Background: Liver damage is frequently observed in patients with cardiovascular disease but infrequently quantified. We hypothesized that in patients with cardiovascular disease undergoing cardiac magnetic resonance, liver T1-times indicate liver damage and are associated with cardiovascular outcome. Methods: We measured hepatic T1-times, displayed on standard cardiac T1-maps, in an all-comer cardiac magnetic resonance-cohort. At the time of cardiac magnetic resonance, we assessed validated general liver fibrosis scores. Kaplan-Meier estimates and Cox-regression models were used to investigate the association between hepatic T1-times and a composite endpoint of non-fatal myocardial infarction, heart failure hospitalization, and death. Results: One thousand seventy-five participants (58±18 year old, 47% female) were included (972 patients, 50 controls, 53 participants with transient elastography). Hepatic T1-times were 590±89 ms in patients and 574±45 ms in controls ( P =0.052). They were significantly correlated with cardiac size and function, presence of atrial fibrillation, NT-pro-BNP levels, and gamma-glutamyl-transferase levels ( P <0.001 for all). During follow-up (58±31 months), a total of 280 (29%) events occurred. On Cox-regression, high hepatic T1-times yielded a significantly higher risk for events (adjusted hazard ratio, 1.66 [95% CI, 1.45–1.89] per 100 ms increase; P 610 ms seems to indicate excessive risk. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04220450.

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.

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.

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.

Background: 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. Methods: 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. Results: 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% CI 0.87–1.19], p value 0.874), all-cause mortality (HR 1.05 [95% CI 0.91–1.22], p value 0.491), MACE (HR 1.10 [95% CI 0.96–1.26], p value 0.170), acute myocardial infarction (HR 1.08 [95% CI 0.90–1.19], p value 0.308), or any revascularization (HR 1.03 [95% CI 0.90–1.19], p value 0.671) between both groups. However, we observed a trend toward lower rates of target lesion revascularization in patients with small vessel disease (HR 0.84 [95% CI 0.68–1.02], p value 0.072), and in side branch lesions (HR 0.79 [95% CI 0.58–1.04], p value 0.096). Conclusion: DCBs demonstrated long-term safety and efficacy in de novo lesions, with promising trends in reducing target lesion revascularization in small vessel disease and side branches. Graphical

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.