Increased metaboreceptor stimulation explains the exaggerated exercise pressor reflex seen in heart failure.
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Animals↗
Biomedical subjects
Andrew J S Coats
Publications and source records attributed to Andrew J S Coats.
The epidemiology of heart failure in Australia.
BACKGROUND: The epidemiology of heart failure is poorly understood. Australia has one of the highest rates of cardiovascular disease in the world with heart failure representing a large proportion of this group, yet there is minimal data on the incidence or prevalence. AIMS: To determine the epidemiological impact of heart failure in Australia by assessing mortality and morbidity data. METHODS: Data were obtained from National and State health organisations in terms of morbidity and mortality of heart failure. Data were obtained from several sources so as to provide a comprehensive picture of the available epidemiological data on heart failure. RESULTS: The mortality rates associated with heart failure have been decreasing substantially over the last 20 years. However, there appears to be a stabilisation of heart failure presentations over the last decade, both nationally and in the state of New South Wales. Extrapolation of the data to assess prevalence of heart failure in the community was not possible. CONCLUSIONS: Currently, mortality rates for heart failure are decreasing in Australia, while there does not appear to be any real increase in the numbers of patients admitted to hospital with a subsequent diagnosis of heart failure over a 10 year period.
Age Distribution↗
Statin use and survival in patients with chronic heart failure--results from two observational studies with 5200 patients.
BACKGROUND: There is minimal evidence that HMG-CoA reductase inhibitors (statins) are beneficial in patients with chronic heart failure (CHF). Treatment with statins may lead to a lower mortality in CHF, independent of cholesterol levels, CHF etiology and clinical status. METHODS: In a first study, we included 3132 patients with CHF from the ELITE 2 study in whom information on body mass index (BMI) and statin use at baseline were available. In a second study, we pooled the databases of 5 tertiary referral centers with 2068 CHF patients. In this cohort 705 patients were on a statin (34%), 585 of 1202 (49%) patients with ischemic etiology, and 120 of 866 (14%) patients with non-ischemic etiology (established by coronary angiography). FINDINGS: Patients in ELITE 2 who received statin therapy at baseline (n=397, 13%) had lower mortality (hazard ratio [HR] 0.61, 95% CI 0.45-0.83; p=0.0007). In univariate analysis, increasing age, NYHA class, creatinine, and decreasing BMI, LVEF, and cholesterol, as well as lack of beta-blocker treatment and ischemic etiology (all p<0.002) related to higher mortality. In multivariable analysis, statin therapy related to lower mortality independently of all these variables (adjusted HR 0.66, 95% CI 0.47-0.93; p=0.017). In the second study CHF patients on statins had lower mortality (adjusted HR 0.58, 95% CI 0.44-0.77; p=0.0001). Both in patients with ischemic (p<0.0001) and non-ischemic etiology (p=0.028) statin treatment related to better survival. INTERPRETATION: In chronic heart failure, treatment with statins is related to lower mortality, independent of cholesterol levels, disease etiology and clinical status.
Aged↗
The Research Quality Framework and its implications for health and medical research: time to take stock?
As the Australian university sector awaits final decisions about the introduction and stipulations of a research quality framework (RQF), to assess the quality and impact of research, we have studied international commentary on the value of such exercises. This suggests there is little hard evidence to recommend the proposed RQF. The UK government led the field in 1986 with its research assessment exercise (RAE), which is widely believed to have compromised clinical academic medicine by failing to satisfactorily acknowledge the contribution of clinical academics, not only to research but also to teaching and clinical practice. After the 2008 RAE, the UK government will move to a simpler, metrics-based system for assessing research quality and allocating funding. The New Zealand Performance Based Review Fund (PBRF), introduced in 2003, is based on a combination of peer review and performance indicators. Several concerns have been raised; among them is the real cost-benefit ratio of participation, with reports that many universities have spent more on the exercise than they will gain in funding increases. The scoring system has received the most criticism and, after the partial round assessment scheduled for this year, the controversial unit of assessment will be reviewed. It might be more cost-effective for Australia to modify existing research assessment processes than to undertake a potentially costly and arduous exercise.
Advisory Committees↗
Redefining heart failure.
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Heart Failure↗
Sleep-disordered breathing in a general heart failure population: relationships to neurohumoral activation and subjective symptoms.
The aim of this study was to determine the prevalence of sleep-related breathing disorders (SDB) in a UK general heart failure (HF) population, and assess its impact on neurohumoral markers and symptoms of sleepiness and quality of life. Eighty-four ambulatory patients (72 male, mean (SD) age 68.6 (10) yrs) attending UK HF clinics underwent an overnight recording of respiratory impedance, SaO2 and heart rate using a portable monitor (Nexan). Brain natriuretic peptide (BNP) and urinary catecholamines were measured. Subjective sleepiness and the impairment in quality of life were assessed (Epworth Sleepiness Scale (ESS), SF-36 Health Performance Score). SDB was classified using the Apnoea/Hypopnoea Index (AHI). The prevalence of SDB (AHI > 15 events h(-1)) was 24%, increasing from 15% in mild-to-moderate HF to 39% in severe HF. Patients with SDB had significantly higher levels of BNP and noradrenaline than those without SDB (mean (SD) BNP: 187 (119) versus 73 (98) pg mL(-1), P = 0.02; noradrenaline: 309 (183) versus 225 (148) nmol/24 h, P = 0.05). There was no significant difference in reported sleepiness or in any domain of SF-36, between groups with and without SDB (ESS: 7.8 (4.7) versus 7.5 (3.6), P = 0.87). In summary, in a general HF clinic population, the prevalence of SDB increased with the severity of HF. Patients with SDB had higher activation of a neurohumoral marker and more severe HF. Unlike obstructive sleep apnoea, SDB in HF had little discernible effect on sleepiness or quality of life as measured by standard subjective scales.
Aged↗
Beta-adrenoceptor antagonists in elderly patients with chronic heart failure: therapeutic potential of third-generation agents.
Chronic heart failure (CHF) is a common and disabling condition with an incidence and prevalence that increase sharply with age. The median age of presentation of new heart failure cases is > 75 years. Effective treatments, including beta-adrenoceptor antagonists, have been proven in randomised, controlled trials. The average age in these placebo-controlled mortality and morbidity studies of beta-adrenoceptor antagonists in heart failure has, however, been < 63 years, and all patients with an ejection fraction > or = 40% were excluded. This lack of a representative sample of elderly patients with heart failure has raised concerns about extrapolating the available evidence for beta-adrenoceptor antagonists to a more elderly heart failure population. Beta-adrenoceptor antagonists may have a less beneficial effect or even an adverse effect in elderly heart failure patients. There is evidence that beta-adrenoceptor antagonists are less frequently prescribed in elderly CHF patients, and that this lack of treatment is associated with impaired outcomes. Establishing which beta-adrenoceptor antagonists, if any, are effective in elderly CHF is therefore of extreme importance. The elderly have a reduced cardiovascular reserve and may be less tolerant of the introduction of a vasoconstricting beta-adrenoceptor antagonist. In addition, the higher proportion of elderly CHF patients with relatively preserved systolic function (for which no treatment has been proven to reduce mortality and morbidity) means that we cannot say with certainty that beta-adrenoceptor antagonists have been proven to be effective in a general elderly CHF population. Third-generation beta-adrenoceptor antagonists with vasodilating actions in addition to their beta-adrenoceptor antagonist effects may offer several theoretical advantages over earlier beta-adrenoceptor antagonists for elderly CHF patients. Three of this class (carvedilol, bucindolol and nebivolol) have been evaluated with respect to their efficacy in reducing mortality and morbidity in CHF, and only two of these (carvedilol and nebivolol) had a proven outcome benefit in a properly powered randomised, controlled trial. Only the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (which used the vasodilating third-generation beta-adrenoceptor antagonist nebivolol) has prospectively investigated the treatment of CHF in elderly patients, including those with preserved systolic function, and demonstrated a significant reduction in the risk of death or cardiovascular hospitalisation. In conclusion, prescribers are advised that nebivolol should be preferred in elderly patients with CHF, because of its proven efficacy in a representative group of elderly CHF patients.
Adrenergic beta-Antagonists↗
Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope.
AIMS: Predicting survival from peak exercise oxygen uptake (peak VO2) in chronic heart failure (CHF) is hindered by its reduction if exercise duration is submaximal. The oxygen uptake efficiency slope (OUES) is a non-linear description of the ventilatory response to exercise, which has the potential to describe abnormalities even early in exercise. We evaluated the physiology of OUES and assessed its potential for prognostic information in patients with CHF. METHODS AND RESULTS: Two hundred and forty-three patients with CHF (mean age 59+/-12 years) underwent cardiopulmonary exercise testing between May 1992 and July 1996. Mean peak VO2 was 16.2+/-6.7 mL/kg/min, VE/VCO2 slope 38+/-12.5, ventilatory anaerobic threshold 10.9+/-3.5 mL/kg/min, and OUES 1.6+/-0.7 L/min. The value for each variable fell across the New York Heart Association classes (P<0.0001 by analysis of variance for each). When only the first 50% of each exercise test was used to calculate the variables, the value obtained for OUES changed the least (peak VO2 25% difference and OUES 1% difference). After a median of 9 years of follow-up, 139 patients (57%) had died. Each of the exercise variables was a significant univariate predictor of prognosis but in a multivariable model, only OUES was identified as the sole significant independent prognostic variable. CONCLUSION: OUES provides an effective, independent measure of pathological exercise physiology. Its numerical value is relatively insensitive to the duration of exercise data from which it is calculated. Its prognostic value seems to be stronger than the best available existing measures of exercise physiology.
Aged↗
The anti-CD14 antibody IC14 suppresses ex vivo endotoxin stimulated tumor necrosis factor-alpha in patients with chronic heart failure.
BACKGROUND: Activation of the endotoxin (LPS) receptor, CD14, leads to tumor necrosis factor-alpha (TNF) production. Plasma LPS activity is elevated in patients with severe chronic heart failure (CHF). An anti-CD14 antibody, IC14, blocks TNF production in healthy volunteers. It is not known whether IC14 prevents TNF production in CHF patients. METHODS AND RESULTS: Blood from 20 CHF patients (age 64+/-2.1 years, NYHA class 2.2+/-0.1, LVEF 27+/-3%, mean+/-SEM) was pre-incubated with 0.5, 1.0, 5.0, 10 and 50 microg/mL IC14 for 1 h followed by incubation with 1 or 10 ng/mL LPS for 6 h. Fourteen subjects served as controls (58+/-2.4 years). LPS-stimulated TNF release was 76% and 60% greater at 1 and 10 ng/mL LPS, respectively, in CHF patients versus controls (p=0.07 and p=0.008). IC14 at concentrations of 5.0, 10 and 50 microg/mL substantially reduced TNF production in response to stimulation with LPS (all p<0.05). CD14 receptor density was similar in patients and controls. In controls, but not in CHF patients, there was a positive correlation between CD14 receptor density and TNF production (r=0.61, p=0.03). CONCLUSION: IC14 suppresses LPS-stimulated whole blood TNF production in patients with CHF and in normal subjects and therefore may represent a novel therapeutic strategy for CHF patients with systemic immune activation.
Aged↗
Top of the charts: download versus citations in the International Journal of Cardiology.
The medical literature is growing at an alarming rate. Research assessment exercises, research quality frameworks, league tables and the like have attempted to quantify the volume, quality and impact of research. Yet the established measures (such as citation rates) are being challenged by the sheer number of journals, variability in the "gold standard" of peer-review and the emergence of open-source or web-based journals. In the last few years, we have seen a growth in downloads to individual journal articles that now easily exceeds formal journal subscriptions. We have recorded the 10 top cited articles over a 12-month period and compared them to the 10 most popular articles being downloaded over the same time period. The citation-based listing included basic and applied, observational and interventional original research reports. For downloaded articles, which have shown a dramatic increase for the International Journal of Cardiology from 48,000 in 2002 to 120,000 in 2003 to 200,000 in 2004, the most popular articles over the same period are very different and are dominated by up-to-date reviews of either cutting-edge topics (such as the potential of stem cells) or of the management of rare or unusual conditions. There is no overlap between the two lists despite covering exactly the same 12-month period and using measures of peer esteem. Perhaps the time has come to look at the usage of articles rather than, or in addition to, their referencing.
Bibliometrics↗
Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure.
OBJECTIVES: The aim of this study was to determine the significance of insulin resistance as an independent risk factor for impaired prognosis in patients with chronic heart failure (CHF). BACKGROUND: In CHF, impaired insulin sensitivity (S(I)) indicates abnormal energy metabolism and is related to decreased exercise capacity and muscle fatigue. The relationship between insulin resistance (i.e., low S(I)) and survival in patients with CHF has not been established. METHODS: We prospectively studied 105 male patients with CHF due to ischemic (63%) or non-ischemic (37%) etiology. All patients were in clinically stable condition (age 62 +/- 1 year, New York Heart Association [NYHA] functional class 2.6 +/- 0.1, left ventricular ejection fraction [LVEF] 28 +/- 2%, peak oxygen uptake [Vo(2)] 18.2 +/- 0.7 ml/kg/min). Insulin sensitivity was assessed from glucose and insulin dynamic profiles during an intravenous glucose tolerance test using the minimal model technique. RESULTS: During a mean follow-up period of 44 +/- 4 months, 53 patients (50%) died. Patients with S(I) below the median value (median: 1.82 min(-1) x microU x ml(-1).10(4); n = 52) had worse survival (at two years 61% [range 47% to 74%]) than patients with S(I) above the median value (n = 53; at two years 83% [range 73% to 93%]; risk ratio [RR] 0.38, 95% confidence interval [CI] 0.21 to 0.67; p = 0.001). Both patient groups were similar in terms of age, NYHA functional class, and body composition parameters (dual-energy X-ray absorptiometric scan; p > 0.2), but patients with a lower S(I) had a lower LVEF (24 +/- 2% vs. 33 +/- 3%) and peak Vo(2) (16.8 +/- 1.0 ml/kg/min vs. 19.7 +/- 1.0 ml/kg/min; both p < 0.05). On univariate Cox analysis, higher S(I) predicted better survival (RR 0.56, 95% CI 0.35 to 0.89; p = 0.015). On stepwise multivariate analysis, S(I) predicted mortality independently of other variables. CONCLUSIONS: In patients with CHF, lower S(I) relates to higher mortality, independent of body composition and established prognosticators. Impaired S(I) may have implications in the pathophysiology of CHF disease progression. Therapeutically targeting impaired insulin sensitivity may potentially be beneficial in patients with CHF.
Chronic Disease↗
Association of deranged adrenal steroid metabolism with anemia in chronic heart failure.
The relation between adrenal steroid hormone imbalance, as quantified by the cortisol/dehydroepiandrosterone (DHEA) ratio, and hemoglobin concentrations was appraised in 92 men with stable chronic heart failure (CHF). The cortisol/DHEA ratio was independently and inversely associated with hemoglobin concentrations, suggesting that alterations of the steroid milieu may play a role in the pathogenesis of anemia in CHF.
Adrenal Glands↗
Carvedilol reduces the costs of medical care in severe heart failure: an economic analysis of the COPERNICUS study applied to the United Kingdom.
BACKGROUND: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). METHODS: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per diem (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. RESULTS: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was pound530,771 ( pound44.89 per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was pound3.49 million in the carvedilol group compared with pound4.24 million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group ( pound479,200 vs. pound548,300). Overall, the cost per patient treated in the carvedilol group was pound3948 compared to pound4279 in the placebo group. This equated to a cost of pound385.98 vs. pound434.18, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. CONCLUSIONS: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.
Adrenergic beta-Antagonists↗
Advances in the non-drug, non-surgical, non-device management of chronic heart failure.
There have been many articles, reviews and editorials about the recent advances in pharmaceutical and device management of chronic heart failure in this and other journals over the last few years. What has been less praised are the significant advances we have made in understanding the best management of heart failure using other non-drug, non-surgical, non-device approaches. Approaches as diverse as nutrition, education, exercise, physiotherapy, psychotherapy and therapies for sleep-disordered breathing have shown considerable promise in improving the lot of our chronic heart failure (CHF) patients. Chronic heart failure is a common condition with a poor prognosis. It generates many debilitating symptoms for the sufferer. Non-pharmacologic treatment modalities play an important role alongside effective modern pharmaceutical, surgical and device therapies in relieving symptoms and improving prognosis. These treatments include those lifestyle measures that reduce the risk of underlying diseases such as coronary artery disease, diabetes, and hypertension lifestyle interventions of benefit in established CHF. Recent advances are reviewed including specialist nursing care, multi-disciplinary heart failure clinics, exercise rehabilitation, the treatment of sleep-disordered breathing, depression, obesity and cachexia. The day of the multi-disciplinary patient-centred CHF clinic has arrived and all sufferers deserve experienced management using all these approaches.
Comorbidity↗
Five years of progress for international journal of cardiology.
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Cardiology↗
Home-based exercise training modulates pro-oxidant substrates in patients with chronic heart failure.
BACKGROUND: In chronic heart failure, oxidative stress is thought to lead to endothelial dysfunction. In this study, we assessed the effect of home-based exercise training on variables of the NO and purine pathways. METHODS AND RESULTS: Eighteen patients and nine controls were randomly assigned in cross-over design to 8 weeks of exercise training (5 days/week, submaximal bicycle ergometer training, 30 min/day; calisthenics 9 min/day) and 8 weeks of sedentary lifestyle. Hypoxanthine, xanthine, l-arginine, asymmetric dimethylarginine (ADMA), symmetric DMA (SDMA) and nitrite were measured. In patients, exercise training led to an increase in peak VO(2) (p<0.003). At baseline hypoxanthine-a pro-oxidant substrate and marker of hypoxia-was higher in patients than in controls (24.6+/-4.3 vs. 11.9+/-4.2 micromol/l; p<0.05). After training there was a reduction in hypoxanthine (p<0.01). Nitrite levels were lower in patients (416+/-31 micromol/l) than in healthy controls (583+/-35 micromol/l, p<0.001). Although nitrite levels were highest after exercise, the changes did not reach statistical significance (p=n.s.). l-Arginine, ADMA, and SDMA levels were not different between groups and were not altered by exercise training. CONCLUSIONS: Chronic heart failure is associated with increased levels of hypoxanthine and decreased levels of nitrite. This imbalance can be beneficially modulated by chronic home-based exercise training.
Adult↗
Exercise training in chronic heart failure: effects on pro-inflammatory markers.
BACKGROUND: Acute bouts of exercise have been shown to induce inflammatory cytokine activation and peripheral hypoxia in patients with chronic heart failure (CHF). In this study, we set out to investigate the impact of chronic exercise training on pro-inflammatory cytokines and markers of endothelial damage. METHODS AND RESULTS: We measured tumor necrosis factor alpha (TNFalpha), its soluble TNF-receptors 1 and 2, interleukin 6 (IL-6), soluble e-selectin, soluble intracellular adhesion molecule-1 (sICAM) and sCD14 in 18 patients with CHF and 9 age-matched controls in a randomized cross-over study of 8 weeks of exercise training (5 days/week, submaximal bicycle ergometer training, 30 min/day; calisthenics 9 min/day) versus 8 weeks of rest. At baseline, patients had a lower peak Vo(2) (p=0.009) and a trend for higher levels of e-selectin (p=0.08) and sCD14 (p=0.06), in addition to significantly elevated levels of sICAM (p=0.02), TNFalpha (p=0.02) and TNF-R2 (p=0.002); TNF-R1 and IL-6 were not elevated. Although exercise training was effective and led to an increase in peak Vo(2) in CHF (p<0.003), there was no activation of any of the above variables observed, neither in patients nor controls. CONCLUSIONS: Chronic heart failure is associated with increased levels of TNFalpha and markers of endothelial damage. Whereas acute bouts of exercise have been reported to lead to an increase in pro-inflammatory cytokines and markers of endothelial damage, these effects are not seen when exercise is performed chronically.
Adult↗
Why ventilatory inefficiency matters in chronic heart failure.
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Carbon Dioxide↗