Background: Heart failure (HF) and chronic kidney disease (CKD) create a mutually reinforcing cycle, escalating disease development, and increasing morbidity and mortality rates. Both are common comorbidities promoting AF and contributing to heightened symptom burden and poorer outcomes in AF. Here our aim was to investigate the relationship of HF and CKD with cardiorenal outcomes in patients with atrial fibrillation (AF). Methods: Patients with AF, treated at a tertiary centre between January 2005 and July 2019, were included. The primary endpoint was a composite of cardiovascular (CV) death and hospitalization for HF (HHF). Secondary outcomes were the individual components of the primary endpoint, all-cause death, renal death, and dialysis. Results: We included a total of 7,412 patients (median age 70 years, 39.7% female) with AF and followed them over a median of 4.5 years. There was a significant stepwise increase in 5-year event rates for the composite of CV death/HHF (no CKD and no HF: 23%, HF: 61%, CKD: 63%, CKD and HF: 82%; P log-rank <0.001). Both CKD (adjusted hazard ratio [HR]: 1.87, 95% confidence interval [CI]: 1.55–2.25) and HF (adjusted HR: 2.57, 95% CI: 2.22–2.98) were significantly associated with CV death/HHF after multivariable adjustment. A similar association was observed for the individual components of the primary endpoint and renal death/dialysis. Conclusions: Both CKD and HF significantly increase the risk of CV death and HHF, as well as renal death/dialysis in patients with AF. Risk assessment should expand beyond stroke and bleeding to cardiorenal complications including HHF, CV, and renal death, as well as kidney failure.

BACKGROUND:Biomarkers of inflammation are reliable predictors of adverse cardiovascular events in coronary artery disease. However, the association between systemic inflammation and percutaneous coronary intervention (PCI)-related adverse events remains widely unclear. OBJECTIVES:The objective of this study was to investigate the association of routinely assessed inflammatory biomarkers C-reactive protein, leukocytes, and neutrophil-to-lymphocyte ratio (NLR) with patient outcomes in an unselected patient cohort undergoing PCI. METHODS:A total of 7,412 patients (median age 64 years, 73.2% male) were enrolled in this single-center observational trial with a median follow-up time of 4.6 years. Target lesion revascularization (TLR) and acute stent thrombosis (ST) were defined as primary endpoints. Further endpoints included mortality, cardiovascular mortality, and 3-point major adverse cardiovascular events (MACE) (composite of cardiovascular mortality, myocardial infarction, and stroke). Cox proportional hazard regression was used for statistical analysis with a level of significance set at P < 0.01. RESULTS:In the total study cohort, patients experiencing subsequent TLR (n = 488, 6.6%) had more comorbidities and underwent more complex primary interventions. Interestingly, no relation was found between systemic inflammation and subsequent TLR (eg, adjusted HR for C-reactive protein: 0.93 [95% CI: 0.85-1.03], P = 0.150), 30-day TLR (0.89 [95% CI: 0.75-1.05], P = 0.177), or acute ST (1.06 [95% CI: 0.79-1.42], P = 0.708) in multivariable analysis, neither in elective nor in acute interventions. All investigated inflammatory biomarkers were, however, significantly associated with all-cause mortality, cardiovascular mortality, and 3-point MACE, even after comprehensive adjustment for clinical and interventional parameters. CONCLUSIONS:While our results emphasize the importance of systemic inflammatory activation for mortality and MACE, elevated baseline inflammatory parameters show no correlation with TLR or acute ST and, therefore, should not delay PCI in the era of second-generation drug-eluting stents.

The use of drug-coated balloons (DCB) in percutaneous coronary interventions (PCI) is increasing due to potential benefits mainly by avoiding foreign material although a widespread application area beyond in-stent restenosis lacks robust clinical data to date. As such, we aimed to assess the safety and efficacy of DCBs in treating de novo lesions. For this analysis, we included all patients treated with DCB in a de novo lesions from 2010 to 2019 at our institution. We performed a 1:1 propensity score matching to pair each DCB intervention with a comparable DES intervention. Follow-up continued until 09/2022 to assess clinical outcomes. A total of 303 patients with de novo lesion were matched to 303 patients with comparable baseline characteristics. The median follow-up time was 5.7 years (IQR 2.7–9.3). There were no significant differences in cardiovascular (CV) mortality (HR 1.01 [95

AIMS:Metabolic disorders are established risk factors for coronary artery disease (CAD) and major adverse cardiovascular events (MACEs). Although obesity is closely associated with metabolic disease, data on its role as a separate cardiovascular risk modifier in metabolically healthy (MH) individuals are limited, particularly in patients with CAD. Thus, this study aims to investigate risk profiles of metabolic phenotypes on outcomes in patients undergoing invasive coronary angiography. METHODS AND RESULTS:A total of 12 760 patients evaluated for chronic coronary syndrome (CCS) were distinguished into four metabolic phenotypes: MH/metabolically unhealthy (MU) non-obese/obese (MHN, MHO, MUN, and MUO). The association of metabolic phenotypes with outcome was assessed using Cox regression models, adjusted for age, sex, and renal dysfunction. Within the total study cohort (median age 68 years, 57.3% male), 56.5% presented MH (43.3% MHN; 13.1% MHO) and 43.5% MU (28.3% MUN; 15.2% MUO). Irrespective of CCS, metabolic phenotypes showed different risks for MACE, all-cause mortality, and revascularization. While metabolic disease emerged as a robust predictor of events, obesity alone did not [e.g. in patients with obstructive CCS: MHO vs. MHN: adj. hazard ratio (HR) 0.947, 95% confidence interval (CI) 0.728-1.231, P = 0.683; MUO vs. MUN: adj. HR 0.974 (95% CI 0.809-1.172), P = 0.780]. However, MH individuals experienced lower event rates with increasing body mass index (BMI). CONCLUSION:This study indicates metabolic health, rather than obesity, is a key predictor of adverse events in CCS prevention, revealing an obesity paradox in MH individuals. Thus, cardiovascular risk assessment should prioritize metabolic health over BMI. Integrating metabolic profiling into routine evaluations may help optimize prevention and personalized treatment strategies.

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk > 0.63 and ≤0.84, High Risk > 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p < 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p < 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization.

Abstract Background Metabolic disorders are established risk factors for the development of coronary artery disease (CAD) and major adverse cardiovascular events (MACE). Although obesity is strongly related with the metabolic health status, its role as a cardiovascular risk modifier in the absence of metabolic disorders remains controversial. Recent implementation of nutrient-stimulated hormone-based therapies (NUSH) including glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of obesity even in metabolically healthy individuals requires further understanding to ensure optimal patient management. Purpose The aim of this study is to investigate the association of metabolic phenotypes with cardiovascular events in primary and secondary prevention of CAD. Methods We included patients over 18 years electively evaluated for CAD by invasive coronary angiography (ICA) between 2010 and 2021 in our tertiary referral centre in one of Europe’s largest university hospitals. Metabolic disorder was considered as the presence of diabetes, irrespective of additional risk factors, or hypertension and hyperlipidaemia, and obesity as a BMI of ≥30 kg/m², distinguishing four metabolic phenotypes: metabolically healthy/unhealthy nonobese/obese (MHN, MHO, MUN, MUO). The primary study endpoint MACE was defined as a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and hospitalization for heart failure. Results The total study population included 12 760 patients (68 [58-76] years; 57.3% male), of whom 56.5% presented metabolically healthy (43.3% MHN; 13.1% MHO) and 43.5% unhealthy (28.3% MUN; 15.2% MUO). During a median follow up time of 3.91 (1.75-7.09) years, 2 592 (20.3%) MACE and 3 351 (26.3%) all-cause deaths occurred. Cox regression analysis adjusted for age, sex, and chronic kidney disease (CKD) showed different risk patterns for distinct metabolic phenotypes (Table 1). While we observed higher event rates in metabolically unhealthy compared to healthy individuals, obesity alone was not associated with increased events (Figure 1). However, metabolically healthy individuals experienced lower event rates with increasing BMI. Among patients without or with nonobstructive CAD, metabolic disease was strongly associated with increased subsequent coronary revascularization regardless of BMI. These patterns were similar across all endpoints irrespective of presence of obstructive or nonobstructive CAD. Conclusions Whereas metabolic disorders are strongly associated with adverse clinical events, obesity alone does not reflect the cardiovascular risk profile in patients with or without obstructive CAD. Thus, focusing on obesity alone for primary or secondary prevention appears unjustified. Particularly after the recent implementation of GLP-1 receptor agonists for the treatment of obesity, precise and individual risk stratification is essential to allow for an optimal personalized patient management.Figure 1Table 1

Abstract Background The global prevalence of prediabetes and diabetes is increasing, highlighting an urgent public health challenge. While the cardiovascular (CV) risk of diabetes is well studied, profound data on the CV risk of prediabetes in patients with heart failure (HF) remain scarce in current literature. Therefore, we aimed to investigate the relationship of prediabetes and diabetes with common HF associated events such as all-cause, CV death and hospitalization for HF (HHF) in patients with HF with reduced ejection fraction (HFrEF). Methods Patients with HFrEF who were admitted to a tertiary academic center between 01/2005 and 07/2019 were included in the present analysis and then stratified according to their glycemic state. Prediabetes was defined as an HbA1c value between 5.7% and 6.4% and the absence of diabetes mellitus. The primary outcome was a composite of CV death and HHF. Secondary outcomes were the individual components of the primary outcome and all-cause death. We used cox regression models adjusted for age, sex, chronic kidney disease, body mass index, prior myocardial infarction, hypertension, CRP, and LDL-C. Results In total, 1,777 patients (median age 69 years, 24.3% female) were included in the present analysis and followed over a median of 4 years. Among them, 35.2% were diabetic, 18.7% prediabetic, and 46.1% showed non-impaired glucose metabolism. NT-proBNP levels were comparable between all glycemic groups. Both prediabetes and diabetes were found to significantly increase the risk of CV-death or HHF compared to those with normal glucose metabolism, with adjusted hazard ratios (HR) of 1.41 (95% Confidence Interval [CI]: 1.05-1.89) and 1.52 (95% CI: 1.17-1.97), respectively. This elevated risk applied to both components of the primary outcome, as illustrated in Figure 1. Notably, the increased risk of all-cause mortality was statistically significant only among diabetic patients (adj. HR 1.75; 95%CI: 1.30-2.36), with prediabetic patients showing a trend towards increased risk but not reaching statistical significance (adj. HR 1.40; 95%CI: 0.99-1.97). Conclusion The findings of this study underscores the independent associations between both prediabetes and diabetes with increased risks of cv-death and HHF in patients diagnosed with HFrEF. This emphasizes the critical role of glycemic status in the prognostication and management of HFrEF. The associations suggest that prediabetes is not merely a transient or benign state but has significant implications for cardiovascular health, particularly in the context of HF. In light of these findings, screening of prediabetes in patients with HFrEF might help to identify patients at risk who are susceptible for the development of HF related adverse events.Forest plot for all study endpointsKaplan-Meier curves for CV-death/HHF

Abstract Background The usage of drug coated ballons (DCB) in percutaneous coronary interventions (PCI) is rising. Initially applied in in-stent restenosis (ISR), wider clinical applications especially in de novo lesions (DNL) are discussed. Here we aim to assess the pattern of usage as well as the clinical and angiographic outcomes associated with DCB. Methods For this analysis we included all patients treated with DCB during PCI, at a tertiary care centre between 01/2015 and 12/2021. Cath lab results of all patients were screened to assess the DCB indication. Patients were followed up until 09/2022 to assess clinical as well as angiographic complications. Results A total of 7608 interventions were carried out between 2015 and 2021, in 462 (6.1%) a DCB was used. The median follow-up time were 3.1 years (IQR 1.6 to 4.4 years), the median age of our patient population was 66 (IQR 58-75) and 24.7% (n=114) were female. There were 92 of 462 (19.9%) cases including a DNL preparation, 335 (72.5%) cases treating an ISR, in 6 (1.3%) cases both, DNL and ISR were treated, and in 29 (6.3%) cases DCB were used for other reasons (e.g. pre-/ postdilatation in coronary stenting). The mean DCB inflation diameter was significantly higher in ISR with 3.50mm (IQR 3.0-3.5mm) compared to DNL with 2.50mm (2.00-2.50mm, p-value <0.001 ) While the number of DCBs used is rising over time (179 cases [38.7%] in 2015-2018, 283 cases [61.3%] in 2019-2021), the proportion of de novo lesions showed no significant difference (37/179 [20.7%] in 2015-2018, 61/282 [21.6%] in 2019-2021, p-value 0.806, Figure 1). Patients with DCB for ISR had significantly higher rates of arterial hypertension (ISR: 255 [76.1%], DNL: 57 [62.0%], both: 3 [50.0%], other: 20 [69.0%] p value 0.029), hyperlipidaemia (ISR: 228 [68.1%], DNL: 56 [60.9%], both: 2 [33.3%], other: 14 [48.3%], p value 0.041) and previous myocardial infarction (ISR: 231 [69.0%], DNL: 33 [35.9%], both: 2 [33.3%], other: 8 [27.6%], p-value <0.001). When analysing the outcomes, patients with DNL showed lower rates of acute myocardial infarction (8 [8.2%] vs 51 [15.0%]) as well as target lesion (6 [6.1%] vs 56 [16.5%]) and any revascularization (27 [27.6%] vs 122 [35.9%])%]), yet a higher rate of cardiovascular mortality (19 [5.6] vs 9 [9.2%]) during the follow up period compared to patients treated for ISR (Figure 2). Both groups showed a very low rate of target lesion thrombosis within 30 days after PCI (1 [1.0%] vs 1 [0.3%], p-value 0.745). Conclusions The use of DCB in PCIs is increasing, yet as we were able to emphasize with our data, they are primarily used in ISR as well as lesions with a small vessel diameter with favourable outcomes indicated by low event rates. Research should expand beyond small-vessel disease and ISR to assess safety and outcomes of DCB in DNL, larger vessels and bifurcation interventions with one stent to further assess its potential benefits in a wider field of indications.

Abstract Background MR-proADM (mid-regional pro-adrenomedullin) is a stable pro-peptide of Adrenomedullin, which is expressed in various cell types such as heart, lung, and renal tissue. It is a prognostic parameter for heart failure (HF) and sepsis as well as all-cause and cardiovascular (CV) mortality. Purpose Considering the characteristics of MR-proADM as a reliable biomarker for adverse events, we aimed to investigate the prognostic impact of MR-proADM in patients undergoing elective cardiac surgery. Methods We prospectively enrolled patients undergoing elective cardiac bypass and/or valve surgery at the department of cardiac surgery between May 2013 and August 2018. Blood samples were taken one day prior to surgery. MR-proADM was measured using an automated immunofluorescence assay. Patients were followed prospectively until endpoints were reached. The primary endpoint was the composite of hospitalization for heart failure (HHF) or CV mortality, the secondary endpoint was postoperative atrial fibrillation (POAF). The multivariate regression model was adjusted for age, sex, NT-proBNP, type of surgery, and CRP-level at baseline. Results A total of 500 patients (146 female [29.2%]; median age 69.8 years [IQR 60.6-75.5]) were followed over a median of 4.6 years (IQR 3.0–5.8). Valve surgery was performed in 214 (42.8%) patients, 160 (32%) underwent a bypass operation and 126 (25.2%) a combined valve and bypass surgery. The median MR-proADM value of the entire study population was 0.58 nmol/L (IQR: 0.44-0.79 nmol/L). Patients were stratified in risk categories based on their MR-proADM values (Low Risk ≤0.63nmol/L, Intermediate Risk 0.63-0.83nmol/L, High Risk >0.84nmol/L). Patients in the highest category presented with higher rates of diabetes mellitus (p <0.001), COPD (p <0.001), HF (p=0.009) and either bypass surgery (p=0.039) or the combination of bypass and valve surgery (p=0.008), compared to patients in the lowest tertile. We observed a significant increase in 5-year’s event rates for HHF/ CV Mortality in patients in higher risk groups (Low Risk 8.6% vs High Risk 37.7%, p <0.001, Figure 1). The adjusted Cox regression model found that MR-pro ADM was independently associated with a risk increase for HHF/ CV Mortality (adjusted HR of 4.45, 95% CI 2.55-8.09; p<0.001, Figure 2) comparing the High Risk to the Low Risk Group. A comparable risk increase could be observed in POAF, with an adjusted HR of 2.61 (High Risk Group vs Low Risk Group, 95% CI 1.46-4.67, p<0.001). Conclusion Within the prospective investigation, MR-pro ADM was found to be an independent predictor for HHF and CV mortality in patients undergoing cardiac bypass and/or valve surgery. Furthermore, there was a consistent predictive potential for POAF. In the era of personalized medicine, preoperative MR-pro ADM levels could help to identify patients at risk for serious adverse events, in order to apply intensified secondary prevention and reduce mortality and morbidity.

Background: Postoperative atrial fibrillation (POAF) represents the most common complication following cardiac surgery. Approximately one-third of patients experiencing POAF transition to atrial fibrillation within a year, challenging the notion of POAF as merely a transient event. Soluble ST2 (sST2) is an established biomarker regarding fibrosis and myocardial stretch, however, its role in predicting the onset of POAF remains unclear. Methods: Preoperative sST2 levels have been assessed in 496 individuals with no prior history of AF who underwent elective cardiac surgery, including valve, coronary artery bypass graft surgery, or a combined procedure. Results: The average age was 70 years, and 29.4 % were female. Overall, 42.3 % developed POAF. sST2 levels were found to be significantly higher in patients with POAF. Interestingly, sST2 was only predictive of POAF in females with an adjusted OR of 1.894 (95 %CI:1.103-3.253; p = 0.021) and not males (OR:1.091; 95 % CI:0.849-1.402; p = 0.495). Furthermore, within a linear regression model it was observed that for every 1 ng/ mL increase in sST2 levels, the average POAF duration extended by 39.5 min (95 %CI:15.8-63.4 min; p = 0.001). Conclusion: sST2 predicts the onset of POAF in women but not men undergoing cardiac surgery. Furthermore, sST2 levels were associated with the subsequent burden of POAF. Thus, assessment of sST2 in addition to clinical risk factors could improve risk stratification for development of POAF following elective cardiac surgery.

Abstract Background Numerous randomized controlled trials have evaluated the efficacy of SGLT2i and demonstrated decreased hospitalization rates for HF and a better cardiorenal outcome in diverse heart failure (HF) populations comprising HF patients with reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction. Since the beneficial effects of SGLT2i in HF patients are well known, real-world data on the clinical implementation of these agents following availability of CV outcome trial data seems of utmost importance. Methods We identified patients presenting with HF who were hospitalized at a university affiliated tertiary care center, between 01/2017 and 10/2022. All prescriptions of SGLT2i (dapagliflozin and empagliflozin) – including marketed fixed-dose combinations with other glucose-lowering drugs – were identified. Results In total, 2,673 patients with HF (median age 75, 39.9% female, 23.1% with diabetes) were included in the present analyses. Among the 2,637 patients with signs and symptoms suggestive of HF, 1086 (40.6%) had a documented left ventricular ejection fraction (LVEF) ≤ 40% (HFrEF), 445 (16.6%) a LVEF between 40-50% (HFmrEF) and 1142 (42.7%) a LVEF > 50% (HFpEF). In the overall cohort, 382 (14.3%) patients received an SGLT2i. As shown in Figure 1, the prescription of SGLT2i significantly increased from the beginning to the end of the inclusion period. In detail, it climbed from 6.8% in 2017 to 56.6% in 2022 in the HFrEF group (p-trend <0.001), from 3.3% to 49.2% in the HFmrEF group (p-trend <0.001) and from 1.9% to a still very low 26.4% in the HFpEF group (p-trend <0.001). While prescription of SGLT2i in HFrEF patients started to increase after the presentation of the DAPA-HF trial, the SGLT2i prescription in HFmrEF and HFpEF patients showed a marked rise after the presentation of the new HF ESC guidelines (2021) and the EMPEROR-Preserved trial. Conclusion The prescription of SGLT2i is constantly rising due to greater awareness among cardiologists and other specialists in internal medicine. Nevertheless, despite a growing evidence on the reduction of CV events by SGLT2i, our data show that there is still room for improvement in prescribing of these cardioprotective agents, especially in patients with HFpEF.Prescription trend of SGLT2i.

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.

Abstract Background Heart failure (HF) and chronic kidney disease (CKD) form a vicious circle, reinforcing each other’s disease development and progression and causing higher rates in both morbidity and mortality. Here, we aimed to investigate the relationship between these two prevalent and interrelated diseases in an unselected patient population with AF. Methods This analysis includes patients with known AF, treated at a tertiary center between 07/2000 and 07/2019. The primary combined endpoint was hospitalization for heart failure (HHF) or cardiovascular (CV) death. We used cox regression models adjusted for age, sex, diabetes, coronary artery disease, hypertension, BMI and CRP-levels. Results We examined 7412 patients with AF and followed them over a median of 5.3 years. The median age was 70 years (IQR 61 to 78 years) and 2,945 (39.7%) were female. 434 (5.0%) patients had known CKD, 1,296 (17.5%) patients had HF, and 372 (5.4%) patients had both CKD and HF. There was a significant stepwise increase in event rates for the composite of CV death/HHF among patients without CKD or HF (KM event rate at 5 years: 23%), patients who had HF but no CKD (KM event rate at 5 years: 61%), patients with CKD but no HF (KM event rate at 5 years: 63%), and those who had both, HF and CKD (KM event rate at 5 years: 82%; P-logrank <0.001; Figure 1A). After multivariable adjustment, both CKD (with an adjusted hazard ratio of 2.22 and a 95% confidence interval of 1.87 to 2.63) and HF (with an adjusted hazard ratio of 2.53 and a 95% confidence interval of 2.26 to 2.84) were significantly associated with CV death/HHF and exerted a similar magnitude of the relationship. Patients with concomitant disease had the highest risk of the primary endpoint (with an adjusted hazard ratio of 3.96 and a 95% confidence interval of 3.34 to 4.68; Figure 1B). Conclusion AF patients with CKD and HF are at very high risk of CV death/HHF. Commonly used risk scores usually focus on stroke as the most dreaded complication in patients with AF. These findings suggest that the influence of CKD and HF expand beyond the risk of stroke to CV death/HHF in an unselected AF patient population.Figure 1

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF). In consideration of emerging evidence that there are clinically relevant sex-related differences in the course of T2DM and subsequent cardiovascular outcomes, it is unknown if SGLT2i therapy is sex-independently utilized in daily clinical practice. Methods: Patients with T2DM and HF admitted to a tertiary academic center between January 2014 and April 2020 were identified through a search of electronic health records. Data on antidiabetic therapy were acquired at discharge and were screened for SGLT2i prescription. Results: Overall, 812 patients (median age 70 years, 29.7% female) were included in the present analysis. Only 17.3% of the study population received an SGLT2i. In comparison between sexes, females show lower rates of SGLT2i prescription (11.2% vs. 19.8%, p = 0.003), despite comparable patient characteristics. Furthermore, male HF patients showed a significantly higher probability of SGLT2i prescription with an adjusted odds ratio of 2.59 (95% confidence interval 1.29-5.19; p = 0.008). Females who did not receive an SGLT2i showed higher rates of chronic kidney disease (25.2% vs. 7.4%, p = 0.039) and greater levels of N-terminal pro b-type natriuretic peptide (NT-proBNP; 2092 vs. 825 pg/mL, p = 0.011) as compared to female SGLT2i recipients, which did not explain the observed sex-related disparities. Conclusion: SGLT2i are potentially underutilized in female patients with HF and T2DM, despite an overall increasing prescription trend during the observation period. Reasons for withholding therapy could not be objectified. The present data indicate a major need to increase awareness of guideline-directed therapy, especially in female HF patients.

Abstract Background Postoperative atrial fibrillation (POAF) constitutes a common complication after cardiac surgery, that is associated with major adverse cardiac events and prolonged hospital stay. Causes for developing POAF are multifactorial. While there are non-modifiable predisposing characteristics such as higher age or comorbidities, several factors of postoperative patient management could be modulated in order to lower the individual risk of POAF. In this regard, inotropic agents (i.e. norepinephrine, dobutamine) in postoperative care are known to possess arrhythmogenic potential. It is unknown, however, to what extent this postoperative catecholamine therapy influences the emergence of POAF. Methods Within this prospective observational study 514 patients were included who underwent elective coronary artery bypass graft (CABG), heart valve, or combined valve/CABG surgery. In total, 438 patients received vasoactive drugs during the postoperative course. These participants were subsequently followed for the occurrence of POAF. Results Overall, 43.4% (n=190) of all catecholamine-receiving patients developed POAF. Interestingly, participants who developed POAF had received significantly higher median doses of norepinephrine as compared to non-POAF individuals (POAF: 0.083μg/kg/min vs. non-POAF: 0.062μg/kg/min; p=0.001), while the median dobutamine dose did not significantly differ between groups (POAF: 3.332 μg/kg/min vs. non-POAF 3.289μg/kg/min; p=0.254). Moreover, regression analysis identified norepinephrine with an adjusted hazard ratio (HR) per standard deviation (1-SD) of 1.388 (95% CI:1.114-1.728; p=0.003) as an independent risk factor for the occurrence of POAF. In addition, a norepinephrine dose of 0.18μg/kg/min was determined as the cut-off value, from which the POAF risk increased significantly. Notably, no association between dobutamine and POAF was found (adjusted HR 1.140 [95% CI:0.773-1.683; p=0.508]). Conclusion Within this prospective observational study, we were able to demonstrate that the postoperative use of norepinephrine, in contrast to dobutamine, represents an independent risk factor for the development of POAF. Furthermore, a dose dependency was found for norepinephrine from which the risk for POAF substantially increased. To prevent POAF episodes and thus prolonged intensive care unit stay it may be suggested to further promote rapid norepinephrine weaning if feasible.

Abstract Background Inflammatory activation plays a pivotal role in the development and progression of atherosclerosis and subsequently in coronary artery disease (CAD). Several biomarkers of inflammation such as C-reactive protein (CRP), leucocytes, and neutrophile-to-lymphocyte ratio (NLR), are considerable predictors of adverse events in CAD patients. The presence of underlying inflammation may also affect net outcomes of patients undergoing coronary angiography and percutaneous coronary intervention (PCI). However, the association between inflammatory activation and patient outcomes after coronary angiography remain widely unclear. Purpose The study goal was to investigate the predictive value of routinely used inflammation biomarkers including CRP, leukocytes and NLR in a large all-comer patient population undergoing coronary angiography. We aimed to gain additional insights into the association of inflammatory markers with patient outcomes to take a step towards personalized risk stratification for CAD patients. Methods A total of 12 642 patients undergoing coronary angiography between 2010 and 2021 with full laboratory analysis were enrolled in this observational study. CRP, leucocytes and NLR were analysed for possible effects on all-cause and cardiovascular mortality. We further investigated target lesion revascularization (TLR) after PCI in the presence of underlying inflammation as an intervention-specific endpoint. Results 3300 (26%) patients presented with acute coronary syndromes (ACS) and 4145 (33%) patients were treated with PCI. All investigated inflammatory biomarkers (CRP, leukocytes, NLR) were significantly associated with all-cause mortality and especially with cardiovascular mortality in both acute and elective patients. This association remained highly significant after adjusting for demographic and clinical variables. While CRP was strongly related with cardiovascular mortality in STEMI patients (ad. HR per 1 SD: 1.35 [95%-CI: 1.14 – 1.59]), no significant association was observed in NSTEMI patients (ad. HR per 1 SD: 1.04 [95%-CI: 0.92 – 1.17]; p for interaction: 0.007; figure 1). Notably, CRP was not found to be associated with TLR in patients undergoing acute or elective PCI (ad. HR per 1 SD: 0.99 [95%-CI: 0.88 – 1.11]; p-value: 0.857). However, we found a highly significant association between NLR and TLR in both acute and elective patients (ad. HR per 1SD: 1.27 [95%-CI: 1.12 – 1.43]; p-value: <0.001). Conclusion Inflammatory activation is associated with increased mortality in patients undergoing coronary angiography. Although the impact of inflammation on interventional outcomes may be assumed, our study did not show significant associations between CRP and TLR. However, NLR emerged as a robust predictor of adverse events after PCI. Thus, while CRP does not impact the interventional outcome of PCI, a modulation of the cellular immune response does.Figure 1