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John G F Cleland

Publications and source records attributed to John G F Cleland.

At least 19 recordsLinked to original sources

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

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

Adolescent↗

Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and 2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty.

This article provides information and a commentary on trials presented at the American Heart Association meeting held in November 2006, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. The OAT study failed to show a benefit of PCI over optimal medical therapy in patients with persistent total occlusion of the infarct related artery following a myocardial infarction. In SALT 1 and 2, tolvaptan was found to correct hyponatraemia of various aetiologies; however, whether this has an impact on heart failure prognosis requires further evaluation. A placebo controlled study of myocardial implantation of skeletal myoblasts in patients with moderate to severe LVSD (MAGIC) showed equivocal/uncertain effects, long term follow-up data are awaited. The ABCD study which compared the ability of an invasive and a non-invasive test to identify patients at risk of arrhythmic events prior to ICD implantation, suggested that the two strategies were comparable, although the practical value of either test remains uncertain and the study had many major flaws. The PABA-CHF study hinted that pulmonary vein antrum isolation might be more effective than AV node ablation with bi-ventricular pacing for the treatment of patients with heart failure in atrial fibrillation. In IMPROVE-CHF, an NT-pro BNP guided treatment strategy was found to reduce the cost of managing patients with acute breathlessness.

American Hospital Association↗

Management of octogenarians hospitalized for heart failure in Euro Heart Failure Survey I.

AIMS: Here, the aim is to study the management of octogenarians hospitalized for heart failure in Euro Heart Failure Survey I. Heart Failure (HF) is common in older people and associated with poor outcome. METHODS AND RESULTS: We compared clinical characteristics, treatment, and short-term outcomes in 2780 octogenarians (group A, median age 85 years) and in 7912 younger patients (group B, median age 69 years) enrolled in the Euro Heart Failure Survey I. There were 37% males in group A vs. 59% in group B (P < 0.001). Co-morbidities were more common in group A. Ejection fraction was measured only in 38% in group A vs. 65% in group B (P < 0.001) and when measured was preserved in 50 vs. 40% (P < 0.001). In-hospital and 12 weeks follow-up mortality were, respectively, 13 vs. 5% (P < 0.001) and 12 vs. 6% (P < 0.001) in groups A and B. Acute cardiac conditions and co-morbidity predicted mortality, whereas the use of angiotensin-converting enzyme inhibitor (ACE-I) and beta-blockers was associated with a better outcome. ACE-I and beta-blockers were used in 50 vs. 66% (P < 0.001) and 24 vs. 42% (P < 0.001) in groups A and B, respectively, whereas diuretics, digitalis, and nitrates were more commonly used in octogenarians. CONCLUSION: Preserved systolic function, multiple co-morbidities, and high mortality are observed in octogenarians with HF. In these patients, cardiac function is assessed in only a minority and treatments known to improve prognosis in younger patients under-utilized. Overall, the management of octogenarians with HF does not follow international guidelines.

Adrenergic beta-Antagonists↗

Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure.

BACKGROUND: No specific guidelines exist on how to manage renal dysfunction (RD) in patients with chronic heart failure (CHF). AIMS: To identify the proportion of patients with moderate to severe RD and CHF who showed an improvement in their renal function in response to a systematic management algorithm. METHODS: Stable patients with CHF and RD (defined by a serum creatinine (SCr) of >130 micromol/l (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following changes were implemented: switching aspirin to clopidogrel, halving the dose of both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching between bisoprolol and carvedilol. RESULTS: Two thirds of patients in whom diuretics were reduced, and one fifth of patients in whom ACE inhibitors were reduced, improved their SCr by >25.5 micromol/l (0.3 mg/dl). All these changes were more marked in the presence of bilateral renal artery stenosis. Compared to a reference group, in whom no changes were implemented, the treatment group showed an improvement in their mean SCr by 35 micromol/l (0.4 mg/dl), p<0.001. CONCLUSION: Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients.

Aged↗

The long-term cost-effectiveness of cardiac resynchronization therapy with or without an implantable cardioverter-defibrillator.

AIMS: Cardiac resynchronization therapy (CRT-P) is an effective treatment for patients with heart failure and cardiac dyssynchrony with moderate or severe symptoms despite pharmacological therapy. The addition of an implantable cardioverter-defibrillator (ICD) function may further reduce the risk of sudden death. We assessed the cost-effectiveness of CRT-P compared with medical therapy (MT) alone, and the cost-effectiveness of CRT-ICD + MT compared with CRT-P + MT, on incremental cost per quality adjusted life year (QALY) and life year using data from two landmark clinical trials. METHODS AND RESULTS: A Markov model with Monte Carlo simulation to assess costs, life years, and QALYs associated with CRT (+/- ICD) and MT in patients with heart failure and cardiac dyssynchrony, on the basis of a UK healthcare perspective was constructed. NYHA class distribution and transitions, associated health utilities, rates and cause of hospitalization and death were estimated from individual patient data from the CArdiac REsychronization in Heart Failure (CARE-HF trial). The estimated additional benefit on survival of an ICD was based on results from COMPANION. The base case analysis used 10 000 individual life-time simulations assuming a battery life of 6 years for CRT-P and 7 years for CRT-ICD. From a life-time perspective in a 65-year-old patient, the incremental cost-effectiveness of CRT-P compared with MT is 7538 euros (95% CI 5325-11,784 euros) per QALY gained and 7011euros (95% CI 5346-10,003 euros) per life year gained. The incremental cost-effectiveness of CRT-ICD compared with CRT-P is 47,909 euros (95% CI 35,703-79,438 euros) per QALY gained, and 35,864 euros (95% CI 26,709-56,353 euros) per life year gained. CONCLUSION: Long-term treatment with CRT-P appears cost-effective compared with MT alone. From a life-time perspective, assuming a reasonable life expectancy when receiving effective treatment for heart failure, CRT-ICD may also be considered cost-effective when compared with CRT-P + MT.

Adolescent↗

Prognostic value of the VE/VCO2 slope calculated from different time intervals in patients with suspected heart failure.

BACKGROUND: Maximal exercises testing, whether involving cycling- or walking-based protocols, are often not well tolerated in patients with chronic heart failure (CHF). The peak oxygen consumption and the slope of the relation between ventilation (V(E)) and carbon dioxide production (V(CO(2))) are independent predictors of outcome and help risk stratification. The prognostic usefulness of submaximal exercise testing is not clear. The aim of the present study was to assess the prognostic value of the V(E)/V(CO(2)) slope when derived from data acquired from submaximal exercise. METHODS: 394 patients referred with breathlessness and suspected heart failure (74% male) (mean+/-S.D.) age 60+/-12 years; BMI 27+/-5 performed a CPET to determine peak V(O(2)) and the V(E)/V(CO(2)) slope. The V(E)/V(CO(2)) slope was calculated using least squares regression from data acquired from the first 25% of exercise (mean V(E)/V(CO(2)) slope+/-SD; 30.6+/-5.7), 50% (29.6+/-6.9), below the ventilatory compensation point (sub-VCP) (29.9+/-6.8), and all data points (full slope) (32.1+/-7.8). For each measure, patients were divided into quartiles and Kaplan-Meier curves were constructed to determine probability of death after 24 months. The prognostic value of the different classifications was assessed using the chi(2) statistic from the Mantel-Cox log-rank test. RESULTS: During a mean follow-up period of 41+/-19 months, 48 patients died. For the V(E)/V(CO(2)) slope, the log-rank statistic was greatest for the full slope (chi(2)=53.7; P=0.0001), followed by the sub-VCP (chi(2)=45.5; P=0.0001), 50% (chi(2)=41.9; P=0.0001), and 25% (chi(2)= 26.0; P=0.01). The pair-wise log-rank statistic between the fourth and third quartiles was also greatest using the full slope (chi(2)=25.4; P=0.001) followed in order by the sub-VCP (chi(2)=20.1; P=0.001), 50% (chi(2)=19.7; P=0.001), and 25% (chi(2)=14.2; P=0.05). Using the stratified slope measurements entered into a Cox regression analysis using a forward LR stepwise elimination procedure; only the full slope remained significant (P=0.0001). CONCLUSIONS: The V(E)/V(CO(2)) slope should be calculated from all data points to optimise prognostic sensitivity. Data acquired from the first 50% of exercise and below the VCP provide adequate prognostic surrogates in patients who may not be able to perform maximal exercise testing (i.e. in patients with a respiratory exchange ratio<1.10).

Aged↗

Clinical trials update from the Heart Failure Society of America meeting: FIX-CHF-4, selective cardiac myosin activator and OPT-CHF.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Failure Society of America meeting held in Seattle in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Devices designed to improve cardiac contractility may have improved exercise tolerance and quality of life in the FIX-CHF-4 study; however, uncertainties in trial interpretation exist. The results of a study reporting the first administration of the selective myosin activator CK-1827452 to human volunteers, support the initiation of clinical trials in heart failure patients. In OPT-CHF, oxypurinol failed to show benefit compared to placebo for the treatment of heart failure, although a retrospective subgroup analysis suggests that it may be beneficial in patients with elevated serum uric acid levels.

Cardiotonic Agents↗

Clinical trials update from the joint European Society and World Congress of Cardiology meeting: PEP-CHF, ACCLAIM and the HHH study.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the joint European Society and World Congress of Cardiology meeting held in Barcelona in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. The PEP-CHF study suggests that perindopril improves symptoms and functional capacity and may reduce heart failure hospitalisations in patients with diastolic heart failure. Although immune modulation therapy failed to reduce the incidence of all-cause mortality and cardiovascular hospitalisations in the ACCLAIM study, the observed differences in outcome in some heart failure patients warrants further investigation. The HHH study failed to show a beneficial effect of telemonitoring over usual care in patients with heart failure but potentially important country interactions were observed.

Aged↗

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

BACKGROUND: Treatment of heart failure (HF) due to left ventricular systolic dysfunction (LVSD) is effective, but many patients are not treated in accordance with guidelines. This may reflect a lack of adequate organisation of care or co-morbidity contra-indicating therapy. AIMS: To evaluate the effect of co-morbidities on the prescription of neurohormonal antagonists for HF. METHODS AND RESULTS: The EuroHeart Failure Survey identified 10,701 patients with suspected or confirmed HF during 2000 and 2001, 64% of whom had an imaging test and 3658 had documented LVSD. This last group constitutes the focus of this report. Renal dysfunction was associated with lower prescription of ACE inhibitors at discharge (74% vs. 83%, p<0.001). Beta-blockers were less often used in patients with respiratory disease (32% vs. 53%, p<0.001). Co-morbidity did not appear to affect the use of spironolactone. There were few important international differences in uptake of key therapies amongst European countries with widely differing cultures and economic status. CONCLUSIONS: Guidelines appear successful in creating a relatively uniform approach to the treatment for HF due to LVSD in diverse medical cultures. Relevant co-morbidity seems to be responsible for a substantial reduction in the prescription of ACE inhibitors and beta-blockers. However, whilst co-morbidity indicates the need for greater caution, it is often not a valid contra-indication to life-saving therapy.

Adrenergic beta-Antagonists↗

The perindopril in elderly people with chronic heart failure (PEP-CHF) study.

AIMS: Many patients who receive a diagnosis of heart failure have neither a low left ventricular (LV) ejection fraction nor valve disease. Few substantial randomized controlled trials have been conducted in this population, none has focussed on patients with evidence of diastolic dysfunction and none has shown clear benefit on symptoms, morbidity, or mortality. METHODS AND RESULTS: This was a randomized double-blind trial, comparing placebo with perindopril, 4 mg/day in patients aged > or =70 years with a diagnosis of heart failure, treated with diuretics and an echocardiogram suggesting diastolic dysfunction and excluding substantial LV systolic dysfunction or valve disease. The primary endpoint was a composite of all-cause mortality and unplanned heart failure related hospitalization with a minimum follow-up of 1 year. A total of 850 patients were randomized. Their mean age was 76 (SD 5) years and 55% were women. Median follow-up was 2.1 (IQR 1.5-2.8) years. Enrollment and event rates were lower than anticipated, reducing the power of the study to show a difference in the primary endpoint to 35%. Many patients withdrew from perindopril (28%) and placebo (26%) after 1 year and started taking open-label ACE-inhibitors. Overall, 107 patients assigned to placebo and 100 assigned to perindopril reached the primary endpoint (HR 0.919: 95% CI 0.700-1.208; P = 0.545). By 1 year, reductions in the primary outcome (HR 0.692: 95% CI 0.474-1.010; P = 0.055) and hospitalization for heart failure (HR 0.628: 95% CI 0.408-0.966; P = 0.033) were observed and functional class (P < 0.030) and 6-min corridor walk distance (P = 0.011) had improved in those assigned to perindopril. CONCLUSION: Uncertainty remains about the effects of perindopril on long-term morbidity and mortality in this clinical setting since this study had insufficient power for its primary endpoint. However, improved symptoms and exercise capacity and fewer hospitalizations for heart failure in the first year were observed on perindopril, during which most patients were on assigned therapy, suggesting that it may be of benefit in this patient population.

Aged↗

The diagnostic utility of N-terminal pro-B-type natriuretic peptide for the detection of major structural heart disease in patients with atrial fibrillation.

AIMS: To assess the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the diagnosis of major structural heart disease (MSHD) in patients with atrial fibrillation (AF) compared with those with sinus rhythm (SR) using receiver operator characteristic (ROC) analysis. NT-proBNP is elevated in MSHD and heart failure (HF). AF, a common finding in HF and MSHD, is also associated with raised plasma NT-proBNP. As a result, the utility of NT-proBNP for predicting MSHD may be reduced. METHODS AND RESULTS: One thousand four hundred and seventy-six patients underwent assessment at a single centre, performed without the knowledge of NT-proBNP levels. MSHD included left ventricular (LV) systolic and diastolic dysfunctions, left-sided valvular disease, right heart disease (including pulmonary hypertension) and severe LV hypertrophy. One hundred and fifty-five patients were excluded due to renal impairment, atrial flutter, or a pacemaker. Seven hundred and ninety-three patients were diagnosed with MSHD. Median NT-proBNP concentrations for patients with MSHD were 960 (IQR 359-2625) pg/mL and 2491 (1443-4368) pg/mL for SR (n = 591) and AF (n = 202), respectively (P < 0.001). Patients without MSHD had NT-proBNP levels of 179 (90-401) pg/mL and 1000 (659-1760) pg/mL for SR (n = 454) and AF (n = 74), respectively (P < 0.001). The area under the ROC curve for NT-proBNP to detect MSHD was 0.79 for SR (95% CI 0.77-0.82) and 0.78 for AF (95% CI 0.72-0.84). NT-proBNP cut-off levels necessary to achieve a 1 in 100 false negative rate were 27.5 (7.5-30.5) pg/ml and 524 (253-662) pg/ml for SR and AF, respectively. CONCLUSION: NT-proBNP performs as well in patients with SR as in those with AF. However, significantly higher cut-off levels are required for patients with AF to achieve similar levels of diagnostic specificity.

Aged↗

New generation 3-dimensional echocardiography for left ventricular volumetric and functional measurements: comparison with cardiac magnetic resonance.

AIMS: Non-invasive assessment of left ventricular (LV) structure and function is important in the evaluation of cardiac patients. This study was designed to test the accuracy and reproducibility of new generation 3-dimensional echocardiography (3DE) in measuring volumetric and functional LV indices as compared with current "gold standard" of non-invasive cardiac imaging, cardiac magnetic resonance (CMR). METHODS AND RESULTS: Sixty-four subjects with good acoustic windows, including 40 cardiac patients with LV ejection fraction (EF)<45%, 14 patients with EF>45% and 10 normal volunteers underwent 3DE using a commercially available Philips Sonos 7500 scanner equipped with a matrix phase-array x4 xMATRIX transducer, and CMR on a 1.5 T Signa CV/i scanner (GE Medical Systems). Volumetric assessment was performed with analytical 4D-LV-Analysis software (TomTec) for 3DE and MRI-Mass software (Medis) for CMR. We found no significant differences in LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF with excellent correlations between the indices measured using 3DE and CMR (r=0.97, r=0.98, and r=0.94, respectively). Bland-Altman analysis showed bias of 7 ml for EDV, 3 ml for ESV and -1% for EF with 3DE with corresponding limits of agreement (2SD) of 28 ml, 22 ml and 10%, respectively. Intraobserver and interobserver variabilities were for EDV: 3% and 4% (3DE) vs 2% and 2% (CMR), for ESV: 3% and 6% (3DE) vs 2% and 3% (CMR), and for EF: 4% and 4% (3DE) vs 2% and 4% (CMR), respectively. CONCLUSION: New generation 3DE provides accurate and reproducible quantification of LV volumetric and functional data in subjects with good acoustic windows as compared with CMR.

Adult↗

Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.

Anemia↗

Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure.

BACKGROUND: Atrial fibrillation/flutter (AF) and heart failure often coexist; however, the effect of cardiac resynchronization therapy (CRT) on the incidence of AF and on the outcome of patients with new-onset AF remains undefined. METHODS AND RESULTS: In the CArdiac REsynchronisation in Heart Failure (CARE-HF) trial, 813 patients with moderate or severe heart failure were randomly assigned to pharmacological therapy alone or with the addition of CRT. The incidence of AF was assessed by adverse event reporting and by ECGs during follow-up, and the impact of new-onset AF on the outcome and efficacy of CRT was evaluated. By the end of the study (mean duration of follow-up 29.4 months), AF had been documented in 66 patients in the CRT group compared with 58 who received medical therapy only (16.1% versus 14.4%; hazard ratio 1.05; 95% confidence interval, 0.73 to 1.50; P=0.79). There was no difference in the time until first onset of AF between groups. Mortality was higher in patients who developed AF, but AF was not a predictor in the multivariable model (hazard ratio 1.17; 95% confidence interval, 0.82 to 1.67; P=0.37). In patients with new-onset AF, CRT significantly reduced the risk for all-cause mortality and all other predefined end points and improved ejection fraction and symptoms (no interaction between AF and CRT; all P>0.2). CONCLUSIONS: Although CRT did not reduce the incidence of AF, CRT improved the outcome regardless of whether AF developed.

Aged↗

Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase].

AIMS: The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction < or =35%, markers of cardiac dyssynchrony, and persistent moderate or severe symptoms of heart failure despite pharmacological therapy, to implantation of a cardiac resynchronization therapy (CRT) device or not. The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [median 29.6, interquartile range (IQR) 23.6-34.6]. Prior to study closure, an extension phase lasting a further 8 months (allowing time for data analysis and presentation) was declared during which cross-over was discouraged. METHODS AND RESULTS: This was an extension of the already reported open-label randomized trial described above. The primary outcome of the extension phase was all-cause mortality from the time of randomization to completion of the extension phase. The secondary outcome was mode of death. The mean follow-up was 37.4 months (median 37.6, IQR 31.5-42.5, range 26.1-52.6 months). There were 154 deaths (38.1%) in 404 patients assigned to medical therapy and 101 deaths (24.7%) in 409 patients assigned to CRT (hazard ratio 0.60, 95% CI 0.47-0.77, P<0.0001) without evidence of heterogeneity in pre-specified subgroups. A reduction in the risk of death due to heart failure (64 vs. 38 deaths; hazard ratio 0.55, 95% CI 0.37-0.82, P=0.003) and sudden death was observed (55 vs. 32; hazard ratio 0.54, 95% CI 0.35-0.84, P=0.005). CONCLUSION: The benefits of CRT observed in the main trial persist or increase with longer follow-up. Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death.

Aged↗

Anemia, renal dysfunction, and their interaction in patients with chronic heart failure.

Anemia and renal dysfunction (RD) are frequent complications seen in chronic heart failure (HF). However, the prevalence and interaction of these co-morbidities in a representative population of outpatients with chronic HF is poorly described. In this study, it was sought to determine the association between RD and anemia in patients with HF enrolled in a community-based HF program. Nine hundred fifty-five patients with HF due to left ventricular systolic dysfunction were investigated for the prevalence of anemia and its cause and followed for a median of 531 days. Anemia was defined as hemoglobin < 12.0 g/dl in women and < 13.0 g/dl in men. RD was defined as a calculated glomerular filtration rate of < 60 ml/min. The prevalence of anemia was 32%. Fifty-three percent of patients with and 27% of those without anemia had > or = 1 test suggesting hematinic deficiency. The prevalence of RD was 54%. Forty-one percent of patients with and 22% of patients without RD had anemia, with similar proportions associated with iron deficiency in the presence or absence of RD. Anemia and RD independently predicted a worse outcome, and this effect was additive. In conclusion, in outpatients with chronic HF, anemia and RD are common and co-exist but confer independent prognostic information. A deficiency of conventional hematinic factors may cause about 1/3 of anemia in this clinical setting.

Aged↗

The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET.

AIMS: Anaemia is a common comorbidity in chronic heart failure (CHF). The predictors of new onset anaemia (NOA) and its long-term prognostic value, particularly in patients treated with beta-blockers, are not known. METHODS AND RESULTS: In COMET, 3029 patients with CHF in NYHA II-IV and EF <35% were randomized to carvedilol or metoprolol tartrate and were followed for an average of 58 months. Plasma haemoglobin (Hb) concentrations were measured at a central laboratory at randomization, at four monthly intervals for the first year and annually thereafter. According to WHO criteria, anaemia was defined when Hb measured <13 g/dL for men and <12 g/dL for women. We considered anaemia to be severe when Hb <11.5 g/dL for men and <10.5 g/dL for women. The baseline mean Hb was 14.2 +/- 1.5 g/dL (n = 2996) and 15.9% of patients had anaemia (males, 16.0%; females, 15.2%). At baseline, severe anaemia was found in 3.3% of patients (males, 3.6%; females, 2.0%). During the study, all-cause mortality (RR 1.47) death or hospitalization (RR 1.28), and heart failure hospitalization (RR 1.43, all P < 0.0001) were higher in anaemic when compared with non-anaemic patients. In patients without anaemia at baseline, at the end of the study, the cumulative frequency of NOA was 28.1% in males and 27.0% in females. NOA increased over time from 14.2% at year 1 to 27.5% at year 5. Predictors of NOA were: higher age, diuretic dose, creatinine (all P < 0.0001), higher serum potassium, lower serum sodium, body mass index, and use of aldosterone antagonists, carvedilol, and digitalis (all P < 0.03). Treatment with carvedilol (vs. metoprolol tartrate) was associated with a 24% increased risk to develop NOA (P = 0.0047), but not severe anaemia (P = 0.18). Patients with a Hb decrease of >3 g/dL (RR 3.37, P < 0.0001) or of 2.0-3.0 g/dL (RR 1.47, P = 0.011) from baseline had an increased subsequent mortality when compared with patients having Hb increases of 0-1.0 g/dL. CONCLUSION: In stable ambulatory CHF patients, development of NOA is frequent and can be predicted by a set of clinical variables. Decreases in Hb over time relate to future increased morbidity and mortality.

Aged↗