Abstract Background GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. Increased concentrations of circulating GDF-15 are associated with increased mortality in patients with acute coronary syndromes or heart failure. Purpose We aimed to describe relation between GDF-15 elevation with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke (AIS). Methods Patients after AIS were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 and 48 hours later to determine the plasma levels of GDF-15 and high-sensitive troponin I (hs-cTnI). Receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy and optimal elevation cut-off values of GDF-15 on day 1 for the severity of acute stroke defined by NIHSS score. The optimal cut off in our group was 1776 pg/ml (Sensitivity 0,8, Specificity 0,52). Myocardial injury was defined by fourth universal definition of myocardial infarction using hs-cTnI. Demographic characteristics, clinical data, functional outcome, and all-cause mortality at 1 year were compared between groups according to GDF-15 levels. National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results Between August 2020 and August 2022, 177 patients after AIS were enrolled. Elevated GDF-15 was observed in 71 patients (40,1%). Most common comorbidities included arterial hypertension, dyslipidemia, type 2 DM and atrial fibrillation. In analysis, we observed a connection between elevated GDF-15 with unfavourable outcome evaluated by mRS at 90 days (HR 2.57, 95% CI 1,44 to 4,57, p=0.001) and with all-cause death at 1 year (HR 4.479, 95% CI 1,81 to 11,09, p=0.001). GDF-15 elevation was associated with myocardial injury (Figure 1C). Moreover, individuals with moderate to severe and severe strokes (NIHSS 16-42) displayed higher GDF-15 levels compared to those with minor to moderate stroke (Figure 1D). The Kaplan-Meier survival curve accentuated a significantly elevated all-cause mortality among patients with increased GDF-15 (p < 0.001) (Figure 2). In multivariate regression analysis elevated GDF-15 was associated with atrial fibrillation and high-sensitive troponin I elevation. Conclusion The conclusions drawn suggest that heightened GDF-15 is associated with increased stroke severity, myocardial injury and unfavourable outcome.
Abstract Background Patients after acute stroke frequently show signs of myocardial injury. The pathophysiology and impact on patient's outcome are not fully understood. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is cytokine known to be associated with cardiovascular events. Purpose We aimed to assess TRAIL level dynamic changes in patients after acute ischemic stroke and its relations to cardiac injury, stroke severity and impact on short-term outcome. Methods Between August 2020 and August 2021, 104 consecutive patients after acute ischemic stroke (AIS) were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24- and 48-hours later to determine levels of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitive Troponin I (hs-cTnI). Twelve lead ECG at admission, 24-, 48-hours later and at the release of the patients were obtained. Patients underwent echocardiographic examination within first 5 days of hospitalization, if eligible. National Institutes of Health Stroke Scale (NIHSS) at admission and modified Rankin Scale (mRS) at 90 days following the patient's discharge from the hospital were performed. Chi-square, Fishers exact test and regression analysis were performed to detect differences between variables using SPSS statistics. Results were considered statistically significant at a significance level of p<0.05. Results We found significant negative association between TRAIL and NT-proBNP at admission (p=0.039), after 24 (p=0.043) and 48 hours (p=0.023) of hospitalization. There was significant negative association between TRAIL and hs-cTnI at admission (p=0.04). Moreover, we found significant negative association between TRAIL and stroke severity evaluated by NIHSS at admission (p=0.044) and negative association with severe disability or death evaluated by mRS at 90 days both after 24 (p=0.0022) and 48 hours (p=0.044) of hospitalization. In ECG analysis, lower TRAIL levels were associated with the occurrence of premature ventricular extrasystoles (p=0.043), and there was a near statistically significant association with prolonged QTc interval (p=0.07). Two patients presented with new left ventricular regional wall motion abnormality. Conclusions Lower TRAIL levels are associated with laboratory markers of cardiac injury, stroke severity and unfavorable functional outcome in patients after acute ischemic stroke. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Charles University Research Program Cooperatio – Cardiovascular sciences
The cardiovascular system is markedly affected by stress after stroke. There is a complex interaction between the brain and heart, and the understanding of the mutual effects has increased in recent decades. Stroke is accompanied by pathological disturbances leading to autonomic dysfunction and systemic inflammation, which leads to changes in cardiomyocyte metabolism. Cardiac injury after stroke may lead to serious complications and long-term cardiac problems. Evidence suggests that blood biomarkers and electrocardiogram analyses can be valuable for estimating the severity, prognosis, and therapy strategy in patients after stroke. It is necessary to distinguish whether these abnormalities presenting in stroke patients are caused by coexisting ischemic heart disease or are caused by brain injury directly. Distinguishing the origin can have a great impact on the treatment of patients after acute stroke. In this article, we focus on epidemiology, pathophysiological mechanisms, and the presentation of cardiac changes in patients after stroke.
Abstract Background/introduction Elevated levels of NT-proBNP in ischemic stroke patients may indicate increased cardiac stress, which can be associated with poor outcome. However, clinical utility and cut offs are not completely known. Purpose We aimed to describe relation between NT-proBNP elevation with stroke severity and poor clinical outcome in patients after acute ischemic stroke (AIS). Methods Patients after AIS were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 and 48 hours later to determine the plasma levels of NT-proBNP. Twelve-lead ECGs were obtained at the time of admission, 24 and 48 h later. Standard echocardiographic examination was performed within the first 7 days of hospitalization if patients were eligible. Demographic characteristics, clinical data, functional outcome, and all-cause mortality were compared between groups according to NT-proBNP levels (NT-proBNP ≤ 125 pg/ml; >125 and ≤450 pg/ml; >450 pg/ml). National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results Between August 2020 and August 2022, 177 patients after AIS were enrolled. Elevated NT-proBNP >125pg/ml was observed in 82 patients (46,3%), 34 patients (19,2%) presented with NT-proBNP >450pg/ml. Most common comorbidities included arterial hypertension, dyslipidemia, type 2 DM and atrial fibrillation. In analysis, we observed a connection between elevated NT-proBNP with unfavorable outcome evaluated by mRS at 90 days (p<0.001) and with all-cause death at 30 days (P=0.001) and 90 days (P<0.001). Kaplan-Meier survival curve showed that all-cause mortality was significantly higher in patients with elevated NT-proBNP (P<0.001), however with no difference between elevation >125pg/ml and >450pg/ml (p=0.14). In survival analysis, there was close to significant association between patients who presented with elevated NT-proBNP>125pg/ml and >20% change in value comparing to those with elevated NT-proBNP without subsequent change >20%. Moreover, we observed a connection with stroke severity evaluated by NIHSS (p=0.005). In ECG analysis, we showed higher occurrence of T wave inversion (P<0.001), ST segment depression (P< 0.001) and QTc prolongation (P=0.003) in patients with elevated NT-proBNP. In multivariate regression analysis elevated NT-proBNP was associated with atrial fibrillation, high-sensitive troponin I elevation and age≥75 years. Conclusion The results show that elevated NT-proBNP is associated with stroke severity, unfavorable functional outcome, and short-term mortality in patients after acute ischemic stroke. Moreover, we described connection between NT-proBNP elevation and ECG changes.Kaplan Meier survival analysisAssociation worse outcome and severity
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to be associated with poor prognosis after cardiovascular events. We aimed to assess the dynamic changes in TRAIL levels and the relation of TRAIL level to stroke severity, its impact on the short-term outcomes, and its association with markers of cardiac injury in patients after acute stroke.Between August 2020 and August 2021, 120 consecutive patients, 104 after acute ischemic stroke (AIS), 76 receiving reperfusion therapy, and 16 patients after intracerebral hemorrhage (ICH) were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 h later, and 48 h later to determine the plasma level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitive Troponin I (hs-TnI). Twelve-lead ECGs were obtained at the time of admission, 24 h later, 48 h later, and at the release of the patients. Evaluations were performed using the National Institutes of Health Stroke Scale (NIHSS) at the time of admission and using the modified Rankin Scale (mRS) 90 days following the patient's discharge from the hospital.We observed a connection between lower TRAIL levels and stroke severity evaluated using the NIHSS (p = 0.044) on the first day. Lower TRAIL showed an association with severe disability and death as evaluated using the mRS at 90 days, both after 24 (p = 0.0022) and 48 h (p = 0.044) of hospitalization. Moreover, we observed an association between lower TRAIL and NT-proBNP elevation at the time of admission (p = 0.039), after 24 (p = 0.043), and after 48 h (p = 0.023) of hospitalization. In the ECG analysis, lower TRAIL levels were associated with the occurrence of premature ventricular extrasystoles (p = 0.043), and there was an association with prolonged QTc interval (p = 0.052).The results show that lower TRAIL is associated with stroke severity, unfavorable functional outcome, and short-term mortality in patients after acute ischemic stroke. Moreover, we described the association with markers of cardiac injury and ECG changes.
Abstract This study examined the prevalence of acute and chronic myocardial injury according to standard criteria in patients after acute ischaemic stroke (AIS) and its relation to stroke severity and short-term prognosis. Between August 2020 and August 2022, 217 consecutive patients with AIS were enrolled. Plasma levels of high-sensitive cardiac troponin I (hs-cTnI) were measured in blood samples obtained at the time of admission and 24 and 48 h later. The patients were divided into three groups according to the Fourth Universal Definition of Myocardial Infarction: no injury, chronic injury, and acute injury. Twelve-lead ECGs were obtained at the time of admission, 24 and 48 h later, and on the day of hospital discharge. A standard echocardiographic examination was performed within the first 7 days of hospitalization in patients with suspected abnormalities of left ventricular function and regional wall motion. Demographic characteristics, clinical data, functional outcomes, and all-cause mortality were compared between the three groups. The National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following hospital discharge were used to assess stroke severity and outcome. Elevated hs-cTnI levels were measured in 59 patients (27.2%): 34 patients (15.7%) had acute myocardial injury and 25 patients (11.5%) had chronic myocardial injury within the acute phase after ischaemic stroke. An unfavourable outcome, evaluated based on the mRS at 90 days, was associated with both acute and chronic myocardial injury. Myocardial injury was also strongly associated with all-cause death, with the strongest association in patients with acute myocardial injury, at 30 days and at 90 days. Kaplan–Meier survival curves showed that all-cause mortality was significantly higher in patients with acute and chronic myocardial injury than in patients without myocardial injury (P < 0.001). Stroke severity, evaluated with the NIHSS, was also associated with acute and chronic myocardial injury. A comparison of the ECG findings between patients with and without myocardial injury showed a higher occurrence in the former of T-wave inversion, ST segment depression, and QTc prolongation. In echocardiographic analysis, a new abnormality in regional wall motion of the left ventricle was identified in six patients. Chronic and acute myocardial injury with hs-cTnI elevation after AIS are associated with stroke severity, unfavourable functional outcome, and short-term mortality.
Abstract Background Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction that could help predict adverse outcomes. Purpose We assessed whether GLS can help predict adverse clinical outcomes in patients after acute ischemic stroke (AIS). Methods Patients without LV dysfunction after AIS were divided into groups according to abnormal GLS (≤15.9%) or normal GLS (≥16%). Blood samples were obtained to determine levels of high-sensitive troponin I (hs-cTnI). Clinical data, functional outcome, and all-cause mortality at 1 year were compared between groups. National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results In our study, between 8/2020-8/2022 155 enrolled patients after AIS had echocardiographic examination, due to image quality or LV dysfunction, GLS was assessed in 110 patients with normal LV function, 28 patients (25.6%) had abnormal GLS. After a year follow-up, the overall mortality was more common in patients with abnormal GLS compared to patients with normal GLS (hazard ratio [HR] 2.9610, 95% confidence interval [CI] 0.9015 to 9.7255, p =0.074) and was significant when comparing mean values (p<0.001) (Fig. 1A). The Kaplan-Meier survival curve accentuated a significantly elevated all-cause mortality among patients with abnormal GLS (Fig 2). Moreover, abnormal GLS was associated with positive hs-cTnI (Fig. 1B), and was connected with unfavorable functional outcome evaluated by mRS at 90 days (Fig. 1C). At last, severe stroke (NIHSS >15) was not significantly associated with abnormal GLS (HR 2.2121, 95% CI 0.7091 to 6.9009, p = 0.1714) Conclusion In patients after AIS, abnormal GLS could be helpful predictor for clinical events and subclinical myocardial injury.
Introduction: Unselected therapy with fibrinolysis in intermediate risk-pulmonary embolism (iPE) is associated with an unacceptable risk of bleeding. Early identification of iPE patients on anticoagulant therapy with ineffective endogenous fibrinolysis (eFL) could optimize treatment-strategy. Aims: The study aims to determine markers of (in)effective eFL in intermediate-risk PE initially on anticoagulant therapy with UFH. Methods: In course of 24 months, iPE patients were enrolled in the prospective study. At admission, and every 24 hours until day 5, levels of 6 selected markers of eFL (i.e., PAI-1 and tPA active assay and total antigen, TAFI, and PAP) were determined. Upon arrival and following a span of 36 hours,defined i) Clinical (heart rate >100 bpm and spontaneous oxygen saturation <90%), ii) Echo (D-shape, RVd/LVd from PLAX>0.7, RV/RA >30mmHg), and iii) CT (RV/LV>0.9) variables were obtained. An (un)successful therapy was assessed by one point for each clinical, Echo and CT criteria, as at least one parameter from initially altered has adjusted at 36 hours. We performed correlation of laboratory markers with the dynamics of clinical and imaging characteristics. Results: Study population consists of 44 patients, 22 men, mean (SD) age 60 (18.3) yr., first (38), repeat (6) PE. Plasminogen activator inhibitor-1 (PAI-1) active assay showed the most promising results. The cut-off for unsuccessful therapy from AUC for PAI-1 was ≥65 U/ml. Mean (IQR) levels of PAI-1 on day 1 were 119 U/ml (27.1 - 155.8) and were significantly higher on day 1 (p=0.019) and day 2 (p=0.055) in those with/without adjustment of initial pathological findings. PAI-1 elevation was associated with unsuccessful restoration of clinical, Echo and CT parameters at 36 hours (Table1). Overall Tx failure was associated with elevated PAI-1 (p=0.011). Conclusions: PAI-1 active assay could help us in identifying patients who would benefit from early indicated therapeutic fibrinolysis.
Abstract Aims As the antithrombotic regimen that may best prevent ischaemic complications along with the lowest bleeding risk offset following transcatheter aortic valve implantation (TAVI) remains unclear, we aimed to compare the safety and efficacy of antithrombotic regimens in patients without having an indication for chronic oral anticoagulation. Methods and results We conducted a PROSPERO-registered (CRD42021247924) systematic review and network meta-analysis of randomized controlled trials evaluating post-TAVI antithrombotic regimens up to April 2022. We estimated the relative risk (RR) and 95% confidence intervals (95% CIs) using a random-effects model in a frequentist pairwise and network metanalytic approach. We included seven studies comprising 4006 patients with a mean weighted follow-up of 12.9 months. Risk of all-cause death was significantly reduced with dual antiplatelet therapy (DAPT) compared with low-dose rivaroxaban + 3-month single antiplatelet therapy (SAPT) (RR 0.60, 95% CI 0.41–0.88), while no significant reduction was observed with SAPT vs. DAPT (RR 1.02, 95% CI 0.67–1.58) and SAPT and DAPT compared with apixaban or edoxaban (RR 0.60, 95% CI 0.32–1.14 and RR 0.59, 95% CI 0.34–1.02, respectively). SAPT was associated with a significant reduction of life-threatening, disabling, or major bleeding compared with DAPT (RR 0.45, 95% CI 0.29–0.70), apixaban or edoxaban alone (RR 0.45, 95% CI 0.25–0.79), and low-dose rivaroxaban + 3-month SAPT (RR 0.30, 95% CI 0.16–0.57). There were no differences between the various regimens with respect to myocardial infarction, stroke, or systemic embolism. Conclusion Following TAVI in patients without an indication for chronic oral anticoagulant, SAPT more than halved the risk of bleeding compared with DAPT and direct oral anticoagulant-based regimens without significant ischaemic offset.
