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Published on: July 10, 2019
Heparanase inhibitor improves clinical study in patients with septic cardiomyopathy
Di Chen1, Honglei Li1, Shitao Huang1
1The First Clinical College of Lanzhou University, Lanzhou, Gansu, China.
Insights
Low molecular weight heparin (LMWH) treatment significantly reduced Heparanase (HPA) levels and improved cardiac function in septic cardiomyopathy (SCM) patients. This intervention also lowered inflammation and mortality, suggesting LMWH as a valuable therapeutic option for SCM.
Area of Science:
- Critical Care Medicine
- Cardiology
- Pharmacology
Background:
- Septic cardiomyopathy (SCM) is a serious complication of sepsis with high mortality.
- The pathogenesis of SCM is not fully understood, and diagnostic markers are lacking.
- Current treatments focus on the underlying sepsis and symptom management.
Purpose of the Study:
- To investigate the effect of low molecular weight heparin (LMWH) on Heparanase (HPA) levels in SCM patients.
- To evaluate the clinical significance of HPA as a diagnostic marker for SCM.
- To assess LMWH's impact on cardiac function, inflammation, and mortality in SCM.
Main Methods:
- A prospective randomized controlled trial involving 105 SCM patients.
- Patients were assigned to a control group (standard therapy) or an intervention group (standard therapy + LMWH).
- Key parameters including HPA, syndecan-1, inflammatory markers, cardiac function indices, and clinical outcomes were measured.
Main Results:
- LMWH treatment significantly reduced HPA and syndecan-1 levels compared to the control group (p<0.05).
- The LMWH group showed improved cardiac function (LVEF, FS, SV, CPI) and reduced inflammatory markers (IL-6, TNF-α).
- ROC analysis suggested HPA combined with NT-proBNP, CTnI, and H-FABP improves SCM diagnostic efficiency.
Conclusions:
- LMWH integration in SCM management effectively reduces HPA levels and improves cardiac function.
- LMWH treatment attenuates inflammation, enhances immune function, and improves microcirculation in SCM patients.
- These improvements correlate with reduced clinical severity, shorter ICU stays, and lower 28-day mortality rates.
Objective:
Septic cardiomyopathy (SCM), a prevalent and critical condition in individuals suffering from sepsis and septic shock, remains elusive in terms of its intricate pathogenesis, thereby lacking definitive diagnostic standards. Current clinical management predominantly revolves around addressing the underlying disease and alleviating symptoms, yet mortality rates persist at elevated levels. This research endeavors to delve into the effects of low molecular weight heparin on Heparanase (HPA) levels in SCM patients, while assessing the clinical significance of HPA as a diagnostic marker in this patient population.
Method:
A comprehensive cohort of 105 patients diagnosed with SCM was recruited from the Department of Critical Care Medicine at the First Hospital of Lanzhou University, spanning the period from September 2022 to October 2023, serving as the primary research subjects for this investigation. A prospective, randomized controlled trial was undertaken, wherein 53 SCM patients were randomly allocated to a control group receiving standard therapy, while 52 patients were randomly assigned to an intervention group receiving conventional treatment augmented with low molecular weight heparin (LMWH). On the 1st, 3rd, and 7th days post-treatment, the following parameters were measured and documented: HPA levels, syndecan-1 levels, IL-6, TNF-α, CD4+/CD8+ cell ratio, anti-Xa factor, antithrombin III (AT-III) levels, left ventricular ejection fraction (LVEF), fractional shortening (FS), E/e' ratio, stroke volume (SV), cardiac performance index (CPI), global end-diastolic volume index (GEDVI), N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (CTnI), heart-type fatty acid-binding protein (H-FABP), lactate (Lac) levels, central venous oxygen saturation (ScvO2), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ICU length of stay, and 28-day mortality rate.
Results:
In comparison to the control group, the LMWH group demonstrated significantly lower levels of HPA and syndecan-1 (p < 0.05), along with reduced levels of IL-6, TNF-α, E/e', NT-proBNP, CTnI, H-FABP, GEDVI, SOFA score, APACHE II score, ICU length of stay, and 28-day mortality (p < 0.05). Additionally, the LMWH group exhibited increased levels of anti-Xa factor, AT-III, CD4+/CD8+ cell, LVEF, FS, SV, and CPI (p < 0.05). ROC curve analysis indicated that HPA can be combined with NT-proBNP, CTnI and H-FABP to improve the diagnostic efficiency of SCM.
Conclusion:
In SCM patient management, the integration of LMWH into conventional treatment significantly reduced HPA levels, mitigated syndecan-1 loss, attenuated inflammatory responses, enhanced immune function, improved microcirculation, cardiac systolic and diastolic functions, myocardial contractility, heart index, and end-diastolic volume. These interventions correlated with decreased clinical severity, ICU stays, and 28-day mortality rates in SCM patients.
Clinical Trial Registration:
https://www.chictr.org.cn.
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