Association of preoperative NT-proBNP with postoperative inflammatory factors levels among children of unrestricted left-to-right shunts congenital heart disease

Association of preoperative NT-proBNP with postoperative inflammatory factors levels among children of unrestricted left-to-right shunts congenital heart disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of preoperative NT-proBNP with postoperative inflammatory factors levels among children of unrestricted left-to-right shunts congenital heart disease Wen-Juan Li, Wen-yuan Shang, Ya-Nan Lu, Ji-hong Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3624458/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study aimed to evaluate preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) in children with pulmonary arterial hypertension (PAH) secondary to unrestricted left-to-right shunts congenital heart disease (CHD) and sought to investigate the correlation between NT-proBNP and inflammatory factor levels following cardiac surgery with cardiopulmonary bypass (CPB). A retrospective observational study was conducted involving 59 infants or children under 2 years old. Echocardiography was employed to measure tricuspid annular peak systolic velocity (TRV). The plasma of preoperative NT-proBNP and perioperative inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1β, and TNF-α were measured. Additionally, postoperative ventilation time, length of Intensive care unit (ICU) and ward stay were recorded. Longer postoperative ventilation time, ICU stay and ward stay exhibited in PAH-CHD patients, and elevated preoperative NT-proBNP levels were associated with preoperative pulmonary artery systolic pressure (PASP). Moreover, there was a significant increase in postoperative inflammatory cytokines, including IL-6, IL-8 and IL-10 (p＜0.05). Importantly, preoperative NT-proBNP was identified as being associated with inflammatory cytokines levels after surgery. Conclusion: Preoperative NT-proBNP level was associated with PASP before surgery in children with unrestricted left-to-right shunts PAH-CHD, and elevated preoperative NT-proBNP levels were associated with significantly increased inflammatory factors after CPB, suggesting a potential correlation with early poor postoperative clinical outcomes. N-terminal pro-B-type natriuretic peptide (NT-proBNP) inflammatory factors pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD) cardiopulmonary bypass Introduction Tremendous progress has occurred in the field of treatment of children with congenital heart disease (CHD) over the past decades, making the continued search for outcome improvement tremendously crucial for CHD children after surgery. Pulmonary arterial hypertension (PAH) secondary to unrestricted left-to-right shunts congenital heart disease (CHD) is a major PAH subtype, which is defined as mean pulmonary arterial pressure (mPAP) > 20 mmHg [ 1 – 2 ]. PAH-CHD exhibits an estimated annual incidence and point prevalence averaged 2.2 and 15.6 cases per million children [ 3 ]. PAH is an essential factor for morbidity and mortality during the perioperative period of cardiac surgery, especially in pediatric CHD for the closure of a large left-to-right shunt and use of cardiopulmonary bypass (CPB) that causes an acute increase in pulmonary artery pressure leading to ventricular dysfunction [ 4 – 6 ]. Susanne et al. detected that the N-terminal pro-B-type natriuretic peptide (NT-proBNP) independently predicts all-cause mortality in a contemporary cohort of PAH-CHD patients [ 7 ]. BNP and NT-proBNP, members of the natriuretic peptide family, are released from cardiac myocytes in response to mechanical load and wall stress. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties upregulated in cardiac diseases [ 8 ]. Given that NT-proBNP carries prognostic information, it may be a helpful marker for predicting outcomes in PAH patients. Nickel et al. discovered that follow-up NT-proBNP levels < 1,800pg/ml indicated better survival in a cohort of 84 Pulmonary arterial hypertension (PAH) patients [ 9 ]. Besides, Ganem et al. found that the levels of BNP of peri-coronary artery bypass grafting correlated with the more extended ICU stay and mechanical ventilation [ 10 ]. Accumulating evidence suggests that NT-proBNP has been shown to have prognostic value in pediatrics with congenital heart disease; Cantinotti et al. showed independent and incremental predictive value of BNP in pediatric cardiac surgery in a prospective study, and Jiangbo et al. revealed that the perioperative NT-proBNP levels might be powerful markers to identify patients at higher risk for worse outcome after CHD surgery [ 11 – 12 ]. However, a few studies focus on the mechanism of the role of NT-proBNP in pediatric CHD surgery with worse outcomes. In our study, we showed the correlation between NT- proBNP and pulmonary artery systolic pressure (PASP) in PAH-CHD with unrestricted left-to-right shunts before surgery and investigated the association between the levels of preoperative NT- proBNP and postoperative inflammatory cytokines to identify a therapeutic approach for minimizing the severity of postoperative complicates in pediatric PAH-CHD with unrestricted left-to-right shunts. Material and Methods Study design This retrospective observational study was conducted in the Department of Pediatric Cardiology at Xinhua Hospital between August 2021 and March 2022. Fifty-nine children (32 males and 27 females) were analyzed. The study cohort consisted of two groups. The PAH-CHD group included 34 patients, and the No PAH-CHD group consisted of 25 patients. Study flow chat was shown in S-Figure 1. All patients had hemodynamic stability before surgery, and none had Eisenmenger syndrome. Continuous-wave Doppler echocardiographic sampling of TRV was used according to the modified Bernoulli Eq. (4 [TRV] 2) [ 13 ]. As estimation of right ventricular systolic pressure (RVSP) by Doppler TTE assessment of tricuspid valve regurgitation (TR) jet peak velocity accurately predicts the pulmonary artery systolic pressure (PASP) observed by invasive measurement, TR velocity > 2.8 m/sec is considered a reasonable cutoff to define elevated pulmonary pressures in the absence of pulmonary stenosis of PAH-CHD [ 14 – 18 ]. Cardiac surgical procedures were performed as routine general anesthesia and CPB, and all patients had no residual shunt and PAH after surgery. Inclusion criteria were operative under 2 years old, diagnosis of unrestricted left-to-right shunts CHD by echocardiography. Exclusion criteria were neonate, acute infection, arrhythmia, respiratory distress, administration of vasoactive drugs one week before surgery, ICU patients before surgery, and residual shunt after surgery. Operation data, including during aortic cross-clamping time and cardiopulmonary bypass time, were counted, and early postoperative outcomes, including duration of mechanism ventilation time and the ICU and ward lengths of stay after surgery, were also measured. Peripheral venous blood samples were taken preoperatively and 2h after CPB. Samples were collected in tubes containing potassium ethylenediaminetetraacetic acid. NT-proBNP was measured by electrochemiluminescence immunoassay. According to the manufacturer's procedure, the levels of IL-1β, TNF-α, IL-6, IL-8, and IL-10 were determined by enzyme-linked immunosorbent assay. Statistical analysis Data were analyzed with SPSS 18.0. Data were expressed as either mean value ± standard deviation or median or medians and interquartile ranges for continuous variables and percentages or numbers for categorical variables. Student’s t-test was used for normally distributed numeric variables analysis, the Mann-Whitney U test was used for nonnormally distributed numeric variables, and the chi-square test was used for categorical variables analysis. The correlation of each variable with clinical outcomes was evaluated using the Spearman test. P value of < 0 .05 was considered statistically significant. Results Patient’s characteristics During the study period, 59 children under two years old were referred to our surgical unit for left to right shunt congenital heart disease; 27 patients were female (45.76%), and 32 patients were male (54.24%). Echocardiography assessed patients before cardiac surgery; 25 patients (42.37%) had no PAH, and 34 patients (57.63%) had PAH. Preoperative PASP was 59.94mmHg±17.56mmHg in the PAH group. All patients underwent successful cardiac shunt closure. Demographic data and associated congenital heart lesions are presented in Table 1. There were no significant differences in the patient’s demographic characteristics between PAH and No PAH patients. The serum preoperative NT-Pro BNP was significantly higher in the PAH group (P＜0.0001) when compared with the No PAH group, and it was correlated with the PASP(rs=0.3656, p=0.0125), as shown in S-Figure 2. No significant difference in preoperative inflammatory cytokines levels, including IL-8, IL-6, IL-10, IL-1β, and TNF-α was found between these two groups. (Table 2). Table 1 Demographic data of patients with and without PAH Variable No PAH group(n=25) PAH group(n=34) P Value Age a (months) 7.90 ± 0.75 6.62 ± 1.06 0.3597 Gender 0.8173 Male (n) 14 18 Female (n) 12 15 Weight a (Kg) 7.49 ± 0.36 6.60 ± 0.39 0.1162 mPAP(mmHg) ＜20mmHg 56.73±20.58 ＜0.0001 Type of CHD 0.1693 VSD (n) 10 17 ASD (n) 8 3 PDA/VSD (n) 1 1 VSD/ASD (n) 4 7 VSD/MR (n) 2 1 DORV/VSD (n) 0 2 COA/VSD (n) 0 3 Abbreviations: PAH, pulmonary atrial hypertension; CHD, congenital heart disease; VSD, ventricular septal defect; ASD, Atrial septal defect; PDA, Patent ductus arteriosus; CAVC, Complete atrioventricular septal defect,; COA, Coarctation of aorta. Table 2 Preoperative variables of patients with and without PAH Variable No PAH group(n=25) PAH group(n=34) P Value Per-NT-ProBNP a (pg/ml) 239.4(181.2,385.1) 1799(713.5, 3486) ＜0.0001 Il-6 (pg/ml) 6.45 ± 2.79 5.52 ± 1.52 0.7616 Il-8 (pg/ml) 76.32 ± 39.34 44.10 ± 16.62 0.4467 Il-10 (pg/ml) 12.31 ± 6.79 7.98 ± 1.43 0.4936 IL-1β(pg/ml) 6.69 ± 0.80 7.18 ± 0.90 0.6940 TNF-α(pg/ml) 20.51± 4.25 21.97 ± 3.09 0.7774 a Descriptive data presented as median and interquartile range. Clinical early postoperative outcomes There was no mortality in both groups. As shown in Table 3, the PAH group had a significant impact on early postoperatively surgical outcomes; the duration of mechanism ventilation time was significantly longer in PAH group (22.76hours ± 2.49hours) compared with No PAH group (13.72 hours ± 2.51 hours) (p=0.0485), Importantly, the lengths of ICU and ward stay after surgery were also longer in the PAH group than the No PAH group (p=0.0432 and 0.0039, respectively). Table 3 Early postoperative outcomes of patients with and without PAH Variable No PAH group(n=25) (Mean±SD) PAH group(n=34) (Mean±SD) P value ventilation time (hours) 13.72 ± 2.51 22.76 ± 2.49 0.0150 ICU lengths of stay (days) 3.33 ± 0.34 4.36 ± 0.34 0.0432 Ward lengths of stay (days) 8.56 ± 0.49 12.31 ± 1.030 0.0039 Abbreviations: CPB, cardiopulmonary bypass; ACC, aortic cross clamp; Change of inflammatory cytokines after surgery After cardiac surgery with CPB, we analyzed the change of postoperative inflammatory cytokines, as shown in Table 4, the levels of inflammatory cytokines, including IL-6, IL-8, and IL-10 increased significantly after CPB both in PAH and No PAH patients (p＜0.05), When compared with No PAH patients, these inflammatory cytokines rose higher in PAH group (P=0.0380, 0.0359 and 0.0078 respectively). However, the IL-1β and TNF-α levels did not change much in the PAH and No PAH groups after the operation. As CPB can produce and release numerous pro-inflammatory cytokines after surgery, we analyze the duration of CPB time and aortic cross-clamping (ACC) time of PAH and No PAH patients, the period of CPB time of PAH and No PAH patients were (66.64 ± 7.53) hours and (75.63 ± 3.65) hours, and the duration of ACC time were (48.19 ± 6.23) hours and (53.22 ± 3.32) hours respectively, no significant difference was found in the period of CPB and ACC in PAH and No PAH patients (p=0.2438 and 0.4510 respectively). Table 4 Changes in proinflammatory factors after cardiac surgery with CPB Inflammatory Factor(pg/ml) No PAH group(n=23) PAH group(n=20) P value IL-6 34.97 ± 6.91* 81.45 ± 18.08 * 0.0380 IL-8 84.22 ± 17.12 * 236.6 ± 59.59 * 0.0359 IL-10 313.3 ± 65.17 * 604.5 ± 74.84 * 0.0078 IL-1β 5.89 ± 0.44 9.87 ± 3.54 0.3550 TNF-α 13.69 ± 1.243 17.77 ± 2.82 0.2643 *Compared with preoperative, p＜0.05 Correlation between perioperative variables and postoperative clinical outcomes The Spearman correlation coefficients between preoperative NT-proBNP and postoperative inflammatory cytokines levels were carried out, as presented in Table 5, preoperative levels of NT-proBNP levels were correlated with postoperative level of IL-6 (rs=0.3656, p=0.0125), IL-8 (rs=0.3005, p=0.0424) and IL-10 (rs=0.3276, p=0.0262), and preoperative PASP also associated with level of IL-6 (rs=0.5156, p=0.0083) and IL-10 (rs=0.5027, p=0.0397), but not the level of IL-8. As we know, BNP is a valuable marker for predicting outcomes in patients with heart disease, and we used ROC to analyze whether postoperative inflammatory cytokines associated with preoperative NT-proBNP have the same reliability to predict the early clinical events after cardiac surgery with CPB in CHD children. As shown in Table 6, the level of preoperative NT-proBNP was a strong predictor of postoperative early clinical outcomes, and the inflammatory factors also have the reliable ability to predict postoperative ventilation time ＞21hours， with an area under the curve(AUC) of 0.698，0.696 and 0.717 for IL-6, IL-8, and IL-10 respectively, and IL-8 can predict ward lengths of stay ＞11 days after surgery; however, there was no correlation found between inflammatory factors and ICU lengths of stay. Table 5 Spearman’s correlation coefficient analysis between NT-proBNP/PASP and postoperative inflammatory cytokines Spearman’s correlation coefficient Post-IL 6 Post-IL 8 Post-IL 10 r s p value r s p value r s p value Pre- NT-proBNP 0.3656 0.0125 0.3005 0.0424 0.3276 0.0262 Pre- PASP 0.5156 0.0083 0.1099 0.6263 0.5027 0.0397 Table 6 Predictive value of variables for prolonged mechanical ventilation, ICU stay and total length of hospital stay Variables Ventilation time ＞ 21hours ICU lengths of stay ＞ 4.5days Ward lengths of stay ＞ 11 days AUC(95%CI) p value AUC(95%CI) p value AUC(95%CI) p value Pre- NTpro-BNP 0.875(0.747-0.953) ＜ 0.0001 0.699(0.550-0.823) 0.0159 0.761(0.616-0.872) 0.0002 Post-IL 6 0.698(0.545-0.825 0.0129 0.656(0.501-0.790) 0.0819 0.659(0.505-0.792) 0.0549 Post-IL 8 0.696(0.546-0.800) 0.0123 0.634(0.483-0.769) 0.1242 0.726(0.578-0.845) 0.0041 Post-IL 10 0.717(0.563-0.841) 0.0072 0.657(0.500-0.792) 0.0915 0.671(0.515-0.803) 0.0536 Discussion PAH is one of the major challenges in pediatric PAH-CHD surgery, which is an essential factor for morbidity and mortality in the early postoperative follow-up [19-20]. PAH associated with unrestricted left-to-right shunts due to high pulmonary arterial flow can be reversed by early shunt closure before a continual increase of pulmonary vascular resistance (PVR) and finally remodeling of the pulmonary vasculature.[21-22] Therefore, To improve cardiac surgery outcomes, it is significant to continue searching for outcome improvement for PAH patients with unrestricted left-to-right shunts CHD. The results of our study demonstrated that levels of preoperative NT-proBNP level, correlated with PASP before surgery, was associated with the levels of inflammatory factors, including IL-6, IL-8, and IL-10 after surgery in children with unrestricted left-to-right shunts CHD, which may be related to the early poor postoperative clinical events. As BNP levels have been shown to parallel hemodynamic and functional responses to PAH therapies [23-26], current PAH guidelines recommend the use of BNP or the NT-proBNP at diagnosis and longitudinal follow-up, and circulating levels of BNP correlate with mPAP and PVR in patients with PAH [27-28]. The study also showed that NT-proBNP is more accurate than BNP for prognosis, especially in females and younger patients [29]. The results of our research confirmed that the level of preoperative NT-proBNP was higher in PAH patients and was correlated with the severity of PAH. CPB is generally accompanied by a systemic inflammatory response that increases the levels of cytokines and acute phase reactants such as CRP, IL-6, IL-8, IL-10, IL-1β, and TNF-α, as surgical trauma, blood contact with the surface of the extracorporeal circulation devices, blood loss, and ischemic reperfusion injury. These proinflammatory cytokines, including IL-6, IL-8, IL-1β, and TNF-α, in turn increase the level of activated neutrophils, inducing cellular damage, further leukocyte activation, chemotaxis, and Leukocyte-endothelial adherence [31-32]. In our study, IL-6, IL-8, and IL-10 were increased significantly after CPB in both groups, but the TNF-α and IL-1β did not change compared with preoperative in both groups; the reason may be that TNF-α and IL-1β are elevated early following cardiac surgery, with IL-6 and IL-8 peaking later. [19] Lei et al. revealed that PAH aggravates the production of inflammatory cytokines compared to No PAH patients by induction of the systemic inflammatory response by activating complement and leukocytes and expressing adherent cytokines [32-34]. In our results, although no difference was found between PAH and No PAH patients during CPB time, IL-6, IL-8, and IL-10 levels increased significantly in PAH patients after CPB. More evidence confirmed that a systemic inflammatory response interacts with the secretion of natriuretic peptides in critically ill patients [35]; Yue revealed that the levels of plasma BNP are associated with the severity of sepsis-induced systemic inflammatory response syndrome in pediatric patients [36]. The results of our study showed that high levels of preoperative NT-proBNP levels may be associated with significantly increasing levels of IL-6, IL-8, and IL-10 induced by systemic inflammatory response after CPB. The reason may be related to an inflammatory response mediated by the induced heat shock factor 1 signaling pathway [37]. Previous studies revealed that cardiac surgery involving CPB is associated with less favorable outcomes, though it activates an inflammatory response releasing cytokines [32-33, 38-39]. Holmes IV et al. demonstrated that patients with an exaggerated inflammatory response to CPB tend to require more respiratory support; thus, the magnitude of the inflammatory response to CPB adversely influences clinical outcomes. [40] Our results confirmed that high levels of IL-6, IL-8, and IL-10 were corrected with postoperative longer ventilation time. Although PAH patients had longer ICU and ward lengths of stay after surgery, no correlation with inflammatory factors was detected in our study by ROC analysis. There are still limitations of this study. First, the SPAP of patients with CHD-PAH was measured by echocardiography, which was not very close compared with cardiac catheterization measurement. Secondly, this is a retrospective study with a small sample size, and further prospective large-scale studies are needed. Conclusion Preoperative NT-proBNP level was associated with the severity of PAH in pediatric unrestricted left-to-right shunts CHD. High levels of preoperative NT-proBNP levels correlated with significantly increasing inflammatory factors after surgery of CPB, and increased inflammatory factors, including IL-6, IL-8, and IL-10 can lead to early poor postoperative clinical events. Declarations Ethical Approval This work was approved by the Xinhua Hospital Ethics Committee (approval number: XHEC-QT-2021-042). All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975. Informed consent was not required in the present study. Funding This work was supported by the Fundamental Research Funds for the Central Universities (grant number YG2023QNB13) and Xinhua Hospital&Shanghai Jiao Tong University Joint Project (grant number 21XJMR04) Availability of data and material The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. Author Contributions Wenjuan Li and Wenyuan Shang gathered data, and formal analysis, Wenjuan Li wrote the original draft; Jihong Huang conceived the study and revised the manuscript; Yanan Lu revised the manuscript. Conflict of interest : none declared. References Dimopoulos K, Wort SJ, Gatzoulis MA. Pulmonary hypertension related to congenital heart disease: a call for action. Eur Heart J. 2014; 35:691–700. Duffels MGJ, Engelfriet PM, Berger RMF, Van Loon RLE, Hoendermis E, Vriend JWJ et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol 2007; 120:198–204 Van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, et al. Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation. 2011 Oct 18;124(16):1755-64. Bando K, Turrentine MW, Sharp TG, Sekine Y, Aufifiero TX, Sun K et al. Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management. J Thorac Cardiovasc Surg 1996; 112:1600–9. Schulze-Neick I, Li J, Penny DJ, Redington AN. Pulmonary vascular resistance after cardiopulmonary bypass in infants: effect on postoperative recovery. J Thorac Cardiovasc Surg 2001;121:1033–9. Kaestner M, Schranz D, Warnecke G, Apitz C, Hansmann G, Miera O. Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016;102:57–66. Maurer SJ, Habdank V, Hörer J, Ewert P, Tutarel O. NT-proBNP Is a Predictor of Mortality in Adults with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. J Clin Med. 2023 Apr 24;12(9):3101. Li N, Zhang Y, Fan S, Xing J, Liu H. BNP and NT-proBNP levels in patients with sepsis. Front Biosci (Landmark Ed). 2013 Jun 1;18(4):1237-43. Nickel N, Golpon H, Greer M, Knudsen L, Olsson K, Westerkamp V et al. The prognostic impact of follow up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2012;39:589–96. Ganem F, Serrano CV, Fernandes JL, Heloísa M, Blotta SL, Souza JA et al. Preoperative B-type natriuretic peptide, and not the inflammation status, predicts an adverse outcome for patients undergoing heart surgery. Interact Cardiovasc Thorac Surg. 2011 May;12(5):778-83. Cantinotti M, Giordano R, Scalese M, Molinaro S, Della Pina F, Storti S et al. Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors. Clin Chem Lab Med. 2015; 53: 1839-1846. Qu J, Liang H, Zhou N, Li L, Wang Y, Li J, Cui Y. Perioperative NT-proBNP level: Potential prognostic markers in children undergoing congenital heart disease surgery. J Thorac Cardiovasc Surg. 2017 Aug;154(2):631-640. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713 McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation. 2001 Dec 4;104(23):2797-802. Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984; 70: 657–626; Berger M, Haimowitz A, Van Tosh A, et al. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol. 1985; 6: 359–365; Currie PJ, Seward JB, Chan KL, et al. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol. 1985; 6: 750–756 Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Fandl A, et al. Tricuspid annular peak systolic velocity (S') in children and young adults with pulmonary artery hypertension secondary to congenital heart diseases, and in those with repaired tetralogy of Fallot: echocardiography and MRI data. J Am Soc Echocardiogr. 2012 Oct;25(10):1041-9.] Wheller J, George B, Mulder DG, Jarmakani JM. Diagnosis and management of postoperative pulmonary hypertensive crisis. Circulation 1979;60:1640–9. Bando K, Turrentine MW, Sharp TG, Sekine Y, Aufiero TX, Sun K et al. Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management. J Thorac Cardiovasc Surg 1996;112:1600–9. Van Der Feen DE, Bartelds B, De Boer RA, Berger RMF. Assessment of reversibility in pulmonary arterial hypertension and congenital heart disease. Heart. 2019; 105(4): 276–82 McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, et al. Treatment goals of pulmonary hypertension. J Am Coll Cardiol . 2013;62:D73–D81 Cuthbertson BH, Card G, Croal Bl, McNeilly J, Hillis GS. The utility of B-type natriuretic peptide in predicting postoperative cardiac events and mortality in patients undergoing major non-cardiac surgery. Anesthesia 2007;62:875–881. Bergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H et al. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 2004;109:2302-8 Eliasdottir SB, Klemenzson G, Torfason B, Valsson F. Brain natriuretic peptide is a good predictor for outcome in cardiac surgery. Acta Anaesthesiol Scand 2008;52:182–187. Jogia PM, Kalkoff M, Sleigh JW, Bertinelli A, La Pine M, Richards AM, Devlin G. NT-pro BNP secretion and clinical endpoints in cardiac surgery intensive care patients. Anaesth Intensive Care 2007;35:363–369 Lewis RA, Durrington C, Condliffe R, Kiely DG. BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing? Eur Respir Rev, 2020 May 15;29(156):200009 Casserly B, Klinger JR. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent. Drug Des Devel Ther. 2009 Dec 29;3:269-87 Kara K, Lehmann N, Neumann T, Kälsch H, Möhlenkamp S, Dykun I et al. NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: the Heinz Nixdorf Recall Study. Int J Cardiol 2015; 183: 155–161. Suleiman MS, Zacharowski K, Angelina GD. Inflammatory response and cardioprotection during open heart surgery; the importance of anaesthetics. Br J Pharm. 2008;153:21-33. 2. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesi- ologist. Anesthesiology. 2002;97:215-252 Soares LC, Ribas D, Spring R, Silva JM, Miyague NI. Clinical profle of systemic infammatory response after pediatric cardiac surgery with cardiopulmonary bypass. Arq Bras Cardiol. 2010;94(1):127–33. Yin X, Xin M, Ding S, Gao F, Wu F, Wang J,et al. Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension. BMC Surg. 2021 Jan 4;21(1):3. Lei Y, Zhen J, Ming XL, Jian HK. Induction of higher expression of IL-beta and TNF-alpha, lower expression of IL-10 and cyclic guanosine monophosphate by pulmonary arterial hypertension following cardiopulmonary bypass.Asian J Surg. 2002 Jul;25(3):203-8 Rudiger A, Fischler M, Harpes P, Gasser S, Hornemann T, von Eckardstein A, et al. In critically ill patients, B-type natriuretic peptide (BNP) and N-terminal pro-BNP levels correlate with C-reactive protein values and leukocyte counts. Int J Cardiol. 2008 May 7;126(1):28-31. Zhang Y, Luo Y, Nijiatijiang G, Balati K, Tuerdi Y, Liu L. Correlations of Changes in Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) with Levels of C-Reactive Protein (CRP) and TNF-α in Pediatric Patients with Sepsis. Med Sci Monit. 2019 Apr 8;25:2561-2566. Xu YC, Luo CQ, Li X. Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway. Clin Exp Pharmacol Physiol. 2016 Oct;43(10):921-9. Hirai S. Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. Ann Thorac Cardiovasc Surg. 2003 Dec;9(6):365-70. Nebelsiek T, Beiras-Fernandez A, Kilger E, Möhnle P, Weis F. Routine use of corticosteroids to prevent inflammation response in cardiac surgery. Recent Pat Cardiovasc Drug Discov. 2012 Dec;7(3):170-4. Holmes JH 4th, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, et al. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res. 2002 Dec;51(12):579-86. Additional Declarations No competing interests reported. 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Pulmonary arterial hypertension (PAH) secondary to unrestricted left-to-right shunts congenital heart disease (CHD) is a major PAH subtype, which is defined as mean pulmonary arterial pressure (mPAP)\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. PAH-CHD exhibits an estimated annual incidence and point prevalence averaged 2.2 and 15.6 cases per million children [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. PAH is an essential factor for morbidity and mortality during the perioperative period of cardiac surgery, especially in pediatric CHD for the closure of a large left-to-right shunt and use of cardiopulmonary bypass (CPB) that causes an acute increase in pulmonary artery pressure leading to ventricular dysfunction [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Susanne et al. detected that the N-terminal pro-B-type natriuretic peptide (NT-proBNP) independently predicts all-cause mortality in a contemporary cohort of PAH-CHD patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBNP and NT-proBNP, members of the natriuretic peptide family, are released from cardiac myocytes in response to mechanical load and wall stress. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties upregulated in cardiac diseases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Given that NT-proBNP carries prognostic information, it may be a helpful marker for predicting outcomes in PAH patients. Nickel et al. discovered that follow-up NT-proBNP levels\u0026thinsp;\u0026lt;\u0026thinsp;1,800pg/ml indicated better survival in a cohort of 84 Pulmonary arterial hypertension (PAH) patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Besides, Ganem et al. found that the levels of BNP of peri-coronary artery bypass grafting correlated with the more extended ICU stay and mechanical ventilation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Accumulating evidence suggests that NT-proBNP has been shown to have prognostic value in pediatrics with congenital heart disease; Cantinotti et al. showed independent and incremental predictive value of BNP in pediatric cardiac surgery in a prospective study, and Jiangbo et al. revealed that the perioperative NT-proBNP levels might be powerful markers to identify patients at higher risk for worse outcome after CHD surgery [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, a few studies focus on the mechanism of the role of NT-proBNP in pediatric CHD surgery with worse outcomes. In our study, we showed the correlation between NT- proBNP and pulmonary artery systolic pressure (PASP) in PAH-CHD with unrestricted left-to-right shunts before surgery and investigated the association between the levels of preoperative NT- proBNP and postoperative inflammatory cytokines to identify a therapeutic approach for minimizing the severity of postoperative complicates in pediatric PAH-CHD with unrestricted left-to-right shunts.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis retrospective observational study was conducted in the Department of Pediatric Cardiology at Xinhua Hospital between August 2021 and March 2022. Fifty-nine children (32 males and 27 females) were analyzed. The study cohort consisted of two groups. The PAH-CHD group included 34 patients, and the No PAH-CHD group consisted of 25 patients. Study flow chat was shown in S-Figure 1.\u003c/p\u003e \u003cp\u003eAll patients had hemodynamic stability before surgery, and none had Eisenmenger syndrome. Continuous-wave Doppler echocardiographic sampling of TRV was used according to the modified Bernoulli Eq.\u0026nbsp;(4 [TRV] 2) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. As estimation of right ventricular systolic pressure (RVSP) by Doppler TTE assessment of tricuspid valve regurgitation (TR) jet peak velocity accurately predicts the pulmonary artery systolic pressure (PASP) observed by invasive measurement, TR velocity\u0026thinsp;\u0026gt;\u0026thinsp;2.8 m/sec is considered a reasonable cutoff to define elevated pulmonary pressures in the absence of pulmonary stenosis of PAH-CHD [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCardiac surgical procedures were performed as routine general anesthesia and CPB, and all patients had no residual shunt and PAH after surgery. Inclusion criteria were operative under 2 years old, diagnosis of unrestricted left-to-right shunts CHD by echocardiography. Exclusion criteria were neonate, acute infection, arrhythmia, respiratory distress, administration of vasoactive drugs one week before surgery, ICU patients before surgery, and residual shunt after surgery. Operation data, including during aortic cross-clamping time and cardiopulmonary bypass time, were counted, and early postoperative outcomes, including duration of mechanism ventilation time and the ICU and ward lengths of stay after surgery, were also measured.\u003c/p\u003e \u003cp\u003ePeripheral venous blood samples were taken preoperatively and 2h after CPB. Samples were collected in tubes containing potassium ethylenediaminetetraacetic acid. NT-proBNP was measured by electrochemiluminescence immunoassay. According to the manufacturer's procedure, the levels of IL-1β, TNF-α, IL-6, IL-8, and IL-10 were determined by enzyme-linked immunosorbent assay.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were analyzed with SPSS 18.0. Data were expressed as either mean value\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median or medians and interquartile ranges for continuous variables and percentages or numbers for categorical variables. Student\u0026rsquo;s t-test was used for normally distributed numeric variables analysis, the Mann-Whitney U test was used for nonnormally distributed numeric variables, and the chi-square test was used for categorical variables analysis. The correlation of each variable with clinical outcomes was evaluated using the Spearman test. P value of \u0026lt;\u0026thinsp;0 .05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient\u0026rsquo;s characteristics\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring the study period, 59 children under two years old were referred to our surgical unit for left to right shunt congenital heart disease; 27 patients were female (45.76%), and 32 patients were male (54.24%). Echocardiography assessed patients before cardiac surgery; 25 patients (42.37%) had no PAH, and 34 patients (57.63%) had PAH. Preoperative PASP was 59.94mmHg\u0026plusmn;17.56mmHg in the PAH group. All patients underwent successful cardiac shunt closure. Demographic data and associated congenital heart lesions are presented in Table 1. There were no significant differences in the patient\u0026rsquo;s demographic characteristics between PAH and No PAH patients. The serum preoperative NT-Pro BNP was significantly higher in the PAH group (P＜0.0001) when compared with the No PAH group, and it was correlated with the PASP(rs=0.3656, p=0.0125), as shown in S-Figure 2. No significant difference in preoperative inflammatory cytokines levels, including IL-8, IL-6, IL-10, IL-1\u0026beta;, and TNF-\u0026alpha; was found between these two groups. (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 \u0026nbsp; Demographic data of patients with and without PAH\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.953445065176908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.236499068901303%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PAH group(n=25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.981378026070765%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePAH group(n=34)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.828677839851025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.953445065176908%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e(months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.236499068901303%\" valign=\"top\"\u003e\n \u003cp\u003e7.90 \u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.981378026070765%\" valign=\"top\"\u003e\n \u003cp\u003e6.62 \u0026plusmn; 1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.828677839851025%\" valign=\"top\"\u003e\n \u003cp\u003e0.3597\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.953445065176908%\" valign=\"top\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.21787709497207%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.828677839851025%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.8173\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003eMale (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.953445065176908%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Weight\u003csup\u003e\u0026nbsp;a\u003c/sup\u003e(Kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.236499068901303%\" valign=\"top\"\u003e\n \u003cp\u003e7.49 \u0026plusmn; 0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.981378026070765%\" valign=\"top\"\u003e\n \u003cp\u003e6.60 \u0026plusmn; 0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.828677839851025%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.1162\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.953445065176908%\" valign=\"top\"\u003e\n \u003cp\u003emPAP(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.236499068901303%\" valign=\"top\"\u003e\n \u003cp\u003e＜20mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.981378026070765%\" valign=\"top\"\u003e\n \u003cp\u003e56.73\u0026plusmn;20.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.828677839851025%\" valign=\"top\"\u003e\n \u003cp\u003e＜0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"84.14179104477611%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;Type of CHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.85820895522388%\" rowspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e0.1693\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; VSD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; ASD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;PDA/VSD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; VSD/ASD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003eVSD/MR (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;DORV/VSD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.646017699115045%\" valign=\"top\"\u003e\n \u003cp\u003eCOA/VSD (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.73451327433628%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.61946902654867%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: PAH, pulmonary atrial hypertension; CHD, congenital heart disease; VSD, ventricular septal defect; ASD,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAtrial septal defect; PDA, Patent ductus arteriosus; CAVC, Complete atrioventricular septal defect,; COA, Coarctation of aorta.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Preoperative variables of patients with and without PAH\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PAH group(n=25)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePAH group(n=34)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003ePer-NT-ProBNP\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e(pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e239.4(181.2,385.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e1799(713.5, 3486)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e＜0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003eIl-6 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e6.45 \u0026plusmn; 2.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e5.52 \u0026plusmn; 1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.7616\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003eIl-8 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e76.32 \u0026plusmn; 39.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e44.10 \u0026plusmn; 16.62\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.4467\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003eIl-10 (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e12.31 \u0026plusmn; 6.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e7.98 \u0026plusmn; 1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.4936\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003eIL-1\u0026beta;(pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e6.69 \u0026plusmn; 0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e7.18 \u0026plusmn; 0.90\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.6940\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.00589390962672%\" valign=\"top\"\u003e\n \u003cp\u003eTNF-\u0026alpha;(pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.897838899803535%\" valign=\"top\"\u003e\n \u003cp\u003e20.51\u0026plusmn; 4.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.165029469548134%\" valign=\"top\"\u003e\n \u003cp\u003e21.97 \u0026plusmn; 3.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.931237721021612%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.7774\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea Descriptive data presented as median and interquartile range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical early postoperative outcomes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no mortality in both groups. As shown in Table 3, the PAH group had a significant impact on early postoperatively surgical outcomes; the duration of mechanism ventilation time was significantly longer in PAH group (22.76hours \u0026plusmn; 2.49hours) compared with No PAH group (13.72 hours \u0026plusmn; 2.51 hours) (p=0.0485), Importantly, the lengths of ICU and ward stay after surgery were also longer in the PAH group than the No PAH group (p=0.0432 and 0.0039, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEarly postoperative outcomes\u0026nbsp;of patients with and without PAH\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.899628252788105%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.066914498141266%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PAH group(n=25)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean\u0026plusmn;SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.53531598513011%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePAH group(n=34)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Mean\u0026plusmn;SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.49814126394052%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.899628252788105%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eventilation time (hours)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.066914498141266%\" valign=\"top\"\u003e\n \u003cp\u003e13.72 \u0026plusmn; 2.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.53531598513011%\" valign=\"top\"\u003e\n \u003cp\u003e22.76 \u0026plusmn; 2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.49814126394052%\" valign=\"top\"\u003e\n \u003cp\u003e0.0150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.899628252788105%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU lengths of stay (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.066914498141266%\" valign=\"top\"\u003e\n \u003cp\u003e3.33 \u0026plusmn; 0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.53531598513011%\" valign=\"top\"\u003e\n \u003cp\u003e4.36 \u0026plusmn; 0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.49814126394052%\" valign=\"top\"\u003e\n \u003cp\u003e0.0432\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"32.899628252788105%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWard lengths of stay (days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.066914498141266%\" valign=\"top\"\u003e\n \u003cp\u003e8.56 \u0026plusmn; 0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.53531598513011%\" valign=\"top\"\u003e\n \u003cp\u003e12.31 \u0026plusmn; 1.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.49814126394052%\" valign=\"top\"\u003e\n \u003cp\u003e0.0039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: CPB, cardiopulmonary bypass; ACC, aortic cross clamp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChange of inflammatory cytokines after surgery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter cardiac surgery with CPB, we analyzed the change of postoperative inflammatory cytokines, as shown in Table 4, the levels of inflammatory cytokines, including IL-6, IL-8, and IL-10 increased significantly after CPB both in PAH and No PAH patients (p＜0.05), When compared with No PAH patients, these inflammatory cytokines rose higher in PAH group (P=0.0380, 0.0359 and 0.0078 respectively). However, the IL-1\u0026beta; and TNF-\u0026alpha; levels did not change much in the PAH and No PAH groups after the operation. As CPB can produce and release numerous pro-inflammatory cytokines after surgery, we analyze the duration of CPB time and aortic cross-clamping (ACC) time of PAH and No PAH patients, the period of CPB time of PAH and No PAH patients were (66.64 \u0026plusmn; 7.53) hours and (75.63 \u0026plusmn; 3.65) hours, and the duration of ACC time were (48.19 \u0026plusmn; 6.23) hours and (53.22 \u0026plusmn; 3.32) hours respectively, no significant difference was found in the period of CPB and ACC in PAH and No PAH patients (p=0.2438 and 0.4510 respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 \u0026nbsp; Changes in proinflammatory factors after cardiac surgery with CPB\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"501\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInflammatory\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFactor(pg/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo PAH group(n=23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePAH group(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003eIL-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e34.97 \u0026plusmn; 6.91*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e81.45 \u0026plusmn; 18.08 *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003e0.0380\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003eIL-8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e84.22 \u0026plusmn; 17.12 *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e236.6 \u0026plusmn; 59.59 *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003e0.0359\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003eIL-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e313.3 \u0026plusmn; 65.17 *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e604.5 \u0026plusmn; 74.84\u0026nbsp;*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003e0.0078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003eIL-1\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e5.89 \u0026plusmn; 0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e9.87 \u0026plusmn; 3.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003e0.3550\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.550898203592816%\" valign=\"top\"\u003e\n \u003cp\u003eTNF-\u0026alpha;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.343313373253494%\" valign=\"top\"\u003e\n \u003cp\u003e13.69 \u0026plusmn; 1.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.139720558882235%\" valign=\"top\"\u003e\n \u003cp\u003e17.77 \u0026plusmn; 2.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.96606786427146%\" valign=\"top\"\u003e\n \u003cp\u003e0.2643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Compared with preoperative, p＜0.05\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation between perioperative variables and postoperative clinical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Spearman correlation coefficients between preoperative NT-proBNP and postoperative inflammatory cytokines levels were carried out, as presented in Table 5, \u0026nbsp; preoperative levels of NT-proBNP levels were correlated with postoperative level of IL-6 (rs=0.3656, p=0.0125), IL-8 (rs=0.3005, p=0.0424) and IL-10 (rs=0.3276, p=0.0262), and preoperative PASP also associated with level of IL-6 (rs=0.5156, p=0.0083) and IL-10 (rs=0.5027, p=0.0397), but not the level of IL-8. As we know, BNP is a valuable marker for predicting outcomes in patients with heart disease, and we used ROC to analyze whether postoperative inflammatory cytokines associated with preoperative NT-proBNP have the same reliability to predict the early clinical events after cardiac surgery with CPB in CHD children. As shown in Table 6, the level of preoperative NT-proBNP was a strong predictor of postoperative early clinical outcomes, and the inflammatory factors also have the reliable ability to predict postoperative ventilation time\u0026nbsp;＞21hours，\u0026nbsp;with an area under the curve(AUC) of 0.698，0.696 and 0.717 for IL-6, IL-8, and IL-10 respectively, and IL-8 can predict ward lengths of stay\u0026nbsp;＞11 days after surgery; however, there was no correlation found between inflammatory factors and ICU lengths of stay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5 Spearman\u0026rsquo;s correlation coefficient analysis between NT-proBNP/PASP and\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003epostoperative inflammatory cytokines\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"7\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u003cstrong\u003eSpearman\u0026rsquo;s correlation coefficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.760563380281692%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.239436619718308%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.295774647887324%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.704225352112676%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.388489208633093%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003er\u003csub\u003es\u003c/sub\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50599520383693%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.587529976019185%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003er\u003csub\u003es\u003c/sub\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50599520383693%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50599520383693%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003er\u003csub\u003es\u003c/sub\u003e\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.50599520383693%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre- NT-proBNP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54481546572935%\" valign=\"top\"\u003e\n \u003cp\u003e0.3656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0125\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.423550087873462%\" valign=\"top\"\u003e\n \u003cp\u003e0.3005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0424\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e0.3276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0262\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.71353251318102%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre- PASP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.54481546572935%\" valign=\"top\"\u003e\n \u003cp\u003e0.5156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0083\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.423550087873462%\" valign=\"top\"\u003e\n \u003cp\u003e0.1099\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.6263\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e0.5027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.829525483304042%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0397\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePredictive\u0026nbsp;value of variables for prolonged mechanical ventilation, ICU stay and total length of hospital stay\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.702479338842975%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.09917355371901%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eVentilation time\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e＞\u003c/strong\u003e\u003cstrong\u003e21hours\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.09917355371901%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eICU lengths of stay\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e＞\u003c/strong\u003e\u003cstrong\u003e4.5days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.09917355371901%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWard lengths of stay\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e＞\u003c/strong\u003e\u003cstrong\u003e11 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.392156862745097%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.941176470588236%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.392156862745097%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.941176470588236%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.392156862745097%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.941176470588236%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre- NTpro-BNP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.875(0.747-0.953)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e＜\u003c/em\u003e\u003cem\u003e0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.699(0.550-0.823)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0159\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.761(0.616-0.872)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0002\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 6\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.698(0.545-0.825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0129\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.656(0.501-0.790)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0819\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.659(0.505-0.792)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0549\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 8\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.696(0.546-0.800)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0123\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.634(0.483-0.769)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.1242\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.726(0.578-0.845)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0041\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-IL 10\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.717(0.563-0.841)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0072\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.657(0.500-0.792)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0915\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.1900826446281%\" valign=\"top\"\u003e\n \u003cp\u003e0.671(0.515-0.803)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.909090909090908%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e0.0536\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u0026nbsp;PAH is one of the major challenges in pediatric PAH-CHD surgery, which is an essential factor for morbidity and mortality in the early postoperative follow-up [19-20]. PAH associated with unrestricted left-to-right shunts due to high pulmonary arterial flow can be reversed by early shunt closure before a continual increase of pulmonary vascular resistance (PVR) and finally remodeling of the pulmonary vasculature.[21-22] Therefore, To improve cardiac surgery outcomes, it is significant to continue searching for outcome improvement for PAH patients with unrestricted left-to-right shunts CHD. The results of our study demonstrated that levels of preoperative NT-proBNP level, correlated with PASP before surgery, was associated with the levels of inflammatory factors, including IL-6, IL-8, and IL-10 after surgery in children with unrestricted left-to-right shunts CHD, which may be related to the early poor postoperative clinical events.\u003c/p\u003e\n\u003cp\u003eAs BNP levels have been shown to parallel hemodynamic and functional responses to PAH therapies [23-26], current PAH guidelines recommend the use of BNP or the NT-proBNP at diagnosis and longitudinal follow-up, and circulating levels of BNP correlate with mPAP and PVR in patients with PAH [27-28]. The study also showed that NT-proBNP is more accurate than BNP for prognosis, especially in females and younger patients [29]. The results of our research confirmed that the level of preoperative NT-proBNP was higher in PAH patients and was correlated with the severity of PAH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCPB is generally accompanied by a systemic inflammatory response that increases the levels of cytokines and acute phase reactants such as CRP, IL-6, IL-8, IL-10, IL-1\u0026beta;, and TNF-\u0026alpha;, as surgical trauma, blood contact with the surface of the extracorporeal circulation devices, blood loss, and ischemic reperfusion injury. These proinflammatory cytokines, including IL-6, IL-8, IL-1\u0026beta;, and TNF-\u0026alpha;, in turn increase the level of activated neutrophils, inducing cellular damage, further leukocyte activation, chemotaxis, and Leukocyte-endothelial adherence [31-32]. In our study, IL-6, IL-8, and IL-10 were increased significantly after CPB in both groups, but the TNF-\u0026alpha; and IL-1\u0026beta; did not change compared with preoperative in both groups; the reason may be that TNF-\u0026alpha; and IL-1\u0026beta; are elevated early following cardiac surgery, with IL-6 and IL-8 peaking later. [19] Lei et al. revealed that PAH aggravates the production of inflammatory cytokines compared to No PAH patients by induction of the systemic inflammatory response by activating complement and leukocytes and expressing adherent cytokines [32-34]. In our results, although no difference was found between PAH and No PAH patients during CPB time, IL-6, IL-8, and IL-10 levels increased significantly in PAH patients after CPB. More evidence confirmed that a systemic inflammatory response interacts with the secretion of natriuretic peptides in critically ill patients [35]; Yue revealed that the levels of plasma BNP are associated with the severity of sepsis-induced systemic inflammatory response syndrome in pediatric patients [36]. The results of our study showed that high levels of preoperative NT-proBNP levels may be associated with significantly increasing levels of IL-6, IL-8, and IL-10 induced by systemic inflammatory response after CPB. The reason may be related to an inflammatory response mediated by the induced heat shock factor 1 signaling pathway [37].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies revealed that cardiac surgery involving CPB is associated with less favorable outcomes, though it activates an inflammatory response releasing cytokines [32-33, 38-39]. Holmes IV et al. demonstrated that patients with an exaggerated inflammatory response to CPB tend to require more respiratory support; thus, the magnitude of the inflammatory response to CPB adversely influences clinical outcomes. [40] Our results confirmed that high levels of IL-6, IL-8, and IL-10 were corrected with postoperative longer ventilation time. Although PAH patients had longer ICU and ward lengths of stay after surgery, no correlation with inflammatory factors was detected in our study by ROC analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are still limitations of this study. First, the SPAP of patients with CHD-PAH was measured by echocardiography, which was not very close compared with cardiac catheterization measurement. Secondly, this is a retrospective study with a small sample size, and further prospective large-scale studies are needed.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePreoperative NT-proBNP level was associated with the severity of PAH in pediatric unrestricted left-to-right shunts CHD. High levels of preoperative NT-proBNP levels correlated with significantly increasing inflammatory factors after surgery of CPB, and increased inflammatory factors, including IL-6, IL-8, and IL-10 can lead to early poor postoperative clinical events.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e This work was approved by the Xinhua Hospital Ethics Committee (approval number: XHEC-QT-2021-042). All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975. Informed consent was not required in the present study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by\u0026nbsp;the Fundamental Research Funds for the Central Universities (grant number YG2023QNB13)\u0026nbsp;and Xinhua Hospital\u0026amp;Shanghai Jiao Tong University Joint Project (grant number\u0026nbsp;21XJMR04)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Wenjuan Li and Wenyuan Shang gathered data, and formal analysis, Wenjuan Li wrote the original draft; Jihong Huang conceived the study and revised the manuscript; Yanan Lu revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e none declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDimopoulos K, Wort SJ, Gatzoulis MA. Pulmonary hypertension related to congenital heart disease: a call for action. Eur Heart J. 2014; 35:691\u0026ndash;700.\u003c/li\u003e\n\u003cli\u003eDuffels MGJ, Engelfriet PM, Berger RMF, Van Loon RLE, Hoendermis E, Vriend JWJ et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol 2007; 120:198\u0026ndash;204\u003c/li\u003e\n\u003cli\u003eVan Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, et al. Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation. 2011 Oct 18;124(16):1755-64.\u003c/li\u003e\n\u003cli\u003eBando K, Turrentine MW, Sharp TG, Sekine Y, Aufifiero TX, Sun K et al. Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management. J Thorac Cardiovasc Surg 1996; 112:1600\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eSchulze-Neick I, Li J, Penny DJ, Redington AN. Pulmonary vascular resistance after cardiopulmonary bypass in infants: effect on postoperative recovery. J Thorac Cardiovasc Surg 2001;121:1033\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eKaestner M, Schranz D, Warnecke G, Apitz C, Hansmann G, Miera O. Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016;102:57\u0026ndash;66.\u003c/li\u003e\n\u003cli\u003eMaurer SJ, Habdank V, H\u0026ouml;rer J, Ewert P, Tutarel O. NT-proBNP Is a Predictor of Mortality in Adults with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. J Clin Med. 2023 Apr 24;12(9):3101.\u003c/li\u003e\n\u003cli\u003eLi N, Zhang Y, Fan S, Xing J, Liu H. BNP and NT-proBNP levels in patients with sepsis. Front Biosci (Landmark Ed). 2013 Jun 1;18(4):1237-43.\u003c/li\u003e\n\u003cli\u003eNickel N, Golpon H, Greer M, Knudsen L, Olsson K, Westerkamp V et al. The prognostic impact of follow up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2012;39:589\u0026ndash;96.\u003c/li\u003e\n\u003cli\u003eGanem F, Serrano CV, Fernandes JL, Helo\u0026iacute;sa M, Blotta SL, Souza JA et al. Preoperative B-type natriuretic peptide, and not the inflammation status, predicts an adverse outcome for patients undergoing heart surgery. Interact Cardiovasc Thorac Surg. 2011 May;12(5):778-83.\u003c/li\u003e\n\u003cli\u003eCantinotti M, Giordano R, Scalese M, Molinaro S, Della Pina F, Storti S et al. Prognostic role of BNP in children undergoing surgery for congenital heart disease: analysis of prediction models incorporating standard risk factors. Clin Chem Lab Med. 2015; 53: 1839-1846.\u003c/li\u003e\n\u003cli\u003eQu J, Liang H, Zhou N, Li L, Wang Y, Li J, Cui Y. Perioperative NT-proBNP level: Potential prognostic markers in children undergoing congenital heart disease surgery. J Thorac Cardiovasc Surg. 2017 Aug;154(2):631-640.\u003c/li\u003e\n\u003cli\u003eRudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685\u0026ndash;713\u003c/li\u003e\n\u003cli\u003eMcQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation. 2001 Dec 4;104(23):2797-802. \u003c/li\u003e\n\u003cli\u003eYock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation. 1984; 70: 657\u0026ndash;626;\u003c/li\u003e\n\u003cli\u003eBerger M, Haimowitz A, Van Tosh A, et al. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol. 1985; 6: 359\u0026ndash;365; \u003c/li\u003e\n\u003cli\u003eCurrie PJ, Seward JB, Chan KL, et al. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol. 1985; 6: 750\u0026ndash;756\u003c/li\u003e\n\u003cli\u003eKoestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Fandl A, et al. Tricuspid annular peak systolic velocity (S\u0026apos;) in children and young adults with pulmonary artery hypertension secondary to congenital heart diseases, and in those with repaired tetralogy of Fallot: echocardiography and MRI data. J Am Soc Echocardiogr. 2012 Oct;25(10):1041-9.]\u003c/li\u003e\n\u003cli\u003eWheller J, George B, Mulder DG, Jarmakani JM. Diagnosis and management of postoperative pulmonary hypertensive crisis. Circulation 1979;60:1640\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBando K, Turrentine MW, Sharp TG, Sekine Y, Aufiero TX, Sun K et al. Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management. J Thorac Cardiovasc Surg 1996;112:1600\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eVan Der Feen DE, Bartelds B, De Boer RA, Berger RMF. Assessment of reversibility in pulmonary arterial hypertension and congenital heart disease. Heart. 2019; 105(4): 276\u0026ndash;82\u003c/li\u003e\n\u003cli\u003eMcLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, et al. Treatment goals of pulmonary hypertension. \u003cem\u003eJ Am Coll Cardiol\u003c/em\u003e. 2013;62:D73\u0026ndash;D81\u003c/li\u003e\n\u003cli\u003eCuthbertson BH, Card G, Croal Bl, McNeilly J, Hillis GS. The utility of B-type natriuretic peptide in predicting postoperative cardiac events and mortality in patients undergoing major non-cardiac surgery. Anesthesia 2007;62:875\u0026ndash;881.\u003c/li\u003e\n\u003cli\u003eBergler-Klein J, Klaar U, Heger M, Rosenhek R, Mundigler G, Gabriel H et al. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 2004;109:2302-8\u003c/li\u003e\n\u003cli\u003eEliasdottir SB, Klemenzson G, Torfason B, Valsson F. Brain natriuretic peptide is a good predictor for outcome in cardiac surgery. Acta Anaesthesiol Scand 2008;52:182\u0026ndash;187.\u003c/li\u003e\n\u003cli\u003eJogia PM, Kalkoff M, Sleigh JW, Bertinelli A, La Pine M, Richards AM, Devlin G. NT-pro BNP secretion and clinical endpoints in cardiac surgery intensive care patients. Anaesth Intensive Care 2007;35:363\u0026ndash;369\u003c/li\u003e\n\u003cli\u003eLewis RA, Durrington C, Condliffe R, Kiely DG. BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing? Eur Respir Rev, 2020 May 15;29(156):200009\u003c/li\u003e\n\u003cli\u003eCasserly B, Klinger JR. Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent. Drug Des Devel Ther. 2009 Dec 29;3:269-87\u003c/li\u003e\n\u003cli\u003eKara K, Lehmann N, Neumann T, K\u0026auml;lsch H, M\u0026ouml;hlenkamp S, Dykun I et al. NT-proBNP is superior to BNP for predicting first cardiovascular events in the general population: the Heinz Nixdorf Recall Study. Int J Cardiol 2015; 183: 155\u0026ndash;161.\u003c/li\u003e\n\u003cli\u003eSuleiman MS, Zacharowski K, Angelina GD. Inflammatory response and cardioprotection during open heart surgery; the importance of anaesthetics. Br J Pharm. 2008;153:21-33. 2. \u003c/li\u003e\n\u003cli\u003eLaffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesi- ologist. Anesthesiology. 2002;97:215-252\u003c/li\u003e\n\u003cli\u003eSoares LC, Ribas D, Spring R, Silva JM, Miyague NI. Clinical profle of systemic infammatory response after pediatric cardiac surgery with cardiopulmonary bypass. Arq Bras Cardiol. 2010;94(1):127\u0026ndash;33.\u003c/li\u003e\n\u003cli\u003eYin X, Xin M, Ding S, Gao F, Wu F, Wang J,et al. Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension. BMC Surg. 2021 Jan 4;21(1):3.\u003c/li\u003e\n\u003cli\u003eLei Y, Zhen J, Ming XL, Jian HK. Induction of higher expression of IL-beta and TNF-alpha, lower expression of IL-10 and cyclic guanosine monophosphate by pulmonary arterial hypertension following cardiopulmonary bypass.Asian J Surg. 2002 Jul;25(3):203-8\u003c/li\u003e\n\u003cli\u003eRudiger A, Fischler M, Harpes P, Gasser S, Hornemann T, von Eckardstein A, et al. In critically ill patients, B-type natriuretic peptide (BNP) and N-terminal pro-BNP levels correlate with C-reactive protein values and leukocyte counts. Int J Cardiol. 2008 May 7;126(1):28-31.\u003c/li\u003e\n\u003cli\u003eZhang Y, Luo Y, Nijiatijiang G, Balati K, Tuerdi Y, Liu L. Correlations of Changes in Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) with Levels of C-Reactive Protein (CRP) and TNF-\u0026alpha; in Pediatric Patients with Sepsis. Med Sci Monit. 2019 Apr 8;25:2561-2566. \u003c/li\u003e\n\u003cli\u003eXu YC, Luo CQ, Li X. Systemic inflammatory response syndrome following burns is mediated by brain natriuretic peptide/natriuretic peptide A receptor-induced shock factor 1 signaling pathway. Clin Exp Pharmacol Physiol. 2016 Oct;43(10):921-9.\u003c/li\u003e\n\u003cli\u003eHirai S. Systemic inflammatory response syndrome after cardiac surgery under cardiopulmonary bypass. Ann Thorac Cardiovasc Surg. 2003 Dec;9(6):365-70.\u003c/li\u003e\n\u003cli\u003eNebelsiek T, Beiras-Fernandez A, Kilger E, M\u0026ouml;hnle P, Weis F. Routine use of corticosteroids to prevent inflammation response in cardiac surgery. Recent Pat Cardiovasc Drug Discov. 2012 Dec;7(3):170-4.\u003c/li\u003e\n\u003cli\u003eHolmes JH 4th, Connolly NC, Paull DL, Hill ME, Guyton SW, Ziegler SF, et al. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res. 2002 Dec;51(12):579-86.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"N-terminal pro-B-type natriuretic peptide (NT-proBNP), inflammatory factors, pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), cardiopulmonary bypass","lastPublishedDoi":"10.21203/rs.3.rs-3624458/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3624458/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to evaluate preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) in children with pulmonary arterial hypertension (PAH) secondary to unrestricted left-to-right shunts congenital heart disease (CHD) and sought to investigate the correlation between NT-proBNP and inflammatory factor levels following cardiac surgery with cardiopulmonary bypass (CPB). A retrospective observational study was conducted involving 59 infants or children under 2 years old. Echocardiography was employed to measure tricuspid annular peak systolic velocity (TRV). The plasma of preoperative NT-proBNP and perioperative inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1β, and TNF-α were measured. Additionally, postoperative ventilation time, length of Intensive care unit (ICU) and ward stay were recorded. Longer postoperative ventilation time, ICU stay and ward stay exhibited in PAH-CHD patients, and elevated preoperative NT-proBNP levels were associated with preoperative pulmonary artery systolic pressure (PASP). Moreover, there was a significant increase in postoperative inflammatory cytokines, including IL-6, IL-8 and IL-10 (p＜0.05). Importantly, preoperative NT-proBNP was identified as being associated with inflammatory cytokines levels after surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Preoperative NT-proBNP level was associated with PASP before surgery in children with unrestricted left-to-right shunts PAH-CHD, and elevated preoperative NT-proBNP levels were associated with significantly increased inflammatory factors after CPB, suggesting a potential correlation with early poor postoperative clinical outcomes.\u003c/p\u003e","manuscriptTitle":"Association of preoperative NT-proBNP with postoperative inflammatory factors levels among children of unrestricted left-to-right shunts congenital heart disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-23 09:17:19","doi":"10.21203/rs.3.rs-3624458/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0cfdbf10-ac4c-4136-8fb0-9a8fa6ac00f0","owner":[],"postedDate":"November 23rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-12-10T23:29:19+00:00","versionOfRecord":[],"versionCreatedAt":"2023-11-23 09:17:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3624458","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3624458","identity":"rs-3624458","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}