Analysis Of Factors Affecting Prognosis And Study Of Intervention Strategies For Patients With Aortic Valve Diseas

BackgroundThe prevalence of aortic regurgitation(AR),a common valvular heart disease,increases sharply with age.Significant AR and left ventricular systolic dysfunction(LVSD)often coexist in the elderly population,with a predominance of moderate AR.In patients with severe AR,reduced left ventricular ejection fraction(LVEF)<50%or 55%is known to be a potent predictor of poor prognosis.However,the prognostic value of LVEF and its best cutoff for risk prediction in patients with moderate AR remain unclear.Moreover,among patients with the failing LV,reduced hemodynamic burden following mechanical relief from significant AR may substantially improve long-term prognosis,but no data is available regarding the potential benefits of aortic valve intervention(AVI)in patients with moderate AR and LVSD.Thus,we aimed to assess the prognostic value of LVEF in patients with moderate AR and explore the potential benefits of AVI.MethodsData were derived from the China Valvular Heart Disease Study(China-VHD,NCT03484806)cohort study on 1211 consecutive patients with moderate AR(jet width,25-64%of LV outflow tract;vena contracta,0.3-0.6 cm;regurgitant volume,30-59 mL/beat;regurgitant fraction,30-49%;effective regurgitation orifice,0.10-0.29 cm2)prospectively registered between April and June 2018 at 46 academic hospitals.The primary outcome was a composite of death or hospitalization for heart failure(HHF).The least absolute shrinkage and selection operator(LASSO)-penalized Cox regression was used to identify the variables associated with the primary outcome.We also employed penalized splines(P-splines)to depict the shape of the association between LVEF and the primary outcome.The optimal LVEF threshold for predicting the primary outcome was determined through the P-spline shape and maximally selected rank statistics.Patients were divided into the medical treatment group and AVI treatment group based on whether AVI performed within 6 months of diagnosis and the impact of AVI on the primary outcome was assessed using inverse probability of treatment weighted(IPTW)Cox regression models with multivariate adjustment.ResultsDuring the 2-year follow-up,125(10.3%)deaths or HHF occurred.LVEF,age,body mass index,prior myocardial infarction,prior coronary artery bypass grafting,atrial fibrillation,chronic kidney disease,New York Heart Association class III/IV,hemoglobin,left ventricular end-systolic diameter>50 mm,pulmonary hypertension,and EuroSCORE-Ⅱ were independent predictor of death or HHF in patients with moderate AR under medical treatment(C-statistics=0.78).In the penalized splines,the relative hazard of death or HHF monotonically increased with decreasing LVEF.In the multivariate analysis,LVEF ≤55%was identified as the best threshold for independently predicting death or HHF under medical treatment(adjusted hazard ratio[HR]:2.18;95%confidence interval[CI]1.38-3.42;P=0.001),with substantial incremental values(integrated discrimination improvement index=0.018,P=0.030;net reclassification improvement index=0.225,P=0.006;likelihood ratio test P<0.001).Among patients with LVEF 35-55%,AVI within 6 months of diagnosis was associated with a reduced risk of death or HHF compared with medical treatment alone(adjusted HR:0.15;95%Cl:0.04-0.50;P=0.002),whereas this benefit was markedly attenuated when LVEF was<35%(adjusted HR:0.65;95%CI:0.21-1.97;P=0.441,P-interaction=0.010)or>55%(adjusted HR:0.40;95%CI:0.14-1.15;P=0.089,P-interaction=0.723).ConclusionsLVEF is an independent and incremental prognostic factor in patients with moderate AR,with LVEF ≤55%being a robust marker of poor prognosis.Patients with LVEF 35-55%may benefit from early surgical correction of moderate AR.BackgroundAortic stenosis(AS)is a common disease in the elderly,and its prevalence continues to rise as the population ages.Despite clear indications for intervention,therapeutic decision-making for elderly patients with severe symptomatic AS remains a complex issue due to the wide variation in individual risk profiles and the involvement of patients’subjective preferences.We aimed to investigate the reasons leading to the decisions against intervention and the consequences thereof on survival.MethodsChina Elderly Valve Disease Cohort Study(China-DVD,NCT02865798)consecutively enrolled 8,227 patients aged>60-year-old with significant native valvular heart disease between September to December 2016,among whom 456 patients were with severe symptomatic aortic stenosis.Patients were analyzed according to the initial therapeutic decisions made by consensus between patients and physicians during hospitalization:intervention group(patients who were evaluated as suitable for intervention and accepted the treatment proposal);patient-refusal group(patients who were evaluated as suitable for intervention but refused due to subjective preferences);physician-deny group(patients who were denied intervention by physicians due to unsuitability for intervention),The least absolute shrinkage and selection operator(LASSO)-penalized logistic regression model was used to identify the factors associated with physicians’decisions against intervention.12-month survival was analyzed using Cox proportional hazards models,with multivariate adjustment using inverse probability treatment weighting(IPTW).ResultsAmong the enrolled 456 elderly patients with severe symptomatic AS,49(10.7%)patients were denied intervention by their physicians due to unsuitability for intervention.Of the patients who were evaluated as suitable for surgical intervention,355(77,9%)patients accepted the intervention proposal and 52(11.4%)patients refused intervention.LASSO-penalized logistic regression model identified that reduced left ventricular ejection fraction(per 10%increase,Odds ratio:0.76;95%confidence interval:0.59-0.97;P=0.027)and increased EuroSCORE-Ⅱ(per 1 point increase,Odds ratio:1.26;95%confidence interval:1.17-1.35;P<0.001)were strongly associated with physicians’decisions against intervention.At 12-month follow-up,only 8(15.4%)patients who initially refused the intervention proposal underwent the subsequent intervention,with an average delay of 195 days.Patients’ decisions against intervention(Hazard ratio:2.61;95%confidence interval:1.09-6.20;P=0.031)and physicians’decisions against intervention(Hazard ratio:7.30;95%confidence interval:3.35-15.92;P=0.031)were both significantly associated with 12-month mortality,even after IPW adjustment.ConclusionsThe decision against intervention was taken in about one-fifth of elderly patients with symptomatic severe AS,half of which were due to patients’ subjective preferences.Surgical risk remains the primary concern for physicians when making therapeutic decisions.Elderly patients’initial decisions against intervention have a profound impact on subsequent intervention rates and prognosis,and therefore should be treated as a "risk factor" at the subjective level.To further improve the management of elderly patients with AS,efforts should be made to enhance patient acceptance of intervention via intensive patient education and increase the intervention rates by utilizing the transcatheter aortic valve replacement technique.