Decreased percentages of plasmacytoid dendritic cells predict survival in critically ill patients.

Critically ill patients admitted to intensive care units (ICUs) experience a broad variety of life-threatening conditions. Irrespective of the initial cause of hospitalization, many experience systemic immune dysregulation. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a pivotal role in regulating the immune response by linking the innate to the adaptive immune system. The aim of this study was to analyze whether DCs or their respective subsets are associated with 30-d mortality in an unselected patient cohort admitted to a medical ICU with a cardiovascular focus. A total of 231 patients were included in this single-center prospective observational study. Blood was drawn at admission and after 72 h. Subsequently, flow cytometry was utilized for the analysis of DCs and their respective subsets. In the total cohort, low percentages of DCs were significantly associated with sepsis, respiratory failure, and septic shock. In particular, a significantly lower percentage of circulating plasmacytoid DCs (pDCs) was found to be a strong and independent predictor of 30-d mortality after adjustment for demographic and clinical variables with an hazard ratio of 4.2 (95% confidence interval: 1.3-13.3, P = 0.015). Additionally, low percentages of pDCs were correlated with additional markers of inflammation and organ dysfunction. In conclusion, we observed low percentages of DCs in patients admitted to an ICU experiencing sepsis, respiratory failure, and cardiogenic shock, suggesting their depletion as a contributing mechanism for the development of immune paralysis. In our cohort, pDCs were identified as the most robust subset to predict 30-d mortality.

Sex-Related Disparities in Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Type 2 Diabetes and Heart Failure.

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.

The Impact of Preclinical High Potent P2Y12 Inhibitors on Decision Making at Discharge and Clinical Outcomes in Patients with Acute Coronary Syndrome.

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.

Relationship of Fibroblast Growth Factor 23 With Hospitalization for Heart Failure and Cardiovascular Outcomes in Patients Undergoing Cardiac Surgery.

Background Fibroblast growth factor 23 (FGF-23) is crucial in regulating phosphate and vitamin D metabolism and is moreover associated with an increased cardiovascular risk. The specific objective of this study was to investigate the influence of FGF-23 on cardiovascular outcomes, including hospitalization for heart failure (HHF), postoperative atrial fibrillation, and cardiovascular death, in an unselected patient population after cardiac surgery. Methods and Results Patients undergoing elective coronary artery bypass graft and/or cardiac valve surgery were prospectively enrolled. FGF-23 blood plasma concentrations were assessed before surgery. A composite of cardiovascular death/HHF was chosen as primary end point. A total of 451 patients (median age 70 years; 28.8% female) were included in the present analysis and followed over a median of 3.9 years. Individuals with higher FGF-23 quartiles showed elevated incidence rates of the composite of cardiovascular death/HHF (quartile 1, 7.1%; quartile 2, 8.6%; quartile 3, 15.1%; and quartile 4, 34.3%). After multivariable adjustment, FGF-23 modeled as a continuous variable (adjusted hazard ratio for a 1-unit increase in standardized log-transformed biomarker, 1.82 [95% CI, 1.34-2.46]) as well as using predefined risk groups and quartiles remained independently associated with the risk of cardiovascular death/HHF and the secondary outcomes, including postoperative atrial fibrillation. Reclassification analysis indicated that the addition of FGF-23 to N-terminal pro-B-type natriuretic peptide provides a significant improvement in risk discrimination (net reclassification improvement at the event rate, 0.58 [95% CI, 0.34-0.81]; P<0.001; integrated discrimination increment, 0.03 [95% CI, 0.01-0.05]; P<0.001). Conclusions FGF-23 is an independent predictor of cardiovascular death/HHF and postoperative atrial fibrillation in individuals undergoing cardiac surgery. Considering an individualized risk assessment, routine preoperative FGF-23 evaluation may improve detection of high-risk patients.

Soluble urokinase plasminogen activator receptor and survival in elective cardiac surgery.

BACKGROUND: The study investigated the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing cardiac surgery and calculated a simplified biomarker score comprising suPAR, N-terminal pro B-type natriuretic peptide (NT-proBNP) and age. METHODS AND RESULTS: Biomarkers were assessed in a cohort of 478 patients undergoing elective cardiac surgery. After a median follow-up of 4.2 years, a total of 72 (15.1%) patients died. SuPAR, NT-proBNP and age were independent prognosticators of mortality in a multivariable Cox regression model after adjustment for EuroScoreII. We then calculated a simplified biomarker score comprising age, suPAR and NT-proBNP, which had a superior prognostic value compared to EuroScoreII (Harrel's C of 0.76 vs. 0.72; P for difference = 0.02). Besides long-term mortality, the biomarker score had an excellent performance predicting one-year mortality and hospitalization due to heart failure. CONCLUSION: The biomarker suPAR and NT-proBNP were strongly and independently associated with mortality in patients undergoing cardiac surgery. A simplified biomarker score comprising only three variables (age, suPAR and NT-proBNP) performed better than the established EuroScoreII with respect to intermediate and long-term outcome as well as hospitalization due to heart failure. As such, integration of established and upcoming biomarkers in clinical practice may provide improved decision support in cardiac surgery.

The age-specific prognostic impact of the platelet-to-lymphocyte ratio on long-term outcome after acute coronary syndrome.

Aims: Personalized risk stratification within the ageing society after acute coronary syndrome (ACS) remains scarce but in urgent need. Increased platelet activity together with inflammatory activation play a key role during ACS. We aimed to evaluate the age-specific prognostic potential of the platelet to lymphocyte ratio (PLR) on long-term cardiovascular mortality after ACS. Methods and results: Patients presenting with ACS admitted to the Vienna General Hospital between December 1996 and January 2010 were enrolled within a clinical registry including assessment of peripheral blood samples. The impact of the PLR on survival was assessed by Cox-regression hazard analysis. We included a total of 681 patients with a median age of 64 years (interquartile range: 45-84). Two hundred (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 1 standard deviation (1 SD) of 1.07 (95% confidence interval, CI: 1.03-1.10); P < 0.001]. After stratification in individuals <65 years (n = 339) and ≥65 years (n = 342), a prognostic effect of the PLR on cardiovascular mortality was solely observed in elderly patients ≥65 years [adj. HR per 1 SD of 1.04 (95% CI: 1.00-1.08); P = 0.039], but not in their younger counterparts <65 years [adj. HR per 1 SD of 0.97 (95% CI: 0.83-1.14); P = 0.901]. 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.

Cardiogenic Shock Does Not Portend Poor Long-Term Survival in Patients Undergoing Primary Percutaneous Coronary Intervention.

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.

Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The impact of left atrial mechanics on adverse events and clinical outcome after cardiac surgery.

OBJECTIVES: Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery that is associated with unfavourable clinical outcome. Identifying patients at risk for POAF is crucial but challenging. This study aimed to investigate the prognostic potential of speckle-tracking echocardiography 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 preoperative speckle-tracking echocardiography. Patients were followed prospectively for the occurrence of POAF within the entire hospitalization and reaching the secondary end points cardiovascular 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% confidence interval (CI): 10.9-17.8] vs non-POAF: 19.4% [95% CI: 14.8-23.5], P < 0.001}. Moreover, global PALS was a strong and independent predictor for POAF [adjusted odds ratio per 1 standard deviation: 0.37 (95% CI: 0.22-0.65), P < 0.001] and independently associated with mortality [adjusted hazard ratio per 1 standard deviation: 0.63 (95% CI: 0.40-0.99), P = 0.048]. Classification and Regression Tree analysis revealed a cut-off value of <17% global PALS as high risk for both POAF and mortality. CONCLUSIONS: 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 <17% face a poor long-term prognosis, routine assessment of global PALS needs to be considered in terms of proper secondary prevention in the era of personalized medicine.

Relationship of diabetes, heart failure, and N-terminal pro-B-type natriuretic peptide with cardiovascular outcomes in patients with atrial fibrillation.

AIMS: We aim to explore the relationship of heart failure (HF) and diabetes with cardiovascular (CV) death or hospitalization for HF (HHF) and to study the clinical utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected patient population with atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF admitted to a tertiary academic center between January 2005 and July 2019 were identified through a search of electronic health records. We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, coronary artery disease, hypertension, smoking, C-reactive protein, and low-density lipoprotein cholesterol. To select the most informative variables, we performed a least absolute shrinkage and selection operator Cox regression with 10-fold cross-validation. In total, 7412 patients (median age 70 years, 39.7% female) were included in this analysis and followed over a median of 4.5 years. Both diabetes [adjusted (Adj.) HR 1.87, 95% CI 1.55-2.25] and HF (Adj. HR 2.57, 95% CI 2.22-2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared with patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. NT-proBNP showed good discriminatory performance (area under the curve 0.78, 95% CI 0.77-0.80) and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant area under the curve improvement (Δ = 0.04, P < 0.001). With least absolute shrinkage and selection operator, the strongest associations for CV death/HHF were obtained for NT-proBNP [HR 1.91 per 1-SD in log-transformed biomarker], HF (HR 1.72), and diabetes (HR 1.56). CONCLUSIONS: Diabetes and HF were independently associated with an increased risk of CV death/HHF in an unselected AF patient population, and NT-proBNP improved risk assessment. These findings suggest that AF patients with diabetes and/or HF should be managed not only for their risk of stroke and systemic embolic events but also for CV death/HHF.

The Prognostic Impact of Anti-thrombotic Treatment Strategies After Biological Aortic Valve Replacement.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors and Cardiovascular Outcomes in Patients with Diabetes Mellitus and Heart Failure.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.001). In propensity score-adjusted pairwise analyses, SGLT2i treatment was inversely associated with long-term cardiovascular mortality in patients with HFrEF presenting with an adjusted HR of 0.33 (95%CI: 0.13-0.86; p = 0.024). CONCLUSION: Despite large outcome trials showing a cardiovascular benefit, SGLT2i remain underutilized in clinical practice in patients with T2DM and HF. National and European Medical Agency remuneration regulations would allow more patients at high risk to receive these cardiovascular protective drugs. Most importantly, an SGLT2i therapy was associated with a survival benefit in patients with HFrEF.

The Prognostic Potential of Growth Differentiation Factor-15 on Bleeding Events and Patient Outcome after Cardiac Surgery-A Prospective Cohort Study.

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 < 0.001). Higher concentrations of GDF-15 were observed in patients reaching the secondary endpoint of major or clinically relevant minor bleeding (for bleeding risk factors adj. OR per 1-SD of 1.70 [95% CI: 1.05-2.75]; p = 0.030) during the first postoperative year, but not for thromboembolic events. GDF-15 was a predictor for cardiovascular mortality (for comorbidities adj. HR [hazard ratio] per 1-SD of 1.67 [95% CI: 1.23-2.27]; p = 0.001) and all-cause mortality (for comorbidities adj. HR per 1-SD of 1.55 [95% CI: 1.19-2.01]; p = 0.001). A combined risk model of GDF-15 and EuroSCORE II outperformed the EuroSCORE II alone for long-term survival (C-index: 0.75 [95% CI: 0.70-0.80], p = 0.046; net reclassification improvement: 33.6%, p < 0.001). 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.

The prognostic impact of left ventricular thrombus resolution after acute coronary syndrome and risk modulation via antithrombotic treatment strategies.

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 antithrombotic 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 major adverse cardiac events (MACE) and thromboembolic 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 = .022), MACE (-37.8%; p = .005), and thromboembolic events (-35.2%; p = .008). Even after adjustment for clinical variables, thrombus resolution showed an independent inverse association with all-cause death with a hazard ratio (HR) of 0.14 (95% CI: 0.03-0.75; p = .021) and as well with MACE with a HR of 0.22 (95% CI: 0.07-0.68; p = .008) and thromboembolic events with a HR of 0.22 (95% CI: 0.06-0.75; p = .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 = .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 antithrombotic treatment approach-in this patient population.

Propensity for Calcification in Serum Associates With 2-Year Cardiovascular Mortality in Ischemic Heart Failure With Reduced Ejection Fraction.

Background: The propensity of serum to calcify, as assessed by the T50-test, associates with mortality in patients with chronic kidney disease. In chronic heart failure, phosphate and fibroblast growth factor-23 (FGF-23), which are important components of the vascular calcification pathway, have been linked to patient survival. Here, we investigated whether T50 associates with overall and cardiovascular survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods: We measured T50, intact and c-terminal FGF-23 levels in a cohort of 306 HFrEF patients. Associations with overall and cardiovascular mortality were analyzed in survival analysis and Cox-regression models. Results: After a median follow-up time of 3.2 years (25th-75th percentile: 2.0-4.9 years), 114 patients (37.3%) died due to any cause and 76 patients (24.8%) died due to cardiovascular causes. 139 patients (45.4%) had ischemic and 167 patients (54.6%) had non-ischemic HFrEF. Patients with ischemic HFrEF in the lowest T50-tertile had significantly greater 2-year cardiovascular mortality compared to patients in higher tertiles (p = 0.011). In ischemic but not in non-ischemic HFrEF, T50 was significantly associated with cardiovascular mortality in univariate (p = 0.041) and fully adjusted (p = 0.046) Cox regression analysis. Significant associations of intact and c-terminal FGF-23 with all-cause and cardiovascular mortality in univariate Cox regression analysis did not remain significant after adjustment for confounding factors. Conclusion: T50 is associated with 2-year cardiovascular mortality in patients with ischemic HFrEF but not in non-ischemic HFrEF. More research on the role of T50 measurements in coronary artery disease is warranted.

The impact of invasive respiratory support on the development of postoperative atrial fibrillation following cardiac surgery.

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.

Prescription Patterns of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Coronary Artery Disease.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Prognostic Potential of Atrial Natriuretic Peptide on the Development of Postoperative Atrial Fibrillation after Cardiac Surgery.

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 < 0.001). MR-proANP showed a strong association with the development of POAF with a crude odds ratio (OR) of 1.68 per 1 standard deviation (1-SD; 95% confidence interval [CI]: 1.31-2.15; p < 0.001), which remained stable after comprehensive adjustment for confounders with an adjusted OR of 1.74 per 1-SD (95% CI: 1.17-2.58; p = 0.006). The discriminatory power of MR-proANP for the development of POAF was validated by the category-free net reclassification improvement (0.23 [95% CI: 0.0349-0.4193]; p = 0.022) and integrated discrimination increment (0.02 [95% CI: 0.0046-0.0397], p = 0.013). 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.