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Introduction:Heart failure (HF) is a key contributor to high mortality and economic burden associated with cardiovascular diseases. Understanding the factors responsible for accelerated HF progression due to comorbid conditions is important in HF management.Hypothesis:The hypothesis of this study was that specific biomarkers related to thrombosis, inflammation, cardiac injury, and remodeling in patients with reduced ejection fraction (HFrEF) and coronary artery disease (CAD) may inform disease progression and aid in evaluating therapeutic efficacy.Methods:This study was a cross-sectional, exploratory assessment of biomarkers related to thrombosis, inflammation, and cardiac injury/remodeling in decompensated heart failure patients with reduced ejection fraction and underlying CAD. Symptomatic HF patients (n=74) with reduced left ventricular ejection fraction (LVEF ≤40%, HF ≥3 months) and significant underlying CAD as evidenced by previous myocardial infarction, prior coronary artery bypass graft, 50% coronary stenosis of one or more arteries, and history of percutaneous coronary intervention with or without stenting were enrolled in the study, and age-matched healthy subjects (n=20) were enrolled for comparative analysis of biomarkers.Results:Significant differences between HF+CAD and Controls were observed for thrombosis biomarkers (TM, p=0.0002, TGA [lag time, p=0.003; endogenous thrombin potential p=0.048], inflammatory biomarkers (CD62P, p=0.006; hsCRP, p=0.0064; S100β, p=0.0004), and cardiac injury/remodeling (GDF-15, p=0.0002; NTproBNP, p<0.0001).Conclusions:Elevated levels of hsCRP and GDF-15 demonstrate heightened systemic inflammation in HF and CAD, and support the hypothesis that targeting inflammation may provide additional treatment options for this patient population. A novel finding of this study was that S100β, previously identified to play a role in maladaptive compensatory mechanisms, was higher in HF+CAD patients and correlated with multiple biomarkers including, CD62P, NTproBNP, and TM. (ClinicalTrials.gov Identifier: NCT03551756).

Cardenas: CirQuest Labs/MLM Medical Labs: Current Employment. Kotha:CirQuest Labs/MLM Medical Labs: Current Employment. Lu:Portola Pharmaceuticals, Inc.: Current Employment. Conley:Portola Pharmaceuticals, Inc.: Current Employment. Bourdin:Diagnostica Stago: Current Employment. Herve:Diagnostica Stago: Current Employment. Jennings:CirQuest Labs/MLM Medical Labs: Current Employment, Current equity holder in private company.

Introduction:The anticoagulants rivaroxaban and apixaban inhibit Factor Xa (FXa) activity and are effective therapeutic agents for the prevention and treatment of thromboembolism. Andexanet alfa (andexanet) is the only specific reversal agent approved for anticoagulation reversal in patients presenting with life-threatening bleeding treated with rivaroxaban or apixaban.

Introduction:Elevated D-dimer levels are expected to represent both patients at high risk for venous thromboembolism (VTE), and those benefiting from extended-duration antithrombotic therapy. Using D-dimer testing as a method for enrichment strategy, the APEX trial compared the clinical benefit of extended-duration betrixaban therapy with enoxaparin standard of care (NEJM 375:534, 2016). D-dimer test results from the local laboratories at the enrollment sites were used for study outcome analyses based on a ≥ 2xULN value to identify subjects with elevated D-dimer (Cohort 1).

No relevant conflicts of interest to declare.

Thrombin cleaves PAR-1 at amino acids arg41-ser42to yield the canonical tethered ligand as well as a soluble peptide, parstatin, which has been reported to have divergent physiological functions. In animal models, this peptide demonstrates anti-angiogenic, anti-inflammatory, and cardioprotective properties. In ex vivostudies, parstatin was also demonstrated to affect platelet aggregation and enhance GPIIb/IIIa-mediated adhesion, suggesting this cleaved peptide may participate in pathological thrombosis. With recent approval of a first-in-class PAR-1 antagonist as an antiplatelet agent, it is clinically imperative to fully appreciate the physiologic mechanisms through which thrombin-activation of PAR-1 contributes to platelet aggregation and thrombosis. As such, the effects of PAR antagonism in modulating parstatin-mediated platelet activation requires evaluation.