Prognostic impact of systemic inflammatory diseases in elderly patients with congestive heart failure.

BACKGROUND AND AIMS: Inflammation is part of the pathophysiology of congestive heart failure (CHF). However, little is known about the impact of the presence of systemic inflammatory disease (SID), defined as inflammatory syndrome with constitutional symptoms and involvement of at least two organs as co-morbidity on the clinical course and prognosis of patients with CHF. METHODS AND RESULTS: This is an analysis of all 622 patients included in TIME-CHF. After an 18 months follow-up, outcomes of patients with and without SID were compared. Primary endpoint was all-cause hospitalization free survival. Secondary endpoints were overall survival and CHF hospitalization free survival. At baseline, 38 patients had history of SID (6.1%). These patients had higher N-terminal pro brain natriuretic peptide and worse renal function than patients without SID. SID was a risk factor for adverse outcome [primary endpoint: hazard ratio (HR) = 1.73 (95% confidence interval: 1.18-2.55, P = 0.005); survival: HR = 2.60 (1.49-4.55, P = 0.001); CHF hospitalization free survival: HR = 2.3 (1.45-3.65, P < 0.001)]. In multivariate models, SID remained the strongest independent risk factor for survival and CHF hospitalization free survival. CONCLUSION: In elderly patients with CHF, SID is independently accompanied with adverse outcome. Given the increasing prevalence of SID in the elderly population, these findings are clinically important for both risk stratification and patient management.

The role of ß-blockers in the management of hypertension: an Asian perspective.

Following publication of the National Institute of Clinical Excellence (NICE) Guidelines in 2006, the use of ß-blockers as first-line therapy in hypertension has been somewhat controversial. However, a recent reappraisal of the European Society of Hypertension guidelines highlights that these agents exhibit similar BP lowering efficacy to other classes of agents, prompting a re-examination of the utility of these agents in various patient populations. The authors felt that it is important to address this controversy and provide an Asian perspective on the place of ß-blockers in current clinical practice and the benefits of ß-blockade in selected patient populations. In addition to their use as a potential first-line therapy in uncomplicated hypertension, ß-blockers have a particular role in patients with hypertension and comorbidities such as heart failure or coronary artery disease, including those who had a myocardial infarction. One advantage which ß-blockers offer is the additional protective effects in patients with prior cardiovascular events. Some of the disadvantages attributed to ß-blockers appear more related to the older drugs in this class and further appraisal of the efficacy and safety profile of newer ß-blockers will lend support to the current guideline recommendations in Asian countries and encourage increased appropriate use of ß-blockade in current clinical practice within Asia.

Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF).

PURPOSE: We performed a survey on acute heart failure (AHF) in nine countries in four continents. We aimed to describe characteristics and management of AHF among various countries, to compare patients with de novo AHF versus patients with a pre-existing episode of AHF, and to describe subpopulations hospitalized in intensive care unit (ICU) versus cardiac care unit (CCU) versus ward. METHODS AND RESULTS: Data from 4,953 patients with AHF were collected via questionnaire from 666 hospitals. Clinical presentation included decompensated congestive HF (38.6%), pulmonary oedema (36.7%) and cardiogenic shock (11.7%). Patients with de novo episode of AHF (36.2%) were younger, had less comorbidities and lower blood pressure despite greater left ventricular ejection fraction (LVEF) and were more often admitted to ICU. Overall, intravenous (IV) diuretics were given in 89.7%, vasodilators in 41.1%, and inotropic agents (dobutamine, dopamine, adrenaline, noradrenaline and levosimendan) in 39% of cases. Overall hospital death rate was 12%, the majority due to cardiogenic shock (43%). More patients with de novo AHF (14.2%) than patients with a pre-existing episode of AHF (10.8%) (p = 0.0007) died. There was graded mortality in ICU, CCU and ward patients with mortality in ICU patients being the highest (17.8%) (p < 0.0001). CONCLUSIONS: Our data demonstrated the existence of different subgroups based on de novo or pre-existing episode(s) of AHF and the site of hospitalization. Recognition of these subgroups might improve management and outcome by defining specific therapeutic requirements.

Ethical considerations in cardiovascular prevention.

The fundamental values in medical ethics include the following aspects of professional conduct: (i) actions in the best interest of patients; (ii) first, do no harm; (iii) patients' right to refuse or choose treatments; (iv) fairness and equality in the distribution of healthcare resources; and (v) truthfulness and honesty (informed consent). These values have to be considered in all diagnostic steps and therapeutic decisions. They should also form the basis for discussions of potential conflicts of interest among patients, doctors, healthcare financers and politicians. Cardiovascular (CV) diseases represent the most frequent cause of death and a major healthcare problem in most regions of the world. CV prevention is therefore an important task both in individual subjects and as a means to improve health in the general population. While the merits of treatment in patients with established CV diseases, i.e. secondary prevention, are widely accepted and regarded as necessary, primary prevention with drugs in apparently healthy individuals at an increased risk of future CV events is not free of controversies. The different types of prevention envisaged also give rise to ethical questions: Should all the growing number of classical and newly recognised CV risk markers be a reason for intervention or should they be preferably used for calculating a total risk score? What are the compelling or only relative indications for anti-hypertensive, cholesterol-lowering, anti-diabetic or platelet-inhibiting drugs? Are pre-hypertension, pre-diabetes and marginally elevated cholesterol levels early diseases justifying drug treatment, regardless of the possibility that some prophylactic interventions may be associated with adverse events? Discussions also often arise concerning the role of age, gender and of non-CV co-morbidities for decisions about long-term prevention with drugs. How reliable and applicable are 'evidence-based' guidelines derived from trials in highly selected patients and healthy subjects for the general population seen in everyday practice? Increasingly, the economic aspects of long-term prevention and problems of a fair allocation of limited healthcare resources are also important issues giving rise to contrasting views among patients, doctors, insurance providers and politicians. What are the priorities and who should decide? Ethical considerations relating to the above questions in CV prevention are discussed in this article.

Amiodarone inhibits arterial thrombus formation and tissue factor translation.

BACKGROUND: In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. METHODS AND RESULTS: Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-alpha and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. Metabolic labeling confirmed that amiodarone inhibited TF protein translation. CONCLUSIONS: Amiodarone impairs thrombus formation in vivo; in line with this, it inhibits TF protein expression and surface activity in human vascular cells. These pleiotropic actions occur within the range of amiodarone concentrations measured in patients, and thus may account at least in part for its beneficial effects in patients with coronary artery disease.

[Heart failure in men and women: important differences in the diagnostic workup and treatment]. / Hartfalen bij mannen en vrouwen: belangrijke verschillen in diagnostiek en behandeling.

OBJECTIVE: To determine gender differences in diagnostic workup and treatment of patients with heart failure. DESIGN: Retrospective. METHOD: The data of 8914 patients (of whom 4166 women; 47%) with confirmed heart failure, who participated in the Euro Heart Survey on Heart Failure (EHS-HF) were analysed. RESULTS: On average, the women in the study were older than the men (75 versus 68 years) and less often suffered from a coronary heart disease (56 versus 66%). Women were more likely to have hypertension (59 versus 49%), diabetes mellitus (29 versus 26%), or valvular heart disease (42 versus 36%). Fewer women had an ultrasonographic evaluation of ventricular function (59 versus 74%) and, among those investigated, fewer had left ventricular systolic dysfunction (44 versus 72%). These observed results remained stable after adjustment for age and other possible confounding variables. Medication with a documented positive impact on survival, i.e. angiotensin converting enzyme (ACE) inhibitors, beta-blocking drugs and the diuretic spironolactone, was prescribed less often to women than men. Women, however, received symptomatic medication such as other diuretics and digoxin more often than men. CONCLUSION: Men and women with heart failure differed with respect to a number of relevant clinical characteristics. Clinicians should take good note of this and take measures to prevent differences in patient care.

Management of patients with heart failure in clinical practice: differences between men and women.

OBJECTIVES: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences. METHODS: A total of 8914 (out of 10 701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses. RESULTS: Women were older (74.7 vs 68.3 years, p<0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and beta-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women. CONCLUSIONS: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them.

[The clinical examination in cardiology]. / Die klinische Untersuchung von Herz und Kreislauf.

The main manifestations of cardiac diseases are dyspnea, chest pain, palpitations, giddiness and syncope. A careful evaluation of subjective symptoms during history taking allows a rapid identification of an ischaemic heart disease, heart failure or cardiac arrhythmias. The additional clinical findings during bedside examination by inspection of the jugular veins, palpation of cardiac impulses and auscultation of heart sounds and murmurs are often sufficient to diagnose most of the frequent underlying disorders, such as valvular diseases, heart failure or pulmonary hypertension. The clinical assessment remains essential to select the most appropriate additional tests, such as echocardiography, scintigraphy, computer tomography or coronarography. Systematic teaching of the clinical skills should remain a central element in the formation of medical students and clinical fellows.

Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey.

AIMS: Due to a lack of clinical trials, scientific evidence regarding the management of patients with chronic heart failure and preserved left ventricular function (PLVF) is scarce. The EuroHeart Failure Survey provided information on the characteristics, treatment and outcomes of patients with PLVF as compared to patients with a left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: We performed a secondary analysis using data from the EuroHeart Failure Survey, only including patients with a measurement of LV function (n = 6806). We selected two groups: patients with LVSD (54%) and patients with a PLVF (46%). Patients with a PLVF were, on average, 4 years older and more often women (55% vs. 29%, respectively, p < 0.001) as compared to LVSD patients, and were more likely to have hypertension (59% vs. 50%, p < 0.001) and atrial fibrillation (25% vs. 23%, p = 0.01). PLVF patients received less cardiovascular medication compared to PLVF patients, with the exception of calcium antagonists. Multivariate analysis revealed that LVSD was an independent predictor for mortality, while no differences in treatment effect on mortality between the two groups was observed. A sensitivity analysis, using different thresholds to separate patients with and without LVSD revealed comparable findings. CONCLUSIONS: In the EuroHeart Failure Survey, a high percentage of heart failure patients had PLVF. Although major clinical differences were seen between the groups, morbidity and mortality was high in both groups.

[Recurrent pneumonia--case report and review of the literature]. / Rezidivierende Pneumonien.

We report the case of a 70-year old man with recurrent pneumonia due to aspiration from an otherwise asymptomatic small oesophageal diverticula in the mid-oesophageal region. The diagnosis was finally established by videofluoroscopy of the oesophagus after repeated bronchoscopies and CT scans in the proceeding months. After thoracoscopic removal of the diverticula the patient remained free of disease. Oesophageal diverticula as a rare cause of repeated pneumonias should be kept in mind, even though there are no symptoms of gastro-oesophageal disease.

[Depression, stress and coronary heart disease--epidemiology, prognosis and therapeutic sequelae]. / Depression, Stress und koronare Herzkrankheit--Epidemiologie, Prognose und therapeutische Folgen.

Depression and coronary heart disease may be related in several ways: (1) There is epidemiological evidence that high levels of depressive symptoms in male and female patients are associated with an increased risk of myocardial infarction and a higher mortality following an acute cardiac event. Furthermore, patients developing depression after myocardial infarction have more complications, including cardiac arrhythmias. (2) In patients with a chronic coronary heart disease depression also results in a worse cardiac functional status with more frequent and severe chest pain, more physical limitation, less treatment satisfaction and a lower perceived quality of life. Non-compliance with drug therapy is also more prevalent in depressed cardiac patients. (3) The possible pathophysiological mechanisms leading to more frequent complications of coronary heart disease in patients with depression are not fully explained, but could partly be due to higher sympatho-adrenergic stimulation and increased platelet aggregation. Some anti-depressant medications, on the other hand, may also cause cardiac symptoms and increase the risk in patients with coronary heart disease. The use of tricyclic antidepressants has been shown to result in a higher relative risk of myocardial infarction even after adjustment for other cardiovascular risk factors. Tricyclic anti-depressants may have direct cardiac effects, such as QT-prolongation with ventricular arrhythmias, orthostatic hypotension and, less frequently, myocardial dysfunction. In contrast such associations were not found with the newer serotonin re-uptake inhibitors. What are the practical consequences of the observed association between coronary artery disease and depression? First of all depression should better and earlier be recognised also by non-psychiatrists and treatment indications be discussed with specialists. At present, however, there is no clear evidence that ant-depressant drugs or psychotherapy will reduce the risk of myocardial infarction and improve prognosis. Further data are urgently needed to clarify the role of therapeutic interventions. Therefore, a closer research co-operation between cardiologists and psychiatrists should be promoted in future.

Clinical applications of B-type natriuretic peptide (BNP) testing.

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the 'normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100 pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical context.

The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis.

BACKGROUND: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. METHODS: The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. RESULTS: A total of 46788 deaths and discharges were screened from which 11327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10434 (13.5%) patients died between admission and 12 weeks follow-up. CONCLUSIONS: Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively.

The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.

BACKGROUND: National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. METHODS: The survey screened discharge summaries of 11304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. RESULTS: Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. CONCLUSION: Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

Management of heart failure in primary care (the IMPROVEMENT of Heart Failure Programme): an international survey.

BACKGROUND: Heart failure is a prevalent condition that is generally treated in primary care. The aim of this study was to assess how primary-care physicians think that heart failure should be managed, how they implement their knowledge, and whether differences exist in practice between countries. METHODS: The survey was undertaken in 15 countries that had membership of the European Society of Cardiology (ESC) between Sept 1, 1999, and May 31, 2000. Primary-care physicians' knowledge and perceptions about the management of heart failure were assessed with a perception survey and how a representative sample of patients was managed with an actual practice survey. FINDINGS: 1363 physicians provided data for 11062 patients, of whom 54% were older than 70 years and 45% were women. 82% of patients had had an echocardiogram but only 51% of these showed left ventricular systolic dysfunction. Ischaemic heart disease, hypertension, diabetes mellitus, atrial fibrillation, and major valve disease were all common. Physicians gave roughly equal priority to improvement of symptoms and prognosis. Most were aware of the benefits of ACE inhibitors and beta blockers. 60% of patients were prescribed ACE inhibitors, 34% beta blockers but only 20% received these drugs in combination. Doses given were about 50% of targets suggested in the ESC guidelines. If systolic dysfunction was documented, ACE inhibitors were more likely and beta blockers less likely to be prescribed than when there was no evidence of systolic dysfunction. INTERPRETATION: Results from this survey suggest that most patients with heart failure are appropriately investigated, although this finding might be as a result of high rates of hospital admissions. However, treatment seems to be less than optimum, and there are substantial variations in practice between countries. The inconsistencies between physicians' knowledge and the treatment that they deliver suggests that improved organisation of care for heart failure is required.

One-year mortality among unselected outpatients with heart failure.

OBJECTIVE: To estimate 1-year mortality and prognostic factors in unselected outpatients with heart failure, and to compare the observed mortality with the estimates of the primary care physicians. METHODS AND RESULTS: Four hundred and eleven consecutive patients with heart failure New York Heart Association (NYHA) class II-IV (mean population age 75 years, 56% males) were enrolled in 71 primary care offices throughout Switzerland. During a mean follow-up period of 1.4 years, 68 patients had died. One-year total mortality was 12.6% compared to 4.3% in the underlying Swiss population (standardized mortality ratio 3.0). Among patients with heart failure NYHA II, III and IV, mortality was 7.1%, 15.0% and 28.0%, respectively. In multivariate Cox regression, statistically significant (P<0.05) predictors of mortality were NYHA class (NYHA III: risk ratio [RR]=1.6; NYHA IV: RR=2.2), recent hospital stay for heart disease (RR=2.3), creatinine>120 micromol.l(-1) (RR=1.8) systolic blood pressure<100 mmHg (RR=2.4), heart rate>100 min(-1) (RR=2.7), age (per 10 years, RR=1.6) and female gender (RR=0.49). Among patients with reduced left ventricular ejection fraction, 1-year mortality was 14.3%, and predictors were similar except that female gender was no longer associated with reduced mortality. Primary care physicians significantly overestimated 1-year mortality (estimated mortality 25.9% vs observed mortality 12.6%,P =0.001). CONCLUSIONS: Unselected outpatients with heart failure have a poor prognosis, particularly those with advanced heart failure and a recent hospital stay for heart disease. Primary care physicians are aware of the high mortality of this growing patient population.