Fermentation of cocoa pod husks with Pleurotus salmoneo-stramineus for food applications.

Cocoa pod husks (CPHs), the major side-stream from cocoa production, were valorized through fermentation with Pleurotus salmoneo-stramineus (PSS). Considering ergosterol as a biomarker for the fungal content, the mycelium accounted for 54% of the total biomass after 8 days in submerged cultures. The crude protein content of fermented CPH (CPHF) increased from 7.3 g/100 g DM in CPH to 18.9 g/100 g DM. CPH fermentation resulted in a high biological value of 86 for the protein. The water and oil binding capacities of CPHF were 3.5 mL/g and 2.1 mL/g, respectively. The particle diameter dv,0,90 of CPHF was 373 µm as compared to 526 µm for CPH. The total dietary fiber was 73.4 g/100 g DM in CPHF and 63.6 g/100 g DM in CPH. The amount of soluble fiber was 2.3 g/100 g DM in CPHF and 10.1 g/100 g DM in CPH; the insoluble fraction accounted for 71.1 g/100 g DM and 53.6 g/100 g DM, respectively. Bread doughs with CPH or CPHF were characterized for texture, color, and farinographic properties. The dough hardness, consistency, and browning index increased with the concentration of CPH, whereas for CPHF, springiness and peak viscosities declined. We demonstrate the upcycling of CPH into nutritious and functional ingredients through PSS fermentation.

Early Initiation of SGLT2 Inhibitors in Acute Heart Failure: a Focus on Diuresis and Renal Protection.

PURPOSE: Acute heart failure (AHF) represents a critical and life-threatening condition characterized by the sudden onset or exacerbation of symptoms, such as dyspnea and fluid retention, due to impaired cardiac function. Despite advances in the treatment of chronic heart failure (HF), the management of AHF remains challenging, with limited therapeutic options available. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a promising drug class in AHF management. METHODS/RESULTS: The objective of this article was to conduct a comprehensive review of the existing literature in the domain of SGLT2 inhibitors and their relevance in the context of AHF. CONCLUSION: The existing evidence underscores the importance of SGLT2 inhibitors in enhancing decongestive therapy for AHF patients. Early initiation appears both practical and beneficial, leading to improved and sustained decongestion, a reduction in heart failure-related events, enhanced quality of life, and decreased mortality rates, all while maintaining a favorable safety profile. Consequently, it should be considered to initiate SGLT2 inhibitor treatment as early and as safely as possible to facilitate effective decongestion. However, careful patient selection and monitoring are essential when considering the use of these drugs in the management of AHF.

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.

Rivaroxaban in Valvular Atrial Fibrillation - a Critical Appraisal of the INVICTUS Trial.

PURPOSE: The efficacy of factor Xa inhibitors in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD) is unknown. METHODS/RESULTS: The objective of this article was to conduct a comprehensive evaluation of the INVICTUS trial, an open-label randomized controlled study that compared vitamin K antagonists (VKA) to rivaroxaban in patients with AF and RHD while also considering the existing evidence from literature in this particular area of research. CONCLUSION: The findings of the INVICTUS trial indicated that rivaroxaban was found to be inferior in efficacy to VKA. However, it is important to note that the primary outcome of the trial was driven by sudden death and death caused by mechanical pump failure. As a result, it is necessary to approach the data from this study with caution, and it would be inappropriate to draw parallel conclusions for other causes of valvular AF. Particularly, the perplexing issue of how rivaroxaban could have contributed to both pump failure and sudden cardiac death requires further explanation. Additional data regarding changes in heart failure medication and ventricular function would be essential for proper interpretation.

Biocatalytic Production of Odor-Active Fatty Aldehydes from Fungal Lipids.

Odor-active fatty aldehydes are important compounds for the flavor and fragrance industry. By a coupled enzymatic reaction using an α-dioxygenase (α-DOX) and an aldehyde dehydrogenase (FALDH), scarcely available aldehydes from the biotransformation of margaroleic acid [17:1(9Z)] were characterized and have shown highly interesting odor profiles, including citrus-like, soapy, herbaceous, and savory notes. In particular, (Z)-8-hexadecenal and (Z)-7-pentadecenal exhibited notable meaty odor characteristics. Submerged cultivation of Mortierella hyalina revealed the accumulation of the above-mentioned, naturally uncommon fatty acid 17:1(9Z). Its production was significantly increased by the modulation of culture conditions, whereas the highest accumulation was observed after 4 days at 24 °C and l-isoleucine supplementation. The lipase-, α-DOX-, and FALDH-mediated biotransformation of M. hyalina lipid extract resulted in a complex aldehyde mixture with a high aldehyde yield of ∼50%. The odor qualities of the formed aldehydes were assessed by means of gas chromatography-olfactometry, and several of the obtained fatty aldehydes have been sensorially described for the first time. To assess the aldehyde mixture's potential as a flavor ingredient, a sensory evaluation was conducted. The obtained product exhibited intense citrus-like, green, and soapy odor impressions.

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.

Rivaroxaban After Transcatheter Aortic Valve Replacement: A Critical Appraisal of the GALILEO Trial.

PURPOSE: The anti-thrombotic approach in individuals undergoing transcatheter aortic valve replacement (TAVR) mirrors a controversial field in clinical practice. METHODS/RESULTS: The aim of this article was to critically appraise the randomized controlled GALILEO trial, where two different antithrombotic regimes (10 mg rivaroxaban + 3 months aspirin vs. aspirin + 3 months clopidogrel) were compared in patients who underwent TAVR as well as available evidence in literature in this field. CONCLUSION: The GALILEO trial was prematurely terminated as a consequence of increased risk of both death or thromboembolic complications and a higher risk of bleeding in the anticoagulation arm, compared to the antiplatelet-based strategy. Various concerns have been raised that the negative results of the GALILEO trial need to be regarded with caution. A routine use of oral anticoagulation (OAC) for the prevention of atherothrombotic events and valve thrombosis after TAVR in individuals who do not have an indication for oral anticoagulation, can currently not be recommended when considering the evidence base of available literature. However, the negative results of the GALILEO trial need to be interpreted with caution - especially in terms of dose of rivaroxaban - and should not discourage from performing further trials investigating safety and efficacy of this therapeutic approach. Additionally, further dose-finding trials for rivaroxaban should be considered.

An enzymatic tandem reaction to produce odor-active fatty aldehydes.

Aldehydes represent a versatile and favored class of flavoring substances. A biocatalytic access to odor-active aldehydes was developed by conversion of fatty acids with two enzymes of the α-dioxygenase pathway. The recombinant enzymes α-dioxygenase (α-DOX) originating from Crocosphaera subtropica and fatty aldehyde dehydrogenase (FALDH) from Vibrio harveyi were heterologously expressed in E. coli, purified, and applied in a coupled (tandem) repetitive reaction. The concept was optimized in terms of number of reaction cycles and production yields. Up to five cycles and aldehyde yields of up to 26% were achieved. Afterward, the approach was applied to sea buckthorn pulp oil as raw material for the enzyme catalyzed production of flavoring/fragrance ingredients based on complex aldehyde mixtures. The most abundant fatty acids in sea buckthorn pulp oil, namely palmitic, palmitoleic, oleic, and linoleic acid, were used as substrates for further biotransformation experiments. Various aldehydes were identified, semi-quantified, and sensorially characterized by means of headspace-solid phase microextraction-gas chromatography-mass spectrometry-olfactometry (HS-SPME-GC-MS-O). Structural validation of unsaturated aldehydes in terms of double-bond positions was performed by multidimensional high-resolution mass spectrometry experiments of their Paternò-Büchi (PB) photoproducts. Retention indices and odor impressions of inter alia (Z,Z)-5,8-tetradecadienal (Z,Z)-6,9-pentadecadienal, (Z)-8-pentadecenal, (Z)-4-tridecenal, (Z)-6-pentadecenal, and (Z)-8-heptadecenal were determined for the first time. KEY POINTS: • Coupled reaction of Csα-DOX and VhFALDH yields chain-shortened fatty aldehydes. • Odors of several Z-unsaturated fatty aldehydes are described for the first time. • Potential for industrial production of aldehyde-based odorants from natural sources.

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.

Retrograde Analysis of Calcium Signaling by CaMPARI2 Shows Cytosolic Calcium in Chondrocytes Is Unaffected by Parabolic Flights.

Calcium (Ca2+) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca2+ signaling with a high spatiotemporal resolution is a key challenge. However, particularly on microgravity platforms, experiment time is limited, allowing only a small number of replicates. Furthermore, experiment hardware is exposed to changes in gravity levels, causing experimental artifacts unless appropriately controlled. We introduce a new experimental setup based on the fluorescent Ca2+ reporter CaMPARI2, onboard LED arrays, and subsequent microscopic analysis on the ground. This setup allows for higher throughput and accuracy due to its retrograde nature. The excellent performance of CaMPARI2 was demonstrated with human chondrocytes during the 75th ESA parabolic flight campaign. CaMPARI2 revealed a strong Ca2+ response triggered by histamine but was not affected by the alternating gravitational load of a parabolic flight.

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.

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.