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Parenica J.,University Hospital Brno | Parenica J.,Masaryk University | Parenica J.,University Hospital St Annes | Nemec P.,University Hospital St Annes | And 17 more authors.
PLoS ONE | Year: 2012

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. © 2012 Parenica et al.


Vaclavik J.,Palacky University | Spinar J.,University Hospital Brno | Vindis D.,Palacky University | Vitovec J.,University Hospital St Annes | And 12 more authors.
Internal and Emergency Medicine | Year: 2014

Initial risk stratification in patients with acute heart failure (AHF) is poorly validated. Previous studies tended to evaluate the prognostic significance of only one or two selected ECG parameters. The aim of this study was to evaluate the impact of multiple ECG parameters on mortality in AHF. The Acute Heart Failure Database (AHEAD) registry collected data from 4,153 patients admitted for AHF to seven hospitals with Catheter Laboratory facilities. Clinical variables, heart rate, duration of QRS, QT and QTC intervals, type of rhythm and ST-T segment changes on admission were collected in a web-based database. 12.7 % patients died during hospitalisation, the remainder were discharged and followed for a median of 16.2 months. The most important parameters were a prolonged QRS and a junctional rhythm, which independently predict both in-hospital mortality [QRS > 100 ms, odds ratio (OR) 1.329, 95 % CI 1.052-1.680; junctional rhythm, OR 3.715, 95 % CI 1.748-7.896] and long-term mortality (QRS > 120 ms, OR 1.428, 95 % CI 1.160-1.757; junctional rhythm, OR 2.629, 95 % CI 1.538-4.496). Increased hospitalisation mortality is predicted by ST segment elevation (OR 1.771, 95 % CI 1.383-2.269) and prolonged QTC interval >475 ms (OR 1.483, 95 % CI 1.016-2.164). Presence of atrial fibrillation and bundle branch block is associated with increased unadjusted long-term mortality, but mostly reflects more advanced heart disease, and their predictive significance is attenuated in the multivariate analysis. ECG in patients admitted for acute heart failure carries significant short- and long-term prognostic information, and should be carefully evaluated. © 2012 SIMI.


Krupicka J.,Charles University | Andruskova A.,Hospital Znojmo | Hegarova M.,Institute for Clinical and Experimental Medicine | Lazarova M.,University Hospital Olomouc | And 5 more authors.
Cor et Vasa | Year: 2015

Introduction The ESC Heart Failure Long-Term Registry (ESC-HFLTR) is a prospective observational study which takes place in 211 cardiology centres of 21 European and Mediterranean countries, members of the European Society of Cardiology. Aim To compare basic demographic and clinical characteristics of both, the patients hospitalized for acute heart failure and the patients observed in outpatient clinics for chronic heart failure in the Czech Republic with published European-wide data. Methods Altogether 692 consecutive patients were included in the Czech part of ESC-HFLTR (5.6% of the whole registry) from May 2011 to April 2013. These patients were either admitted to hospital or examined in the outpatient clinic for HF during one predefined day of the week. The basic characteristics of 160 hospitalized (25.3%) and 532 ambulatory (74.7%) patients were analysed statistically, compared with each other and finally contrasted with available data from the whole ESC-HFLTR. Results Czech in-hospital patients were generally older than the ambulatory patients with HF (73 vs. 66 years; p < 0.001) and were less frequently men (62.5 vs. 75.7%). They had also significantly higher incidence of comorbidities. On the contrary, the outpatients underwent more often pacemaker implantation and coronary revascularization than hospitalized patients. The dominant HF aetiology was ischaemic in both groups. The HF with preserved ejection fraction was more frequently represented among the hospitalized HF patients. On the other hand, more ambulatory patients had dilated cardiomyopathy as the primary cause of HF. In comparison with the data from the whole ESC-HFLTR Czech HF patients in both groups had significantly higher body weight, systolic blood pressure and higher incidence of comorbidities. In addition, they had more frequently implanted a pacemaker. Conclusion Czech HF patients had worse cardiovascular risk profile as well as higher incidence of comorbidities compared to the patients from the whole ESC-HFLTR. © 2015 The Czech Society of Cardiology.


Parenica J.,University Hospital Brno | Parenica J.,Masaryk University | Parenica J.,University Hospital St Annes | Spinar J.,University Hospital Brno | And 21 more authors.
European Journal of Internal Medicine | Year: 2013

Background The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged. Methods The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival. Results The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age > 70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub-analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality. Conclusion The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival. © 2012 European Federation of Internal Medicine.


Krupicka J.,Charles University | Andruskova A.,Hospital Znojmo | Hegarova M.,Institute for Clinical and Experimental Medicine | Lazarova M.,University Hospital Olomouc | And 5 more authors.
Cor et Vasa | Year: 2016

Introduction: The ESC Heart Failure Long-Term Registry (ESC-HFLTR) is a prospective observational study which takes place in 211 cardiology centres of 21 European and Mediterranean countries, members of the European Society of Cardiology. Aim: To compare pharmacological and device therapy of both, the patients hospitalized for acute heart failure (HF) and the patients observed in outpatient clinics for chronic HF in the Czech Republic with published European-wide data. Methods: Altogether 692 consecutive patients were included into the Czech part of HFLTR (5.6% of the whole registry) from May 2011 to April 2013. These patients were either admitted to hospital or examined in outpatient clinic for HF during one predefined day of the week. The pharmacological and device therapy of 160 hospitalized (25.3%) and 532 ambulatory (74.7%) patients was analyzed statistically. The treatment of Czech ambulatory patients was finally compared with available data from the whole HFLTR. Results: The Czech in-hospital patients were intravenously treated generally with furosemide (in 89.3%), less frequently with nitrates (in 21.9%) and occasionally with inotropic agents (in 15.0%). In comparison with therapy before the hospital admission the patients at discharge received more frequently diuretics (69.4 vs. 87.5%; p <. 0.001) and mineralocorticoid receptor antagonist (MRA) (32.4 vs. 55.0%; p <. 0.001). The majority of Czech patients with chronic HF were treated according to current European guidelines. All prognostically relevant drugs used in HF were administered more often in the Czech HF population than in the whole HFLTR population (inhibitor of angiotensin converting enzyme or angiotensin receptor blocker in 92.8 vs. 89.2%; p = 0.018, betablocker in 95.1 vs. 88.9%; p <. 0.001, MRA in 67.0 vs. 59.3%; p <. 0.001, respectively). The recommended target doses of these drugs were reached in about 20% of the Czech as well as the European HF patients. In addition, the Czech ambulatory HF patients underwent more often pacemaker implantation (47 vs. 42%; p = 0.028), mainly due to more frequently indicated resynchronization therapy (56 vs. 30.2%; p <. 0.001). Conclusion: Czech ambulatory HF patients are pharmacologically treated in accordance with current European HF guidelines and significantly better than the patients in the whole HFLTR. However, the recommended target doses were reached only in the minority of the patients. © 2016 The Czech Society of Cardiology.


PubMed | University Hospital St Annes, Masaryk University, Institute of Clinical and Experimental Medicine, University Hospital Brno and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2015

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.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.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.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.


Helanova K.,Masaryk University | Spinar J.,Masaryk University | Spinar J.,University Hospital St Annes | Parenica J.,Masaryk University | Parenica J.,University Hospital St Annes
Kidney and Blood Pressure Research | Year: 2014

NGAL (neutrophil gelatinase-associated lipocalin) is an acute phase protein, participating in antibacterial immunity. NGAL forms a complex with metalloproteinase 9 (MMP-9), thereby increasing its activity and preventing its degradation. NGAL is freely filtered through the glomerular membrane and reabsorbed by endocytosis in the proximal tubule. NGAL detected in urine is produced mainly in the distal nephron. Elevated serum and urine NGAL allows diagnosis of acute kidney injury approximately 24 hours earlier than plasma creatinine concentration. Increased levels of NGAL were detected in patients with acute myocardial infarction, heart failure or stroke and were demonstrated to be strong predictors of adverse prognosis. © 2014 S. Karger AG, Basel.


Lipkova J.,Masaryk University | Splichal Z.,Masaryk University | Bienertova-Vasku J.A.,Masaryk University | Jurajda M.,Masaryk University | And 5 more authors.
Chronobiology International | Year: 2014

It is well established that the incidence and infarct size in acute myocardial infarction (AMI) is subject to circadian variations. At the molecular level, circadian clocks in distinct cells, including cardiomyocytes, generate 24-h cycles of biochemical processes. Possible imbalance or impairment in the cell clock mechanism may alter the cardiac metabolism and function and increase the susceptibility of cardiovascular diseases. One of the key components of the human clock system PERIOD3 (PER3) has been recently demonstrated to affect circadian expression of various genes in different tissues, including the heart. The variable number tandem repeat (VNTR) polymorphism (rs57875989) in gene Period3 (Per3) is related to multiple phenotypic parameters, including diurnal preference, sleep homeostasis, infection and cancer. The aim of our study was to investigate the effect of this polymorphism in AMI with ST elevation (STEMI). The study subjects (314 patients of Caucasian origin with STEMI, and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific polymerase chain reaction. A gender difference in circadian rhythmicity of pain onset was observed with significant circadian pattern in men. Furthermore, the Per35/5variant carriers were associated with higher levels of interleukin-6, B-type natriuretic peptide and lower vitamin A levels. By using cosinor analysis we observed different circadian distribution patterns of AMI onset at the level of genotype and allelic frequencies. Genotypes with at least one 4-repeat allele (Per34/5and Per34/4) (N=264) showed remarkable circadian activity in comparison with Per35/5(N=50), especially in men. No significant differences in genotype and/or allele frequencies of Per3 VNTR polymorphism were observed when comparing STEMI cases and controls. Our results indicate that the Per3 VNTR may contribute to modulation of cardiac functions and interindividual differences in development and progression of myocardial infarction. © Informa Healthcare USA, Inc.


Lipkova J.,Masaryk University | Parenica J.,University Hospital Brno | Parenica J.,Masaryk University | Parenica J.,University Hospital St Annes | And 9 more authors.
Clinical and Experimental Medicine | Year: 2015

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES −403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES −403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES −403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction. © 2014, Springer-Verlag Italia.


Goldbergova M.P.,Masaryk University | Parenica J.,Masaryk University | Parenica J.,University Hospital St Annes | Jarkovsky J.,Masaryk University | And 15 more authors.
Genetic Testing and Molecular Biomarkers | Year: 2012

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 24h 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. © Copyright 2012, Mary Ann Liebert, Inc.

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