Baseline characteristics associated with developing a clinical event or a markedly abnormal risk stratifying test were similar: rest anginal episode accompanied by ST-segment depression and occurring despite treatment with aspirin and heparin, a history of angina, older age, and family history of coronary disease. Patients with these characteristics are appropriate candidates for expeditious cardiac catheterization and consideration for revascularization, while patients without them may be suitable for medical management alone.
Introduction
Tranexamic acid (TXA) is widely used as an antifibrinolytic agent in hemorrhagic trauma patients. The beneficial effects of TXA exceed the suppression of blood loss and include the ability to decrease inflammation and edema. We found that TXA suppresses the release of mitochondrial DNA and enhances mitochondrial respiration. These results allude that TXA could operate through plasmin‐independent mechanisms. To address this hypothesis, we compared the effects of TXA on lipopolysaccharide (LPS)‐induced expression of proinflammatory cytokines in plasminogen (Plg) null and Plg heterozygous mice.
Methods
Plg null and Plg heterozygous mice were injected with LPS and TXA or LPS only. Four hours later, mice were sacrificed and total RNA was prepared from livers and hearts. Real time quantitative polymerase chain reaction with specific primers was used to assess the effects of LPS and TXA on the expression of pro‐inflammatory cytokines.
Results
LPS enhanced the expression of Tnfα in the livers and hearts of recipient mice. The co‐injection of TXA significantly decreased the effect of LPS both in Plg null and heterozygous mice. A similar trend was observed with LPS‐induced Il1α expression in hearts and livers.
Conclusions
The effects of TXA on the endotoxin‐stimulated expression of Tnfα and Il1α in mice do not depend on the inhibition of plasmin generation. These results indicate that TXA has other biologically important target(s) besides plasminogen/plasmin. Fully understanding the molecular mechanisms behind the extensive beneficial effects of TXA and future identification of its targets may lead to improvement in the use of TXA in trauma, cardiac, and orthopedic surgical patients.
BACKGROUND: Decreased hydraulic forces during diastole contribute to reduced left ventricular (LV) filling and heart failure with preserved ejection fraction.
OBJECTIVES: To determine the association between diastolic hydraulic forces, estimated by atrioventricular area difference (AVAD), and both diastolic function and survival. We hypothesized that decreased diastolic hydraulic forces, estimated as AVAD, would associate with survival independent of conventional diastolic dysfunction measures.
METHODS: Patients (n=11,734, median [interquartile range] 3.9 [2.4-5.0] years follow-up, 1,213 events) were selected from the National Echo Database Australia based on the presence of relevant transthoracic echocardiographic measures, LV ejection fraction (LVEF) ≥ 50%, heart rate 50-100 beats/minute, the absence of moderate or severe valvular disease, and no prior cardiac surgery. AVAD was calculated as the cross-sectional area difference between the LV and left atrium. LV diastolic dysfunction was graded according to 2016 guidelines.
RESULTS: AVAD was weakly associated with E/e prime, left atrial volume index, and LVEF (multivariable global R2=0.15, p<0.001), and not associated with e prime and peak tricuspid regurgitation velocity. Decreased AVAD was independently associated with poorer survival, and demonstrated improved model discrimination after adjustment for diastolic function grading (C-statistic 0.645 vs 0.607) and E/e prime (C-statistic 0.639 vs 0.621), respectively.
CONCLUSIONS: Decreased hydraulic forces, estimated by AVAD, are weakly associated with diastolic dysfunction and provide an incremental prognostic association with survival beyond conventional measures used to grade diastolic dysfunction.
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