ACE gene insertion/deletion polymorphism has a mild influence on the acute development of left ventricular dysfunction in patients with ST elevation myocardial infarction treated with primary PCI

<p>Abstract</p> <p>Background</p> <p>We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI).</p> <p>Methods</p> <p>A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI.</p> <p>Results</p> <p>In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]).</p> <p>Conclusions</p> <p>These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.</p

Cytocompatibility and Bioactive Ion Release Profiles of Phosphoserine Bone Adhesive : Bridge from In Vitro to In Vivo

One major challenge when developing new biomaterials is translating in vitro testing to in vivo models. We have recently shown that a single formulation of a bone tissue adhesive, phosphoserine modified cement (PMC), is safe and resorbable in vivo. Herein, we screened many new adhesive formulations, for cytocompatibility and bioactive ion release, with three cell lines: MDPC23 odontoblasts, MC3T3 preosteoblasts, and L929 fibroblasts. Most formulations were cytocompatible by indirect contact testing (ISO 10993-12). Formulations with larger amounts of phosphoserine (&gt;50%) had delayed setting times, greater ion release, and cytotoxicity in vitro. The trends in ion release from the adhesive that were cured for 24 h (standard for in vitro) were similar to release from the adhesives cured only for 5-10 min (standard for in vivo), suggesting that we may be able to predict the material behavior in vivo, using in vitro methods. Adhesives containing calcium phosphate and silicate were both cytocompatible for seven days in direct contact with cell monolayers, and ion release increased the alkaline phosphatase (ALP) activity in odontoblasts, but not pre-osteoblasts. This is the first study evaluating how PMC formulation affects osteogenic cell differentiation (ALP), cytocompatibility, and ion release, using in situ curing conditions similar to conditions in vivo

Prognostic value of NT-proBNP added to clinical parameters to predict two-year prognosis of chronic heart failure patients with mid-range and reduced ejection fraction - A report from FAR NHL prospective registry.

BACKGROUND:According to guidelines, the prognosis of patients with chronic heart failure can be predicted by determining the levels of natriuretic peptides, the NYHA classification and comorbidities. The aim our work was to develop a prognostic score in chronic heart failure patients that would take account of patients' comorbidities, NYHA and NT-proBNP levels. METHODS AND RESULTS:A total of 1,088 patients with chronic heart failure with reduced ejection fraction (HFrEF) (LVEF1000 ng/L respectively. Discrimination abilities of NYHA and NT-proBNP were AUC 0.670 (p40 mg daily) (AUC 0.773; p<0.001) was increased by adding the NT-proBNP level (AUC 0.790). CONCLUSION:The use of prediction models in patients with chronic heart failure, namely those taking account of natriuretic peptides, should become a standard in routine clinical practice. It might contribute to a better identification of a high-risk group of patients in which more intense treatment needs to be considered, such as heart transplantation or LVAD implantation

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2&prime;-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker&rsquo;s ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2′-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker’s ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin

Prognostic Value of Pentraxin-3 Level in Patients with STEMI and Its Relationship with Heart Failure and Markers of Oxidative Stress

Objective. Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). Methods. Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. Results. ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2′-deoxyguanosine, and nitrite/nitrate. Conclusions. Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year

Evaluation of additional benefit of biomarkers to clinical model (EuroSCORE) by net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for prediction of combined safety endpoint at 30 days and combined endpoint (0–365 days) in groups of patients treated by TAVI and by SAVR and TAVI.

<p>Evaluation of additional benefit of biomarkers to clinical model (EuroSCORE) by net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) for prediction of combined safety endpoint at 30 days and combined endpoint (0–365 days) in groups of patients treated by TAVI and by SAVR and TAVI.</p

ROC analysis for prediction of endpoints in patients treated with TAVI.

<p>ROC analysis for prediction of endpoints in patients treated with TAVI.</p