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Biomedical subjects

Michal Tendera

Publications and source records attributed to Michal Tendera.

At least 19 recordsLinked to original sources
PubMed2006

The perindopril in elderly people with chronic heart failure (PEP-CHF) study.

AIMS: Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality. METHODS AND RESULTS: This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in patients aged > or =70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5-2.8) years. Enrollment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700-1.208; P = 0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474-1.010; P = 0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408-0.966; P = 0.033) were observed and functional class (P < 0.030) and 6-min corridor walk distance (P = 0.011) had improved in those assigned to perindopril. CONCLUSION: Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.

Aged↗
PubMed2006

The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart.

A task force has been established by the European Society of Cardiology to investigate the role of progenitor/stem cell therapy in the treatment of cardiovascular disease. This article is the consensus of this group, of what clinical studies are needed in this field, and the challenges to be addressed in the translation of progenitor/stem cell biology to repair of the heart.

Adult Stem Cells↗
PubMed2006

Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology.

Cardiovascular diseases (CVD) are the leading cause of mortality both in men and women. In Europe, about 55% of all females' deaths are caused by CVD, especially coronary heart disease and stroke. Unfortunately, however, the risk of heart disease in women is underestimated because of the perception that women are 'protected' against ischaemic heart disease. What is not fully understood is that women during the fertile age have a lower risk of cardiac events, but this protection fades after menopause thus leaving women with untreated risk factors vulnerable to develop myocardial infarction, heart failure, and sudden cardiac death. Furthermore, clinical manifestations of ischaemic heart disease in women may be different from those commonly observed in males and this factor may account for under-recognition of the disease. The European Society of Cardiology has recently initiated an extensive 'Women at heart' program to coordinate research and educational initiatives on CVD in women. A Policy Conference on CVD in Women was one of the first steps in the development of this program. The objective of the conference was to collect the opinion of experts in the field coming from the European Society of Cardiology member countries to: (1) summarize the state-of-the-art from an European perspective; (2) to identify the scientific gaps on CVD in women; and (3) to delineate the strategies for changing the misperception of CVD in women, improving risk stratification, diagnosis, and therapy from a gender perspective and increasing women representation in clinical trials. The Policy Conference has provided the opportunity to review and comment on the current status of knowledge on CVD in women and to prioritize the actions needed to advance this area of knowledge in cardiology. In the preparation of this document we intend to provide the medical community and the stakeholders of this field with an overview of the more critical aspects that have emerged during the discussion. We also propose some immediate actions that should be undertaken with the hope that synergic activities will be implemented at European level with the support of national health care authorities.

Age Distribution↗
PubMed2006

Rationale and design of a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction: the morBidity-mortality EvAlUaTion of the I(f) inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) study.

BACKGROUND: Raised resting heart rate (HR) is associated with increased cardiovascular and total mortality. Ivabradine is a new specific HR-reducing agent, which has been shown to have antianginal and anti-ischemic properties in patients with stable angina. Because patients with coronary artery disease and left ventricular dysfunction are at high risk of cardiac events and death, we hypothesized that they could derive particular benefit from a specific HR-lowering agent such as ivabradine. METHODS: BEAUTIFUL is a multicenter, randomized, international, double-blind placebo-controlled trial to evaluate the superiority of ivabradine over placebo in reducing cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction < or = 39%). The primary end point is the composite of cardiovascular mortality and hospital admission for acute myocardial infarction or new onset or worsening of heart failure. This event-driven study will randomize 9650 patients and continue until 950 primary end points have occurred, providing 90% power to detect a 19% reduction in relative risk. In approximately 660 centers, men and women aged > or = 55 years if nondiabetic and > or = 18 years if diabetic are randomized to placebo or oral ivabradine (5 mg twice daily for 2 weeks then target dose of 7.5 mg twice daily). Follow-up is expected to last between 18 and 36 months. RESULTS: The first patient was randomized in January 2005. CONCLUSION: BEAUTIFUL will be the first major outcome trial of a specific HR-reducing agent. The study results are expected in 2008.

Adult↗
PubMed2006

Future directions: what data do we need?

Pure heart rate reduction by ivabradine during exercise results in the decrease in oxygen demand and the increase in oxygen supply through the prolongation of diastole. These properties are crucial for its beneficial effect in patients with chronic stable angina. The ability of ivabradine to reduce the heart rate at rest can also have a potential use in clinical practice. In fact, the new directions for future clinical research are focused on this property. Chronic coronary artery disease, acute coronary syndromes and heart failure represent the areas in which resting heart rate reduction may improve cardiovascular prognosis. Application of ivabradine in these conditions deserves full attention, with dedicated and properly powered outcome trials.

Adrenergic beta-Antagonists↗
PubMed2005

Mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells is correlated with left ventricular ejection fraction and plasma NT-proBNP levels in patients with acute myocardial infarction.

AIMS: The aim of the study was to assess the correlation between the number of CD34(+), CD117(+), c-met(+), CXCR4(+) stem cells mobilized into peripheral blood, left ventricular ejection fraction (LVEF), NT-proBNP levels, and myocardial necrosis markers in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: 43 patients with STEMI were enrolled. Stem cells number was measured using flow-cytometer and concentrations of NT-proBNP, SDF-1, G-CSF, VEGF, IL-6, and HGF were measured using ELISA kits. The number of stem cells mobilized early (<12 h) in AMI was significantly, positively correlated with LVEF: r=0.49 (P=0.0012) for CD34(+) cells, r=0.48 (P=0.0018) for CXCR4(+) cells, r=0.45 (P=0.0043) for CD117(+) cells, and r=0.41 (P=0.01) for c-met(+) cells and negatively correlated with NT-proBNP levels on admission r=-0.35 (P=0.024) for CD34(+) cells, r=-0.42 (P=0.007) for CXCR4(+) cells, r=-0.33 (P=0.04). In patients with LVEF </=40%, the peak number of CD34(+), CXCR4(+), CD117(+), and c-met(+) stem cells was significantly lower when compared patients with LVEF >40%. The number of CXCR4(+) cells on admission and after 24 h was negatively correlated with respective cardiac Troponin I levels (r=-0.37; P=0.029 and r=-0.45, P=0.02) and maximum activity of CK-MB (r=-0.37; P=0.021). No significant correlations between levels of haematopoietic cytokines and LVEF were found. CONCLUSION: The mobilization of CD34(+), CD117(+), CXCR4(+), c-met(+) stem cells into peripheral blood early in STEMI is positively correlated with LVEF and negatively correlated with NT-proBNP levels and myocardial necrosis markers.

Antigens, CD34↗
PubMed2005

Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.

AIMS: Ivabradine, a new I(f) inhibitor which acts specifically on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent. Ivabradine has shown anti-ischaemic and anti-anginal activity in a placebo-controlled trial. The objective of this study was to compare the anti-anginal and anti-ischaemic effects of ivabradine and the beta-blocker atenolol. METHODS AND RESULTS: In a double-blinded trial, 939 patients with stable angina were randomized to receive ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks or atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks. Patients underwent treadmill exercise tests at randomization (M(0)) and after 4 (M(1)) and 16 (M(4)) weeks of therapy. Increases in total exercise duration (TED) at trough at M(4) were 86.8+/-129.0 and 91.7+/-118.8 s with ivabradine 7.5 and 10 mg, respectively and 78.8+/-133.4 s with atenolol 100 mg. Mean differences (SE) when compared with atenolol 100 mg were 10.3 (9.4) and 15.7 (9.5) s in favour of ivabradine 7.5 and 10 mg (P<0.001 for non-inferiority). TED at M(1) improved by 64.2+/-104.0 s with ivabradine 5 mg and by 60.0+/-114.4 s with atenolol 50 mg (P<0.001 for non-inferiority). Non-inferiority of ivabradine was shown at all doses and for all criteria. The number of angina attacks was decreased by two-thirds with both ivabradine and atenolol. CONCLUSION: Ivabradine is as effective as atenolol in patients with stable angina.

Adrenergic beta-Antagonists↗
PubMed2005

Evidence-based vs. 'impressionist' medicine: how best to implement guidelines.

Implementing clinical practice guidelines improves outcomes. This has been shown by several large scale registries. However, in spite of this, guidelines are poorly implemented in clinical practice for a wide variety of reasons. We examine the reasons behind the low uptake of guidelines into routine medical practice. Many physicians are simply not aware that guidelines exist; or they do not believe in them; or they simply do not care to implement them. Economic and social factors may also influence uptake of guidelines. It is the role of professional societies to disseminate best scientific knowledge, and ensure optimum implementation of guidelines. This can be achieved through educational activities and CME credit. Close collaboration between the profession, health authorities, and maybe even the industry could improve uptake of clinical practice guidelines, and thereby improve patient outcome.

Coronary Disease↗
PubMed2005

Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac disease and manifests predominantly as left ventricular hypertrophy. Mutations in the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease in about 30% of cases where mutations were identified. We clinically evaluated a large group of 147 consecutive HCM patients from three cardiology centers in Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the patients was systematically analyzed in the whole coding region of the MYH7 gene using PCR, single-strand conformation polymorphism analysis, and automated sequencing. Eleven different missense mutations (including seven novel ones) in 11 unrelated patients were identified, showing a mutation frequency of 7.5% in the study population. We further examined the families of five patients (three of German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We observed a clear, age-dependent penetrance with onset of disease symptoms in the fourth decade of life. Genotype-phenotype correlations were different for each mutation, whereas the majority was associated with an intermediate/malign phenotype. In conclusion, we report a systematic molecular screening of the complete MYH7 gene in a large group of consecutive HCM patients, leading to a genetic diagnosis in 38 individuals. Information about the genotype in an individual from one family could be very useful for the clinician, especially when dealing with healthy relatives in doubt of their risk about developing HCM. The increasing application of genetic screening and the increasing knowledge about genotype-phenotype correlations will hopefully lead to an improved clinical management of HCM patients.

Adolescent↗
PubMed2005

Heart rate variability fraction--a new reportable measure of 24-hour R-R interval variation.

BACKGROUND: The scatterplot of R-R intervals has several unique features. Its numerical evaluation may produce a new useful index of global heart rate variability (HRV) from Holter recordings. METHODS: Two-hundred and ten middle-aged healthy subjects were enrolled in this study. The study was repeated the next day in 165 subjects. Each subject had a 24-hour ECG recording taken. Preprocessed data were transferred into a personal computer and the standard HRV time-domain indices: standard deviation of total normal R-R intervals (SDNN), standard deviation of averaged means of normal R-R intervals over 5-minute periods (SDANN), triangular index (TI), and pNN50 were determined. The scatterplot area (0.2-1.8 second) was divided into 256 boxes, each of 0.1-second interval, and the number of paired R-R intervals was counted. The heart rate variability fraction (HRVF) was calculated as the two highest counts divided by the number of total beats differing from the consecutive beat by <50 ms. The HRVF was obtained by subtracting this fraction from 1, and converting the result to a percentage. RESULTS: The normal value of the HRVF was 52.7 +/- 8.6%. The 2-98% range calculated from the normal probability plot was 35.1-70.3%. The HRVF varied significantly with gender (female 48.7 +/- 8.4% vs male 53.6 +/- 8.6%, P = 0.002). The HRVF correlated with RRI (r = 0.525) and showed a similar or better relationship with SDNN (0.851), SDANN (0.653), and TI (0.845) than did the standard HRV measures with each other. Bland-Altman plot showed a good day-by-day reproducibility of the HRVF, with the intraclass correlation coefficient of 0.839 and a low relative standard error difference (1.8%). CONCLUSION: We introduced a new index of HRV, which is easy for computation, robust, reproducible, easy to understand, and may overcome the limitations that belong to the standard HRV measures. This index, named HRV fraction, by combining magnitude, distribution, and heart-rate influences, might become a clinically useful index of global HRV.

Analysis of Variance↗
PubMed2004

Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

BACKGROUND: The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion. METHODS AND RESULTS: Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP). CONCLUSIONS: NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Adrenergic beta-Antagonists↗
PubMed2004

Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure: the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study.

OBJECTIVES: We sought to evaluate the influence of pretreatment systolic blood pressure (SBP) on the efficacy and safety of carvedilol in patients with chronic heart failure (CHF). BACKGROUND: Although beta-blockers reduce the risk of death in CHF, there is little reported experience with these drugs in patients with a low pretreatment SBP, who may respond poorly to beta-blockade. METHODS: We studied 2,289 patients with severe CHF who participated in the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. RESULTS: Compared with placebo, carvedilol improved the clinical status and reduced the risk of death and the combined risk of death or hospitalization for any reason, for a cardiovascular reason, or for worsening heart failure (p < 0.001 for all). The relative magnitude of these benefits did not vary as a function of the pretreatment SBP (all interaction: p > 0.10). However, because patients with the lowest SBP were at highest risk of an event, they experienced the greatest absolute benefit from treatment with carvedilol. The lower the pretreatment SBP, the more likely that patients would report an adverse event, be intolerant of high doses of the study drug, or require permanent withdrawal of treatment (p < 0.001 for all). However, these risks were primarily related to the severity of the underlying illness and not to treatment with carvedilol. CONCLUSIONS: The current study provides little support for concerns about using beta-blockers (particularly those with vasodilatory actions) in patients with severe CHF who have a low SBP. Pretreatment blood pressure can identify patients who have the greatest need for risk reduction with carvedilol.

Adrenergic beta-Antagonists↗
PubMed2004

NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy.

BACKGROUND: Neither profiles nor prognostic value of cardiac N-terminal proBNP (NT-proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo. METHODS: Baseline and follow-up plasma concentrations of NT-proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol. RESULTS: NT-proBNP concentrations were increased at baseline (mean+/-S.D.=579+/-822 pmol/l, median=322.5 pmol/l) with a marked decrease during follow-up in the carvedilol, but not in the placebo group. One-year mortality rates were 3.9, 12 and 27.9% in the lower, middle and upper tertiles of NT-proBNP, respectively. When mortality was calculated separately in the placebo and carvedilol group, rates were 0.8, 6.3 and 19.1% in the carvedilol treated but 6.7, 17.9 and 36.9% in the placebo treated patients. CONCLUSIONS: NT-proBNP was a powerful predictor of subsequent all-cause mortality in patients with severe CHF. This marker should therefore be further evaluated for risk stratification and monitoring of therapy in CHF.

Aged↗