Relationship between plasma Neuregulin-1 and cardiac function in patients with ST-elevation myocardial infarction.

BACKGROUND: Neuregulin-1 (NRG-1) is a stress-mediated transmembrane growth factor. Reduced myocardial damage and higher NRG-1 levels upon treatment with remote ischemic conditioning (RIC) has been described in rats. However, the role of NRG-1 in patients with acute myocardial infarction (MI) is unknown. Thus, we conducted a post hoc analysis of a randomized controlled trial that tested RIC in patients with MI scheduled for primary percutaneous coronary intervention (PCI). METHODS: Blood was drawn from 30 patients before RIC/PCI, within 1 hour, 4 days and 1 month later. Median left ventricular ejection fraction (LVEF) in the overall study population following MI was 48.5%. RESULTS: NRG-1 plasma levels decreased significantly following PCI/RIC and remained decreased up to 1 month following MI (p < 0.0001). We observed no association of NRG-1 with other variables, including total ischemic time, LVEF or RIC. CONCLUSIONS: Thus, we identified NRG-1 may be independently affected by MI. However, further large clinical trials are warranted to clarify this hypothesis.

Mid-regional pro-atrial natriuretic peptide independently predicts short-term mortality in COVID-19.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet. METHODS: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP. CONCLUSION: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality.

Immature cell fractions after cessation of chronic P2Y12-inhibition in patients with coronary artery diseases.

Changes in circulating cell populations may promote ischemic events that occur soon after discontinuation of P2Y12-inhibition. The aim of the study was to track the course of thrombopoietic and erythropoietic cells in patients with coronary artery diseases (CAD) after planned and physician-driven cessation of chronic P2Y12-inhibition (clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID). Cell fractions were determined in 62 patients at baseline (the last day of P2Y12-inhibitor intake), on day-10, day-30, and day-180 thereafter. Immature platelet fraction (IPF), immature reticulocyte fraction (IRF), reticulocyte hemoglobin content (Ret-Hb) and red blood cell count (RBC) significantly increased from baseline to day-180 (IPF: p = .003; IRF: p = .013; Ret-Hb: p < .001; RBC: p = .044). Platelet count, leucocyte count and immature granulocyte fraction did not change over time (p = .561, p = .869, and p = .161, respectively). Fibrinogen levels significantly declined over time (p = .011), thrombopoietin levels increased in a non-significant manner (p = .379). We did not observe any significant interaction with choice of P2Y12-inhibitor, therefore suggesting a drug class-effect. Our data shows, that discontinuation of dual antiplatelet therapy is associated with raised thrombopoietic and erythropoietic activity in the bone marrow, without significant upregulation of thrombopoietin. This provides further evidence for a direct stimulation of precursor cells by P2Y12-inhibitors.

Effect of marathon and ultra-marathon on inflammation and iron homeostasis.

The physiological response to high-level endurance exercise, such as running a marathon, poses several beneficial but also potentially harmful metabolic changes. The objective of this study was to determine the impact of marathon (M) and ultra-marathon (UM) on inflammation and iron homeostasis in paired samples. Fifteen well-trained, non-professional endurance athletes (14 males, 1 female) performed both a 130 km ultra-marathon and a traditional 42.195 km marathon. We determined markers of inflammation and iron homeostasis before, immediately after, and within 5 days after finishing each run, respectively. Biomarkers of inflammation (leucocytes, neutrophil granulocytes, monocytes, and c-reactive protein [CRP]) increased significantly after both marathon and ultra-marathon with higher levels of CRP after ultra-marathon compared with marathon both immediately after the race (18.15 ± 12.41 vs 5.58 ± 9.65 mg/L, P < .001) and at follow-up (15.67 ± 16.97 vs 7.19 ± 7.75 mg/L, P = .045) Concentrations of ferritin also increased significantly after both races and remained high at follow-up. Higher levels of ferritin immediately after the race (111.5 ± 103.2 vs 84.8 ± 86.3, P = .001) and at follow-up (102.7 ± 79.5 vs 74.6 ± 65.6, P = .001) were found in ultra-marathon finishers. The observed increase of serum iron and transferrin saturation (TSAT) after marathon and the decrease of serum iron and TSAT after ultra-marathon resulted in a significant absolute difference between the two races. The present data suggest a higher degree of inflammation after ultra-marathon compared with marathon. Markers of iron homeostasis also showed different response patterns with regard to running distance.

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction.

BACKGROUND: Little is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission. METHODS: Biomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender. RESULTS: Overall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8-100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5-99.8; and women, NPV = 98.7%, CI: 97.5-100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61-3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96-0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19-3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33-9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23-5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23-7.24), atrial fibrillation (OR = 2.90, CI: 1.26-6.70) and syncope-like events (OR = 7.56, CI: 2.26-25.30) were significant predictors of copeptin elevation. CONCLUSIONS: Men with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.

The association of P2Y12 inhibitors with pro-coagulatory extracellular vesicles and microRNAs in stable coronary artery disease.

Extracellular vesicles (EV) act as a cellular communication tool by carrying lipids, proteins and micro RNA (miR) between cells, thereby playing a pivotal role in thromboembolic processes. The effect of P2Y12 inhibitors on pro-coagulatory, phosphatidylserine (PS)-expressing EV has been investigated previously, but only in vitro or during confounding clinical conditions, such as acute coronary syndrome. Hence, we enrolled 62 consecutive patients 12 month after percutaneous coronary intervention and stent implantation and consequent treatment with dual-antiplatelet therapy consisting of low-dose aspirin and P2Y12 inhibitors. Blood for platelet function testing and EV and miR measurements was taken on the last day of P2Y12 inhibitor intake (baseline, on-treatment) and 10, 30 and 180 days thereafter (off-treatment). We did not observe any influence of P2Y12 inhibitors on the levels of PS-EV or EV sub-population from platelets, erythrocytes, monocytes or endothelial cells, respectively. There was no relationship between platelet function and EV levels in plasma. However, the association of miR-21 and miR-150 with platelet EVs was significantly different between on- and off-treatment measurements. Hence, our study suggests no influence of P2Y12 inhibition on the count of EVs in plasma, but on the potential cargo of platelet-derived EV.

Course of platelet miRNAs after cessation of P2Y12 antagonists.

BACKGROUND: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. DESIGN: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12-inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. RESULTS: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. CONCLUSION: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors.

Impact of an Ultra-Endurance Marathon on Cardiac Function in Association with Cardiovascular Biomarkers.

BACKGROUND: Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP). METHODS AND RESULTS: Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median. CONCLUSION: A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.

Jaundice increases the rate of complications and one-year mortality in patients with hypoxic hepatitis.

UNLABELLED: Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n = 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One-year-survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3-8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One-year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow-up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow-up. CONCLUSION: Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH.

Nebivolol treatment increases splanchnic blood flow and portal pressure in cirrhotic rats via modulation of nitric oxide signalling.

BACKGROUND: We evaluated the effects of nebivolol, a third generation beta-blocker capable of increasing NO-bioavailability on portal pressure, and on splachnic and systemic haemodynamics in a cirrhotic portal hypertensive rat model. METHODS: Male Sprague-Dawley rats underwent sham operation (SO) or bile duct ligation (BDL). When cirrhosis was fully developed, the animals were orally treated with low-dose (5 mg/kg) or high-dose (10 mg/kg) nebivolol (NEBI) or vehicle (VEH) for 7 days. Heart rate (HR), mean arterial pressure (MAP), portal pressure (PP) and superior mesenteric artery blood flow (SMABF) were measured. Portosystemic collateral blood flow (PSCBF) was quantified using radioactive microspheres. Hepatic and splanchnic NOx levels and GSH/GSSG ratios (RedOx state) were determined using commercially available kits. RESULTS: BDL-VEH rats showed increased HR, PP and PSCBF, whereas MAP was decreased compared to SO-VEH rats. Nebivolol significantly reduced HR both in SO (P < 0.001) and BDL (P < 0.001) rats. BDL-NEBI animals had significantly higher PP (15.5 vs. 12.6 mmHg; P = 0.006) and SMABF (5.3 vs. 3.7 ml/min/100g; P = 0.016) than BDL-VEH animals. The increase in PP and SMABF was noted both in low-dose and high-dose BDL-NEBI rats. While no beneficial effects on hepatic RedOx state were observed, splanchnic NOx levels were significantly increased by NEBI treatment in a dose-dependent manner. Nebivolol treatment did not affect PSCBF in SO and BDL animals. CONCLUSION: Nebivolol increases portal pressure in cirrhotic animals by increasing splanchnic blood flow via modulation of NO signalling. Portosystemic collateral blood flow remained unchanged. These data do not support the use of nebivolol for treatment of cirrhotic patients with portal hypertension.

Low-density lipoprotein cholesterol reduction with immediate combination therapy of statin and ezetimibe compared to statin monotherapy after percutaneous coronary intervention.

BACKGROUND: Current guidelines recommend a stepwise initiation of lipid-lowering therapy after percutaneous coronary interventions (PCI) in treatment-naïve individuals. Patients might benefit from an earlier and stronger low-density lipoprotein-cholesterol (LDL-C) reduction through upfront combination therapies. METHODS: This retrospective study included patients without previous lipid-lowering therapy undergoing acute or elective PCI with stent implantation between January 2016 and December 2019. Patients initiated on statin monotherapy vs. a combination of statin and ezetimibe were compared. The primary endpoint was an LDL­C reduction into the target range of < 55 mg/dL at 3 months. The secondary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: A total of 204 lipid-lowering therapy naive patients were included, of whom 157 (77.0%) received statin monotherapy and 47 (23.0%) combination therapy. Median LDL­C levels were higher in patients initiated on combination therapy vs. monotherapy (140 mg/dL, interquartile range, IQR, 123-167 mg/dL vs. 102 mg/dL, IQR 80-136 mg/dL, p < 0.001). The LDL­C reduction was greater in patients treated with combination therapy vs. statin monotherapy (-73 mg/dL, -52.1% vs. -43 mg/dL, -42.2%, p < 0.001). While the primary endpoint was similar between groups (44.7% vs. 36.1%, p = 0.275), combination therapy significantly increased the proportion of patients achieving the treatment target in the presence of an admission LDL-C > 120 mg/dL (46.2% vs. 26.2%, p = 0.031). The rates of MACE were similar between the two groups (10.6% vs. 17.8%, p = 0.237) at a median follow-up of 2.2 years, IQR 1.46-3.10 years. CONCLUSION: Immediate initiation of high-intensity statin and ezetimibe treatment might be considered as the default strategy in treatment-naïve patients with high admission LDL­C undergoing PCI.

The LIPL study: Postprandial lipid profile, inflammation, and platelet activity in patients with chronic coronary syndrome.

Background and aims: It is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state. Methods: The studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat. Results: Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups. Conclusion: This study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity.

Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19.

BACKGROUND: Excess cardiovascular (CV) morbidity and mortality has been observed in patients with COVID-19. Both interleukin-32 (IL-32) and interleukin-34 (IL-34) have been hypothesized to contribute to CV involvement in COVID-19. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from 6 June to 22 December 2020 in a tertiary care hospital in Vienna, Austria. IL-32 and IL-34 levels on admission were collected and tested for their association with CV disease and short-term mortality in patients with COVID-19. CV disease was defined by the presence of coronary artery disease, heart failure, stroke or atrial fibrillation and patients were stratified by CV disease burden. RESULTS: A total of 245 eligible patients with COVID-19 were included, of whom 37 (15.1%) reached the primary endpoint of 28-day mortality. Of the total sample, 161 had no CV disease (65.7%), 69 had one or two CV diseases (28.2%) and 15 patients had ≥three CV diseases (6.1%). Median levels of IL-32 and IL-34 at admission were comparable across the three groups of CV disease burden. IL-32 and IL-34 failed to predict mortality upon both univariable and multivariable Cox regression analysis. The two CV disease groups, however, had a significantly higher risk of mortality within 28 days (one or two CV diseases: crude HR 4.085 (95% CI, 1.913-8.725), p < 0.001 and ≥three CV diseases: crude HR 13.173 (95% CI, 5.425-31.985), p < 0.001). This association persisted for those with ≥three CV diseases after adjustment for age, gender and CV risk factors (adjusted HR 3.942 (95% CI, 1.288-12.068), p = 0.016). CONCLUSION: In our study population of hospitalized patients with COVID-19, IL-32 and IL-34 did not show any associations with CV disease or 28-day mortality in the context of COVID-19. Patients with multiple CV diseases, however, had a significantly increased risk of short-term mortality.

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease.

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of "the lower, the better", we also discuss the concept of "the earlier, the better", which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

Similarities and Differences between EU Platforms in the AHA and AAL Domains from a Software Viewpoint.

The EU PlatformUptake project's main goal is to investigate the usage of EU open and partly-open platforms in active and healthy aging (AHA) and ambient-assisted living (AAL) domains, from a software viewpoint. The aim of the project was to provide tools for a deeper interpretation and examination of the platforms, gather user feedback, and use it to improve the state-of-the-art approach in the AHA and AAL domains, and define instructions to enhance the platforms within the recommended order. The emphasis is on the software viewpoint for decision makers. In this paper, we present (i) the PlatformUptake methodology for AHA open platform assessments and its main objectives; (ii) clustering of the analyzed platforms; and (iii) the taxonomies generated from the text descriptions of the chosen platforms. With the use of the clustering tools, we present which platforms could be grouped together due to their similarities. Different numbers of clusters were obtained with two clustering approaches, resulting in the most informative two and four cluster groups. The platforms could be rather neatly presented in this way and, thus, potentially guide future platform structuring. Moreover, taxonomies, i.e., decision trees of platforms, were generated to easily determine each specific platform or to find platforms with the desired properties. Altogether, the computer comprehension of the platforms may be important additions to the human way of dealing with the AHA platforms, influencing future design, publications, related work, and research.

Biomarkers Associated with Cardiovascular Disease in COVID-19.

Coronavirus disease-19 (COVID-19) emerged late December 2019 in the city of Wuhan, China and has since spread rapidly all over the world causing a global pandemic. While the respiratory system is the primary target of disease manifestation, COVID-19 has been shown to also affect several other organs, making it a rather complex, multi-system disease. As such, cardiovascular involvement has been a topic of discussion since the beginning of the COVID-19 pandemic, primarily due to early reports of excessive myocardial injury in these patients. Treating physicians are faced with multiple challenges in the management and early triage of patients with COVID-19, as disease severity is highly variable ranging from an asymptomatic infection to critical cases rapidly deteriorating to intensive care treatment or even fatality. Laboratory biomarkers provide important prognostic information which can guide decision making in the emergency department, especially in patients with atypical presentations. Several cardiac biomarkers, most notably high-sensitive cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have emerged as valuable predictors of prognosis in patients with COVID-19. The purpose of this review was to offer a concise summary on prognostic cardiac biomarkers in COVID-19 and discuss whether routine measurements of these biomarkers are warranted upon hospital admission.

Association of Plasma Methylglyoxal Increase after Myocardial Infarction and the Left Ventricular Ejection Fraction.

Background: Preclinical studies suggest that methylglyoxal (MG) increases within the myocardium upon acute myocardial infarction (AMI) and thereafter contributes to adverse postinfarct remodeling. The aims of this study were to test whether MG increases in plasma of humans after AMI and whether this increase is related to the left ventricular ejection fraction (LVEF). Methods: The plasma samples of 37 patients with ST elevation AMI undergoing primary percutaneous coronary intervention (pPCI) acquired in a previously conducted randomized controlled trial testing remote ischemic conditioning (RIC) were analyzed by means of high-performance liquid chromatography. Time courses of the variables were analyzed by means of mixed linear models. Multiple regression analyses served to explore the relationship between MG levels and the LVEF. Results: Compared to the MG levels upon admission due to AMI, the levels were increased 2.4-fold (95% CI, 1.6−3.6) 0.5 h after reperfusion facilitated by pPCI, 2.6-fold (1.7−4.0) after 24 h and largely returned to the baseline after 30 d (1.1-fold, 0.8−1.5). The magnitude of the MG increase was largely independent of that of cardiac necrosis markers. Overall, the highest MG values within 24 h after AMI were associated with the lowest LVEF after 4 d. While markers of myocardial necrosis and stretch quantified within the first 24 h explained 52% of the variance of the LVEF, MG explained additional 23% of the variance (p < 0.001). Conclusions: Considering these observational data, it is plausible that the preclinical finding of MG generation after AMI negatively affecting the LVEF also applies to humans. Inhibition of MG generation or MG scavenging might provide a novel therapeutic strategy to target post-AMI myocardial remodeling and dysfunction.

Prothrombotic Milieu, Thrombotic Events and Prophylactic Anticoagulation in Hospitalized COVID-19 Positive Patients: A Review.

The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Although initial reports concentrated on severe respiratory illness, emerging literature has indicated a substantially elevated risk of thromboembolic events in patients with COVID-19 disease. Pro-inflammatory cytokine release has been linked to endothelial dysfunction and activation of coagulation pathways, as evident by elevated D-dimer levels and deranged coagulation parameters. Both macrovascular and microvascular thromboses have been described in observational cohort and post-mortem studies. Concurrently, preliminary data have suggested the role of therapeutic anticoagulation in preventing major thromboembolic complications in moderately but not critically ill patients. However, pending results from randomized controlled trials, clear guidance is lacking regarding the intensity and duration of anticoagulation in such patients. Herein, we review the existing evidence on incidence and pathophysiology of COVID-19 related thromboembolic complications and guide anticoagulation therapy based on current literature and societal consensus statements.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin.

BACKGROUND: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and high-sensitive cardiac troponin I (hs-cTnI) levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P < 0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.3 pmol/L for copeptin and 16.8 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P < 0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. CONCLUSION: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of ICU admission or 28-day mortality in hospitalized patients with COVID-19.

Direct cardiovascular complications and indirect collateral damage during the COVID-19 pandemic : A review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), puts a heavy strain on healthcare systems around the globe with high numbers of infected patients. Pre-existing cardiovascular disease is a major risk factor for a severe clinical course of COVID-19 and is associated with adverse outcome. COVID-19 may directly exacerbate underlying heart disease and is frequently aggravated by cardiovascular complications, including arterial and venous thromboembolic events, malignant arrhythmia and myocardial injury. In addition to these direct cardiac manifestations of COVID-19, patients with cardiovascular disease face further indirect consequences of the pandemic, as the respective resources in the healthcare systems need to be redirected to cope with the high numbers of infected patients. Consecutively, a substantial decrease in cardiac procedures was reported during the pandemic with lower numbers of coronary angiographies and device implantations worldwide. As a consequence an increased number of out-of-hospital cardiac arrests, late-comers with subacute myocardial infarction and of patients presenting in cardiogenic shock or preshock were observed. Maintenance of high-quality cardiac care by avoiding a reduction of cardiac services is of utmost importance, especially in times of a pandemic.