A Study On Prognostic Factors And Prediction Models Of All-cause Mortality In Patients With Implantable Cardioverter Defibrillators

Part Ⅰ The influence of BMI on the prognosis of patients with an implantable cardioverter-defibrillatorBackground:Results from studies on the effects of BMI on clinical outcome in patients with an implantable cardioverter-defibrillator are inconsistent.Our study aimed to explore the impact of BMI on the prognosis in patients with an ICD.Methods:We retrospectively analyzed the data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-implanted Patients in China.After inclusion and exclusion criteria,nine hundred and seventy ICD patients were enrolled.The primary outcome was all-cause death and the second outcome was the first occurrence of ventricular tachycardia/ventricular fibrillation(VT/VF)requiring appropriate ICD therapy.Kaplan-Meier curves for cumulative incidence of all-cause death and VAs over time were plotted.Univariate Cox model and multivariate Cox model were used to analysis the influence of BMI on death and VT/VF.A cubic spline function model and smooth curve fitting(penalized spline method)to further exploretheassociationbetween BMI and clinical outcome.Results:After a median follow-up of 5 years(interquartile,4.3-5.8 years),213(22.0%)patients experienced all-cause death.After a median follow-up of 5.17 years(interquartile,4.3-5.8 years),352(36.3%)patients experienced VT/VF requiring appropriate ICD therapy.BMI,whether as a continuous variable or a categorical variable classified by various BMI classification criteria,had no significant effect on death and VT/VF according to a multivariable Cox proportional hazards model with adjustment for potential confounders.A cubic spline function model and smooth curve fitting showed linear association between BMI and death,the risk of death had the trend of decrease but did not achieve statistically significance(Per 1 kg/m2 increase of BMI,risk for death HR 0.97[0.93-1.02],P=0.2644).However,a nonlinear association between BMI and VT/VF was identified using a cubic spline function model and smooth curve fitting.The inflection point for the curve was found at a BMI level of 23 kg/m2.The hazard ratios(95%confidence intervals)for VT/VF were 1.12(1.01-1.24)and 0.96(0.90-1.02)to the left and right of the inflection point,respectively.Conclusions:BMI has no impact on all-cause death but is related to VT/VF in a nonlinear manner in patients with an ICD.Our research suggests a complicated role of BMI in VT/VF with different impacts at different ranges.Part Ⅱ The influence of BMI on the prognosis of nonischemic cardiomyopathy patients with an implantable cardioverter-defibrillatorBackground:Previous studies have reported inconsistent results on the relationship between body mass index(BMI)and clinical outcomes in implantable cardioverter defibrillator(ICD)patients.Additionally,research on ICD patients with nonischemic cardiomyopathy(NICM)is lacking.This study aimed to investigate the impact of BMI on mortality and ventricular arrhythmias(VAs)in NICM patients with an ICD.Methods:This study retrospectively analyzed the data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device-implanted patients(SUMMIT)in China.Four hundred and eighty NICM patients with an ICD were enrolled and clinical data were collected.Patients were divided into two groups:underweight and normal range group(BMI<24 kg/m2);overweight and obese group(BMI≥24 kg/m2).The primary endpoint was all-cause mortality.The secondary endpoint was the first occurrence of VAs requiring appropriate ICD therapy.Kaplan-Meier curves for cumulative incidence of all-cause death and VAs over time were plotted.Univariate Cox model and multivariate Cox model were used to analysis the influence of BMI on death and VAs.A cubic spline function model and smooth curve fitting(penalized spline method)to further exploretheassociationbetween BMI and clinical outcome.Results:During a median follow-up of 61(1-95)months,70 patients(14.6%)died,173 patients(36%)experienced VAs requiring appropriate ICD therapy.A cubic spline function model and smooth curve fitting showed linear association between BMI and death and VAs(Per 1 kg/m2 increase of BMI,risk for death HR 0.97[0.93-1.02],P=0.2644;Per 1 kg/m2 increase of BMI,risk for VAs HR 1.09[0.74-1.59],P=0.663).Multivariate Cox regression modeling indicated a decreased mortality risk in the overweight and obese group compared with the underweight and normal range group(hazard ratio[HR]0.44,95%confidence interval[CI]0.26-0.77,p=0.003).However,the risk of VAs was similar in both groups in univariate and multivariate Cox models.Conclusions:Compared with underweight and normal weight,overweight and obesity are protective against mortality but have only a neutral impact on VAs risk in NICM patients with an ICD.Part Ⅲ Development and validation of a nomogram predicting all-cause mortality for patients with an implantable cardioverter-defibrillatorBackground:for patients with high risk of sudden cardiac death,despite the benefits of an implantable cardioverter defibrillator(ICD),some patients are still at a high risk of death.Death risk assessment of ICD patients is beneficial to the clinical management of such patients.The purpose of this study was to develop and validate a nomogram predicting all-cause mortality for patients with an ICD.Methods:We retrospectively analyzed the data of multicenter ICD registration study(SUMMIT study)from 2010 to 2014 in China.After inclusion and exclusion criteria,eight hundred and thirtheen ICD patients were enrolled.A total of 617 ICD patients from regions where the enrollment ranked top five formed a development cohort.The physical activity monitored by ICD and clinical data were collected.Univariate and multivariate COX regression analyses were used to screen mortality predictors and construct the nomogram.The performance of nomogram was evaluated by the C index and the calibration curve.A total of 196 ICD patients from other regions formed a validation cohort,and the nomogram constructed by the development cohort was further evaluated in the verification cohort.Results:In the development cohort,daily activity,diabetes and left ventricular end-diastolic diameter were selected as mortality predictors by univariate and multivariate proportional hazard model analysis.The nomogram was constructed by these three factors.The C index of the nomogram was 0.80(95%confidence interval,0.75-0.84).The calibration curve showed that the predicted survival probability of the nomogram was in good agreement with the actual survival probability.In the validation cohort,the C index of the nomogram was 0.74(95%confidence interval,0.64-0.84),and the calibration curve still maintained good consistency.Conclusion:Our study develops and validates a nomogram predicting all-cause mortality for patients with an ICD by integrating the physical activity monitored by ICD and clinical data(diabetes and left ventricular end-diastolic diameter).The nomogram performs well and can provide personalized death risk assessment for ICD patients.