Predictive Value Of Biomarkers And Physical Activity For Ventricular Arrhythmia And Death

Background:Endothelin system plays an important role in cardiovascular diseases.It is unclear whether plasma big endothelin-1(ET-1),which is commonly used in clinic,can predict ventricular arrhythmia events in primary prevention implantable cardioverter-defibrillator indication patients.Objective:To investigate whether plasma big ET-1 predicts ventricular arrythmias(VAs)and end-stage events in primary prevention implantable cardioverter-defibrillator(ICD)indication patients.To provide a new risk stratification method for screening patients with high risk of sudden cardiac death(SCD).Methods:This study is designed as a retrospective case-control analysis.Heart failure patients in Fuwai Hospital from January 2013 to December 2015 were enrolled,and the inclusion criteria were with indication for primary prevention of SCD.All patients were followed up regularly at 3,6,12,24 and 36 months through outpatient or telephone.The primary endpoints were VAs.The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation.Kaplan-Meier curve was used to compare the end events between groups,and Cox proportional hazard model was used to evaluate the influence of baseline big ET-1 on endpoints.Results:In total,207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analysed.The cohort was divided into three groups according to baseline plasma big ET-1 tertiles:tertile 1(<0.38 pmol/L,n=68),tertile 2(0.38-0.7 pmol/L,n=69),and tertile 3(>0.7 pmol/L,n=70).During a mean follow-up period of 25.6±13.9 months,38(18.4%)VAs and 78(37.7%)end-stage events occurred.Big ET-1 was positively correlated with NYHA class(r=0.165,P=0.018).Scr(r=0.147,P=0.034),hs-CRP(r=0.217,P=0.002),Lg NT-proBNP(r=0.463,P<0.001).LVEDD(r=0.234,P=0.001)and negatively correlated with LVEF(r=-0.256,P<0.001).Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events(P<0.05).In multivariate Cox regression models,big ET-1 was an independent risk factor for VAs(hazard ratio(HR)3.477,95%confidence interval(CI):1.352-8.940,P=0.010,tertile 2 vs tertile 1;HR 4.112,95%CI:1.604-10.540,P=0.003,tertile 3 vs tertile 1)and end-stage events(HR 2.804,95%CI:1.354-5.806,P=0.005,tertile 2 vs tertile 1;HR 4.652,95%CI:2.288-9.459,P<0.001,tertile 3 vs tertile 1).Conclusions:In primary prevention ICD indication patients,plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.Background:N-terminal pro-brain natriuretic peptide(NT-proBNP)plays an important role in the diagnosis and prognosis of cardiovascular diseases,especially heart failure.Previous studies have shown that NT-proBNP can predict ventricular arrhythmia events.Under the current situation of implantable cardioverter defibrillator(ICD)/implantation in China,the predictive value of NT-proBNP for ventricular arrhythmia events in those patients remains unclear.Objective:To investigate the predictive value of N-terminal pro-brain natriuretic peptide in outcomes of patients with implantable cardioverter-defibrillator(ICD)/cardiac resynchronization therapy defibrillator(CRTD).Methods:This study was designed as a retrospective case-control analysis.Patients who met the inclusion criteria were included in the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-implanted patients registry(SUMMIT study).The inclusion criteria were that all patients with NT-proBNP results at the baseline of device implantation,and the home monitoring function was turned on.The population was divided into two sub-groups based on an optimal cut off value of NT-pro BNP predicting appropriate therapy:high NT-proBNP and low NT-proBNP.Through the remote home monitoring function and regular follow-up,the outcome information of ventricular arrhythmia and mortality were recorded.The main end point was appropriate therapy,including ATP and shock.Secondary endpoints were all-cause mortality and cardiac death during the follow-up.Kaplan-Meier curve was used to compare the end events between groups,and Cox proportional hazard model was used to evaluate the influence of baseline NT-proBNP on endpoints.Results:According to the inclusion criteria,233 patients with ICD/CRTD implantation were followed up for 43.9±16.7 months(range:0.7-75.5 months),125 patients(53.6%)had VAs.75 patients(32.2%)experiences shock events,and 36 patients(15.5%)died,of which 27 was cardiac.In Kaplan-Meier survival analysis,compared with low NT-proBNP group,high NT-proBNP group had significantly higher cumulative incidence of primary and secondary endpoints.Multivariate Cox regression model showed that high NT-proBNP was an independent risk factor for VAs(HR[hazard ratio]:2.205,95%CI[confidence interval]:1.438-3.381,P<0.001),shock(HR:2.397,95%CI:1.333-4.310,P=0.003),all-cause mortality(HR:2.701,95%CI:1.142-6.391,P=0.024)and cardiac death(HR:3.490,95%CI:1.142-10.667,P=0.028).Conclusion:NT-proBNP has predictive value for ventricular arrhythmias and mortality in patients with ICDs.As a relatively unexpensive marker,NT-proBNP may contribute to the risk stratification of SCD and the postoperative management of ICD/CRTD patients.Background:ICD is an effective therapy stop ventricular arrhythmia and prevent sudden cardiac death(SCD).However,the prognosis of patients post ICD implantation,especially the quality of life of those patients,has not attracted enough attention.A large number of studies have shown that proper exercise can bring significant survival benefits.It has been confirmed in people with or without heart disease.Because the patients implanted with ICD are very special,and those patients’ physical activity may decrease due to their worries about the illness and the implantation of devices.In these patients,the correlation between PA and prognosis,especially the dose-response association remains unclear.Objective:The dose-response association of implantable cardioverter-defibrillator(ICD)and cardiac resynchronization therapy defibrillator(CRTD)-measured PA with cardiovascular outcomes in patients at high risk of sudden cardiac death(SCD)was investigated.And the differences between the older and adults were further discussed.Methods:The data of this study comes from a large-scale,multi-center study(SUMMIT registry).Patients with continuous daily PA data and complete follow-up were included from the database.The clinical outcomes of patients were from home monitoring.The primary endpoint was all-cause mortality and cardiac death(ICD-10 100-109、111、120-151),the secondary endpoint was ventricular arrhythmia events(appropriate device therapies,including ATP and shock).Multivariate COX analysis was used to evaluate the correlation between daily PA and long-term clinical outcome of those patients.Restricted cubic spline(RCS)curve was used to analyze the dose-response association between baseline PA and prognosis,and to discuss the differences among different age groups.Results:In total,822 patients fulfilling the inclusion criteria were included and divided into three groups according to baseline PA tertiles:tertile 1(<8.04%,n=274),tertile 2(8.04-13.24%,n=274),and tertile 3(>13.24%,n=274).Most patients were male(73.8%).The mean age was 60.8±13.8 years,During a mean follow-up of 59.7±22.4 months,there were 90 cardiac deaths(10.9%),191 all-cause deaths(23.2%)and 411 ventricular arrhythmia events(50%).Cardiac death(1 8.6%vs 8.8%vs 5.5%,tertiles 1-3,P<0.001)and all-cause mortality(39.4%vs 20.4%vs 9.9%,tertiles 1-3,P<0.001)events decreased according to PA tertiles.There was no significant difference in ventricular arrhythmia among the three groups(47.1%vs 48.2%vs 54.7%,P=0.173).Compared with patients younger than 60 years old,older patients had a lower average PA level(9.6%vs 12.8%,P<0.001)but higher rates of cardiac death(13.2%vs 8.1%,P=0.024)and all-cause mortality(28.4%vs 16.7%,P<0.001)events.Adjusted multivariate Cox regression analyses showed that a higher tertile of PA was associated with a lower risk of cardiac death(hazard ratio(HR)0.41,95%confidence interval(CI);0.25-0.68,tertile 2 vs tertile 1;HR 0.28,95%CI:0.15-0.51,tertile 3 vs tertile 1,Ptrend<0.001).Similar results were observed for all-cause mortality.The dose-response curve showed an inverse non-linear pattern,and a significant reduction in endpoint risk was observed at the low-moderate PA level.The HR for cardiac death was reduced by half with 12.32%PA(177 min),and the HR for all-cause mortality was reduced by half with 11.92%PA(172 min).Subgroup analysis results indicated that older adults could benefit from PA and the range for achieving optimal benefits might be lower.Conclusions:PA monitoring may aid in long-term management of patients at high risk of SCD.More PA will generate better survival benefits,but even low-moderate PA is already good especially for older adults,which is relatively easy to achieve.