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.

The use of ketorolac may reduce opioid exposure in infants less than 6 months of age undergoing congenital heart surgery.

OBJECTIVES: Pain management for infants undergoing cardiothoracic surgery primarily utilises opioid analgesics. There is a paucity of data available for the use of non-steroidal anti-inflammatory medications such as ketorolac in this patient population. MATERIALS AND METHODS: This retrospective study evaluated patients between 30 days and 6 months undergoing cardiothoracic surgery. The primary endpoint evaluates ketorolac on reducing post-operative opioid use. RESULTS: Of 243 evaluated patient, 145 met inclusion. Baseline demographics were similar amongst the cohorts. Patients administered ketorolac used less cumulative opiates, in morphine milligram equivalents, for post-op days (POD) 1-3 after surgery compared to patients not receiving ketorolac (9.47 versus 12.68; p = 0.002). The no-ketorolac group required more opiates on POD 1 (10.9 versus 5; p < 0.001) and POD 2 (4.2 versus 2.5; p = 0.006) with no difference found on POD 3 (2 versus 1.6; p = 0.2). There was a mean increase from baseline to highest serum creatinine level on POD 1-3 in the no-ketorolac group compared to the ketorolac group (0.15 versus 0.09 mg/dL; p < 0.014), with no difference in stage 1 or stage 2 acute kidney injury. There were no differences in average chest tube output in mL/kg/day (0.24 versus 0.32; p = 0.569) or need for transfusion (36% versus 24%; p = 0.125), respectively. DISCUSSION: Scheduled administration of ketorolac after cardiothoracic surgery resulted in a significant reduction in opioid exposure, with no difference in rates of acute kidney injury or bleeding.

Durable Vascular Access in Neonates in the Cardiac ICU: A Novel Technique for Tunneled Femoral Central Venous Catheters.

OBJECTIVES: There is an ongoing need for a method of obtaining long-term venous access in critically ill pediatric patients that can be completed at the bedside and results in a durable, highly functional device. We designed a novel technique for tunneled femoral access to address this need. Herein, we describe the procedure and review the outcomes at our institution. DESIGN: A single-center retrospective chart review identifying patients who underwent tunneled femoral central venous catheter (tfCVC) placement between 2017 and 2021 using a two-puncture technique developed by our team. SETTING: Academic, Quaternary Children's Hospital with a dedicated pediatric cardiac ICU (CICU). PATIENTS: Patients in our pediatric CICU who underwent this procedure. INTERVENTIONS: Tunneled femoral central line placement. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-two encounters were identified in 161 patients. The median age and weight at the time of catheter placement was 22 days and 3.2 kg. The median duration of the line was 22 days. The central line-associated bloodstream infection (CLABSI) rate was 0.75 per 1,000-line days. The prevalence rate of thrombi necessitating pharmacologic treatment was 2.0 thrombi per 1,000-line days. There was no significant difference in CLABSI rate per 1,000-line days between the tfCVC and nontunneled peripherally inserted central catheters placed over the same period in a similar population (-0.40 [95% CI, -1.61 to 0.82; p = 0.52]) and no difference in thrombus rates per 1,000-line days (1.37 [95% CI, -0.15 to 2.89; p = 0.081]). CONCLUSIONS: tfCVCs can be placed by the intensivist team using a two-puncture technique at the bedside with a high-rate of procedural success and low rate of complications. Advantages of this novel technique of obtaining vascular access include a low rate of CLABSIs, the ability to place it at the bedside, and preservation of the upper extremity vasculature.

Continuous Prostanoid Initiation in Severe Pulmonary Hypertension in the Pediatric Cardiac Intensive Care Unit.

OBJECTIVE: Limited data exists regarding prostanoid (PGI2) use in critically ill patients with pulmonary hypertension. (PH) in the pediatric cardiac intensive care unit (CICU) setting. MATERIALS AND METHODS: Single center, retrospective study of patients with diagnosis of PH who received continuous PGI2 and were admitted to CICU from January/2015 to April/2022. Data collected included patient demographics and clinical characteristics including diagnosis, etiology of PH, vasoactive and ventilatory support, length of stay, and survival. Type, initial, maximum, and final dose of PGI2 as well as hemodynamic data was obtained. Data reported as mean ± standard deviation. Significance taken p value < 0.05. RESULTS: 24 patients received PGI2 therapy at a mean age of 3.1 years, range (0-16.6 years). PGI2 was in the form of IV epoprostenol in 12 patients, IV treprostinil in 6, and SQ treprostinil in 6 patients. Mean initial dose was 2.79 ng/kg/min, max dose 18.75 ng/kg/min, and mean duration of therapy was 38.5 days. At PGI2 initiation, 21 (87.5%) were on vasoactive infusions, 19 (79.2%) mechanically ventilated (MV), and 6 (25%) were on extracorporeal membrane oxygenation (ECMO). The in-hospital mortality rate was 37.5% (n = 9). Patients MV and on ECMO support had higher risk of death (p = 0.04, and < 0.01, respectively). CONCLUSION: PGI2 therapy was tolerated in approximately 50% of patients with the most common side effect being hypotension leading to discontinuation in 1/3rd of patients. Ongoing evaluation of the benefits of PGI2 for patients in the CICU setting will help better identify patient selection, type, and dosing of PGI2.

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.

Milrinone for treatment of elevated lactate in the pre-operative newborn with hypoplastic left heart syndrome.

BACKGROUND: There is a paucity of information reported regarding the use of milrinone in patients with hypoplastic left heart syndrome prior to the Norwood procedure. At our institution, milrinone is initiated in the pre-operative setting when over-circulation and elevated serum lactate levels develop. We aimed to review the responses associated with the administration of milrinone in the pre-operative hypoplastic left heart syndrome patient. Second, we compared patients who received high- versus low-dose milrinone prior to Norwood procedure. METHODS: Single-centre retrospective study of patients diagnosed with hypoplastic left heart syndrome between January 2000 and December 2019 who underwent Norwood procedure. Patient characteristics and outcomes were compared. RESULTS: During the study period, 375 patients were identified; 79 (21%) received milrinone prior to the Norwood procedure with median lactate 2.55 mmol/l, and SpO2 93%. Patients who received milrinone were older at the time of Norwood procedure (6 vs. 5 days) and were more likely to be intubated and sedated. In a subset analysis stratifying patients to low- versus high-dose milrinone, median lactate decreased from time of initiation (2.39 vs 2.75 to 1.6 vs 1.8 mmol/l) at 12 hours post-initiation, respectively. Repeated measures analysis showed a significant decrease in lactate levels by 4 hours following initiation of milrinone, that persisted over time, with no significant difference in mean arterial pressure. CONCLUSIONS: The use of milrinone in the pre-operative over-circulated hypoplastic left heart syndrome patient is well tolerated, is associated with decreased lactate levels, and was not associated with significant hypotension or worsening of excess pulmonary blood flow.

Utilisation of RAM cannula for non-invasive respiratory support for infants in the cardiac ICU.

BACKGROUND: Children with CHD carry an additional burden of pulmonary insufficiency, often necessitating prolonged ventilatory support, especially in the peri-operative phase. There has been an increase in the utilisation of non-invasive ventilatory support for these children. The objective of this study was to evaluate the utilisation, safety, and outcomes of RAM cannula as a tool for escalation and de-escalation of respiratory support in paediatric cardiac patients less than one year of age. METHODS: A single-centre retrospective cohort study of patients supported with RAM cannula. RESULTS: A total of 275 instances of RAM use were included in the study, 81.1% being post-operative. Patients were stratified into escalation and de-escalation cohorts based on the indication of non-invasive ventilation. The success rate of using RAM cannula was 69.5% overall, 66.1% in the escalation group, and 72.8% in the de-escalation group. At baseline, age at cardiac ICU admission >30 days, FiO2 ≤ 40%, PaCO2 ≤ 50 mmHg; and after 12 hours of non-invasive ventilation support respiratory rate ≤ 60/min, PaO2 ≥ 50 mmHg, PaCO2 ≤ 50 mmHg; and absence of worsening on follow-up chest X-ray predicted the success with a sensitivity of 95% in the logistic regression model. Successful support was associated with a significantly shorter unit stay. CONCLUSIONS: RAM cannula can be safely used to provide non-invasive support to infants in the cardiac ICU for escalation and de-escalation of respiratory support. Factors associated with success can be used to make decisions about candidacy and appropriate timing of non-invasive ventilation use to maximise effectiveness.

Clinical and Hematological Outcomes of Aminocaproic Acid Use During Pediatric Cardiac ECMO.

Bleeding and thrombosis-related complications are common in pediatric cardiac patients supported by extracorporeal membrane oxygenation (ECMO) and are associated with morbidity and mortality. The purpose of this study was to evaluate the utility of aminocaproic acid (ACA), an antifibrinolytic agent, as it pertains to bleeding in pediatric cardiac patients on ECMO. This included a retrospective cohort study of pediatric cardiac patients receiving ACA while supported on ECMO between 2013 and 2017. For each patient, data were collected in three time intervals: the 24 hours before ACA initiation, and then 0-24 and 24-48 hours following ACA initiation. For each time frame, bleeding, component transfusion, and laboratory data were collected and analyzed. A total of 62 patients were included, representing 42% of our cardiac ECMO patients during the time period. ACA was initiated at 16.3 ± 8.7 hours following initiation of ECMO. The mean bleeding rate before ACA was 10.57 mL/kg/h, which reduced to 7.8 mL/kg/h in the 24-hour period after initiation of ACA and a further decrease to 3.65 mL/kg/h during the 24- to 48-hour time period following ACA initiation. ACA administration was associated with reduction in bleeding (p < .001) and packed red blood cell transfusions (p = .02), administration of fresh frozen plasma (p < .001), platelets (p = .017), cryoprecipitate (p = .05), factor VII (p = .002), and Cell Saver (p = .005). Hemoglobin and platelet count were stable, whereas prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR) showed significant reduction over the time course. ACA administration was not associated with specific adverse effects. A clinically significant reduction in bleeding amount, red blood cell transfusions, and other hematologic interventions occurred following ACA administration for pediatric patients on ECMO. Wider consideration for ACA use as a part of a multipronged strategy to manage bleeding during ECMO should be considered.

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.

In Vitro Examination of the VentriFlo True Pulse Pump for Failing Fontan Support.

The current methodology of Fontan palliation results in a one "pump" circulatory system with passive flow to the lungs. Inherent hemodynamic differences exist between a biventricular circulatory system and this modified physiology, leading to a host of long-term complications. Mechanical circulatory support (MCS) is a potential option to combat these pathophysiological conditions. In this study, we examine the VentriFlo True Pulse Pump as a MCS option to support a failing Fontan patient. An in vitro circulatory loop was used to model a failing Fontan patient, reproducing pathophysiological pressures and flow rates. The VentriFlo True Pulse Pump was positioned as a right sided support, testing multiple cannulation and baffle restriction strategies, as well as various pumping parameters including flow rate, frequency, stroke volume and the ejection to filling time ratio. A 10 mm Hg decrease in IVC pressure and 0.75 L/min increase in cardiac output were achieved using a complete baffle restriction strategy. Additional cannulation and banding strategies were not as successful. Pump flow rate and frequency significantly impacted hemodynamics, while the ejection to filling time ratio did not. Though not ideal, complete baffle restriction was necessary to achieve successful support. The ability to tune individual pumping parameters for a given MCS device will have a substantial impact on the pressures and flow augmentation seen in a Fontan circulation. Both future pump design and off-label VADs for Fontan use should consider the pump configuration and parameter combinations presented here, which offered successful support.

A Method for In Vitro TCPC Compliance Verification.

The Fontan procedure is a common palliative intervention for sufferers of single ventricle congenital heart defects that results in an anastomosis of the venous return to the pulmonary arteries called the total cavopulmonary connection (TCPC). Local TCPC and global Fontan circulation hemodynamics are studied with in vitro circulatory models because of hemodynamic ties to Fontan patient long-term complications. The majority of in vitro studies, to date, employ a rigid TCPC model. Recently, a few studies have incorporated flexible TCPC models, but provide no justification for the model material properties. The method set forth in this study successfully utilizes patient-specific flow and pressure data from phase contrast magnetic resonance images (PCMRI) (n = 1) and retrospective pulse-pressure data from an age-matched patient cohort (n = 10) to verify the compliance of an in vitro TCPC model. These data were analyzed, and the target compliance was determined as 1.36 ± 0.78 mL/mm Hg. A method of in vitro compliance testing and computational simulations was employed to determine the in vitro flexible TCPC model material properties and then use those material properties to estimate the wall thickness necessary to match the patient-specific target compliance. The resulting in vitro TCPC model compliance was 1.37 ± 0.1 mL/mm Hg-a value within 1% of the patient-specific compliance. The presented method is useful to verify in vitro model accuracy of patient-specific TCPC compliance and thus improve patient-specific hemodynamic modeling.

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.

Outcomes and hospital costs associated with the Norwood operation: beyond morbidity and mortality--CORRIGENDUM.

This paper contains an error in Table 4. The authors apologise for this error. In the last row of the Table, it states: Reimbursement (charges/collections)=46% It should actually be: Reimbursement (collections/ charges)=46%

Outcomes and hospital costs associated with the Norwood operation: beyond morbidity and mortality.

BACKGROUND: Although much is known about morbidity and mortality, there are limited data focussing on the financial aspect of the Norwood operation. Our objective is to characterise the hospitalisation and detail the hospital costs. METHODS: We retrospectively studied 86 newborns with hypoplastic left heart syndrome who underwent Norwood palliation between 2008 and 2012. Clinical and financial data were collected. Financial data have been reported for 2011-2012. RESULTS: At surgery, median age and weight of the patients were 4 days (range 1-13) and 3 kg (range 2-4.8), respectively. The median time from admission to surgery was 4 days (range 1-10), with the postoperative ICU stay and total length of stay at the hospital being 10 days (range 4-135) and 16 days (range 5-136), respectively. Discharge mortality was 14/86 (16%) patients. For patients operated on between 2011 and 2012 (n=40), median hospital costs, charges, and collections per patient were $117,021, $433,054, and $198,453, respectively, and mean hospital costs, charges, and collections per patient were $322,765, $1,109,500, and $511,271, respectively. A breakdown of total hospital costs (direct and indirect) by department showed that the top four areas of resource utilisation (excluding physician fees) were as follows: the cardiac ICU (35%), laboratory (12%), pharmacy (12%), and operating room (7%). Interestingly, point-of-care laboratory evaluations accounted for almost half of the laboratory total (5%). Extracorporeal membrane oxygenation, although only utilised in eight patients between 2011 and 2012, accounted for 7% of utilisation.General radiology only accounted for 2%, despite numerous radiographs. CONCLUSIONS: Limited data are available that detail the hospitalisation and costs associated with the Norwood operation. We hope that this analysis will identify areas for quality and value improvement from both system and patient perspectives.

SpeechMirror: A Multimodal Visual Analytics System for Personalized Reflection of Online Public Speaking Effectiveness.

As communications are increasingly taking place virtually, the ability to present well online is becoming an indispensable skill. Online speakers are facing unique challenges in engaging with remote audiences. However, there has been a lack of evidence-based analytical systems for people to comprehensively evaluate online speeches and further discover possibilities for improvement. This paper introduces SpeechMirror, a visual analytics system facilitating reflection on a speech based on insights from a collection of online speeches. The system estimates the impact of different speech techniques on effectiveness and applies them to a speech to give users awareness of the performance of speech techniques. A similarity recommendation approach based on speech factors or script content supports guided exploration to expand knowledge of presentation evidence and accelerate the discovery of speech delivery possibilities. SpeechMirror provides intuitive visualizations and interactions for users to understand speech factors. Among them, SpeechTwin, a novel multimodal visual summary of speech, supports rapid understanding of critical speech factors and comparison of different speech samples, and SpeechPlayer augments the speech video by integrating visualization of the speaker's body language with interaction, for focused analysis. The system utilizes visualizations suited to the distinct nature of different speech factors for user comprehension. The proposed system and visualization techniques were evaluated with domain experts and amateurs, demonstrating usability for users with low visualization literacy and its efficacy in assisting users to develop insights for potential improvement.

Novel tubing connectors reduce ECMO circuit thrombosis.

BACKGROUND: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. METHODS: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. RESULTS: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). CONCLUSION: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

Hemodynamic effects of implanting a unidirectional valve in the inferior vena cava of the Fontan circulation pathway: an in vitro investigation.

The Fontan surgical procedure used for treating patients with single ventricle congenital heart disorders results in a total cavopulmonary connection (TCPC) of the vena cavae to the pulmonary arteries (PAs). Sluggish TCPC flow and elevated hepatic venous pressures are commonly observed in this altered physiology, which in turn can lead to long-term complications including liver congestion and cirrhosis. The hypothesis of this study is that placement of a unidirectional valve within the inferior vena cava (IVC) will improve hemodynamics of the Fontan circulation by preventing retrograde flow and lowering hepatic venous pressure. An in vitro experimental setup consisting of an idealized TCPC model with flexible walls was used for investigation, and a bovine venous valve was inserted in the IVC below the TCPC. Pressure fluctuations were introduced in the flow through the model to simulate venous pulsatility. Hemodynamics of baseline and valve-implanted conditions were compared across total caval flows ranging from 1.0 to 2.5 l/min with varying caval flow distributions. The results indicated that valve closure occurred for 15-20% of the total cycle, with consequent reduction in the upstream hepatic venous pressure by 5 to 10 mmHg. Energy loss (EL) through the TCPC was lowered with valve implantation to 20-50% of baseline, occurring across all flow conditions considered with mean caval and PA pressures greater than 10 mmHg. The results of this in vitro modeling suggest that IVC valve placement has the potential to improve hemodynamics in the Fontan circulation by decreasing hepatic venous hypertension and EL.

Safe and effective use of a glycemic control protocol for neonates in a cardiac ICU.

OBJECTIVE: To investigate the safety and efficacy of a hyperglycemia protocol in neonates with critical cardiac illness. Neonates are often regarded as high risk for hypoglycemia while receiving continuous insulin infusions and thus have been excluded from some clinical trials. DESIGN: A retrospective review. SETTING: A pediatric cardiac ICU in a tertiary academic center. INTERVENTIONS: Neonates with critical cardiac illness who developed hyperglycemia were placed on an insulin-hyperglycemia protocol at the attending physician's discretion. Insulin infusions were titrated based on frequent blood glucose monitoring. MEASUREMENTS: Critical illness hyperglycemia was defined as a blood glucose less than 140 mg/dL. Hypoglycemia was defined as moderate (≤ 60 mg/dL) or severe (≤ 40 mg/dL). Initiating blood glucose, lowest blood glucose during insulin infusion, doses of insulin, duration of insulin, and time to blood glucose greater than 140 mg/dL were evaluated. MAIN RESULTS: A total of 44 patients were placed on the protocol between January 2009 and October 2011. The majority of insulin infusions were initiated in the early postoperative period (33 of 44, 75%). Moderate hypoglycemia occurred in two patients (4.5%), with blood glucose levels of 49 and 53 mg/dL. No episodes of severe hypoglycemia occurred. A total of 345 discrete blood glucose levels were analyzed; two of these being greater than 60 mg/dL (0.58%). Mean blood glucose prior to starting insulin was 252 ± 45 mg/dL and time until euglycemia was 6.1 ± 3.9 hours. The mean duration of insulin infusion was 24.6 ± 38.7 hours, mean peak dose was 0.10 ± 0.05 units/kg/hour, and mean insulin dose was 0.06 ± 0.02 units/kg/hour. For postoperative patients, mean time after bypass until onset of hyperglycemia was 2.2 ± 2.6 hours. CONCLUSIONS: A glycemic control protocol can safely and effectively be applied to neonates with critical cardiac disease. Neonates with critical cardiac illness should be included in clinical trials evaluating the benefits of glycemic control.

Space microgravity increases expression of genes associated with proliferation and differentiation in human cardiac spheres.

Efficient generation of cardiomyocytes from human-induced pluripotent stem cells (hiPSCs) is important for their application in basic and translational studies. Space microgravity can significantly change cell activities and function. Previously, we reported upregulation of genes associated with cardiac proliferation in cardiac progenitors derived from hiPSCs that were exposed to space microgravity for 3 days. Here we investigated the effect of long-term exposure of hiPSC-cardiac progenitors to space microgravity on global gene expression. Cryopreserved 3D hiPSC-cardiac progenitors were sent to the International Space Station (ISS) and cultured for 3 weeks under ISS microgravity and ISS 1 G conditions. RNA-sequencing analyses revealed upregulation of genes associated with cardiac differentiation, proliferation, and cardiac structure/function and downregulation of genes associated with extracellular matrix regulation in the ISS microgravity cultures compared with the ISS 1 G cultures. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes mapping identified the upregulation of biological processes, molecular function, cellular components, and pathways associated with cell cycle, cardiac differentiation, and cardiac function. Taking together, these results suggest that space microgravity has a beneficial effect on the differentiation and growth of cardiac progenitors.