Showing papers by "Philip A. Poole-Wilson published in 2005"
TL;DR: Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.
Abstract: Aims Large randomized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure. The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain. The SENIORS study was performed to assess effects of the beta-blocker, nebivolol, in patients ≥70 years, regardless of ejection fraction.
Methods and results We randomly assigned 2128 patients aged ≥70 years with a history of heart failure (hospital admission for heart failure within the previous year or known ejection fraction ≤35%), 1067 to nebivolol (titrated from 1.25 mg once daily to 10 mg once daily), and 1061 to placebo. The primary outcome was a composite of all cause mortality or cardiovascular hospital admission (time to first event). Analysis was by intention to treat. Mean duration of follow-up was 21 months. Mean age was 76 years (SD 4.7), 37% were female, mean ejection fraction was 36% (with 35% having ejection fraction >35%), and 68% had a prior history of coronary heart disease. The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg. The primary outcome occurred in 332 patients (31.1%) on nebivolol compared with 375 (35.3%) on placebo [hazard ratio (HR) 0.86, 95% CI 0.74–0.99; P =0.039]. There was no significant influence of age, gender, or ejection fraction on the effect of nebivolol on the primary outcome. Death (all causes) occurred in 169 (15.8%) on nebivolol and 192 (18.1%) on placebo (HR 0.88, 95% CI 0.71–1.08; P =0.21).
Conclusion Nebivolol, a beta-blocker with vasodilating properties, is an effective and well-tolerated treatment for heart failure in the elderly.
1,397 citations
TL;DR: In cardiac amyloidosis, CMR shows a characteristic pattern of global subendocardial late enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics and may prove to have value in diagnosis and treatment follow-up.
Abstract: Background— Cardiac amyloidosis can be diagnostically challenging. Cardiovascular magnetic resonance (CMR) can assess abnormal myocardial interstitium. Methods and Results— Late gadolinium enhancement CMR was performed in 30 patients with cardiac amyloidosis. In 22 of these, myocardial gadolinium kinetics with T1 mapping was compared with that in 16 hypertensive controls. One patient had CMR and autopsy only. Subendocardial T1 in amyloid patients was shorter than in controls (at 4 minutes: 427±73 versus 579±75 ms; P<0.01), was shorter than subepicardium T1 for the first 8 minutes (P≤0.01), and was correlated with markers of increased myocardial amyloid load, as follows: left ventricular (LV) mass (r=−0.51, P=0.013); wall thickness (r=−0.54 to −0.63, P<0.04); interatrial septal thickness (r=−0.52, P=0.001); and diastolic function (r=−0.42, P=0.025). Global subendocardial late gadolinium enhancement was found in 20 amyloid patients (69%); these patients had greater LV mass (126±30 versus 93±25 g/m2; P=0.009...
841 citations
TL;DR: Exercise capacity is depressed in ACHD patients (even in allegedly asymptomatic patients) on a par with chronic heart failure subjects and is related to the frequency and duration of hospitalization.
Abstract: BACKGROUND: Although some patients with adult congenital heart disease (ACHD) report limitations in exercise capacity, we hypothesized that depressed exercise capacity may be more widespread than s ...
762 citations
TL;DR: Onset of new atrial fibrillation in patients on long-term beta-blocker therapy is associated with significant increased subsequent risk of mortality and morbidity, but is not an independent risk factor for mortality after adjusting for other predictors of prognosis.
Abstract: Aims Atrial fibrillation is common in patients with chronic heart failure (CHF) We analysed the risk associated with atrial fibrillation in a large cohort of patients with chronic heart failure all treated with a beta-blocker Methods and results In COMET, 3029 patients with CHF were randomized to carvedilol or metoprolol tartrate and followed for a mean of 58 months We analysed the prognostic relevance on other outcomes of atrial fibrillation on the baseline electrocardiogram compared with no atrial fibrillation and the impact of new onset atrial fibrillation during follow-up A multivariate analysis was performed using a Cox regression model where 10 baseline covariates were entered together with study treatment allocation Six hundred patients (198%) had atrial fibrillation at baseline These patients were older (65 vs 61 years), included more men (88 vs78%), had more severe symptoms [higher New York Heart Association (NYHA) class] and a longer duration of heart failure (all P , 00001) Atrial fibrillation was associated with significantly increased mortality [relative risk (RR) 129: 95% CI 112–148; P , 00001], higher all-cause death or hospitalization (RR 125: CI 113–138), and cardiovascular death or hospitalization for worsening heart failure (RR 134: CI 120–152), both P , 00001 By multivariable analysis, atrial fibrillation no longer independently predicted mortality Beneficial effects on mortality by carvedilol remained significant (RR 0836: CI 074–094; P ¼ 00042) New onset atrial fibrillation during followup (n ¼ 580) was associated with significant increased risk for subsequent death in a time-dependent analysis (RR 190: CI 154–235; P , 00001) regardless of treatment allocation and changes in NYHA class Conclusion In CHF, atrial fibrillation significantly increases the risk for death and heart failure hospitalization, but is not an independent risk factor for mortality after adjusting for other predictors of prognosis Treatment with carvedilol compared with metoprolol offers additional benefits among patients with atrial fibrillation Onset of new atrial fibrillation in patients on long-term beta-blocker therapy is associated with significant increased subsequent risk of mortality and morbidity
621 citations
TL;DR: In patients with non-ST-elevation acute coronary syndrome, a routine invasive strategy leads to long-term reduction in risk of death or non-fatal myocardial infarction, and this benefit is mainly in high-risk patients.
364 citations
TL;DR: It is demonstrated that adherence of physicians to treatment guidelines is a strong predictor of fewer CV hospitalizations in actual practice and there is a need to develop further quality improvement programmes in this condition.
Abstract: Aims The impact on outcome of the implementation of European guidelines for the treatment of chronic heart failure (CHF) has not been evaluated. We investigated the consequences of adherence to care by cardiologists on the rate of CHF and cardiovascular (CV) hospitalizations and time to CV hospitalization. Methods and results We constructed class adherence indicators for angiotensin-converting enzyme (ACE) -inhibitors, beta-blockers, spironotactone, diuretics, and cardiac glycosides and GAls (GAl3 adherence to first three classes of heart failure medication, GAl5 adherence to five classes). In the study, 1410 evaluable patients (mean age 69, 69% mates, New York Heart Association (NYHA) II: 64%, III: 34%, IV: 2%) were enrolled and followed up for 6 months by 150 randomly selected cardiologists/cardiology departments from six European countries (France, Germany, Italy, The Netherlands, Spain, and UK). Overall, adherence to treatment guidelines was 60 (GAl3) and 63% (GAl5) and was better for ACE-] (88%) or diuretics (82%) than for cardiac gtycosides (52%), beta-blockers (58%), and spironolactone (36%). In the three tertites of the population defined by a decreasing mean adherence score value, CHF and CV hospitalization rates were, respectively, 6.7, 9.7, and 14.7% and 11. 2, 15.9, and 20.6% (P <0.002 and P <0.001, respectively). Global adherence indicator GAl3 was an independent predictor of time to CV hospitalization in a multi-variable model together with NYHA Class, history of CHF hospitalization, ischaemic aetiology, diabetes mellitus, and hypertension. Conclusion We demonstrate that adherence of physicians to treatment guidelines is a strong predictor of fewer CV hospitalizations in actual practice. There is a need to develop further quality improvement programmes in this condition.
353 citations
TL;DR: Asymmetric dimethylarginine is an endogenous inhibitor of mobilization, differentiation, and function of EPCs and contributes to the cardiovascular risk in patients with high ADMA levels.
238 citations
TL;DR: Fatigue and breathlessness, common symptoms in CHF, have important and independent long-term prognostic implications and need to be effectively evaluated not only because symptom alleviation is a target for treatment, but also because they guide prognosis in patients with CHF.
197 citations
TL;DR: It is proposed that apoptosis of transplanted cells modulates local tissue reactions, which leads to reduced scar formation, repressed myocardial apoptosis, and improved cardiac outcome.
183 citations
TL;DR: Beta-blocker dose, HR, and SBP achieved during beta- blocker therapy have independent prognostic value in heart failure.
Abstract: Aims We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy).
Methods and results By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152–1.542; P 120 mmHg 0.78; 95% CI 0.671–0.907; P <0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662–0.916; P <0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663–0.887; P =0.0004) and there was no interaction with HR, SBP, or beta-blocker dose.
Conclusion Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.
TL;DR: A risk score is an objective aid in deciding on further management of patients with stable angina who require treatment for angina and have preserved left ventricular function with the aim of reducing serious outcome events.
Abstract: Objective To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function.
Design Multivariate Cox regression analysis of data from a large multicentre trial.
Setting Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand.
Participants 7311 patients with all required data available.
Main outcome measure Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years.
Results 1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressure ≥ 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients.
Conclusion This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.
TL;DR: The salutary effects of the addition of nifedipine GITS to the basic regimen of patients with concurrent stable symptomatic coronary artery disease and hypertension emphasize the need for blood pressure control.
Abstract: ObjectiveTo examine the effects of nifedipine GITS on clinical outcome in patients with concurrent stable angina and hypertension.MethodsData from the double-blind placebo-controlled ACTION trial was stratified for hypertension (blood pressure ≥ 140/90 mmHg), at baseline.ResultsA total of 52% of 766
TL;DR: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death,death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.
TL;DR: There are few large population‐based studies of the incidence and outcome of heart failure where the diagnosis ofHeart failure has been made by a General Practitioner (GP) in the community.
Abstract: Background:
There are few large population-based studies of the incidence and outcome of heart failure where the diagnosis of heart failure (HF) has been made by a General Practitioner (GP) in the community.
Methods:
From the General Practice Research Database in the UK, we selected a population of 686,884 people 45 years or older. Incident cases of HF in 1991 were classified definite HF, possible HF, or a first prescription of diuretics without a diagnosis of HF. The population was followed for 3-year mortality.
Results:
A total of 6478 patients had definite HF (mean age 77.2 years, 55.5% women), 14,050 had possible HF and 6076 persons were prescribed diuretics without a definite or possible diagnosis of HF. The overall incidence of definite HF was 9.3/1000 persons/year and of possible HF 20.2/1000 persons/year. Diuretics were prescribed for the first time for other reasons for 8.7 persons/1000/year. The incidence of HF was higher in men. The incidence of definite HF increased with age. Survival curves showed higher mortality rates in the first 3 months after the diagnosis of HF. One-year cumulative probability of death for patients with definite HF was 15.9 times higher in men and 14.7 times higher in women in comparison with the UK population.
Conclusion:
The diagnosis of HF by a GP successfully identifies patients at high risk of death, comparable to patients with HF identified by cardiologists on the basis of defined diagnostic criteria. HF is common in the general population, increases sharply with age, and has a poor prognosis.
TL;DR: It is not known if low‐dose LPS is sufficient to stimulate immune activation, but the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations is investigated.
Abstract: Background
Endotoxin [lipopolysaccharide (LPS)] may be an important stimulus for cytokine release in patients with chronic heart failure (CHF). We sought to investigate the relationship between whole blood endotoxin responsiveness and serum lipoprotein concentrations. It is not known if low-dose LPS is sufficient to stimulate immune activation.
Methods and results
Whole blood from 32 CHF patients (mean age 66±2 years, NYHA class 2.7±0.2, five female) and 11 healthy control subjects (mean age 47±4 years, six female) was stimulated with LPS at nine different concentrations (0.001 to 10 ng/mL), and tumor necrosis factor (TNF-α) release was quantified. Reference standard endotoxin at concentrations of 0, 0.6, 1, and 3 EU/ml was added to whole blood from nine CHF patients (age 64α9.1 years, all NYHA class II, eight male) and incubated for 6 h, the TNF-α production being measured. Serum lipoproteins were quantified using standard techniques. In CHF patients, there was an inverse relationship between whole blood TNF-α release and serum cholesterol which was strongest at 0.6 ng/mL of LPS (r=−0.53, p=0.002). A similar although weaker relationship was found for serum HDL. No such correlation was found in healthy subjects or with serum LDL (all r2<0.1). Low concentrations of LPS induced a stepwise increase in TNF-± release from whole blood to concentrations well above those seen in CHF.
Conclusions
Serum lipoproteins may play an important role in regulating LPS bioactivity in CHF. Very low LPS activity, at levels seen in vivo in CHF, can induce significant TNF-α production ex vivo.
TL;DR: The similarity of the findings in the present analysis supports a role for angiotensin-receptor antagonists in this patient population and the effects of losartan on HF-related outcomes, NYHA class, and QoL were not superior to those of captopril.
TL;DR: Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF), with specific down‐regulation of LPS‐mediated cellular tumor necrosis factor (TNF‐α) production which does not affect other cytokine parameters.
Abstract: Background
Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF). LPS can induce cellular desensitization, with specific down-regulation of LPS-mediated cellular tumor necrosis factor (TNF-α) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF.
Methods and results
Mononuclear cells from 24 CHF patients (mean age 70±2 years, age range 58 to 78 years, NYHA class 3.0±0.2) and 11 healthy controls (mean age 53±3 years, age range 39 to 75 years) were separated from venous blood and cultured for 24 h with LPS (E. coli, 0−10 ng/mL). Culture supernatants were tested for TNF-α and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age, mononuclear cells from patients with severe heart failure produced less TNF-α than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05). IL-1RA release was higher for CHF patients as a group, compared with controls (p<0.05). There was no significant difference in IL-1RA release between CHF patient subgroups.
Conclusions
Mononuclear cells from patients with severe heart failure produce significantly less TNF-α than healthy controls or patients with mild to moderate disease. Production of IL-1RA is not affected. This resembles a picture indicative of LPS desensitization occurring in patients with severe CHF.
TL;DR: Among patients routinely eligible for resynchronization, those with restrictive filling may show significantly less (and possibly no) improvement in symptom class and ventricular dimensions after resynchronized.
TL;DR: It is demonstrated that noradrenaline and isoproterenol inhibit TNF-alpha production in patients with CHF in ex vivo whole blood in a dose-dependent fashion and the beta-blocker bisoprolol abolishes this effect.
Abstract: Increased levels of tumor necrosis factor-α (TNF-α) correlate with poor prognoses in chronic heart failure (CHF). This study demonstrated that noradrenaline and isoproterenol inhibit TNF-α production in patients with CHF in ex vivo whole blood in a dose-dependent fashion. The β-blocker bisoprolol abolishes this effect.
TL;DR: Doctors, particularly cardiovascular physicians and cardiologists, must play a much greater role in linking with the public, other health workers, epidemiologists), media, industry, academia and politicians in achieving the common goal of disease prevention.
Abstract: Cardiovascular disease is the commonest chronic illness in both developed and developing countries, causing the most deaths and the greatest impact on morbidity. The superiority of disease prevention over treatment was appreciated at least 5,000 years ago in China. The link between the existence of disease in society and the political and social circumstances of a country was emphasised by Virchow in the nineteenth century. The scientific basis and methods for prevention of cardiovascular disease are known. What are lacking are the will and the means to implement change. The well-intentioned often have a dominant sense of entitlement in the pursuit of the common goal of disease prevention. There is a failure of many organisations to acknowledge the importance of other groups within society in achieving the common goal. Doctors, particularly cardiovascular physicians and cardiologists, must play a much greater role in linking with the public, other health workers, epidemiologists, media, industry, academia and politicians. Too many vested interests obstruct progress in the prevention of cardiovascular disease.
TL;DR: Ventricular long-axis function in cardiac amyloidosis and idiopathic restrictive cardiomyopathy has quite distinct pathophysiologic profiles, raising some concerns about the appropriateness of considering them as 2 subtypes of a single nosographic entity.
Abstract: To investigate ventricular long-axis function in cardiac amyloidosis (CA) and idiopathic restrictive cardiomyopathy (IRC), 16 patients with CA and 14 with IRC were studied. Left ventricular (LV) long-axis function was depressed in all patients with CA compared with only 36% of patients with IRC. Impairment in longitudinal function was clearly evident, even if fractional shortening and LV filling were normal. Ventricular long-axis function may be used as a sensitive marker of early systolic dysfunction. CA and IRC have quite distinct pathophysiologic profiles, raising some concerns about the appropriateness of considering them as 2 subtypes of a single nosographic entity.
TL;DR: In this paper, the relation between cortisol/dehydroepiandrosterone (DHEA) ratio and hemoglobin concentrations was assessed in 92 men with stable chronic heart failure.
Abstract: 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.
TL;DR: For the majority of patients with chronic stable angina not on a calcium-antagonist, medical treatment with other anti-anginal drugs is sufficient to control symptoms and only a minority of patients are refractory to medical treatment.
TL;DR: In this paper, a plethora of studies have suggested that not only is anaemia more common in chronic heart failure than could be accounted for by age and other demographic characteristics, but that its presence is associated with greater symptoms, exercise intolerance, and an amplified risk of mortality.
Abstract: This editorial refers to ‘Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure’† by C. Opasich et al., on page 2232
Elucidating disease pathogenesis constitutes an important aim of scientific endeavour, being critical for the identification of novel therapeutic strategies for the alleviation of suffering. Nowhere has this been more apparent than in chronic heart failure (CHF), where impressive survival benefits have been achieved as a long-term consequence of mechanistic studies into the role of neurohormonal activation in disease progression.1 Therefore, given this magnitude of potential benefit, illuminating the mechanisms that drive adverse phenomena in CHF remains an agenda of substantial importance.
Anaemia is a prevalent and adverse comorbidity in CHF, but little is known about its origins. Over the past 5 years, a plethora of studies have suggested that not only is anaemia more common in CHF than could be accounted for by age and other demographic characteristics, but that its presence is associated with greater symptoms, exercise intolerance, and an amplified risk of mortality.2–4 Pilot studies indicate that its empirical treatment with recombinant erythropoietin (EPO) and intravenous iron may confer clinical benefits in anaemic CHF patients.5 However, rational anaemia correction involves targeting its underlying cause(s), which have yet to be resolved in CHF. Conceptually, an attenuated erythrocyte mass (‘true anaemia’) may be acquired subsequent to haemolysis or to EPO, iron, folate, and/or vitamin B12 deficiency. Prominent among these factors are EPO and iron. EPO is the principal humoral regulator of erythropoiesis, is elaborated by renal parenchymal cells in response …
*Corresponding author. Tel: +44 20 7351 8127; fax: +44 20 7351 8733. E-mail address : d.okonko{at}imperial.ac.uk