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Background: About half of patients with severe aortic stenosis present with concomitant coronary artery disease. The optimal timing of percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and concomitant coronary artery disease remains unknown., Study Design: The TAVI PCI trial is a prospective, international, multicenter, randomized, 2-arm, open-label study planning to enroll a total of 986 patients. It is designed to investigate whether the strategy "angiography-guided complete revascularization after (within 1-45 days) TAVI" is noninferior to the strategy "angiography-guided complete revascularization before (within 1-45 days) TAVI" using the Edwards SAPIEN 3 or 3 Ultra Transcatheter Heart Valve in patients with severe aortic stenosis and concomitant coronary artery disease. Patients are randomized in a 1:1 ratio to one of the 2 treatment strategies. The primary end point is a composite of all-cause death, nonfatal myocardial infarction, ischemia-driven revascularization, rehospitalization (valve- or procedure-related including heart failure), or life-threatening/disabling or major bleeding at 1 year., Conclusions: The TAVI PCI trial tests the hypothesis that the strategy "PCI after TAVI" is noninferior to the strategy "PCI before TAVI" in patients with severe aortic stenosis and concomitant coronary artery disease., Competing Interests: Declaration of competing interest TAVI PCI is supported as investigator-initiated research by Edwards Lifesciences (THV-I20-061)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Empagliflozin administered after acute myocardial infarction proofed to improve cardiometabolic parameters and biomarkers, but the impact on cardiac function is still largely unknown. The aim of this post-hoc echocardiographic sub-analysis of the EMMY trial was to provide in-depth echocardiographic analysis on the effects of empagliflozin versus placebo on standard and novel echocardiographic structural and functional parameters after acute myocardial infarction., Methods: In this post-hoc analysis of the EMMY trial a subset of 313 patients (157 empagliflozin vs. 156 placebo) was enrolled for post-processing analysis of echocardiographic structural and functional parameters. On top of two-dimensional and Doppler parameters, myocardial deformation analyses were performed to assess ventricular and atrial strain values., Results: Left ventricular volumes showed significant differences in favor of empagliflozin over the course of the trial (change in left ventricular end-diastolic volume median [interquartile range] 8 [-3;19]% versus 13 [0;29]%, p = 0.048; left ventricular end-systolic volume -3 [-15;12]% versus 4 [-12;18]%, p = 0.044). This effect persisted after adjusting for baseline values, age, and sex. Left ventricular systolic and diastolic function overall improved over the course of the trial and parameters for diastolic function showed a distinct trend between groups but did not meet statistical significance in this cohort., Conclusion: In this post-hoc analysis among patients with acute myocardial infarction, treatment with empagliflozin resulted in a significant beneficial effect on left ventricular end-diastolic and end-systolic volume, without significantly improving left ventricular or right ventricular functional parameters compared to placebo after 26 weeks., Gov Registration: NCT03087773., (© 2024. The Author(s).)

Introduction: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. Recent technical advances such as radial access, third generation drug-eluting stents and highly effective antiplatelet therapy have substantially improved the safety profile of coronary procedures. Despite several practice guidelines and a clear patient preference of early hospital discharge, the percentage of coronary procedures performed in an outpatient setting in Austria remains low, mostly due to safety concerns., Methods: The aim of this consensus statement is to provide a practical framework for the safe and effective implementation of coronary outpatient clinics in Austria. Based on a structured literature review and an in-depth analysis of available practice guidelines a consensus statement was developed and peer-reviewed within the working group of interventional cardiology (AGIK) of the Austrian Society of Cardiology., Results: Based on the available literature same-day discharge coronary procedures show a favorable safety profile with no increase in the risk of major adverse events compared to an overnight stay. This document provides a detailed consensus in various clinical settings. The most important prerequisite for same-day discharge is, however, adequate selection of suitable patients and a structured peri-interventional and postinterventional management plan., Conclusion: Based on the data analysis this consensus document provides detailed practice guidelines for the safe operation of daycare cathlab programs in Austria., (© 2024. The Author(s).)

Introduction: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries., Methods: The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures., Results: A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1‑month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I 2 0%), indicating a noninferiority in carefully selected patients., Conclusion: Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay., (© 2024. The Author(s).)

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adj HR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adj HR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Objective: The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe a real-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals., Methods: Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type 9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using a Monte Carlo simulation., Results: A cohort of patients (N = 144) with a mean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with a decrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall., Conclusions: The SANTORINI real-world data in Austria suggest that a proportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits., (© 2023. The Author(s).)

Aims: Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking., Methods and Results: In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. Baseline median (interquartile range) NT-proBNP was 1294 (757-2246) pg/mL. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower [95% confidence interval (CI) -4.4% to -23.6%] after adjusting for baseline NT-proBNP, sex, and diabetes status (P = 0.026). Absolute left-ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2-2.9%, P = 0.029), mean E/e' reduction was 6.8% (95% CI 1.3-11.3%, P = 0.015) greater, and left-ventricular end-systolic and end-diastolic volumes were lower by 7.5 mL (95% CI 3.4-11.5 mL, P = 0.0003) and 9.7 mL (95% CI 3.7-15.7 mL, P = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalized for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups., Conclusion: In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters., Clinicaltrials.gov Registration: NCT03087773., Competing Interests: Conflict of interest: H.S. is on the advisory board and speakers bureau of by Boehringer Ingelheim, NovoNordisk, Sanofi-Aventis, Amgen, AstraZeneca, Bayer, Eli Lilly, Kapsch, MSD, and Daiichi Sankyo. D.V.L. is on the advisory board and speakers’ bureau of Abiomed, AstraZeneca, Bayer, Daiichi Sankyo, Orion, Sanofi, and Servier and receives consulting fees from Recardio Inc, Bayer, TLL, Vaxxinity Inc. P.M.Z. received speaker fees from AstraZeneca, Pfizer, Medtronic, and Boehringer Ingelheim. R.R.H. reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Anji Pharmaceuticals, AstraZeneca, Novartis, and Novo Nordisk. M.W. receives speaker fees from Bayer, Novartis and consulting fees from Radcliff Cardiology. A.Z. receives fees from Boehringer Ingelheim, AstraZeneca, NovoNordisk, Bayer, Daiichi Sankyo, Amgen, and Sanofi. C.R. receives payment or Honoria for lectures from Boehringer Ingelheim, Pfizer, and AstraZeneca and support for attending meetings from Boehringer Ingelheim and Pfizer. T.R.P. receives consulting fees and payment of honoraria for lectures from Arecor and Novo Nordisk and grants from Arecor, Sanofi, and Novo Nordisk. H.A. receives Honoria for lectures from Boehringer Ingelheim and AstraZeneca and financial support for attending meetings and transport from Boehringer Ingelheim and AstraZeneca. P.A. reports speakers’ fee from Bayer and Pfizer. J.M.S.M. received speaker or consultant fees from Chiesi, Boehringer Ingelheim, Biosensors, P&F, Gruenenthal, Bayer, Medtronic, and Boston Scientific within the last 3 years. D.M. receives consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Vifor, further he receives payment for lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Vifor, and BMS. C.H.S. reports grants and consulting fees from AstraZeneca, Boehringer Ingelheim, and MSD. M.L. receives consulting fees from Johnson and Johnson and support for attending meetings from MSD. R.B. received a grant from Abbott and speaker or consultant fees from Abbott, Amgen, AstraZeneca, Biotronik, Bayer, Boehringer Ingelheim, Novartis, and Vivorpharma within the last 3 years. The remaining authors have no relevant conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients ( n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

Calibration is a vital aspect of the performance of risk prediction models, but research in the context of ordinal outcomes is scarce. This study compared calibration measures for risk models predicting a discrete ordinal outcome, and investigated the impact of the proportional odds assumption on calibration and overfitting. We studied the multinomial, cumulative, adjacent category, continuation ratio, and stereotype logit/logistic models. To assess calibration, we investigated calibration intercepts and slopes, calibration plots, and the estimated calibration index. Using large sample simulations, we studied the performance of models for risk estimation under various conditions, assuming that the true model has either a multinomial logistic form or a cumulative logit proportional odds form. Small sample simulations were used to compare the tendency for overfitting between models. As a case study, we developed models to diagnose the degree of coronary artery disease (five categories) in symptomatic patients. When the true model was multinomial logistic, proportional odds models often yielded poor risk estimates, with calibration slopes deviating considerably from unity even on large model development datasets. The stereotype logistic model improved the calibration slope, but still provided biased risk estimates for individual patients. When the true model had a cumulative logit proportional odds form, multinomial logistic regression provided biased risk estimates, although these biases were modest. Nonproportional odds models require more parameters to be estimated from the data, and hence suffered more from overfitting. Despite larger sample size requirements, we generally recommend multinomial logistic regression for risk prediction modeling of discrete ordinal outcomes., (© 2021 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Sodium glucose cotransporter 2 (SGLT2) have proven profound positive effects in heart failure with reduced ejection fraction (HFrEF). These effects are independent from the presence of diabetes. Metabolic effects, antiinflammatory, and antifibrotic properties are discussed as underlying mechanisms. Despite a strong correlation of ventricular arrhythmias with HFrEF, the impact of ertugliflozin on the ventricular arrhythmic burden has not been investigated, yet. Therefore, the Ertugliflozin to Reduce Arrhythmic burden in ICD ± CRT patientS (ERASe) trial was designed to investigate the efficacy and safety of ertugliflozin in patients with reduced and midrange ejection fraction (EF) with or without diabetes. METHODS: Within a multicentre, national, randomized, double-blind, placebo-controlled, phase 3b trial we aim to enrol a total of 402 patients across Austria. Patients with reduced or midrange EF and ICD ± CRT therapy >3 months and previous ventricular tachycardia (at least 10 documented VT episodes within the last 12 months) are randomized in a 1:1 ratio to ertugliflozin (5 mg once daily orally administered) or matching placebo. The primary endpoint of the ERASe trial is to investigate the impact of ertugliflozin on total burden of ventricular arrhythmias. Further objectives will include number of therapeutic interventions of implanted devices, atrial fibrillation and heart failure biomarkers. CONCLUSION: The ERASe trial will be the first trial to test ertugliflozin in heart failure patients with nonpreserved ejection fraction and ongoing ICD ± CRT therapy regardless of their diabetic status. The ERASe trial may therefore extend the concept of SGLT2 inhibition to improve cardiac remodelling, including reduced arrhythmic burden. Trial registration Identifier EudraCT Nr. 2020-002581-14 / ClinicalTrials.gov Identifier: NCT04600921., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19., Methods: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUC SOFA ), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596., Findings: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUC SOFA (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group., Interpretation: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options., Funding: Austrian Science Fund and German Center for Cardiovascular Research., Competing Interests: Declaration of interests AB received research funding from Pfizer and Medtronic as well as speaker honoraria from Bayer, Boehringer Ingelheim, Edwards, Medtronic and Novartis. KDR received a research grant from Daiichi-Sankyo Europe GmbH. UM received fees for participation in a data and safety monitoring board from Thermosome. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Randomised controlled trials have shown diverse results for radial access in patients undergoing primary percutaneous coronary intervention (PPCI). Moreover, it is questionable whether radial access improves outcome in patients with cardiogenic shock undergoing PPCI. We aimed to investigate the outcome according to access site in patients with or without cardiogenic shock, in daily clinical practice., Methods: For the present analysis we included 9,980 patients undergoing PPCI between 2012 and 2018, registered in the multi-centre, nationwide registry on PCI for myocardial infarction (MI). In-hospital mortality, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE) until discharge were compared between 4,498 patients with radial (45%) and 5,482 patients with femoral (55%) access., Results: Radial compared to femoral access was associated with lower in-hospital mortality (3.5% vs. 7.7%; P<0.01). Multivariable logistic regression analysis confirmed reduced in-hospital mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.43 to 0.75]. Furthermore, MACE (OR 0.60, 95% CI: 0.47 to 0.78) as well as NACE (OR 0.59, 95% CI: 0.46 to 0.75) occurred less frequently in patients with radial access. Interaction analysis with cardiogenic shock showed an effect modification, resulting in lower mortality in PCI via radial access in patients without, but no difference in those with cardiogenic shock (OR 1.78, 95% CI: 1.07 to 2.96)., Conclusions: Radial access for patients with acute MI undergoing PPCI is associated with improved survival in a large contemporary cohort of daily practice. However, this beneficial effect is restricted to hemodynamically stable patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-977). The authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Background and Aims: Recently published criteria by 2019 Cirrhotic Cardiomyopathy Consortium set a lower threshold for reduced ejection fraction to diagnose systolic dysfunction in cirrhotic patients, and stress testing was replaced by echocardiography strain imaging. The criteria to diagnose diastolic dysfunction are in general concordant with the 2016 ASE/EACVI guidelines and differ considerably from the 2005 Montreal recommendations. We aimed to assess the prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria., Methods: Cirrhotic patients without another structural heart disease, arterial hypertension, portal vein thrombosis, HCC outside Milan criteria and presence of TIPS were enrolled. Speckle-tracking echocardiography was performed by EACVI certified investigators., Results: A total of 122 patients with cirrhosis fulfilled the inclusion criteria. Overall prevalence of cirrhotic cardiomyopathy was similar for 2005 Montreal and 2019 CCC: 67.2% vs 55.7% (P = .09); and significantly higher compared to 2009 ASE/EACVI criteria: 67.2% vs 35.2% (P < .0001) and 55.7% vs 35.2% (P = .002) respectively. Significantly more patients had diastolic dysfunction according to the 2005 Montreal compared to the 2009 ASE/EACVI and 2019 CCC criteria: 64.8% vs 32.8% (P < .0001) and 64.8% vs 7.4% (P < .0001). Systolic dysfunction was more frequently diagnosed according to 2019 CCC criteria compared to 2005 Montreal (53.3% vs 16.4%,P < .0001) or ASE/EACVI criteria (53.3% vs 4.9%,P < .0001)., Conclusion: Cirrhotic cardiomyopathy was present in around 60% of cirrhotic patients when applying the hepatological criteria. A considerably higher prevalence of systolic dysfunction according to the 2019 CCC criteria was observed. Long-term follow-up studies are needed to establish the validity of these criteria to predict clinically relevant outcomes., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Heart failure (HF) is common and is associated with high morbidity, mortality and high health expenditure. A multidisciplinary disease management plan (DMP) can reduce morbidity and mortality, save costs and improve the quality of life. In Austria, three HF-specific DMPs are currently in a project phase and four established DMPs are active. Although programs are widely heterogeneous with respect to their intervention type, they pursue the same interventional goal by supporting seamless care between inpatient and community care settings with a multidisciplinary team. This survey presents a systematic survey of the HF-specific DMPs in Austria. Disparities between programs are highlighted and discussed. The nationwide establishment of HF-specific DMPs that integrate primary care and cardiology services including a regulation of the remuneration of stakeholders and program infrastructure is needed to decrease the burden of HF for both the individual and society.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors are established antidiabetic drugs with proven cardiovascular benefit. Although growing evidence suggests beneficial effects on myocardial remodeling, fluid balance and cardiac function, the impact of empagliflozin initiated early after acute myocardial infarction (AMI) has not been investigated yet. Therefore, the impact of EMpagliflozin on cardiac function and biomarkers of heart failure in patients with acute MYocardial infarction (EMMY) trial was designed to investigate the efficacy and safety of empagliflozin in diabetic and non-diabetic patients after severe AMI., Methods: Within a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial we will enroll patients with AMI and characteristics suggestive of severe myocardial necrosis are randomized in a 1:1 ratio to empagliflozin (10 mg once daily) or matching placebo. The primary endpoint is the impact of empagliflozin on changes in NT-proBNP within 6 months after AMI. Secondary endpoints include changes in echocardiographic parameters, levels of ketone body concentrations, HbA1c levels and body weight, respectively. Hospitalization rate due to heart failure or other causes, the duration of hospital stay and all-cause mortality will be assessed as exploratory secondary endpoints., Discussion: The EMMY trial will test empagliflozin in patients with AMI regardless of their diabetic status. The EMMY trial may therefore underpin the concept of SGLT2 inhibition to improve cardiac remodeling, pre-and afterload reduction and cardiac metabolism regardless of its antidiabetic effects. Results will provide the rationale for the conduct of a cardiovascular outcome trial to test the effect of empagliflozin in patients with AMI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking., Objectives: To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation., Methods: Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed., Results: Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase., Conclusions: In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions., Competing Interests: Prasugrel was provided without charge by Eli Lilly Europe, Windlesham, UK, and Daiichy Sankyo Europe, Munich, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Duration and compostion of dual antiplatelet therapy has been increasingly changed within the past few years as also indicated in the firmer ESC guidelines. The current manuscript summarizes the most important changes in dual antiplatelet therapy as shown by a recent ESC position paper and offers quick insight into these new developments.

Purpose: The Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort is aimed to gain a better understanding of cardiovascular risk factors and their relation to the diagnosis and severity of coronary artery disease, as well as to the long-term prognosis in consecutive (including revascularised) patients referred for elective coronary angiography., Participants: The included patients visited the University Clinic of Cardiology at Innsbruck (Austria), which fulfils a secondary and tertiary hospital function. Inclusion took place in the period between February 2004 and April 2008 and resulted in a total of 8296 patients aged 18-91 years; 65% of them were men., Findings to Date: There was one follow-up round on vital status through record linkage for 84% of the cohort (those with residence in Tyrol), resulting in a follow-up duration of over 5.5 to nearly 10.0 years among survivors. The data contain basic patient characteristics, cardiovascular risk factors, laboratory measurements, medications, detailed information on the extent and severity of coronary artery disease, revascularisation history, treatment strategy and mortality specifics. A few studies have already been published., Future Plans: Various diagnostic and prognostic studies are planned, also concerning complications, competing risks and cost-effectiveness. Collaboration with other research groups is welcomed., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The long-term increased cardiovascular risk of patients with an acute coronary syndrome (ACS) is a challenging and common clinical problem. Recent evidence demonstrated an ischemic benefit for a prolonged dual antiplatelet therapy beyond the initial 12 months at the cost of an increased bleeding risk. Individual, careful and repeated risk-benefit analyses are essential for an optimized patient management in which cardiovascular rehabilitation providers may play a central role.

Randomized controlled trials have shown conflicting results regarding the outcome of bivalirudin in primary percutaneous coronary intervention (PPCI). The aim of this study was to evaluate the in-hospital outcomes of patients receiving heparin or bivalirudin in a real-world setting of PPCI: 7,023 consecutive patients enrolled in the Austrian Acute PCI Registry were included between January 2010 and December 2014. Patients were classified according to the peri-interventional anticoagulation regimen receiving heparin (n = 6430) or bivalirudin (n = 593) with or without GpIIb/IIIa inhibitors (GPIs). In-hospital mortality (odds ratio [OR] 1.13, 95% confidence interval [CI] 0.57 to 2.25, p = 0.72), major adverse cardiovascular events (OR 1.18, 95% CI 0.65 to 2.14, p = 0.59), net adverse clinical events (OR 1.01, 95% CI 0.57 to 1.77, p = 0.99), and TIMI non-coronary artery bypass graft-related major bleeding (OR 0.41, 95% CI 0.09 to 1.86, p = 0.25) were not significantly different between the groups. However, we detected potential effect modifications of anticoagulants on mortality by GPIs (OR 0.12, 95% CI 0.01 to 1.07, p = 0.06) and access site (OR 0.25, 95% CI 0.06 to 1.03, p = 0.06) favoring bivalirudin in femoral access. In conclusion, this large real-world cohort of PPCI, heparin-based anticoagulation showed similar results of short-term mortality compared with bivalirudin. We observed a potential effect modification by additional GPI use and access favoring bivalirudin over heparin in femoral, but not radial, access., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Spasticity is a very common syndrome in patients with multiple sclerosis (pwMS), but available treatments lead to sufficient symptom control only in one third., Objective: To investigate the impact of an individualized training program on improving spasticity in a prospective pilot trial in pwMS suffering from moderate spasticity (defined as ≥ 4 on a normative rating scale; NRS)., Methods: PwMS were familiarized with predefined exercises targeting spasticity while undergoing inpatient rehabilitation (IR). After IR, 20 pwMS were 1:1 randomized either to a newly designed APP-based home therapy program providing suitable exercises on a daily basis or to a paper-based home therapy program for 3 months. At month 3, all patients received the APP-based home program for another 3 months. Degree of spasticity was rated on the NRS., Results: Undergoing inpatient rehabilitation for a mean of 32 days led to a significant reduction in spasticity in pwMS (p = 0.00). Further self-training with the APP-based home program for 3 months led to 1.2 lower mean NRS as compared to training with the conventional paper-based program (p = 0.09). Spasticity was found to be on low levels again in both groups after 6 months., Conclusion: In pwMS, an individually tailored anti-spasticity program delivered by a software APP is a feasible tool for increasing long-term adherence to self-training thereby positively impacting spasticity in pwMS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To externally validate and extend a recently proposed prediction model to diagnose obstructive coronary artery disease (CAD), with the ultimate aim to better select patients for coronary angiography., Design: Analysis of individual baseline data of a prospective cardiology cohort., Setting: Single-centre secondary and tertiary cardiology clinic., Participants: 4888 patients with suspected CAD, without known previous CAD or other heart diseases, who underwent an elective coronary angiography between 2004 and 2008 as part of the prospective Coronary Artery disease Risk Determination In Innsbruck by diaGnostic ANgiography (CARDIIGAN) cohort. Relevant data were recorded as in routine clinical practice., Main Outcome Measures: The probability of obstructive CAD, defined as a stenosis of minimally 50% diameter in at least one of the main coronary arteries, estimated with the predictors age, sex, type of chest pain, diabetes status, hypertension, dyslipidaemia, smoking status and laboratory data. Missing predictor data were multiply imputed. Performance of the suggested models was evaluated according to discrimination (area under the receiver operating characteristic curve, depicted by the c statistic) and calibration. Logistic regression modelling was applied for model updating., Results: Among the 4888 participants (38% women and 62% men), 2127 (44%) had an obstructive CAD. The previously proposed model had a c statistic of 0.69 (95% CI 0.67 to 0.70), which was lower than the expected c statistic while correcting for case mix (c=0.80). Regarding calibration, there was overprediction of risk for high-risk patients. All logistic regression coefficients were smaller than expected, especially for the predictor 'chest pain'. Extension of the model with high-density lipoprotein and low-density lipoprotein cholesterol, fibrinogen, and C reactive protein led to better discrimination (c=0.72, 95% CI 0.71 to 0.74, p<0.001 for improvement)., Conclusions: The proposed prediction model has a moderate performance to diagnose obstructive CAD in an unselected patient group with suspected CAD referred for elective CA. A small, but significant improvement was attained by including easily available and measurable cardiovascular risk factors., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS., Methods/results: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective., Conclusion: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length., (© 2016 John Wiley & Sons Ltd.)

The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT.

Background: Drug-eluting stents (DES) improve outcomes in elderly patients with small coronary artery disease compared with bare-metal stents (BMS), but randomized data in elderly patients in need of large coronary stents are not available., Methods: Planned secondary analysis of patients ≥75 years recruited to the "BASKET-PROVE" trial, in which 2,314 patients undergoing percutaneous coronary intervention for large (≥3.0 mm) native vessel disease were randomized 2:1 to DES (everolimus- vs sirolimus-eluting stents 1:1) versus BMS. All patients received 12 months of dual antiplatelet therapy. The primary end point was a composite of cardiac death or nonfatal myocardial infarction at 2 years., Results: Comparison of DES versus BMS among 405 patients ≥75 years showed significantly lower rates of the primary end point for DES (5.0% vs 11.6%; hazard ration (HR) 0.64 [0.44-0.91]; P = .014). Rates of nonfatal myocardial infarction (1.2% vs 5.5%, hazard ration (HR) 0.44 [0.21-0.83]; P = .009), all-cause death (7.4% vs 14.4%; HR 0.7 [0.51-0.95]; P = .02), and target vessel revascularization (TVR) (2.3% vs 6.2%; HR 0.59 [0.34-0.99]; P = .046) were also lower, whereas stent thrombosis and bleeding rates were similar. In contrast, among patients <75 years (n = 1,909), the only significant benefit of DES was a reduced rate of TVR (4.0% vs 8.7%, HR 0.66 [0.55-0.80]; P < .0001)., Conclusions: In patients ≥75 years requiring large (≥3.0 mm) coronary stents, use of DES was beneficial compared with BMS and reduced the rate of ischemic events, mortality, and TVR. These data suggest that DES should be preferred over BMS in elderly patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to evaluate the extent of phenoconversion of CYP2C19 enzyme activity caused by commonly prescribed proton pump inhibitors (PPI) omeprazole and esomprazole. The Ptz-BT was administered to 26 healthy volunteers and 8 stable cardiovascular patients twice at baseline and after 28 days of PPI therapy to evaluate reproducibility of the Ptz-BT and changes in CYP2C19 enzyme activity (phenoconversion) after PPI therapy. The average intrapatient interday variability in CYP2C19 phenotype (n = 31) determined by Ptz-BT was considerably low (coefficient of variation, 17%). Phenotype conversion resulted in 25 of 26 (96%) nonpoor metabolizer (non-PM) volunteers/patients as measured by the Ptz-BT at baseline and after PPI therapy. The incidence of PM status by phenotype following administration of omeprazole/esomeprazole (known inhibitors of CYP2C19) was 10-fold higher than those who are genetically PMs in the general population, which could have critical clinical implications for personalizing medications primarily metabolized by CYP2C19, such as clopidogrel, PPI, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, phenytoin, etc. The Ptz-BT can rapidly (30 minutes) evaluate CYP2C19 phenotype and, more importantly, can identify patients with phenoconversion in CYP2C19 enzyme activity caused by nongenetic factors such as concomitant drugs., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear., Methods and Results: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES., Conclusions: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01166685., (© 2014 American Heart Association, Inc.)

Background: Women undergoing coronary angiography (CA) due to chest pain are more likely to present with less extensive coronary artery disease (CAD) than men, which might be attributed to different effects of cardiovascular risk factors on coronary atherogenesis between sexes. The aim of the present study was to evaluate sex differences in independent factors associated with obstructive and non-obstructive CAD in a large consecutive cohort of patients undergoing elective CA., Methods: Data from 7819 patients (2653 women and 5184 men), including cardiovascular risk factors, clinical presentation, CAD severity and treatment decisions were analysed., Results: Women were older than men (65 ± 11 vs. 63 ± 11 years, p < 0.001); low-density lipoprotein cholesterol (LDL; 125 ± 38 vs. 122 ± 37 mg/dL, p < 0.001) and high-density lipoprotein cholesterol (HDL) cholesterol levels (62 ± 18 vs. 51 ± 15 mg/dL, p < 0.001) were higher in women; and smokers were more frequently men (14.4 vs. 20.1%, p < 0.001). Men more frequently had an obstructive CAD (41.1 vs. 65.6%, p < 0.001). Multivariable analyses revealed age, HDL cholesterol, hypercholesterolaemia, diabetes mellitus, arterial hypertension and a positive family history being associated with obstructive CAD in both sexes, whereas smoking was independently associated with obstructive CAD only in women. The association of hypercholesterolaemia with obstructive CAD was stronger in men. For non-obstructive CAD, no sex-specific associated factors could be identified., Conclusion: The impact of smoking and hypercholesterolaemia on coronary atherosclerosis is different between women and men. This might be taken into account when planning individual interventions to reduce cardiovascular risk.

Background: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined., Methods: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models., Results: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT., Conclusion: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: The use of drug-eluting stents (DES) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is controversial and not yet endorsed in clinical guidelines., Methods and Results: This was an a priori planned post hoc analysis involving 754 NSTE-ACS patients from the randomised BASKET-PROVE trial (sirolimus-eluting stent vs. everolimus-eluting stent vs. bare metal stent in large-vessel stenting). The primary endpoint was the combined two-year rate of cardiovascular death or non-fatal myocardial infarction (MI). Secondary endpoints were each component of the primary endpoint, and clinically indicated target vessel revascularisation (TVR) and stent thrombosis. Compared to patients with BMS, those treated with SES and EES had a strong trend towards lower two-year rates of the primary endpoint (HR: 0.31 [CI: 0.11-0.90], p=0.03, and HR: 0.74 [CI: 0.44-1.24], p=0.25), and of TVR (HR: 0.58 [CI: 0.29-1.15], p=0.12) and (HR: 0.52 [CI: 0.34-0.78], p=0.002). When the SES and EES groups were combined and compared to BMS, significant reductions in both cardiovascular death/MI and TVR were found., Conclusions: Compared with BMS, use of DES in NSTE-ACS patients undergoing stent implantation in large vessels was associated with a reduction in both TVR and the combined endpoint consisting of cardiovascular death/MI. Thus, DES use improves both efficacy and safety. These findings support the use of DES in NSTE-ACS patients.

Aim: Data regarding the prognostic value of peripheral endothelial function testing in patients with cardiovascular disease are conflicting. Peripheral arterial tonometry(PAT) is increasingly used to measure the peripheral endothelial function. The prognostic value of this method has not been investigated thus far in patients with cardiovascular disease and/or a high cardiovascular risk profile., Methods: In 96 patients with significant coronary artery disease(CAD) or＜70% stenosis and ≥ three cardiovascular risk factors, reactive hyperemia was induced following upper arm occlusion and the PAT-ratio between baseline and hyperemia was calculated. The patients were followed for cardiovascular events(revascularization, acute coronary syndrome, ischemic stroke, cardiovascular death, repeat coronary angiography due to chest pain) for 44±14 months. The first event was included in the combined end point., Results: The study cohort was divided according to the median PAT-ratio(1.91). The combined end point occurred in 14 patients with a PAT-ratio below the median(1.91) and in 12 patients with a PAT-ratio of ≥1.91 (p=0.65). In a subgroup of 76 patients, the PAT-ratio was reassessed after six months. No differences in the event rate were found between the patients who exhibited deterioration(n=50) and those who exhibited an improvement in the PAT-ratio of ＞0.1(n=26; 22 vs. 32%, p=0.32). The combined end point occurred earlier in the patients with a PAT-ratio within the 1st tertile than in those with a PAT-ratio within the 2nd/3rd tertile(11.3±11.0 vs. 27.5±18.6 months, p=0.03)., Conclusions: In patients with established CAD or a high cardiovascular risk profile, the PAT-ratio cannot be used to predict the risk of future cardiovascular events. However, a lower PAT-ratio may be associated with the earlier occurrence of cardiovascular events.

Background: Elevated heart rate (HR) is associated with mortality in a number of heart diseases. We examined the long-term prognostic significance of HR at discharge in a contemporary population of patients with stable angina (SAP), non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) revascularized with percutaneous coronary intervention (PCI)., Methods: Patients from the BASKET-PROVE trial, an 11-center randomized all-comers trial comparing bare-metal and drug-eluting stenting in large coronary vessels, were included. Discharge HR was determined from a resting ECG. Long-term outcomes (7 days to 2 years) were evaluated for all-cause mortality and cardiovascular death and non-fatal myocardial infarction., Results: A total of 2029 patients with sinus rhythm were included, 722 (35.6%) SAP, 647 (31.9%) NSTE-ACS, and 660 (32.5%) STEMI. Elevated discharge HR was associated significantly with all-cause mortality: when compared to a reference of <60 beats per minute (bpm), the adjusted hazard ratios were (95% CI) 4.5 (1.5-13.5, p=0.006) for 60-69 bpm, 3.8 (1.2-11.9, p=0.022) for 70-79 bpm, 4.3 (1.2-15.6, p=0.025) for 80-89 bpm, and 16.9 (5.2-55.0, p<0.001) for >90 bpm. For cardiovascular death/myocardial infarction, a discharge HR >90 bpm was associated with a hazard ratio of 6.2 (2.5-15.5, p<0.001) compared to a HR <60 bpm. No interaction was found for disease presentation, diabetes or betablocker use., Conclusion: In patients revascularized with PCI for stable angina or acute coronary syndromes an elevated discharge HR was independently associated with poor prognosis. Conversely, a HR <60 bpm at discharge was associated with a good long-term prognosis irrespective of indication for PCI., (© 2013.)

Aims: Chronic kidney disease (CKD) is associated with worse outcomes in patients with coronary artery disease (CAD). How CKD influences the benefit-risk balance of drug-eluting stents (DES) versus bare-metal stents (BMS) is less known., Methods and Results: In the multicentre BASKET-PROVE trial, 2314 patients in need of large coronary stenting (≥ 3.0mm) were randomised 2:1 to DES or BMS. In an a priori planned secondary analysis, outcomes were evaluated according to renal function defined by estimated glomerular filtration rates (eGFR; normal: eGFR ≥ 60 ml/min/1.73 m(2); CKD: eGFR<60 ml/min/1.73 m(2)). The primary endpoint was the first major adverse cardiac event (MACE: cardiac death, myocardial infarction, target vessel revascularisation) up to 2 years. A Cox proportional-hazard model was used to evaluate adjusted relative risks (hazard rates, HRs) for BMS versus DES. The interaction of stent type and renal function was tested. CKD patients (189 (11.2%)/1681 with such data) had a 2-year MACE rate of 8.5% versus 7.4% in those without CKD [HR 0.98 (0.56-1.72), p=0.95] with cardiac mortalities of 5.3% and 1.5%, respectively (p=0.002, non-significant after baseline adjustments). The MACE rate was lower in CKD patients with DES than with BMS [4.9% versus 15.2%, p=0.017, HR 0.29(0.10-0.80)] as was the MACE rate in patients without CKD [5.6% with DES versus 11.1% with BMS, p<0.0001, HR 0.51(0.35-0.75)]. No significant interaction between stent type and renal function was found., Conclusions: This analysis of patients needing large coronary artery stenting confirms the increased mortality of CKD patients and documents a long-term benefit of DES compared to BMS irrespective of kidney function., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

An increased brachial artery intima media thickness (BA-IMT) has been shown to be of prognostic value. Conflicting prognostic data have been reported for brachial artery flow-mediated vasodilation (BA-FMD), and the longest evaluated follow-up period to date is 5.5 years. We sought to investigate the very late prognostic value of BA-IMT and BA-FMD in 396 consecutive patients (age 54 ± 9 years) admitted for invasive evaluation of chest pain. BA-IMT and BA-FMD were measured using high-resolution ultrasonography. The patients were divided according to the median BA-IMT (0.37 mm) and median BA-FMD (7.6%). After a mean follow-up of 141 ± 12 months, cardiovascular events were documented. More cardiovascular events were found in patients with an increased BA-IMT (50 vs 78 events, p = 0.003). When the groups were compared according to the median BA-FMD, no differences in the number of events were documented (70 vs 75 events, p = 0.60). On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of coronary artery disease, BA-FMD, and BA-IMT, only the presence of coronary artery disease and BA-IMT remained significantly associated with outcome. In conclusion, BA-IMT, but not BA-FMD, predicted cardiovascular events and cardiovascular death with ≤12 years of follow-up in patients undergoing an invasive evaluation of chest pain. Our results represent, by far, the longest follow-up of BA-IMT and peripheral endothelial function testing compared with previously reported data., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to compare N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, and gamma-glutamyl transferase (γ-GT) with traditional risk markers for estimating prognosis in patients with stable coronary artery disease (CAD)., Materials and Methods: Evaluation of mortality and a combined clinical endpoint (mortality, need for coronary revascularization, myocardial infarction, hospitalization for cardiac causes, or stroke) during an average 3.2-year follow-up in 394 consecutive patients (73% male patients, age: 67±9 years) with angiographically proven stable CAD., Results: Univariate Kaplan-Meier survival rate analysis showed that traditional risk markers, apart from impaired renal function, three-vessel CAD, and a reduced left ventricular function at the time of coronary angiography, were not of prognostic relevance for prediction of outcome. NT-proBNP, high-sensitivity C-reactive protein, and gamma-glutamyl transferase were significant predictors of mortality; however, only NT-proBNP was a significant predictor of the combined endpoint. In age-adjusted and sex-adjusted multivariate Cox regression analysis, NT-proBNP was the strongest independent predictor of the combined endpoint (odds ratio 2.92, 95% confidence interval: 1.72-4.94, first vs. third tertile). All three laboratory parameters remained independent risk markers for mortality in multivariate analysis. NT-proBNP, however, revealed the highest odds ratio (5.23, 95% confidence interval: 1.17-23.23, first vs. third tertile). Concentrations greater than 356 ng/l predicted mortality with a sensitivity of 70%, a specificity of 71%, a positive likelihood ratio of 2.4, and a negative likelihood ratio of 0.42., Conclusion: In comparison with other tested novel biomarkers and traditional risk markers, NT-proBNP was the most predictive prognostic marker in multivariate analysis in patients with stable CAD.

Background: In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known., Methods: In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels ≥3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy., Results: By the end of 2010, 878 patients (37% of those planned) were enrolled., Conclusions: This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting., (Copyright © 2012 Mosby, Inc. All rights reserved.)

AIMS Pre-treatment with clopidogrel results in a reduction of ischaemic events in non-ST-elevation acute coronary syndromes. Data on upstream clopidogrel in the setting of primary percutaneous coronary intervention (PCI) are limited. The aim of this study was to investigate whether clopidogrel loading before arrival at the PCI centre may result in an improved outcome of primary PCI for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS In a multicentre registry of acute PCI, 5955 patients undergoing primary PCI in Austria between January 2005 and December 2009 were prospectively enrolled. The patients consisted of two groups, a clopidogrel pre-treatment group (n = 1635 patients) receiving clopidogrel before arrival at the PCI centre and a peri-interventional clopidogrel group (n = 4320 patients) receiving clopidogrel at a later stage. Multiple logistic regression analysis including major confounding factors stratified by the participating centres was applied to investigate the effect of pre-treatment with clopidogrel on the in-hospital mortality. Additionally, two subgroups, with or without the use of GP IIb/IIIa antagonist therapy in the catheterization laboratory, were analysed. On univariate analysis, clopidogrel pre-treatment was associated with a reduced in-hospital mortality (3.4 vs. 6.1%, P< 0.01) after primary PCI. On multivariate analysis, clopidogrel pre-treatment remained an independent predictor of in-hospital mortality [odds ratio (OR) = 0.60, 95% confidence interval (CI) 0.35-0.99; P =0.048], especially in patients receiving additional GP IIb/IIIa antagonist therapy in the catheterization laboratory (OR = 0.40, 95% CI 0.19-0.83; P =0.01). CONCLUSION Clopidogrel pre-treatment before arrival at the PCI centre is associated with reduced mortality in a real world setting of primary PCI. These results strongly support the recommendation of clopidogrel treatment 'as soon as possible' in patients with STEMI undergoing pimary PCI.

Background: The best second arterial conduit for multiple arterial revascularization (MAR) is still a matter of debate. Previous studies on the benefit of either using the radial artery (RA) or the right internal thoracic artery (RITA) in coronary artery bypass grafting are not conclusive. The aim of our study was to compare the perioperative and long-term outcome of either RA or RITA grafts as second conduits for MAR., Methods and Results: A consecutive series of 1001 patients undergoing first nonemergent coronary artery bypass grafting receiving either RA or RITA as second graft for MAR between 2001 and 2010 were studied. There were 277 patients receiving a RITA and 724 patients receiving a RA in addition to a left internal thoracic artery (LITA). Concomitant saphenous vein grafts (SVG) were grafted in addition as necessary. Propensity score-matched analysis was performed to compare the 2 groups, bilateral ITA±SVG (BITA±SVG group) and the LITA+RA±SVG group relative to overall survival and major adverse cardiac and cerebrovascular events-free survival. Hazard ratios and their 95% confidence intervals were estimated by COX regression stratified on matched pairs. The incidence of perioperative major adverse cardiac and cerebrovascular events was significantly lower in the BITA±SVG group (1.4% versus 7.6%, P<0.001). Overall survival (hazard ratio 0.23; 95% confidence interval 0.066-0.81; P=0.022) and major adverse cardiac and cerebrovascular events-free survival (hazard ratio 0.18; 95% confidence interval 0.08-0.42; P<0.001) were significantly better in the BITA±SVG group compared to the LITA+RA±SVG group., Conclusions: The results of our study provide strong evidence for the superiority of a RITA graft compared to RA as a second conduit in MAR.

Acute coronary syndromes (ACS) are still associated with significant morbidity and mortality. Dual antiplatelet therapy with clopidogrel and acetyl-salicylic acid has become the standard of care for patients with ACS in the last 2 decades. However, clopidogrel has drawbacks including delayed therapeutic effect, significant interindividual variability of platelet aggregation inhibition or reduced action on thrombocytes due to interaction with other drugs or genetic polymorphisms. Consequently, new antiplatelet drugs have been developed. Two of these drugs, namely prasugrel and ticagrelor, have been approved by the European Medicines Agency (EMA) and are already available in many European countries. For each substance a "mega-trial" has been published. Both agents were clearly superior compared to clopidogrel and should be therefore preferred in patients with ACS. However, no study has directly compared efficacy as well as safety of prasugrel and ticagrelor so far. Hence, clinicians will be claimed to decide which one to choose in everyday practice. The aim of this manuscript is to summarize the current literature and to provide a guide for individual decision-making between prasugrel and ticagrelor in ACS in daily routine.

Shift working is related to increased cardiovascular morbidity. Peripheral endothelial dysfunction, an inherent feature of early atherosclerosis, has been suggested as a surrogate marker of cardiovascular risk. Whether shift working is associated with peripheral endothelial dysfunction has not been investigated to date. A total of 48 male shift workers (SWs) and 47 male nonshift workers (NSWs) (mean age 43 ± 5 years) were recruited from a glass manufactory. The SWs and NSWs were matched according to age, body mass index, smoking habits, family history of premature coronary artery disease, prevalence of hypercholesterolemia and hypertension, and work place. Their sport habits were also documented. Peripheral endothelial function was assessed using the EndoPAT technique to determine the peripheral arterial tone (PAT) index. According to the study design, no difference was found in the risk factor profiles between the SWs and NSWs. Despite a greater percentage of regular physical activity among the SWs (16.7 vs 4.3%, p = 0.05), shift working was associated with a reduced PAT index compared to working only on the day shift (PAT index 1.73 ± 0.4 vs 1.94 ± 0.5, p = 0.03). In the NSW group, the participants with regular physical training (n = 16) had a greater PAT index than those without regular physical activity (n = 12; PAT index 2.28 ± 0.45 vs 1.86 ± 0.51, p = 0.03). No such difference was found in the SWs. In conclusion, SWs had a reduced PAT index compared with NSWs, suggesting endothelial dysfunction. Therefore, the known increased cardiovascular risk in those shift working might be related to endothelial dysfunction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether this increase in risk was also seen with second-generation drug-eluting stents., Methods: We randomly assigned 2314 patients needing stents that were 3.0 mm or more in diameter to receive sirolimus-eluting, everolimus-eluting, or bare-metal stents. The primary end point was the composite of death from cardiac causes or nonfatal myocardial infarction at 2 years. Late events (occurring during months 7 to 24) and target-vessel revascularization were the main secondary end points., Results: The rates of the primary end point were 2.6% among patients receiving sirolimus-eluting stents, 3.2% among those receiving everolimus-eluting stents, and 4.8% among those receiving bare-metal stents, with no significant differences between patients receiving either drug-eluting stent and those receiving bare-metal stents. There were also no significant between-group differences in the rate of late events or in the rate of death, myocardial infarction, or stent thrombosis. Rates of target-vessel revascularization for reasons unrelated to myocardial infarction were 3.7% among patients receiving sirolimus-eluting stents, 3.1% among those receiving everolimus-eluting stents, and 8.9% among those receiving bare-metal stents. The rate of target-vessel revascularization was significantly reduced among patients receiving either drug-eluting stent, as compared with a bare-metal stent, with no significant difference between the two types of drug-eluting stents., Conclusions: In patients requiring stenting of large coronary arteries, no significant differences were found among sirolimus-eluting, everolimus-eluting, and bare-metal stents with respect to the rate of death or myocardial infarction. With the two drug-eluting stents, similar reductions in rates of target-vessel revascularization were seen. (Funded by the Basel Cardiovascular Research Foundation and the Swiss National Foundation for Research; Current Controlled Trials number, ISRCTN72444640.).

Background: Primary percutaneous coronary intervention (PPCI) has become the preferred reperfusion strategy in ST-elevation myocardial infarction (STEMI). Implementation of networks of care and registries providing continuous quality assessment are key components for optimal management in patients with STEMI., Aim: To analyze procedural success and in-hospital outcome of interventional therapy of STEMI in Austria., Methods: We evaluated a total number of 4016 consecutive STEMI patients registered in the first three years after implementation of the Austrian acute PCI registry in January 2005., Results: The rate of PPCI as an indication for acute coronary intervention increased from 83.5% in 2005 to 92.4% in 2007 (P < 0.0001). During this period the median door-to-balloon time decreased from 60.0 (40.0-90.0) min to 53.0 (30.0-80.0) min (P = 0.012). The percentage of patients receiving adequate adjunctive antithrombotic therapy with ASA/heparin and clopidogrel significantly increased (78.8-85.1% and 67.8-90.3%, respectively; P < 0.001). Overall in-hospital mortality was 9.6% in rescue PCI, 6.4% in facilitated PCI and 5.1% in PPCI. On multivariate analysis, cardiogenic shock (OR: 20.21, 95% CI: 12.21-33.44, P < 0.001), resuscitation (OR: 2.62, 95% CI: 1.47-4.69, P = 0.01), age (OR: 1.04, 95% CI: 1.02-1.06, P < 0.001) and angiographic success (OR: 5.93, 95% CI: 3.33-10.57, P < 0.001) were independent predictors of in-hospital death., Conclusion: Continuous nationwide efforts to establish regional networks for STEMI treatment in the years 2005-2007 led to a decrease in door-to-balloon time, improved adjunctive antithrombotic therapy and an in-hospital mortality of 5%. Results of interventional STEMI treatment in Austria are in accordance with current guidelines and with other contemporary registries.

2008 new guidelines for the management of patients with ST-elevation myocardial infarction were published by the European Society of Cardiology. For daily clinical practice, changes in recommendations concerning the preferred revascularization therapy according to different time delays are of great interest. This review focuses on possible implications of these new guidelines on the choice of reperfusion strategies in rural areas.

Aim of the study was to assess health-related quality of life as well as anxiety and depression in patients undergoing coronary artery bypass graft (CABG). A total of 54 patients answered questionnaires assessing quality of life (SF-36, MacNew), anxiety and depression (STAI, HADS-D) before surgery as well as 4 weeks and 3 months afterwards. Significant improvements in health-related quality of life (MacNew) were identified 3 months after surgery. Whereas preoperative anxiety significantly correlated with health-related quality of life (MacNew) three months after surgery, correlations between preoperative depression and postoperative quality of life were only found for singular scales. Regarding clinical practice providing information about the probable course of quality of life and explaining surgery as a kind of input for the benefit of long-term enhancement seems necessary. Furthermore the assessment of preoperative well-being should be integrated in routine care in order to identify and support patients with higher levels of anxiety and/or depression.