Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Many studies have shown enhanced plasma levels of proinflammatory cytokines [i.e. tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6] in patients with CHF. However, there are only few reports on the regulation of anti-inflammatory cytokines such as IL-10. IL-10 has potent deactivating properties in macrophages and T-cells and thus acts as a down-regulator of cell-mediated immune responses. The aim of the present study was to assess whether serum concentrations of IL-10 significantly differ between patients with CHF and healthy control subjects. Patients with CHF [ n =50; 66.9+/-12.6 years; mean ejection fraction, 22.1+/-9.2%; New York Heart Association (NYHA) class II-IV] and 25 healthy controls (63.6+/-10.2 years) were examined. Of the 50 patients with CHF, 32 patients were taking aspirin (100 mg/day) and 33 patients had lipid-lowering therapy with a statin. Serum IL-10 as well as TNF-alpha concentrations were measured using commercially available immunoassays. Patients with CHF showed significantly lower IL-10 concentrations (2.3+/-1.9 compared with 5.2+/-2.3 pg/ml; P <0.001). Patients with advanced CHF (NYHA class III and IV) had the lowest IL-10 plasma levels. Aspirin and statin therapy did not significantly influence serum levels of IL-10. The ratio of TNF-alpha to IL-10 was significantly higher in patients with advanced CHF (NYHA class III and IV, ratio 3.2+/-1.2 and 3.1+/-1.1 respectively, compared with control 0.4+/-0.2; P <0.01). Our present study demonstrates significantly decreased serum levels of IL-10 in patients with advanced CHF. Since IL-10 is known as a potent anti-inflammatory cytokine, its decrease in advanced CHF may favour the inflammatory milieu in CHF.

Background: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-a and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 intitiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. Methods: Fifty patients with CHF (aged 66.9"12.6 years, mean ejection fraction 22.1"9.2%, NYHA II-IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5"9.8 years) were examined. Thirty-two patients were taking aspirin (100 mgyday). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry. Results: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity wMFIx, P-0.001; P-selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P-0.001). CD154 expression on platelets positively correlated with increasing NYHA-class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet-therapy with aspirin did not influence CD154 or P-selectin expression on platelets. Conclusion: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40-CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.

Background Stillbirth rates have shown little improvement for two decades in Australia. Perinatal mortality audit is key to prevention, but the literature suggests that implementation is suboptimal. Aim To determine the proportion of perinatal deaths which are associated with contributing factors relating to care in Queensland, Australia. Materials and Methods Retrospective audit of perinatal deaths ≥ 34 weeks gestation by the Health Department in Queensland was undertaken. Cases and demographic information were obtained from the Queensland Perinatal Data Collection. A multidisciplinary panel used the Perinatal Society of Australia and New Zealand (PSANZ) perinatal mortality audit guidelines to classify the cause of death and to identify contributing factors. Contributing factors were classified as ‘insignificant’, ‘possible’, or ‘significant’. Results From 1 January to 31 December 2018, 65 deaths (56 stillbirths and nine neonatal deaths) were eligible and audited. Most deaths were classified as unexplained (51.8% of stillbirths). Contributing factors were identified in 46 (71%) deaths: six insignificant (all stillbirths), 20 possibly related to outcome (17 stillbirths), and 20 significantly (16 stillbirths). Areas for practice improvements mainly related to the care for women with risk factors for stillbirth, especially antenatal care. The PSANZ guidelines were applied and enabled a systematic approach. Conclusions A high proportion of late gestation perinatal deaths are associated with contributing factors relating to care. Improving antenatal care for women with risk factors for stillbirth is a priority. Perinatal mortality audit is a valuable step in stillbirth prevention and the PSANZ guidelines allow a systematic approach to aid implementation and reporting.

Platelets can contribute to enhanced MCP-1 levels in CHF. MCP-1 is markedly elevated in serum of CHF patients showing a direct correlation with the severity of symptoms and the degree of left ventricular dysfunction. Further studies are required to test whether MCP-1 blocking or sophisticated anti-platelet strategies may represent new therapeutic options in CHF.

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