Kinetics of Renin Concentrations in Infants Undergoing Congenital Cardiac Surgery.

BACKGROUND: Elevated renin has been shown to predict poor response to standard vasoactive therapies and is associated with poor outcomes in adults. Similarly, elevated renin was associated with mortality in children with septic shock. Renin concentration profiles after pediatric cardiac surgery are unknown. The purpose of this study was to characterize renin kinetics after pediatric cardiac surgery. METHODS: Single-center retrospective study of infants who underwent cardiac surgery with cardiopulmonary bypass (CPB) utilizing serum samples obtained in the perioperative period to measure plasma renin concentrations (pg/mL). Time points included pre-bypass and 1, 4, and 24 h after initiation of CPB. RESULTS: Fifty patients (65% male) with a median age 5 months (interquartile range (IQR) 3.5, 6.5) were included. Renin concentrations peaked 4 h after CPB. There was a significant difference in preoperative and 4 h post-CPB renin concentration (4 h post-CPB vs preoperative: mean difference 100.6, 95% confidence interval (CI) 48.9-152.4, P < .001). Median renin concentration at 24 h after CPB was lower than the preoperative baseline. CONCLUSIONS: We describe renin kinetics in infants after CPB. Future studies based on these data can now be performed to evaluate the associations of elevated renin concentrations with adverse outcomes.

Neonatal Chylothorax and Early Fluid Overload After Cardiac Surgery: Retrospective Analysis of the Neonatal and Pediatric Heart and Renal Outcomes Network Registry (2015-2018).

OBJECTIVES: To evaluate the association between postoperative cumulative fluid balance (FB) and development of chylothorax in neonates after cardiac surgery. DESIGN: Multicenter, retrospective cohort identified within the Neonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) Registry. SETTING: Twenty-two hospitals were involved with NEPHRON, from September 2015 to January 2018. PATIENTS: Neonates (< 30 d old) undergoing index cardiac operation with or without cardiopulmonary bypass (CPB) entered into the NEPHRON Registry. Postoperative chylothorax was defined in the Pediatric Cardiac Critical Care Consortium as lymphatic fluid in the pleural space secondary to a leak from the thoracic duct or its branches. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2240 NEPHRON patients, 4% ( n = 89) were treated for chylothorax during postoperative day (POD) 2-21. Median (interquartile range [IQR]) time to diagnosis was 8 (IQR 6, 12) days. Of patients treated for chylothorax, 81 of 89 (91%) had CPB and 68 of 89 (76%) had Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery Congenital Heart Surgery 4-5 operations. On bivariate analysis, chylothorax patients had higher POD 1 FB (3.2 vs. 1.1%, p = 0.014), higher cumulative POD 2 FB (1.5 vs. -1.5%, p < 0.001), achieved negative daily FB by POD 1 less often (69% vs. 79%, p = 0.039), and had lower POD 1 urine output (1.9 vs. 3. 2 mL/kg/day, p ≤ 0.001) than those without chylothorax. We failed to identify an association between presence or absence of chylothorax and peak FB (5.2 vs. 4.9%, p = 0.9). Multivariable analysis shows that higher cumulative FB on POD 2 was associated with greater odds (odds ratio [OR], 95% CI) of chylothorax development (OR 1.5 [95% CI, 1.1-2.2]). Further multivariable analysis shows that chylothorax was independently associated with greater odds of longer durations of mechanical ventilation (OR 5.5 [95% CI, 3.7-8.0]), respiratory support (OR 4.3 [95% CI, 2.9-6.2]), use of inotropic support (OR 2.9 [95% CI, 2.0-4.3]), and longer hospital length of stay (OR 3.7 [95% CI, 2.5-5.4]). CONCLUSIONS: Chylothorax after neonatal cardiac surgery for congenital heart disease (CHD) is independently associated with greater odds of longer duration of cardiorespiratory support and hospitalization. Higher early (POD 2) cumulative FB is associated with greater odds of chylothorax. Contemporary, prospective studies are needed to assess whether early fluid mitigation strategies decrease postoperative chylothorax development.

Impact of inflammation and steroids on anti-coagulation in children supported on a ventricular assist device.

Critically ill pediatric patients supported on ventricular assist devices (VADs) are increasingly being anticoagulated on bivalirudin, but with difficulty monitoring anticoagulation. Activated partial thromboplastin time (aPTT) has recently been shown to poorly correlate with bivalirudin plasma concentrations, while dTT had excellent correlation. However, aPTT is the more common monitoring test and dTT testing is rarely used. In addition, effects of frequent clinical VAD scenarios (such as inflammation) on the accuracy of aPTT and dTT testing remains uncertain. We reviewed the effects of clinical scenarios (infection/inflammation, chylothorax, and steroids administration) on anticoagulation monitoring in 10 pediatric VAD patients less than 3 years at Cincinnati Children's Hospital Medical Center from 10/27/2020 to 5/6/2022 using bivalirudin for anticoagulation. There were 16 inflammation/infection, 3 chylothorax, and 6 steroids events. Correlation between dTT and aPTT was significantly lower after infection/inflammation, with dTT increasing prior to inflammation/infection while aPTT remained unchanged. In addition, steroids are administered to VAD patients to reduce inflammation and thus additionally stabilize anticoagulation. However, this anticoagulation stabilization effect was reflected more accurately by dTT compared to aPTT. In children requiring VAD support utilizing bivalirudin anticoagulation, inflammation/infection is a common occurrence resulting in anticoagulation changes that may be more accurately reflected by dTT as opposed to aPTT.

Cardiology across continents: an interactive, case-based learning series.

Heart University [https://www.heartuniversity.org/] is a free educational website providing structured training curricula with knowledge-based testing and access to webinars and conference recordings for practicing and in-training providers of paediatric and congenital cardiac care. To date, there are over 15,000 registered website users from over 140 countries on Heart University, with over 2,000 training modules and/or recorded educational videos. Heart University has developed an "asynchronous" educational lecture series entitled "Pediatric and Congenital Cardiac Care in Resource-Limited Settings." This recorded lecture series is specifically focused on topics relevant to practicing paediatric and/or congenital cardiac care in low-resource settings.A relatively new initiative, "Cardiology Across Continents," supplements the existing educational resources for providers of paediatric and/or congenital cardiac care in low-income countries and lower-middle-income countries by providing an additional live, interactive, case-based forum. Sessions occur every 1-2 months and focus on challenging cases from diagnostic or management perspective with a view to promote collaboration between partnered institutions. "Cardiology Across Continents" is an expanding initiative that facilitates learning and collaboration between clinicians across varied practice settings via interactive case discussions. We welcome trainees and providers of paediatric and congenital cardiac care to join the sessions and invite any insight that can enhance learning for clinicians around the world. This manuscript describes "Cardiology Across Continents" and discusses the development, history, current status, and future plans of Heart University.

Assessment of fluid balance after neonatal cardiac surgery: a description of intake/output vs. weight-based methods.

BACKGROUND: Fluid overload associates with poor outcomes after neonatal cardiac surgery, but consensus does not exist for the most clinically relevant method of measuring fluid balance (FB). While weight change-based FB (FB-W) is standard in neonatal intensive care units, weighing infants after cardiac surgery may be challenging. We aimed to identify characteristics associated with obtaining weights and to understand how intake/output-based FB (FB-IO) and FB-W compare in the early postoperative period in this population. METHODS: Observational retrospective study of 2235 neonates undergoing cardiac surgery from 22 hospitals comprising the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) database. RESULTS: Forty-five percent (n = 998) of patients were weighed on postoperative day (POD) 2, varying from 2 to 98% among centers. Odds of being weighed were lower for STAT categories 4 and 5 (OR 0.72; 95% CI 0.53-0.98), cardiopulmonary bypass (0.59; 0.42-0.83), delayed sternal closure (0.27; 0.19-0.38), prophylactic peritoneal dialysis use (0.58; 0.34-0.99), and mechanical ventilation on POD 2 (0.23; 0.16-0.33). Correlation between FB-IO and FB-W was weak for every POD 1-6 and within the entire cohort (correlation coefficient 0.15; 95% CI 0.12-0.17). FB-W measured higher than paired FB-IO (mean bias 12.5%; 95% CI 11.6-13.4%) with wide 95% limits of agreement (- 15.4-40.4%). CONCLUSIONS: Weighing neonates early after cardiac surgery is uncommon, with significant practice variation among centers. Patients with increased severity of illness are less likely to be weighed. FB-W and FB-IO have weak correlation, and further study is needed to determine which cumulative FB metric most associates with adverse outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Early postoperative weight-based fluid overload is associated with worse outcomes after neonatal cardiac surgery.

OBJECTIVES: Evaluate the association of postoperative day (POD) 2 weight-based fluid balance (FB-W) > 10% with outcomes after neonatal cardiac surgery. METHODS: Retrospective cohort study of 22 hospitals in the NEonatal and Pediatric Heart and Renal Outcomes Network (NEPHRON) registry from September 2015 to January 2018. Of 2240 eligible patients, 997 neonates (cardiopulmonary bypass (CPB) n = 658, non-CPB n = 339) were weighed on POD2 and included. RESULTS: Forty-five percent (n = 444) of patients had FB-W > 10%. Patients with POD2 FB-W > 10% had higher acuity of illness and worse outcomes. Hospital mortality was 2.8% (n = 28) and not independently associated with POD2 FB-W > 10% (OR 1.04; 95% CI 0.29-3.68). POD2 FB-W > 10% was associated with all utilization outcomes, including duration of mechanical ventilation (multiplicative rate of 1.19; 95% CI 1.04-1.36), respiratory support (1.28; 95% CI 1.07-1.54), inotropic support (1.38; 95% CI 1.10-1.73), and postoperative hospital length of stay (LOS 1.15; 95% CI 1.03-1.27). In secondary analyses, POD2 FB-W as a continuous variable demonstrated association with prolonged durations of mechanical ventilation (OR 1.04; 95% CI 1.02-1.06], respiratory support (1.03; 95% CI 1.01-1.05), inotropic support (1.03; 95% CI 1.00-1.05), and postoperative hospital LOS (1.02; 95% CI 1.00-1.04). POD2 intake-output based fluid balance (FB-IO) was not associated with any outcome. CONCLUSIONS: POD2 weight-based fluid balance > 10% occurs frequently after neonatal cardiac surgery and is associated with longer cardiorespiratory support and postoperative hospital LOS. However, POD2 FB-IO was not associated with clinical outcomes. Mitigating early postoperative fluid accumulation may improve outcomes but requires safely weighing neonates in the early postoperative period. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cardiac arrest during endotracheal intubation of children with systolic dysfunction.

This multicenter study aimed to describe peri-intubation cardiac arrest in paediatric cardiac patients with significant (moderate or severe) systolic dysfunction of the systemic ventricle. Intubation data were collected from 4 paediatric cardiac ICUs in the United States (January 2015 - December 2017). Clinician practices during intubation of patients with significant dysfunction were compared to practices during intubation of patients without significant systolic dysfunction. There were 67 intubations in patients with significant systolic dysfunction. Peri-intubation cardiac arrest rate in this population was 14.9% (10/67); peri-intubation mortality was 3%. Majority (6/10; 60%) of the cardiac arrests were classified as pulseless electrical activity. Patients with cardiac arrest upon intubation had a higher serum lactate and lower serum pH than patients without peri-intubation cardiac arrest in the significant systolic dysfunction group.In comparing cardiac ICU patients with significant systolic dysfunction (n = 67) to patients from the same time period with normal ventricular function or mild dysfunction (n = 183), clinicians were less likely to use midazolam (11.9% versus 25.1%; p = 0.03) and more likely to use etomidate (16.4% versus 4.4%; p = 0.002) for intubation. Use of other sedative agents, video laryngoscopy, atropine, inotrope initiation, and consultation of an anaesthesiologist for intubation were not statistically different between the groups.This is the first study to describe the rate of and risk factors for peri-intubation cardiac arrest in paediatric cardiac ICU patients with systolic dysfunction. There was a higher peri-intubation cardiac arrest rate compared to published rates in critically ill children with heart disease and compared to children with significant systolic dysfunction undergoing elective general anaesthesia.

Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study.

OBJECTIVES: Endotracheal intubation is associated with hemodynamic adverse events, including cardiac arrest, especially in patients with cardiac disease. There are only a few studies that have evaluated the rate of and risk factors for endotracheal intubation hemodynamic complications in critically ill pediatric patients. Although some of these studies have assessed hemodynamic complications during intubation in pediatric cardiac patients, the frequency of and risk factors for peri-intubation cardiac arrest have not been adequately described in high acuity cardiac patients. This study aims to describe the frequency of and risk factors for peri-intubation cardiac arrest in critically ill pediatric cardiac patients admitted to specialized cardiac ICUs. DESIGN: Multicenter retrospective cohort study. SETTING: Three pediatric cardiac ICUs in the United States. PATIENTS: Critically ill pediatric patients with congenital or acquired heart disease requiring endotracheal intubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endotracheal intubations performed in three cardiac ICUs between January 2015 and December 2017 were reviewed. Clinical variables-including data on patients, clinical providers, and procedure-were evaluated for their association with peri-intubation cardiac arrest. There was a total of 186 intubation events studied, occurring in 151 individual (index) patients. The rates of peri-intubation cardiac arrest and peri-intubation mortality in this cohort were 7% and 1.6%, respectively. Among those patients with moderate or severe systolic dysfunction of the systemic ventricle, peri-intubation cardiac arrest rate was 20.7%. Statistically significant risk factors for peri-intubation cardiac arrest included: significant systolic dysfunction of the systemic ventricle, pre-intubation hypotension, pre-intubation lactate elevation, lower pre-intubation pH, and documented oxygen desaturations (> 10%) during intubation procedure. CONCLUSIONS: Our most significant finding was a peri-intubation cardiac arrest rate which was much higher than previously published rates for both cardiac and noncardiac children who underwent endotracheal intubation in ICUs. Peri-intubation mortality was also high in our cohort. Regarding risk factors for peri-intubation arrest, significant systolic dysfunction of the systemic ventricle was strongly associated with cardiac arrest in this cohort.

Single Center Experience With Durable Continuous Flow Single Ventricle Assist Device: A Viable Option in Fontan Circulatory Failure.

Ventricular assist devices are increasingly used for patients with single ventricle physiology. We describe the use of durable, continuous flow, single ventricular assist device (SVAD) therapy in Fontan circulatory failure patients. Retrospective, single-center review of patients with Fontan circulation implanted with a SVAD between 2017 and 2022. Patient characteristics and outcomes were obtained by chart review. Nine patients underwent SVAD implantation (median age 24 years). Most patients had a total cavopulmonary connection; one had an atriopulmonary Fontan. Five patients had a systemic right ventricle. SVAD was most often utilized as bridge to candidacy (67%). Eight patients had at least moderate systemic ventricular systolic dysfunction. SVAD support continued for a median of 65 days (longest duration, 1,105 days) and one patient remains on support at time of submission. Of five patients discharged home, median length of stay after SVAD was 24 days. Six patients were transplanted (median 96 days from SVAD). Two patients died from pretransplant multisystem organ failure before transplant. All transplanted patients remain alive (median time since transplant 593 days). Continuous flow SVAD therapy can be effective for patients with Fontan circulatory failure and systolic dysfunction. Further studies should investigate feasibility and optimal SVAD timing with more advanced Fontan associated end-organ dysfunction.

Renal accumulation of biglycan and lipid retention accelerates diabetic nephropathy.

Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy.

Chronic Ventricular Assist Device Support in Adult Congenital Heart Disease Patients: A Children's Hospital Perspective.

With improvement in early surgical outcomes in patients with complex congenital heart disease, most patients are now expected to survive to adulthood. As adult congenital heart disease (ACHD) patients age, they are at risk of heart failure, which has become the leading cause of mortality in ACHD. Some who develop advanced heart failure may not be candidates for transplant, and chronic ventricular assist device (VAD) therapy may be the only means of survival. There is limited experience with chronic VAD therapy in ACHD patients, and the outcomes are not well delineated. We describe our center's experience with chronic VAD therapy in ACHD patients receiving care exclusively within our children's hospital.

Reversibility of renal injury with cholesterol lowering in hyperlipidemic diabetic mice.

Hyperlipidemia is a risk factor for development and progression of diabetic nephropathy. However, it is not known if reduction of hyperlipidemia is protective against progression of disease. The goal of this study was to determine if reduction of hypercholesterolemia could limit progression of diabetic nephropathy. Diabetic and nondiabetic LDL receptor deficient (LDLR(-/-)) mice were fed diets containing either no cholesterol (0%) or high cholesterol (0.12%) for 36 weeks. One group each of diabetic and nondiabetic mice were fed the high-cholesterol diet for 26 weeks then changed to the 0% cholesterol diet for the last 10 weeks. Consumption of the high-cholesterol diet exacerbated the development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Increased glomerular lipid and apolipoprotein B accumulation was found in diabetic mice that consumed the 0.12% cholesterol diet compared with other groups. However, diabetic mice that changed from the high-cholesterol diet to the 0% cholesterol diet for the last 10 weeks had lower urine albumin excretion and mesangial matrix expansion compared with mice that consumed the 0.12% cholesterol diet throughout. This suggests that hyperlipidemia causes continuous renal injury, and that lowering cholesterol levels by dietary means can improve renal function in diabetic LDLR(-/-) mice.