Funding Source Research Articles

Promises and challenges of populational proteomics in health and disease.

Advances in proteomic assay technologies has significantly increased coverage and throughput, enabling recent increases in the number of large-scale population-based proteomic studies of human plasma and serum. Improvement in multiplexed protein assays have facilitated quantification of thousands of proteins over a large dynamic range, a key requirement for detecting the lowest ranging, and potentially the most disease relevant, blood circulating proteins. In this perspective, we examine how populational proteomic datasets in conjunction with other concurrent omic measures can be leveraged to better understand the genomic and non-genomic correlates of the soluble proteome, constructing biomarker panels for disease prediction, among others. Mass spectrometry workflows are discussed as they are becoming increasingly competitive with the affinity-based array platforms in terms of speed, cost and proteome coverage due to advances in both instrumentation and workflows. Despite much success, there remains considerable challenges such as orthogonal validation and absolute quantification. We also highlight emergent challenges associated with study design, analytical considerations and data integration as population scale studies are run in batches and may involve longitudinal samples collated over many years. Lastly, we take a look at the future of what the nascent next-generation proteomic technologies might provide to the analysis of large sets of blood samples, as well as the difficulties in designing large-scale studies that will likely require participation from multiple and complex funding sources and where data sharing, study designs and financing must be solved.

SWOT Analysis and QSPM as a Strategy for Developing Village Owned Business Units (BUMDes) Tanjung Beringin Village

SWOT Analysis and QSPM as a Strategy for Developing Village Owned Business Units (BUMDes) Tanjung Beringin Village

Identifying minibonds issued level’s determinants to empower companies’ funding managerial strategies

PurposeThis paper aims to explore the determinants of the level of minibonds issued by companies. In doing so, it discusses the importance of minibonds in providing a market-based funding source. In the empirical analysis, special attention is paid to the study of the recovery from the COVID-19 crisis.Design/methodology/approachThe analysis is carried out through an econometric approach, on the basis of a high-quality empirical dataset related to the Italian small- and medium-sized enterprises (SMEs). The reference period covers the recent pandemic. From a theoretical point of view, a regression model is implemented, including a multicollinearity analysis and an outlier detection procedure.FindingsThe results of the study indicate that factors such as leverage, cash flow, firm collaterals and seniority can explain the amount of minibonds issued. These findings provide valuable insights into the drivers of minibond issuance and highlight the potential benefits of minibonds as a funding option for Italian SMEs.Practical implicationsImportantly, results highlight relevant managerial implications at two levels. On one side, we carry on a managerial discussion about the worthiness of accessing the minibonds market; on the other side, we give insights on the managerial implications related to the features of the companies issuing minibonds.Originality/valueThe paper investigates an innovative financial instrument that has been introduced recently and has not yet been studied in depth. To the best of our knowledge, this is the first contribution assessing the main drivers for minibonds issuance level, which is a timely and relevant managerial research topic. In addition, this study also takes into account the impact of the COVID-19 pandemic on minibond issuance, making the analysis appropriate for explaining the current economic context.

Globalisation of Professional Sport Finance

The objective of the present paper is to put a milestone on the roadmap toward a global economic system of professional sport, at least as regards its financial dimension, i.e., its model of finance, its ownership, and some new trends in global sport finance. Professional sport went through a radical change during the 1990s when switching from gate receipts to TV rights revenues as its major source of finance and from local/domestic to internationalised/globalised sources of revenue. This change was more marked in European soccer (football) before spreading throughout other professional sport disciplines. In fact, the whole distribution of sport financing was restructured as shown in this paper. Starting from this evidence of the first stage of sport finance globalisation, it appears that new transformations have been at work in sport finance more recently. In particular, soccer moved from globalisation of flows (revenues, finance) to asset globalisation in terms of club ownership. At last, this paper discusses the emergence of new trends in global sport finance such as treating professional (soccer) players as financial assets and crypto-assets penetrating the sports business.

SMEs, Trade Finance Markets and Instruments: A Review of the Issues with Reference to Asia

Abstract Small and Medium Enterprises (SMEs) are an important source of employment and economic activity, but their expansion and growth may be limited by the existence of trade finance constraints due mainly to a lack of access to external sources of finance. We present a conceptual framework for understanding trade finance transactions, instruments, and participants; and map this framework to the available data used to measure trade finance. Finally, we present some stylized facts on the relationship between various trade finance instruments, and their possible links to SME outcomes with reference to ASEAN countries. We find that there are many (though imperfect) proxies for trade finance activities; and that improving trade finance is associated with more desirable SME outcomes.

Some Positive Trends in the Development of University Science in Russia at the Present Time

The development of university science is one of the state policy priorities in Russia today. To determine this process prospects, it is important to identify positive trends and best practices of leading Russian universities scientific activity. For this purpose, the article considers the organizational features and sources of university science funding, analyzes the main indicators of research performance and practices of research policy implementation, summarizes the scientific achievements of leading Russian universities. The article uses the methods of universities monitoring activities statistical analysis and substantive analysis of information about the universities` scientific activities posted in open sources. The conclusions are drawn about the formation in Russia leading universities group with a stable priority of research activities, the core of which is formed by leading technical sectoral universities and regional polytechnic universities, the practices of science organization and the main scientific achievements of which can significantly influence the further development of domestic university science, as well as the world scientific knowledge expansion and Russian society socio-economic development issues solution.

An Assessment of the Critical Success Factors of Microfinance Institutions (MFIs) in Lusaka, Zambia

This research focuses on the critical success and failure factors of microfinance institutions (MFIs) in Lusaka, Zambia, addressing a vital aspect of the financial landscape that impacts small businesses and low-income individuals. Despite the positive role of MFIs in providing financial assistance to entrepreneurs, recent closures of six institutions in Zambia underscore the need to understand the factors influencing their success or failure. The problem statement highlights the potential consequences of MFI closures, such as negative impacts on women, increased poverty levels, income inequality, child labor, and barriers to sustainable local economic development. Notably, the study aims to fill a research gap by assessing factors affecting MFIs' operations in Zambia, particularly those leading to closures, which the Bank of Zambia has not yet addressed or documented. The research objectives are clear and specific, intending to assess both critical failure factors from MFIs that have closed in Lusaka and critical success factors for the functioning of MFIs in the region. Additionally, the study aims to suggest measures to enhance the application of these critical success factors. Moving into the research methodology, an exploratory research design is chosen, providing a foundation for assessing the critical success factors of MFIs in Zambia. The mixed-method approach, incorporating qualitative and quantitative strategies, enhances the comprehensiveness of the study. The target population comprises 29 registered MFIs in Lusaka, and a one-stage cluster sampling technique is applied to select 10 MFIs with 60 key informants. The use of questionnaires for data collection, both open and closed-ended, facilitates the gathering of both qualitative and quantitative information. Ethical considerations are diligently addressed, ensuring informed consent, confidentiality, justice, anonymity, and protection from harm. In the discussion of findings, a demographic analysis reveals important characteristics of the respondent base, emphasizing the predominantly male representation and the prevalence of tertiary education among participants. Objective one focuses on assessing critical failure factors, with limited access to funding, operational efficiency, and limited financial literacy emerging as primary challenges. Objective two delves into critical success factors, highlighting financial stability, marketing strategies, technology adoption, and outreach to the underserved population as significant considerations. Objective three provides insights into measures employed by MFIs, such as technology integration, capacity building, customer-centric approaches, and risk management systems. The recommendations emphasize diversification of funding sources, tailored financial literacy initiatives, operational efficiency optimization, and enhanced community engagement to address identified challenges. In summary, this study contributes valuable insights into the dynamics of MFIs in Lusaka, offering practical recommendations for their sustained success and impact on local communities.

Attracting investments through crowdfunding platforms as a method for agro-industrial enterprises to enter the international market

Since agriculture is an important sector of the Russian economy, the problem of lack of capital in this sector is still relevant. The article shows that in the era of digital technologies, new sources of fundraising are emerging in the agro-industrial complex. Crowdfunding is one of such modern sources of financing in the world practice which is able to significantly expand the basis of the investment pyramid of the agricultural sector. In the course of the study, a review of domestic and foreign literature on this method of raising funds was conducted. General scientific methods were used: observation, comparison, measurement, analysis and synthesis, the method of logical reasoning, and specific scientific method of static analysis. A critical review of domestic and foreign practice has shown the main advantages and disadvantages of attracting financing through crowdfunding platforms. Also, as a result of the conducted research, it was found that this way of attracting investments not only solves problems of financing the agricultural sector, but is also a successful method for agricultural enterprises to enter foreign markets. In the era of innovative finance, this article contributes to the growing literature and initiatives to introduce and develop crowdfunding in the agri-food industry.

A Study On: Taxation as a Major Source of Government Fundings - Special Reference to Implementation of GST

Taxation is the major source of funding for the government in India. The total revenue obtained by the government is used for the nation’s expenses such as railway, road construction, health and education etc. this research paper provides quantitative and qualitative analysis regarding whether taxation is the major source of government funding or not. It is worth noting that the government requires funding in order to conduct its operations in an efficient manner. This can be related to how a human requires money in order to fulfil their needs and desires. However, in this case the government will require the funds for its activities such as health care, transportation, defenses etc. tax is generally considered to be a reliable and viable source of finance for the Indian government. Additionally, this research paper provides a thorough understanding on the role the GDP plays in this context.

Characterization and mid-term outcomes of current out-of-hospital cardiac arrest patients admitted to intensive cardiovascular care units

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Consell Català de Resuscitació. Background Out-of-hospital cardiac arrest (OHCA) accounts the 50% of cardiovascular deaths. Being aware of characteristics and outcomes of our OHCA population is important in order to apply measures in the weaker areas to improve the results of the process. Purpose To investigate current outcomes, at 6-month follow-up, of patients admitted to an Intensive Cardiac Care Unit (ICCU) in a mediterranean area during the 2020s. Current characteristics, prehospital management and factors related to outcomes were also analyzed. Methods PCR-Cat was a prospective observational multicentre registry. OHCA patients admitted to the ICCU of 8 hospitals were included from October/2020 to December/2021. Those who survived with good neurological status, no disabilities, and remained independent for usual life activities, were classified as Good Outcome (GO). Those patients who died or had a poor neurological status, with high dependency or rested in permanent vegetative status were classified as Poor Outcome (PO). A multinomial logistic regression was done to analyze the factors independently related to PO. Results 288 patients were included, only 50 (17.36%) were women. At 6-month follow-up, 48.95% of patients had GO. Most events happened in the first month (Figure 1). The cause of death was neurological in 72.9%. Patients with PO were significantly older (63.74 vs. 58.88, p=0.003) and had more comorbidities (Table 1A). The most frequent location was on a public space (54.84%) and most were witnessed (88.93%). Cardiopulmonary resuscitation maneuvers were initiated by a bystander in 69.18% until EMS arrival, being only 20.79% done by an experienced bystander. The medium no-flow time was low (2 min) but total time until ROSC was of 28 min. First rhythm was shockable in 80%, but an automatic external defibrillator was only used in 58% of cases. Statistically significant lower values of first pH and higher values of first lactate, glucose and creatinine were related to PO (Table 1B). Patients with PO had a higher APACHE II (26 vs. 20, p<0.001) and SOFA (10.39 vs. 7.14, p<0.001) scores at admission, and required a longer time on mechanical ventilation (6 vs. 3.5 days, p=0.001). The main cause of the OHCA was acute coronary syndrome (53.82%), followed by chronic coronary syndrome (7.64%) and dilated myocardiopathy (7.64%). In the multinomial logistic regression, older age (p=0.005), male sex (p=0.016), previous stroke (p=0.046), longer ROSC time (p<0.001) and non-shockable first rhythm (p<0.001) were independently related to PO. Receiving cardiopulmonary resuscitation maneuvers by an experienced bystander was related to a reduction of 17 min of ROSC (p=0.001). Conclusions Less than a half of patients admitted to an ICCU because of an OHCA had GO at 6-month follow-up. Age, male sex, previous stroke, longer ROSC time and non-shockable first rhythm were factors independently related to PO. Interventions addressed to reduce ROSC time are urgently needed.

Levels of high-sensitive troponin T and mid-regional pro-adrenomedullin after COVID-19 vaccination

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Federal Ministry of Education and Research. Background/Introduction To increase vaccine safety, adverse events of COVID-19 vaccines are continuously monitored. This also includes rare complications of the cardiovascular system. However, it has so far been scarcely investigated whether chronic and subtle, clinically inapparent myocardial and/or vascular injury occurs in a COVID-19 vaccinated population on a broader basis. Purpose The aim of this study was to analyse chronic and subclinical adverse effects of COVID-19 vaccines on the cardiovascular system. Vaccine-associated myocardial involvement was examined by measuring high-sensitive troponin T (hsTnT) while mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction. Methods This was a prospective observational study with a vulnerable population of healthcare workers (HCWs) and elderly (> 70 years) patients who were vaccinated with either the ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) and the BNT162b2 mRNA vaccine (BNT), or with BNT/BNT between the 12th of January and 30th of November 2021 (Figure 1). HsTnT and MR-proADM was measured in blood samples at three visits (V1: 1st baseline, immediately before vaccination; V2: 3-4 weeks after 1st vaccination; V3: 3-4 weeks after 2nd vaccination). HsTnT levels were further compared with a healthy reference cohort. Results 120 participants were included (V1=119, V2=120, V3=120). 50 (41.7%) received AZ/BNT. 70 (58.3%) were vaccinated with BNT/BNT of whom 20 (16.7%) were elderly and 50 (41.7%) were HCWs. Median hsTnT levels were at 4ng/L, 5ng/L and 4ng/L (V1-V3) for AZ/BNT and at 6ng/L, 6ng/L and 6ng/L (V1-V3) for BNT/BNT, respectively (Figure 2). Levels of MR-proADM were 0.43nmol/L, 0.46nmol/L and 0.44nmol/L (V1-V3) in the AZ/BNT cohort and 0.49nmol/L, 0.43nmol/L and 0.49nmol/L in the BNT/BNT group. Change of hsTnT and MR-proADM values between visits did not show significant increases. Two cases had a transient (7ng/L, 19ng/L, 5ng/L; male, 29 years) or permanent (15ng/L, 21ng/L, 25ng/L; male, 37 years) increase in hsTnT levels, exceeding the upper reference limit (≥ 14ng/L). Compared to the reference population (n=300), median hsTnT was significantly higher at all visits for both vaccination groups (p<0.05), without significant differences between the AZ/BNT and BNT/BNT cohorts. Conclusion(s) With two individual exceptions, no overall chronic myocardial injury or endothelial involvement was observed up to 4 weeks after the 2nd SARS-CoV-2 vaccination when comparing hsTnT and MR-proADM after both vaccinations to baseline values.Figure 1Vaccination scheme.Figure 2.hsTnT values at V1-V3.

Intra-abdominal hypertension in acute decompensated heart failure - an overlooked piece in the puzzle of diuretic resistance

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Wroclaw Medical University, Insitute of Heart Diseases, Wroclaw, Poland. Introduction Intra-abdominal pressure (IAP) is a frequently overlooked aspect in clinical assessment which can have a significant impact on organ dysfunction in patients with acute decompensated heart failure (ADHF). Purpose To investigate prevalence and dynamics of IAP in patients with ADHF and its impact on diuretic response. Methods 30 patients admitted for ADHF, class III or IV in New York Heart Association classification were enrolled into a prospective, observational pilot study. In every individual serial transurethral IAP measurements, blood and urine samples were taken upon admission, on the second and the third day of hospitalization. Results The study showed 63.3% prevalence of intra-abdominal hypertension (IAH) defined as IAP ≥ 12 mmHg upon admission, while only roughly 13% presented overt signs of abdominal congestion. Patients diagnosed with IAH upon admission had significantly poorer diuresis in the first day of hospitalization, despite receiving similar doses of loop diuretics (p = 0.038). Moreover, IAP was negatively correlated with urine output (p = 0.011) and positively correlated with urine osmolality (p = 0.033), while there was no relationship between IAP and natriuresis. There was a significant reduction of IAP among patients with IAH treated according to the European Society of Cardiology guidelines. Conclusions The investigation revealed an exepctionally high prevalence of elevated IAP among patients hospitalized for ADHF and highlights the limitations of physical examination in assessing abdominal congestion, as most patients remain asymptomatic. The observed poorer diuresis in patients diagnosed with IAH and the established association between IAP and the reduced urinary output, despite achieving target levels of natriuresis, add another piece to the puzzle of understanding the phenomenon of diuretic resistance in ADHF and set directions for future studies.

All lactate are not equal substudy of the BOX trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The BOX trial was supported by a grant (NNF17OC0028706) from the Novo Nordisk Foundation. Dr. Hassager's work is funded by a grant (R186-2015-2132) from the Lundbeck Foundation. Background Lactate levels following out-of-hospital cardiac arrest (OHCA) are associated with arrest duration (time to ROSC) and mortality. However, given the complexity of lactate generation and clearance, lactate levels assessed at hospital arrival represent not only time to ROSC but also the quality of resuscitation, circulatory stability following ROSC, dose of epinephrine administered, kidney, liver, and mitochondrial function in the early post-cardiac arrest phase. Accordingly, we describe the lactate levels at hospital arrival according to time to ROSC and one-year mortality. Method In this sub-study of the randomized clinical BOX trial, blood lactate levels were measured immediately at hospital arrival. Time to ROSC was registered in the medical records. Patients were divided into two groups according to median time to ROSC (≤ 18 min or > 18 min). The primary outcome was one-year mortality. Results The study included 768 (97% of the randomized population) patients of which 386 (50%) patients had ≤ 18 min and 382 (50%) patients had > 18 min to ROSC. The median age (64 (54-73) years) and sex distribution (81% men) was similar in both groups. One-year mortality was 76 (20%) and 199 (52%) in the ≤ 18 min and > 18 min to ROSC groups respectively. Mean lactate levels were 3.8 mmol/L (95%CI: 3.5-4.1) and 5.9 mmol/L (95%CI: 5.4-6.2), respectively. Lactate levels differed significantly between one-year survivors and non-survivors in the patients with ≤ 18 min to ROSC (mean difference: 1.9 mmol/L, 95%CI: 1.0 - 2.8) but not for patients with > 18 min to ROSC (mean difference: 0.6 mmol/L, 95%CI: -0.1-1.3), Figure 1. Further, lactate’s ability to predict one-year mortality was fair in the ≤ 18 min group with an Area Under Receiver Operating Characteristic Curve (AUC) of 0.68 (95%CI: 0.62-0.75) but poor for the > 18 min groups with an AUC of 0.55 (95%CI: 0.50-0.61) (DeLong's test for two ROC curves, p = 0.004), Figure 2. Conclusion Lactate's predictive value for one-year mortality decreases with increasing time to ROSC in OHCA. This highlights the importance of individualized clinical approaches based on lactate dynamics in OHCA patients.Figure 1Figure 2

Admission plasma concentration of neutrophil gelatinase-associated lipocalin and -C-reactive protein have additive prognostic value in patients with STEMI

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Righospitalets Forskningsfond (07IO) Lundbeck Foundation (R186-2015-2132). Background Inflammation plays an apparent critical role in patients with acute coronary syndrome (ACS) and is associated with mortality. However, the complex process is poorly understood. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker originating from mature neutrophils and renal tubular cells. It has previously been shown to be associated with mortality and acute kidney injury in ACS patients. In this study we sought to assess the potential additive prognostic value of NGAL and its relation to other markers of inflammation. Methods In 1556 consecutive ST-elevation myocardial infarction (STEMI) patients, NGAL and C-reactive protein (CRP) plasma concentration were measured at hospital admission, before acute coronary angiography. Patients were stratified to plasma concentration of both biomarkers >/< the median concentration into 4 groups (low NGAL/ low CRP (group 1), low NGAL/high CRP (2), high NGAL/low CRP (3), high NGAL/high CRP(4)). Primary outcome was 30-day all-cause mortality. Results In total, 477 (31%), 324 (21%), 316 (20%), and 439 (28%) patients were stratified in group 1-4, respectively. With 0, 1, or 2 biomarker plasma concentration above the median (group 1 – 4), patients were older (61 – 67 years old, p<0.0001), had more comorbidity (hypertension (40 – 53%), p=0.002; previous stroke (4.0 – 9.9%), p=0.007; peripheral arterial disease (PAD) (2.6 – 10%), p<0.0001; chronic kidney dysfunction (CKD) (0.6 – 11%), p<0.0001) and more critical per-infarction circumstances (time from symptom debut to angiography (170 – 229 minutes), p<0.0001; cardiogenic shock (1.3 – 14%), p<0.0001, cardiac arrest (0.8 – 3.4%), p=0.0002) and lower left ventricular ejection fraction (LVEF) (48 – 43%, p<0.0001). Increased NGAL and CRP was associated with 30-day all-cause mortality (Figure A). Only high NGAL/high CRP was independently associated with 30-day mortality in a cox proportional hazard model when adjusting for age, hypertension, previous stroke, CKD, LVEF, and cardiogenic shock (HR (95% CI) 5.19 (1.20 – 22.52), p=0.03). Both CRP and NGAL had significant predictive value of 30-day mortality (AUC ROC 0.67, p<0.0001 and 0.78, p<0.0001, respectively). Combining NGAL and CRP did, however, not increase the predictive value of NGAL alone (AUC ROC 0.77, p=0.86) (Figure B). Conclusion Combined admission NGAL and CRP plasma concentration was independently associated with 30-day all-cause mortality in STEMI patients. Adding CRP to NGAL did, however, not increase the predictive value.Figure AFigure B

Risk assessment by acute bedside echocardiography prior to acute coronary angiography in patients with ST-elevation myocardial infarction: a feasibility study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation. Background Early risk assessment by hemodynamic measurements in patients with ST-elevation myocardial infarction (STEMI) could be useful for early detection of patients at risk of developing hemodynamic instability after primary percutaneous coronary intervention (pPCI). Anterior STEMI patients have larger infarct size and may be of particular interest. Transthoracic echocardiography (TTE) is a quick, non-invasive, and available tool, however, evidence regarding the use of acute TTE prior to acute coronary angiography (CAG) is limited. Purpose To assess the feasibility of acute bedside hemodynamic assessment in the cath. lab. by TTE in addition to clinical examination, and blood samples in STEMI patients without CS at arrival in the cath. lab. Methods STEMI patients without CS at hospital arrival and treated with pPCI were included in the study during a five week period. Clinical examination (Killip class), blood sampling (lactate, troponin T (TNT), proB-type natriuretic peptide (proBNP), and focused bedside 2D TTE with Doppler were performed prior to the acute CAG. The TTE protocol was focused (approx. 5 minutes) on hemodynamic measurements, infarction related complications, and differential diagnoses e.g. aortic dissection. The TTE was performed during preparation for the acute CAG. Patients were stratified in anterior- vs. non-anterior STEMI based on the culprit artery and prehospital ECG. Feasibility was estimated by all of the following echocardiographic parameters; left ventricular ejection fraction (LVEF), left ventricular outflow tract (LVOT) velocity time integral (VTI), and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)). Results A total of 60 STEMI patients (aged mean 63 years, 18% female) were included, and 47% had an anterior STEMI. No differences in baseline characteristics between the two groups were found including comorbidities, clinical parameters, and time from cath. lab. arrival to first wire over the culprit lesion (median (IQR) 28 (23; 38) vs 32 (24; 40) minutes). Admission biomarkers of blood glucose, lactate, and proBNP plasma concentrations were similar between the two groups. Whereas admission TNT were higher for patients with anterior STEMI (median (IQR) 110 (37; 449) vs. 37 (20; 94) ng/L, p=0.01). The feasibility of TTE-study protocol was 93%. Patients with anterior STEMI had lower LVEF (mean: 36±11 vs. 48±9%, p=0.0003; missing: n=0), and a trend to lower LVOT VTI (19 (6.4) vs. 22 (5.0) cm, p=0.06; missing: n=4). No difference in parameters of diastolic function or TAPSE (missing: n=0) were found. None of the included patients had echocardiographic visible complications related to the infarction. Conclusion Acute TTE is to a high degree feasible and does not delay time to acute revascularization in STEMI patients. Patients with anterior STEMI have significantly higher admission TNT levels, lower LVEF, and a trend to lower LVOT VTI compared with non-anterior STEMI patients.

Heparin monitoring in ImpellaTM-supported cardiogenic shock patients: the benefit of parallel dual testing

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Coagulopathic complications often jeopardize the outcome of critically ill patients in cardiogenic shock (CS) during percutaneous mechanical circulatory support (pMCS). Therefore, meticulous management of heparin therapy is mandatory to ensure appropriate anticoagulation management. In this context, the most convenient and most frequently used test is the activated partial thromboplastin time (APTT). However, the APTT-test can be prolonged or shortened independent of the patient's anticoagulation status due to various confounding factors during critical illness (e.g., sepsis, liver failure, factor XI/XII consumption). Alternatively, the anti-Xa assay directly measures heparin activity. Therefore, to optimize heparin anticoagulation during critical illness, an anti-Xa-guided protocol for heparin titration combined with parallel APTT measurements to assess both bleeding and thrombotic risk has recently been proposed. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa and APTT-measurements in an anti-Xa-guided heparin anticoagulated CS population during left-sided ImpellaTM support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (>24h) and heparin anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. Anti-Xa was considered in range between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile (per center protocol, underlying atrial fibrillation or venous thromboembolism). In range APTT values were considered 40-55s and 55-80s respectively. Correlation between parallel anti-Xa and APTT values was assessed by Pearson correlation. A Pearson correlation coefficient of 0.7 or lower was considered to confer a weak correlation. Results Ninety-three ImpellaTM-patient runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support duration was 6 days (IQR 4-12). In total, 2447 parallel anti-Xa/APTT samples were analyzed, showing an overall Pearson correlation coefficient of 0.50 (p<0.001) (Fig. 1A). For samples with in-range anti-Xa (N=1914), matching APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples (Fig. 1B). Conclusions We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided heparin anticoagulated CS population during left-sided ImpellaTM support. Heparin titration based on APTT alone would result in over- (24%) or undertitration (24%) in 48% of our cases, due to confounding factors influencing the APTT-assay in critically ill, exposing these patients to coagulopathy associated problems. Therefore, we strongly advocate a combined (anti-Xa/APTT) testing anticoagulation monitoring strategy to adequately manage the coagulation state of this critically ill population. Future trials will investigate whether this approach will effectively reduce the high coagulopathy associated morbidity and mortality on pMCS.

Markers of hemophagocytic lymphohistiocytosis are associated with survival in critically ill patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) and the Ludwig Boltzmann Cluster for Cardiovascular Research Background/Introduction Patients admitted to the intensive care unit (ICU) often show systemic immune dysregulation paired with significantly increased inflammatory activity. Haemophagocytic lymphohistiocytosis (HLH) represents a rare syndrome characterized by fever, inflammation, cytopenia, and organ dysfunction. Inappropriate survival of cytotoxic T cells as well as histiocytes triggers cytokine storm, accompanied by the occurrence of hemophagocytosis and multi-organ failure. prevalence of HLH in critical illness continues to be a topic of discussion but most certainly remains underreported. This circumstance often leads to delays in the necessary immunosuppressive therapy due to difficulty in early diagnosis. Purpose In the present study, we aimed to illuminate the prospective value of the individual HLH criteria in a cohort of critically ill patients. Although the prevalence of this syndrome might be low, isolated markers of HLH could help to assess the extent of inflammatory activation and further be of use in predicting the outcome of patients admitted to the ICU. Methods This was a prospective, observational cohort study. 176 consecutive patients admitted to a cardiac ICU were included over the course of one year. Available HLH criteria were recorded except for biopsy samples of bone marrow and measurements of low or absent natural killer cell activity. For soluble CD25 (sCD25) a specific ELISA kit was used according to the manufacturer's instructions. Results The median age was 67.51 years (IQR: 57.50-77.41) and 38.64% of the included patients were female. The total 30-day mortality was calculated to be 25.57% and positivity for two or more criteria of HLH was found to be associated with depicted mortality (p = 0.033). Analyzing the individual parameters, only sCD25 was found to be a predictor of death within the first 30 days (p < 0.001). The combination of triglycerides and fibrinogen did not predict outcomes. However, low fibrinogen values were found to possess prognostic merit in regard to mortality (p= 0.019). In multivariate analysis, both sCD25 and fibrinogen remained a significant predictor of 30-day survival after adjustment for age, sex, and BMI (sCD25 p < 0.001, fibrinogen p = 0.042). Finally, the addition of fibrinogen was able to improve the prognostic value of the SAPS II score significantly (ROC curve, SAPS II – AUC: 0.790, SAPS II & fibrinogen – AUC: 0.827, p = 0.045). Conclusion We provided evidence for the prognostic value of certain markers of HLH in critically ill patients. Positivity for two or more criteria was found to be associated with an increased 30-day mortality. Moreover, sCD25 and fibrinogen independently predicted outcomes in multivariate analysis after adjustment for age, sex, and BMI. The addition of fibrinogen was able to improve the prognostic properties of the SAPS II score.Figure 1Figure 2

Impella vs Veno-arterial extracorporeal membrane oxygenation in cardiogenic shock: a systematic review and meta-analysis of propensity score matched studies

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Abiomed Singapore PTE. Ltd. Background/Introduction Cardiogenic shock is a life-threatening condition associated with multi-organ failure and death. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is well-established in the management of cardiogenic shock; however, mortality rates have remained relatively consistent over the past two decades. Impella is a transluminal microaxial ventricular assist device that improves haemodynamics by unloading the left ventricle and represents an alternative to VA-ECMO. No randomised controlled trials exist to date comparing Impella versus VA-ECMO given difficulties in recruiting patients due to the acute nature of the condition. Whilst a plethora of non-randomised, comparative studies have been published, many are confounded by underlying differences in baseline disease characteristics. Propensity score matched / adjusted studies may mitigate confounding by accounting for differences in important covariates that impact outcomes. Purpose The objective of this study was to conduct a systematic review and meta-analysis of propensity score matched / adjusted studies to assess the clinical outcomes of Impella versus VA-ECMO in cardiogenic shock patients. Methods A systematic review was undertaken to identify all comparative studies of Impella and VA-ECMO in cardiogenic shock which performed propensity score matching / adjustment of outcomes to account for important covariates. The study limitations were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. In-hospital/30-day survival and bleedings requiring transfusion were meta-analysed using the random effects method. Results Six propensity score matched / adjusted studies comparing Impella versus VA-ECMO in cardiogenic shock were included in the meta-analysis. A statistically significant difference in in-hospital/30-day mortality was detected between patients treated with Impella (39.6%) versus VA-ECMO (53.8%) (odds ratio [OR] 95% confidence interval [95% CI]: 0.57 [0.44, 0.74]; p<0.0001). Similarly, Impella (19.9%) was associated with statistically significantly fewer bleeding events requiring transfusion compared with VA-ECMO (28.8%) (OR=0.61 [0.46, 0.80]; p=0.0004). Conclusion(s) This systematic review identified no randomised controlled trials of Impella versus VA-ECMO. The meta-analysis of propensity matched observational trials, represents the highest level of evidence available to date, and suggests that Impella may be associated with increased survival rates and decreased bleeding. Randomised controlled trials are urgently needed to assess cardiac support modalities in cardiogenic shock.

Oxygen targets following immediate percutaneous coronary intervention in comatose survivors of out-of-hospital cardiac arrest - a BOX sub-study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Novo Nordisk Foundation The Lundbeck Foundation. Background Treatment with supplemental oxygen in patients with acute myocardial infarction (AMI) has previously been associated with poorer outcomes. However, in patients with AMI resuscitated from out-of-hospital cardiac arrest (OHCA) and undergoing immediate revascularization, evidence regarding specific oxygen targets is sparse. Purpose To assess the impact of a restrictive versus a liberal oxygen target on infarct size in OHCA patients undergoing immediate percutaneous coronary intervention (PCI). Methods The current study is a sub-study of the BOX trial, a randomized trial with a 2-by-2 factorial design, in which comatose OHCA patients with a presumed cardiac cause of arrest were randomly assigned to either a restrictive oxygen target (partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa) or a liberal oxygen target (Pao2 of 13 to 14 kPa). In this sub-study we included patients who underwent immediate revascularization with PCI. The primary outcome was myocardial infarct size as assessed by the cardiac enzyme troponin-T (TnT). TnT was measured repeatedly during the first 72 hours and analyzed with a repeated measures variance component model with baseline adjustment. Secondary outcome was one-year all-cause mortality assessed by Kaplan-Meier and Cox proportional hazards analyses. Results A total of 329 patients underwent immediate PCI, whereof 172 patients were randomized to the restrictive oxygen target and 157 to the liberal oxygen target. The oxygen intervention was successful with a significantly higher PaO2 in the liberal oxygen target group during the first 72 hours (p<0.0001). Baseline characteristics and findings on coronary angiography (CAG) were similar in the two oxygen target groups. Thus, median age was 63 (interquartile range (IQR) 55–71), 81% were male, and estimated left ventricular ejection fraction on arrival to hospital was 35% (IQR 25–45%). Further, 74% of the patients had an initial postresuscitation electrocardiogram with ST-segment elevations, and the left anterior descending artery was deemed as culprit lesion in 49% of the patients. There was no difference in peak TnT between the restrictive and liberal oxygen target group (median 2540 (IQR 925–6420) versus 3410 (792–8630), ng/l, p=0.23), nor did TnT differ between the groups during the first 72 hours after admission (Figure 1, p=1.00). Within one year from admission, 120 patients (36.5%) had died. There was no difference in mortality between the restrictive (34%) and liberal (39%) oxygen target group (hazard ratio, 0.80; 95% CI, 0.56-1.14; p=0.21) (Figure 2). Conclusion Targeting a restrictive versus a liberal oxygen level in comatose survivors of OHCA who underwent immediate revascularization did not affect infarct size nor did it result in a significant difference in one-year mortality rate.Figure 1:Troponin-T levelsFigure 2:Kaplan-Meier curves

Anti-Xa/APTT discrepancy in heparinized ImpellaTM-supported cardiogenic shock patients can predict mortality

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Meticulous management of unfractionated heparin (UFH) is important to avoid complications in patients receiving percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). Whereas the anti-Xa assay directly measures UFH activity, the activated partial thromboplastin time (APTT) remains the most frequently used test. The APTT covers the intrinsic and common coagulation pathway and can be influenced by various confounding (laboratory) factors during critical illness, unrelated to the patient’s (anti)coagulation state. Purpose We investigated a CS population supported with isolated left-sided Impella™ and UFH-anticoagulation. UFH-levels were guided by anti-Xa with APTT in parallel. Here, we focus on those samples with anti-Xa in-range and discrepantly prolonged parallel APTT-measurements. We differentiated the APTT-prolongation according to reduced fibrinogen levels and/or prolonged INR (factor XI/XII consumption vs. concomitant conditions) and correlated this with mortality during Impella™-support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (>24h) and UFH anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. In-range anti-Xa samples (between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile) were selected. In-range APTT values were considered between 40-55s and 55-80s respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were allocated in 4 groups based on fibrinogen (<1.5g/dL or ≥ 1.5g/dL) and INR (<1.5 or ≥1.5) on the same day as the sample with prolonged APTT. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). Among the 1914 in-range anti-Xa samples, parallel APTT was prolonged in 468 samples (24%) across 59 patients. 80 Samples from 2 patients were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (10% vs. 32%; p=0.043). Conclusions Fibrinogen-levels and INR uncover the underlying etiology in discrepant APTT-prolongation as compared to an in-range anti-Xa value in a CS population during left-sided ImpellaTM support. In patients with prolonged APTT and reduced fibrinogen (<1.5 g/dL) and/or prolonged INR (≥1.5), the risk of mortality is significantly elevated. This is due to concomitant conditions with high mortality (liver failure, sepsis, DIC,…). We advocate to monitor such patients carefully and treat them in a patient/disease tailored approach.