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The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case–control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity. Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia. [ABSTRACT FROM AUTHOR]

ObjectiveSoluble suppression of tumorigenicity 2 (sST2) is associated with the prognosis of some cardiac diseases, but studies on sST2 and the prognosis of patients with myocarditis are rare. This study investigated the relationship between major adverse cardiovascular events (MACEs) and sST2 during hospitalization in pediatric patients with myocarditis.MethodsThis was a single-center retrospective cohort study. A total of 252 patients aged ≤14 years diagnosed with myocarditis were enrolled. Events during the hospitalization were defined as MACEs (all-cause death > new heart failure > ventricular arrhythmia).ResultsA total of 25 people had MACEs during their hospital stay. The mortality during hospitalization was 6/23 (26%) in patients with heart failure and 3/10 (30%) in patients with ventricular arrhythmias. After including these risk factors in a multivariate logistic regression analysis, NT-proBNP (OR 4.323; 95% CI, 2.433–7.679; p

Zhigan Lv,1,2,&ast; Guohua Liang,3,4,&ast; Mengyu Cheng5,6 1Department of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Anesthesiology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Intensive Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengyu Cheng, Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99, Longcheng Street, Taiyuan, Shanxi, 030032, People’s Republic of China, Tel +8613994237390, Email cmyy1979@163.comObjective: To confirm whether growth differentiation factor-15 (GDF-15) and soluble suppression of tumorigenicity 2 (sST2) are indicators of pulmonary hypertension in acute exacerbation of chronic obstructive pulmonary disease (AECOPD-PH).Methods: All patients admitted to the hospital with AECOPD between July 2020 and October 2021 were enrolled. The patients were then categorized into AECOPD and AECOPD-PH groups according to PH probability, and the differences in GDF-15 and sST2 serum levels in the AECOPD and AECOPD-PH groups were compared. Correlation analysis was carried out to explore the association between GDF-15 and sST2 serum levels and the length of hospital stay of patients with AECOPD-PH. Receiver operating characteristic curve analysis was used to assess the clinical significance of GDF-15 and sST2 in predicting patients with AECOPD-PH.Results: Included in this study were 126 patients with AECOPD, including 69 with AECOPD and 57 with AECOPD-PH. The serum levels of GDF-15 and sST2 in the AECOPD-PH group were significantly higher than those in the AECOPD group (P < 0.05). There was no significant correlation between the length of hospital stay in AECOPD-PH patients and GDF-15 and sST2 serum levels (P > 0.05). The area under the curves of GDF-15, sST2, and GDF-15 + sST2 for predicting AECOPD-PH and AECOPD-PH patients with poor prognosis were > 0.60 and 0.70, respectively. The optimal cutoff values of GDF-15 and sST2 for predicting AECOPD-PH were 1125.33 pg/mL and 80.68 ng/mL and 1309.72 pg/mL and 59.10 ng/mL for predicting AECOPD-PH patients with poor prognosis, respectively.Conclusion: GDF-15 and sST2 levels may be useful in the prediction of AECOPD-PH.Keywords: acute exacerbation of chronic obstructive pulmonary disease, pulmonary hypertension, soluble suppression of tumorigenicity 2, growth differentiation factor-15

Abstract Long‐term, intense endurance exercise training can occasionally induce endothelial micro‐damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well‐trained male participants (10 runners and 10 cyclists) performed a strenuous high‐intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal‐3 and sST2 concentrations were investigated by enzyme‐linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal‐3 and sST2 concentrations and ECs were elevated after exercise (P

PurposeAtrial fibrosis is the main pathological basis for the pathogenesis and progression of atrial fibrillation (AF). Soluble suppression of tumorigenicity 2 (sST2) is involved in fibrosis. Recent studies have explored its predictive value in AF outcomes. We performed this study to assess whether sST2 is an independent biomarker of AF outcomes and explore the potential mechanism.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library databases were searched systematically from inception through July 1, 2023, to identify relevant studies. Outcomes of interest included occurrence, recurrence, and major adverse cardiac events (MACEs) of AF. This meta-analysis was reported following the criteria outlined in PRISMA 2020, and the protocol was registered in PROSPERO (number: CRD42023459789). All statistical analyses were performed using the STATA version 16.ResultTwenty four studies with 14,755 patients were included in the meta-analysis. The meta-analyses found that sST2 was significantly associated with the risk of occurrence [HR:1.04, 95% CI: 1.02–1.07, P

Long‐term, intense endurance exercise training can occasionally induce endothelial micro‐damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well‐trained male participants (10 runners and 10 cyclists) performed a strenuous high‐intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal‐3 and sST2 concentrations were investigated by enzyme‐linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal‐3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal‐3 and sST2 concentrations both showed a positive relationship with ECs (rrm = 0.68, P = 0.001 and rrm = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal‐3 was significant only in cyclists, but equally strong for both modalities. Gal‐3 was also related to exercise‐induced CTi (rrm = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise‐released Gal‐3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise‐induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long‐term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. New Findings: What is the central question of this study?Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear.What is the main finding and its importance?We show that galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal‐3 is an enhanced cardiac contractility. Acute exercise‐released Gal‐3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations. [ABSTRACT FROM AUTHOR]

Background: The soluble suppression of tumorigenicity 2 (sST2) is closely associated with stroke and atrial fibrillation (AF). However, no studies on sST2 and AF detected after stroke (AFDAS) have been reported. This study investigated the correlation between sST2 and AFDAS. Methods: This was a single-center, retrospective, clinical observational study. Patients diagnosed with a transient ischemic attack (TIA) or acute ischemic stroke were enrolled, and all patients underwent sST2 detection and electrocardiogram (ECG) or Holter monitoring for at least 24 h. Results: In total, 970 patients were enrolled, including 72 (7.4 %) with AFDAS. Multivariate analysis showed that age (OR 1.078; 95 % CI, 1.050–1.107; p

Purpose: Major cardiovascular events (MACE) are the leading cause of mortality in patients with chronic kidney disease. Although hemodialysis (HD) and peritoneal dialysis (PD) are comparable in survival, patients with HD have a significantly higher risk of developing MACE. Soluble suppression of tumorigenicity 2 (sST2) is a cardiac biomarker, that does not vary with age, gender, and kidney function. This study aimed to compare arterial stiffness, fluid status, and sST2 levels, between patients with PD and those with in-center HD. Methods: This was a cross-sectional study, which was conducted with 36 PD patients, 36 HD patients, and 36 age, and gender-matched healthy controls. We used noninvasive methods for the assessment of arterial stiffness and fluid status. Results: The patients with PD overhydrated compared to HD patients and healthy control (p < 0.001, and p = 0.05, respectively). Patients with PD had higher central systolic blood pressure and central pulse pressure than patients with HD and the control group (p = 0.004, and p = 0.01; p < 0.001, and p = 0.004, respectively). HD patients had a significantly higher level of plasma sST2 level compared to PD patients and the control group (p = 0.03, and p = 0.005). HD as maintenance dialysis modality and dialysis vintage was associated with higher plasma sST2 concentration, and having a residual renal function in dialysis patients was related to the lower plasma sST2 concentration. Conclusion: PD is associated with better sST2 levels even though higher volume load than HD. In addition, the loss of RRF may be the most important factor related to increased sST2. [ABSTRACT FROM AUTHOR]

Background: Elevated soluble suppression of tumorigenicity 2 (sST2) levels may predict mortality in heart failure (HF) patients. The AFIAS ST2 assay (AFIAS ST2, Boditech Med Inc., Chuncheon, Korea) and ichroma ST2 assay (ichroma ST2, Boditech Med Inc.) are newly developed point-of-care (POC) assays for measuring sST2 level. We evaluated the performance of these assays, in terms of cut-off validation and prognosis, and compared them with that of the Presage ST2 assay (Presage ST2, Critical Diagnostics, San Diego, CA, USA). Methods: We validated the US FDA-claimed sST2 clinical cut-off of 35 ng/mL using 420 serum samples (298 samples from the universal sample bank of the American Association for Clinical Chemistry and 122 samples from reference individuals from Konkuk University Medical Center). We compared AFIAS ST2 and ichroma ST2 with Presage ST2, using 206 samples from patients with HF. We assessed prognosis using the three assays in 252 samples from the Barcelona ambulatory HF cohort subsets. Results: The upper reference limits of AFIAS ST2 and ichroma ST2 were within the clinical cut-off of Presage ST2. The results of AFIAS ST2 and ichroma ST2 were highly correlated with those of Presage ST2 (r = 0.82 and 0.81, respectively). Based on this cut-off, all three assays predicted cardiovascular death. Conclusions: The new POC assays, AFIAS ST2 and ichroma ST2, would be useful in clinical practice for managing HF patients, with performances equivalent to that of Presage ST2. [ABSTRACT FROM AUTHOR]

Background: The combination of acute myocardial infarction (AMI) and atrial fibrillation (AF) is still a thorny problem in the clinic. At present, there are few reports on the role of soluble suppression of tumorigenicity 2 (sST2) in AF after AMI. This study was to explore the predictive value of sST2 in patients with AMI for new-onset AF. Methods: This is a single-center retrospective clinical observation study. We continuously included AMI patients from September 2019 to November 2021. The concentration of sST2 in blood samples was determined. During admission, a suspicious heart rhythm was recorded by electrocardiogram (ECG) monitoring, and new-onset AF was confirmed by immediate body surface ECG. Results: After multiple factors were included, age, right coronary artery, high-sensitivity C-reactive protein, left ventricular ejection fraction, and sST2 were still risk factors for new-onset AF. The area under curve value of age and sST2 was more than 0.7, which showed good diagnostic value. For reevaluation, the sST2 was added to the clinical new-onset AF prediction model. It was found that the integrated discrimination improvement and net reclassification index in the model were improved significantly. Conclusion: sST2 is an independent predictor of new-onset AF in patients with AMI and can improve the accuracy of the AF risk model. [ABSTRACT FROM AUTHOR]

We investigated whether there were associations between coronary artery disease (CAD) and soluble suppression of tumorigenicity (sST2) and galectin-3 levels at the time of coronary artery computed tomography angiography (CCTA) for CAD screening. The subjects consisted of 429 patients who underwent CCTA examination. CAD was diagnosed when there was 50% or more stenosis in the coronary artery. Patient backgrounds were collected and plasma levels of sST2 and galectin-3 were measured. The presence or absence of CAD and factors that contributed to CAD were analyzed for all patients and for those with or without hypertension (HTN). The CAD group had significantly higher sST2 levels than the non-CAD group, whereas there was no significant difference in galectin-3 levels. The number of patients in the non-HTN and HTN groups was 174 and 255, respectively. In the HTN group, the CAD group was significantly older than the non-CAD group and had higher sST2 levels. Multivariate analysis showed that the factors that contributed to CAD in the HTN group were age and sST2 levels. On the other hand, in the non-HTN group, the CAD group was significantly older than the non-CAD group, and had a higher proportion of males and higher sST2 levels, while the contributing factors for the CAD group were age and male gender, but not sST2. In conclusion, a higher level of sST2, but not galectin-3, was a contributing factor for CAD in HTN patients. However, in non-HTN patients, a high level of sST2 was not a contributing factor for CAD., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is a growing public health burden, with mortality and rehospitalization rates comparable to HF with reduced ejection fraction (HFrEF). The evidence for the clinical usefulness of soluble suppression of tumorigenicity 2 (sST2) in HFpEF is contradictory. Therefore, we conducted the following systematic review and meta-analysis to assess the diagnostic and prognostic value of serum sST2 in HFpEF.MethodsPubMed and Scopus were searched exhaustively from their inception until March 15, 2022. In diagnostic analysis, we compared the diagnostic value of serum sST2 in HFpEF to NT pro-BNP. We separately pooled the unadjusted and multivariate-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) in prognostic analysis.ResultsA total of 16 publications from 2008 to 2021 were examined. The results of this analysis were as follow: Firstly, compared with NT pro-BNP, sST2 obtains poor diagnostic performance in independently identifying HFpEF from healthy controls, hypertensive patients, and HFrEF patient. Nevertheless, it may provide incremental value to other biomarkers for diagnosing HFpEF and deserves further investigation. Secondly, log sST2 was independently associated with adverse endpoints on multivariable analysis after adjusting for variables such as age, sex, race, and NYHA class. Per log unit rise in sST2, there was a 2.76-fold increased risk of all-cause death [HR:2.76; 95% CI (1.24, 6.16); p = 0.516, I2 = 0%; P = 0.013] and a 6.52-fold increased risk in the composite endpoint of all-cause death and HF hospitalization [HR:6.52; 95% CI (2.34, 18.19); p = 0.985, I2 = 0%; P = 0.000]. Finally, the optimal threshold levels of serum sST2 need further determined.ConclusionsHigher sST2 was strongly linked to an increased risk of adverse outcomes in HFpEE. Especially, log sST2 independently predicted all-cause death and the composite endpoint of all-cause death and HF hospitalization. However, prospective and multicenter studies with large-sample and extended follow-up periods are required to validate our results due to limitations in our research.

Abstract Background Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction. Methods This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model. Results Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan–Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (

Resistin and soluble suppression of tumorigenicity 2 (sST2) are useful predictors in patients with coronary artery disease (CAD). Their serum levels are significantly attributed to variations in RETN and IL1RL1 loci. We investigated candidate variants in the RETN locus for resistin levels and those in the IL1RL1 locus for sST2 levels and evaluated the prognostication of these two biomarkers and the corresponding variants for long-term outcomes in the patients with CAD. We included 4652, 557, and 512 Chinese participants from the Taiwan Biobank (TWB), cardiovascular health examination (CH), and CAD cohorts, respectively. Candidate variants in RETN and IL1RL1 were investigated using whole-genome sequence (WGS) and genome-wide association study (GWAS) data in the TWB cohort. The weighted genetic risk scores (WGRS) of RETN and IL1RL1 with resistin and sST2 levels were calculated. Kaplan–Meier curves were used to analyze the prognostication of resistin and sST2 levels, WGRS of RETN and IL1RL1, and their combinations. Three RETN variants (rs3219175, rs370006313, and rs3745368) and two IL1RL1 variants (rs10183388 and rs4142132) were independently associated with resistin and sST2 levels as per the WGS and GWAS data in the TWB cohort and were further validated in the CH and CAD cohorts. In combination, these variants explained 53.7% and 28.0% of the variation in resistin and sST2 levels, respectively. In the CAD cohort, higher resistin and sST2 levels predicted higher rates of all-cause mortality and major adverse cardiac events (MACEs) during long-term follow-up, but WGRS of RETN and IL1RL1 variants had no impact on these outcomes. A synergistic effect of certain combinations of biomarkers with RETN and IL1RL1 variants was found on the prognostication of long-term outcomes: Patients with high resistin levels/low RETN WGRS and those with high sST2 levels/low IL1RL1 WGRS had significantly higher all-cause mortality and MACEs rates, and those with both these combinations had the poorest outcomes. Both higher resistin and sST2 levels, but not RETN and IL1RL1 variants, predict poor long-term outcomes in patients with CAD. Furthermore, combining resistin and sST2 levels with the WGRS of RETN and IL1RL1 genotyping exerts a synergistic effect on the prognostication of CAD outcomes. Future studies including a large sample size of participants with different ethnic populations are needed to verify this finding. [ABSTRACT FROM AUTHOR]

Background Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients. Methods A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version. Results 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP. Conclusions Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP.

Objectives: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes. Methods: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality. Results: A total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta-analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I2: 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99–1.27, P = 0.07; I2: 88%). In chronic heart failure, sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27–2.12, P

Background: Inflammation is one of the principal triggering mechanisms for left ventricular fibrosis and remodeling in heart failure, leading to adverse clinical outcomes. Soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the fibrotic response to inflammation. Left ventricular mass index (LVMI) is a parameter of the prefibrotic inflammatory phase of heart failure preceding remodeling. The present study aimed to investigate the prognostic value of the sST2/LVMI ratio in heart failure with reduced ejection fraction.Methods: This was a prospective cohort study. A total of 45 consecutive patients with heart failure with reduced ejection fraction, treated between September 2015 and December 2016, were enrolled. The sST2/LVMI ratio was measured at baseline. The primary endpoint was a composite of cardiovascular mortality and readmission for heart failure. The prognostic impact of the sST2/LVMI ratio was evaluated using a multivariable Cox proportional hazards regression model.Results: Forty-five patients were enrolled in this study. Their average age was 48 ± 14 years, and approximately 20% of them were men. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. Kaplan-Meier analysis showed that patients with a high sST2/LVMI ratio (≥ 0.39) had shorter event-free survival than those with intermediate (between 0.39 and 0.24) and low ratios (< 0.24) (log-rank, P = 0.022). The fully adjusted multivariable Cox regression analysis showed that the sST2/LVMI ratio was positively associated with the composite outcome in patients with heart failure with reduced ejection fraction after adjusting for confounders (hazard ratio 1.64, 95% confidence interval 1.06 to 2.54). By subgroup analysis, a stronger association was found with age between 40 and 55 years, systolic blood pressure < 115 or ≥ 129 mmHg, diastolic blood pressure < 74 mmHg, hematocrit < 44.5%, and interventricular septum thickness ≥ 8.5 mm.Conclusion: In patients with heart failure with reduced ejection fraction, the relationship between the sST2/LVMI ratio and the composite outcome was linear. A higher baseline ratio of sST2/LVMI was associated with an increased risk of cardiovascular mortality and heart failure rehospitalization in the short-term follow-up. [ABSTRACT FROM AUTHOR]

Background and purpose: Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD. Methods: A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24‐item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2. Results: Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10–3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category‐free NRI = 19.34%, 95% confidence interval = 4.39%–34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%–2.15%, p = 0.014). Conclusions: Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors. [ABSTRACT FROM AUTHOR]

Resistin and soluble suppression of tumorigenicity 2 (sST2) are useful predictors in patients with coronary artery disease (CAD). Their serum levels are significantly attributed to variations in RETN and IL1RL1 loci. We investigated candidate variants in the RETN locus for resistin levels and those in the IL1RL1 locus for sST2 levels and evaluated the prognostication of these two biomarkers and the corresponding variants for long-term outcomes in the patients with CAD. We included 4652, 557, and 512 Chinese participants from the Taiwan Biobank (TWB), cardiovascular health examination (CH), and CAD cohorts, respectively. Candidate variants in RETN and IL1RL1 were investigated using whole-genome sequence (WGS) and genome-wide association study (GWAS) data in the TWB cohort. The weighted genetic risk scores (WGRS) of RETN and IL1RL1 with resistin and sST2 levels were calculated. Kaplan–Meier curves were used to analyze the prognostication of resistin and sST2 levels, WGRS of RETN and IL1RL1, and their combinations. Three RETN variants (rs3219175, rs370006313, and rs3745368) and two IL1RL1 variants (rs10183388 and rs4142132) were independently associated with resistin and sST2 levels as per the WGS and GWAS data in the TWB cohort and were further validated in the CH and CAD cohorts. In combination, these variants explained 53.7% and 28.0% of the variation in resistin and sST2 levels, respectively. In the CAD cohort, higher resistin and sST2 levels predicted higher rates of all-cause mortality and major adverse cardiac events (MACEs) during long-term follow-up, but WGRS of RETN and IL1RL1 variants had no impact on these outcomes. A synergistic effect of certain combinations of biomarkers with RETN and IL1RL1 variants was found on the prognostication of long-term outcomes: Patients with high resistin levels/low RETN WGRS and those with high sST2 levels/low IL1RL1 WGRS had significantly higher all-cause mortality and MACEs rates, and those with both these combinations had the poorest outcomes. Both higher resistin and sST2 levels, but not RETN and IL1RL1 variants, predict poor long-term outcomes in patients with CAD. Furthermore, combining resistin and sST2 levels with the WGRS of RETN and IL1RL1 genotyping exerts a synergistic effect on the prognostication of CAD outcomes. Future studies including a large sample size of participants with different ethnic populations are needed to verify this finding.

Objective: Soluble suppression of tumorigenicity 2 (sST2) is associated with the prognosis of some cardiac diseases, but studies on sST2 and the prognosis of patients with myocarditis are rare. This study investigated the relationship between major adverse cardiovascular events (MACEs) and sST2 during hospitalization in pediatric patients with myocarditis., Methods: This was a single-center retrospective cohort study. A total of 252 patients aged ≤14 years diagnosed with myocarditis were enrolled. Events during the hospitalization were defined as MACEs (all-cause death > new heart failure > ventricular arrhythmia)., Results: A total of 25 people had MACEs during their hospital stay. The mortality during hospitalization was 6/23 (26%) in patients with heart failure and 3/10 (30%) in patients with ventricular arrhythmias. After including these risk factors in a multivariate logistic regression analysis, NT-proBNP (OR 4.323; 95% CI, 2.433-7.679; p  < 0.001) and sST2 (OR 1.020; 95% CI, 1.003-1.037; p  = 0.022) remained statistically significant and were independent risk factors for MACEs during hospitalization in pediatric myocarditis patients., Conclusions: Elevated levels of NT-proBNP and sST2 were independently associated with major adverse cardiovascular events during hospitalization in children with myocarditis, and both showed good predictive efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Shi, Ge, Li and Zhang.)

Both soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are promising biomarkers associated with the adverse clinical outcomes of dialysis patients. Our research aims at exploring and comparing the roles of sST2 and NT-proBNP in predicting the short-term and long-term mortality of maintenance hemodialysis (MHD) patients. A prospective cohort study was performed. Patients undergoing hemodialysis in July 2014 were enrolled from the Blood Purification Center of Ruijin Hospital. MHD patients were followed up for 3 years. The primary outcome was all-cause mortality at the 1-year and 3-year follow-up, while the secondary outcome was cardiovascular mortality. Serum sST2 level was detected by quantified ELISA kits. Clinical data were analyzed by SPSS 23.0 version. 205 patients were recruited. The median sST2 level was 15.99 (11.60, 20.49) ng/ml. After 3 years of follow-up, both all-cause and cardiovascular mortality in 1 year and all-cause and cardiovascular mortality in 3 years increased significantly with serum sST2. For short-term mortality, no significant difference was observed in patients with increasing NT-proBNP levels. Cox regression analysis indicated that only sST2 was independent in predicting the risk of short-term outcomes. For long-term mortality, both sST2 and NT-proBNP were independent risk factors, while a higher hazard ratio was observed for NT-proBNP. Serum sST2 is a novel biomarker associated with adverse clinical outcomes in MHD patients. It was significant for both all-cause and cardiovascular mortality in MHD patients and may provide better prognostic value in short-term prognosis than the classic biomarker NT-proBNP. [ABSTRACT FROM AUTHOR]

Purpose: Cardiovascular disease can be detected in individuals with prediabetes. The purpose of this study was to determine whether soluble suppression of tumorigenicity 2 (sST2), which is elevated in cardiovascular disease and/or type 2 diabetes, is correlated with glycated haemoglobin in individuals with glycemia in the normal/prediabetes range. Patients and Methods: The anthropometric, biochemical and metabolic parameters were measured in 30 adults, and the plasma levels of sST2 were quantified. Results: sST2 was directly correlated with glycated hemoglobin in individuals with glycemia in the normal/prediabetes range. Participants who were at the higher end of glycated hemoglobin (5.8– 6.4%) had significantly higher sST2 compared to those at the lower end (≤ 5.5%). Moreover, sST2 was directly correlated with homeostatic model assessment of insulin resistance (HOMA-IR), alkaline phosphatase, and waist circumference. However, the correlation between sST2 and HOMA-IR or waist circumference was lost after adjusting for age, gender or body mass index. Conclusion: Circulating sST2 may be used to establish a cut-off value for cardiometabolic risk/disease in individuals with glycemia in the normal/prediabetes range. [ABSTRACT FROM AUTHOR]

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Type B aortic dissection (TBAD) and intramural aortic hematoma (IMH) are common manifestations of Acute Aortic Syndrome (AAS), exhibiting overlapping clinical features. The timely and accurate diagnosis and differentiation between TBAD and IMH are critical for appropriate management. Tumorigenicity 2 (sST2) and D-dimer have been shown to elevate levels in both TBAD and IMH, making them valuable as "rule-out" markers. Hence, we aimed to assess the diagnostic utility of sST2 and D-dimer in distinguishing TBAD from IMH. In this retrospective study, we analyzed serum levels of sST2 and D-dimer in 182 AAS patients, comprising 90 TBAD cases, 92 IMH cases, and 90 non-AAS cases. Serial measurements were taken at 1 h, 6 h, 12 h, 24 h, and 72 h post-admission. Comparative analyses were conducted between TBAD and non-AAS cases, IMH and non-AAS cases, and TBAD and IMH cases. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of sST2 and D-dimer in identifying TBAD or IMH cases. Both TBAD and IMH patients displayed elevated levels of sST2 and D-dimer compared to non-AAS cases. Notably, sST2 levels were significantly higher in TBAD patients than in IMH patients, whereas D-dimer levels exhibited moderate differences. TBAD patients tended to exhibit elevated levels of either sST2 or D-dimer, with a modest correlation between the two (Pearson correlation coefficient = 0.3614). In contrast, IMH patients showed elevations in both markers, with a positive correlation between them (Pearson correlation coefficient = 0.6814). The ROC analysis revealed that both sST2 (AUC, 0.657; 95 % CI, 0.552–0.753; cutoff value, 27.54 ng/ml) and D-dimer (AUC, 0.695; 95 % CI, 0.591–0.787, cutoff value, 1.215 ng/ml) demonstrated favorable diagnostic performance for TBAD. sST2 exhibited a sensitivity of 80.92 % and a specificity of 75.00 %, while D-dimer showed a sensitivity of 80.92 % and a specificity of 75.00 %. For the diagnosis of IMH, the combined assessment of sST2 and D-dimer (AUC, 0.674; 95 % CI, 0.599–0.768; sensitivity, 69.20 %; specificity, 80.00 %) proved effective. Our results indicate that both sST2 and D-dimer show diagnostic potential for TBAD. Elevated levels of either serve as an indicator of TBAD onset. However, concurrent elevation of both markers seems to be indicative of IMH. The combination of increased sST2 and D-dimer levels demonstrates strong diagnostic performance in identifying IMH cases. • Diagnostic potential of sST2 and D-dimer • Biomarker accuracy in TBAD and IMH • Clinical implications for AAS management • Distinct biomarker patterns in TBAD and IMH • The key role of sST2 and D-dimer in AAS [ABSTRACT FROM AUTHOR]

Purpose: Atrial fibrosis is the main pathological basis for the pathogenesis and progression of atrial fibrillation (AF). Soluble suppression of tumorigenicity 2 (sST2) is involved in fibrosis. Recent studies have explored its predictive value in AF outcomes. We performed this study to assess whether sST2 is an independent biomarker of AF outcomes and explore the potential mechanism., Methods: PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched systematically from inception through July 1, 2023, to identify relevant studies. Outcomes of interest included occurrence, recurrence, and major adverse cardiac events (MACEs) of AF. This meta-analysis was reported following the criteria outlined in PRISMA 2020, and the protocol was registered in PROSPERO (number: CRD42023459789). All statistical analyses were performed using the STATA version 16., Result: Twenty four studies with 14,755 patients were included in the meta-analysis. The meta-analyses found that sST2 was significantly associated with the risk of occurrence [HR:1.04, 95% CI: 1.02-1.07, P  < 0.01; I 2  = 67.8%], recurrence [HR:1.09, 95% CI: 1.02-1.16, P  < 0.01; I 2  = 89.5%], and MACEs (HR:1.60, 95% CI: 1.13-2.27, P  < 0.01; I 2  = 82.0%) of AF. Furthermore, patients with AF showed higher sST2 than controls without AF (SMD: 0.41, 95% CI: 0.27-0.54, P  < 0.01; I 2   = 0%), and AF patients with recurrence after catheter ablation (CA) showed significantly higher sST2 than those without recurrence (SMD: 0.81, 95% CI: 0.33-1.28, P  < 0.01; I 2  = 83.9%). Sensitivity analyses showed that the outcomes were stable., Conclusions: Higher sST2 was association with an increased risk of occurrence, recurrence, and MACEs of AF. Assessing sST2 can be used as a potential screening method to predict AF outcomes., Systematic Review Registration: PROSPERO (CRD42023459789)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chen, Zhang, Du, Shi and Zhang.)

Objective: To investigate the changes and clinical significance of serum levels of Soluble human matrix lysin 2(sST2), Interleukin -6 (IL-6) and peptide in patients with chronic heart failure(CHF). Methods: 122 cases of CHF patients who were admitted in our hospital fromJanuary 2017 to January 2018 were included in CHF group. According to the New York Heart Association (NYHA),the patients were divided into II group with 34 cases, III group with 48 cases and IV group with 40 cases. Another 35 non arrhythmic patients hospitalized in the same period were selected as control group in the same period. The serum levels of sST2, peptide and IL-6 were detected and compared between the CHF group and the control group. The serumsST2, peptide and IL-6 levels in CHF patients with different NYHA heart function classification were compared, the correlation between serum sST2, IL-6 and peptide were analyzed by Pearson correlation analysis. Results: The serum levels of sST2, peptide and IL-6 in CHF group were higher than those in control group (P<0.05). There were significant differences in serum sST2, peptide and IL-6 levels in CHF patients with different NYHA cardiac function grades (P<0.05). The serum levels of sST2, peptide and IL-6 in the IV group and III group were higher than those in the II group, and the IV group was higher than that of the III group, the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serumsST2 and IL-6 levels were positively correlated with peptide(P<0.05). Conclusion: The levels of serumsST2, peptide and IL-6 is closely related to the severity of CHF. It can be used as biological indexes for clinical diagnosis of CHF. [ABSTRACT FROM AUTHOR]

Background: The soluble suppression of tumorigenicity 2 (sST2) is closely associated with stroke and atrial fibrillation (AF). However, no studies on sST2 and AF detected after stroke (AFDAS) have been reported. This study investigated the correlation between sST2 and AFDAS., Methods: This was a single-center, retrospective, clinical observational study. Patients diagnosed with a transient ischemic attack (TIA) or acute ischemic stroke were enrolled, and all patients underwent sST2 detection and electrocardiogram (ECG) or Holter monitoring for at least 24 h., Results: In total, 970 patients were enrolled, including 72 (7.4 %) with AFDAS. Multivariate analysis showed that age (OR 1.078; 95 % CI, 1.050-1.107; p < 0.001), heart rate (HR) (OR 1.025; 95 % CI, 1.007-1.044; p = 0.007), national institutes of health stroke scale (NIHSS) score (OR 1.089; 95 % CI, 1.029-1.152; p = 0.003), high sensitivity C-reactive protein (hs-CRP) (OR 1.006; 95 % CI, 1.002-1.009; p = 0.001), and sST2 (OR 1.018; 95 % CI, 1.010-1.026; p < 0.001) were independent risk factors of AFDAS. The areas under the curve (AUCs) for age, HR, sST2, hs-CRP, and NIHSS were 0.731, 0.599, 0.815, 0.664, and 0.700, respectively. The conventional model included age, HR, NIHSS score, and hs-CRP level based on multivariate results. After adding sST2 to the model, the model's performance in predicting AFDAS increased significantly., Conclusion: Higher sST2 levels were associated with the occurrence of AFDAS. Thus, sST2 can improve the risk model for AFDAS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

New-onset post-transplantation diabetes mellitus (PTDM) occurs commonly after allogeneic hematopoietic cell transplantation (HCT) and is associated with inferior survival. We hypothesize that PTDM and nonrelapse mortality (NRM) are related to IL-33/suppression of tumorigenicity 2 (ST2) signaling and that soluble ST2 (sST2) levels will predict PTDM diagnosis. sST2 was measured at engraftment and day +30 in 36 euglycemic HCT recipients followed prospectively for PTDM (cohort 1). Results were confirmed in a validation cohort of 26 patients without pre-existing diabetes analyzed retrospectively for PTDM (cohort 2). Twelve patients with established diabetes before HCT were analyzed in cohort 3. When compared with recipients without PTDM, patients developing PTDM (n = 24) from cohort 1 had elevated sST2 levels at engraftment ( P  = .02) and at day +30 ( P  < .01). Cohort 2 confirmed this finding at engraftment ( P  = .01). Cohort 3 patients with pretransplantation diabetes had higher sST2 at engraftment than patients maintaining euglycemia after HCT from cohort 2 ( P  = .03). Multivariate analysis of cohorts 1 and 2 showed high engraftment sST2 predicted increased PTDM and NRM risk, independent of conditioning and grades 3 to 4 acute graft-versus-host-disease. sST2 was elevated in PTDM, indicating a relationship between glucose homeostasis and the IL-33/ST2 axis after transplantation. Correction of metabolic complications may decrease sST2 and improve NRM. [ABSTRACT FROM AUTHOR]

Background: Elevated soluble suppression of tumorigenicity 2 (sST2) levels may predict mortality in heart failure (HF) patients. The AFIAS ST2 assay (AFIAS ST2, Boditech Med Inc., Chuncheon, Korea) and ichroma ST2 assay (ichroma ST2, Boditech Med Inc.) are newly developed point-of-care (POC) assays for measuring sST2 level. We evaluated the performance of these assays, in terms of cut-off validation and prognosis, and compared them with that of the Presage ST2 assay (Presage ST2, Critical Diagnostics, San Diego, CA, USA)., Methods: We validated the US FDA-claimed sST2 clinical cut-off of 35 ng/mL using 420 serum samples (298 samples from the universal sample bank of the American Association for Clinical Chemistry and 122 samples from reference individuals from Konkuk University Medical Center). We compared AFIAS ST2 and ichroma ST2 with Presage ST2, using 206 samples from patients with HF. We assessed prognosis using the three assays in 252 samples from the Barcelona ambulatory HF cohort subsets., Results: The upper reference limits of AFIAS ST2 and ichroma ST2 were within the clinical cut-off of Presage ST2. The results of AFIAS ST2 and ichroma ST2 were highly correlated with those of Presage ST2 (r = 0.82 and 0.81, respectively). Based on this cut-off, all three assays predicted cardiovascular death., Conclusions: The new POC assays, AFIAS ST2 and ichroma ST2, would be useful in clinical practice for managing HF patients, with performances equivalent to that of Presage ST2., Competing Interests: The authors declare no conflict of interest. The Boditech Med’s support did not affect the results and conclusions of this study., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: Soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NTproBNP), high sensitive troponin I (hs-TnI), and high sensitive troponin T (hs-TnT) are representative cardiac biomarkers. The reference intervals (RIs) of these biomarkers have been rarely investigated in umbilical cord blood (UCB). We explored the distribution of these cardiac markers and established their RIs in UCB. Methods: In a total of 293 UCB specimens, sST2, NT- proBNP, hs-TnI, and hs-TnT concentrations were analyzed according to the gestational age, presence of premature membrane rupture (PROM), presence of gestational diabetes mellitus (GDM), and Apgar score at 1 min. Their RIs were defined in 133 UCB specimens from healthy, fullterm neonates, using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guideline (EP28-A3C). Results: The concentrations of four cardiac markers in UCB were different between full-term neonates and preterm neonates. The concentrations of NT-proBNP and hs-TnI differed according to the presence or absence of PROM. Their concentrations did not differ regardless of the presence of GDM. The concentrations of sST2 and NT- proBNP differed according to the Apgar score at 1 min. The 97.5th percentile upper reference limits were: sST2, 59.9 ng/mL; NT pro-BNP, 1415.3 pg/mL; hs-TnI, 27.8 pg/mL; and hs-TnT, 86.5 pg/mL. Conclusions: The distribution of sST2, NT pro-BNP, hs- TnI, and hs-TnT in UCB together with their RIs would provide fundamental data for future researches and clinical practice. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is prevalent in patients with chronic kidney disease (CKD) and it is responsible for approximately half of all CKD-related deaths. CVDs are the primary cause of death in hemodialysis patients due to major adverse cardiovascular events. Therefore, better approaches for differentiating chronic hemodialysis patients at higher cardiovascular risk will help physicians improve clinical outcomes. Hence, there is an urgent need to discover feasible and reliable cardiac biomarkers to improve diagnostic accuracy, reflect myocardial injury, and identify high-risk patients. Numerous biomarkers that have significant prognostic value with respect to adverse CVD outcomes in the setting of mild to severe CKD have been identified. Therefore, a better understanding of the positive clinical impact of cardiac biomarkers on CVD patient outcomes is an important step toward prevention and improving treatment in the future. In this review, we address the relationship between cardiovascular biomarkers and CKD treatment strategies to elucidate the underlying importance of these biomarkers to patient outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Background: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant., Aims: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM., Methods: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA., Results: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001)., Conclusions: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

Background: Soluble suppression of tumorigenicity 2 (ST2) is closely related to the development of cardiovascular disease, but the level of acute coronary syndrome (ACS) and the relationship between ST2 and ACS are unclear., Patients and Methods: Patients with the acute coronary syndrome were divided into the unstable angina pectoris (USAP) group (n = 65) and non-ST-segment elevation myocardial infarction (NSTEMI) group (n = 58), and the healthy population, without chest pain and with normal coronary CT, was included as a control group (n = 55). Laboratory index levels were collected from each participant. The baseline information was reviewed and analyzed. The binary logistic regression was used to explore the relation of ST2 levels with the occurrence of ACS and NSTEMI, and the diagnostic performance of ST2 for diagnosing ACS or NSTEMI was evaluated using a receiver-operating characteristic (ROC) curve., Results: The level of ST2 was found significantly higher in NSTEMI than in USAP and was higher in USAP than in control (p < 0.01). ST2 levels were positively correlated with ALT, AST, and BNP in the control group, were negatively correlated with HGB and TG in the USAP group, and were positively correlated with WBC, GLU, BNP, and Gensini scores in the NSTEMI group. Multivariate analysis revealed that the occurrence of ACS was associated with ST2, BNP, GLU, TC, BUN, WBC, and PLT, and the occurrence of NSTEMI was associated with AST, WBC, LDL-C, and ST2. Meanwhile, ST2 levels achieved good performance for ACS and NSTEMI diagnostician., Conclusion: ST2 could be used as an auxiliary diagnostic indicator for the occurrence of ACS and NSTEMI., (© 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD)., Objectives: To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD., Design: A prospective, observational cohort study with serial blood biomarker measurements., Settings: Single-center study in the inpatient setting with outpatient follow-up., Participants: Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020., Exposure: We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points., Measures: Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge ( Δ Hospitalization ) and between discharge and 1st clinical follow-up visit ( Δ Post - discharge ). Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF., Results: A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 kg [IQR -5.1, -1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p = 0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n = 8, vs. n = 16 who did not experience the outcome; Δ Post-discharge hsCRP +5.1 vs. -1.0 mg/l, p = 0.061; NT-proBNP +785.0 vs. +130.0 pg/ml, p = 0.220)., Conclusions: Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD.

Objectives: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta -analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes., Methods: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality., Results: A total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta -analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I 2 : 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99-1.27, P = 0.07; I 2 : 88%). In chronic heart failure , sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I 2 : 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27-2.12, P < 0.001; I 2 : 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 ± 0.46 ng/ml; P = 0.001; I 2 : 98%). Finally, in stable coronary artery disease, sST2 levels were higher in non-survivors than survivors (MD: 3.0 ± 1.1 ng/ml; P = 0.005; I 2 : 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04-1.68, P < 0.05; I 2 : 57%)., Conclusions: sST2 significantly predicts disease severity and mortality in cardiovascular disease and is a good predictor of mortality in patients with stable coronary artery disease and chronic heart failure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses., Aim: To investigate the role of sST2 in AP., Methods: We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria., Results: Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001-1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003-1.009), P = 0.000, OR: 1.002 (1.001-1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups., Conclusion: sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis., Competing Interests: Conflict-of-interest statement: All the authors have no potential conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning. Methods: select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP. Results: 4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group ( P <0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission ( P <0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group ( P <0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission ( P <0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission ( P <0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores ( R =0.634, 0.723, P <0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion: sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.