Showing papers in "European Journal of Heart Failure in 2008"

Who is an author

Abstract: Authorship of scientific papers is an important activity for the academic researcher, as papers provide a forum for communication of scientific results and can be used to provide references of scientific merit. Authors are responsible for the content of reports, and of course, the presentation of results should be as accurate and unbiased as possible. However, manuscripts can be written in a variety of ways using different words and expressions. In addition, each scientific author does not need to write every single word in the manuscript nor is he/she a novelist. The definition of scientific authorship is not clear-cut and is interpreted differently in various scientific communities. This issue is far from new, and during my years I have seen several commentaries on this subject. Kassirer and Angell, Editors of the New England Journal of Medicine, discussed the issue of authorship in an Editorial published in 1991. I consider this Editorial important as it emphasizes the importance of scientific input and the need to define the contribution of an author particularly in multicenter trials [1]. In order to define roles more clearly, Rennie et al. suggested using “contributors” as a more appropriate designation for some authors [2]. The scientific paper when published is open for discussion, and all authors should be able to provide input of scientific value. All submissions to the European Journal of Heart Failure must include a statement about the role of each author and a signed document defining each author's contribution. This requirement was implemented as a consequence of several reports of papers being published without the knowledge of some of the co-authors. An example is the Sudbo paper, published in the Lancet in 2005, in which several of the 13 co-authors claimed that they were not aware of the submission or the full result [3]. The European Journal of Heart Failure complies with the definitions of authorship as outlined by the International Committee of Medical Journal Editors which is available online at: http://www.icmje.org. We have no further requirement more than an author should have made a scientific contribution. In our May issue, we published an Ethics statement from the HEART network [4]. In this statement, we repeat what we have stated on our website since June last year. The purpose of the statement is to ensure transparency

State of the art: using natriuretic peptide levels in clinical practice.

Abstract: Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: 1) NP levels are quantitative plasma biomarkers of heart failure (HF). 2) NP levels are accurate in the diagnosis of HF. 3) NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. 4) NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. 5) NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. 6) NP levels at discharge aid in risk stratification of the HF patient. 7) NP-guided therapy may improve morbidity and/or mortality in chronic HF. 8) The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. 9) NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. 10) NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients.

Worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance.

Abstract: Background: Renal function is a powerful prognostic variable in patients with heart failure (HF). Hospitalisations for acute HF (AHF) may be associated with further worsening of renal function (WRF). Methods and results: We analysed the clinical significance of WRF in 318 consecutive patients admitted at our institute for AHF. WRF was defined as the occurrence, at any time during the hospitalisation, of both a ≥25% and a ≥0.3 mg/dL increase in serum creatinine (s-Cr) from admission (WRF-Abs-%). Results: Patients were followed for 480±363 days. Fifty-three patients (17%) died and 132 (41%) were rehospitalised for HF. WRF-Abs-% occurred in 107 (34%) patients. At multivariable survival analysis, WRF-Abs-% was an independent predictor of death or HF rehospitalisation (adjusted HR, 1.47; 95%CI, 1.13–1.81; p=0.024). The independent predictors of WRF-Abs-%, evaluated using multivariable logistic regression, were history of chronic kidney disease (p=0.002), LV ejection fraction (p=0.012), furosemide daily dose (p=0.03) and NYHA class (p=0.05) on admission. Conclusion: WRF is a frequent finding in patients hospitalised for AHF and is associated with a poor prognosis. Severity of HF and daily furosemide dose are the most important predictors of the occurrence of WRF.

Long term vagal stimulation in patients with advanced heart failure: first experience in man.

Abstract: Background: Experimentally, vagal stimulation (VS) is protective in chronic heart failure (HF). In man, VS is used in refractory epilepsy but has never been used in cardiovascular diseases. Increased sympathetic and reduced vagal activity predict increased mortality in HF. Aims: This pilot study assessed feasibility and safety and tested possible efficacy of chronic VS in HF patients. Methods: We studied 8 patients (mean age 54 years). CardioFit (BioControl Medical), a VS implantable system delivering pulses synchronous with heart beats through a multiple contact bipolar cuff electrode, was used. VS was started 2–4 weeks after implant, slowly raising intensity; patients were followed 1, 3 and 6 months thereafter. Results: All procedures were successful: as sole surgical side effect, one patient had transient hoarseness. VS was well tolerated, with onlymild side effects (cough and sensation of electrical stimulation). There was a significant improvement in NYHA class, Minnesota quality of life® (from 52±14 to 31±18, p<0.001), left ventricular end-systolic volume (from 208±71 to 190±83 ml, p=0.03), and a favourable trend toward reduction in enddiastolic volume. Conclusions: This novel approach to the treatment of patients with HF is feasible, and appears safe and tolerable. The preliminary efficacy results appear promising. These findings suggest the opportunity to proceed with a larger multicentre study.

Fluid overload in acute heart failure--re-distribution and other mechanisms beyond fluid accumulation.

Abstract: Although fluid overload is one of the most prominent features of acute heart failure (AHF), its mechanism remains challenging, due to the lack of consistent data from prospective studies. Traditionally, fluid overload was thought to be mainly the result of either increased intake of fluid and salt or non-adherence with diuretic therapy. However, recent data showed little weight change before or during an AHF event suggesting that in many cases fluid overload is caused by other mechanisms such as fluid redistribution and neurohormonal or inflammatory activation. Redistribution may be the result of a combined vascular and cardiac process reducing capacitance in the venous system (and hence increasing preload) and increasing arterial stiffness and resistance (and hence afterload). When these vascular processes occur acutely and are superimposed on reduced cardiac function; fluid is redistributed to the lungs instigating pulmonary congestion. In this paper we elaborate on this possible pathophysiological mechanism and review its potential causes and amplifiers.

Accuracy of a heart failure diagnosis in administrative registers.

Abstract: Background: The incidence of heart failure is frequently reported using hospital discharge diagnoses. The specificity of a diagnosis has been shown to be high but the sensitivity of a reported diagnosis is unknown. Purpose: To study the accuracy of a heart failure diagnosis reported to the Danish National Patient Registers during routine clinical work. Methods: The patient population consisted of 3644 consecutive patients admitted to all departments in one hospital. Diagnoses reported to the National Patient Register were recorded. A study team evaluated each patient independently of routine care, performed an echocardiogram and evaluated whether clinical symptoms of heart failure were present. Heart failure was defined in accordance with current ESC guidelines as symptoms of heart failure and evidence of cardiac dysfunction. Results: A registered diagnosis of heart failure (n=126) carried a specificity of 99% and a sensitivity of 29% for all patients. The positive predictive value was 81%, the negative predictive value 90%. Conclusion: The diagnosis of Heart Failure in the Danish National Registers is underreported, but very specific.

Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction.

Abstract: Aims: To determine the effect of transplantation of undifferentiated and cardiac pre-differentiated adipose stem cells compared with bone marrow mononuclear cells (BM-MNC) in a chronic model of myocardial infarction. Methods: Ninety-five Sprague–Dawley rats underwent left coronary artery ligation and after 1month received by direct intramyocardial injection either adipose derived stem cells (ADSC), cardiomyogenic cells (AD-CMG) or BM-MNC from enhanced-Green Fluorescent Protein (eGFP) mice. The control group was treated with culture medium. Heart function was assessed by echocardiography and 18F-FDG microPET. Cell engraftment, differentiation, angiogenesis and fibrosis in the scar tissue were also evaluated by (immuno)histochemistry and immunofluorescence. Results: One month after cell transplantation, ADSC induced a significant improvement in heart function (LVEF 46.3±9.6% versus 27.7±8% pre-transplant) and tissue viability (64.78±7.2% versus 55.89±6.3% pre-transplant). An increase in the degree of angiogenesis and a decrease in fibrosis were also detected. Although transplantation of AD-CMG or BM-MNC also had a positive, albeit smaller, effect on angiogenesis and fibrosis in the infarcted hearts, this benefit did not translate into a significant improvement in heart function or tissue viability. Conclusion: These results indicate that transplantation of adipose derived cells in chronic infarct provides a superior benefit to cardiac pre-differentiated ADSC and BM-MNC.

Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: A comparison with natriuretic peptides☆

Abstract: Background: Acute dyspnoea as a presenting symptom is a frequent diagnostic challenge for physicians. The main differential diagnosis is between dyspnoea of cardiac and non-cardiac origin. Natriuretic peptides have been shown to be useful in this setting. Ultrasound lung comets (ULCs) are a simple, echographic method which can be used to assess pulmonary congestion. Aim: To evaluate the accuracy of ULCs for predicting dyspnoea of cardiac origin compared to natriuretic peptides. Methods: We evaluated 149 patients admitted with acute dyspnoea. Chest sonography and NT-proBNP assessments were performed a maximum of 4 h apart and independently analyzed. ULCs were evaluated via cardiac probes placed on the anterior and lateral chest. Two independent physicians, blinded to ULCs and NT-proBNP findings, reviewed all the medical records to establish the aetiologic diagnosis of dyspnoea. Results: Cardiogenic dyspnoea was confirmed in 122 patients and ruled-out in 27 patients. The number of ULCs was significantly correlated to NT-proBNP values (r=.69, p<.0001). Receiver operating characteristic analysis, showed an area under the curve of .893 for ULCs and .978 (p=.001) for NT-proBNP, in predicting the cardiac origin of dyspnoea. Conclusions: In patients admitted with acute dyspnoea, pulmonary congestion, sonographically imaged as ULCs, is significantly correlated to NT-proBNP values. The accuracy of ULCs in predicting the cardiac origin of dyspnoea is high.

Heart failure with preserved ejection fraction: clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial.

Abstract: Background We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction - the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). Methods and results 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV. Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Conclusions Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to "real world" patients with heart failure and preserved ejection fraction.

Urinary neutrophil gelatinase associated lipocalin (NGAL), a marker of tubular damage, is increased in patients with chronic heart failure.

Abstract: Renal impairment, as measured by reduced glomerular filtration rate (GFR) and increased urinary albumin excretion (UAE), is prevalent in patients with chronic heart failure (CHF) and is associated with reduced survival. The prevalence of structural tubular damage in CHF is unknown. We investigated 90 CHF patients and 20 age and sex matched healthy controls, and determined estimated GFR, UAE, N terminal-pro brain natriuretic peptide (NT-proBNP) and urinary neutrophil gelatinase associated lipocalin (NGAL) as a marker for tubular damage. CHF patients had significantly lower averaged estimated GFR (64+/-17 vs 90+/-12 mL/min/1.73 m(2), P<0.0001), but higher NT-proBNP and UAE levels (both P<0.0001). Median urinary NGAL levels were markedly increased in CHF patients compared to controls (175 (70-346) vs 37 (6-58) microg/gCr, P<0.0001). Both serum creatinine (r=0.26, P=0.006) and eGFR (r=-0.29, P=0.002) were significantly associated with urinary NGAL levels as were NT-proBNP and UAE but to a lesser extent. In conclusion, renal impairment in CHF patients is not only characterised by decreased eGFR and increased UAE, but also by the presence of tubular damage, as measured by increased urinary NGAL concentrations.

Reversal of IFN‐γ, oxLDL and prolactin serum levels correlate with clinical improvement in patients with peripartum cardiomyopathy

Abstract: Aim: Peripartum cardiomyopathy (PPCM) is characterized by acute onset of heart failure of unknown aetiology. We aimed to identify mechanisms involved in initiation and progression of the disease. Methods and results: Serum markers related to cardiac function, apoptosis, oxidative stress, remodelling, inflammation and the nursing hormone prolactin were analyzed in PPCM patients and healthy controls. The kinetics of these markers were compared between patients who improved cardiac function (IMP) and those patients who did not improve (NIMP), over 6 months follow-up. All patients received ACE-inhibitors, beta-blockers and diuretics. Baseline levels of TGF-beta-1 were significantly lower, MMP-9 and VEGF were not different; all other markers were significantly higher in PPCM compared with controls. Only baseline NT-proBNP levels were higher in NIMP compared with IMP. After 6 months, NT-proBNP, oxLDL and IFN-γ were significantly lower in IMP and the decrease in oxLDL, IFN-γ and prolactin was significant in IMP but not in NIMP. Significant correlations were observed between the kinetics of NT-proBNP, oxLDL, prolactin and IFN-γ in PPCM patients. Conclusion: Baseline NT-proBNP and the failure to decrease oxLDL, IFN-γ and prolactin are associated with poor outcome in PPCM, suggesting a potential role of these factors in the pathophysiology of PPCM and for risk stratification of PPCM patients.

Gender related differences in patients presenting with acute heart failure: results from EuroHeart Failure Survey II

Abstract: 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.

The role of apelin in cardiovascular function and heart failure.

Abstract: Apelin is a novel peptide that acts through the APJ receptor, sharing similarities with the angiotensin II-angiotensin II type 1 receptor pathway. It is a peripheral vasodilator, powerful inotrope and may affect central fluid homeostasis. Animal and human studies suggest that it may play a role in the pathogenesis of heart failure by modulating the harmful effects of angiotensin II. Apelin is reduced in patients with heart failure and up regulated following favourable left ventricular remodelling. It is widely distributed in a number of tissues, mainly restricted to vascular endothelium. This comprehensive review of the literature highlights the important studies that have led to the discovery of apelin and its role in cardiovascular function and heart failure.

Adaptive servoventilation improves cardiac function in patients with chronic heart failure and Cheyne–Stokes respiration

Abstract: Background and aims Sleep disordered breathing (SDB), especially Cheyne–Stokes respiration (CSR) is common in patients with chronic heart failure (CHF). Adaptive servoventilation (ASV) was recently introduced to treat CSR in CHF. The aim of this study was to investigate the effects of ASV on CSR and CHF parameters. Methods In 29 male patients (63.9±9 years, NYHA≥II, left ventricular ejection fraction [LV-EF]≤40%), cardiorespiratory polygraphy, cardiopulmonary exercise (CPX) testing, and echocardiography were performed and concentrations of NT-proBNP determined before and after 5.8±3.5 months (median 5.7 months) of ASV (AutoSet CS™2, ResMed) treatment. All patients also received guideline-driven CHF therapy. Results Apnoea–hypopnoea-index was reduced from 37.4±9.4/h to 3.9±4.1/h (p<0.001). Workload during CPX testing increased from 81±26 to 100±31 W (p=0.005), oxygen uptake (VO2) at the anaerobic threshold from 12.6±3 to 15.3±4 ml/kg/min (p=0.01) and predicted peak VO2 from 58±12% to 69±17% (p=0.007). LV-EF increased from 28.2±7% to 35.2±11% (p=0.001), and NT-proBNP levels decreased significantly (2285±2192 pg/ml to 1061±1293 pg/ml, p=0.01). Conclusions In selected patients with CHF and CSR, addition of ASV to standard heart failure therapy is able to improve SDB, CPX test results, LV-EF and NT-proBNP concentrations.

Predicting hospitalization due to worsening heart failure using daily weight measurement: analysis of the Trans-European Network-Home-Care Management System (TEN-HMS) study

Abstract: Aims We sought to test the utility of weight gain algorithms to predict episodes of worsening heart failure (WHF) using home-telemonitoring data collected as part of the TEN-HMS study. Methods and results Simple rule-of-thumb (RoT) algorithms (i.e. 3 lbs in 1 day and 5 lbs in 3 days) and a moving average convergence divergence (MACD) algorithm were compared. WHF was defined as hospitalization for WHF or worsening of breathlessness or leg oedema. Of 168 patients, 45 were hospitalized with WHF and 76 were hospitalized for other reasons. On average, weight gain occurred in the 14 days prior to WHF hospitalizations but not in the 14 days prior to non-WHF hospitalizations [1.9 ± 4.7 lbs (0.9 ± 2.1 kg) vs. −0.4 ± 2.5 lbs (−0.2 ± 1.1 kg), P < 0.0001]. The true alerts rate was higher for the RoT algorithms compared with the MACD (58 and 65% vs. 20%). However, the RoT algorithms had much higher false alert rates (54 and 58% vs. 9%) rendering them of little practical use for predicting WHF events. Conclusion A MACD algorithm is more specific but less sensitive than RoT when trying to predict episodes of WHF based on daily weight measurements. However, many episodes of WHF do not appear to be associated with weight gain and therefore telemonitoring of weight alone may not have great value for heart failure management.

Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice.

Abstract: Background: Cardiac inflammation and generation of oxidative stress are known to contribute to doxorubicin (Dox)-induced cardiomyopathy. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signalling, we investigated whether or not TLR4 is involved in Dox-induced cardiotoxicity. Methods and results: Five days after a single injection of Dox (20 mg/kg; i.p.), left ventricular pressure–volume loops were measured in wild-type and TLR4-deficient mice (TLR4−/−) Dox-treated and control mice. Analyses of possible pathophysiological mechanisms were performed in left ventricular tissue and isolated myocytes, respectively. Dox injection resulted in an impairment of left ventricular function and neurohumoral activation, indexed by increased ET-1 expression. This was further associated with an increase in cardiac oxidative stress, inflammation and apoptosis, as indicated by an up-regulation of cardiac lipid peroxidation, TNF-α expression and enhanced content of TUNEL-positive cells. In contrast, TLR4−/−Dox mice showed improved left ventricular function with reduced oxidative and inflammatory stress response including reduced cardiac apoptosis. These results were found to be associated with an increase of GATA-4 expression. Conclusions: TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in Dox-induced cardiomyopathy.

Long-term prognosis of the transient left ventricular dysfunction syndrome (Tako-Tsubo cardiomyopathy): focus on malignancies.

Abstract: Background: The pathophysiology and long-term prognosis of the transient left ventricular dysfunction syndrome (LVDS, Tako-Tsubo cardiomyopathy) is largely unknown. Aims: To investigate the prevalence of malignancies and long-term mortality in patients with LVDS. Methods and results: Fifty patients with LVDS (47 females and 3 men, age 70±10 years) and 50 age- and gender-matched control patients with acute anterior myocardial infarction (MI) were evaluated. Nine patients (18%) with LVDS and 3 patients (6%) with MI had a previous history of malignancy at the time of the index event. On follow-up (2.9±1.6 years), 7 malignancies were newly diagnosed in the LVDS cohort whereas no new case of malignancy was found in the control group (p=0.01, odds ratio 16.95, 95% confidence interval [CI] 1.93–304.60). Overall mortality during follow-up did not differ significantly between both groups (hazard ratio 1.44 for death in LVDS patients, 95% CI 0.52–3.95, p=0.49); however, of those patients who died, cardiac deaths were more frequent in patients with MI (100% versus 11%in patients with LVDS, p<0.001). Conclusions: Our data suggest an association of LVDS with malignancies, potentially as a result of paraneoplastic phenomena. Long-term prognosis of patients with LVDS is no better than in patients with acute MI.

Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium.

Abstract: Background: The discrepancy between the functional improvements yielded experimentally by skeletal myoblasts (SM) transplanted in infarcted myocardium and the paucity of their long-term engraftment has raised the hypothesis of cell-mediated paracrine mechanisms. Methods and results: We analyzed gene expression and growth factors released by undifferentiated human SM (CD56 + ), myotubes (SM cultured until confluence) and fibroblasts-like cells (CD56 � ). Gene expression revealed up-regulation of pro-angiogenic (PGF), antiapoptotics (BAG-1, BCL-2), heart development (TNNT2, TNNC1) and extracellular matrix remodelling (MMP-2, MMP-7) genes in SM. In line with the gene expression profile, the analysis of culture supernatants of SM by ELISA identified the release of growth factors involved in angiogenesis (VEGF, PIGF, angiogenin, angiopoietin, HGF and PDGF-BB) as well as proteases involved in matrix remodelling (MMP2, MMP9 and MMP10) and their inhibitors (TIMPs). Culture of smooth muscle cells (SMC), cardiomyocytes (HL-1) and human umbilical vein endothelial cells (HUVECs) with SM-released conditioned media demonstrated an increased proliferation of HUVEC, SMC and cardiomyocytes (pb0.05) and a decrease in apoptosis of cardiomyocytes (pb0.05). Analysis of nude rats transplanted with human SM demonstrated expression of human-specific MMP-2, TNNI3, CNN3, PGF, TNNT2, PAX7, TGF-β, and IGF-1 1 month after transplant. Conclusions: Our data support the paracrine hypothesis whereby myoblast-secreted factors may contribute to the beneficial effects of myogenic cell transplantation in infarcted myocardium.

Poor outcome in end-stage heart failure patients with low circulating calcitriol levels.

Abstract: Background: Vitamin D receptor knockout mice develop typical signs of congestive heart failure (CHF). In approximately 20% of stable CHF patients, frankly low concentrations of the vitamin D hormone calcitriol are found. Aims: We investigated whether serum calcitriol concentrations predict clinical outcome in end-stage CHF. Methods and results: We collected blood samples in 383 end-stage CHF patients who were on a waiting list for cardiac transplantation. We assessed associations of calcitriol with disease severity and freedom from event (death or cardiac transplantation) during 1-year follow-up. In electively listed patients (n=325), 31% had deficient calcitriol levels (<43pmol/l) compared to 47% in urgently/high urgently listed patients (n=58; P<0.001). As determined by multivariable logistic regression, calcitriol was an independent predictor of the listing status ‘urgent/high urgent’ (P<0.001). Calcitriol concentrations were also significantly lower in patients with an event (n=233) compared to those who survived on the waiting list (P<0.001). Cox regression analysis revealed that patients in the highest calcitriol tertile had a hazard ratio (95% CI) for an event of 0.506 (0.334–0.767) compared with patients in the lowest calcitriol tertile (P=0.005), after adjustment for potential confounders. Conclusion: Data indicate that low serum calcitriol concentrations are independently associated with poor clinical outcome in end-stage CHF.

BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction

Abstract: Aims: To evaluate the best combination of clinical parameters and brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), to predict diastolic dysfunction (DD) in heart failure with preserved left ventricular ejection fraction (HF-PLEF) as determined by Doppler-echocardiography. Methods and Results: HF patients with EF > 40% in the CHARM Echocardiographic Substudy were included and classified to have normal diastolic function, or mild, moderate or severe diastolic dysfunction. Plasma BNP and NT-proBNP levels were measured and relevant clinical characteristics recorded. 181 participants were included in this analysis, 72 (40%) had moderate to severe DD. A model including age, sex, BNP, body mass index, history of atrial fibrillation, coronary artery disease, diabetes mellitus, hypertension and left atrial volume was highly predictive of moderate to severe DD; AUC 0.81 (0.73–0.88; p 100 pg/ml (OR 6.24 CI 2.42–16.09, p=0.0002), history of diabetes (OR 3.52 CI 1.43–8.70, p=0.006) and NT-proBNP > 600 pg/ml (OR 5.93 CI 2.21–15.92, p=0.0004), history of diabetes mellitus (OR 2.75 CI 1.12–6.76, p=0.03) respectively remained independent predictors of DD in HF-PLEF. Conclusions: Natriuretic peptides were the strongest independent predictors of DD, as determined by Doppler-echocardiography, in HF-PLEF.

Left ventricular solid body rotation in non-compaction cardiomyopathy : A potential new objective and quantitative functional diagnostic criterion?

Abstract: Background: Left ventricular (LV) twist originates from the interaction between myocardial fibre helices that are formed during the formation of compact myocardium in the final stages of the development of myocardial architecture. Since non-compaction cardiomyopathy (NCCM) is probably caused by intrauterine arrest of this final stage, it may be anticipated that LV twist characteristics are altered in NCCM patients, beyond that seen in patients with impaired LV function and normal compaction. Aims: The purpose of this study was to assess LV twist characteristics in NCCM patients compared to patients with non-ischaemic dilated cardiomyopathy (DCM) and normal subjects. Methods and results: The study population consisted of 10 patients with NCCM, 10 patients with DCM, and 10 healthy controls. LV twist was determined by speckle tracking echocardiography. In all controls and DCM patients, rotation was clockwise at the basal level and counterclockwise at the apical level. In contrast, in all NCCM patients the LV base and apex rotated in the same direction. Conclusions: These findings suggest that 'LV solid body rotation', with near absent LV twist, may be a new sensitive and specific, objective and quantitative, functional diagnostic criterion for NCCM.

Acute heart failure in the emergency department: Short and long-term outcomes of elderly patients with heart failure

Abstract: Aims: Previous epidemiologic studies of acute heart failure (AHF) have involved patients admitted to hospital and fail to account for that unknown proportion discharged directly from the emergency department (ED). We examined discharge rates, and whether outcomes, including mortality, differed based on admission status in AHF. Methods and results: This population-based cohort included all patients ≥65 years presenting to an Alberta ED with HF (ICD9-CM 428.x; 1998 to 2001). Patients were either not admitted (Not-ADM) or directly admitted to hospital (ADM) and followed for one-year. Of 10,415 AHF patients evaluated in the ED, 35% were Not-ADM whereas 65% were ADM. Thirty days after ED presentation the rates of death, re-ED or initial/re-hospitalisation were 3.3%, 44% and 19% for Not-ADM, and 10.9%, 33% and 21% for the ADM patients, respectively (all p<0.0001). At one-year, the rates of death, re-ED or initial/re-hospitalisation were 20%, 82% and 58% for Not-ADM, and 34%, 72% and 60% for ADM, respectively (all p<0.0001). Conclusions: One third of AHF patients were not immediately admitted after an ED visit but most present again to the ED, two-thirds were hospitalised and 20% died within the first year. Our findings provide new impetus to undertake risk assessment and treatment strategies in the ED for AHF.

Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure.

Abstract: Background: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective If current inhibitor) in advanced HF patients. Aims: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function. Methods and results: Ten NYHA class III patients (50±12 years, LVejection fraction 21±7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90′, followed by 0.05–0.075 mg/kg in the subsequent 90′. Baseline HR was 93±8 bpm, cardiac index (CI) 2.2±0.6 l/min⁎m 2 ; LV stroke volume 44±11 ml and systolic work 39±13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68±9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66±17 ml) and 53% (to 58±20 g) at 4 h. No serious adverse events occurred. Conclusion: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure.

The risk of heart failure in patients with type 2 diabetes treated with oral agent monotherapy.

Abstract: Aim To determine if the risk of developing heart failure (HF) is associated with the use of sulfonylurea or metformin in patients with diabetes. Methods Retrospective cohort study of all adults without HF newly treated with oral antidiabetic drugs in Saskatchewan, Canada between 1991 and 1999. Results Of 5631 diabetic subjects (mean age 66±13years) newly treated with a single oral agent and followed for 4.7 (±2.2) years, 981 developed HF (4.1 cases per 100 patient years). The incidence of HF was greater in patients using sulfonylurea monotherapy (4.4 cases per 100 treatment years) than those taking metformin monotherapy (3.3 cases per 100 years), and users of high-dose sulfonylureas were more likely to develop incident HF than users of high-dose metformin (adjusted HR 1.24, 95% CI 1.01–1.54). Users of high-dose sulfonylureas were also more likely to develop HF (HR 1.38, 95% CI 1.20–1.60) than users of low-dose sulfonylureas; no such association existed for metformin users (HR 1.06, 95% CI 0.81–1.41). Conclusions Users of higher doses of sulfonylurea exhibited a greater risk of developing HF. Clinicians should carefully weigh the need for high-dose sulfonylurea therapy in diabetic subjects with, or at high risk of, HF.

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure.

Abstract: Background: An adequate energy-protein intake (EPI) when combined with amino acid supplementation may have a positive impact nutritional and metabolic status in patients with chronic heart failure (CHF). Methods and results: Thirty eight stable CHF patients (27 males, 73.5±4 years; BMI 22.5±1.4 kg/m2), with severe depletion of muscle mass and were randomised to oral supplements of essential amino acids 8 g/day (EAA group; n=21) or no supplements (controls; n=17). patients had adequate EPI (energy ≥ 30 kcal/kg; proteins >1.1 g/kg). At baseline and 2-months after randomisation, the patients underwent metabolic (plasma lactate, pyruvate concentration; serum insulin level; estimate of insulin resistance by HOMA index), nutritional (measure of nitrogen balance), and functional (exercise test, walking test) evaluations. Body weight increased by >1 kg in 80% of supplemented patients (mean 2.96 kg) and in 30% of controls (mean 2.3 kg) (interaction <0.05). Changes in arm muscle area, nitrogen balance, and HOMA index were similar between the two treatment groups. Plasma lactate and pyruvate levels increased in controls (p<0.01 for both) but decreased in the supplemented group (p<0.01 and 0.02 respectively). EAA supplemented patients but not controls improved both exercise output and peak oxygen consumption and walking test. Conclusions: Adequate EPI when combined with essential amino acid supplementation may improve nutritional and metabolic status in most muscle-depleted CHF patients.

Low-dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit.

Abstract: Background: Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects. Aim: To investigate the haematocrit independent effects of EPO on cardiac function. Methods and results: Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 μg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 μg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p<0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dtmax) and relaxation (dP/dtmin) indices of the LV at 9-weeks (all p<0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p<0.01) and 27% in MI-EPO-low (p<0.05)) and an attenuated switch to slow β-MHC isoforms in both EPO groups. Conclusions: EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.

The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial.

Abstract: Background: Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add-on-treatment are available. Therefore a large morbidity/mortality trial was performed. Aim: To investigate the efficacy and safety of an add-on treatment with Crataegus extract WS® 1442 in patients with congestive heart failure. Methods: In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF≤35%) were included and received 900 mg/day WS® 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event. Results: 2681 patients (WS® 1442: 1338; placebo: 1343) were randomised. Average time to first cardiac event was 620 days for WS® 1442 and 606 days for placebo (event rates: 27.9% and 28.9%, hazard ratio (HR): 0.95, 95% CI [0.82;1.10]; p=0.476). The trend for cardiac mortality reduction with WS® 1442 (9.7% at month 24; HR: 0.89 [0.73;1.09]) was not statistically significant (p=0.269). In the subgroup with LVEF ≥ 25%, WS® 1442 reduced sudden cardiac death by 39.7% (HR 0.59 [0.37;0.94] at month 24; p=0.025). Adverse events were comparable in both groups. Conclusions: In this study, WS® 1442 had no significant effect on the primary endpoint. WS® 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS® 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.

Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure

Abstract: Background: Connective tissue growth factor (CTGF) has been recently reported as a mediator of myocardial fibrosis; however, the significance of plasma CTGF concentration has not been evaluated in patients with heart failure. The aim of this study was to investigate the clinical utility of plasma CTGF concentration for the diagnosis of heart failure. Methods and results: We evaluated fifty-two patients with chronic heart failure. The plasma concentration of CTGF and other markers of fibrosis were assessed and compared with clinical and echocardiographic data. Plasma CTGF was significantly elevated in symptomatic patients in proportion to their NYHA classes and was significantly correlated with plasma brain natriuretic peptide (BNP) concentration (r = 0.395, P < 0.01). Plasma CTGF was also correlated with plasma transforming growth factor beta (TGF-β) (r = 0.512, P < 0.01), matrix metalloproteinase (MMP)-2 (r = 0.391, P < 0.05) and tissue inhibitor of MMP (TIMP)-2 (r = 0.354, P < 0.05) concentrations. Interestingly, plasma CTGF was correlated with E/E' value evaluated by tissue Doppler echocardiography (r = 0.593, P = 0.012), but not with systolic function and left ventricular mass. Conclusion: Our study suggests that plasma CTGF concentration is a novel diagnostic marker for cardiac dysfunction and may provide additional specific information about myocardial fibrosis in chronic heart failure patients.

Adenosine and kidney function: potential implications in patients with heart failure.

Abstract: Therapy of heart failure is more difficult when renal function is impaired. Here, we outline the effects on kidney function of the autacoid, adenosine, which forms the basis for adenosine A(1) receptor (A(1)R) antagonists as treatment for decompensated heart failure. A(1)R antagonists induce a eukaliuretic natriuresis and diuresis by blocking A(1)R-mediated NaCl reabsorption in the proximal tubule and the collecting duct. Normally, suppressing proximal reabsorption will lower glomerular filtration rate (GFR) through the tubuloglomerular feedback mechanism (TGF). But the TGF response, itself, is mediated by A(1)R in the preglomerular arteriole, so blocking A(1)R allows natriuresis to proceed while GFR remains constant or increases. The influence of A(1)R over vascular resistance in the kidney is augmented by angiotensin II while A(1)R activation directly suppresses renin secretion. These interactions could modulate the overall impact of A(1)R blockade on kidney function in patients taking angiotensin II blockers. A(1)R blockers may increase the energy utilized for transport in the semi-hypoxic medullary thick ascending limb, an effect that could be prevented with loop diuretics. Finally, while the vasodilatory effect of A(1)R blockade could protect against renal ischaemia, A(1)R blockade may act on non-resident cells to exacerbate reperfusion injury, where ischaemia to occur. Despite these uncertainties, the available data on A(1)R antagonist therapy in patients with decompensated heart failure are promising and warrant confirmation in further studies.