Evaluation of the functional status questionnaire in heart failure: a sub-study of the second cardiac insufficiency bisoprolol survival study (CIBIS-II).

AIMS: We evaluated a generic quality of life (QoL) Functional Status Questionnaire (FSQ), in patients with chronic heart failure (CHF). The FSQ assesses the 3 main dimensions of QoL: physical functioning, mental health and social role. It also includes 6 single item questions about: work status, frequency of social interactions, satisfaction with sexual relationships, days in bed, days with restricted activity and overall satisfaction with health status. The FSQ was compared to the Minnesota Living with Heart Failure questionnaire (MLwHF). METHODS AND RESULTS: The FSQ was evaluated in a substudy (n = 340) of the second Cardiac Insufficiency Bisoprolol Survival study (CIBIS-II), a placebo-controlled mortality trial. 265 patients (75%) patients completed both questionnaires at 6 months of follow-up. Both questionnaires indicated substantially impaired QoL. The FSQ demonstrated high internal consistency (Cronbach's α > 0.7 for all items except "social activity" = 0.66) and construct and concurrent validity. After 6 months, the only item on either questionnaire to show a difference between the placebo- and bisoprolol-treatment groups was the single item FSQ question about "days in bed" (p = 0.018 in favour of bisoprolol). CONCLUSIONS: The FSQ performed well in this study, provided additional information to the MLwHF questionnaire and allowed interesting comparisons with other chronic medical conditions. The FSQ may be a useful general QoL instrument for studies in CHF.

Clinical review: practical recommendations on the management of perioperative heart failure in cardiac surgery.

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.

Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II.

AIMS: International guidelines are frequently not implemented in the elderly population with heart failure (HF). This study determined the management of octogenarians with HF enrolled in Euro Heart Failure Survey II (EHFS II) (2004-05). METHODS AND RESULTS: We compared the clinical profile, 12 month outcomes, and management modalities between 741 octogenarians (median age 83.7 years) and 2836 younger patients (median age 68.4 years) hospitalized for acute/decompensated HF. Management modalities were also compared with those observed in EHFS I (2000-01). Female gender, new onset HF (de novo), hypertension, atrial fibrillation, co-morbidities, disabilities, and low quality of life were more common in the elderly (all P < 0.001). Mortality rates during hospital stay and during 12 months after discharge were increased in octogenarians (10.7 vs. 5.6% and 28.4 vs. 18.5%, P < 0.001). Underuse and underdosage of medications recommended for HF were observed in the elderly. However, a significant improvement was observed when compared with EHFS I both in the overall HF octogenarian population and in the subgroup with ejection fraction < or =45% for prescription rates of ACE-I/ARBs, beta-blockers, and aldosterone antagonists at discharge (82 vs. 71%; 56 vs. 29%; 54 vs. 18.5%, respectively, all P < 0.01), as well as for recommended combinations and dosage. Prescription rates remained stable for 12 months after discharge in survivors. CONCLUSION: Our study confirms that the contemporary management of very elderly patients with HF remains suboptimal but that the situation is improving.

Presentation and outcome of critically ill medical and cardiac-surgery patients with acute heart failure.

BACKGROUND: The aim of the study was to investigate presentation and outcome of consecutive acute heart failure (AHF) patients admitted to the intensive care unit (ICU) including also patients undergoing cardiac surgery, thereby providing comparative information on all critically ill AHF subgroups. METHODS: The prospective observational study with 6-month follow up was performed in the cardio-thoracic and the medical ICU of a university hospital. AHF was defined according to the European Society of Cardiology guidelines. Univariate Cox regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for risk factors. RESULTS: A total of 192 patients fulfilled the AHF criteria, of whom 86 and 24 underwent elective and emergency cardiac surgery, respectively. The remaining 82 medical patients had no surgical interventions. Cardiogenic shock was diagnosed in 32% of all patients and was the most common AHF presentation. Medical, elective surgery and emergency surgery AHF patients had a mortality at 30 days of 31%, 4.7% and 22% (<0.05) and at 180 days of 42%, 6.1% and 23% (<0.05), respectively. While the presence of cardiogenic shock was associated with a poor outcome (HR 1.8, CI 1.0-3.0; p=0.04), post-operative cardiac stunning had a good prognosis (HR 0.06, CI 0.01-0.47; p<0.01). Mortality worsened when infections (HR 2.8, CI 1.5-5.7; p<0.01) or renal dysfunction (HR 4.4, CI 2.2-8.4, p<0.01) were present on ICU admission. CONCLUSIONS: Medical patients, patients undergoing elective cardiac surgery and patients requiring emergency cardiac surgery are three distinct AHF-subpopulations. Co-morbidities and surgical treatment options affect long-term outcome.

New-onset atrial fibrillation is an independent predictor of in-hospital mortality in hospitalized heart failure patients: results of the EuroHeart Failure Survey.

AIMS: The prognostic significance of atrial fibrillation (AF) in hospitalized patients with heart failure (HF) remains poorly understood. To evaluate in what way AF and its different modes of presentation affect the in-hospital mortality in patients admitted with HF. METHODS AND RESULTS: The EuroHeart Failure Survey was conducted to ascertain how hospitalized HF patients are managed in Europe. The survey enrolled patients over a 6-week period in 115 hospitals from 24 countries. For this analysis, patients were categorized into three groups according to the type of AF, previous AF (patients known to have had AF prior to admission), new-onset AF (no previous AF with AF diagnosed during hospitalization), and no AF (no previous AF and no AF during hospitalization). Clinical variables, duration of hospitalization, and in-hospital survival status were assessed and compared among groups. Of the 10 701 patients included in the survey; 6027 (57%) had no AF, 3673 (34%) had previous AF, and 1001 (9%) had new-onset AF. Patients with new-onset AF had a longer stay in the intensive care unit (ICU) when compared with previous AF and no AF patients (mean 2.6 +/- 5.3, 1.2 +/- 3.5, and 1.5 +/- 4.1 days, respectively; P < 0.001). In-hospital mortality was higher among patients with new-onset AF when compared with previous AF or no AF patients (12, 7, and 7% respectively; P < 0.001). After adjusting for multiple clinical variables, new-onset AF (not previous AF) was an independent predictor of in-hospital mortality (odds ratio 1.53, 95% CI 1.1-2.0). CONCLUSION: In hospitalized patients with HF, new-onset AF is an independent predictor of in-hospital mortality and a longer ICU and hospital stay.

Amiodarone alters late endosomes and inhibits SARS coronavirus infection at a post-endosomal level.

Amiodarone interferes with the endocytic pathway, inhibits proteolysis, and causes the formation of vacuoles, but uptake and intracellular distribution of the drug, origin of vacuoles, and functional consequences of amiodarone accumulation remain unclear. Our objective was to study amiodarone uptake, clarify the origin of vacuoles, and investigate the effect of amiodarone on the life cycle of the coronavirus responsible for the Severe Acute Respiratory Syndrome (SARS), which, to enter cells, relies on the proteolytic cleavage of a viral spike protein by the endosomal proteinase cathepsin L. Using alveolar macrophages, we studied uptake of (125)I-amiodarone and (125)I-B2, an analog lacking the lateral group diethylamino-beta-ethoxy, and analyzed the effects of amiodarone on the distribution of endosomal markers and on the uptake of an acidotropic dye. Furthermore, using Vero cells, we tested the impact of amiodarone on the in vitro spreading of the SARS coronavirus. We found that (1) amiodarone associates with different cell membranes and accumulates in acidic organelles; (2) the diethylamino-beta-ethoxy group is an important determinant of uptake; (3) vacuoles forming upon exposure to amiodarone are enlarged late endosomes; (4) amiodarone inhibits the spreading in vitro of SARS coronavirus; and (5) trypsin cleavage of the viral spike protein before infection, which permits virus entry through the plasma membrane, does not impair amiodarone antiviral activity. We conclude that amiodarone alters late compartments of the endocytic pathway and inhibits SARS coronavirus infection by acting after the transit of the virus through endosomes.

Practical recommendations for prehospital and early in-hospital management of patients presenting with acute heart failure syndromes.

Guideline recommendations for the prehospital and early in-hospital (first 6-12 hrs after presentation) management of acute heart failure syndromes are lacking. The American College of Cardiology/American Heart Association and European Society of Cardiology guidelines direct the management of these acute heart failure patients, but specific consensus on early management has not been published, primarily because few early management trials have been conducted. This article summarizes practical recommendations for the prehospital and early management of patients with acute heart failure syndromes; the recommendations were developed from a meeting of experts in cardiology, emergency medicine, and intensive care medicine from Europe and the United States. The recommendations are based on a unique clinical classification system considering the initial systolic blood pressure and other symptoms: 1) dyspnea and/or congestion with systolic blood pressure >140 mm Hg; 2) dyspnea and/or congestion with systolic blood pressure 100-140 mm Hg; 3) dyspnea and/or congestion with systolic blood pressure <100 mm Hg; 4) dyspnea and/or congestion with signs of acute coronary syndrome; and 5) isolated right ventricular failure. These practical recommendations are not intended to replace existing guidelines. Rather, they are meant to serve as a tool to facilitate guideline implementation where data are available and to provide suggested treatment approaches where formal guidelines and definitive evidence are lacking.

Gender related differences in patients presenting with acute heart failure. Results from EuroHeart Failure Survey II.

AIMS: This analysis evaluates the gender differences in patients hospitalised for acute heart failure (AHF) in the EuroHeart Failure Survey II (EHFS). RESULTS: Of the 3580 patients included in EHFS II, 1384 (39%) were women, mean age 73 years. 2196 (61%) were men, mean age 68 years. Women more frequently had new-onset AHF, hypertension and valvular disease and less frequently coronary heart disease or dilated cardiomyopathy compared with men. Smoking, chronic obstructive pulmonary disease, peripheral arterial disease and renal failure were less common, but diabetes and anaemia significantly more frequent in women. Atrial fibrillation and preserved left ventricular function were more common in women. Men were more often non-compliant with medication. After adjustment for indications and age, there were no significant gender differences in prescription of HF medication. All-cause readmission rate during the one-year follow-up was lower in women. However, the proportion of HF hospitalisation and one-year mortality after discharge (20%) were similar in both genders. CONCLUSION: Women frequently present with new-onset AHF. A significant gender difference exists in aetiology, ventricular function and co-morbidities. Women's use of HF medication has improved. These findings emphasize the importance of individualised management and need for more comprehensive recruitment of women in clinical trials.

Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Nonpharmacologic measures and drug compliance in patients with heart failure: data from the EuroHeart Failure Survey.

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.

International variations in the treatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey.

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.

Recall of lifestyle advice in patients recently hospitalised with heart failure: a EuroHeart Failure Survey analysis.

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.

Prevalence of ECG abnormalities in an international survey of patients with suspected or confirmed heart failure at death or discharge.

BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS: The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115 hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934 had cardiac imaging tests. The utility of the ECG was assessed for excluding or diagnosing major structural heart disease (MSHD) or major left ventricular systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%, respectively, if the ECG was entirely normal. However, <2% of patients had a normal ECG. No single ECG characteristic identified a probability <25% of MSHD or <20% of MLVSD. Patients with QRS width >or=120 ms or anterior pathological Q-waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models suggested that electrocardiographic criteria alone were not accurate for the diagnosis or exclusion of important heart disease in this population. However, 2468 patients (42%) had an electrocardiographic finding that should be used to guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with suspected HF but has limited diagnostic value in this setting. The ECG has an important role in guiding therapy.

Synthesis and cytotoxicity properties of amiodarone analogues.

Amiodarone (AMI) is a potent antiarrhythmic agent; however, its clinical use is limited due to numerous side effects. In order to investigate the structure--cytotoxicity relationship, AMI analogues were synthesized, and then, using rabbit alveolar macrophages, were tested for viability and for the ability to interfere with the degradation of surfactant protein A (SP-A) and with the accumulation of an acidotropic dye. Our data revealed that modification of the diethylamino-beta-ethoxy group of the AMI molecule may affect viability, the ability to degrade SP-A and vacuolation differently. In particular, PIPAM (2d), an analogue with a piperidyl moiety, acts toward the cells in a similar manner to AMI, but is less toxic. Thus, it would be possible to reduce the cytotoxicity of AMI by modifying its chemical structure.

Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III.

BACKGROUND: In patients with chronic heart failure (CHF), a beta-blocker is generally added to a regimen containing an angiotensin-converting-enzyme (ACE) inhibitor. It is unknown whether beta-blockade as initial therapy may be as useful. METHODS AND RESULTS: We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction < or =35%, who were not receiving ACE inhibitor, beta-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol (target dose 10 mg QD; n=505) or enalapril (target dose 10 mg BID; n=505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95% confidence interval (CI) for the absolute between-group difference was <5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment (absolute difference -1.6%, 95% CI -7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment (absolute difference -0.7%, 95% CI -6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment (HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized (HR 0.95; 95% CI 0.76 to 1.19). CONCLUSIONS: Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril.

Body mass index in acute heart failure: association with clinical profile, therapeutic management and in-hospital outcome.

BACKGROUND: Increased body mass index (BMI) is a risk factor for heart failure, but evidence regarding BMI in acute heart failure (AHF) remains inconclusive. We sought to compare the clinical profile, treatment and in-hospital outcome across BMI categories in a large international AHF cohort. METHODS: The Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF) is a retrospective survey on 4953 patients admitted for AHF from nine countries in Europe, Latin America, and Australia. Patients with unavailable BMI data or BMI <18.5 kg/m(2) were excluded. Clinical data and in-hospital mortality were compared among the following BMI categories: 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight) and ≥30 kg/m(2) (obese). RESULTS: Overweight/obese patients represented 75.7% of patients and had worse New York Heart Association class (P < 0.001) and higher admission systolic blood pressure (P < 0.001). The prevalence of comorbidities increased in parallel with BMI and included arterial hypertension, diabetes mellitus, dyslipidaemia (all P < 0.001), chronic obstructive pulmonary disease (P = 0.041) and chronic kidney disease (P = 0.056). Use of guideline-recommended medications also increased in parallel with BMI (angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, P < 0.001; ß-blockers P < 0.001; mineralocorticoid receptors antagonist, P = 0.002). In-hospital mortality had a U-shaped relationship with BMI, with overweight patients having significantly lower rate (log-rank P = 0.027); this relationship vanished after adjustment for confounders. CONCLUSIONS: Overweight/obese patients represented the vast majority of AHF cases, had a higher prevalence of non-cardiovascular comorbidities and were more likely to receive guideline-recommended medications. The U-shaped relationship between in-hospital mortality and BMI may be explained by differences in clinical profile and treatment and not by an effect of body composition per se.

European experience on the practical use of levosimendan in patients with acute heart failure syndromes.

The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and post-interventional myocardial dysfunction (stunning) indicate that the inotropic and vasodilating actions of levosimendan may be of value in a wider range of indications. Dose recommendations, combination with other drugs, and potential side effects are discussed in this overview.

Acute heart failure: clinical presentation, one-year mortality and prognostic factors.

AIMS: Acute heart failure (HF) is a common but ill-defined clinical entity. We describe patients hospitalised with acute HF in regard of clinical presentation, mortality, and risk factors for an unfavourable outcome. METHODS AND RESULTS: We conducted a prospective study including 312 consecutive patients from two European centers hospitalised with acute HF, defined as new onset or worsening of symptoms and signs of HF within 7 days. The mean age was 73 years and 56% were men. Twenty-eight percent had de-novo acute HF and 72% a decompensation of chronic HF. Coronary heart disease (CHD) was the most frequent underlying heart disease, elevated blood pressure >150 mmHg and acute ischemia being the most important triggers. Four percent of the patients had cardiogenic shock, 13% presented with pulmonary edema. LV-EF was <35%, 35-50% and >50% in 35%, 32% and 33% of the patients, respectively. ICU-treatment was necessary in 39% of the patients. Thirty-day mortality (11%) was increased in the presence of shock or elevated troponin T levels. Twelve-month all-cause mortality (29%) increased in the presence of shock, left ventricular dysfunction, renal insufficiency, CHD, and age. CONCLUSIONS: This prospective study shows that despite modern treatment, morbidity and mortality of patients hospitalised with acute HF remain high.

Identification and quantitation of novel metabolites of amiodarone in plasma of treated patients.

In mammals, mono-N-desethylamiodarone (MDEA) is the only known metabolite of amiodarone. Our previous experiments demonstrated that in vitro MDEA may be hydroxylated, N-dealkylated, and deaminated. In this report, we investigated the concentration of these microsomal metabolites in the plasma of patients receiving amiodarone. The presence of the hydroxy-amiodarone and deiodinated amiodarone was also additionally investigated. A high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry (HPLC-APCI-MS/MS) quantitative assay using morpholine-amiodarone as internal standard was developed for measuring these metabolites in the range of 3-250 ng ml(-1). In the concentration ranges 5-50 and 50-250 ng ml(-1), the coefficients of variation of the measurements were less than 14 and 7%, respectively. The concentrations of investigated compounds in plasma of patients (n=14) receiving amiodarone (0.2 g day(-1), orally for >2 months) varied inter-individually and were 140.0+/-85.2, 39.1+/-20.8, and 26.2+/-15.2 ng ml(-1) for 3'OH-mono-N-desethylamiodarone, di-N-desethylamiodarone, and deaminated amiodarone, respectively. The concentrations of MDEA and amiodarone in these samples were 970+/-347 and 11163+/-435 ng ml(-1), respectively. In contrast, the studied compounds were not detectable in plasma samples from eight patients receiving amiodarone intravenously. Qualitatively, in the plasma of patients receiving amiodarone orally, hydroxylated amiodarone was also positively detected by assaying the [M+H](+) ions at m/z 662, but the deiodo-metabolites of amiodarone were not detected using mass spectrometry. Thus, in humans, amiodarone and MDEA were biotransformed by dealkylation, hydroxylation, and deamination.

[Cardiovascular drugs in aged and multimorbid patients]. / CME. Kardiovaskuläre Medikamente bei alten und multimorbiden Patienten.

Cardiovascular diseases, such as arterial hypertension, heart failure, coronary artery disease, peripheral circulatory problems and atrial fibrillation are increasingly present in aged patients. Comorbidities, mainly diabetes, renal dysfunction, chronic bronchitis and degenerative joint diseases, are also frequent and need additional drug treatment. The usual polypharmacy often causes side effects due to overdosage and/or drug interactions. The main difficulty in choosing the proper therapeutic regimen consists in the lack of suitable dosing guidelines with adapted therapeutic targets for the older multimorbid population, usually not represented in the large controlled trials forming the basis of general recommendations. European guidelines for hypertension and heart failure are discussed as examples.