Simona Littnerová

Bacteriocin-encoding genes and ExPEC virulence determinants are associated in human fecal Escherichia coli strains

BackgroundA set of 1181 E. coli strains of human fecal origin isolated in the South Moravia region of the Czech Republic was collected during the years 2007–2010. Altogether, 17 virulence determinants and 31 bacteriocin-encoding genes were tested in each of them.ResultsThe occurrence of bacteriocin-encoding genes was found to be positively correlated with the occurrence of E. coli virulence factors. Based on the presence of virulence factors and their combinations, E. coli strains were classified as non-pathogenic E. coli (n = 399), diarrhea-associated E. coli (n = 179) and ExPEC strains (n = 603). Non-pathogenic and diarrhea-associated E. coli strains had a low frequency of bacteriocinogeny (32.6% and 36.9%, respectively). ExPEC strains encoding S-fimbriae (sfa), P-fimbriae (pap) and having genes for aerobactin biosynthesis (aer, iucC), α-hemolysis (α-hly) and cytotoxic necrosis factor (cnf1) were often bacteriocinogenic (73.8%), had a high prevalence of bacteriocin multi-producers and showed a higher frequency of genes encoding microcins H47, M, V, B17 and colicins E1, Ia and S4.ConclusionsThe occurrence of bacteriocin-encoding genes and ExPEC virulence determinants correlate positively in E. coli strains of human fecal origin. Bacteriocin synthesis appears to modulate the ability of E. coli strains to reside in the human intestine and/or the virulence of the corresponding strains.

GRACE Score among Six Risk Scoring Systems (CADILLAC, PAMI, TIMI, Dynamic TIMI, Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction.

Aim To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients. Methods and Results A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores—the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE—showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73–0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80–0.83). Conclusions All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.

AHEAD score--Long-term risk classification in acute heart failure.

BACKGROUND The role of co-morbidities in the prognosis of patients hospitalized for AHF was examined using the AHEAD (A--atrial fibrillation, H--haemoglobin<130 g/l for men and 120 g/l for women (anaemia), E--elderly (age>70years), A--abnormal renal parameters (creatinine>130 μmol/l), D--diabetes mellitus) scoring system. METHODS AHEAD--multicentre prospective Czech registry of AHF patients; GREAT registry--international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). RESULTS Main outcome was one year all-cause mortality. The mean age of patients was 72±12 years, with 61.6% of patients aged >70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine>130 mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0-5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p<0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p<0.001). CONCLUSION The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

Prognostic utility of biomarkers in predicting of one-year outcomes in patients with aortic stenosis treated with transcatheter or surgical aortic valve implantation.

Objectives The aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE). Background There is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available. Methods The multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0%) allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29), or SAVR with the Edwards Perimount bioprosthesis (n = 13). Standardized endpoints were prospectively followed during the 12-month follow-up. Results The clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis) = 0.872 for TAVI group, resp. 0.765 (p<0.05) for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1), ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750–0.948; p<0.05 for all). The addition of MDA to a currently used clinical model (EuroSCORE) significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0–365 days) by the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) (p<0.05). Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up. Conclusion We identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical “TAVIscore” would be highly appreciated. Such dedicated scoring system would enable further testing of adjunctive value of various biomarkers.

Prevalence and clinical significance of liver function abnormalities in patients with acute heart failure

AIMS Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). METHODS The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. RESULTS In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. CONCLUSIONS Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

Positive Influence of Being Overweight/Obese on Long Term Survival in Patients Hospitalised Due to Acute Heart Failure

Background Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the “obesity paradox” on a large cohort with long-term follow-up are lacking. Methods Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5–25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. Results In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26–1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09–1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11–1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. Conclusion These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study

Objectives Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). Design Prospective observational cohort study. Setting One university/tertiary centre. Participants A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. Outcomes Primary outcome: 1-year mortality. Secondary outcomes: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. Statistical methods Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). Results The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%. Conclusions The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

Heart failure oral therapies at discharge are associated with better outcome in acute heart failure: a propensity-score matched study

Heart failure oral therapies (HFOTs), including beta‐blockers (BB), renin–angiotensin system inhibitors (RASi) and mineralocorticoid receptor antagonists, administered before hospital discharge after acute heart failure (AHF) might improve outcome. However, concerns have been raised because early administration of HFOTs may worsen patients condition. We hypothesized that HFOTs at hospital discharge might be associated with better post‐discharge survival.

The Association Between Levels of Tissue Inhibitor of Metalloproteinase-1 with Acute Heart Failure and Left Ventricular Dysfunction in Patients with ST Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

AIMS Tissue inhibitors of metalloproteinase (TIMPs) bind to active matrix metalloproteinase (MMPs), and thereby inhibit their proteolytic activity. We investigated the role of polymorphisms in the gene for TIMP-1 and serum levels of TIMP-1 in association with postmyocardial infarction (MI), left ventricular (LV) dysfunction, and symptoms of acute heart failure (AHF) in patients treated with primary percutaneous coronary intervention. METHODS In total, 556 patients with STEMI were evaluated. Levels of TIMP-1 were measured at admission and 24 h after MI onset. The TIMP-1 exon 5 SNP rs4898 (F124F with T>C) located at X chromosome was assayed. RESULTS TIMP-1 levels were higher for men with AHF as well as for men with LV dysfunction (ejection fraction [EF]<40%). According to multivariate analysis, the TIMP-1 level was a factor with an independent negative relationship to EF and AHF in men. An independent relationship between exon 5 TIMP-1 gene polymorphism and EF, AHF or TIMP-1 level was not documented. CONCLUSION These results provide evidence that a higher level of circulating TIMP-1 is independently associated with worse EF and AHF.

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.