| 1 Multi-biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart FailureObjective:The alternative biomarkers of multi-biomarkers strategies for prognosis evaluation and risk stratification in patients with heart failure are still under investigation.This study aimed to identify related biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure.Methods:884 consecutive patients hospitalized with heart failure from July 2015 to December 2017 were enrolled.Twelve biomarkers were measured on admission,and the relationships between biomarkers and outcomes were assessed.The primary endpoint event was the composite of all-cause death,heart transplantation,or left ventricular assist device.Results:Soluble growth stimulation expressed gene 2(sST2)(per log[unit]increase,adjusted HR[95%CI]:1.39[1.13,1.72],P=0.002)and big endothelin-1(big ET-1)(per log[unit]increase,adjusted HR[95%CI]:1.56[1.23,1.97],P<0.001)were independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide(NT-proBNP)and high-sensitivity cardiac troponin T(hs-cTnT).Both sST2 and big ET-1 significantly improved the predictive value for primary endpoint event at 1 year and 3 years.However,only big ET-1 significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers.According to the number of elevated biomarkers(including NT-proBNP,hs-cTnT,sST2,and big ET-1),patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers,as well as in patients with two elevated biomarkers compared to those with one elevated biomarker.However,the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker.Furthermore,high-sensitivity cardiac troponin I,heart-type fatty acid binding protein(HFABP),creatinine,blood urea nitrogen,and neutrophil gelatinase-associated lipocalin could provide better prognostic values for patients with left ventricular ejection fraction(LVEF)≥50%than for those with LVEF<50%(all P values for interaction<0.05).However,serum amyloid A(SAA)and C-reactive protein could provide better prognostic values for patients with LVEF<50%than for those with LVEF>50%(both P values for interaction<0.05).Hs-cTnT,SAA,and C-reactive protein could provide better prognostic values for patients with non-ischemic heart failure than for those with ischemic heart failure(all P values for interaction<0.05).However,H-FABP could provide a better prognostic value for patients with ischemic heart failure than for those with non-ischemic heart failure(P value for interaction=0.043).Conclusion:Multiple biomarkers in combination could provide a better prognostic value than a single biomarker.Notably,sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.2 Point of Care Test for Soluble ST2 in Risk Factors and Predicting the Prognosis of Heart FailureObjective:Studies on the prognostic value of soluble growth stimulation expressed gene 2(sST2)in patients hospitalized with heart failure after adjusting for clinical predictors and known biomarkers are lacking.And the prognostic value of point of care test for sST2 in patients with heart failure is also lacking.This study aimed to investigate the point of care test for sST2 in risk factors and predicting the prognosis of heart failure.Methods:1726 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to December 2021 were enrolled.Baseline serum sST2 concentration was tested by immunofluorescence assay.According to serum sST2 levels,patients were divided into three groups:low sST2 group(≤16.3ng/mL),middle sST2 group(16.3-30.1ng/mL),and high sST2 group(≥30.1ng/mL).The general clinical characteristics among the three groups were collected and compared.Multivariate linear regression analysis was conducted to investigate the independent risk factors of sST2.The primary endpoint event was the composite of all-cause death,heart transplantation,or left ventricular assist device.Multivariate COX regression analyses,receiver operating characteristic(ROC)curves,and Kaplan-Meier analyses were conducted to investigate the relationship between sST2 and the prognosis of heart failure.Results:During the median follow-up duration of 682 days(IQR:251-1032 days),434 patients(25.1%)suffered from primary endpoint event.Multivariate linear regression analysis showed that age,hypertension,atrial fibrillation,albumin,alanine aminotransferase,sodium,high sensitivity C-reactive protein,N-terminal pro-B type natriuretic peptide(NT-proBNP),and high-sensitivity cardiac troponin T(hs-cTnT)were independent predictors of sST2(all P values<0.05).Multivariate COX regression analysis showed that baseline sST2 remained an independent predictor of all-cause death,heart transplantation,or left ventricular assist device in patients hospitalized with heart failure after adjusting for clinical predictors and known biomarkers(including NT-proBNP and hs-cTnT)(per log[unit]increase,adjusted HR[95%CI]:1.20[1.09,1.32],P<0.001).Stratified analyses showed that baseline sST2 had a better prognostic value for patients with normal weight and overweight than for those with underweight and obesity(P value for interaction=0.039).Furthermore,sST2 had a better prognostic value for patients with New York Heart Association(NYHA)functional class Ⅰ-Ⅱthan for those with NYHA functional class Ⅲ-Ⅳ(P value for interaction<0.001).ROC curves showed that baseline sST2 was a good predictor of all-cause death,heart transplantation,or left ventricular assist device in patients with heart failure at 3 months,1 year,and 2 years(areas under the curves were 0.775,0.736,and 0.733,respectively),and the best cut-off values were 27.1ng/mL,27.1ng/mL,and 25.1ng/mL,respectively.Furthermore,baseline sST2 could provide additional prognostic value in predicting all-cause death,heart transplantation,or left ventricular assist device for patients with heart failure when added to baseline NT-proBNP and hs-cTnT(all P values<0.05).Taking 26ng/mL and trisected levels of sST2 as cut-off values respectively,Kaplan-Meier analyses showed that the rates of primary endpoint event were significantly different among the two or three groups(both P values<0.001).According to the number of elevated biomarkers(including NT-proBNP,hs-cTnT,and sST2),patients with three elevated biomarkers had a significantly higher risk of all-cause death,heart transplantation,or left ventricular assist device compared to those with one or two elevated biomarkers(all P values<0.05).Conclusion:Baseline sST2 was the independent predictor of all-cause death,heart transplantation,or left ventricular assist device in patients with heart failure,particularly in patients with NYHA functional class Ⅰ-Ⅱ,normal weight,or overweight.And in the basis of baseline NT-proBNP and hs-cTnT,adding baseline sST2 could provide additional prognostic value in predicting adverse events for patients with heart failure.3 Creation and Validation of A Risk-prediction Model for Patients Hospitalized with Heart FailureObjective:Biomarkers applied to risk-prediction models for heart failure are lacking,and clinical predictors combining with biomarkers may contribute to risk stratification and prognosis evaluation for heart failure.This study aimed to investigate the predictors of adverse events at 1 year in patients hospitalized with heart failure in the basis of clinical predictors and biomarkers,so as to create and validate a risk-prediction model for patients hospitalized with heart failure.Methods:Consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to December 2021 were enrolled.The enrolled patients from July 2015 to December 2018 were used as the derivation group,and those from January 2019 to December 2021 were used as the validation group.The primary endpoint event was the composite of all-cause death,heart transplantation,or left ventricular assist device.Results:1430 patients with heart failure were enrolled.The derivation group consisted of 1023 patients with heart failure,and 175 patients(17.1%)suffered from primary endpoint event at 1 year.The validation group consisted of 407 patients with heart failure,and 83 patients(20.4%)suffered from primary endpoint event at 1 year.Multivariate Logistic regression analysis showed that body mass index(BMI),systolic blood pressure,angiotensin converting enzyme inhibitor(ACEI)/angiotensin receptor blocker(ARB)/angiotensin receptor neprilysin inhibitor(ARNI),hyponatremia,and N-terminal pro-B-type natriuretic peptide(NT-proBNP)were independent predictors of all-cause death,heart transplantation,or left ventricular assist device at 1 year in patients with heart failure(all P values<0.05).The five predictors in combination were used to create a simple risk-prediction model for patients hospitalized with heart failure.The receiver operating characteristic(ROC)curve showed that the risk-prediction model had a good predictive value for all-cause death,heart transplantation,or left ventricular assist device at 1 year in patients with heart failure(area under the curve(AUC)[95%CI]:0.813[0.777,0.848]),and Hosmer-Lemeshow test showed that the risk-prediction model had a good calibration(Hosmer-Lemeshow P=0.627).According to the risk-prediction probabilities,patients with heart failure were divided into low risk group(all point≤1),middle risk group(all point:2-4),high risk group(all point:5-7),and very high risk group(all point>8).Middle risk group had a significantly higher risk of all-cause death,heart transplantation,or left ventricular assist device at 1 year compared to low risk group(OR[95%CI]:5.66[2.63,12.17],P<0.001).High risk group had a significantly higher risk of all-cause death,heart transplantation,or left ventricular assist device at 1 year compared to middle risk group(OR[95%CI]:3.53[2.36,5.30],P<0.001).Very high risk group had a significantly higher risk of all-cause death,heart transplantation,or left ventricular assist device at 1 year compared to high risk group(OR[95%CI]:3.90[1.81,8.44],P=0.001).ROC curve showed that the riskprediction model also had a good predictive value for all-cause death,heart transplantation,or left ventricular assist device at 1 year in the validation group(AUC[95%CI]:0.798[0.738,0.858]),and Hosmer-Lemeshow test showed that the risk-prediction model also had a good calibration in the validation group(Hosmer-Lemeshow P=0.667).Conclusion:BMI,systolic blood pressure,ACEI/ARB/ARNI,hyponatremia,and NT-proBNP in combination were used to create a simple risk-prediction model,which could provide a good predictive value for all-cause death,heart transplantation,or left ventricular assist device at 1 year in patients hospitalized with heart failure. |
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