Background and Aims: Fulminant myocarditis (FM) is a complex clinical syndrome characterized by acute myocardial inflammation and cardiogenic shock. Evidence on long-term outcomes, mortality risk factors, and targeted treatment options remains limited. Methods: This retrospective analysis included consecutive adult patients admitted for FM between January 2012 and November 2022 at 26 European tertiary centres. According to endomyocardial biopsy (EMB) findings, patients were categorized as lymphocytic (LM), eosinophilic (EM), necrotizing eosinophilic (NEM), and giant-cell myocarditis (GCM) for the main analyses. Patients with inconclusive histopathology and those who did not undergo EMB were analysed separately. Primary outcomes were in-hospital and 1-year mortality. Multivariable logistic regression models were employed as generalized linear models to analyse the association of prespecified risk factors with mortality. Estimated associations are reported as odds ratios, generalized marginal effects, and adjusted prediction plots. Results: A total of 271 patients [median age 43 years (interquartile range: 33–55 years), 58% male] were included in the analysis, of whom 146 fulfilled histopathologic criteria of LM (n = 99), EM (n = 18), NEM (n = 3), or GCM (n = 26). In the remaining 125 cases, EMB was inconclusive (n = 48) or not performed (n = 77). While there were no significant differences in cardiac arrest rate, admission Simplified Acute Physiology Score (SAPS) II, ventricular function, initial pH, and liver and kidney function parameters between histopathologic subgroups, the use of immunosuppressive medications and need for organ replacement varied. In the overall population, in-hospital and 1-year mortality were 31% and 34%, respectively. The highest 1-year mortality rate was observed among patients with GCM (LM: 25%, EM: 28%, NEM: 33%, GCM: 54%, P = .04). Patients who survived to discharge had an excellent functional outcome and long-term recovery of ventricular function. In total, 17 patients (6%) received a heart transplant during follow-up. Older age, lower pH, and histopathologic diagnosis of GCM were independently associated with in-hospital and 1-year mortality. Conclusions: In-hospital mortality among patients with FM remains high. Age, pH, and histopathological findings may serve as prognostic markers to identify high-risk patients and to guide treatment strategies. Long-term outcomes are excellent among those who survive to discharge.

Background: Hemolysis, a common adverse event associated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), may affect neuron-specific enolase (NSE) levels and potentially confound its prognostic value in predicting neurological outcomes in resuscitated patients without return of spontaneous circulation (ROSC) that require extracorporeal cardiopulmonary resuscitation (eCPR). Therefore, a better understanding of the relationship between hemolysis and NSE levels could help to improve the accuracy of NSE as a prognostic marker in this patient population. Methods: We retrospectively analyzed the records of patients who received a VA-ECMO for eCPR between 2004 and 2021 and were treated in the medical intensive care unit (ICU) of the University Hospital Jena. The outcome was measured clinically by using the Cerebral Performance Category Scale (CPC) four weeks after eCPR. The serum concentration of NSE (baseline until 96 h) was analyzed by enzyme-linked immunosorbent assay (ELISA). To evaluate the ability of individual NSE measurements to discriminate, receiver operating characteristic (ROC) curves were calculated. Serum-free hemoglobin (fHb, baseline until 96 h) served as a marker for identifying a confounding effect of parallel hemolysis. Results: 190 patients were included in our study. A total of 86.8% died within 4 weeks after ICU admission or remained unconscious (CPC 3–5), and 13.2% survived with a residual mild to moderate neurological deficit (CPC 1–2). Starting 24h after CPR, NSE was significantly lower and continued to decrease in patients with CPC 1–2 compared to the group with an unfavorable outcome of CPC 3–5. In addition, when evaluating on the basis of receiver operating characteristic curves (ROC), relevant and stable area under the curve (AUC) values for NSE could be calculated (48 h: 0.85 // 72 h: 0.84 // 96 h: 0.80; p < 0.01), and on the basis of a binary logistic regression model, relevant odds ratios for the NSE values were found even after adjusting for fHb regarding the prediction of an unfavorable outcome of CPC 3–5. The respective adjusted AUCs of the combined predictive probabilities were significant (48 h: 0.79 // 72 h: 0.76 // 96 h: 0.72; p ≤ 0.05). Conclusions: Our study confirms NSE as a reliable prognostic marker for poor neurological outcomes in resuscitated patients receiving VA-ECMO therapy. Furthermore, our results demonstrate that potential hemolysis during VA-ECMO does not significantly impact NSE’s prognostic value. These findings are crucial for clinical decision making and prognostic assessment in this patient population.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve prognosis in chronic heart failure as part of currently recommended therapeutic strategies. Transthoracic echocardiography (TTE) is frequently used to assess heart function and dimensions in acute heart failure to lead therapy and assess volume status. Immediate changes, especially of left heart haemodynamic parameters, measured by echocardiography in patients with acute heart failure treated with SGLT2 inhibitors, remain unknown. Aim: The aim of this pre-defined secondary analysis was to assess whether treatment with empagliflozin 25 mg/day in patients with acute heart failure improves echocardiographic parameters of load, left ventricular or right ventricular function. Methods and results: In the single-centre, prospective, double-blind, placebo-controlled EMPAG-HF trial, patients with acute decompensated heart failure (ADHF) were screened and randomized within 12 h following hospital admission to receive either empagliflozin or placebo in addition to standard medical treatment over 5 days. Sixty patients were enrolled and randomized irrespective of left ventricular ejection fraction or diabetes. All patients received 2D TTE on admission (tB = at baseline) and after completing the study treatment (tC = time after completing study medication) (according to study design). The recorded loops were analysed using dedicated software (Image-Arena™ Version 4.6; TomTec Imaging Systems). After 5 days of treatment, patients in the empagliflozin cohort showed a relevant decrease in left atrial volume [LAV: ∆tB-tC = 30.9 ± 27.4; 95% confidence interval (CI) 20.1–41.7) compared to placebo ∆tB-tC = 10.5 ± 26; 95% CI 0.4–20.5; P = <0.001] and left atrial end-systolic volume index (LAESVI: ∆tB-tC = 15.7 ± 15.1; 95% CI 9.8–21.6 vs. placebo ∆tB-tC = 9.7 ± 10.2; 95% CI 5.7–13.6; P = 0.016) compared to placebo. Conclusion: Immediate addition of empagliflozin to standard therapy improves echocardiographic parameters of LAV in patients following recompensation of ADHF.

Background: Multiple organ dysfunction syndrome (MODS) is common in intensive care units (ICUs) and is associated with high mortality. Although there have been multiple investigations into a multitude of organ dysfunctions, little is known about the role of liver dysfunction. In addition, clinical and laboratory findings of liver dysfunction may occur with a significant delay. Therefore, the aim of this study was to investigate whether a liver function test, based on indocyanine green (ICG)-clearance, contains prognostic information for patients in the early phase of MODS. Methods: The data of this analysis were based on the MODIFY study, which included 70 critically ill patients of a tertiary medical ICU in the early phase of MODS (≤24 h after diagnosis by an APACHE II score ≥ 20 and a sinus rhythm ≥ 90 beats per minute, with the following subgroups: cardiogenic (cMODS) and septic MODS (sMODS)) over a period of 18 months. ICG clearance was characterized by plasma disappearance rate = PDR (%/min); it was measured non-invasively by using the LiMON system (PULSION Medical Systems, Feldkirchen, Germany). The PDR was determined on the day of study inclusion (baseline) and after 96 h. The primary endpoint of this analysis was 28-day mortality. Results: ICG clearance was measured in 44 patients of the MODIFY trial cohort, of which 9 patients had cMODS (20%) and 35 patients had sMODS (80%). Mean age: 59.7 ± 16.5 years; 31 patients were men; mean APACHE II score: 33.6 ± 6.3; 28-day mortality was 47.7%. Liver function was reduced in the total cohort as measured by a PDR of 13.4 ± 6.3%/min At baseline, there were no relevant differences between survivors and non-survivors regarding ICG clearance (PDR: 14.6 ± 6.1%/min vs. 12.1 ± 6.5%/min; p = 0.21). However, survivors showed better liver function than non-survivors after 96 h (PDR: 21.9 ± 6.3%/min vs. 9.2 ± 6.3%/min, p < 0.05). Consistent with these findings, survivors but not non-survivors show a significant improvement in the PDR (7.3 ± 6.3%/min vs. −2.9 ± 2.6%/min; p < 0.01) within 96 h. In accordance, receiver-operating characteristic curves (ROCs) at 96 h but not at baseline show a link between the PDR and 28-day mortality (PDR at 96 h: AUC: 0.87, 95% CI: 0.76–0.98; p < 0.01. Conclusions: In our study, we found that ICG clearance at baseline did not provide prognostic information in patients in the early stages of MODS despite being reduced in the total cohort. However, improvement of ICG clearance 96 h after ICU admission is associated with reduced 28-day mortality.

(1) Background: Sepsis still represents a major health care challenge, with mortality rates exceeding 25% in the western world. To further improve outcomes in this patient collective, new cardiovascular biomarkers present a promising opportunity as they target the paramount prognostic processes in sepsis: inflammation and ischemia. However, in contrast to cardiovascular diseases, a detailed analysis of novel biomarkers in sepsis is still lacking. (2) Objective: In this project, we aimed to perform a comparative analysis of biomarker levels in ischemic cardiovascular disease and sepsis. Analyzed markers comprised soluble suppression of tumorigenicity 2 (sST2; hemodynamics and inflammation), growth-differentiation factor 15 (GDF-15; injury, remodelling), soluble urokinase-type plasminogen activator receptor (suPAR; inflammation and remodeling) and heart-type fatty acid binding protein (H-FABP; myocardial ischemia). (3) Methods: In total, 311 patients were included in the study: 123 heart-failure (HF) patients, 60 patients with ST-segment elevation myocardial infarction (STEMI) and 53 sepsis patients. A total of 75 patients without coronary artery disease or signs of heart failure served as a control group. Plasma samples were analyzed by use of ELISA after informed consent. (4) Results: Patients with sepsis showed significantly increased plasma levels in all tested biomarkers compared to cardiovascular disease entities (sST2, suPAR, GDF-15: p < 0.001; H-FABP: compared to HF p < 0.001) and controls (sST2: 7.4-fold, suPAR: 3.4-fold, GDF-15: 6.5-fold and H-FABP: 15.3-fold increased plasma levels, p < 0.001). Moreover, in patients with sepsis, serum concentrations of sST2 and suPAR were significantly elevated in patients with HF and patients with STEMI (sST2: HF: 1.6-fold increase and STEMI: 2.5-fold increase, p < 0.001; suPAR: HF: 1.4-fold increase, p < 0.001 and STEMI: 1.4-fold increase, p < 0.01), whereas plasma levels of GDF-15 and H-FABP were markedly elevated in patients with STEMI only (GDF-15: 1.6-fold increase, H-FABP: 6.4-fold increase, p < 0.001). (5) Conclusions: All tested novel cardiac biomarkers showed significantly elevated levels in sepsis patients. Interestingly, a secretion pattern similar to STEMI was observed with regards to sST2 and HFABP. Thus, by providing an assessment tool especially covering the cardiovascular component of the disease, novel biomarkers offer a promising tool in sepsis patients.

Background: Cardiogenic shock and arrest present as critical, life-threatening emergencies characterized by severely compromised tissue perfusion and inadequate oxygen supply. Veno–arterial extracorporeal membrane oxygenation (VA–ECMO) serves as a mechanical support system for patients suffering shock refractory to conventional resuscitation. Despite the utilization of VA–ECMO, clinical deterioration due to systemic inflammatory response syndrome (SIRS) resulting from the underlying shock and exposure of blood cells to the artificial surfaces of the ECMO circuit may occur. To address this issue, cytokine adsorbers offer a valuable solution by eliminating blood proteins, thereby controlling SIRS and potentially improving hemodynamics. Consequently, a prospective, randomized, blinded clinical trial will be carried out with ECMOsorb. Methods and Study Design: ECMOsorb is a single-center, controlled, randomized, triple-blinded trial that will compare the hemodynamic effects of treatment with a VA–ECMO in combination with a cytokine adsorber (CytoSorb^®, intervention) to treatment with VA–ECMO only (control) in patients with cardiogenic shock (with or without prior cardiopulmonary resuscitation (CPR)) requiring extracorporeal, hemodynamic support. Fifty-four patients will be randomized in a 1:1 fashion to the intervention or control group over a 36-month period. The primary endpoint of ECMOsorb is the improvement of the Inotropic Score (IS) 72 h after the intervention. Prognostic indicators, including mortality rates, hemodynamic parameters, laboratory findings, echocardiographic assessments, quality of life measurements, and clinical parameters, will serve as secondary outcome measures. The safety evaluation encompasses endpoints such as air embolisms, allergic reactions, peripheral ischemic complications, vascular complications, bleeding incidents, and stroke occurrences. Conclusions: The ECMOsorb trial seeks to assess the efficacy of a cytokine adsorber (CytoSorb^®; CytoSorbents Europe GmbH, Berlin, Germany) in reducing SIRS and improving hemodynamics in patients with cardiogenic shock who are receiving VA–ECMO. We hypothesize that a reduction in cytokine levels can lead to faster weaning from inotropic and mechanical circulatory support, and ultimately to improved recovery.