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Background: Purinergic signaling receptor Y12 (P2Y12) inhibitors are a fundamental part of pharmacological therapy in acute coronary syndrome (ACS) for preventing recurrent ischemic events. Current guidelines support the use of prasugrel over ticagrelor—however, ticagrelor is widely used for preclinical loading during ACS due to its ease of administration. In this regard, it remains unknown whether the preclinical loading with P2Y12 inhibitors impacts decision-making for the long-term dual antiplatelet strategy, as well as cardiovascular outcomes, including re-percutaneous coronary intervention in real-world settings. Methods: Within this population-based prospective observational study, all patients with ACS who received medical care via the Emergency Medical Service (EMS) in the city of Vienna between January 2018 and October 2020 were enrolled. Patients were stratified according to their P2Y12 inhibitor loading regimen. Subsequently, the association of P2Y12 inhibitor loading on long-term prescription at discharge and outcome was assessed. Results: The entire study cohort consisted of 1176 individuals with ST-elevation myocardial infarction (STEMI), of whom 47.5% received prasugrel and 52.5% ticagrelor. The likelihood of adhering to the initial P2Y12 inhibitor strategy during the clinical stay was high for both ticagrelor (84%; OR: 10.00; p < 0.001) and prasugrel (77%; OR: 21.26; p < 0.001). During patient follow-up (median follow-up time three years), 84 (7.1%) patients died due to cardiovascular causes, and 82 (7.0%) patients required re-PCI. Notably, there was no difference in cardiovascular mortality (6.6% ticagrelor vs. 7.7% prasugrel) or re-PCI rates (6.6% ticagrelor vs. 7.3% prasugrel) addressing the P2Y12 inhibition strategy. Conclusion: We observed that, regardless of the initial antiplatelet inhibitor strategy, the in-hospital P2Y12 adherence was exceedingly high, and there was a minimal occurrence of switching to another P2Y12 inhibitor. Most importantly, no significant difference in cardiovascular death/re-PCI between ticagrelor and prasugrel-based preclinical loading has been observed. Consequently, the choice of high potent P2Y12 did not influence the cardiac outcome from a long-term perspective.

Background: Left ventricular thrombus (LVT) is a rare but dreaded complication during the acute phase of acute coronary syndrome (ACS). However, profound data on long-term outcome and associated anti-thrombotic treatment strategies of this highly vulnerable patient population are scarce in current literature. Methods: Patients presenting with ACS were screened for presence of LVT and subsequently included within a prospective clinical registry. All-cause mortality and the composite of MACE and thrombo-embolic events were defined as primary and secondary endpoint. Results: Within 43 patients presenting with LVT, thrombus resolution during patient follow-up was observed in 27 individuals (62.8%). Patients that reached a resolution of LVT experienced lower incidence rates of death (-23.9%; p=0.022), MACE (-37.8%; p=0.005) and thrombo-embolic events (-35.2%; p=0.008). Even after adjustment for clinical variables, thrombus resolution showed an independent inverse association with all-cause death with an hazard ratio (HR) of 0.14 (95%CI: 0.03-0.75; p=0.021) and as well as with MACE with a HR of 0.22 (95%CI: 0.07-0.68; p=0.008) and thrombo-embolic events with a HR of 0.22 (95%CI: 0.06-0.75; p=0.015). Triple antithrombotic therapy (TAT) with ticagrelor/prasugrel showed a strong and independent association with thrombus resolution with an adjusted HR of 3.25 (95%CI: 1.22-8.68; p=0.019) compared to other strategies. Conclusion: The presented data indicate a poor outcome of ACS patients experiencing LVT. In terms of a personalized risk stratification, thrombus resolution has a strong protective impact on both all-cause death and MACE with the potential to tailor treatment decisions – including an intensified anti-thrombotic treatment approach – in this patient population.

Objectives Post-operative atrial fibrillation (POAF) represents a common complication after cardiac surgery that is associated with unfavorable clinical outcome. Identifying patients at risk for POAF is crucial but challenging. Purpose This study aimed to investigate the prognostic potential of speckle tracking echocardiography (STE) on POAF and fatal adverse events from a long-term perspective. Methods A total of 124 patients undergoing elective cardiac surgery were prospectively enrolled and underwent pre-operative STE. Patients were followed prospectively for the occurrence of POAF within the entire hospitalization and reaching the secondary endpoints cardiovascular (CV) and all-cause mortality. Results Within the study population 43.5% (n=53) of enrolled individuals developed POAF. After a median follow-up of 3.9 years, 25 (20.2%) patients died. We observed that patients presenting with POAF had lower global peak atrial longitudinal strain (PALS) values compared to the non-POAF arm (POAF: 14.8% [95% CI: 10.9–17.8] vs. non-POAF: 19.4% [95% CI: 14.8–23.5], p Conclusion Global PALS is associated with the development of POAF following surgery in an unselected patient population undergoing CABG and/or valve surgery. Since patients with global PALS Funding Acknowledgement Type of funding sources: None.

Although a strong association of cardiogenic shock (CS) with in-hospital mortality in patients with acute coronary syndrome (ACS) is well established, less attention has been paid to its prognostic influence on long-term outcome. We evaluated the impact of CS in 1173 patients undergoing primary percutaneous coronary interventions between 1997 and 2009. Patients were followed up until the primary study endpoint (cardiovascular mortality) was reached. Within the entire study population, 112 (10.4%) patients presented with CS at admission. After initial survival, CS had no impact on mortality (non-CS: 23.5% vs. CS: 24.0%; p = 0.923), with an adjusted hazard ratio of 1.18 (95% CI: 0.77–1.81; p = 0.457). CS patients ≥ 55 years (p = 0.021) with moderately or severely impaired left ventricular function (LVF; p = 0.039) and chronic kidney disease (CKD; p = 0.013) had increased risk of cardiovascular mortality during follow-up. The present investigation extends currently available evidence that cardiovascular survival in CS is comparable with non-CS patients after the acute event. CS patients over 55 years presenting with impaired LVF and CKD at the time of ACS are at increased risk for long-term mortality and could benefit from personalized secondary prevention.

To assess real-world data on the clinical implementation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in cardiovascular patients and to investigate barriers to prescribe these agents. Patients presenting with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) between 01/2014 and 04/2020 were included in the present analysis and followed prospectively. All first-time prescriptions of SGLT2i and GLP-1RA were identified. Among 1498 patients with CAD and T2DM, 17.6% of patients received an SGLT2i and 5.5% a GLP-1RA. The prescription of SGLT2i (+38.7%; p < 0.001) and GLP-1RA (+8%; p = 0.007) significantly increased during the observation period. Considering remuneration criteria for SGLT2i therapy, lowering the GFR cut-off to 30 ml/min/1.73 m2 would allow additional 26.6% of patients to qualify for an SGLT2i therapy. While SGLT2i therapy was inversely associated with CV mortality (adjusted hazard ratio of 0.18 [95% CI: 0.05–0.76]; p = 0.019), GLP-1RA therapy showed a trend for risk reduction. The present analysis revealed an infrequent prescription of SGLT2i and GLP-1RAs in patients with T2DM and CAD in clinical practice. Remuneration regulations that better reflect the inclusion criteria of the CV outcome trials would allow more patients at high risk to receive these CV protective drugs. Most importantly, while GLP-1RA therapy showed a trend for risk reduction of cardiovascular mortality, the use of SGLT2i had a strong inverse impact on cardiovascular mortality from a long-term perspective.

Background Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8+CD28null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue. Methods A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69). Results Comparing patients developing POAF to individuals free of POAF, the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8+CD28null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8+CD28null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01–10.18; p = 0.048). Conclusion We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.

Meditation as a form of body–mind interaction for primary and secondary prevention in cardiovascular disease has been discussed critically in the past. However, data that aimed to link this intervention to a reduction of various aspects of cardiovascular disease, rendering it a potential part of a cost-effective treatment approach in patients at risk, remain scarce and inconclusive. This article aims to provide an overview of currently available evidence in the literature and the potential impact of meditation on cardiovascular health. However, the data highlighted in this article cannot render with certainty directly reproducible effects of meditation on patients’ cardiovascular disease profiles. Meditation may be suggested only as an additional link in the chain of primary and secondary prevention until future research provides sufficient data on this topic.

Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation.The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery.Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery.The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P.001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15-1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4-5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16-2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL).The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.

Background GDF-15 (growth/differentiation factor 15) is induced by myocardial stretch, volume overload, inflammation, and oxidative stress. Its expression is tightly linked with cardiovascular events as well as the risk for major bleeding and all-cause mortality. The present study aimed to elucidate the prognostic potential of GDF-15 in patients after cardiac surgery. Methods A total of 504 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were prospectively enrolled. GDF-15 levels were measured prior to surgery to evaluate the impact on bleeding events, thromboembolic events, and mortality. Results Preoperative GDF-15 was associated with the primary endpoint of intra- and postoperative red blood cell transfusion (for bleeding risk factors adjusted [adj] OR [odds ratio] per 1-SD [standard deviation] of 1.62 [95% confidence interval [CI]: 1.31–2.00]; p Conclusion Preoperative GDF-15 concentration is an independent predictor for intra- and postoperative major bleeding, major bleeding during the first year, and for long-term cardiovascular or all-cause mortality after cardiac surgery.

Background Diabetes and heart failure (HF) promote atrial fibrillation (AF) and are associated with an increased risk of adverse cardiovascular (CV) events in patients with AF. Because of effective anticoagulation options, AF patients are now more likely to develop HF than a stroke or a systemic embolic event. Appropriate risk stratification of patients with AF should therefore not only consider the risk for stroke but also for HF events. Methods Patients with AF admitted to a tertiary academic center between 01/2005 and 07/2019 were identified through a search of electronic health records. The primary outcome of interest was CV death or hospitalization for HF (HHF). We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, hypertension, smoking, C-reactive protein, and LDL-C. To select the most informative variables and overcome the limitations of stepwise regression procedures, we performed a least absolute shrinkage and selection operator logistic regression in a model that incorporated diabetes, HF, NT-proBNP, and the covariates for adjustment in combination with 10-fold cross-validation. Results In total, 7,412 patients (median age 70 years, 39.7% female) were included in the present analysis and followed over a median of 4.6 years. Both diabetes (Adjusted (Adj.) hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.55 to 2.25) and HF (Adj. HR 2.57, 95% CI 2.22 to 2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared to patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. There was a robust relationship between CV death/HHF and NT-proBNP (Adj. HR for 1-unit increase in standardized log-transformed biomarker 1.86, 95% CI 1.67 to 2.07). NT-proBNP showed good discriminatory performance (AUC 0.78, 95% CI 0.77–0.80), and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant AUC improvement (Δ=0.04, P Conclusion These findings suggest that the influence of diabetes and HF expand beyond the risk of stroke and systemic embolic events to CV death/HHF in an unselected AF patient population. NT-proBNP may provide improved risk assessment in AF patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Forest Plot

Background GDF-15 (growth/differentiation factor 15) is induced by myocardial stretch, volume overload, inflammation and oxidative stress. Its expression is tightly linked with cardiovascular events as well as the risk for major bleeding and all-cause mortality. Objective The objective of the present study was to elucidate the prognostic potential of GDF-15 in patients after cardiac surgery. Methods 504 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were prospectively enrolled. GDF-15 levels were measured prior surgery to evaluate the impact on bleeding events, thromboembolic events and mortality. Results Preoperative GDF-15 was associated with the primary endpoint of intra- and postoperative red blood cell transfusion (for bleeding risk factors adjusted [adj] OR [odds ratio] per 1-SD [standard deviation] of 1.62 [95% CI: 1.31–2.00]; p Conclusion Preoperative GDF-15 concentration is an independent predictor for intra- and postoperative major bleeding, major bleeding during the first year and for long-term cardiovascular or all-cause mortality after cardiac surgery. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Vienna Central illustration

Background Fibroblast growth factor 23 (FGF-23) participates in phosphate and vitamin D metabolism and proved to be associated with an increased risk for fatal events in individuals presenting with cardiovascular disease. In the era of personalized medicine and individualized prognostication, the identification of novel risk markers seems of major importance in terms of state-of-the-art patient care. Since data on the prognostic potential of FGF-23 in individuals undergoing cardiac valve and/or coronary artery bypass graft (CABG) surgery remain scarce, we aimed to investigate the impact of FGF-23 on cardiovascular (CV) death in an unselected patient population after cardiac surgery. Methods Within the present investigation, patients undergoing elective cardiac valve and/or CABG surgery were prospectively enrolled at the Department of Cardiac Surgery of our Medical University. Preoperative blood values were assessed immediately before the surgical intervention. FGF-23 concentrations were measured via FGF Quantikine ELISA Kit (R&D Systems, Minneapolis, USA). Patients were followed prospectively until the primary study endpoint (CV death) was reached. Cox regression models were calculated and adjusted for age, sex, diabetes, heart failure, body mass index, prior myocardial infarction, hypertension and coronary artery disease. Results In total, 462 patients were included in the present analysis and followed over a median of 3.9 years. During follow-up 67 (14.5%) patients died. The patients' median age was 70 years (interquartile range [IQR] 60 to 75) and 133 (28.8%) were female. The median FGF level in the entire study population was 1.9 pmol/L (IQR 1.2 to 3.5). After stratification into tertiles (T) of FGF-23 (median FGF-23 T1: 0.95 pmol/L [IQR 0.65 to 1.19], T2: 1.93 pmol/L [IQR 1.64 to 2.28] T3: 4.80 pmol/L [IQR 3.54 to 8.09]), patients in the highest FGF-23 tertile had highest rates of CV death (T1: 4.8%, T2: 6.8%, T3: 19.1%; P-logrank Conclusion FGF-23 proved to be a strong and independent predictor for CV death in individuals undergoing elective cardiac valve and/or CABG surgery. This biomarker may provide improved risk assessment and fosters individualized patient care in this highly vulnerable patient population in the era of personalized medicine. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan Meier curves

Optimal antithrombotic therapy in patients who underwent surgical biological aortic valve replacement (AVR) represents an issue of ongoing discussion. Additionally, the prognostic impact of anti-thrombotic treatment strategies after biological AVR and real-life data on anticoagulation strategies (AC) of patients presenting with short-term postoperative atrial fibrillation (POAF) has not clearly been investigated so far. Therefore, this study aimed to investigate the impact of therapeutic AC after biological AVR on patient outcome and whether the presence of POAF affects decision making on anti-thrombotic management. Within this prospective observational study, 200 individuals that underwent biological AVR surgery were enrolled. Participants were followed prospectively until the primary study endpoint was reached. Multivariate logistic regression analysis was performed to elucidate the effect of therapeutic AC on outcome. Overall, 106 individuals received therapeutic AC at the time of discharge. The fraction of patients presenting with POAF was balanced between individuals receiving AC and the non-AC subgroup (p = 0.617). After a median follow-up time of 1418 days, 31 (15.5%) individuals died, referring to 15 (13.9%) POAF-free patients and 16 (17.4%) with POAF. We observed a strong inverse association of therapeutic AC and cardiovascular mortality, which remained stable after adjustment for potential confounders showing a HR of 0.437 (95% CI 0.202–0.943; p = 0.035), while bleeding risk was comparable (p = 0.680). Within this investigation, therapeutic AC showed a strong and independent inverse association with long-term mortality in patients that underwent biological AVR. Although POAF is associated with thromboembolic adverse events, the development of this arrhythmia did not affect decision-making of the anti-thrombotic management.

The benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) has been unequivocally proven in randomized, controlled trials. However, real-world evidence assessing the implementation of SGLT2i in clinical practice and their benefit in HF outside of highly selected study populations is limited. Patients with HF and T2DM admitted to the cardiology ward of the Medical University of Vienna between 01/2014 and 04/2020 were included in the present analysis. All first-time prescriptions of SGLT2i were identified. The outcome of interest was cardiovascular mortality. The median follow-up time was 2.3 years. Out of 812 patients with T2DM and HF (median age 70.4 [IQR 62.4–76.9] years; 70.3% males), 17.3% received an SGLT2i. The frequency of SGLT2i prescriptions significantly increased over the past 6 years (+ 36.6%, p

Blood urea nitrogen (BUN) has been shown to independently predict short- and intermediate-term outcomes in patients with acute myocardial infarction (AMI). We aimed to assess the additive predictive value of BUN beyond estimated glomerular filtration rate (eGFR) in AMI patients with an 8.6-year follow-up.This retrospective, observational single-centre study included 1332 consecutive AMI patients (median age 64 years, 58.4% male). BUN, creatinine and eGFR were determined at hospital admission.During a median follow-up of 8.6 years (interquartile range [IQR] 4.0-11.6), 408 patients (30.6%) experienced the study endpoint of cardiovascular mortality. BUN (median 17.0 mg/dL [IQR 13.5-22.7]) was a significant predictor of cardiovascular mortality in univariate Cox regression (hazard ratio (HR) per 1 standard deviation increase 2.10, 95% confidence interval [CI] 1.94-2.28, p .001). This association remained significant after multivariable adjustment for demographics, clinical variables and eGFR (adjusted HR 1.52 [CI 1.16-2.00, p = .003]). The association between BUN and outcome was more pronounced in patients with eGFR60 mL/min/1.73mCirculating BUN on admission is an independent predictor of long-term cardiovascular mortality in AMI patients and adds predictive power beyond eGFR. BUN reflects not only kidney function, but also acute haemodynamic and neurohumoral alterations during AMI, and may help to identify high-risk patients.

Background Personalized risk stratification within the ageing society after ACS remains scarce. With increasing general life expectancy, easily applicable age-specific strategies for the prediction of fatal adverse events are in urgent need. Increased platelet activity together with inflammatory activation play a key role during ACS. Objective We aimed to evaluate the age-specific prognostic potential of the platelet to lymphocyte ratio (PLR) on long-term cardiovascular mortality after ACS. Methods Patients presenting with ACS admitted to a tertiary care centre with a high-volume cardiac catheterization unit between December 1996 and January 2010 were recruited within a clinical registry including assessment of peripheral blood samples. The impact of the PLR on survival was assessed by Cox-regression hazard analysis. Results We included a total of 681 patients with a median age of 64 years (IQR:45–84). 200 (29.4%) individuals died during the median follow-up time of 8.5 years. A strong and independent association of the PLR with cardiovascular mortality was found in the total study population (adjusted [adj.] hazard ratio [HR] per one standard deviation [1-SD] of 1.52 [95% CI: 1.18–1.96; p Conclusion The present investigation highlights a strong and independent age-specific association of the PLR with cardiovascular mortality in patients with ACS. The PLR only allows to identify patients ≥65 years at high risk for fatal events after ACS – even from a long-term perspective. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Vienna Effect of PLR stratified by age

Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery associated with major adverse events and poor patient outcome. Tools for risk stratification of this arrhythmia remain scarce. Atrial natriuretic peptide (ANP) represents an easily assessable biomarker picturing atrial function and strain; however, its prognostic potential on the development of POAF has not been investigated so far. Methods Within the present investigation, 314 patients undergoing elective cardiac surgery were prospectively enrolled. Preoperative mid-region proANP (MR-proANP) values were assessed before the surgical intervention. Patients were followed prospectively and continuously screened for the development of arrhythmic events. Results A total of 138 individuals (43.9%) developed POAF. Median concentrations of MR-proANP were significantly higher within the POAF group (p Conclusion MR-proANP proved to be a strong and independent predictor of the development of POAF. Considering a personalized diagnostic and prognostic preoperative work-up, a standardized preoperative evaluation of MR-proANP levels might help to identify patients at risk for development of POAF after cardiac surgery.

Background Personalized risk stratification after acute coronary syndrome (ACS) remains a challenging field in the aging society. Easily applicable strategies for risk prediction of adverse events from an age-specific perspective are needed. Considering the association of cellular immunity with coronary vessel disease, these cell lines mirror a reasonable value for risk assessment. Therefore, we aimed to elucidate the prognostic value of cellular immunity on long-term outcome after ACS from an age-specific perspective. Methods Patients presenting with ACS at the Vienna General Hospital admitted between December 1996 and January 2010 were enrolled within a clinical registry including standardized assessment of peripheral blood samples and immune phenotyping. Cox-regression hazards analysis was performed to elucidate the impact of cellular immunity on survival. Results A total of 832 patients were included within the final analysis and stratified according to age into individuals Conclusion The present investigation highlighted a strong and independent age-specific effect of both the fraction of neutrophil granulocytes and lymphocytes as well as the NLR on outcome. Considering an age-dependent risk stratification, these routinely available values can be easily used to identify patients at risk for fatal events and contribute to proper secondary prevention after ACS.

Background Secondary prevention after acute coronary syndrome (ACS) mirrors a key position in the reduction of morbidity and mortality in this highly vulnerable patient population. Especially dual anti-platelet therapy (DAPT) – including aspirin plus a P2Y12 inhibitor – proved to be one of the most beneficial therapeutic approaches for the reduction of re-events and stent thrombosis. However, profound epidemiological measures on adherence to DAPT intake after ACS remain scare, but seem of major importance in terms of preventing fatal cardiac adverse events. Therefore, we aimed to investigate adherence to DAPT after ACS and its impact on patient outcome from an Austrian nationwide perspective. Methods Within this population-based national observation all patients presenting with ACS between 04/2011 and 8/2015 in Austria were enrolled. Patient characteristics and co-morbidities were assessed via the Austrian national health insurance system and elucidated according to ICD10 definitions. Adherence to DAPT was investigated according to handing in prescriptions for aspirin and P2Y12 inhibitors at local pharmacies. Patients were followed prospectively until the primary study endpoint (=mortality) was reached. Cox Regression hazard analysis was used to investigate the impact of non-adherence to DAPT on patient outcome and was adjusted for a comprehensive subset of confounders within the multivariate model. Results During the observation period a total of 22.331 patients (median age: 65 years [55–75]; male: 69.7% [n=15.176]) met the inclusion criteria. Patients presenting with the indication for oral anticoagulation (n=2165; 9.7%), individuals that died during the index event (n=151; 0.7%), patients that presented with a re-ACS (n=396; 1.7%) or those who were lost during follow-up (n=96; 0.4%) were not included within the final analysis. Of alarming importance 70.7% (n=15.792) of all patients presenting with ACS did not take DAPT as recommended by current guidelines. The highest rate of drug interruption/end of therapy was observed within the first month after the index event with almost 50% of all cases. During patient follow-up until 14 months after the index event 513 individuals died. Non-adherence to DAPT proved a strong an independent association with mortality with an adjusted hazard ratio of 1.25 (95% CI: 1.09–1.41; p Conclusion The present nationwide investigation highlighted an overall low adherence to DAPT after ACS, with the highest interruption/end of therapy rate within the first month after the index event. Since the intake of DAPT after ACS was associated with a 20% risk reduction for fatal cardiovascular events during the observation period, awareness in terms of drug-adherence and intensified patient follow-up should be promoted, in order to prevent fatal atherothrombotic events. Figure 1. Cumulative Mortality Funding Acknowledgement Type of funding source: None

Background Left ventricular thrombus (LVT) is a rare but dreaded complication during the acute phase of acute coronary syndrome (ACS). Incidence rates differ among the observational studies from 1.6% up to 39.0% indicating that many LVT cases might remain undetected. While the prognosis of patients presenting with LVT after ACS has been controversially discussed, it seems intuitive that individuals in whom the thrombus remains have an increased risk for cardiovascular events and mortality. However, profound data on long-term outcome of this highly vulnerable patient population are not available in current literature. Therefore, we aimed to investigate the impact of LVT resolution on patient's outcome from a long-term perspective. Methods We collected data of patients with acute coronary syndrome (n=2011) who underwent treatment between 01/2016 and 09/2019. Patients with a confirmed LVT were included in this analysis. Repeated echocardiographic data, treatment management and clinical outcomes were collected during follow-up. All-cause mortality and major adverse cardiac events (MACE), defined as nonfatal stroke, nonfatal myocardial infarction, nonfatal systemic embolism and cardiovascular death were chosen as primary and secondary endpoint. Results Among 2011 patients with ACS, 52 patients (2.6%) developed left ventricular thrombosis (median age: 63±13). 80.5% of LVT patients presented with STEMI. Out of those 52 patients with LVT, 6 died before hospital discharge and 3 did not receive follow-up imaging. In total 13 patients (24%) died. Mean time to thrombus resolution was 23±31 weeks. Mean follow-up time was 98±69.6 weeks. 43 patients received oral anticoagulation including 7 patients (16%) receiving novel oral anticoagulants (NOACs) and 32 patients (84%) Vitamin K antagonists (VKA). All patients developed LVT after anterior wall infarction. From the time of hospital admission all patients were followed prospectively until the primary endpoint was reached. Thrombus resolution was observed in 27 patients (62.8). As expected, thrombus resolution was associated with a significant lower risk of MACE with a crude hazard ratio (HR) of 3.89 (95% CI 1.30–11.65; P=0.015) and mortality with a crude HR of 5.59 (95% CI 1.07–29.07; P=0.041). Notably, the prognostic impact remained stable after comprehensive adjustment for potential confounders with an adjusted HR of 5.38 for MACE and an adjusted HR of 6.10 for overall mortality. Conclusion Present data clearly highlighted the prognostic potential of thrombus resolution on both MACE and all-cause mortality in individuals presenting with LVT after ACS. Therefore, thrombus resolution might be considered for risk stratification and an intensified anti-thrombotic approach should be taken into account in this highly vulnerable patient population. Survival curves Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of Vienna

Background Secondary prevention after acute coronary syndrome (ACS) mirrors a key position in the reduction of morbidity and mortality in this highly vulnerable patient population. Especially cardiac rehabilitation proved to be one of the most beneficial therapeutic approaches for the reduction of re-events and overall modification of cardiovascular risk factors. However, profound epidemiological measures on adherence to a recommended cardiac rehabilitation after ACS remain scare, but seem of major importance in terms of preventing fatal cardiac adverse events. Therefore, we aimed to investigate adherence to cardiac rehabilitation after ACS and its impact on patient outcome from an Austrian nationwide perspective. Methods Within this population-based national observation all patients presenting with ACS between 04/2011 and 8/2015 in Austria were enrolled. Patient characteristics and co-morbidities were assessed via the Austrian national health insurance system and elucidated according to ICD10 definitions. Adherence to recommended cardiac rehabilitation was investigated according to health insurance documentation. Patients were followed prospectively until the primary study endpoint (= mortality) was reached. Cox Regression hazard analysis was used to investigate the impact of non-adherence to cardiac rehabilitation on patient outcome and was adjusted for a comprehensive subset of confounders within the multivariate model. Results During the observation period a total of 16.518 patients (median age: 64 years [54–74]; male: 68.4% [n=11.306]) met the inclusion criteria. Of alarming importance 86.6% (n=14.305) of all patients presenting with ACS did not perform any cardiac rehabilitation as recommended by current guidelines. During patient follow-up until 01/2018 a total of 1774 (10.7%) individuals died. Adherence to recommended cardiac rehabilitation had a strong an independent inverse association with mortality with an adjusted hazard ratio of 0.73 (95% CI: 0.54–0.98; p=0.036) (see Figure 1). Conclusion The present nationwide investigation highlighted an overall low adherence to recommended cardiac rehabilitation after ACS. Since cardiac rehabilitation after ACS was associated with a 27% risk reduction for fatal cardiovascular events during the observation period, awareness in terms of cardiac rehabilitation and associated intensified risk factor modification should be promoted, in order to prevent fatal atherothrombotic events. Figure 1. Cumulative mortality Funding Acknowledgement Type of funding source: None

Background Secondary prevention after acute coronary syndrome (ACS) mirrors a key position in the reduction of morbidity and mortality in this highly vulnerable patient population. Especially lipid lowering therapy – via high-intensity statins (atorvastatin and rosuvastatin) – proved to be one of the most beneficial therapeutic approaches for the reduction of re-events and stent thrombosis. However, profound epidemiological measures on adherence to statin intake after ACS remain scare, but seem of major importance in terms of preventing fatal cardiac adverse events. Therefore, we aimed to investigate adherence to high-intensity statin therapy after ACS and its impact on patient outcome from an Austrian nationwide perspective. Methods Within this population-based national observation all patients presenting with ACS between 04/2011 and 8/2015 in Austria were enrolled. Patient characteristics and co-morbidities were assessed via the Austrian national health insurance system and elucidated according to ICD10 definitions. Adherence to high-intensity statins was investigated according to handing in prescriptions for rosuvastatin and atorvastatin at local pharmacies. Patients were followed prospectively until the primary study endpoint (=mortality) was reached. Cox Regression hazard analysis was used to investigate the impact of non-adherence to high-intensity statin therapy on patient outcome and was adjusted for a comprehensive subset of confounders within the multivariate model. Results During the observation period a total of 23.240 patients (median age: 65 years [55–75]; male: 67.7% [n=15.728]) met the inclusion criteria. Individuals that died during the index event (n=366; 1.6%), presented with a re-ACS (n=569; 2.4%) or were lost during follow-up (n=158; 0.6%) were not included within the final analysis. Of alarming importance 66.4% (n=15.422) of all patients presenting with ACS did not take high-intensity statins as recommended by current guidelines. The highest rate of drug interruption/end of therapy was observed within the first month after the index event with more than 50% of all cases. During patient follow-up until 01/2018 a total of 3522 (15.2%) individuals died. Non-adherence to high-intensity statins had a strong an independent association with mortality with an adjusted hazard ratio of 1.16 (95% CI: 1.06–1.25; p Conclusion The present nationwide investigation highlighted an overall low adherence to high-intensity statins after ACS, with the highest interruption/end of therapy rate within the first month after the index event. Since the intake of high-intensity statins after ACS was associated with a 14% risk reduction for fatal cardiovascular events during the observation period, awareness in terms of drug-adherence and intensified patient follow-up should be promoted, in order to prevent fatal atherothrombotic events. Figure 1. Cumulative mortality Funding Acknowledgement Type of funding source: None

Background Recent guidelines state that in patients with surgical biological aortic valve replacement (AVR), the use of anti-platelet therapy is as a valid alternative to postoperative anticoagulation (AC) in the absence of a further indication for AC. However, the prognostic impact of different anti-thrombotic strategies after biological AVR has not clearly been investigated so far and outcome data remain scare and inconclusive. Moreover, the AC strategy of patients presenting with post-operative atrial fibrillation (POAF), has not been investigated so far. Therefore, we aim to picture the therapeutic AC approach after biological AVR and whether the presence of POAF effects decision making with regard to anti-thrombotic management. Methods Within this prospective observational study 515 patients undergoing elective cardiac valve and or coronary artery bypass graft (CABG) surgery were enrolled. All patients were continuously screened for the development of POAF and followed until the primary endpoint (mortality) was reached. Logistic regression analysis was performed to elucidate the effect of AC on outcome. Results A total of 200 individuals underwent biological AVR (including 81 [40.3%] combined AVR+CABG surgeries, median age: 77 years [IQR: 71–80 years]; 133 [66.3%] male gender). 97 (48.3%) patients received therapeutic AC at the time of discharge, including 42 (43.4%) on vitamin K antagonists (VKA), 53 (54.6%) on low-dose low-molecular weight heparin (LMWH) and 2 (2.0%) non-vitamin K antagonist oral anticoagulants (NOACs). 103 (51.2%) patients received another anti-thrombotic approach including 23 (22.3%) on dual anti-platelet therapy (DAPT) and 72 (69.9%) with prophylactic LMWH. Interestingly, the fraction of patients that received AC were comparable between POAF (CHA2DS2-Vasc score 4, IQR: 3–5) and non-POAF individuals (51.9% vs. 44.6%; p=0.304). After a median follow-up time of 1069 days (IQR: 673–1475 days) 21 patients (10.4%) died, referring to 9 (8.3%) non-POAF and 12 (13.0%) POAF individuals. We found that a therapeutic AC after surgery showed a strong and inverse association with 3-year mortality with a crude odds ratio (OR) of 0.31 (95% CI 0.12–0.79; p=0.015). The prognostic potential remained stable after adjustment for potential confounders (p=0.029). Conclusion Therapeutic AC showed a strong and independent inverse association with 3-year mortality, mirroring a potential benefit on outcome compared to anti-platelet therapy or low-dose LMWH. However, the fraction of patients receiving therapeutic AC was considerably low – especially NOACs were not commonly used. Despite its association with fatal cardiac adverse events, the presence of POAF was not a relevant value for decision making for the initiation of AC. Further prognostic data on both thromboembolic and bleeding events are needed to elucidate a net-benefit of therapeutic AC in patients with surgical biological AVR who have an indication for AC or present with POAF. Kaplan-Meier Survival plot Funding Acknowledgement Type of funding source: None

Nosocomial infections are a common complication in clinical practice with major impact on surgical success and patient outcome. The probability of nosocomial infections is rapidly increasing during hospitalization. Therefore, we investigated the impact of a prolonged pre-operative hospital stay on the development of post-operative infection. Within this prospective observational study, 200 patients scheduled for elective cardiac surgery were enrolled. Patients were followed during hospital admission and screened for the development of nosocomial infection. Logistic regression analysis was used to assess the impact of a prolonged pre-operative hospital stay on the development of infection. A total of 195 patients were suitable for the final analysis. We found a strong and direct association of the duration of pre-operative hospital stay and the number of patients developing infection (+23.5%; p = 0.006). Additionally, the length of patients’ pre-operative hospital stay was independently associated with the development of post-operative nosocomial infection, with an adjusted OR per day of 1.38 (95%CI: 1.02–1.86; p = 0.036). A prolonged pre-operative hospital stay was significantly associated with the development of nosocomial infection after cardiac surgery. Those findings need to be considered in future clinical patient management in order to prevent unnecessary antibiotic use and potential harm to patients.

Aims While the prognosis of patients presenting with de novo atrial fibrillation (AF) during the acute phase of myocardial infarction has been controversially discussed, it seems intuitive that affected individuals have an increased risk for both thrombo-embolic events and mortality. However, profound data on long-term outcome of this highly vulnerable patient population are not available in current literature. Therefore, we aimed to investigate the impact of de novo AF and associated anti-thrombotic treatment strategies on the patient outcome from a long-term perspective. Methods and results Patients presenting with acute myocardial infarction, treated at the Medical University of Vienna, were enrolled within a clinical registry and screened for the development of de novo AF. After discharge, participants were followed prospectively over a median time of 8.6 years. Primary study endpoint was defined as cardiovascular mortality. Out of 1372 enrolled individuals 149 (10.9%) developed de novo AF during the acute phase of acute myocardial infarction. After a median follow-up time of 8.6 years, a total of 418 (30.5%) died due to cardiovascular causes, including 93 (62.4%) in the de novo AF subgroup. We found that de novo AF was significantly associated with long-term cardiovascular mortality with an adjusted HR of 1.45 (95% CI 1.19–2.57; P Conclusion De novo AF was independently associated with a poor prognosis with a 67% increased risk of long-term cardiovascular mortality. Intensified anti-thrombotic treatment in this high-risk patient population might be considered.

Background. Heart failure with reduced ejection fraction (HFrEF) constitutes a global health issue. While proinflammatory cytokines proved to have a pivotal role in the development and progression of HFrEF, less attention has been paid to the cellular immunity. Regulatory T lymphocytes (Tregs) seem to have an important role in the induction and maintenance of immune homeostasis. Therefore, we aimed to investigate the impact of Tregs on the outcome in HFrEF. Methods. We prospectively enrolled 112 patients with HFrEF and performed flow cytometry for cell phenotyping. Individuals were stratified in ischemic (iHFrEF, n=57) and nonischemic etiology (niHFrEF, n=55). Cox regression hazard analysis was used to assess the influence of Tregs on survival. Results. Comparing patients with iHFrEF to niHFrEF, we found a significantly lower fraction of Tregs within lymphocytes in the ischemic subgroup (0.42% vs. 0.56%; p=0.009). After a mean follow-up time of 4.5 years, 32 (28.6%) patients died due to cardiovascular causes. We found that Tregs were significantly associated with cardiovascular survival in the entire study cohort with an adjusted HR per one standard deviation (1-SD) of 0.60 (95% CI: 0.39-0.92; p=0.017). A significant inverse association of Tregs and cardiovascular mortality in patients with iHFrEF with an adj. HR per 1-SD of 0.59 (95% CI: 0.36-0.96; p=0.034) has been observed, while this association was not evident in the nonischemic subgroup (adj. HR per 1-SD of 0.62 (95% CI: 0.17-2.31); p=0.486). Conclusion. Our results indicate a potential influence of Tregs in the pathogenesis and progression of iHFrEF, fostering the implication of cellular immunity in iHFrEF pathophysiology and proving Tregs as a predictor for long-term survival among iHFrEF patients. A preview of this study has been presented at a meeting of the European Society of Cardiology earlier this year.

Deleterious inflammatory responses are seen to be the trigger of heart failure in myocarditis and therapies directed towards immunomodulation have been assumed to be beneficial. The objective of the present review was to systematically assess the effect of immunomodulation in lymphocytic myocarditis. Studies were included if diagnosis of lymphocytic myocarditis was based on EMB as well as on the exclusion of other etiologies of heart failure and if the patients had at least moderately decreased left ventricular ejection fraction (

Growth differentiation factor (GDF)‐15 and soluble ST2 (sST2) are established prognostic markers in acute and chronic heart failure. Assessment of these biomarkers might improve arrhythmic risk stratification of patients with non‐ischaemic, dilated cardiomyopathy (DCM) based on left ventricular ejection fraction (LVEF). We studied the prognostic value of GDF‐15 and sST2 for prediction of arrhythmic death (AD) and all‐cause mortality in patients with DCM. We prospectively enrolled 52 patients with DCM and LVEF ≤ 50%. Primary end‐points were time to AD or resuscitated cardiac arrest (RCA), and secondary end‐point was all‐cause mortality. The median follow‐up time was 7 years. A cardiac death was observed in 20 patients, where 10 patients had an AD and 2 patients had a RCA. One patient died a non‐cardiac death. GDF‐15, but not sST2, was associated with increased risk of the AD/RCA with a hazard ratio (HR) of 2.1 (95% CI = 1.1‐4.3; P = .031). GDF‐15 remained an independent predictor of AD/RCA after adjustment for LVEF with adjusted HR of 2.2 (95% CI = 1.1‐4.5; P = .028). Both GDF‐15 and sST2 were independent predictors of all‐cause mortality (adjusted HR = 2.4; 95% CI = 1.4‐4.2; P = .003 vs HR = 1.6; 95% CI = 1.05‐2.7; P = .030). In a model including GDF‐15, sST2, LVEF and NYHA functional class, only GDF‐15 was significantly associated with the secondary end‐point (adjusted HR = 2.2; 95% CI = 1.05‐5.2; P = .038). GDF‐15 is superior to sST2 in prediction of fatal arrhythmic events and all‐cause mortality in DCM. Assessment of GDF‐15 could provide additional information on top of LVEF and help identifying patients at risk of arrhythmic death.

Study objective Postoperative atrial fibrillation (POAF) is a frequent complication after cardiac valve- or coronary artery bypass (CABG) surgery and is associated with increased mortality. While it is known that prolonged postoperative invasive ventilation triggers POAF, the impact of ventilatory settings on POAF development has not been studied yet. Design Prospective observational study. Setting Postoperative Intensive Care Unit. Patients Patients having undergone elective CABG and/or cardiac valve surgery. Measurements Screening for the development of POAF. Patients' clinical data and postoperative ventilatory settings (driving pressure, controlled pressure above positive endexpiratory pressure (PEEP), respiration rate, and FiO2) were investigated to elucidate their impact on POAF. Main results Out of 441 enrolled individuals, a total of 192 participants developed POAF (43.5%). We observed that POAF patients received a higher peak driving pressure, and a higher peak respiration rate than non-POAF individuals. Within the multivariate regression model, plateau pressure (adjusted OR 1.199 [1.038–1.661], p = 0.019), driving pressure (adjusted OR 1.244 [1.103–1.713], p = 0.021), and peak respiration rate (adjusted OR 1.206 [1.005–1.601], p = 0.040) proved to be independently associated with the development of POAF. CART analysis revealed a cut-off of ≥17.5 cmH2O of plateau pressure, ≥11.5 cmH2O of driving pressure and ≥ 17 respirations per minute as high-risk for POAF development. Conclusions The ventilatory settings of plateau pressure, driving pressure, and respiration rate after cardiac surgery influence POAF occurrence probability. Optimized postoperative care such as lung-protective ventilation and increased awareness towards postoperative ventilatory efforts should be considered to prevent POAF development and poor patient outcome.

This study investigated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) in patients with chronic heart failure (CHF).SuPAR originates from proteolytic cleavage of the membrane-bound receptor from activated immune and endothelial cells and reflects the level of immune activation. As inflammation plays a crucial role in the complex pathophysiology of CHF, we hypothesized that suPAR might be a suitable prognostic biomarker in patients with CHF.SuPAR levels were determined in 319 patients with CHF admitted to our outpatient department for heart failure and in a second cohort consisting of 346 patients with CHF, for validation.During a median follow-up time of 3.2 years, 119 patients (37.3%) died. SuPAR was a strong predictor of mortality with a crude hazard ratio (HR) per increase of 1 SD (HR per 1 SD) of 1.96 (95% confidence interval [CI]: 1.63 to 2.35; p 0.001) in univariate analysis and remained significant after comprehensive multivariate adjustment with an adjusted HR per 1 SD of 1.38 (95% CI: 1.04 to 1.83; p = 0.026). SuPAR added prognostic value beyond the multivariate model indicated by improvements in C-statistics (area under the curve: 0.72 vs 0.74, respectively; p = 0.02), the category-free net reclassification index (24.9%; p = 0.032), and the integrated discrimination improvement (0.011; p = 0.05). Validation in the second cohort yielded consistent results.SuPAR is a strong and independent predictor of mortality in patients with CHF, potentially suitable to refine risk assessment in this vulnerable group of patients. Our results emphasize the impact of immune activation on survival in patients with CHF.

SummaryAtrial fibrillation (AF) represents the most common cardiac arrhythmia. Especially in patients with chronic heart failure (CHF) the development of AF represents a severe complication resulting in haemodynamic deterioration. While pro-inflammatory cytokines proved to have a pivotal role in the development and progression of both AF and CHF, less attention has been paid to the cellular immunity. Therefore we prospectively enrolled 112 patients with CHF and performed fluorescein-activated cell sorting (FACS). Patients were stratified in two subgroups according to patients presenting with AF (n=56) and patients free of AF (n=56). Comparing AF to non-AF patients we found a significantly lower fraction of regulatory T cells (pSupplementary Material to this article is available online at www.thrombosis-online.com.

Background Post-infarction cardiac rupture (CR) such as ventricular septal rupture (VSR), free wall rupture (FWR), atrial septal rupture (ASR) or papillary muscle rupture (PMR) is a rare but dreaded complication in patients with acute myocardial infarction (AMI) associated with a very poor prognosis with reported mortality rates between 60 and 100%. Therefore suitable risk stratification for secondary prevention seems crucial, but data on long-term survival und risk prediction in this especially vulnerable patient collective remains scarce. Methods Out of 11,641 patients presenting with AMI a total of 28 individuals suffering post-infarction CR were identified and stratified in "acute survivors of CR" (n=10) and "non-survivors of CR" (n=18). Cox regression hazard analysis was used to assess prognosticators on long-term survival. Results Ten patients (35.7%) survived the initial event. After a median follow-up time of 9years 2 (20%) of the survivors died, both due to cardiovascular causes. Younger age (p=0.023) and higher systolic blood pressure at admission (p=0.018) turned out to be significant predictors of long-term survival. Systolic blood pressure 48h after CR proved to be a strong and independent predictor for survival with an adjusted hazard ratio per one standard deviation of 0.89 (95% CI: 0.72–0.99; 0.048). Conclusion Hemodynamic stabilization and severity of cardiogenic shock were detected as clinically most common among patients suffering post-infarction CR and proved to be of major importance for survival. If survival of the initial event was achieved, satisfying long-term mortality could be reached.

Background Heart failure with reduce ejection fraction (HFrEF) constitutes a global health issue representing a prevalent clinical syndrome. While pro-inflammatory cytokines proved to have a pivotal role in the development and progression of HFrEF, less attention has been paid to the cellular immunity. Regulatory T lymphocytes (Tregs) seem to have an important role in the induction and maintenance of immune homeostasis especially in patients after acute coronary syndrome and coronary vessel disease. Therefore, we aimed to investigate the impact of Tregs on the outcome of patients presenting with ischemic HFrEF. Methods We prospectively enrolled 112 patients with HFrEF defined by New York Heart Association (NYHA) functional class >II and left ventricular ejection fraction (LVEF) Results Comparing patients with iHFrEF to dHFrEF we found a significantly lower fraction of Tregs within lymphocytes in the ischemic subgroup (0.42% vs. 0.56%; p=0.009). After a mean follow-up time of 4.5 years 32 (28.6%) patients died due to cardiovascular causes. We found that Tregs were significantly associated with cardiovascular survival in the entire study cohort with an adjusted HR per one standard deviation (1-SD) of 0.60 (95% CI 0.39–0.92; p=0.017). Interestingly while there was no association with cardiovascular survival independently in the dHFrEFsubgroup (adj. HR per 1-SD of 0.62 (95% CI 0.17–2.31); p=0.486), we found a significant inverse association of Tregs and cardiovascular survival in patients with iHFrEFwith an adj. HR per 1-SD of 0.59 (95% CI 0.36–0.96; p=0.034). Figure 1. Survival Curves of Cardiovascular Mortality. Kaplan-Meier plots showing survival free of cardiovascular mortality in the total study collective (A) and patients stratified in ischemic CMP (B) as well dilative CMP (C) according to tertiles of frequencies of regulatory T cells. Tertile 1 = high; Tertile 2 = mid; Tertile 3 = low. Conclusion Our results indicate a potential influence of Tregs in the pathogenesis and progression of iHFrEF, fostering the implication of cellular immunity in iHFrEF pathophysiology and proving Tregs as a predictor for long-term survival among iHFrEF -patients.

Background Post-operative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as a main trigger of this specific type of atrial fibrillation. CD8+ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so called CD8+CD28null T cells are known to present with auto-aggressive behavior and deleterious cytotoxic effects on human tissue. Therefore, the impact of cellular immunity on the development of POAF was sought to assess. Methods To elucidate the impact of cellular immunity on the development of POAF, we prospectively enrolled 129 patients undergoing elective cardiac valve and/or coronary-artery-bypass-graft surgery. Fluorescein-activated cell sorting (FACS) was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n=60) and individuals free of POAF (n=69). Binary logistic regression analysis was performed to assess the impact of cellular immunity on the development of POAF. Results Comparing patients developing POAF to individuals free of POAF the fraction of CD8+ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [non-POAF]; p=0.021) Interestingly, the fraction of CD8+CD28nullT-lymphocytes was significantly higher in the POAF sub-group (66.7% [POAF] vs. 61.6% [non-POAF]; p=0.043). Binary logistic regression further proved that the fraction of CD8+CD28null T cells was a strong prognosticator for the development of POAF with a crude odds ratio per one standard deviation of 3.45 (95% CI 1.11–10.70; p=0.032). The prognostic potential remained stable after adjustment for potential confounders (age, male gender and type of surgery) within the multivariate model with an adjusted odds ratio per one standard deviation of 3.21 (95% CI 1.01–10.18; p=0.048). Conclusion We found that cytotoxic CD8+CD28null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an auto-immune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF. Acknowledgement/Funding Verein zur Förderung der Forschung – Atherosclerosis Thrombosis and Vascular Biology (Vienna, Austria)

Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac valve or coronary artery bypass surgery. Etiologically, multifactorial causes such as the patients' age, weight, comorbidities or local remodeling proved a strong association with this common arrhythmia. While strain of atrial tissue is known to induce atrial fibrillating impulses, less attention has been paid to potentially strain-promoting values during the peri- and post-operative period. Therefore, we aimed to determine the association of peri- and post-operative volume substitution on markers of cardiac strain and subsequently its impact on the promotion and development of POAF. Methods In this prospective observational study 271 patients undergoing elective cardiac surgery in our Medical University were enrolled (median age: 69 years [IQR: 60–75 years]; 195 [72%] male gender). Intra- and post-operative data was collected from anesthesiologic and intensive care unit protocols. Multivariate binary logistic regression analysis was used to identify the prognostic value of volume substitution on the development of POAF. Results A total of 123 (45.4%) individuals developed POAF. The average intra-operative transfusion volume was significantly elevated in the POAF subgroup (605.6ml [POAF] vs. 227.1ml [non-POAF]; p Conclusion Within the present analysis we were able to demonstrate that substitution of larger transfusion volumes presents a strong and independent predictor for the development of POAF. Via the observed distinct association with NT-proBNP values, it can reasonably be assumed that post-operative atrial fibrillating impulses are triggered via volume-induced cardiac strain.

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67&ndash, 77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17&ndash, 63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p &lt, 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65&ndash, 2.79, p &lt, 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03&ndash, 1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15&ndash, 2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58&ndash, 0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.