Showing papers in "European Journal of Heart Failure in 2007"

Sleep-disordered breathing in patients with symptomatic heart failure: a contemporary study of prevalence in and characteristics of 700 patients.

Abstract: Aim: Evaluation of the prevalence and nature of sleep-disordered breathing (SDB) in patients with symptomatic chronic heart failure (CHF) receiving therapy according to current guidelines. Methods and results: We prospectively screened 700 patients with CHF (NYHA class ≥II, LV-EF ≤40%) for SDB using cardiorespiratory polygraphy (Embletta™). Furthermore, echocardiography, cardiopulmonary exercise and 6-min walk testing were performed. Medication included ACE-inhibitors and/or AT1-receptor blockers in at least 94%, diuretics in 87%, β-blockers in 85%, digitalis in 61% and spironolactone in 62% of patients. SDB was present in 76% of patients (40% central (CSA), 36% obstructive sleep apnoea (OSA)). CSA patients were more symptomatic (NYHA class 2.9±0.5 vs. no SDB 2.57±0.5 or OSA 2.57±0.5; pb0.05) and had a lower LV-EF (27.4±6.6% vs. 29.3±2.6%, pb0.05) than OSA patients. Oxygen uptake (VO2) was lowest in CSA patients: predicted peak VO2 57±16% vs. 64±18% in OSA and 63±17% in no SDB, pb0.05. 6-min walking distances were 331±111 m in CSA, 373±108 m in OSA and 377±118 m in no SDB (pb0.05). Conclusions: This study confirms the high prevalence of SDB, particularly CSA in CHF patients. CSA seems to be a marker of heart failure severity.

Cognitive impairment in heart failure: a systematic review of the literature.

Abstract: Background: Heart failure (HF) and cognitive impairment are common medical conditions that are becoming increasingly prevalent in theaging Western population. They are associated with frequent hospitalisation and increased mortality, particularly when they occursimultaneously. Evidence from a number of studies suggests that HF is independently associated with impairment in various cognitivedomains.Aims: This systematic literature review evaluates the relation between cognitive deterioration and heart failure.Methods: We searched electronic databases from 1966 to May 2006 for studies that investigated cognitive function in HF patients. Twenty-two controlled studies that met the inclusion criteria were selected for analysis. Study characteristics and data on global cognitiveperformance, memory scores, psychomotor speed and depression scores were extracted and analysed using the Cochrane Review Managersoftware.Results: Pooled analysis shows diminished neuropsychological performance in HF patients, as compared to control subjects. In a pooledsample of 2937 heart-failure patients and 14,848 control subjects, the odds ratio for cognitive impairment was 1.62 (95% confidenceinterval:1.48–1.79, pb0.0001) among subjects with HF.Conclusion: This review confirms the relationship between HF and cognitive impairment, but it also stresses the need for additionalsystematic neuropsychological data and adequate neuro-imaging from representative populations of HF patients.© 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction.

Abstract: Background: Renal failure in heart failure is related to decreased cardiac output. However, little is known about its association with venous congestion. Aims: To investigate the relationship between venous congestion and glomerular filtration rate (GFR) in patients with cardiac dysfunction. Methods and results: Right atrial pressure (RAP) and cardiac index (CI) were determined by right heart catheterisation in 51 patients with cardiac dysfunction, secondary to pulmonary hypertension. GFR and renal blood flow (RBF) were measured as I-125-lothalamate and I-131- Hippuran clearances, respectively. Mean age was 40 +/- 11 years and 69% of patients were female. GFR was 73 +/- 19 ml/min/1.73 m(2) with a CI of 2.1 +/- 0.7 l/min/m(2). In multivariate analysis, RBF (r=0.664, p Conclusion: RBF is the main factor determining GFR in patients with cardiac dysfunction. Venous congestion, characterised by an increased RAP, adjusted for RBF is also related to GFR. Treatment to preserve GFR should not only focus on improvement of renal perfusion, but also on decreasing venous congestion. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Relation between dose of loop diuretics and outcomes in a heart failure population: Results of the ESCAPE Trial

Abstract: Loop diuretics are often given early in the course of treatment of hospitalised decompensated heart failure (HF) patients. Because clinical trial data defining the ideal diuretic dose are lacking, dosing is largely based on iterative increases with observation of patients for urine output. Factors that typically drive dose selection include diuretic dose before admission, renal function, severity of volume overload, and whether the patient is believed to be diuretic resistant. The relation between weight loss, symptomatic improvement, adverse events, and dose has not been well described in these patients. Diuretic dose selection may have important implications for long-term outcomes. Worsening renal function is a known predictor of poor outcomes in this population (1,2). Renal insufficiency can be induced or worsened by the administration of diuretics. It is unknown if a relation exists between diuretic-induced worsening renal function and clinical outcomes. In addition, the cardio-renal syndrome is increasingly recognized as an important component of HF pathophysiology (3,4). Several retrospective studies have also suggested that chronic diuretic use was a predictor of worse outcomes, even after adjustments for other markers of severity (5,6). However, the association between high doses of diuretics and outcomes of patients with acute HF has not been similarly investigated. High doses of diuretic are commonly used in hospitalised HF patients who have chronic severe left ventricular (LV) systolic dysfunction; however, data evaluating dose-response are lacking. These concerns emphasize the need to further evaluate the relation between diuretic dose and clinical outcomes. We analyzed the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheter Effectiveness (ESCAPE) trial database to describe the patterns of diuretic use, and to examine the relation between diuretic dose and clinical outcomes in patients with severe chronic HF admitted for an episode of decompensation (7).

Advanced chronic heart failure : A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Abstract: Therapy has improved the survival of heart failure (HF) patients However, many patients progress to advanced chronic HF (ACHF) We propose a practical clinical definition and describe the characteristics of this condition Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction 1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives

Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications.

Abstract: Advanced glycation end-products (AGEs) are molecules formed during a non-enzymatic reaction between proteins and sugar residues, called the Maillard reaction. AGEs accumulate in the human body with age, and accumulation is accelerated in the presence of diabetes mellitus. In patients with diabetes, AGE accumulation is associated with the development of cardiac dysfunction. Enhanced AGE accumulation is not restricted to patients with diabetes, but can also occur in renal failure, enhanced states of oxidative stress, and by an increased intake of AGEs. Several lines of evidence suggest that AGEs are related to the development and progression of heart failure in non-diabetic patients as well. Preliminary small intervention studies with AGE cross-link breakers in heart failure patients have shown promising results. In this review, the role of AGEs in the development of heart failure and the role of AGE intervention as a possible treatment for heart failure are discussed.

Right ventricular dysfunction as an independent predictor of short- and long-term mortality in patients with heart failure.

Abstract: Background: The prognostic importance of right ventricular (RV) dysfunction in heart failure (HF) has been suggested in patients with severe systolic heart failure. Tricuspid annular plane systolic excursion (TAPSE) is a simple echocardiographic measure of RV ejection fraction, but may be affected by co-existing chronic obstructive pulmonary disease (COPD). Aims: To examine the prognostic information from TAPSE adjusted for the potential confounding effects of co-existing cardiovascular and COPD in a large series of patients admitted for new onset or worsening HF. Methods and results: Eight hundred and seventeen patients screened for participation in a large clinical trial by trans-thoracic echocardiography, including measurement of TAPSE, were followed for a median of 4.1 years (maximum 5.5 years). Decreased TAPSE as well as presence of COPD were independently associated with adverse short- and long-term survival, hazard ratio was 0.74 (p=0.004) for every doubling of TAPSE; and 2.4 (p=0.0001) for the presence of COPD. Conclusion: Decreased RV systolic function as estimated by TAPSE is associated with increased mortality in patients admitted for HF, and is independent of other risk factors in HF including left ventricular function. The co-existence of COPD is also associated with an adverse prognosis independent of the RV systolic function.

Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM.

Abstract: Background: Limited comparative studies assessing the health-related quality of life (HRQL) in heart failure (HF) patients with preserved vs. low ejection fraction (LVEF) have been disparate. Aims: The aims of this study were a) to characterize HRQL in a large population of HF patients with preserved and low LVEF and b) to determine the factors associated with worse HRQL. Methods: Patients with symptomatic HF (NYHA Class II—IV) enrolled in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL study completed the Minnesota Living with Heart Failure questionnaire at randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%) and low LVEF (≤40%). Results: In 2709 of the eligible 2744 (98.6%) patients, the summary scores ranged from 0 to 105 (mean 40.9). There were no differences in overall responses of HF patients with preserved vs. low LVEF (41.1 vs. 40.8). Independent factors associated with worse HRQL in both populations included female gender, younger age, higher body mass index, lower systolic blood pressure, greater symptom burden, and worse functional status. Conclusions: In symptomatic HF patients, HRQL is equally impaired in both preserved and low LVEF populations. Targeting improvement in symptoms and HRQL is an important treatment objective in all HF patients.

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

Abstract: Background: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. Aim: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. Methods and results: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO2 slope [median (inter-quartile range) 31.1 (28–37) vs. 28.1 (27–30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean±sd: 2.4±1.6 vs. 1.5±0.7%VE Max/mmHg CO2 respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. Conclusions: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

Chronic heart failure slows late sodium current in human and canine ventricular myocytes: implications for repolarization variability.

Abstract: Background: Late Na+ current (INaL) in human and dog hearts has been implicated in abnormal repolarization associated with heart failure (HF). HF slows inactivation gating of late Na+ channels, which could contribute to these abnormalities. Aims: To test how altered gating affects INaL time course, Na+ influx, and action potential (AP) repolarization. Methods: INaL and AP were measured by patch clamp in left ventricular cardiomyocytes from normal and failing hearts of humans and dogs. Canine HF was induced by coronary microembolization. Results: INaL decay was slower and INaL density was greater in failing hearts than in normal hearts at 24 °C (human hearts: τ659±16 vs. 529±21ms; n=16 and 4 hearts, respectively; mean±SEM; p<0.002; dog hearts: 561±13 vs. 420±17ms; and 0.307±0.014 vs. 0.235±0.019pA/pF; n=25 and 14 hearts, respectively; p<0.005) and at 37°C this difference tended to increase. These INaL changes resulted in much greater (53.6%) total Na+ influx in failing cardiomyocytes. INaL was sensitive to cadmium but not to cyanide and exhibited low sensitivity to saxitoxin (IC50=62nM) or tetrodotoxin (IC50=1.2 μM), tested in dogs. A 50% INaL inhibition by toxins or passing current opposite to INaL, decreased beat-to-beat AP variability and eliminated early afterdepolarizations in failing cardiomyocytes. Conclusions: Chronic HF leads to larger and slower INaL generated mainly by the cardiac-type Na+ channel isoform, contributing to larger Na+ influx and AP duration variability. Interventions designed to reduce/normalize INaL represent a potential cardioprotective mechanism in HF via reduction of related Na+ and Ca2+ overload and improvement of repolarization.

The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT-proBNP and cardiac troponin-T.

Abstract: Aims Brain natriuretic peptide (BNP), NT-proBNP and troponins are useful for the assessment of patients with heart failure. Few data exist about their serial changes and their prognostic value in patients with acute heart failure (AHF). Methods and results NT-proBNP and troponin-T plasma levels were measured at baseline, after 6, 12, 24, 48 h and at discharge in 116 consecutive patients with AHF and no evidence of acute coronary syndrome. NT-proBNP levels were 4421 pg/mL at baseline, declined after 24 h and reached their nadir at 48 h (2703 pg/mL). Troponin-T was detectable in 48% of patients. During a median follow-up of 184 days, 52 patients died or had a non-fatal cardiovascular hospitalisation. At a multivariable analysis including clinical and echo-Doppler variables, NT-proBNP plasma levels at discharge, detectable troponin-T plasma levels, and NYHA class at discharge were the only independent prognostic factors. Conclusion In patients with AHF, NT-proBNP levels decline 24 h after the initiation of intravenous therapy and troponin-T is detectable in 48% of cases. NT-proBNP levels at discharge, detectable troponin-T levels, NYHA class and serum sodium have independent prognostic value.

Reasons for seeking acute care in chronic heart failure.

Abstract: Background: Patients with chronic heart failure (CHF) have frequent episodes of exacerbation leading to recurrent hospitalization. Aims: To explore factors related to patients seeking care for worsening CHF. Methods: Eighty-eight patients diagnosed with a deteriorating CHF condition were interviewed. Data were analysed using content analysis. Results: Overall, 51 (58%) patients sought emergency care because of their symptoms while 37 (42%) were either sent by relatives or referred from outpatient clinics. Delay in seeking care was explained by 62 (71%) patients as a “wait and see” strategy, 9 (10%) were reluctant to use the health care system and 10 (11%) felt that it was futile to seek care. Fifty percent of the patients were uncertain about their current deteriorating status. Only 4 patients reported their symptoms to be related to heart failure. Conclusions: Although symptoms were the dominant reason for seeking emergency care, only a few patients related their symptoms to worsening CHF, which might be an important factor for not seeking emergency care earlier. Patient education programs should make efforts to improve understanding of symptom recognition.

Left bundle branch block as a risk factor for progression to heart failure

Abstract: The prevalence of conduction disturbances, particularly left bundle branch block (LBBB), is strongly correlated with age and with the presence of cardiovascular disease. LBBB has been reported to affect approximately 25% of the heart failure (HF) population and it is likely that the deleterious role of such conduction disorders in the progression to HF has been underestimated. The purpose of this article is to review the data from the literature indicating that LBBB may have a causative role, mediated through the resulting intra-ventricular asynchrony, in the deterioration of cardiac function and the development of cardiac remodelling and HF. It also aims to address the potential for future clinical therapies for this conduction disorder.

Brain magnetic resonance imaging abnormalities in patients with heart failure

Abstract: Background: Although heart failure (HF) is a common cardiovascular disorder, to date little research has been conducted into possible associations between HF and structural abnormalities of the brain. Aims: To determine the frequency and pattern of magnetic resonance imaging (MRI) abnormalities in outpatients with chronic HF, and to identify any demographic and clinical correlates. Methods: Brain MRI scans were compared between a sample of 58 HF patients, 48 controls diagnosed with cardiovascular disease uncomplicated by HF (cardiac controls) and 42 healthy controls. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated. Results: Compared to cardiac and healthy controls, HF patients had significantly more WMH, lacunar infarcts and MTA, whereas cardiac controls only had more MTA, compared to healthy controls. Age and left ventricular ejection fraction (LVEF) were independently associated with total WMH. Age and systolic hypotension were associated with MTA in HF patients and cardiac controls. Conclusion: Our results suggest that cardiac dysfunction contributes independently to the development of cerebral MRI abnormalities in patients with HF. Age and low LVEF are the principal predictors of cerebral WMH in patients with HF and in cardiac controls.

Is the gap between guidelines and clinical practice in heart failure treatment being filled? Insights from the IMPACT RECO survey

Abstract: Background Recent registries have shown that recommended drugs for the treatment of chronic heart failure (CHF) are under-prescribed in daily practice. Aims To determine prescription rates of CHF drugs, and to assess predictive factors for drug prescription using data from a large panel of French cardiologists. Methods and results We included 1919 outpatients, with NYHA class II–IV heart failure and a left ventricular ejection fraction 75 years was an independent factor associated with under-prescription of ACE-I-ARBs, beta-blockers or spironolactone. Renal failure was associated with a lower prescription of ACE-I-ARB and spironolactone, and asthma was a predictor of under-prescription of beta-blockers. Conclusions In this contemporary survey, prescription rates of CHF drugs were higher than previously reported. However, dosages were lower than those recommended in guidelines. Age remained an independent predictor of under-prescription of CHF drugs.

Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol.

Abstract: Background: Evidence suggests that carvedilol decreases muscle sympathetic nerve activity (MSNA) in patients with heart failure (HF) but carvedilol fails to improve forearm vascular resistance and overall functional capacity. Exercise training in HF reduces MSNA and improves forearm vascular resistance and functional capacity. Aims: To investigate whether the beneficial effects exercise training on MSNA are maintained in the presence of carvedilol. Methods and results: Twenty seven HF patients, NYHA Class II–III, EF b35%, peak VO2 b20 ml/kg/min, treated with carvedilol were randomly divided into two groups: exercise training (n=15) and untrained (n=12). MSNA was recorded by microneurography. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The four-month training program consisted of three 60-min exercise/ week on a cycloergometer. Baseline parameters were similar between groups. Exercise training reduced MSNA (−14±3.3 bursts/100 HB, p=0.001) and increased forearm blood flow (0.6±0.1 mL/min/100 g, pb0.001) in HF patients on carvedilol. In addition, exercise training improved peak VO2 in HF patients (20±6%, p=0.002). MSNA, FBF and peak VO2 were unchanged in untrained HF patients on carvedilol. Conclusion: Exercise training reduces MSNA in heart failure patients treated with carvedilol. In addition, the beneficial effects of exercise training on muscle blood flow and functional capacity are still realized in patients on carvedilol. © 2007 European Society of Cardiology. Published by Elsevier B.V.

Non-invasive predictors of survival in cardiac amyloidosis.

Abstract: Background: Patients with cardiac amyloidosis (CA) have increased mortality. Aims: Clinical, electrocardiographic, and echocardiographic parameters were assessed for risk-stratification of CA. Methods and results: CA was confirmed by endomyocardial biopsy in 59 patients (54.8±1.2 years) with light-chain (n = 43) or transthyretin amyloidosis (n = 16). Six patients without CA served as controls (NCA). Clinical symptoms, electrocardiographic, and echocardiographic parameters were analyzed for prognostic significance. Of the patients with light-chain amyloidosis, 14 died and 2 underwent heart transplantation. 1-/3-year survival was 68%/63%. Survival depended on left ventricular function (LV-EF), LV mass, radius/wall thickness, septum thickness, low voltage pattern (LVP), conduction delay, NYHA class, and stem cell transplantation. A multivariate model only contained LV-EF and LVP; the beneficial effect of stem cell transplantation was cancelled out as this treatment was withheld in patients with highest cardiac risk. Survival was most limited if both risk factors occurred. Cardiac involvement in transthyretin amyloidosis showed better survival (2 deaths, 1-/3-year survival 91%/83%). Analysis of prognostic risk factor utility in all amyloid patients (light-chain and transthyretin) again revealed LVP and LV-EF, and aetiology of amyloidosis as independent survival parameters. Conclusion: Prognosis of CA is poor, but aetiology of amyloid, LVP, and LV-EF allows identification of patients at highest risk of death, who may require individual treatment approaches (heart transplantation prior to causative therapy).

Caregiver burden in partners of Heart Failure patients; limited influence of disease severity

Abstract: BACKGROUND: In complying with required life style changes Heart Failure (HF) patients often depend on their partners. However providing care may cause burden and affect the health of these partners ...

The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure

Abstract: Aims: To investigate the prevalence and the prognostic impact of chronic obstructive pulmonary disease (COPD), in patients hospitalised with chronic heart failure (CHF). Methods and results: In an observational study based on longitudinal information from administrative registers, 1020 patients aged ≥60 years, who were chronically treated for and hospitalised with CHF were identified and followed-up for major events up to 1 year. Median age was 80 years, half of the patients were female and 241 patients (23.6%) had concomitant COPD. There were no differences in the prevalence of cardiovascular and non-cardiovascular comorbidities between CHF patients with or without COPD. However, COPD patients were more often male (60.6% vs. 46.3%), more frequently treated with diuretics (95.9% vs. 91.5%) but less often exposed to β-blockers (16.2% vs. 22.0%). Significantly higher adjusted in-hospital (HR 1.50 [95%CI 1.00–2.26]) and out-of-hospital (1.42 [1.09–1.86]) mortality rates were found in CHF patients with concomitant COPD. A higher occurrence of non-fatal AMI/stroke/rehospitalisation for CHF (1.26 [1.01–1.58]) as well as hospitalisation for CHF (1.35 [1.00–1.82]) was associated with COPD. Conclusions: COPD is a frequent concomitant disease in patients with heart failure and it is an independent short-term prognostic indicator of mortality and cardiovascular comorbidity in patients who have been admitted to hospital for heart failure.

Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium.

Abstract: Objective To determine the optimal bone marrow (BM) cell types, and their potential mechanisms of action for neovascularization in chronic ischaemic myocardium. Methods and results The functional effects, angiogenic potential and cytokine expression of direct intramyocardial implantation of autologous BM CD31-positive endothelial progenitor cells (EPC, n=9), BM mononuclear cells (MNCs, n=9), and saline (n=9) were compared in a swine model of chronic ischaemic myocardium. Autologous BM cells were harvested and catheter-based electromechanical mapping-guided direct intramyocardial injection was performed to target ischaemic myocardium. After 12 weeks, injection of BM-MNC resulted in significant improvements in left ventricular dP/dt (+21±8%, P=0.032), left ventricular pressure (+17±4%, P=0.048) and regional microsphere myocardial perfusion over ischaemic endocardium (+74±28%, P<0.05) and epicardium (+73±29%, P<0.05). No significant effects were observed following injection of BM-EPC or saline. Capillary density (1132±69 versus 903±44 per mm2, P=0.047) and expression of mRNA of vascular endothelial growth factor (VEGF, 32.3±5.6 versus 13.1±3.7, P<0.05,) and angiopoietin-2 (23.9±3.6 versus 13.7±3.1, P<0.05) in ischaemic myocardium was significantly greater in the BM-MNC group than the saline group. The capillary density in ischaemic myocardium demonstrated a significant positive correlation with VEGF expression (r=0.61, P<0.001). Conclusion Catheter-based direct intramyocardial injection of BM-MNC enhanced angiogenesis more effectively than BM-EPC or saline, possibly via a paracrine effect, with increased expression of VEGF that subsequently improved cardiac performance of ischaemic myocardium.

Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.

Abstract: Aims: To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure. Methods and results: This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 μg/kg followed by a continuous infusion of 0.1–0.2 μg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7–9 days, and in CO was 12–13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3. Conclusions: Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1–3 days after starting the infusion, effects were sustained for up to at least a week.

Influence of cardiac resynchronisation therapy on different types of sleep disordered breathing

Abstract: Aims This study investigates the influence of cardiac resynchronisation therapy (CRT) on sleep disordered breathing (SDB) in patients with severe heart failure (HF). Methods and results Seventy-seven patients with HF (19 females; 62.6±10 years) eligible for CRT were screened for presence, type, and severity of SDB before and after CRT initiation (5.3±3 months) using cardiorespiratory polygraphy. NYHA class, frequency of nycturia, cardiopulmonary exercise, 6-minute walking test results, and echocardiography parameters were obtained at baseline and follow-up. Central sleep apnoea (CSA) was documented in 36 (47%), obstructive sleep apnoea (OSA) in 26 (34%), and no SDB in 15 (19%) patients. CRT improved clinical and haemodynamic parameters. SDB parameters improved in CSA patients only (apnoea hypopnoea index: 31.2±15.5 to 17.3±13.7/h, p<0.001; SaO2min: 81.8±6.6 to 84.8±3.3%, p=0.02, desaturation: 6.5±2.3 to 5.5±0.8%, p=0.004). Daytime capillary pCO2 was significantly lower in CSA patients compared to those without SDB with a trend towards increase with CRT (35.5±4.2 to 37.9±5.7 mm Hg, ns). After classifying short term clinical and haemodynamic CRT effects, improved SDB parameters in CSA occurred in responders only. Conclusions In patients with severe HF eligible for CRT, CSA is common and can be influenced by CRT, this improvement depends on good clinical and haemodynamic response to CRT.

Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET.

Abstract: Background It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. Methods Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. Results In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p Conclusions HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients.

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

Abstract: 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, = 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. (C) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Hyperuricaemia and long-term outcome after hospital discharge in acute heart failure patients.

Abstract: Background Uric acid (UA) may be involved in chronic heart failure (HF) pathogenesis, entailing a worse outcome. The purpose of this study was to examine the role of hyperuricaemia as a prognostic marker after hospital discharge in acute HF patients. Methods We studied 212 patients consecutively discharged after an episode of acute HF with LVEF<40%. Blood samples for UA measurement were extracted in the morning prior to discharge. The evaluated endpoints were death and new HF hospitalization. Results Mean UA levels were 7.4±2.4 mg/dl (range 1.6 to 16 mg/dl), with 127 (60%) of patients being within the range of hyperuricaemia. Hyperuricaemia was associated with a higher risk of death (n=48) (HR 2.0, 95% CI 1.1–3.9, p=0.028), new HF readmission (n=67) (HR 1.8, 95% CI 1.1–3.1, p=0.023) and the combined event (n=100) (HR 1.9, 95% CI 1.2–2.9, p=0.004). At 24 months, cumulative event-free survival was lower in the two higher UA quartiles (36.9% and 40.7% vs. 63.5% and 59.5%, log rank=0.006). After adjustment for potential confounders, hyperuricaemia remains an independent risk factor for adverse outcomes (HR 1.6, 95% CI 1.1–2.6, p=0.02). Conclusions In hospitalized patients with acute HF and LV systolic dysfunction, hyperuricaemia is a long-term prognostic marker for death and/or new HF readmission.

Cardiomyocyte-restricted over-expression of C-type natriuretic peptide prevents cardiac hypertrophy induced by myocardial infarction in mice.

Abstract: Objective: Infused C-type natriuretic peptide (CNP) was recently found to play a cardioprotective role in preventing myocardial ischaemia/reperfusion (I/R) injury and improving cardiac remodelling after myocardial infarction (MI) in rats. Our study aimed to investigate the effect of cardiomyocyte-specific CNP over-expression on I/R injury and MI in transgenic mice. Methods and results: We generated transgenic (TG) mice over-expressing CNP in cardiomyocytes. Elevated CNP expression on RNA and protein levels was demonstrated by RNase-protection assay and radioimmunoassay. Male TG mice and age-matched wild-type (WT) littermates were subjected to 1-hour global myocardial ischaemia and 23 h of reperfusion or permanent ligation of the coronary artery for 3 weeks. Infarct size did not differ between the WT and TG groups in mice subjected to I/R. In mice that underwent permanent ligation of coronary arteries, both left and right ventricular hypertrophy were prevented by CNP over-expression 3 weeks post-MI. Histological analysis revealed less necrosis, muscular degeneration and inflammation in infarcted TG mice. Impairment of cardiac function was less pronounced in transgenic animals than in the wild-type controls. Conclusions: Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin.

Abstract: Background: Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF. Methods and results: Fourteen patients (9 men, 5 women, mean age 68±13years) undergoing biventricular pace-maker/ICD implantation were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma apelin and NT-proBNP levels. The evaluation was repeated 48h and 9±2months after device implantation to assess the acute and chronic effects of CRT on apelin and NT-proBNP levels. Eight healthy age- and sex-matched subjects served as controls. In CHF patients, baseline apelin levels were reduced and NT-proBNP increased compared to control subjects (apelin: 0.47±0.2 vs. 0.97±0.3ng/mL, p<0.001; NT-proBNP: 2007±114 vs. 229±72pmol/L, p<0.001). Short-term evaluation did not reveal any effect of CRT on apelin or NT-proBNP levels. By contrast, at 9±2months follow-up, CRT responders showed left ventricular reverse remodelling and an increase in ejection fraction, together with a significant increase in plasma apelin levels (0.99±0.1 vs. 0.47±0.2ng/mL, p<0.001) and decrease in NT-proBNP (938±591 vs. 2007±114pmol/L, p<0.05). Conclusions: Long-term CRT increases plasma levels of the endogenous inotrope apelin in patients with CHF.

Rationale and design of a randomised, controlled, multicenter trial investigating the effects of selective serotonin re-uptake inhibition on morbidity, mortality and mood in depressed heart failure patients (MOOD-HF).

Abstract: Background: Depression and chronic heart failure (CHF) are common conditions, both of which are clinically and economically highly relevant. Major depression affects 20–40% of CHF patients and predicts adverse outcomes in terms of quality of life, morbidity and mortality as well as health care expenditure, independent of other factors of prognostic relevance. Aims: The purpose of the MOOD-HF trial is to clarify whether antidepressant pharmacotherapy improves outcome in CHF patients, and if so by which mechanism(s). Methods: MOOD-HF is a prospective, randomised, double-blind, placebo-controlled, 2-armed, parallel-group multicenter trial investigating the effects of the serotonin re-uptake inhibitor (SSRI) escitalopram on morbidity and mortality (primary endpoint), severity of depression, anxiety, cognitive function, quality of life and health care expenditure in 700 patients with symptomatic systolic CHF and major depression diagnosed by structured clinical interview. All patients will receive optimised pharmacotherapy for CHF. Duration of follow-up, including close safety monitoring, is 12–24 months from randomisation. Perspective: MOOD-HFisthefirstprospectiverandomisedcontrolledtrialtoassesstheeffectsofantidepressantpharmacotherapyonhardsomatic endpoints,themechanism(s)of actionof SSRItreatment,as wellassafetyinNewYorkHeartAssociationfunctional classII-IVCHFpatients.The results are expected to promote the development of evidence-based recommendations for managing depression in the context of CHF. Trial registration: ISRCTN.org. Identifier: ISRCTN33128015

Lifestyle changes and clinical profile in coronary heart disease patients with an ejection fraction of ≤40% or >40% in the Multicenter Lifestyle Demonstration Project†

Abstract: Background: Lifestyle changes are recommended for coronary heart disease (CHD) patients at risk for heart failure (HF) [ACC/AHA stage B; left ventricular ejection fraction (LVEF)≤40%]. However, it is not clear whether changes in lifestyle are feasible and beneficial in these patients. Aim: To investigate the feasibility of intensive lifestyle changes for CHD patients at risk for HF. Methods: We compared 50 patients (18% female) with angiographically documented LVEF≤40% (mean=33.4±7.3; range: 15–40%) to 186 patients (18% female) with LVEF>40% (mean=58.2±9.6; range: 42–87%), who were participants in the Multicenter Lifestyle Demonstration Project (MLDP). All were non-smoking CHD patients. The MLDP was a community-based, insurance-sponsored intervention (low-fat, plant-based diet; exercise; stress management) implemented at 8 sites in the US. Coronary risk factors, lifestyle and quality of life (SF-36) were assessed at baseline, 3 and 12 months. Results: Regardless of LVEF, patients showed significant improvements (all p<.05) in lifestyle behaviours, body weight, body fat, blood pressure, resting heart rate, total and LDL-cholesterol, exercise capacity, and quality of life by 3 months; most improvements were maintained over 12 months. Conclusion: CHD patients at risk for heart failure with an LVEF≤40%, can make changes in lifestyle to achieve similar medical and psychosocial benefit to patients with an LVEF>40%.

Depression and survival in chronic heart failure: does gender play a role?

Abstract: Background: Data regarding the influence of depression on outcome in chronic heart failure are conflicting and neglect possible gender differences. Aims: To investigate prevalence and prognostic importance of depression in a cohort of patients with symptomatic heart failure and to compare findings in males and females. Methods: Depression was measured at study entry using a self-reported 9-item Patient Health Questionnaire (PHQ-9) in 231 consecutive outpatients. The median follow-up time was 986 (IQR=664–1120) days. Results: The prevalence of suspected major depression was 13% (minor depression, 17%) and was not different between the sexes. Major (but not minor) depression was associated with an increased mortality risk (hazard ratio [HR]=3.3, 95% confidence interval=1.8–6.1, pb0.001). This relationship remained significant after adjustment for other prognostically relevant factors as age, sex, heart failure aetiology, degree and type of left ventricular dysfunction, and New York Heart Association functional class. However, testing the effect of the interaction between gender and depression failed to reach significance (p=0.37). Conclusion: Our data confirm a high prevalence of depression in chronic heart failure. Further, they prove an independent prognostic impact of major, but not minor, depression. Possible gender differences regarding the prognostic impact of depression require further investigation in a larger patient cohort.