Dataset on the prognostic value of cardiac biomarkers used in clinical routine in patients with severe aortic stenosis undergoing valve replacement

Hereby, the supplemental data of the research article “Long-Term Prognostic Value of High-Sensitivity Troponin T added to N-Terminal Pro Brain Natriuretic Peptide Plasma Levels before Valve Replacement for Severe Aortic Stenosis” are presented [1]. It offers enhanced input on the predictive value of these biomarkers considering the influence of the presence of concomitant coronary artery disease (CAD) in various severities as well as an additional cox proportional hazard model on cardiovascular mortality. Furthermore, the receiver operating characteristic (ROC) curves are shown as figures. The material described increases therefore the understanding of the predictive value of these already routinely available biomarkers and reduces the risk of potential bias due to possible confounding factors. It also underlines the urge for a multi-factorial approach in diagnostics to detect the optimal point for referral to valve replacement other than just symptomatic status, an observed reduction in left ventricular ejection fraction or the presence of CAD with the necessity for coronary artery bypass grafting (CABG) [2]. The data of the 3595 patients were gathered retrospectively at a consortium of four university hospital centers in Austria and combined with prospectively collected data on cardiovascular and all-cause mortality.


Keywords:
High sensitivity troponin T N-terminal pro brain natiuretic peptide Severe aortic stenosis Valve replacement Survival Risk stratification cox proportional hazard model on cardiovascular mortality. Furthermore, the receiver operating characteristic (ROC) curves are shown as figures. The material described increases therefore the understanding of the predictive value of these already routinely available biomarkers and reduces the risk of potential bias due to possible confounding factors. It also underlines the urge for a multi-factorial approach in diagnostics to detect the optimal point for referral to valve replacement other than just symptomatic status, an observed reduction in left ventricular ejection fraction or the presence of CAD with the necessity for coronary artery bypass grafting (CABG) [2]. The data of the 3595 patients were gathered retrospectively at a consortium of four university hospital centers in Austria and combined with prospectively collected data on cardiovascular and all-cause mortality. ©
Occurrence of significant CAD separated by high-sensitivity Troponin T (hsTnT) groups is displayed in Table 1. Occurrence of CAD was significantly increased in patients with pathological hsTnT (14 ng/l; p < 0.001). For further analysis of the influence of CAD on hsTnT and its prognostic value patients were  divided into four groups as following: no significant CAD and normal hsTnT (group 1; n ¼ 862, 25.5%), significant CAD and normal hsTnT (group 2; n ¼ 373, 11.0%), no significant CAD but pathological hsTnT (group 3; n ¼ 1227, 36.3%), significant CAD and pathological hsTnT (group 4, n ¼ 919, 27.2%). Assessment of cardiovascular mortality as well as all-cause mortality by using above mentioned groups is shown in Fig. 1A, B. Three-vessel disease was found in 284 patients of whom 61 had normal hsTnT and 223 had elevated hsTnT. Kaplan-Meier curves for the prediction of cardiovascular and all-cause mortality by using the hsTnT groups in patients with three-vessel disease are presented in Fig. 2A, B. The ROC curves of Nterminal pro brain natriuretic peptide (NT-proBNP) and hsTnT on all-cause mortality are displayed in Fig. 3. The Youden index, which describes the most sensitive and specific value for the prediction of mortality, was detected to be at 1295 ng/l for NT-proBNP and at 25 ng/l for hsTnT. The cox regression hazard model on cardiovascular mortality is presented in Table 2.

Experimental design, materials, and methods
Data was acquired locally at each of the contributing hospitals in a retrospective way by using the electronic hospital information system or the electronic patient record. Patients were enrolled consecutively at all participating centers, inclusion and exclusion criteria were described in the main Fig. 2. Kaplan-Meier estimates of cardiovascular (A) and all-cause mortality (B) in patients with three-vessel coronary artery disease after aortic valve replacement due to severe stenosis, stratified to pre-procedural high sensitivity troponin t plasma levels by using a cut-off point at 14 ng/l. publication [1]. Then, it was paired with prospective data on mortality and cause of death defined by ICD-10 codes. This data was obtained by "Statistics Austria", the governmental statistic department.
Severitiy of aortic valve stenosis was graded according to current guidelines [2]. The coronary anatomic status was assessed by using coronary angiography in every patient as part of the diagnostic examination prior to valve replacement. Significant CAD was defined as a stenosis of at least 70% or previously performed coronary intervention including CABG. In case of a transcutaneous aortic valve replacement, percutaneous coronary intervention was performed in advance during a separated hospital stay. Revascularisation by coronary artery bypass grafting was conducted as part of the aortic valve replacement surgery.
Chi-square tests were used for the assessment of differences in the prevalence of CAD and hsTnT groups. Analysis of survival was performed by using either the Kaplan-Meier method (univariate) or a cox regression hazard model (multivariate). Calculations were conducted with IBM SPSS version 24 (IBM Corporation, Armonk, NY, USA). Graphics were designed by using GraphPad PRISM, version 5 (GraphPad Software, Inc., La Jolla, CA, USA). Abbreviations: CAD, coronary artery disease; CI, confidence interval; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; HR, hazard ratio; hsTnT, high sensitivity troponin T; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro brain natriuretic peptide; SAVR, surgical aortic valve replacement; STS-PROM score, Society of Thoracic Surgeons predicted risk of mortality score; TAVR, transcatheter aortic valve replacement. Fig. 3. Receiver operating characteristic curve for the evaluation of the predictive value of pre-procedural high sensitivity troponin t and N-terminal pro brain natriuretic peptide plasma levels on all-cause mortality.