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Presents a letter to the editor in response to an article which described a case of fulminant ulcerative colitis during pregnancy with complicating intra-abdominal sepsis and abscess.

Study objectives: To determine the BP response to the Valsalva maneuver (VM) at baseline and after changes in therapy and to compare this response to the invasively measured pulmonary capillary wedge pressure (PCWP). Design: Comparison of the BP response to the VM with invasively measured PCWP. In a subset of patients, direct PCWP and pulse amplitude ratio (PAR) measurements were repeated (mean ± SD) 3.2 ± 4.5 months later after adjusting the therapy. Setting: Tertiary-care center. Patients: Forty-two stable patients (8 women; mean age, 58 ± 13 years) undergoing right heart catheterization who were in sinus rhythm. Measurements: PAR calculated between the end and the beginning of the VM using the last two beats and the first three beats of the straining phase and simultaneous measurement of PCWP. Results: There was a highly significant correlation between the invasively measured PCWP (range, 2 to 32 mm Hg) and the PAR (range, 0.28 to 1.15; R² = 0.75; p < 0.001). In addition, changes of PCWP during follow-up (-16 to 13 mm Hg) were well-correlated (R² = 0.93; p < 0.001; n = 11) with changes in PAR (-0.44 to 0.47). The administration of medication (eg, β-blockers, amiodarone, angiotensin-converting enzyme inhibitor, and digoxin) did not influence the results. Conclusions: PCWP and changes during therapy can be estimated noninvasively by measuring the PAR during the VM with acceptable accuracy in stable patients with cardiac conditions. Thus, this method may be a useful tool in detecting an elevated PCWP and hemodynamic response to therapy. [ABSTRACT FROM AUTHOR]

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; β-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. [ABSTRACT FROM AUTHOR]

Abstract: Aim and methods: Gender-related differences in clinical phenotype, in-hospital management and prognosis of acute heart failure (AHF) patients have been previously reported in European and US registries. The ALARM-HF survey is the first to include a cohort of 4953 patients hospitalized for AHF in 666 hospitals in 6 European countries, Mexico and Australia. Results: Women accounted for 37% of the study population, were older and had higher rates of de novo heart failure (45% vs 36%, p<0.001) than men. An acute coronary syndrome (ACS) was the predominant precipitating factor in both genders, but to a lesser extent in females (30% vs 42%, p<0.001). Between genders comparison showed higher incidence of atrial fibrillation, valvular heart disease, diabetes, obesity, anemia and depression in women (p<0.05). Similarly, women had higher left ventricular ejection fraction (LVEF) on admission (42±15% vs 36±13%, p<0.001) and systolic blood pressure (135±40mmHg vs 131±39mmHg, p=0.001) than men. On the other hand, men had more often coronary artery disease, renal failure and chronic obstructive pulmonary disease (p<0.05). Importantly, in-hospital mortality was similar in both genders (11.1% in females vs 10.5% in males, p=0.475), and its common predictors were: systolic blood pressure at admission, creatinine>1.5mg/dL and diabetes. Furthermore, recent ACS, valvular heart disease and dementia contributed to prognosis in women, while LVEF, hypertension and anemia were independent predictors in men. Conclusion: Among patients with AHF, there are significant differences in co-morbidities, precipitating factors and predictors of in-hospital mortality between genders. Nevertheless, in-hospital mortality remains similar between genders. [Copyright &y& Elsevier]

Aims Specific causes and modes of death (COD and MOD) of patients with heart failure (HF) are not well described, particularly in those with preserved ejection fraction >45% (HFPEF) and at old age. Thus, using the database of the TIME-CHF study, patients with HFPEF were compared with those with reduced ejection fraction ≤45% (HFREF), and patients ≥75 with those 60–74 years of age to identify MOD and COD, predictors of death, and event rates before death as compared with survivors. Methods and results During the 18-month follow-up, 132/622 patients (21%) died, with similar rates in patients with HFPEF and HFREF and a trend to higher rates in patients aged ≥75 years (24% vs. 17%, P = 0.06). COD and MOD (ACME system) were not different in the age groups. COD was more often non-cardiovascular in HFPEF patients than in HFREF patients (33% vs. 16%, P < 0.05) and cardiac MOD were more frequent in HFREF patients (75% vs. 56%, P < 0.05), mainly due to more sudden deaths (25% vs. 7%, P < 0.05). Patients who died experienced a median of four adverse events (interquartile range 1–7) and one (0–1) hospitalization within 60 days prior to death compared with 0.7 (0.4–1.4) and 0.1 (0.0–0.2) during a randomly selected 60 days in survivors (all P < 0.0001). Conclusion Despite similar 18-month mortality in patients with HFREF and those with HFPEF, important differences in COD and MOD were found which were not observed between the two age groups. A high rate of adverse events and hospitalizations preceded death. These observations may be relevant for the management of HF patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective/methods: ALARM-HF was an in-hospital observational survey that included 4953 patients admitted for acute heart failure (AHF) in six European countries, Mexico and Australia. This article is a secondary analysis of the survey which evaluates differences in clinical phenotype, treatment regimens and in-hospital outcomes in AHF patients with diabetes mellitus (DM) compared to non-diabetics. The data were collected retrospectively by the investigators, and the diagnosis of AHF (reported at discharge) was based on the definition and classification of ESC guidelines, while the diagnosis of DM was based on medical record (past medical and medication history). Results: This sub-analysis demonstrates substantial differences regarding both baseline features and in-hospital outcome among diabetic and non-diabetic AHF patients. Diabetic patients (n=2229, 45%) presented more frequently with acute pulmonary edema (p<0.001) than non-diabetics, had more often acute coronary syndrome (p<0.001) as precipitating factors of AHF, and multiple comorbidities such as renal dysfunction (p<0.001), arterial hypertension (p<0.001), anemia (p<0.001) and peripheral vascular disease (p<0.001). All-cause in-hospital mortality of diabetics was higher compared to non-diabetics (11.7% vs 9.8%, p=0.01). The multivariate analysis revealed that older age (p=0.032), systolic blood pressure <100mm Hg (p<0.001), acute coronary syndrome and non compliance as precipitating factors (p=0.05 and p=0.005, respectively), history of arterial hypertension (p=0.022), LVEF<50% (p<0.001), serum creatinine >1.5mg/dl (p=0.029), absence of life saving therapies such as ACE inhibitors/ARBs (p<0.001) and beta-blockers (p=0.014) at admission, as well as absence of interventional treatment by PCI (p<0.001), were independently associated with adverse in-hospital outcome. Conclusion: Diabetics with AHF have higher in-hospital mortality than non-diabetics despite their intensive treatment regimens (regarding care for HF and ACS), possibly due to underlying ischemic heart disease and the presence of multiple comorbidities. [Copyright &y& Elsevier]

Aims Loop diuretics are recommended to treat congestion in heart failure (HF), despite limited quality evidence. High-dose (HD) loop diuretics seem to worsen outcomes in chronic HF, though; data for acute HF are scarce, with equivocal results. Methods and results The ALARM-HF study recorded in-hospital HF therapy in 4953 patients from nine countries. A post-hoc analysis was performed to determine if there was an interaction between intravenous (iv) bolus diuretic dosing and outcomes. Patients were classified as receiving high- or low-dose iv furosemide if their total initial 24 h dose was above (HD) or below [low dose (LD)] 1 mg/kg. Propensity scoring, matching an extensive list of variables, was performed. High-dose and LD patients were matched by propensity scores and outcomes determined. We identified 2460 LD and 848 HD patients, with overall in-hospital mortality of 9 and 13% (P= 0.002), respectively. After propensity matching, there were 506 patients in each subgroup, with the matched LD and HD cohorts having similar mortality (13 vs. 15%; P= 0.4). We further investigated in which subgroups of patients HD diuretics influenced mortality. Before matching, HD diuretics were associated with a greater risk of in-hospital death in some subgroups, including patients aged >80 years, those with an acute coronary syndrome, or with a left ventricular ejection fraction <40%. However, after propensity score matching, no association was found between diuretic dosing and death in any of the studied subgroups. Conclusions In the initial management of acute HF, HD iv diuretics, per se, do not influence short-term mortality. [ABSTRACT FROM AUTHOR]

Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. Methods and results In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6–24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. Conclusion The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months. [ABSTRACT FROM AUTHOR]

Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort. [ABSTRACT FROM AUTHOR]

Purpose: To date, treatment with intravenous (IV) agents such as vasodilators, diuretics, and inotropes has shown marginal or mixed benefits in acute heart failure (AHF) trials. The aim of this study was to identify the risks and benefits of IV drugs in patients hospitalized with acute decompensated heart failure. Methods: The AHF global survey of standard treatment (ALARM-HF) reviewed in-hospital treatments in eight countries. The present study was a post hoc analysis of ALARM-HF data in which propensity scoring was used to identify groups of patients who differed by treatment but had the same multivariate distribution of covariates. Such propensity matching allowed estimations of the effect of specific treatments on the outcome of in-hospital mortality. Results: Unadjusted analysis showed a lower in-hospital mortality rate in AHF patients receiving 'diuretics + vasodilators' ( n = 1,805) compared to those receiving 'diuretics alone' ( n = 2,362) (7.6 vs. 14.2%, p < 0.0001). Propensity-based matching ( n = 1,007 matched pairs) confirmed the lower mortality of AHF patients receiving diuretics + vasodilators: 7.8 versus 11.0% ( p = 0.016). Unadjusted analysis showed a much greater in-hospital mortality rate in patients receiving IV inotropes (25.9%) compared to those who did not (5.2%) ( p < 0.0001). Propensity-based matching ( n = 954 pairs) confirmed that IV catecholamine use was associated with 1.5-fold increase for dopamine or dobutamine use and a >2.5-fold increase for norepinephrine or epinephrine use. Conclusions: In terms of in-hospital survival, a vasodilator in combination with a diuretic fared better than treatment with only a diuretic. Catecholamine inotropes should be used cautiously as it has been seen that they actually increase the risk for in-hospital mortality. [ABSTRACT FROM AUTHOR]

Acute heart failure (AHF) with preserved left ventricular ejection fraction (PLVEF) represents a significant part of AHF syndromes featuring particular characteristics. We sought to determine the clinical profile and predictors of in-hospital mortality in patients with AHF and PLVEF in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). This survey is an international observational study of 4,953 patients admitted for AHF in 9 countries (6 European countries, Mexico, and Australia) from October 2006 to March 2007. Patients with PLVEF were defined by an LVEF ≥45%. Of the total cohort, 25% of patients had PLVEF. In-hospital mortality was significantly lower in this subgroup (7% vs 11% in patients with decreased LVEF, p = 0.013). Candidate variables included demographics, baseline clinical findings, and treatment. Multivariate logistic regression analysis showed that the variables independently associated with in-hospital mortality included systolic blood pressure at admission (p <0.001), serum sodium (p = 0.041), positive troponin result (p = 0.023), serum creatinine >2 mg/dl (p = 0.042), history of peripheral vascular disease and anemia (p = 0.004 and p = 0.015, respectively), secondary (hospitalization for other reason) versus primary AHF diagnosis (p = 0.043), and previous treatment with diuretics (p = 0.023) and angiotensin-converting enzyme inhibitors (p = 0.021). In conclusion, patients with AHF and PLVEF have lower in-hospital mortality than those with decreased LVEF. Low systolic blood pressure, low serum sodium, renal dysfunction, positive markers of myocardial injury, presence of co-morbidities such as peripheral vascular disease and anemia, secondary versus primary AHF diagnosis, and absence of treatment with diuretics and angiotensin-converting enzyme inhibitors at admission may identify high-risk patients with AHF and PLVEF. [ABSTRACT FROM AUTHOR]

Aims Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Methods and results ALARM-HF included a total of 4953 patients hospitalized for AHF in Europe, Latin America, and Australia. The final diagnosis was made at discharge, and patients were classified according to European Society of Cardiology guidelines. Patients with APE had higher in-hospital mortality (7.4 vs. 6.0%, P = 0.057) compared with ADHF patients (n = 1911, 38.5%), and APE patients exhibited higher systolic blood pressures (P < 0.001) at admission and higher left ventricular ejection fraction (LVEF, P < 0.01) than those with ADHF. These patients also had a higher prevalence of diabetes (P < 0.01), arterial hypertension (P < 0.001), peripheral vascular disease (P < 0.001), and chronic renal disease (P < 0.05). They were also more likely to receive intravenous (i.v.) diuretics (P < 0.001), i.v. nitrates (P < 0.01), dopamine (P < 0.05), and non-invasive ventilation (P < 0.001). Low systolic blood pressure (P < 0.001), low LVEF (<0.05), serum creatinine ≥1.4 mg/dL (P < 0.001), history of cardiomyopathy (P < 0.05), and previous cardiovascular event (P < 0.001) were independently associated with increased in-hospital mortality in the APE population. Conclusion APE differs in clinical profile, in-hospital management, and mortality compared with ADHF. Admission characteristics (systolic blood pressure and LVEF), renal function, and history may identify high-risk APE patients. [ABSTRACT FROM AUTHOR]

Aims: Information on the effectiveness of beta-blockade in patients with heart failure (HF) and concomitant renal impairment is scarce and beta-blockers are underutilized in these patients. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: To identify factors associated with short term mortality in hospitalised patients with heart failure. Background: Hospitalisation is frequent in patients with heart failure and is associated with a high mortality. Methods: The Euro Heart Failure survey collected data from patients with suspected heart failure. We searched this data for predictors of short term mortality. Results: Of 10,701 patients, 1404 (13%) died within 12 weeks of admission. On univariate analysis, increasing age, hyponatraemia, renal impairment, hyperkalaemia, anaemia, severe mitral regurgitation, severe LV systolic dysfunction(LVSD), increasing QRS and female sex carried adverse prognosis. ACEI, beta-blockers, nitrates, anti-thrombotic and lipid lowering drugs were associated with a better prognosis. On multivariable analysis the following provided independent prognostic information: increasing age (OR per SD=1.5, 95% CI 1.4–1.6), severe LVSD (1.8, 1.5–2.1), serum creatinine (1.2, 1.2–1.3), sodium (0.9, 0.8–0.9), Hb (0.9, 0.8–0.9) and treatment with ACEI (0.5, 0.5–0.6), beta-blockers (0.7, 0.6–0.8), statins (0.6, 0.5–0.7), calcium channel blockers (0.7, 0.6–0.8), warfarin (0.5, 0.4–0.6), heparin (1.7, 1.4–1.9), anti-platelet drugs (0.6, 0.5–0.6) and need for inotropes (5.5, 4.6–6.6). A simple risk score (range 0–11) identified cohorts with a 12 week mortality ranging from 2% to 44%. Conclusions: Simple and readily available clinical variables and a risk score based on medical history and routine tests that all patients admitted with heart failure have, can identify patients with good, intermediate and high short term mortality. [Copyright &y& Elsevier]

Abstract: 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-β-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. [Copyright &y& Elsevier]

Abstract: 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 3–250ngml−1. In the concentration ranges 5–50 and 50–250ngml−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 (0.2gday−1, orally for >2 months) varied inter-individually and were 140.0±85.2, 39.1±20.8, and 26.2±15.2ngml−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±435ngml−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. [Copyright &y& Elsevier]

Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1) MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2) dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3) the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages. [ABSTRACT FROM AUTHOR]

Background: In patients with ischemic heart disease (IHD), secondary preventive drug therapy improves overall prognosis. Therefore, this study evaluated cardiovascular drug utilization in patients suffering from IHD, identified factors influencing drug utilization, and determined the prevalence of shortfalls of antithrombotic, β-blocker, and lipid-lowering drug use. Methods: This study is based on data recorded prospectively between 1996 and 1998 in two Swiss teaching hospitals for the SAS/CHDM pharmacoepidemiologic database project. Drug utilization was evaluated in all 987 monitored medical inpatients with IHD. Results: At discharge, only 64% of patients with IHD received platelet aggregation inhibitors, 42% β-blockers, and 26% lipid-lowering drugs. Secondary preventive drugs were more frequently administered to patients with acute myocardial infarction and less frequently in the elderly. After including other co-factors, no gender difference could be detected. Shortfalls of antithrombotic therapy occurred in 6.5–8.3% of patients and shortfalls in β-blocker use in 9.9–23.3%. Only about half of all patients with IHD and elevated cholesterol received lipid-lowering drugs. Conclusions: Drugs for secondary prevention are prescribed to the majority of patients with IHD. However, their use could be further increased, especially in the elderly and in patients with IHD who are admitted to the hospital for reasons other than acute myocardial infarction. Lipid-lowering drugs should also be prescribed more often for patients with hypercholesterolemia. [Copyright &y& Elsevier]

Examines the epidemiology of drug exposure and adverse drug reaction (ADR) in two Swiss departments of internal medicine. Concept of ADR; Feasibility of the developed event monitoring system; Use of pharmacoepidemiological database.

Aims Saquinavir is a potent HIV protease inhibitor whose effectiveness is limited in vivo by its low bioavailability. Since saquinavir is metabolized by CYP3A4, the effect of grapefruit juice, an inhibitor of CYP3A4, was investigated on its bioavailability. Methods After an overnight fast, eight healthy volunteers were treated with either 400 ml grapefruit juice or water before intravenous (12 mg) or oral saquinavir (600 mg) was administered. Serial blood samples were obtained over the following 24 h and standardized meals were served 5 and 10 h after the administration of saquinavir. The plasma concentrations of saquinavir were determined by high-performance liquid chromatography and pharmacokinetic parameters were calculated by routine methods. Results The AUC was not affected by grapefruit juice after intravenous administration, but it increased significantly from 76±96 (water, mean (s.d.) to 114±70 (μg l[sup -1] h (grapefruit juice) after oral saquinavir. Similarly, the oral bioavailability of saquinavir increased by a factor of 2 with grapefruit juice (from 0.7% to 1.4%). In contrast, clearance, volume of distribution and elimination half-life of saquinavir were not affected by grapefruit juice. After oral, but not after intravenous administration, the plasma concentration-time curve showed a second peak after lunch irrespective of pretreatment, suggesting enhancement of absorption by food. Conclusions The studies demonstrate that grapefruit juice increases the bioavailability of saquinavir without affecting its clearance, suggesting that inhibition of intestinal CYP3A4 may contribute. Since the antiretroviral effect of saquinavir is dose-dependent, inhibition of CYP3A4 may represent a way to enhance its effectiveness without increasing the dose. [ABSTRACT FROM AUTHOR]

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 ≤4 items of advice were younger and more often received angiotensin-converting enzyme inhibitors (71% vs 62%), β-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. [Copyright &y& Elsevier]

Aim-Methods: ALARM-HF was a retrospective, observational registry that included 4,953 patients admitted for acute heart failure (AHF) in six European countries, Turkey, Mexico and Australia. Data about respiratory disorders and related medications were available for 4,616 patients with AHF., Results: Chronic obstructive pulmonary disease (COPD) patients (n = 1,143, 24.8%) were older and more frequently men (p < 0.001) when compared to non-COPD patients. Despite the equivalent left ventricular ejection fraction (38.6 ± 13.7 vs. 38.2 ± 14.5%, p > 0.05), COPD patients more frequently presented with acutely decompensated heart failure (p < 0.001). Moreover, a worse cardiovascular profile was observed in the COPD group, including more atrial fibrillation/flutter, diabetes, hypertension, obesity, peripheral vascular disease (p < 0.001). Before admission, a higher percentage of COPD patients had experienced infections (25.0 vs. 14.0 %, p < 0.001), and were more likely to receive diuretics (p = 0.006), ACE inhibitors (p = 0.042), nitrates (p = 0.003), and digoxin (p = 0.034). With the exception of ACE inhibitors, those differences maintained at discharge, with concomitant increase in ARBs prescription (p = 0.01). Notably, β-blockers were less prescribed before admission (21.1 vs. 23.8%, p = 0.055) in COPD patients, and remained underutilized at discharge (p < 0.001). Correcting for baseline differences, all-cause in-hospital mortality did not differ between COPD and non-COPD groups (10.1 vs. 10.9%, p = 0.085)., Conclusion: A large proportion of AHF patients presented with concomitant COPD, had different clinical characteristics/co-morbidities, and less frequently received evidence-based pharmacological therapy compared to non-COPD patients. However, the in-hospital mortality was not higher in COPD group.

The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K(+) channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K(+) channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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.

Background: Hospitalised patients with acute heart failure (AHF) suffer from a high morbidity and mortality, which might, at least partly, be influenced by concomitant infections. The aim of this observational study was to investigate the impact of infections on the clinical course of critically ill patients with AHF, both present on intensive care unit (ICU) admission and acquired during the ICU stay., Methods: From 178 consecutive AHF patients, 76 were treated medically and 21 required emergency cardiac surgery. The remaining 81 patients, who underwent elective cardiac surgery, were excluded from the assessment of infections on ICU admission, but were included in the analysis of nosocomial infections during the ICU stay., Results: A total of 16% of patients (16/97) had infections on ICU admission. These patients had longer ICU (6 vs. 3 days, p = 0.04) and hospital (19 vs. 11 days, p = 0.04) stays than patients without infections. Although not statistically significant, there was a trend for increased mortality at 30 days (44% vs. 24%, p = 0.13) and 6 months (57% vs. 31%, p = 0.13) in AHF patients with infections on ICU admission. Infection complications during the ICU stay occurred in 17% (30/178) of AHF patients and significantly increased their mortality at 30 days (33% vs. 14%, p = 0.02) and 6 months (41% vs. 18%, p = 0.02)., Conclusions: In this observational study, infections present on ICU admission or occurring during the ICU stay had a negative impact on the morbidity and mortality of critically ill patients with AHF. Future studies are needed to gain a better understanding of the interactions between heart failure and infections, as a better knowledge of this field may have an important therapeutic potential.