Longitudinally Measured Fibrinolysis Factors are Strong Predictors of Clinical Outcome in Patients with Chronic Heart Failure: The Bio-SHiFT Study

2019 ◽  
Vol 119 (12) ◽  
pp. 1947-1955
Author(s):  
Victor J. van den Berg ◽  
Elke Bouwens ◽  
Victor A. W. M. Umans ◽  
Moniek de Maat ◽  
Olivier C. Manintveld ◽  
...  

Abstract Objective This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). Methods A median of 9 (interquartile range [IQR] 5–10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4–2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. Results Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28–3.45) for PAI-1, 1.91 (1.18–3.24) for uPA, and 3.96 (2.48–6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. Conclusion Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.

Author(s):  
Hanaa Shafiek ◽  
Andres Grau ◽  
Jaume Pons ◽  
Pere Pericas ◽  
Xavier Rossello ◽  
...  

Background: Cardiopulmonary exercise test (CPET) is a crucial tool for the functional evaluation of cardiac patients. We hypothesized that VO2 max and VE/VCO2 slope are not the only parameters of CPET able to predict major cardiac events (mortality or cardiac transplantation urgently or elective). Objectives: We aimed to identify the best CPET predictors of major cardiac events in patients with severe chronic heart failure and to propose an integrated score that could be applied for their prognostic evaluation. Methods: We evaluated 140 patients with chronic heart failure who underwent CPET between 2011 and 2019. Major cardiac events were evaluated during follow-up. Univariate and multivariate logistic regression analysis were applied to study the predictive value of different clinical, echocardiographic and CPET parameters in relation to the major cardiac events. A score was generated and c-statistic was used for the comparisons. Results: Thirty-nine patients (27.9%) died or underwent cardiac transplantation over a median follow-up of 48 months. Five parameters (maximal workload, breathing reserve, left ventricular ejection fraction, diastolic dysfunction and non-idiopathic cardiomyopathy) were used to generate a risk score that had better risk discrimination than NYHA dyspnea scale, VO2 max, VE/VCO2 slope > 35 alone, and combined VO2 max and VE/VCO2 slope (p= 0.009, 0.004, < 0.001 and 0.005 respectively) in predicting major cardiac events. Conclusions: A composite score of CPET and clinical/echocardiographic data is more reliable than the single use of VO2max or combined with VE/VCO2 slope to predict major cardiac events.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xiling Shou ◽  
Jing Lin ◽  
Cui Xie ◽  
Yi Wang ◽  
Chaofeng Sun

A great number of basic and clinical studies have demonstrated that inflammatory cytokines play an important role in the development and progression of chronic heart failure (CHF). However, there is limited information about the role of novel cytokine interleukin-37 (IL-37) in heart failure. We measured plasma IL-37 levels by enzyme-linked immunosorbent assay (ELISA) in 158 patients with chronic heart failure and 30 control subjects. Our results showed that plasma IL-37 levels were significantly elevated in patients with CHF compared with healthy controls (143.73 ± 26.83 pg/ml versus 45.2 ± 11.56 pg/ml,P<0.001). Furthermore, plasma IL-37 levels were positively correlated with hs-CRP, hs-TnT, and NT-proBNP and negatively correlated with left ventricular ejection function (LVEF). 11 patients died of cardiovascular cause, and 27 HF patients were rehospitalized for worsening HF within 12 months. Multivariate Cox regression analysis showed that plasma IL-37 is an independent predictor of major adverse cardiac events (MACE). Furthermore, CHF patients with >99 pg/ml plasma IL-37 had significantly higher incidences of MACE within 12 months. Our data suggest that plasma IL-37 may play a role in the pathogenesis of CHF and may be a novel predictor of poor prognosis in HF patients.


Kardiologiia ◽  
2020 ◽  
Vol 60 (4) ◽  
pp. 48-53
Author(s):  
A. D. Gasanova ◽  
D. O. Dragunov ◽  
A. V. Sokolova ◽  
G. P. Arutyunov

Aim To evaluate the risk of major cardiovascular complications (CVC) in patients with chronic heart failure (CHF) with intermediate and preserved ejection fraction (EF) depending on the presence of bendopnea symptom.Material and methods The study included 104 patients with stage II CHF and left ventricular EF ≥40 %. Mean age of the patients was 72.8±10.6 years. A test for detection of bendopnea symptom was performed for all patients. Two groups were formed: group 1, 69 patients with the bendopnea symptom and group 2, 35 patients with a negative test. Follow-up duration was 24 months. The composite endpoint (CEP) was death and hospitalization for any CVC.Results Mean time to the bendopnea symptom was 17.3±6.61 s. At two years of follow-up, the CEP was observed in 36 (34.6 %) patients, including 30 (43.5 %) patients in group 1 and 6 (17.1 %) patients in group 2. 12 patients died, and 9 of them had the bendopnea symptom. 21 patients of group 1 were hospitalized for CVC. Risk of CEP was significantly 1.7 times higher for men (relative risk, RR 1.7 [1.1; 2.6]) than for women. The presence of bendopnea symptom increased the risk of CEP 1.4 times (ОР 1.4 [1.1;1.9]) for women and 2.3 times (RR 2.3 [1.4; 3.6]) for men.Conclusion Results of the study demonstrated an unfavorable effect of bendopnea symptom on risk of CEP during the two-year follow-up of CHF patients with preserved and intermediate EF.


1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.


1992 ◽  
Vol 68 (05) ◽  
pp. 486-494 ◽  
Author(s):  
Malou Philips ◽  
Anne-Grethe Juul ◽  
Johan Selmer ◽  
Bent Lind ◽  
Sixtus Thorsen

SummaryA new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-l complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.


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