Dose-response Relationship And Risk Prediction Model For The Prognosis Of Cardiac Resynchronization Therapy

Background:While N-terminal pro-B-type natriuretic peptide(NT-proBNP)was commonly accepted as a biomarker for the prognosis of cardiac resynchronization therapy(CRT),the dose-response relationship between them was still unknown.Our study aimed at describing the quantitative associations between baseline NT-proBNP and CRT superresponse(SR)or a composite endpoint including all-cause mortality and the first rehospitalization due to heart failure(HF).Methods:This was a single-center,retrospective study which consecutively included 398 patients without the history of ventricular tachycardia/fibrillation and unexplained syncope before CRT from 2009 to 2018.Multivariable Logistic regression model and Cox proportional hazard regression model were used to analyze the associations between baseline NT-proBNP quartiles(Q1:≤697.6pg/mL,Q2:>697.6 pg/mL and ≤1348.5pg/mL,Q3:>1348.5 pg/mL and ≤2630.7pg/mL,Q4:>2630.7 pg/mL)and SR or the composite endpoint respectively.Restricted cubic spline was applied to show the doseresponse relationship of baseline NT-proBNP concentration and CRT prognosis.Moreover,subgroup analysis was performed to explore possible heterogeneity.Results:Compared with Q1,patients in Q4 showed 71%reduced likelihood of SR(aOR:0.29,95%CI:0.11-0.73,P=0.01)and more than twice the risk of clinical endpoints(aHR:2.36,95%CI:1.19-4.69,P=0.01)after multivariable adjustment.The dose-response associations between NT-proBNP quartiles and either SR or the composite endpoint were significant(P for trend=0.02 and<0.01 separately),which remained in most subgroups and possibly interacted with diabetes(P for interaction=0.05).When baseline NT-proBNP was considered as a continuous variable,non-linear dose-response curves were presented regarding the likelihood of SR and the composite endpoint.The likelihood of SR halved when NT-proBNP was 2145 pg/mL and the risk of composite endpoint increased 50%when NT-proBNP was 2242 pg/mL.Beyond 4000 pg/mL,both the probability of SR and composite endpoint would be stable.Conclusions:Our study described the dose-response associations between baseline NTproBNP(as quartiles and a continuous variable)and CRT prognosis,which might be useful to determine a better time-window for CRT intervention and implantation.Aims:Left ventricular ejection fraction(LVEF)is considered an indicator of cardiac resynchronization therapy(CRT).Longitudinal studies on the predictive value of LVEF are scarce.We aimed to comprehensively evaluate the prognostic role of LVEF in the outcomes of Chinese patients with CRT.Methods:Three hundred ninety-two patients were divided into three tertiles of LVEF:≤25%,25-30%,and 30-35%,and four groups by LVEF changes:<0%(negative response);≥0%and ≤5%(non-response);>5%and ≤15%(response);and>15%(super-response).Logistic regression was used to explore the association of CRT super-response and LVEF tertiles;Cox proportional hazard regression was performed to discover the relationship between the composite endpoint and baseline LVEF and its longitudinal change.Cubic spline regression was implemented to show non-linear association between baseline LVEF and CRT super-response.Results:Totally,106 were super-responders.During a median follow-up of 3.6 years,141 reached the composite endpoint.Odds ratios(ORs)for super-response depicted a reversed U-shaped relationship for baseline LVEF with a peak at 25-30%.Independent predictors of super-response were smaller left atrial diameter[odds ratio 0.897,95%confidence interval(CI)0.844-0.955,P=0.001],smaller left ventricular end-diastolic diameter(OR 0.937,95%CI 0.889-0.989,P=0.018),and higher estimated glomerular filtration rate(OR 1.018,95%CI 1.001-1.035,P=0.042)in Tertile 1;atrial fibrillation(OR 0.278,95%CI 0.086-0.901,P=0.033),left bundle branch block(OR 4.096,95%CI 1.046-16.037,P=0.043),and left ventricular end-diastolic diameter(OR 0.929,95%CI 0.876-0.986,P=0.016)in Tertile 2;while female sex(OR 2.778,95%CI 1.082-7.132,P=0.034)and higher systolic blood pressure(OR 1.045,95%CI 1.013-1.079,P=0.006)in Tertile 3.An inverse association with the composite endpoint was found in Tertile 1 vs.Tertile 2(hazard ratio 1.934,95%CI 1.248-2.996,P=0.003).The prognostic effects of CRT response in Tertile 3 and Tertile 1 varied significantly(P for trend=0.017 and<0.001).Among three tertiles in super-responders,event-free survival was similar(P for trend=0.143).Conclusions:Left ventricular ejection fraction of 25-30%is associated with a better prognosis of super-response.Predictors of super-response are different for LVEF tertiles.CRT responses would have better prognostic performance than LVEF tertiles at baseline,which should be considered when clinicians screening eligible patients for CRT.Background:Atrial fibrillation(AF),one of the most common comorbidities of heart failure(HF),is associated with worse long-term prognosis in HF patients receiving cardiac resynchronization therapy(CRT).However,there is still no convenient tool to identify CRT candidates with AF who are at high risk of mortality and hospitalization due to HF.Methods:We included 152 consecutive patients with AF for CRT in our hospital from January 2009 to July 2019.Multiple imputation was used for missing values.With imputed datasets,a multivariate Cox regression model was performed for variable selection using the backward stepwise method to predict all-cause mortality and HF readmissions.A nomogram and nomogram-based scoring system were constructed from the selected predictors.Then,internal validation and calibration were achieved by the bootstrap method,deriving the corrected concordance index and calibration curves.Sensitivity analysis was also performed to validate our selected predictors and the nomogram.Results:Five predictors were incorporated in the nomogram,including N-terminal pro brain natriuretic protein(NT-proBNP)>1745 pg/mL,history of syncope,previous pulmonary hypertension,moderate or severe tricuspid regurgitation,thyroid-stimulating hormone(TSH)>4 mIU/L.The concordance index(0.70,95%CI 0.62-0.77),corrected concordance index(0.67,95%CI 0.59-0.74)and calibration curve showed optimal discrimination and calibration of the established nomogram.A significant difference in overall event-free survival was recognized by the nomogram-derived scores for patients with high risk(>50 points),intermediate risk(21-50 points)and low risk(0-20 points)before CRT.Conclusion:Our internally validated nomogram and its corresponding score may be an applicable tool for the early risk stratification of CRT candidates with AF.