Background: Statin therapy promotes the progression of coronary artery calcification (CAC). Comparing patients on high (HIST) vs. low-to-intermediate intensity statin therapy (LIST), randomized controlled trials with a one-year follow-up failed to document a relevant difference in the Agatston score and CAC volume. We evaluated whether statin intensity modifies CAC density at one year. Methods: We performed a pooled analysis of two randomized-controlled trials (BELLES, EBEAT), comparing the effects of HIST (Atorvastatin 80 mg) vs. LIST (Pravastatin 40 mg, Atorvastatin 10 mg) on CAC measures after one year. The differences in CAC density and its change were compared using the two-sided t-test. Results: Data from 852 patients (66.7% female) with available baseline and follow-up CT were evaluated from both trials. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −45.8 ± 38.5 vs. −72.9 ± 46.0 mg/dL, p < 0.001). Mean CAC density increased from 228.8 ± 35.4 HU to 232.6 ± 37.0 HU (p < 0.0001) at one-year follow-up. Comparing patients on HIST vs. LIST, CAC density at follow-up (HIST: 231.9 ± 36.1 HU vs. LIST: 233.3 ± 37.7 HU, p = 0.59) and its change from baseline (HIST: 4.0 ± 19.1 HU vs. LIST: 3.6 ± 19.6 HU, p = 0.73) did not differ. Subgroup analyses, stratifying by LDL reduction (<median: 2.0 ± 24.3 HU, ≥median: 3.6 ± 21.9 HU, p = 0.34), Agatston score at baseline (<100: 2.6 ± 22.5 HU vs. 3.2 ± 25.6 HU, p = 0.82; ≥100: 4.8 ± 17.0 HU vs. 3.8 ± 16.6 HU, p = 0.44, for HIST vs. LIST; respectively), and equal number of lesions in both CT scans (3.7 ± 20.3 HU vs. 7.0 ± 22.2 HU, p = 0.24) showed similar results. Conclusion: HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up.

Introduction The modified Duke score is the currently recommended diagnostic algorithm in suspected infective endocarditis (IE). The categorization in major and minor criteria enables an easy clinical application, but may not optimally utilize individual patient's information. In contrast, detailed statistical evaluation of multiple characteristics using artificial intelligence and logistic regression report improved prediction of various cardiovascular diseases over conventional clinical strategies. We tested the hypothesis that neuronal nets and logistic regression analysis would provide improved prediction of IE as compared to the modified Duke score. Methods This post-hoc evaluation of the prospective observational PRO-ENDOCARDITIS study was conducted at the West German Heart and Vascular center between December 2017 and May 2019 and includes 261 patients. Duke criteria and clinical characteristics were prospectively collected. Transesophageal echocardiography (TEE) imaging was evaluated by a blinded cardiologist at a central core-lab. IE as primary endpoint was adjudicated by an independent clinical endpoint committee. The database was divided into a training (70%) and validation cohort (30%). We compared the value of the Duke score, neuronal nets and logistic regression analysis for prediction of the primary endpoint. Results The mean age was 60.1±16.1 years, 37.2% were female. In 47 cases, IE was present. The modified Duke score achieved an AUC of 0.863 in the training cohort and 0.913 within the validation cohort. The logistic regression and the neural net exceeded the predictive value in both cohorts (training cohort: 0.992 and 0.986; validation cohort: 0.964, 0.957; for logistic regression and neuronal nets, respectively, Figure 1). Without the use of TEE, the remaining Duke criteria only poorly predicted IE (training cohort: 0.771, 0.951 and 0.938; validation cohort: 0.835, 0.862 and 0.780, for the Duke score, logistic regression and neuronal nets, respectively). Discussion Logistic regression analysis and neuronal nets provide improved prediction of IE as compared to the clinically established modified Duke score. Further studies on larger databases are needed to confirm our results and provide algorithms for clinical routine. Funding Acknowledgement Type of funding sources: None.

Background Natriuretic peptides (BNP/NT-proBNP) are predominantly used for risk stratification, diagnosis and therapeutic monitoring in heart failure patients. A potential value of BNP/NT-proBNP serum levels for the prediction of prognosis in the general population and for non-heart failure patient cohorts is suggested in the literature. However, for non-heart failure patients, no thresholds are established. We aimed to determine cut-off levels that allow prediction of long-term survival in patients without known heart failure. Methods The present analysis is based on a registry of patients undergoing coronary angiography between 2004 and 2019. Patients with existing diagnosis of heart failure or elevated natriuretic peptides (BNP &gt;100pg/nl, NT-proBNP &gt;400pg/nl), with missing follow-up information or without BNP/NT-proBNP levels at admission were excluded. As either BNP or NT-proBNP was available for singular patients and to adjust for the skewed distribution, BNP/NT-proBNP levels ranked based on gender specific percentile from 0 to 99. The cohort was then divided into a derivation and a validation cohort using random sampling. Incidence of death of any cause during follow-up was recorded. In the derivation cohort, cox regression analysis was used to determine the association of natriuretic peptides with incident mortality per 1 standard deviation increase in BNP/NT-proBNP rank. Multivariable models controlled for age, sex, LDL-cholesterol, systolic blood pressure, smoking status, and family history of premature cardiovascular disease. Receiver operating characteristics curve analysis was performed, with corresponding area under the curve, along with Youden's J index assessment, to establish a threshold for prediction of survival. The association of this threshold with incident mortality was tested in the validation cohort. Results Overall, 3,687 patients (age 62.9±12.5 years, 71% male) were included. During a mean follow-up of 2.6±3.4 years, 169 deaths occurred. In the derivation cohort, BNP/NT-proBNP was significantly associated with mortality (Hazard ratio [95% confidence interval]: 1.25 [1.01–1.54], p=0.04). Based on Youden's J index, BNP-thresholds of 9.6 and 29pg/ml and NT-proBNP thresholds of 65 and 77pg/ml for men and women, respectively, were determined. In the derivation cohort, BNP/NT-proBNP levels above these thresholds were significantly associated with increased mortality (2.44 [1.32–4.53], p=0.005). The predictive value of the determined thresholds was confirmed in the validation cohort (2.78 [1.26–6.14], p=0.01). Conclusion We here describe gender-specific BNP/NT-proBNP thresholds that allow prediction of impaired survival in patients without heart failure. Utilization of these thresholds in clinical routine may qualify for risk prediction in non-heart failure cohorts, independent of traditional cardiovascular risk factors. FUNDunding Acknowledgement Type of funding sources: None.

Introduction High-dose statin therapy (HIST) halts coronary plaque progression and reduces the risk of cardiovascular events by increasing atheroma calcification. The Agatston score is well established in the clinical routine for assessment of coronary artery calcification using non-contrast computed tomography. However, randomized controlled trials failed to detect an influence of HIST vs. low-to-intermediate statin therapy (LIST) on the Agatston and CAC volume score after one year. Coronary plaques with lower density including spotty calcifications may represent dynamic and early stages of atherosclerosis. We evaluated whether CAC density differentiates in HIST- vs. LIST-treated patients after one year. Methods The meta-analysis contains data from two prospective, randomized, double-blind studies (BELLES, EBEAT) that were designed to detect CAC changes after one year comparing HIST vs. LIST. In both studies, patient's coronary calcification burden was measured at baseline and one-year follow-up using electron beam computed tomography (EBCT). Patients data were pooled and stratified by intensity of statin therapy. Furthermore, the cohort was divided into several subgroup analyses, accounting for LDL-Cholesterol reduction, initial Agatston score and a consistent number of lesions. Results Data from 852 patients, 66% female were included. The amount of CAC overall increased after 1 year [Agatston score: 169.3 (80.0, 377.1) vs. 214.9 (95.4, 450.0); p&lt;0.0001NP; volume score: 292.1±445.4 vs. 355.5±482.4; p&lt;0.0001; number of lesions: 6 (3,10) vs. 7 (4,12); p&lt;0.0001NP, at baseline and follow-up, respectively]. Likewise, the average CAC density was higher at follow-up [CAC density: 228.8±35.4 vs. 232.6±37.0; p&lt;0.0001]. HIST vs. LIST more effectively reduced LDL-cholesterol (annualized change: −58.6±50.9 vs. −44.4±43.7 mg/dL, p=0.005). Comparing patients on HIST vs. LIST, CAC density at follow-up (231.9±36.1 HU vs. 233.3±37.7, p=0.59) and its change from baseline (4.0±19.1 HU vs. 3.6±19.6 HU, p=0.73) did not differ. Subgroup analyses, stratifying by LDL-reduction ( Conclusion HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up. Funding Acknowledgement Type of funding sources: None.