RESUMEN

BACKGROUND: Opioids are commonly used to provide analgesia during and after congenital heart surgery. The effects of exposure to opioids on neurodevelopment in neonates and infants are not well understood. OBJECTIVES: This study sought to evaluate the associations between cumulative opioid exposure (measured in morphine mg equivalent) over the first year of life and 2-year neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-Third/Fourth Edition [Bayley-III/IV] cognitive, language, and motor scores). METHODS: A single-center retrospective cohort study of infants undergoing congenital heart surgery was performed. Adjustment for measurable confounders was performed through multivariable linear regression. RESULTS: A total of 526 subjects were studied, of whom 32% underwent Society for Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 or 5 operations. In unadjusted analyses, higher total exposure to opioids was associated with worse scores across all 3 Bayley-III/IV domain scores (all P < 0.05). After adjustment for measured confounders, greater opioid exposure was associated with lower Bayley-III/IV scores (cognitive: ß = -1.0 per log-transformed morphine mg equivalents, P = 0.04; language: ß = -1.2, P = 0.04; and motor: ß = -1.1, P = 0.02). Total hospital length of stay, prematurity, genetic syndromes, and worse neighborhood socioeconomic status (represented either by Social Vulnerability Index or Childhood Opportunity Index) were all associated with worse Bayley-III/IV scores across all domains (all P < 0.05). CONCLUSIONS: Greater postnatal exposure to opioids was associated with worse neurodevelopmental outcomes across cognitive, language, and motor domains, independent of other less modifiable factors. This finding should motivate research and efforts to explore reduction in opioid exposure while preserving quality cardiac intensive care.

Asunto(s)

RESUMEN

Breakthroughs in surgical and medical techniques have significantly improved outcomes for children with congenital heart disease (CHD), but research continues to address the ongoing challenge of organ dysfunction after surgery, particularly in neonates and infants. Our study explored circular RNAs (circRNAs) within plasma-derived extracellular vesicles (EVs) in neonates and infants undergoing CHD surgery. Post-surgery EV circRNAs showed dramatic expression changes between organ dysfunction (OD) and control groups. Tissue injury-related pathways were consistent across pre- and post-surgery in OD. The top two significant predicted tissue sources of these circRNAs originated from the respiratory system, aligning with the fact that all patients in the OD arm experienced respiratory dysfunction. Five of these circRNAs, namely circ-CELSR1, circ-PLXNA1, circ-OBSL1, circ-DAB2IP, and circ-KANK1, significantly correlated with PELOD (Pediatric Logistic Organ Dysfunction) score and demonstrated high performance (AUC = 0.95), supporting the potential of circRNAs as prognostic markers. These findings pave the way for EV circRNAs as promising tools for managing post-surgical organ dysfunction and potentially guiding therapeutic strategies in children with CHD.

Asunto(s)

RESUMEN

Neutrophil-to-lymphocyte ratio (NLR) as a predictor in determining low cardiac output syndrome (LCOS) has not been widely reported. The aim of this study was to explore the role of pre-surgery, 0-, 4-, and 8-hour post-surgery NLR as predictors of LCOS incidence after open heart surgery in children with congenital heart disease (CHD). This study used a prognostic test with a prospective cohort design and was conducted from December 2020 until June 2021 at the cardiac intensive care unit (CICU) of Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The subject consisted of children aged one month to 18 years who underwent open heart surgery using a cardiopulmonary bypass (CPB) machine. A receiver operating characteristic curve was applied to identify the predictive performance of NLR for poor outcomes (LCOS incidence). Out of 90 patients included in the study, 25 (27.8%) of them developed LCOS between 3 to 53 hours post-surgery. All NLR values (pre-surgery and 0-, 4-, and 8-hours post-surgery) were associated with the incidence of LCOS. Pre-surgery NLR (cut-off value ≥0.88) had a fair predictive value (area under curve (AUC) 70; 95%CI: 57-83) for predicting LCOS incidence with sensitivity and specificity of 64% and 64.62%, respectively. NLR 0-hour post-surgery (cut-off value ≥4.73) had a good predictive value (AUC 81; 95%CI: 69-94) for predicting LCOS incidence, with 80% sensitivity and 80% specificity. NLR 4- and 8-hours post-surgery had very good predictive values (AUC 97%; 95%CI: 92-100 and 98; 95%CI: 94-100, respectively), with cut-off values ≥6.19 and ≥6.78, had the same 92% sensitivity and the same 96% sensitivity. The presence of LCOS was associated with mortality (odds ratio of 5.11 with 95%CI: 3.09-8.46). This study highlights that pre-surgery, 0-, 4-, and 8-hours post-surgery NLR can be predictors of LCOS after open heart surgery in children with CHD.

Asunto(s)

RESUMEN

BACKGROUND: Branch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions. METHODS: This is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2-4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL. DISCUSSION: This trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05809310. Registered on March 15, 2023.

Asunto(s)

RESUMEN

BACKGROUND: The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. METHODS AND RESULTS: Gut microbiomes of 155 consecutive patients with Fontan pathophysiology and 44 healthy individuals were analyzed using 16S rRNA sequencing of bacterial DNA extracted from fecal samples. GD was evaluated on the basis of α and ß diversities of the gut microbiome and was compared with natural log-transformed C-reactive protein, hemodynamics, von Willebrand factor antigen (a bacterial translocation marker), Mac-2 binding protein glycosylation isomer (a liver fibrosis indicator), peak oxygen uptake, and heart failure hospitalization. Patients with Fontan exhibited GD in terms of α and ß diversities as compared with controls (P<0.01). Reduced α diversity was associated with a failed hemodynamic phenotype, hypoxia, high natural log-transformed C-reactive protein levels, and elevated von Willebrand factor antigen and Mac-2 binding protein glycosylation isomer levels (P<0.05-0.01). In addition to elevated von Willebrand factor antigen and hypoxia, decreased α diversity was independently correlated with a high natural log-transformed C-reactive protein level (P<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (P<0.01 for both). CONCLUSIONS: Patients with Fontan pathophysiology exhibited GD compared with healthy individuals, and GD was linked to failed hemodynamics and systemic inflammation with a poor prognosis. Therefore, GD may play a pivotal role in a failing Fontan status, including Fontan-associated liver disease, through GD-associated systemic inflammation.

Asunto(s)

RESUMEN

BACKGROUND: Two common indications for pediatric heart transplantation are congenital heart disease and cardiomyopathy. Prior studies suggest differences in chronotropy on cardiopulmonary exercise testing outcomes depending on indication for heart transplantation. We aimed to determine whether the number of pretransplant sternotomies is associated with differences in heart rate response during exercise testing. METHODS: A retrospective analysis of our institutional pediatric heart transplant data between 2004 and 2022 was performed. Patients were categorized by indication for transplantation into a cardiomyopathy (CM) group if they had a congenital or acquired cardiomyopathy or a congenital heart disease (CHD) group including all other forms of congenital cardiac anatomic abnormalities. RESULTS: CHD patients (n = 40) differed from CM patients (n = 53) by mean number of sternotomies prior to transplant (2.4 ± 1.8 vs. 0.5 ± 0.9, p < 0.001). There were no significant differences in echocardiographic function or catheterization hemodynamics. In cardiopulmonary exercise testing performance, the congenital heart disease group had a significantly higher resting heart rate (91.8 ± 11.2 vs. 86.4 ± 10.2 bpm, p = 0.019), lower percent predicted age-predicted maximal heart rate achieved (78.3 ± 8.5% vs. 83.2 ± 11.4%, p = 0.032), and lower heart rate reserve (68.6 ± 19.8 vs. 84.4 ± 24.0 bpm, p = 0.001) despite a similar age and average time from transplantation. Regression analysis confirmed number of pretransplant sternotomies as a main predictor of heart rate metrics. CONCLUSIONS: There is greater chronotropic incompetence in patients who underwent transplantation due to congenital heart disease compared to cardiomyopathy. The groups differ significantly by number of sternotomies, potentially supporting the hypothesis that prior surgical disruption of cardiac innervation may cause decreased chronotropic response to exercise following transplantation.

Asunto(s)

RESUMEN

INTRODUCTION: Congenital heart disease is a common birth defect, but advancements in diagnosis and treatment have improved survival rates. Enhanced recovery after surgery (ERAS) programmes have emerged in paediatric cardiac surgery. Multimodal pain management, as a vital part of ERAS programmes, has been found to be effective in reducing pain and improving outcomes in cardiac surgery patients. Traditional methods of pain control using high-dose opioids can lead to complications, so nonopioid analgesics and regional anaesthesia techniques are being used to reduce the consumption. However, there is a significant variability in pain management practices in paediatric cardiac surgery. A network meta-analysis (NMA) is needed to comprehensively compare the effects of different analgesic interventions in this population. METHODS AND ANALYSIS: A comprehensive electronic literature database search will be performed using electronic databases, mainly including PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials. All randomised controlled trials associated with perioperative pain management for paediatric cardiac surgery will be included. The primary outcome will be visual analogue score or numeric rating scale of pain and total opioid consumption (or equivalent) 24 hours after postoperative tracheal extubation. The Revised Cochrane Risk of Bias Tool will be employed to assess the quality of included articles. A random-effects pairwise meta-analysis will be performed to report the head-to-head comparison. Following the assessment of individual articles, an NMA will be conducted using a Bayesian framework with random-effects' models. ETHICS AND DISSEMINATION: Ethics approval is not necessary because this study will be based on publications. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023477520.

Asunto(s)

RESUMEN

BACKGROUND: This study aimed to compare targeted next-generation sequencing (tNGS) with metagenomic next-generation sequencing (mNGS) for pathogen detection in infants with severe postoperative pneumonia after congenital heart surgery. METHODS: We conducted a retrospective observational study using data from the electronic medical record system of infants who developed severe pneumonia after surgery for congenital heart disease from August 2021 to August 2022. Infants were divided into tNGS and mNGS groups based on the pathogen detection methods. The primary outcome was the efficiency of pathogen detection, and the secondary outcomes were the timeliness and cost of each method. RESULTS: In the study, 91 infants were included, with tNGS detecting pathogens in 84.6% (77/91) and mNGS in 81.3% (74/91) of cases (P = 0.55). No significant differences were found in sensitivity, specificity, PPA, and NPA between the two methods (P > 0.05). tNGS identified five strains with resistance genes, while mNGS detected one strain. Furthermore, tNGS had a faster detection time (12 vs. 24 h) and lower cost ($150 vs. $500) compared to mNGS. CONCLUSION: tNGS offers similar sensitivity to mNGS but with greater efficiency and cost-effectiveness, making it a promising approach for respiratory pathogen detection.

Asunto(s)

RESUMEN

Various scoring systems have been used to predict mortality and morbidity after congenital heart surgery. While the ideal system is still controversial, the technical performance score (TPS) has recently gained popularity. In this study, was investigated the effect of the TPS in predicting mortality and morbidity in pediatric patients who underwent congenital heart surgery in our clinic. Patients aged < 18 years who underwent congenital heart surgery between 2020 and 2023, were retrospectively analyzed. The patients' TPS categorizations were assigned according to their echocardiographic results at discharge and whether they required reintervention. The primary endpoints of the study were mortality (death within 30 days postoperatively) and morbidity. The secondary endpoint was a comparison of the effectiveness of TPS with that of the widely used Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score. Included in this study were 1075 patients. The median patient age was 3 months (interquartile range, 1-5 months). The mortality and morbidity rates were 11% and 24%, respectively. Of the patients, 60% were categorized as TPS I (optimal), 25% as TPS 2 (adequate, minimal residual defect), and 15% as TPS 3 (inadequate, hemodynamically significant residual defect). Being categorized as TPS 3 was associated with mortality, prolonged ICU stay, and major adverse events. The predictive power of TPS for mortality and morbidity was an area under the receiver operating characteristic curve (AUC) of 0.810 (95% CI: 0.79-0.839, P < .001) and 0.78 (95% CI: 0.76-0.80, P < .001), respectively. These values were similar to those of the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score (0.81 vs 0.83 and 0.78 vs 0.80 for mortality and morbidity, respectively). In patients with highly heterogeneous congenital heart disease, the use of intraoperative TPS may be helpful in predicting mortality and morbidity.

Asunto(s)

RESUMEN

PURPOSE OF REVIEW: Present an updated overview of the prevention, diagnosis, and management of infective endocarditis in adult patients with congenital heart disease. RECENT FINDINGS: Care for patients with infective endocarditis is changing in the areas of specialized teams, diagnostics, and prevention. Endocarditis teams should be involved in the care of ACHD patients. The 2023 Duke Criteria for Infective Endocarditis and the 2023 European Society of Cardiology Guidelines have updated the criteria for diagnosis including new major criteria such as CT and positron emission computed tomography with 18F-fluorodeoxyglucose (FDG) scans. Immunological, PCR, and nucleic acid-based tests are now acceptable means to isolate infective organisms. Clindamycin is no longer recommended for antibiotic prophylaxis due to resistance and side effect profile. Special considerations for antibiotic prophylaxis and management must be made for specific congenital heart diseases in adulthood and pregnant ACHD patients. Infective endocarditis (IE), a potentially devastating clinical entity, is a feared threat to the health of adults with congenital heart disease (ACHD). IE needs a systematic approach for its prevention, early diagnosis and management with a multidisciplinary IE team's involvement. There have been changes in the diagnostics and management of IE, which is reflected in updated diagnostic criteria. Timely blood cultures and imaging continue to be the mainstay of diagnosis, however the timing of blood cultures, microbiological testing, and types of diagnostic imaging such as the positron emission computed tomography with 18F-fluorodeoxyglucose (FDG) scan are new. Bicuspid aortic valves, ventricular septal defects, transcatheter pulmonary valve replacements, and tetralogy of Fallot are diagnoses at higher risk for IE in the ACHD population. The following article will focus on the preventive strategies, in addition to novel diagnostic and therapeutic approaches of IE in ACHD patients.

Asunto(s)

RESUMEN

INTRODUCTION: Surgical repair is the standard of care for most infants and children with congenital heart disease. Cardiopulmonary bypass (CPB) is required to facilitate these operations but elicits a systemic inflammatory response, leading to postoperative organ dysfunction, morbidity and prolonged recovery after the surgery. Subzero-balance ultrafiltration (SBUF) has been shown to extract proinflammatory cytokines continuously throughout the CPB exposure. We hypothesize that a high-exchange SBUF (H-SBUF) will have a clinically relevant anti-inflammatory effect compared with a low-exchange SBUF (L-SBUF). METHODS AND ANALYSIS: The ULTrafiltration to enhance Recovery After paediatric cardiac surgery (ULTRA) trial is a randomised, double-blind, parallel-group randomised trial conducted in a single paediatric cardiac surgery centre. Ninety-six patients less than 15 kg undergoing cardiac surgery with CPB will be randomly assigned to H-SBUF during CPB or L-SBUF during CPB in a 1:1 ratio with stratification by The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score 1 and STAT score 2-5. The primary outcome is peak postoperative vasoactive-ventilation-renal score. Time series and peak values of vasoactive-ventilation renal score, vasoactive-inotrope score, ventilation index and oxygenation index will be collected. Secondary clinical outcomes include acute kidney injury, ventilator-free days, inotrope-free days, low cardiac output syndrome, mechanical circulatory support, intensive care unit length of stay and operative mortality. Secondary biomarker data include cytokine, chemokine and complement factor concentrations at baseline before CPB, at the end of CPB exposure and 24 hours following CPB. Analyses will be conducted on an intention-to-treat principle. ETHICS AND DISSEMINATION: The study has ethics approval (#1024932 dated August 31, 2021) and enrolment commenced in September 2021. The primary manuscript and any subsequent analyses will be submitted for peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT04920643.

Asunto(s)

RESUMEN

PURPOSE OF REVIEW: Mechanical circulatory support is used frequently as a method of stabilizing patients with end stage heart failure who are unable to safely await allograft availability. While this technology has been fundamentally important in supporting patients with normal cardiac anatomy, it is still used infrequently in adult patients with congenital heart disease and end-stage heart failure. Here, we review the data on mechanical circulatory support technology in this small but growing population of patients with chronic heart disease prone to the development of circulatory failure. RECENT FINDINGS: Mechanical circulatory support (MCS) has been increasingly employed in adults with congenital heart disease (ACHD) as a bridge to transplant. The new United Network for Organ Sharing listing system favoring temporary MCS use with a higher listing status offers another tool to stabilize ACHD patients and potentially shorten wait times. Both temporary and Durable MCS could help improve transplant candidacy and posttransplant outcomes in select groups of ACHD patients. SUMMARY: Durable and temporary MCS have the potential to significantly improve access to transplant and overall transplant outcomes in ACHD patients.

Asunto(s)

RESUMEN

PURPOSE OF REVIEW: With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients. RECENT FINDINGS: The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool. SUMMARY: The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.

Asunto(s)

RESUMEN

BACKGROUND: Despite a rigorous screening process, including cardiac catheterization, a subset of patients with a single right ventricle (SRV) demonstrates suboptimal short-term outcomes after the Fontan operation. The goal of this study was to perform a comprehensive assessment of diastolic function in pre-Fontan patients with an SRV using invasive reference-standard measures and determine their associations with post-Fontan outcomes. METHODS AND RESULTS: Children aged 2 to 6 years with SRV physiology undergoing pre-Fontan heart catheterization were recruited prospectively. Patients were divided into those who had an optimal or suboptimal outcome. A suboptimal outcome was defined as length of stay ≥14 days or heart transplant/cardiac death in first year after Fontan. Patients underwent pressure-volume loop analysis using reference-standard methods. The measure of ventricular stiffness, ß, was obtained via preload reduction. Cardiac magnetic resonance imaging for extracellular volume and serum draws for matrix metalloproteinase activity were performed. Of 19 patients with an SRV, 9 (47%) had a suboptimal outcome. Mean age was 4.2±0.7 years. Patients with suboptimal outcomes had lower ventricular stiffness (0.021 [0.009-0.049] versus 0.090 [0.031-0.118] mL-1; P=0.02), lower extracellular volume (25% [28%-32%] versus 31% [28%-33%]; P=0.02), and lower matrix metalloproteinase-2 (90 [79-104] versus 108 [79-128] ng/mL; P=0.01) compared with patients with optimal outcomes. The only invasive measure that had an association with suboptimal outcome was ß (P=0.038). CONCLUSIONS: Patients with an SRV with suboptimal outcome after the Fontan operation had lower ventricular stiffness and evidence of maladaptive extracellular matrix metabolism compared with patients with optimal outcome. This appears to be a novel phenotype that may have important clinical implications and requires further study.

Asunto(s)

RESUMEN

BACKGROUND: Peak oxygen consumption (peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$) is routinely measured in people who have congenital heart disease and is reported as a percentage of predicted value, based upon age- and sex-matched normative reference values (NRVs). This study aimed to identify which NRVs are being used, assess whether NRVs are being applied appropriately, and evaluate if recommended NRVs are valid when applied to people with congenital heart disease. METHODS AND RESULTS: A systematic scoping review identified studies that reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value in people with congenital heart disease. A modified risk of bias tool evaluated the included studies. Forty-five studies reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value, and only 21 (47%) studies described or provided a reference on how their percentage of predicted value was calculated. The most cited NRVs were from Wasserman (n=12) and Cooper and Weiler-Ravell (n=7). Risk of bias analysis judged 63% of studies as having some concerns. The NRVs recommended by the American Heart Association were applied to participants with a Fontan circulation (n=70; aged 26.5±6.4 years; 59% women) to examine validity. Predicted peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values from the Wasserman NRV was not significantly associated to measured peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values (men: b=0.31, R2≤0.01; women: b=0.07, R2=0.02). CONCLUSIONS: Numerous NRVs have been applied to individuals with congenital heart disease and are often poorly reported and inappropriately matched to participants. The Wasserman NRV was the most cited but showed poor validity when applied to a Fontan cohort.

Asunto(s)

RESUMEN

Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children's peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Ɲ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Ɲ-CECs increased in both CHD groups and that Ɲ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD.

Asunto(s)

RESUMEN

BACKGROUND: The CRUCIAL trial (NCT04217421) is investigating the effect of postnatal and perioperative administration of allopurinol on postoperative brain injury in neonates with critical congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB) shortly after birth. OBJECTIVE: This study aimed to characterize the pharmacokinetics (PK) of allopurinol and oxypurinol during the preoperative, intraoperative, and postoperative phases in this population, and to evaluate target attainment of the current dosing strategy. METHODS: Nonlinear mixed-effects modeling was used to develop population PK models in 14 neonates from the CRUCIAL trial who received up to five intravenous allopurinol administrations throughout the postnatal and perioperative periods. Target attainment was defined as achieving an allopurinol concentration >2 mg/L in at least two-thirds of the patients during the first 24 h after birth and between the start and 36 h after cardiac surgery with CPB. RESULTS: A two-compartment model for allopurinol was connected to a one-compartment model for oxypurinol with an auto-inhibition effect on the conversion, which best described the PK. In a typical neonate weighing 3.5 kg who underwent cardiac surgery at a postnatal age (PNA) of 5.6 days, the clearance (CL) of allopurinol and oxypurinol at birth was 0.95 L/h (95% confidence interval 0.75-1.2) and 0.21 L/h (0.17-0.27), respectively, which subsequently increased with PNA to 2.97 L/h and 0.41 L/h, respectively, before CPB. During CPB, allopurinol and oxypurinol CL decreased to 1.38 L/h (0.9-1.87) and 0.12 L/h (0.05-0.22), respectively. Post-CPB, allopurinol CL increased to 2.21 L/h (1.74-2.83), while oxypurinol CL dropped to 0.05 L/h (0.01-0.1). Target attainment was 100%, 53.8%, and 100% at 24 h postnatally, 24 h after the start of CPB, and 36 h after the end of cardiac surgery, respectively. The combined concentrations of allopurinol and oxypurinol maintained ≥ 90% inhibition of xanthine oxidase (IC90XO) throughout the postnatal and perioperative period. CONCLUSIONS: The minimal target concentration of allopurinol was not achieved at every predefined time interval in the CRUCIAL trial; however, the dosing strategy used was deemed adequate, since it yielded concentrations well exceeding the IC90XO. The decreased CL of both compounds during CPB suggests influence of the hypothermia, hemofiltration, and the potential sequestration of allopurinol in the circuit. The reduced CL of oxypurinol after CPB is likely attributable to impaired kidney function.

Asunto(s)

RESUMEN

Heart valve disease patients undergo multiple surgeries to replace structurally degraded valve prostheses, highlighting the need for valve replacements with growth and self-repair capacity. Given allogeneic valve transplantation's promise in meeting these goals by delivering a living valve replacement, we propose a framework for preserving and rehabilitating living valves ex vivo.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: Systemic-to-pulmonary shunt is a palliative procedure used to decrease pulmonary blood flow in congenital heart diseases. Shunt stenosis or occlusion has been reported to be associated with mortality; therefore, the management of thrombotic complications remains a challenge for most congenital cardiovascular surgeons. Despite its importance, the optimal method for shunt anastomosis remains unclear. OBJECTIVE: The study investigates the clinical benefits of the punch-out technique over conventional methods in the anastomosis process of Systemic-to-pulmonary shunt, focusing on its potential to reduce shunt-related complications. METHODS: Anastomotic models were created by two different surgeons employing both traditional slit and innovative punch-out techniques. Computational tomography was performed to construct three-dimensional models for computational fluid dynamics (CFD) analysis. We assessed the flow pattern, helicity, magnitude of wall shear stress, and its gradient. RESULTS: The anastomotic flow area was larger in the model using the punch-out technique than in the slit model. In CFD simulation, we found that using the punch-out technique decreases the likelihood of establishing a high wall shear stress distribution around the anastomosis line in the model. CONCLUSION: The punch-out technique emerges as a promising method in SPS anastomosis, offering a reproducible and less skill-dependent alternative that potentially diminishes the risk of shunt occlusion, thereby enhancing patient outcomes.

Asunto(s)