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Cardiac biomarkers are very important in diagnosis, risk stratification, and management of patients with heart failure. Although not meeting all criteria for an ideal biomarker, natriuretic peptides primarily have a diagnostic and prognostic role. Other routinely available and newly emerging biomarkers have a complementary role in patient management; thus multimarker strategy might be warranted in future. The quest for a single marker or a combination is ongoing and several established, widely available biomarkers might have been overlooked in the field of heart failure. The authors review some of those biomarkers and speculate on the possible roles of combining two or more of them.

Chronic heart failure is viewed as a state of chronic inflammation. Many inflammatory markers have been shown to be up-regulated in patients who have this condition, but the markers' roles in clinical decision making have not yet been fully elucidated. A panel of biomarkers is likely to have a strong impact on patient management. Inflammatory biomarkers are interesting candidates that could answer specific clinical questions on their own or complement a multi-marker approach. This article provides a broad overview of several inflammatory biomarkers, including the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-6, IL-1, IL-18, and the soluble receptors TNFR-1, TNFR-2, IL-6R, and gp130. In addition to these acute phase reactants, several adhesion molecules, and lipopolysaccharide-signaling pathways are discussed.

Chronic heart failure (CHF) is of constantly growing importance regarding incidence, prevalence and social and economic burden. The classical mere hemodynamic perception of CHF pathophysiology has been expanded towards a much more complex and inclusive approach combining neuroendocrine, inflammatory, metabolic and immunological factors. With this advance, new parameters and targets have been shifted into the focus of current investigations, and new therapeutic approaches have been tested. Several recent studies have failed, however, despite intriguing pathophysiological concepts and promising pilot data. In other studies, significant benefits have been observed in certain subgroups only, suggesting a tailored approach for individual risk and co-morbidity situations. The contemporary concept of CHF treatment is designed to shield the heart from adverse (over)compensatory mechanisms particularly of neuroendocrine activation. This shield needs to be expanded on systemic effects including both immunologic and metabolic aspects within CHF pathophysiology. New and future concepts in CHF therapy may not yield a homogenous treatment option applicable for every patient, but may require a new range of diagnostic strategies to design a tailored therapy, adapted to the patient's pathophysiological fingerprint. This review will focus on recent developments and potential future candidates of pharmacological CHF therapy.

Aims: In patients with chronic heart failure (CHF), there is limited information on self-rated health (SRH). We aimed to examine the distribution of SRH and whether SRH is associated with mortality in patients with stable CHF., Methods and Results: We enrolled 100 patients (71 +/- 11 years, 54% men, left ventricular ejection fraction 47 +/- 11%) in a prospective study with 48 months of follow-up. Self-rated health was assessed using a seven-grade descriptive scale: very good, good, quite good, average, quite poor, poor, and very poor. Median SRH was quite poor and the most frequent SRH (31 patients) was average. During an average follow-up of 1005 +/- 507 days, 58 patients died. More patients in the group that rated their health as quite poor or worse died (70% vs. 43%, P = 0.008). In a Cox proportional hazard model, SRH as a seven-grade descriptive scale [hazard ratios (HR) 1.39, 95% CI 1.10-1.74] or as a median value (HR 2.13, 95% CI 1.23-3.69) predicted mortality. The association remained significant after adjustment for patient characteristics and biomarkers (P < 0.05 for both)., Conclusion: In patients with stable CHF, SRH independently predicts mortality. This suggests that SRH could be used in everyday clinical practice to obtain important prognostic information beyond clinical examination and laboratory work-up.

Cardiac biomarkers play an important role in heart failure. The family of natriuretic peptides, especially B-type natriuretic peptide, was identified as a valued diagnostic and prognostic tool. Not unexpectedly, the natriuretic peptides fail to fulfill all the criteria of an ideal biochemical marker. The quest for a single marker or a combination is therefore still on and several established, widely available biomarkers might have been overlooked in the field of heart failure. This review puts forward some of those biomarkers, and we speculate on the possible roles of combining two or more biomarkers. In that sense, any blood parameter including hemoglobin, cholesterol, uric acid, and recently identified proteins might function as a biomarker. Additionally, several biomarkers are discussed and we try to anticipate their diagnostic and prognostic value along with the natriuretic peptides and established biomarkers. Finally, we speculate about the potential of sharing the biomarkers over a variety of chronic diseases with similar pathophysiology.

Cardiac cachexia as a terminal stage of chronic heart failure carries a poor prognosis. The definition of this clinical syndrome has been a matter of debate in recent years. This review describes the ongoing discussion about this issue and the complex pathophysiology of cardiac cachexia and chronic heart failure with particular focus on immunological, metabolic, and hormonal aspects at the intracellular and extracellular level. These include regulators such as neuropeptide Y, leptin, melanocortins, ghrelin, growth hormone, and insulin. The regulation of feeding is discussed as are nutritional aspects in the treatment of the disease. The mechanisms of wasting in different body compartments are described. Moreover, we discuss several therapeutic approaches. These include appetite stimulants like megestrol acetate, medroxyprogesterone acetate, and cannabinoids. Other drug classes of interest comprise angiotensin-converting enzyme inhibitors, beta-blockers, anabolic steroids, beta-adrenergic agonists, anti-inflammatory substances, statins, thalidomide, proteasome inhibitors, and pentoxifylline.

Decision-making in the care for patients with chronic heart failure (CHF) has become increasingly difficult. The many available therapeutic strategies and novel treatment modalities with borderline or modest benefit call for careful risk stratification in patients with CHF. Rather than relying on highly sophisticated and expensive procedures, we may find routinely available parameters of clinical value. This review considers the importance and validity of serum biomarkers (like natriuretic peptides, uric acid, lipoproteins, and cytokines), metabolic changes (like insulin resistance or body mass index), patient measures of symptom status and exercise capacity, as well as prognostic scoring systems. There is limited evidence that the use of prognostic markers to make treatment decisions improves the outcome in CHF. Many studies still need to be done to this end.

Objectives: Like chronic heart failure, chronic obstructive pulmonary disease (COPD) is an enormous public health problem in industrialized countries. Our aim was to determine the prevalence and clinical impact of COPD among patients hospitalized for heart failure in a community hospital serving a population of 125,000 people., Methods: Between 2001 and 2003 a total of 638 patients (73 +/- 10 years, 48% men, 74% NYHA class III) were identified with a discharge diagnosis of heart failure. Medical charts were reviewed and vital status was obtained from a Central Population Registry., Results: COPD was diagnosed in 106 (17%) patients whose age was similar to those without COPD (73 +/- 9 vs. 73 +/- 11 years, P = 0.35). Patients with COPD were more often males (65% vs. 45%, P < 0.001). There were no differences in arterial hypertension, atrial fibrillation, diabetes mellitus and most laboratory markers except hemoglobin (141 +/- 20 vs. 132 +/- 20 g/l, P < 0.001) and uric acid (453 +/- 136 vs. 414 +/- 139 mmol/l, P = 0.013). At discharge, patients with COPD were less likely to receive beta-blockers (12% vs. 28%, odds ratio 0.35, 95% CI0.19-0.64). During follow-up, patients with COPD had higher mortality (73% vs. 60%, P = 0.016, hazard ratio 1.48, 95% CI 1.15-1.90). Kaplan-Meier (log-rank test, P = 0.002) and Cox proportional hazard analysis, adjusted for age, sex, hemoglobin, uric acid, and treatment with beta-blockers and furosemide (hazard ratio 1.38, 95% CI1.04-1.83, P = 0.024) demonstrated the prognostic importance of COPD., Conclusions: COPD is frequent among hospitalized patients with heart failure. Beta-blockers are largely underused, which is probably a major reason for the higher mortality observed in patients with concomitant chronic heart failure and COPD.

Chronic cardiopulmonary disease typically induces and maintains (over)activation of several phylogenetically old adaptational and defensive mechanisms. Activation was usually needed for a limited period during acute danger or injury. In chronic disease conditions, however, those mechanisms are kept activated for longer periods. Eventually, irreversible damage is done and this contributes to impaired function and worse prognosis in a variety of chronic disease. Landmark trials in chronic heart failure have provided robust evidence for prognostic benefit for neurohormonal antagonists. Retrospective and epidemiological data for their beneficial effect in chronic obstructive pulmonary disease begin to accumulate and new fields (e.g. cancer and stroke) could be pending in the future.

Background: Data on self-rated health (SRH) in patients with chronic obstructive pulmonary disease (COPD) are very limited; we therefore initiated this study to investigate the distribution of SRH and association with established parameters of disease severity., Patients and Methods: We included 135 clinically stable patients with COPD (64 +/- 8 years, 71% men, GOLD stage: II -59; III -55; IV -21) and 25 healthy control persons. SRH was evaluated using the 5-grade Likert scale (1-very poor to 5-very good)., Results: Patients with COPD had poorer SRH when compared with controls (3.0 +/- 0.7 vs. 3.8 +/- 0.6, P < 0.001). SRH decreased over GOLD stage (P = 0.016) and 27 (20%) patients reported poor or very poor SRH. In univariate analysis, GOLD stage (P = 0.022), Center for Epidemiologic Studies Depression (CES-D) score (P = 0.001), BODE index score (P < 0.001), score on the modified Medical Research Council (MMRC) dyspnea scale (P < 0.001) and 6-minute walk test (6MWT) distance (P < 0.001) determined poor or very poor SRH. In a multivariate model which included BODE index score, a CES-D score > or = 16 (P = 0.013) and BODE index score (P = 0.012) determined poor or very poor SRH. In the model with individual components of the BODE index, a CES-D score > or = 16 (P = 0.012), MMRC score of 3 or 4 (P = 0.019) and 6MWT distance < or = 249 m (P = 0.019) determined poor or very poor SRH., Conclusion: In patients with COPD, SRH is worse than in healthy control persons and deteriorates over GOLD stage. Perception of health as poor or very poor is associated with psychological components (CES-D score) and disease severity (BODE index score, 6MWT distance and MMRC dyspnea score).

Background: Guidelines for prevention of venous thromboembolism recognize pneumonia and changes in respiratory status as risk factors. There is little information on the preventive use of low-molecular-weight heparin (LMWH) in hospitalized patients with pneumonia., Methods: We prospectively screened 1067 admissions to our hospital for preventive use of LMWH according to the American College of Chest Physicians (ACCP) guidelines. The analysis included 168 patients with pneumonia (age 74 +/- 16 years, 56% men). The primary and secondary outcomes were treatment with LMWH in eligible patients and LMWH use according to guidelines (daily dose, duration of treatment)., Results: LMWH use was indicated in 126 (75%) patients and 119 (94%) were actually treated. In 41% of patients treatment was according to the ACCP guidelines. The dose and duration of LMWH treatment were appropriate in 61% and 66% of patients, respectively. Non-use of LMWHs was not associated with clinical and demographic characteristics. Adverse effects included bleeding (N = 7) and thrombocytopenia (N = 2) but were not associated with fatality. Prolonged treatment with LMWH was associated with adverse effects (P < 0.05)., Conclusions: Implementation of LMWH prophylaxis for venous thromboembolism in hospitalized patients with pneumonia reached 94%. Adherence to ACCP guidelines was complete in 41% of patients. Prolonged treatment with LMWH was associated with non-fatal adverse effects, which calls for timely withdrawal of LMWH once no longer indicated.

Background: Chronic heart failure (CHF) is a widespread disease with severe quality of life impairment and a poor prognosis. Beta-blockers are the mainstay of CHF therapy; yet they are under-prescribed and under-dosed in clinical practice. This is particularly evident in elderly patients, which may be due to a fear of side-effects or intolerance. Beta-blockers have further not been adequately tested in patients with diastolic CHF, which is particularly common in elderly patients. Finally, comparative data on the use of different beta-blockers in patients with CHF is scarce., Aim: To compare the tolerance of bisoprolol and carvedilol in elderly patients with CHF., Methods: CIBIS-ELD is an investigator-initiated, multi-centre, 1:1 randomised, double-blind, phase III trial comparing bisoprolol and carvedilol in patients >or=65 years with systolic or diastolic CHF. Recruitment started in April 2005 and is anticipated to be completed by April 2008 with at least 800 patients enrolled., Perspective: This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF.

Atrial fibrillation is the most common arrhythmia, and is associated with increased risk of stroke and death. Most of present knowledge is derived from studies in patients with cardiac disease whilst limited information is available for patients with several chronic non-cardiac conditions like cancer, chronic obstructive pulmonary disease and chronic kidney disease. Although millions of patients are affected and are at risk of adverse prognosis due to co-existent atrial fibrillation, we are left with very limited guidance for management of atrial fibrillation itself and prevention of complications in those patients. In this paper, we review data on incidence, prognostic importance and treatment modalities of atrial fibrillation in patients with cancer, chronic obstructive pulmonary disease, and chronic kidney disease.

Cachexia--sometimes also referred to as wasting disease, malnutrition, or hypercatabolism--has been described for centuries and has always raised ominous thoughts that "the end is near." The disease is encountered in many malignant and nonmalignant chronic, ultimately fatal, illnesses. Yet, although cachexia is a deadly syndrome, little is known about its pathophysiology, and the debate regarding its definition is ongoing. Thus, the data on epidemiology can be contested, but a few things are certain: Cachexia is associated with exceedingly high mortality once the syndrome has fully developed, irrespective of the definition we apply, and it is associated with weakness, weight loss, muscle wasting, and inflammation. It is not simply an ancillary event, and it may contribute to the death of the patient either through effects on neuroendocrine and immune defense mechanisms or through protein calorie malnutrition. The therapeutic standard of care for cachexia remains undefined to date, with a few exceptions. Among the recognized approaches, exogenous oral amino acid supplementation appears very promising. Further research efforts are needed and they are ongoing.

The existing guidelines for the treatment of patients who have heart failure limit the administration of antiplatelet and anticoagulant agents to patients who have specific comorbidities, including coronary artery disease, atrial fibrillation, history of thromboembolic events, and left ventricular mural thrombus. Retrospective analyses of large clinical trials or smaller nonrandomized studies indicate that the use of statins may be beneficial both in ischemic and idiopathic dilated cardiomyopathy. This article outlines the current knowledge regarding the use of antiplatelet and anticoagulant agents and statins in patients who have heart failure.

Background: Chronic heart failure (CHF) is characterized by increased insulin resistance and hyperleptinaemia. We aimed to study effects of selective and non-selective beta-blockers on body weight, insulin resistance, plasma concentrations of leptin and resistin in patients with CHF., Methods: Twenty-six non-cachectic beta-blocker-naive patients with CHF were randomized and treated with either carvedilol or bisoprolol. Body weight, plasma concentrations of leptin, resistin, fasting glucose and insulin were measured at baseline and after 6 months of therapy. Insulin resistance was estimated by homeostasis model assessment- estimated insulin resistance (HOMA-IR)., Results: Body weight increased significantly in the carvedilol group (mean change + 2.30 kg, p = 0.023) while it did not change in the bisoprolol group (mean change -0.30 kg, p = 0.623) (ns between groups). Plasma leptin concentration increased only in the carvedilol group (mean change + 4.20 ng/ml, p = 0.019) (ns between groups). Fasting glucose and resistin remained unchanged in both groups. After 6 months, mean plasma insulin concentration changed significantly differently (p = 0.015) in the bisoprolol (mean change +3.1 microU/ml) compared to the carvedilol group (mean change -6.3 microU/ml) and HOMA-IR was consequently higher in the bisoprolol compared to the carvedilol group (5.2 +/- 4.2 vs 2.8 +/- 1.6, p = 0.046)., Conclusion: This study found different metabolic effects of carvedilol and bisoprolol in non-cachectic patients with CHF. With unchanged fasting plasma glucose concentration after 6 months of treatment, carvedilol significantly decreased plasma insulin concentration and insulin resistance compared to bisoprolol.

Purpose of Review: Metabolic, immunological and neurohormonal disturbances, body wasting, and poor patient performance frequently accompany chronic disease. Ultimately, cachexia may develop in 10-15% of patients, who usually perish soon after. We currently have neither a globally accepted definition of cachexia nor any treatment to prevent or treat cachexia., Recent Findings: Cachexia remains an unresolved issue in modern medicine. Despite its significant prevalence and poor prognosis, debate on the global definition of cachexia continues. We require a clinical definition, which should include the significant weight loss and its dynamics. There is accumulating evidence that various chronic diseases share pathophysiological mechanisms that lead to wasting and ultimately cachexia. Reversal of traditional cardiovascular risk factors is of value not only in chronic heart failure but also in chronic kidney disease and chronic obstructive pulmonary disease., Summary: Future trials to improve prognosis in patients with cachexia will require a global definition of cachexia and identification of key underlying mechanisms. Results with neurohormonal antagonists are intriguing, and clinical use of these agents would be feasible. While searching for treatments for full-blown cachexia, we should also aim to identify treatments directed at the causes in order to prevent its development.

Background: Beta-blockers are well established for treatment of chronic heart failure (CHF). However, the extent of implementation of trial results and guidelines in daily practice remains limited, and information regarding how patients feel is scarce., Methods: In this prospective observational survey of 6 months duration, 531 physicians from 10 countries recruited 3748 beta-blockers untreated patients with CHF. We assessed the efficacy, tolerability and achieved dosage of carvedilol. In addition, patients assessed their well-being 3 times: at baseline, after 3 and 6 months of treatment., Results: Carvedilol was started in 3721 patients with CHF (median age 65 years, 60% men). NYHA class, clinical symptoms and signs, vital signs, 5-item well-being rating scale and visual analogue scale improved during the survey. Side effects, mostly fatigue, hypotension, and dizziness, were reported for 6.5% and 5% of patients at 3 and 6 months and carvedilol had to be discontinued in 63 patients. A total of 55 deaths (1.5%) and 520 hospitalisations in 466 patients (13%) were recorded. At 6 months the mean daily dose of carvedilol was 31+/-11 mg; 25 mg/day was prescribed to 35% and 50 mg/day to 26% of patients., Conclusions: Initiation and up-titration of carvedilol in ambulatory care patients with CHF is feasible and safe. Its efficacy and tolerability were at least as good as in clinical trials, while the amelioration of patients' well-being was significant despite sub-optimal dosing. An additional effort should be done by physicians to treat their patients with CHF in daily practice with the recommended beta-blockers at optimal doses.

Background: There are limited data on recall and implementation of lifestyle advice in patients with heart failure (HF)., Aim: To investigate what advice patients with HF recall being given, and whether they report following the advice they remember., Methods and Results: 3261 patients with suspected HF participating in the EuroHeart Failure Survey were interviewed by a health professional 12 weeks after hospital discharge. Patients recalled receiving 46% of pre-specified items of advice and 67% reported that they followed these completely. Both recall (53%) and implementation (71%) was best in patients with left ventricular systolic dysfunction (LVSD). In multivariate analysis, younger age, male sex, patient awareness of the condition and patients reporting that they received a clear explanation of the diagnosis by a health professional, all factors associated with having LVSD, were the strongest predictors of recall., Conclusions: Recall of and adherence to advice by patients with HF in this large European cross-sectional survey was disappointing. Responsibility for patient education lies with health professionals who should ensure that patients receive and understand advice, and are able to recall and follow it. A greater awareness of the issues surrounding lifestyle advice and more evidence supporting its value could improve patient care.

Physical inactivity is the second most important risk factor for development of cardiovascular diseases. Various field tests were developed for assessment of the fitness in general population. We aimed to assess the applicability and effectiveness of the specific software for UKK 2-km walking test data management. Descriptive results and statistical analysis on physical fitness of 383 adults are presented. The UKK 2-km walking test could be used as a feasible alternative for measurement of cardiovascular fitness. The test was integrated to exercise related health promotion programme, and widely available information technologies will be used for data management.

With the broad employment of immunosuppressive therapy, the incidence of Pseudallescheria boydii infections is rising. We report a first case of the localized subcutaneous P. boydii infection in a patient with microscopic polyangiitis. Favorable outcome related to the treatment with voriconazole adds to the growing body of evidence supporting the use of this particular agent in P. boydii infections.

Advice on lifestyle, diet, vaccination, and therapy are part of the standard management of heart failure (HF). However, there is little information on whether patients with HF recall receiving such recommendations and, if so, whether they report following them. We obtained information on the recall of and adherence to nonpharmacologic advice from patients enrolled in the EuroHeart Failure Survey. This article focuses on 2,331 patients who had a clinical diagnosis of HF during the index admission and attended an interview 12 weeks after discharge. Their mean age was 67 +/- 12 years and 38% were women. Patients recalled receiving 4.1 +/- 2.7 items of advice with higher rates in Central Europe and the Mediterranean region. Recall of dietary advice (cholesterol or fat intake, 63%; dietary salt, 60%) was higher than for some other interventions (influenza vaccination, 36%; avoidance of nonsteroidal anti-inflammatory drugs, 17%). Among those who recalled the advice, a substantial proportion indicated that they did not follow advice completely (cholesterol and fat intake, 61%; dietary salt, 63%; influenza vaccination, 75%; avoidance of nonsteroidal anti-inflammatory drugs, 80%), although few patients indicated they ignored the advice completely. Patients who recalled >4 items versus < or =4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), beta-blockers (51% vs 38%), and spironolactone (25% vs 21%). In conclusion, after hospitalization for HF, many patients do not recall nonpharmacologic advice. In addition, a substantial proportion of those who recall the advice follow it incompletely. Younger age and prescription of appropriate pharmacologic treatment are associated with higher rates of recall and implementation.

Background: Treatment of heart failure (HF) due to left ventricular systolic dysfunction (LVSD) is effective, but many patients are not treated in accordance with guidelines. This may reflect a lack of adequate organisation of care or co-morbidity contra-indicating therapy., Aims: To evaluate the effect of co-morbidities on the prescription of neurohormonal antagonists for HF., Methods and Results: The EuroHeart Failure Survey identified 10,701 patients with suspected or confirmed HF during 2000 and 2001, 64% of whom had an imaging test and 3658 had documented LVSD. This last group constitutes the focus of this report. Renal dysfunction was associated with lower prescription of ACE inhibitors at discharge (74% vs. 83%, p<0.001). Beta-blockers were less often used in patients with respiratory disease (32% vs. 53%, p<0.001). Co-morbidity did not appear to affect the use of spironolactone. There were few important international differences in uptake of key therapies amongst European countries with widely differing cultures and economic status., Conclusions: Guidelines appear successful in creating a relatively uniform approach to the treatment for HF due to LVSD in diverse medical cultures. Relevant co-morbidity seems to be responsible for a substantial reduction in the prescription of ACE inhibitors and beta-blockers. However, whilst co-morbidity indicates the need for greater caution, it is often not a valid contra-indication to life-saving therapy.

In recent years, biomarkers have been recognized as important tools for diagnosis, risk stratification, and therapeutic decision-making in cardiovascular diseases. Currently, the clinical potential of several natriuretic peptides is under scientific investigation. The well-known counter-regulatory hormones are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP) and urodilatin, which play an important role in the homeostasis of body fluid volume. ANP and BNP have already been demonstrated to have diagnostic usefulness in a great number of studies, which have progressed from bench to bedside. This article summarizes existing data on ANP and related peptides in cardiovascular and other disorders, and outlines the potential clinical usefulness of these markers.

Cardiac biomarkers play an important role in and provide better pathophysiological understanding of chronic heart failure (CHF). Natriuretic peptides, especially B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), were found to be useful in the diagnostic assessment and prognostic stratification of patients with CHF. However, they fail to fulfill all the criteria of an ideal biomarker. Currently, we still do not have a single biomarker or a combination of biomarkers to answer all the clinically relevant questions in CHF. Consequently, some widely available biomarkers might have been overlooked in the field of heart failure. This review discusses several biomarkers, and speculates on the possible roles of combining two or more of them. In this respect, hemoglobin, cholesterol, uric acid, and recently identified proteins may prove to be relevant to the field of CHF. Lastly, we anticipate the potential of biomarkers in a variety of chronic diseases with similar pathophysiology.

Principles: Heart failure is associated with a grim prognosis. Disease management programmes can improve prognosis in heart failure patients but the applicability to the general population remains limited. We aimed to compare the outcome, pharmacological therapy, and quality of life in unselected heart failure patients from a community hospital area who were managed either in the heart failure clinic or who received the usual care., Methods and Results: We followed 115 patients receiving care in the heart failure clinic (n = 50) or the usual care (n = 65) for at least twelve months. During the follow-up of 561 (463, 701) days significantly less patients from the heart failure clinic were rehospitalized due to heart failure or died (42% vs 65%). Assignment to the heart failure clinic (Hazard ratio [HR] 0.39, 95% Confidence interval [CI] 0.20-0.75), New York Heart Association class (HR 2.32, 95% CI 1.22-4.41), and systolic blood pressure (HR 0.98, 95% CI 0.96-0.99) independently predicted occurrence of heart failure rehospitalisations or death. At the end of the follow-up patients from the heart failure clinic received more optimal pharmacological therapy and reported better quality of life., Conclusions: Patient management in the community hospital heart failure clinic reduced the incidence of heart failure rehospitalisation or death with further benefits in terms of pharmacological therapy and quality of life.

Aims: Warfarin is a frequently used anticoagulant drug with narrow therapeutic index and high interindividual variability in the dose requirement. We have previously shown that warfarin dose is influenced by cytochrome P450 (CYP) 2C9 genotype, age, body weight and co-treatment with drugs that interfere with warfarin metabolism. As, in many patients, drug co-treatment cannot be avoided, we investigated the effect of co-treatment with carbamazepine, amiodarone and statins on warfarin metabolism and maintenance dose., Methods: Caucasian patients on stable maintenance warfarin therapy with CYP2C9*1/*1 genotype (n=82) were included in the study. Plasma concentrations of (S)- and (R)-warfarin as well as warfarin hydroxylated metabolites were determined using HPLC assay and corresponding clearances of (S)- and (R)-warfarin were calculated., Results: Patients co-treated with carbamazepine (n=5) had significantly higher plasma 10-hydroxywarfarin concentrations than patients not taking any interacting drugs (n=54) (median: 0.327 microg/ml vs 0.030 microg/ml, p=0.003). (S)- and (R)-warfarin clearances were also higher in the carbamazepine co-treated group (p=0.003), as were warfarin dose requirements (median: 9.00 mg/day vs 3.86 mg/day, p=0.003). Under the conditions of this study, patients co-treated with amiodarone (n=6) did not differ significantly regarding any measured characteristic from patients with no interacting drug treatment, while patients co-treated with simvastatin or lovastatin (n=17) had lower 10-hydroxywarfarin concentration (p=0.02)., Conclusions: We confirmed important interaction between carbamazepine and warfarin metabolism which can be of major clinical importance. If treatment with carbamazepine cannot be avoided, patients taking warfarin should be frequently monitored, especially when initiating or stopping carbamazepine therapy.

Background: Several studies have shown improvement of prognosis in patients managed in heart failure (HF) clinics. However, the value of the individual management components is not well established., Aim: To assess the prognostic value of pharmacological treatment and patient's knowledge in patients receiving care in a HF clinic., Methods and Results: In our prospective cohort study we followed 115 patients (50 from an HF clinic and 65 receiving usual care) for at least 12 months. Knowledge was assessed using a Patient Knowledge Questionnaire (PKQ). During a median follow-up of 561 days, fewer patients from the HF clinic died or were rehospitalized due to HF than those receiving usual care (42% vs. 65%, p = 0.016). The prescription rates of ACE inhibitors (94% to 98%) and beta blockers (40% to 94%) increased in the patients from the HF clinic. In these patients the PKQ score also increased from 4.8 (1.5) to 7.9 (1.3), p<0.001. In the Cox proportional hazard model, treatment with beta blockers at > or = 50% of the target daily dose (Hazard Ratio [HR] 0.3, 95% Confidence Interval [CI] 0.10-0.95) and a PKQ score <7 (HR 3.92, 95% CI 1.39-11.03) predicted prognosis in the patients from the HF clinic., Conclusions: Patient management in the HF clinic reduced the incidence of death or of HF rehospitalization. Poor prognosis of patients receiving care in the HF clinic was predicted by poor patient knowledge and underdosing with beta blockers.

Background: Cachexia is an independent risk factor for mortality in chronic heart failure (CHF). Beta blockers can reduce body energy expenditure and improve efficiency of substrate utilization., Aim: To assess the changes in body composition in non-cachectic patients with CHF treated with beta blockers., Methods: We prospectively followed 41 non-cachectic ambulatory CHF patients (mean age 67 +/- 10 years, ejection fraction 37 +/- 4%) treated with beta blockers for at least 6 months. Body composition was measured by bioimpedance., Results: At baseline 16/41 patients were treated with beta blockers while at the end of follow-up all patients received beta blockers (31/41 at full recommended dose). During follow up of 263 +/- 106 days body weight (83.1 +/- 16.7 vs. 83.0 +/- 16.9 kg), body mass index (29.3 +/- 5.5 vs. 29.3 +/- 5.6) and total body water did not change (51.2 +/- 6.4% vs. 51.0 +/- 6.4%), while total body fat mass (27.4 +/- 9.6 to 28.3 +/- 10.2 kg, median change +0.89 kg, p = 0.01) and percent of total body fat increased (32.3 +/- 7.4% to 33.4 +/- 7.5%, median change +0.7%, p < 0.001). New York Heart Association class and Minnesota Living with Heart Failure Questionnaire improved from 2.9 +/- 0.4 and 48 +/- 15 to 2.3 +/- 0.6 and 32 +/- 16, respectively (p < 0.001 for both)., Conclusion: In patients with CHF, treatment with beta blockers can increase total body fat mass and total body fat content.

Background: Several studies showed insufficient knowledge and poor compliance to non-pharmacological management in heart failure patients. Only a limited number of validated tools are available to assess their knowledge. The aim of the study was to test our 10-item Patient knowledge questionnaire., Methods: The Patient knowledge questionnaire was administered to 42 heart failure patients from Heart failure clinic and to 40 heart failure patients receiving usual care. Construct validity (Pearson correlation coefficient), internal consistency (Cronbach alpha), reproducibility (Wilcoxon signed rank test), and reliability (chi-square test and Student's t-test for independent samples) were assessed., Results: Overall score of the Patient knowledge questionnaire had the strongest correlation to the question about regular weighing (r=0.69) and the weakest to the question about presence of heart disease (r=0.33). There was a strong correlation between question about fluid retention and questions assessing regular weighing, (r=0.86), weight of one litre of water (r=0.86), and salt restriction (r=0.57). The Cronbach alpha was 0.74 and could be improved by exclusion of questions about clear explanation (Chronbach alpha 0.75), importance of fruit, soup, and vegetables (Chronbach alpha 0.75), and self adjustment of diuretic (Chronbach alpha 0.81). During reproducibility testing 91% to 98% of questions were answered equally. Patients from Heart failure clinic scored significantly better than patients receiving usual care (7.9 (1.3) vs. 5.7 (2.2), p<0.001)., Conclusions: Patient knowledge questionnaire is a valid and reliable tool to measure knowledge of heart failure patients.

Focal meningoencephalitis is commonly caused by Herpes simplex virus infection, which typically affects temporal or frontal lobes, and carries a mortality rate of 70% if untreated. On rare occasions, however, the infection is restricted to the brain stem. Polymerase chain reaction analysis of cerebrospinal fluid is the gold standard for the diagnosis of herpes simplex encephalitis. A 46-year-old male was admitted to the hospital with a three-day history of headache and fever up to 39 degrees C. Cerebrospinal fluid findings were in accordance with aseptic meningitis. On the third hospital day, the patient presented with double vision followed by confusion, and gaze paresis developed. The condition rapidly progressed from stupor to coma. A second examination of cerebrospinal fluid revealed a low glucose level (1.2 mmol/l) and cefotaxime with ampicillin were started empirically. All cerebrospinal fluid specimens were negative for bacteria and fungi. Serum IgG antibodies for herpes simplex virus type 1 were found with no intrathecal specific antibody synthesis. A polymerase chain reaction analysis of cerebrospinal fluid sample performed on the seventh day of his illness was negative for herpes simplex virus 1 and 2. A computer tomography scan of the brain did not show any abnormality. Despite antimicrobial and supportive intensive care, the condition of the patient progressively deteriorated and he died on the 11th day after admission. An autopsy revealed hemorrhagic and necrotic brainstem meningoencephalitis, and herpes simplex virus type 1 infection was confirmed by hybridization in situ. Herpes simplex virus encephalitis carries a mortality rate of 70% if untreated. The atypical location of the infection, as well as an atypical clinical manifestation with negative radiological and microbiological tests, could be the reasons for false diagnoses and mistreatment. Many authors advocate the use of empiric acyclovir in any patients with unexplained encephalopathy, since delay in treatment may greatly affect outcome. We describe a patient who died due to a herpes simplex virus 1 encephalitis affecting the brainstem, where nucleic acids were found post mortem by in situ hybridization. On rare occasions, the herpes simplex viral infection, as well as clinical manifestations and pathological changes, is restricted solely to the brainstem.

Background and Aim of the Study: Endocarditis due to Abiotrophia sp. is rare and often associated with negative blood cultures. The rates of treatment failure, infection relapse and mortality are higher than in endocarditis caused by other viridans streptococci., Methods: A retrospective review of A. defectiva endocarditis in a patient with prosthetic aortic valve and in a patient with Marfan syndrome was performed., Results: A. defectiva, susceptible to penicillin (MIC 0.064 mg/l and 0.016 mg/l, respectively) was isolated from blood cultures of both patients. Treatment with penicillin and gentamicin was started in both patients. Since the first patient developed a macular rash and leukopenia, penicillin was substituted with ceftriaxone. Both patients responded well to antibiotic treatment, did not need prosthetic valve insertion or reinsertion, and were without any sequelae at one year follow up., Conclusion: Standard treatment of bacterial endocarditis with penicillin and gentamicin was effective in both patients. In contrast to previous reports, the present patients had a favorable outcome on completion of treatment and at one-year follow up.

Background: Patients with heart failure have scarce knowledge of their condition and frequently report poor quality of life. In spite of numerous studies showing improvement of survival and reduction in hospitalizations, several epidemiological studies showed that substantial proportion of patients are not receiving appropriate treatment. Intensive multidisciplinary approach can improve management of the patients with heart failure., Aim: To assess the efficacy of intensive patient management in heart failure clinic with respect to patient knowledge, pharmacological management, and quality of life., Methods: From outpatients, visiting the heart failure clinic in period form March 2002 to March 2003, we prospectively enrolled patients with heart failure due to systolic dysfunction. Patient knowledge about their condition was assessed by a knowledge questionnaire. Data on their clinical characteristics, diagnostic and pharmacological management were analyzed. Quality of life was assessed with Minnesota Living with Heart Failure Questionnaire (MLHFQ). Patients rated their quality of life and heath on a seven-category descriptive scale from 1 (best) to 7 (worst). Data are shown as mean (S.D.)., Results: In this period we treated 50 patients (33 men), aged 67 (12) years. Patient knowledge about their condition improved after two visits to heart failure clinic (4.8 (1.5) vs. 7.3 (1.4), p<0.001). More patients were treated with beta blockers (40% vs. 84%, p<0.001) while there was a positive trend for treatment with angiotensin-converting enzyme inhibitors (94% vs. 98%) and spironolactone (54% vs. 70%). Equivalent mean daily dose of enalapril (11.0 (11.0) mg to 16.7 (8.7) mg, p<0.001) and carvedilol (13.0 (11.5) mg to 32.1 (18.2) mg, p<0.001) increased. Out-patient management was associated with improvement of MLHFQ score (47 (18) vs. 34 (16)), NYHA class (2.9 (0.4) vs. 2.5 (0.7)), quality of life score (5.3 (1.1) vs. 3.7 (1.0)), and health score (5.1 (1.1) vs. 3.7 (1.1)) (p<0.001 for all)., Conclusions: Intensive management in heart failure clinic can be effective for translation of guidelines into clinical practice. It also improves patient's knowledge and quality of life as well as reduces the hospitalizations in heart failure patients.

Background: Non-pharmacological management is one of heart failure treatment cornerstones. Despite its importance several studies showed lack of clinical advising by medical staff as well as poor patient compliance to education and pharmacological treatment. Hospitalizations and symptoms of heart failure negatively influence patients' quality of life. In Slovenia there is a scarcity of non-pharmacological management and quality of life data in heart failure patients., Aims: We wanted to obtain data on heart failure patient's quality of life and their satisfaction with management of the condition in Slovenia., Methods: During 6 weeks, patients from one university and two community Slovenian hospitals were prospectively enrolled to the EuroHeart survey. We invited 415 patients (mean age 70.6+/-11.4 years, 53% men) to attend an interview 12 weeks after the discharge. Out of 415 eligible patients 25 (6%) died during follow up period and 187 (45%) attended the interview. Twenty-three percent of them were re-hospitalized. Vast majority (89%) of interviewed patients were aware of their heart condition but only 61% were satisfied with the explanation of their clinical condition given by medical staff. On average they were taking 6.3+/-2.3 drugs. General clinical advice (salt intake 65%, cholesterol or fat intake 63%) was more common than specific (daily weighing 35%, avoidance of non-steroidal anti-inflammatory drugs 17%). Patients reported high adherence as only 3% of given advice were neglected. Symptoms of heart failure were much less common at rest than during daily activity (breathlessness in 20% and 78%, fatigue in 18% and 81%, respectively). Psychological symptoms as anxiety (70%), depression (50%) and stress (48%) were common, as well as cognitive and sleep disturbances, both present in more than half of the patients., Conclusions: Patients with heart failure experienced restrictions in quality of life and psychological status. Non-pharmacological and pharmacological management and patient's satisfaction with medical care were below optimal. Educational strategies for medical staff and patients as well as organization of an out-patient setting in community hospitals are needed.

Background: Heart failure is a common and serious disease associated with poor prognosis. Despite the encouraging results of many clinical trials and the availability of published guidelines, epidemiological studies still show a gap between recommendations and clinical practice. There is a scarcity of data on changes in the management of patients hospitalized with heart failure., Aim: To investigate how evidence-based guidelines on heart failure are being followed in clinical practice in patients hospitalized for heart failure in a community hospital and whether there have been any changes during the period from 1997 to 2000., Methods: Two cohorts of patients with heart failure were studied. A retrospective analysis of medical charts from patients hospitalized for heart failure in 1997 was compared with a prospective registry (EuroHeart Failure survey) of patients hospitalized for heart failure during six consecutive weeks in April and May 2000. The data on diagnostic and therapeutic interventions during hospitalization in both periods were obtained from medical records., Results: We included 122 patients, aged 72 +/- 10 years, in 1997 and 126 patients, aged 73 +/- 12 years, in 2000. There was no significant difference in sex, NYHA class on admission, rate of recurrent hospitalizations, hospital stay (11.8 +/- 6.2 days vs. 12.8 +/- 9.6 days, respectively) or in-hospital mortality (17% vs. 16%). In the year 2000 significantly more patients had an echocardiography report than in 1997 (37% vs. 13%, p < 0.001), and they were significantly more often discharged with angiotensin-converting enzyme inhibitors (48% vs. 30%, p < 0.01) and beta-adrenergic blockers (9% vs. 2%, p = 0.04)., Conclusions: A considerable gap exists between evidence-based guidelines on heart failure and clinical practice in the management of patients with heart failure in a community hospital. There was some improvement between the two observed cohorts, but the recommendations were still not adequately implemented in the year 2000. Further improvement requires new hospital strategies for the management of heart failure and the creation of an outpatient setting.