Opioid Utilization after Cardiac Surgery in the Pediatric Medicaid-Insured Population.

OBJECTIVE: To determine the variation of outpatient opioid prescribing across the US in postoperative pediatric cardiac patients. STUDY DESIGN: Retrospective, cross-sectional study using a concatenated database of Medicaid claims between from 2016 through 2018 of children 0-17 years, discharged after cardiac surgery and receiving an opioid prescription within 30 days. Filled prescriptions were identified and converted to morphine milligram equivalents (MME). Use, duration, and dose were analyzed by sex, race, ethnicity, residence urbanicity, and region. RESULTS: Among 17 186 Medicaid-enrolled children after cardiac surgery, 2129 received opioids within 30 days of discharge. Females received lower doses than males (coefficient -0.17, P = .022). Hispanic individuals were less likely to receive opioids (coefficient 0.53, P < .05, 95% CI: 0.38-0.71) and for shorter periods (coefficient 0.83, P < .001). Midwest (MW) (OR 0.61, 95% P-values < 0.05, 95% CI: 0.46-0.80) and Northeast (NE) (OR 0.43, 95% P-values < 0.05, 95% CI: 0.30-0.61) regions were less likely to receive opioids but used higher doses compared with the Southeast (SE) (MW coefficient 0.41, Southwest (SW) coefficient 0.18, NE coefficient 0.32, West (W) coefficient 0.19, P < .05). CONCLUSIONS: There were significant variations in opioid prescribing after cardiac surgery by race, ethnicity, sex, and region. National guidelines for outpatient use of opioids in children after cardiac surgery may help limit practice variation and reduce potential harms in outpatient opioid usage.

Risk Factors for Extubation Failure After Pediatric Cardiac Surgery and Impact on Outcomes: A Multicenter Analysis.

IMPORTANCE: Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES: We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES: We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS: Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE: Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Impact of Antegrade Pulmonary Blood Flow as Patients Progress Through Single-Ventricle Palliations.

BACKGROUND: The impact of antegrade pulmonary blood flow (APBF) during single-ventricle (SV) palliation continues to be debated. We sought to assess its impact on the hemodynamic profile and the short- and long-term outcomes of patients progressing through stages of SV palliation. METHODS: A retrospective single-center study was conducted of SV patients who underwent surgery between January 2010 and December 2020. Patients with APBF were matched to those with no APBF by a propensity score based on body surface area, sex, and type of systemic ventricle. Analysis was performed using appropriate statistics with a significance level of P = .05. RESULTS: Sixty-three patients with APBF were matched with 95 patients with no APBF. At the pre-stage 2 catheterization, APBF patients had a larger left pulmonary artery diameter (z score, 0.1 vs -0.8; P < .042). Patients with APBF had shorter cardiopulmonary bypass time (57.0 vs 79.0 minutes), shorter duration of mechanical ventilation (14.1 vs 17.4 hours), and shorter hospital length of stay (5.0 vs 7.0 days) at stage 2 palliation (P < .05). In the multivariable Cox regression analysis, patients with hypoplastic pulmonary arteries (z scores < -2; adjusted hazard ratio, 9.17) and patients with chromosomal abnormalities/genetic syndrome (adjusted hazard ratio, 4.03) were at increased risk for poor outcomes (P < .05). During the follow-up period, there was no significant difference in risk of the composite poor outcome and long-term survival between groups. CONCLUSIONS: SV patients with APBF had shorter cardiopulmonary bypass time, duration of mechanical ventilation, and hospital length of stay after stage 2 palliation. Patients with hypoplastic pulmonary arteries or chromosomal abnormalities/genetic syndromes had increased risk for poor outcomes. Maintaining APBF has better short-term outcomes, but there are no long-term hemodynamic or survival benefits.

External airway splint placement for severe pediatric tracheobronchomalacia.

OBJECTIVE: To present external airway splinting with bioabsorbable airway supportive devices (ASD) for severe, life-threatening cases of pediatric tracheomalacia (TM) or tracheobronchomalacia (TBM). METHODS: A retrospective cohort was performed for 5 pediatric patients with severe TM or TBM who underwent ASD placement. Devices were designed and 3D-printed from a bioabsorbable material, polycaprolactone (PCL). Pre-operative planning included 3-dimensional airway modeling of tracheal collapse and tracheal suture placement using nonlinear finite element (FE) methods. Pre-operative modeling revealed that triads along the ASD open edges and center were the most effective suture locations for optimizing airway patency. Pediatric cardiothoracic surgery and otolaryngology applied the ASDs by suspending the trachea to the ASD with synchronous bronchoscopy. Respiratory needs were trended for all cases. Data from pediatric patients with tracheostomy and diagnosis of TM or TBM, but without ASD, were included for discussion. RESULTS: Five patients (2 Females, 3 Males, ages 2-9 months at time of ASD) were included. Three patients were unable to wean from respiratory support after vascular ring division; all three weaned to room air post-ASD. Two patients received tracheostomies prior to ASD placement, but continued to experience apparent life-threatening events (ALTE) and required ventilation with supraphysiologic ventilator settings. One patient weaned respiratory support successfully after ASD placement. The last patient died post-ASD due to significant respiratory co-morbidity. CONCLUSION: ASD can significantly benefit patients with severe, unrelenting tracheomalacia or tracheobronchomalacia. Proper multidisciplinary case deliberation and selection are key to success with ASD. Pre-operative airway modeling allows proper suture placement to optimally address the underlying airway collapse.

A comparison of high-flow nasal cannula versus non-invasive positive pressure ventilation for respiratory support in infants following cardiac surgery.

BACKGROUND: Following cardiac surgery, infants often remain endotracheally intubated upon arrival to the cardiac ICU. High-flow nasal cannula and non-invasive positive pressure ventilation are used to support patients following extubation. There are limited data on the superiority of either mode to prevent extubation failure. METHODS: We conducted a single-centre retrospective study for infants (<1 year) and/or <10 kg who underwent cardiac surgery between 3/2019-3/2020. Data included patient and clinical characteristics and operative variables. The study aimed to compare high-flow nasal cannula versus non-invasive positive pressure ventilation following extubation and their association with extubation failure. Secondarily, we examined risk factors associated with extubation failure. RESULTS: There were 424 patients who met inclusion criteria, 320 (75%) were extubated to high-flow nasal cannula, 104 (25%) to non-invasive positive pressure ventilation, and 64 patients (15%) failed extubation. The high-flow nasal cannula group had lower rates of extubation failure (11%, versus 29%, p = 0.001). Infants failing extubation were younger and had higher STAT score (p < 0.05). Compared to high-flow nasal cannula, non-invasive positive pressure ventilation patients were at 3.30 times higher odds of failing extubation after adjusting for patient factors (p < 0.0001). CONCLUSIONS: Extubation failure after cardiac surgery occurs in smaller, younger infants, and those with higher risk surgical procedures. Patients extubated to non-invasive positive pressure ventilation had 3.30 higher odds to fail extubation than patients extubated to high-flow nasal cannula. The optimal mode of respiratory support in this patient population is unknown.

Incidence and recovery of post-surgical heart block in children following cardiac surgery.

BACKGROUND: A subset of patients who develop post-surgical heart block have recovery of atrioventricular node function. Factors predicting recovery are not understood. We investigated our centre's incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular node function. METHODS: We conducted a single-centre retrospective study of patients 0 - 21 years who underwent cardiac surgery between January 2010 and December 2019 and experienced post-operative heart block. Data including patient and clinical characteristics and operative variables were collected and analysed. RESULTS: Of 6333 surgical hospitalisations, 128 (2%) patients developed post-operative heart block. Of the 128 patients, 90 (70%) had return of atrioventricular node function, and 38 (30%) had pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular node function noted on long-term follow-up. Median time from onset of heart block to late atrioventricular node recovery was 13 days (Interquartile range: 5 - 117). Patients with single-ventricle physiology (p = 0.04), greater weight (p = 0.03), and shorter cardiopulmonary bypass time (p = 0.015) were more likely to have recovery. The use of post-operative steroids was similar between all groups (p = 0.445). Infectious or wound complications were similar between pacemaker groups (p = 1). CONCLUSIONS: Two per cent of patients who underwent congenital cardiac surgery developed post-operative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular node was associated with greater weight at the time of surgery, single-ventricle physiology, and shorter cardiopulmonary bypass time. Late recovery of atrioventricular node conduction following pacemaker placement occurred in 15.8% of patients.

Comparison of Invasive and Oscillometric Blood Pressure Measurement in Obese and Nonobese Children.

BACKGROUND: Obesity and hypertension are public health priorities, with obesity considered to be a potential cause of hypertension. Accurate blood pressure (BP) determination is required and often obtained by automated oscillometric cuff devices. We sought to determine the correlation of oscillometric measurement in children, and if obesity was associated with worse correlation between methods than nonobese children. METHODS: Retrospective matched case-controlled study of 100 obese (97-99th percentile) and 100 nonobese (25-70th percentile) children after cardiac surgery with simultaneous systolic, diastolic, and mean invasive and oscillometric measurements. Matching was 1:1 for age, sex, race, and Risk Adjustment for Congenital Heart Surgery-1 score. Intraclass correlation coefficients and Bland-Altman plots were used to determine agreement with 0.75 as threshold. RESULTS: Median age was 13 years (10-15). Agreement was low for systolic (0.65 and 0.61), diastolic (0.68 and 0.61), and mean measurements (0.73 and 0.69) (obese/nonobese). Bland-Altman plots demonstrated oscillometric BP measurements underestimated systolic hypertension (oscillometric readings lower than intra-arterial). Oscillometric measurements underestimated hypotension (systolic oscillometric measurements were higher than intra-arterial). This occurred in obese and nonobese patients. Correlation of oscillometric measurements was similar for nonobese and obese patients. CONCLUSIONS: In this first ever study of simultaneous BP measurement by oscillometric vs. intra-arterial in obese and nonobese children, correlation is below accepted norms. The correlation of oscillometric cuff measurements is not affected by habitus in children. There is less correlation between oscillometric measurements and intra-arterial measurements during hypertension or hypotension. Healthcare providers should be aware of the limitations of oscillometric measurements.

Atrial septostomy in patients supported with venoarterial extracorporeal membrane oxygenation: Analysis of the IMPACT registry data.

BACKGROUND: Patients with severe cardiac dysfunction, supported on extra-corporeal membrane oxygenation (ECMO), develop left atrial hypertension and often warrant atrial decompression. The procedural risks and outcomes, however, are not well established. Objective of this study is to understand the utilization, safety, and outcomes of atrial septostomy in children supported on venoarterial ECMO utilizing the IMPACT registry database. METHODS: Data from 55 independent sites reporting to the registry was used for this descriptive study. Patients supported with cardiac ECMO that underwent percutaneous atrial septostomy (PAS) were included and data analyzed. RESULTS: Between 2011 and 2018, 223 patients underwent atrial septostomy and were reported to the registry. Mean age was 4.65 years with 52% being males. Diagnoses of heart failure, sepsis, arrhythmia, and renal insufficiency were commonly noted prior to ECMO. The procedure was performed urgently or emergently in most cases (80%). PAS was associated with significant procedural complications such as arrhythmia (6.8%), tamponade (5.4%), and unplanned surgery (3.6%) but no procedural mortality. Overall hospital mortality was 46% (103/223) with 46 of these deaths occurring within 7 days of procedure. Regression analysis showed that African American race (vs Caucasian), race other than Caucasian, chronic lung disease and emergent procedure need were significantly associated with early post-procedural mortality (all p < 0.05). CONCLUSION: Using a large multicenter cardiac catheterization registry, we found that left atrial decompression can be performed without procedural mortality but is associated with significant morbidity. Impact of race, chronic lung disease and procedural urgency on early mortality warrant further studies.

Using pulse oximetry waveforms to detect coarctation of the aorta.

BACKGROUND: Coarctation of the aorta is a common form of critical congenital heart disease that remains challenging to diagnose prior to clinical deterioration. Despite current screening methods, infants with coarctation may present with life-threatening cardiogenic shock requiring urgent hospitalization and intervention. We sought to improve critical congenital heart disease screening by using a novel pulse oximetry waveform analysis, specifically focused on detection of coarctation of the aorta. METHODS AND RESULTS: Over a 2-year period, we obtained pulse oximetry waveform data on 18 neonates with coarctation of the aorta and 18 age-matched controls hospitalized in the cardiac intensive care unit at Children's Healthcare of Atlanta. Patients with coarctation were receiving prostaglandin E1 and had a patent ductus arteriosus. By analyzing discrete features in the waveforms, we identified statistically significant differences in the maximum rate of fall between patients with and without coarctation. This was accentuated when comparing the difference between the upper and lower extremities, with the lower extremities having a shallow slope angle when a coarctation was present (p-value 0.001). Postoperatively, there were still differences in the maximum rate of fall between the repaired coarctation patients and controls; however, these differences normalized when compared with the same individual's upper vs. lower extremities. Coarctation patients compared to themselves (preoperatively and postoperatively), demonstrated waveform differences between upper and lower extremities that were significantly reduced after successful surgery (p-value 0.028). This screening algorithm had an accuracy of detection of 72% with 0.61 sensitivity and 0.94 specificity. CONCLUSIONS: We were able to identify specific features in pulse oximetry waveforms that were able to accurately identify patients with coarctation and further demonstrated that these changes normalized after surgical repair. Pulse oximetry screening for congenital heart disease in neonates may thus be improved by including waveform analysis, aiming to identify coarctation of the aorta prior to critical illness. Further large-scale testing is required to validate this screening model among patients in a newborn nursery setting who are low risk for having coarctation.

Nonopioid analgesics for perioperative and cardiac surgery pain in children: Current evidence and knowledge gaps.

OBJECTIVE: The purpose of this review is to present the available literature on the use of nonopioid analgesics such as nonsteroidal anti-inflammatory drugs in postcardiac surgery pediatric patients, mainly to focus on patients <1 year of age, and to provide the foundation for future research. MATERIALS AND METHODS: Published studies that address the use on nonopioid medications for postoperative sedation and analgesia in infants and children undergoing cardiac surgery were identified from online sources. Studies were reviewed by two authors independently to assess the quality of the data as well as the evidence. Due to limited availability of such studies, the review was then expanded to include use in noncardiac procedures as well as to expanded age groups. All studies that met the primary objective were included. RESULTS/DATA SYNTHESIS: Majority of the studies in the population of interest were related to use of ketorolac. Five studies specifically addressed ketorolac use in cardiac patients. In addition, studies were reviewed for nonopioid analgesia in noncardiac patients and included as a part of the available evidence as in the case of acetaminophen use. Newer agents as well as agents with very limited information were also acknowledged. CONCLUSION: Nonopioid medications appear to show promise for analgesia in infants undergoing cardiac surgery, with ketorolac being the most potent agent as a potential substitute for opioids. These agents demonstrate a reasonable safety profile even in the very young. There continue to be significant gaps in knowledge before their adoption becomes routine. However, gives the awareness regarding short-term and long-term impact of opioid use in this vulnerable population, and studies of such agents are an urgent need.

Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling and Precision Medicine: A Scientific Statement From the American Heart Association.

Induced pluripotent stem cells (iPSCs) offer an unprece-dented opportunity to study human physiology and disease at the cellular level. They also have the potential to be leveraged in the practice of precision medicine, for example, personalized drug testing. This statement comprehensively describes the provenance of iPSC lines, their use for cardiovascular disease modeling, their use for precision medicine, and strategies through which to promote their wider use for biomedical applications. Human iPSCs exhibit properties that render them uniquely qualified as model systems for studying human diseases: they are of human origin, which means they carry human genomes; they are pluripotent, which means that in principle, they can be differentiated into any of the human body's somatic cell types; and they are stem cells, which means they can be expanded from a single cell into millions or even billions of cell progeny. iPSCs offer the opportunity to study cells that are genetically matched to individual patients, and genome-editing tools allow introduction or correction of genetic variants. Initial progress has been made in using iPSCs to better understand cardiomyopathies, rhythm disorders, valvular and vascular disorders, and metabolic risk factors for ischemic heart disease. This promising work is still in its infancy. Similarly, iPSCs are only just starting to be used to identify the optimal medications to be used in patients from whom the cells were derived. This statement is intended to (1) summarize the state of the science with respect to the use of iPSCs for modeling of cardiovascular traits and disorders and for therapeutic screening; (2) identify opportunities and challenges in the use of iPSCs for disease modeling and precision medicine; and (3) outline strategies that will facilitate the use of iPSCs for biomedical applications. This statement is not intended to address the use of stem cells as regenerative therapy, such as transplantation into the body to treat ischemic heart disease or heart failure.

Identification of targeting peptides for the diagnosis of myocarditis.

AIM: Current diagnostic tests for myocarditis are invasive and have low diagnostic value. Our aim was to identify potential targeting peptides to detect early myocarditis following intravenous delivery. MATERIALS & METHODS: We used an animal model of experimental autoimmune myocarditis and a phage display library to identify potential targeting peptides. After several steps, we selected two peptides, MyH-PhD-05 and MyH-PhD-120, for in vivo screening using fluorescent imaging. Immunofluorescence and proteonomic analysis was used to identify potential cellular and molecular targets of MyH-PhD-05. Echocardiography was used to assess functional changes. RESULTS: Peptide MyH-PhD-05 was able to detect animals with severe myocarditis even in the absence of functional changes. Immunofluorescence demonstrated that MyH-PhD-05 colocalizes with CD4+ T cells and monocytes (CD11b+) in cardiac infiltrates. CONCLUSION: We identified potential targeting peptides for the diagnosis of myocarditis. Future studies will focus on better identification of potential targets and translating this technology to clinically relevant imaging modalities.

Novel surface-enhanced Raman scattering-based assays for ultra-sensitive detection of human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, but their derivatives need to be rigorously evaluated for residual stem cells to prevent teratoma formation. Here, we report the development of novel surface-enhanced Raman scattering (SERS)-based assays that can detect trace numbers of undifferentiated hPSCs in mixed cell populations in a highly specific, ultra-sensitive, and time-efficient manner. By targeting stem cell surface markers SSEA-5 and TRA-1-60 individually or simultaneously, these SERS assays were able to identify as few as 1 stem cell in 10(6) cells, a sensitivity (0.0001%) which was ∼2000 to 15,000-fold higher than that of flow cytometry assays. Using the SERS assay, we demonstrate that the aggregation of hPSC-based cardiomyocyte differentiation cultures into 3D spheres significantly reduced SSEA-5(+) and TRA-1-60(+) cells compared with parallel 2D cultures. Thus, SERS may provide a powerful new technology for quality control of hPSC-derived products for preclinical and clinical applications.

Aortic and Mitral Valve Disease and Left Ventricular Dysfunction in Children.

OBJECTIVES: In this review, we will discuss aortic stenosis, aortic regurgitation, mitral regurgitation, and mitral stenosis. We will review the etiology, anatomy, pathophysiology, presentation, and treatment of aortic and mitral valve disease. Age and lesion specific treatments are outlined based on the severity of valve disease with an aim at long-term preservation of left ventricular function. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Mitral and aortic valve disease leads to unique hemodynamic burdens that can impact left ventricular function, quality of life, and longevity. The primary challenge in the management of mitral and aortic valve disease is to apply appropriate medical management and identify that point in time at which the surgery is necessary. Although guidelines have been established for the management of aortic and mitral valve disease in adults, the challenges of early presentation, maintenance of growth potential, and apparent increased tolerance of hemodynamic burden in children makes decision making challenging.

Innovation in Pediatric Cardiac Intensive Care: An Exponential Convergence Toward Transformation of Care.

The word innovation is derived from the Latin noun innovatus, meaning renewal or change. Although companies such as Google and Apple are nearly synonymous with innovation, virtually all sectors in our current lives are imbued with yearn for innovation. This has led to organizational focus on innovative strategies as well as recruitment of chief innovation officers and teams in a myriad of organizations. At times, however, the word innovation seems like an overused cliché, as there are now more than 5,000 books in print with the word "innovation" in the title. More recently, innovation has garnered significant attention in health care. The future of health care is expected to innovate on a large scale in order to deliver sustained value for an overall transformative care. To date, there are no published reports on the state of the art in innovation in pediatric health care and in particular, pediatric cardiac intensive care. This report will address the issue of innovation in pediatric medicine with relevance to cardiac intensive care and delineate possible future directions and strategies in pediatric cardiac intensive care.

Early postoperative bleeding is independently associated with increased surgical mortality in infants after cardiopulmonary bypass.

OBJECTIVE: Infants undergoing cardiac surgery often have postoperative bleeding contributing to the occurrence of adverse events. A quantitative evaluation of postoperative bleeding has not been well described. METHODS: We identified 1071 infants who had undergone cardiopulmonary bypass from August 1, 2008 to December 31, 2011. The volume of postoperative bleeding and its effect on mortality were reviewed. RESULTS: Postoperative bleeding during the first 12 hours postoperatively was stratified by quartiles. Bleeding was significantly associated with increased mortality (odds ratio [OR], 1.15; 95% confidence interval [CI] 1.10-1.21; P < .001). Other risk factors significantly associated with mortality included greater Risk Adjustment for Congenital Heart Surgery score (OR, 1.5; 95% CI, 1.22-1.85; P < .001), single ventricle anatomy (OR, 3.09; 95% CI, 1.68-5.67; P < .001), younger age (OR, 0.99; 95% CI, 0.98-0.99; P < .001), and longer perfusion time (OR, 1.01; 95% CI, 1.01-1.02; P < .001). Subjects with greater bleeding volumes experienced a longer postoperative mechanical ventilation and intensive care unit stay. The overall hospital mortality was 4.1%. On multivariate analysis, adjusting for age, single ventricle anatomy, Risk Adjustment for Congenital Heart Surgery score, and perfusion time, an increasing bleeding volume was independently associated with increased mortality. Packed red blood cell transfusion was independently associated with an increased duration of mechanical ventilation (P = .01) and intensive care unit length of stay (P = .003). CONCLUSIONS: Early postoperative hemorrhage was independently associated with an increased mortality in infants after cardiac surgery. The longer interval from surgery to death suggests that other factors, aside from the bleeding itself, including the transfusion volume, might contribute to mortality. Initiatives to limit postoperative bleeding and to critically appraise packed red blood cell transfusion practices are warranted.

Marching towards regenerative cardiac therapy with human pluripotent stem cells.

Damage in cardiac tissues from ischemia or other pathological conditions leads to heart failure; and cell loss or dysfunction in pacemaker tissues due to congenital heart defects, aging, and acquired diseases can cause severe arrhythmias. The promise of successful therapies with stem cells to treat these conditions has remained elusive to the scientific community. However, recent advances in this field have opened new opportunities for regenerative cardiac therapy. Transplantation of cardiomyocytes derived from human pluripotent stem cells has the potential to alleviate heart disease. Since the initial derivation of human embryonic stem cells, significant progress has been made in the generation and characterization of enriched cardiomyocytes and the demonstration of the ability of these cardiomyocytes to survive, integrate, and function in animal models. The scope of therapeutic potential from pluripotent stem cell-derived cardiomyocytes has been further expanded with the invention of induced pluripotent stem cells, which can be induced to generate functional cardiomyocytes for regenerative cardiac therapy in a patient specific manner. The reprogramming technology has also inspired the recent discovery of direct conversion of fibroblasts into cardiomyocyte-like cells, which may allow endogenous cardiac repair. Regenerative cardiac therapy with human pluripotent stem cells is now moving closer to clinic testing.

Short-term outcomes in premature neonates adhering to the philosophy of supportive care allowing for weight gain and organ maturation prior to cardiac surgery.

BACKGROUND: Prematurity is a recognized risk factor for morbidity and mortality following cardiac surgery. The purpose of this study was to examine short-term outcomes following cardiac surgery in premature neonates adhering to our institutional philosophy of supportive care allowing for weight gain and organ maturation. METHODS: Retrospective review of all neonates undergoing cardiac surgery from January 2002 to May 2008. A total of 810 neonates (<30 days of age) were identified. Prematurity defined as less than 36 weeks of gestation. Neonates undergoing ductus arteriosus ligation alone were excluded. In all, 63 neonates comprised the premature group. Term group comprised 244 randomly selected term neonates in a 1:4 ratio. Outcome variables were compared between the 2 groups. RESULTS: Median gestation 34 weeks, range 24 to 35 weeks. Defects: 2 ventricle, normal arch (41% premature vs 44% term; P = .7), 2 ventricle, abnormal arch (24% vs 22%; P = .8), single ventricle, normal arch (21% vs 15%; P = .2), single ventricle, abnormal arch (14% vs 19%; P = .4). Premature neonates were older and smaller at surgery. Cardiopulmonary bypass procedures were performed less frequently in premature neonates (49% vs 69%; P = .004). Length of mechanical ventilation at our institution (6 days [0.5-54) vs 4 days [0.5-49); P = .06); postoperative hospital stay at our institution (17 days [1-161) vs 15 days [0-153); P = .06); and mortality (16% vs 11%; P = .2) was not different between the 2 groups. CONCLUSION: Early outcome seems independent of weight, prematurity, cardiopulmonary bypass, and type of first intervention. Importantly, there was no statistical difference in mortality between the 2 groups, regardless of how they were treated. Further long-term follow-up is needed in this patient population.

Red blood cell transfusion for infants with single-ventricle physiology.

The purpose of this study was to assess how red blood cell (RBC) transfusions impact hemodynamic parameters in infants with single-ventricle lesions. This was a retrospective chart review. The setting was a pediatric cardiac intensive care unit at a tertiary care children's hospital. Fifty-nine patients <1 year of age with single-ventricle physiology who received a blood transfusion between December 2007 and April 2009 were analyzed. They received a total of 183 transfusions. Exclusion criteria included transfusions given within 72 h of cardiac surgery or transfusions given to patients with active bleeding. There were no interventions. The study population was divided into terciles based on pretransfusion hemoglobin (Hgb) concentration. The pretransfusion Hgb concentration in group A was 7.8 to 12.3 gm/dl, in group B was 12.4 to 13.2 gm/dl, and in group C was 13.3 to 15.7 gm/dl. Heart rate, blood pressure, arterial saturation, and cerebral near-infrared spectroscopy (cNIRS) values before transfusion, as well as at 1, 2, 4, 8, and 12 h after transfusion, were collected. There was significant improvement in diastolic blood pressure, arterial saturation, and cNIRS in group A after 12 h. Transfusions given in group B also resulted in improvement in diastolic blood pressure and arterial saturation, with less robust response of cNIRS. In group C, only arterial saturation values increased significantly. RBC transfusions can improve hemodynamics and markers of oxygen delivery in infants with single-ventricle physiology, but further studies are needed to determine an optimal Hgb level in this population. Interventions to increase Hgb above this level may be of limited benefit.