size and function culminating in eventual biventricular circulation. Despite staged ventricular recruitment, some patients cannot undergo biventricular conversion. Strategies to address these complex patients, including the "reverse" double switch, are the next frontier in biventricular repair.

Platelet Inhibition With IV Glycoprotein IIb/IIIa Inhibitor to Prevent Thrombosis in Pediatric Patients Undergoing Aortopulmonary Shunting.

OBJECTIVES: Shunt thrombosis, a potential complication of aortopulmonary shunting, is associated with high mortality. Commonly used oral antiplatelet drugs such as aspirin demonstrate variable absorption and inconsistent antiplatelet effect in critically ill patients early after surgery. IV glycoprotein IIb/IIIa inhibitors are antiplatelet agents with rapid and reproducible effect that may be beneficial as a bridge to oral therapy. DESIGN: Retrospective review of pediatric patients undergoing treatment with IV tirofiban. Discarded blood samples were used to determine pharmacokinetic parameters. SETTING: Pediatric cardiac ICU at a single institution. PATIENTS: Fifty-two pediatric patients (< 18 yr) undergoing surgical aortopulmonary shunt procedure who received tirofiban infusion as a bridge to oral aspirin. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were shunt thrombosis and bleeding events, whereas secondary outcomes included measurement of platelet inhibition by thromboelastography with platelet mapping and pharmacokinetic analysis (performed in a subset of 15 patients). Shunt thrombosis occurred in two of 52 patients (3.9%) after prophylaxis treatment with tirofiban; both thrombosis events occurred after discontinuation of the drug. One patient (1.9%) experienced bleeding complication during the infusion. A tirofiban bolus of 10 µg/kg and infusion of 0.15 µg/kg/min resulted in significantly increased platelet inhibition via adenosine diphosphate pathway (median 66% [43-96] pre-tirofiban compared with 97% [92-99%] at 2 hr; p < 0.05). Half-life of tirofiban in plasma was 142 ± 1.5 minutes, and the average steady-state concentration was 112 ± 62 ng/mL. Age and serum creatinine were significant covariates associated with systemic clearance. Dosing simulations were generated based upon one compartment model. CONCLUSIONS: IV glycoprotein IIb/IIIa inhibitor as a bridge to oral antiplatelet therapy is safe in pediatric patients after aortopulmonary shunting. Dosing considerations should include both age and renal function. Randomized trials are warranted to establish efficacy compared with current anticoagulation practices.

Expandable Valves, Annuloplasty Rings, Shunts, and Bands for Growing Children.

In congenital heart surgery, the surgeon must constantly consider how a palliative or corrective procedure could be impacted by the child's somatic growth. Within pediatric valve surgery, existing valve repair techniques lack growth-accommodating prostheses. Valve replacement options are fixed in size and unable to grow with the child, thus subjecting children to repeated valve reoperations. When creating a systemic-to-pulmonary artery shunt, replacing a branch pulmonary artery or conduit, creating an extracardiac Fontan pathway, or banding the pulmonary artery, the implant size must factor in both the child's current size and his or her anticipated growth. A variety of growth-accommodating technologies have been developed to fill this unmet need. Some devices have reached the clinical arena, while several are in preclinical development. The purpose of this review is to characterize the clinical need for growing device technology, and then review established and developing technologies for growth accommodation in congenital heart surgery.

Intraoperative Coronary Artery Imaging for Planning.

A clear understanding of coronary anatomy is critical in congenital heart surgery, especially when a ventriculotomy is planned, as in right ventricular outflow tract reconstructions and biventricular repairs. Typically, major epicardial coronary arteries are easily identified during first-time operations. However, in reoperative surgery, epicardial adhesions can obscure coronary vessels making their identification challenging. This paper describes the application of intraoperative fluorescence imaging in congenital heart surgery to obtain real-time coronary artery visualization for operative planning in order to avoid coronary injury. The fluorescence imaging utilizes indocyanine green (ICG). ICG is diluted to 0.28 mg/mL, and 0.1-1.0 mL of ICG solution is delivered via the cardioplegia cannula into the coronaries. A handheld imaging probe illuminates the field with near-infrared laser light, which excites ICG fluorescence. The fluorescence is captured by a camera, and the signal is transmitted to a monitor for real-time viewing. The imaging probe shows the precise coronary anatomy, enabling identification of the optimal ventriculotomy site. Intraoperative fluorescence imaging is a safe and effective technique for characterizing coronary anatomy. This technique enhances procedural planning and helps minimize the risk of coronary injury during reoperative congenital heart surgery.

Comparison of outcomes following thoracoscopic versus thoracotomy closure for persistent patent ductus arteriosus.

BACKGROUND: Patent ductus arteriosus closure is traditionally performed by thoracotomy approach. Video-assisted thoracoscopic surgery is a less frequently utilised alternative. We sought to compare elective surgical outcomes between the two methods via a single-centre retrospective cohort analysis. METHODS: All patients >3.2 kg undergoing surgical patent ductus arteriosus ligation at a single institution from 2000 to 2018 were retrospectively reviewed. Propensity matching for age, weight, diuretic usage, and preterm status was conducted to adjust for differences in baseline patient characteristics. Outcome measures included operative time, hospitalisation duration, post-operative complications, and re-operation. RESULTS: A total of 173 patients were included, 127 thoracoscopy and 46 thoracotomy. In the unmatched cohorts, no significant difference in closure success was found (94% thoracoscopy versus 100% thoracotomy, p = 0.192). Although median operative time was longer for thoracoscopy (87 versus 56 minutes, p < 0.001), hospitalisation duration was shorter (1.05 versus 2.41 days, p < 0.001), as was ICU stay (0.00 versus 0.75 days, p < 0.001). There were no significant differences in re-operation or complication rates, except chest tube placement (11% thoracoscopy versus 50% thoracotomy, p < 0.001). After matching (69 thoracoscopy versus 20 thoracotomy), these differences persisted, including median operative time (81 versus 56 minutes, p = 0.007; thoracoscopy versus thoracotomy), hospitalisation duration (1.25 versus 2.27 days, p < 0.001), and chest tube placement (17% versus 60%, p < 0.001). There remained no significant difference in complications or re-operations. CONCLUSIONS: Thoracoscopic ligation was associated with shorter ICU and hospital stays and less frequent chest tube placement, but longer operative times. Other risks, including bleeding, chylothorax, and recurrent laryngeal nerve injury, were similar.

A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP. The ESHP circuit consists of an oxygenator, a heart-lung machine, a heater-cooler unit, an anesthesia gas blender, and a collection funnel. Female Yorkshire pig hearts (n = 10) had del Nido cardioplegia (4°C) administered, excised, and attached to the perfusion system. Hearts were perfused retrogradely into the aortic root for 2 hours before converting the system to an isovolumic mode or a working mode for further 2 hours. Blood samples were analyzed to measure metabolic parameters. During the isovolumic mode (n = 5), a balloon inserted in the left ventricular (LV) cavity was inflated so that an end-diastolic pressure of 6-8 mmHg was reached. During the working mode (n = 5), perfusion in the aortic root was redirected into left atrium (LA) using a compliance chamber which maintained an LA pressure of 6-8 mmHg. Another compliance chamber was used to provide an afterload of 40-50 mmHg. Hemodynamic and metabolic conditions remained stable and consistent for a period of 4 hours of ESHP in both isovolumic mode (LV developed pressure: 101.0 ± 3.5 vs. 99.7 ± 6.8 mmHg, p = .979, at 2 and 4 hours, respectively) and working mode (LV developed pressure: 91.0 ± 2.6 vs. 90.7 ± 2.5 mmHg, p = .942, at 2 and 4 hours, respectively). The present study proposed a novel ESHP system that enables comprehensive functional and metabolic assessment of large mammalian hearts. This system allowed for stable myocardial function for up to 4 hours of perfusion, which would offer great potential for the development of translational therapeutic protocols to improve dysfunctional donated hearts.