The use of andexanet alfa and 4-factor prothrombin complex concentrate in intracranial hemorrhage.

OBJECTIVE: to describe the clinical and safety outcomes between andexanet alfa (AA) and 4-factor prothrombin complex concentrate (4F-PCC) for the reversal of apixaban or rivaroxaban in the setting of an intracranial hemorrhage (ICH). METHODS: A retrospective, multicentered descriptive study was conducted in hospitalized patients 18 years of age or older from June 2018 to October 2019 who received AA or 4F-PCC for the reversal of apixaban or rivaroxaban in the setting of ICH. Patients were excluded if they had received 4F-PCC prior to AA after its addition to the institution wide formulary. Other exclusion criteria were history or presence of heparin-induced thrombocytopenia or disseminated intravascular coagulation, estimated hematoma volume of >60 mL, Glasgow Coma Scores <7, or no repeat CT head scan. Information was collected from the electronic medical records. The primary outcome was the achievement of excellent or good hemostatic efficacy upon the repeat computer tomography (CT) scan performed after the infusion of study drugs. Secondary outcomes included disposition, survival to hospital discharge, 30-day readmission, length of hospital stay, length of ICU stay, incidence of thromboembolic events. RESULTS: A total of 24 patients were included in the study, of which 9 received AA and 15 received 4F-PCC. The achievement of excellent or good hemostatic efficacy upon repeat CT scan occurred in 7 (77.8%) patients in the AA group and in 14 (93.3%) patients in the 4-F PCC group. All patients in the AA group survived to hospital discharge with no 30-day morality and 86.7% patients in the 4F-PCC group. CONCLUSION: This study suggests that real-world clinical and safety outcomes between andexanet alfa and 4F-PCC for the reversal of factor Xa inhibitors in the setting of ICH are similar to ones reported in clinical trials.

[Acute heart failure and cardiogenic shock : An update]. / Akute Herzinsuffizienz und kardiogener Schock : Ein Update.

Acute heart failure is a clinical syndrome resulting from elevated intracardiac filling pressures and a systemic venous congestion. In general, patients can present acutely without a history of structural cardiac disease (de novo heart failure) or with acute worsening of a pre-existing dysfunction of the right or left ventricle. The patient population is overall very inhomogeneous and as a result there is also a distinct heterogeneity with respect to the underlying cardiac pathology that leads to the acute presentation. Ultimately, ventricular dysfunction leads to increased preload and afterload resulting in decreased perfusion and retrograde congestion. The forward failure (hypoperfusion) and backwards failure (systemic congestion) can lead to impaired end organ function or even organ failure resulting in cardiogenic shock, in which sufficient organ and tissue perfusion is no longer possible. Consequently, therapeutic strategies currently focus on rectification of the underlying cardiac dysfunction, reduction of volume overload (decongestion) and hemodynamic stabilization with drugs supporting the circulation in the case of a hypoperfusion syndrome. Despite numerous new therapeutic strategies within the last two decades, the empirical data based on randomized trials is considerably less solid than in chronic heart failure, which is expressed in the almost unchanged 1­year mortality of approximately 20-30%.

Deoxyribonuclease is prognostic in patients undergoing transcatheter aortic valve replacement.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Prognostication of neurologic outcome using gray-white-matter-ratio in comatose patients after cardiac arrest.

BACKGROUND: This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest. METHODS: We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event. RESULTS: Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592-0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320-0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed. CONCLUSIONS: A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.

Admission Body Temperature in Critically Ill Patients as an Independent Risk Predictor for Overall Outcome.

INTRODUCTION: Body temperature (BT) abnormalities are frequently observed in critically ill patients. We aimed to assess admission BT in a heterogeneous critically ill patient population admitted to an intensive care unit (ICU) as a prognostic parameter for intra-ICU and long-term mortality. METHODS: A total of 6,514 medical patients (64 ± 15 years) admitted to a German ICU between 2004 and 2009 were included. A follow-up of patients was performed retrospectively. The association of admission BT with both intra-ICU and long-term mortality was investigated by logistic regression. RESULTS: Patients with hypothermia (<36°C BT) were clinically worse and had more pronounced signs of multi-organ failure. Admission BT was associated with adverse overall outcome, with a 2-fold increase for hyperthermia (mortality 12%; odds ratio [OR] 1.80, 95% confidence interval [CI] 1.43-2.26; p < 0.001), and a 4-fold increase for the risk of hypothermia (mortality 24%; OR 4.05, 95% CI 3.38-4.85; p < 0.001) with respect to intra-ICU and long-term mortality. Moreover, hypothermia was even more harmful than hyperthermia, and both were strongly associated with intra-ICU mortality, especially in patients admitted with acute coronary syndrome (hypothermia: hazard ratio 6.12, 95% CI 4.12-9.11; p < 0.001; hyperthermia: OR 2.70, 95% CI 1.52-4.79; p< 0.001). CONCLUSION: Admission BT is an independent risk predictor for both overall intra-ICU and long-term mortality in critically ill patients admitted to an ICU. Therefore, BT at admission might not only serve as a parameter for individual risk stratification but can also influence individual therapeutic decision-making.

Correction to: Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

After publication of the original article [1], we were notified that an author's name is not complete.

Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

BACKGROUND: Colchicine has been used as anti-inflammatory agent in pericardial effusion (PE). We sought to perform a meta-analysis of randomized trials assessing the efficacy and safety of colchicine in patients with pericarditis or postpericardiotomy syndrome (PPS). METHODS: In the systematic literature search following the PRISMA statement, 10 prospective randomized controlled studies with 1981 patients with an average follow-up duration of 13.6 months were identified. RESULTS: Colchicine reduced the recurrence rate of pericarditis in patients with acute and recurrent pericarditis and reduced the incidence of PPS (RR: 0.57, 95% CI: 0.44-0.74). Additionally, the rate of rehospitalizations as well as the symptom duration after 72 h was significantly decreased in pericarditis (RR 0.33; 95% CI 0.18-0.60; and RR 0.43; 95% CI 0.34-0.54; respectively), but not in PPS. Treatment with colchicine was associated with significantly higher adverse event (AE) rates (RR 1.42; 95% CI 1.05-1.92), with gastrointestinal intolerance being the leading AE. The reported number needed to treat (NNT) for the prevention of recurrent pericarditis ranged between 3 and 5. The reported NNT for PPS prevention was 10, and the number needed to harm (NNH) was 12, respectively. Late colchicine administration > 7 days after heart surgery did not reduce postoperative PE. CONCLUSIONS: Our meta-analysis confirms that colchicine is efficacious and safe for prevention of recurrent pericarditis and PPS, while it reduces rehospitalizations and symptom duration in pericarditis. The clinical use of colchicine for the setting of PPS and postoperative PE after heart surgery should be investigated in further multicenter RCT.

Hypoglycemia but Not Hyperglycemia Is Associated with Mortality in Critically Ill Patients with Diabetes.

BACKGROUND: Both severe hyperglycemia (> 200 mg/dL) and hypoglycemia (≤70 mg/dL) are known to be associated with increased mortality in critically ill patients. Therefore, we investigated associations of a single episode of blood glucose deviation (concentration either ≤70 mg/dL and/or > 200 mg/dL) during an intensive care unit (ICU) stay with mortality in these patients. METHODS: A total of 4,986 patients (age 65 ± 15 years; 39% female; 14% type 2 diabetes [T2DM] based on medical records) admitted to a German ICU in a tertiary care hospital were investigated retrospectively. The intra-ICU and long-term mortality of patients between 4 and 7 years after their ICU submission were assessed. RESULTS: A total 62,659 glucose measurements were analyzed. A single glucose deviation was associated with adverse outcomes compared to patients without a glucose deviation, represented by both intra-ICU mortality (22 vs. 10%; OR 2.62; 95% CI 2.23-3.09; p < 0.001) and long-term mortality (HR 2.01; 95% CI 1.81-2.24; p < 0.001). In patients suffering from T2DM hypoglycemia (30 vs. 13%; OR 2.94; 95% CI 2.28-3.80; p < 0.001) but not hyperglycemia (16 vs. 14%; OR 1.05; 95% CI 0.68-1.62; p = 0.84) was associated with mortality. CONCLUSION: In patients with dia-betes, hypo- but not hyperglycemia was associated with increased mortality, whereas in patients without diabetes, both hyper- and hypoglycemia were associated with adverse outcome. Blood glucose concentration might need differential approaches depending on concomitant diseases.

Specifics of fetuin-A levels in distinct types of chronic heart failure.

INTRODUCTION: Fetuin-A has been described to correlate inversely with vascular calcification both in animal models but also in patients with heart and renal disease. In this current study, we sought to investigate whether fetuin-A might be a useful marker for the discrimination of ischemic (ICM) from dilated cardiomyopathy (DCM). METHODS: A total of 124 non-consecutive patients were included in this study, 59 patients suffered from ICM and 65 patients from DCM. Serum samples were obtained during out-patient visits and analyzed for fetuin-A by ELISA. RESULTS: Median fetuin-A concentration in the overall cohort was significantly lower in ICM patients compared to DCM patients (62.2±16.4 µg/mL vs. 129.6±56.6 µg/mL; P<.001). A positive correlation of fetuin-A levels was found with BMI, cholesterol, LDL/HDL ratio and triglycerides and an inverse correlation with age (r=-.36; P<.001). Moreover, patients suffering from (stable) angina pectoris evidenced lower fetuin-A levels compared to non-symptomatic patients (73.1±22.7 µg/mL vs. 83.7±26.2 µg/mL; P=.047) CONCLUSIONS: Fetuin-A was shown to be a potential discriminator and biomarker for the differential diagnosis between ICM and DCM. Fetuin-A levels might also be helpful in the process of diagnostic decision-making in regards to invasive management or medical therapy.

Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure.

BACKGROUND: Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied. METHODS AND RESULTS: Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload. CONCLUSIONS: BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15-mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.

Multibiomarker analysis in patients with acute myocardial infarction.

BACKGROUND: Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied. METHODS: We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed. RESULTS: Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in µg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers. CONCLUSION: Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.

Predictors of future arrhythmic events in patients with unexplained syncope.

AIMS: The purpose of this study was to examine the usefulness of implantable loop recorders (ILRs) for symptom-rhythm correlation and to identify predictors of future arrhythmic events. PATIENTS AND METHODS: In our dual-centre study, we analysed ILR data of 189 patients (mean age 67.4 ± 15.2 years, 114 male) with unexplained syncope (single syncope 21 patients, recurrent 168 patients, traumatic injury 43 patients). Patients had severe comorbidities such as hypertension (n = 127), coronary artery disease (n = 31), diabetes mellitus (n = 33) and chronic renal insufficiency (n = 18). The median ILR usage was 29 months (M), with a range between 1 and 46 M. RESULTS: Forty-nine (26%) patients experienced syncope during the study, with a median of 8 M to first recurrence of syncope. In 43 patients, pacemaker implantation was performed because of sinus node disease (n = 29), high-degree AV-block (n = 6) or atrial fibrillation with slow ventricular rate (n = 8). In five patients, an ICD was implanted because of documented ventricular tachycardia (n = 4) or left ventricular ejection fraction <35% (n = 1). One patient received ablation of the cavotricuspid isthmus because of documented atrial flutter. Concerning the clinical course, in five patients explantation of the ILR was necessary due to pocket infection. Three patients died due to non-cardiac causes. Logistic regression analysis revealed that older patients had a significantly higher risk for future arrhythmic events (OR 1.3, p = .039). CONCLUSIONS: ILR monitoring is effective in indicating causes of unexplained syncope by providing symptom-rhythm associations. Only age was a predictor of future arrhythmic events. The mortality in patients with unexplained syncope was very low.

The Lactate/Albumin Ratio: A Valuable Tool for Risk Stratification in Septic Patients Admitted to ICU.

The lactate/albumin ratio has been reported to be associated with mortality in pediatric patients with sepsis. We aimed to evaluate the lactate/albumin ratio for its prognostic relevance in a larger collective of critically ill (adult) patients admitted to an intensive care unit (ICU). A total of 348 medical patients admitted to a German ICU for sepsis between 2004 and 2009 were included. Follow-up of patients was performed retrospectively between May 2013 and November 2013. The association of the lactate/albumin ratio (cut-off 0.15) and both in-hospital and post-discharge mortality was investigated. An optimal cut-off was calculated by means of Youden's index. The lactate/albumin ratio was elevated in non-survivors (p < 0.001). Patients with an increased lactate/albumin ratio were of similar age, but clinically in a poorer condition and had more pronounced laboratory signs of multi-organ failure. An increased lactate/albumin ratio was associated with adverse in-hospital mortality. An optimal cut-off of 0.15 was calculated and was associated with adverse long-term outcome even after correction for APACHE2 and SAPS2. We matched 99 patients with a lactate/albumin ratio >0.15 to case-controls with a lactate/albumin ratio <0.15 corrected for APACHE2 scores: The group with a lactate/albumin ratio >0.15 evidenced adverse in-hospital outcome in a paired analysis with a difference of 27% (95%CI 10-43%; p < 0.01). Regarding long-term mortality, again, patients in the group with a lactate/albumin ratio >0.15 showed adverse outcomes (p < 0.001). An increased lactate/albumin ratio was significantly associated with an adverse outcome in critically ill patients admitted to an ICU, even after correction for confounders. The lactate/albumin ratio might constitute an independent, readily available, and important parameter for risk stratification in the critically ill.

Increased Number of Mast Cells in Atherosclerotic Lesions Correlates with the Presence of Myeloid but not Plasmacytoid Dendritic Cells as well as Pro-inflammatory T Cells.

BACKGROUND: Atherosclerosis is an inflammatory disease of the vessel wall promoted by different immune cells and inflammatory mediators. METHODS: In this study, 26 human plaques and 12 control vessels without atherosclerosis were immunohistochemically stained to analyze the emergence of mast cells dependent on plaque morphology and to correlate mast cell occurrence with the emergence of myeloid as well as plasmacytoid dendritic cells. Also, mast cell emergence was correlated with the number of pro-inflammatory T cells. For this, plaques were classified as stable or unstable according to established histological criteria. RESULTS: As expected, atherosclerotic lesions showed significantly higher numbers of tryptase+, chymase+, and cathepsin G+ mast cells compared to control vessels, particularly in lesions with unstable morphology. As a novel finding, we detected significant correlations between mast cells and myeloid dendritic cells (fascin, CD83, r > 0.3, p < 0.01), but not plasmacytoid dendritic cells (CD123, CD304). Also, we observed significant correlations of mast cells and different subgroups of pro-inflammatory T cells (CD3, CD8, CD161, CD25; r > 0.35, p < 0.05). CONCLUSIONS: Overall, the higher number of mast cells in plaques, particularly with unstable morphology, suggests that mast cells might be involved in the progression of atherosclerosis. The correlation of mast cells with other immune cells that are pivotal in atherogenesis, e.g., myeloid dendritic cells and pro-inflammatory T cells, also suggests an interplay leading to plaque destabilization. Therefore, modulating local mast cell function and invasion into the plaque might be a therapeutic tool for plaque stabilization.

Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy.

UNLABELLED: Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors. METHODS: Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10 m, 1 h, 2 h, 6 h, 12 h, 24 h, 1 week, 2 weeks, 1 months and 2 months) after surgery (n=3 per time point, n=18 total). RESULTS: Cardiac and circulating MSTN upregulation occurred as early as 10 min after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin-proteasome system in the skeletal muscle was also evident. Serum from 24h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1. CONCLUSION: Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1.

Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.

Clinical presentation, shock severity and mortality in patients with de novo versus acute-on-chronic heart failure-related cardiogenic shock.

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

Association between left ventricular ejection fraction, mortality and use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

BACKGROUND: Currently, use of mechanical circulatory support (MCS) in non-ischaemic cardiogenic shock (CS) is predominantly guided by shock-specific markers, and not by markers of cardiac function. We hypothesise that left ventricular ejection fraction (LVEF) can identify patients with a higher likelihood to benefit from MCS and thus help to optimise their expected benefit. METHODS: Patients with non-ischaemic CS and available data on LVEF from 16 tertiary-care centres in five countries were analysed. Cox regression models were fitted to evaluate the association between LVEF and mortality, as well as the interaction between LVEF, MCS use and mortality. RESULTS: N = 807 patients were analysed: mean age 63 [interquartile range (IQR) 51.5-72.0] years, 601 (74.5%) male, lactate 4.9 (IQR 2.6-8.5) mmol/l, LVEF 20 (IQR 15-30) %. Lower LVEF was more frequent amongst patients with more severe CS, and MCS was more likely used in patients with lower LVEF. There was no association between LVEF and 30-day mortality risk in the overall study cohort. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with LVEF ≤ 20% (hazard ratio 0.72, 95% confidence interval 0.51-1.02 for LVEF ≤ 20% vs. hazard ratio 1.31, 95% confidence interval 0.85-2.01 for LVEF > 20%, interaction-p = 0.017). CONCLUSION: This retrospective study may indicate a lower mortality risk with MCS use only in patients with severely reduced LVEF. This may propose the inclusion of LVEF as an adjunctive parameter for MCS decision-making in non-ischaemic CS, aiming to optimise the benefit-risk ratio.