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Biomedical subjects

N Sharpe

Publications and source records attributed to N Sharpe.

At least 55 records · Page 3Linked to original sources
PubMed1998

Selection bias in clinical research when subjects are excluded because of failure to estimate left ventricular mass by echocardiography.

Quantitative echocardiographic imaging often is used in clinical research, but the method is not successful in all patients. The goals of this study were as follows: (1) to determine the frequency with which left ventricular mass (LVM) could be estimated by echocardiography, (2) to characterize persons in whom LVM could not be estimated from echocardiography, and (3) to determine whether failure to estimate LVM was independently related to any common cardiovascular risk factors, thereby suggesting a potential for selection bias. This research was part of a community-based case-control study of risk factors in hypertension. Five hundred hypertensive subjects and 506 normotensive age- and sex-matched control subjects were studied prospectively. The mean age was 61 years (range: 39 to 76 years), the mean weight was 74 kg (range: 37 to 127 kg), 46% of the subjects were men, and 56% had a history of smoking. Two-dimensionally guided M-mode echocardiography was attempted in all subjects for determination of LVM (Penn convention). LVM was estimated when the endocardial borders could be accurately identified from a true radial cavity diameter. LVM was estimated in 803 subjects (79.8%). Subjects in whom estimates of LVM could not be obtained were older and had the following characteristics: higher systolic blood pressure; larger chest, waist, and abdominal circumferences; higher waist/hip ratio; and larger body mass index (all P <.02). In multivariate analysis the only independent predictors of failure to estimate LVM by echocardiography were advanced age (P =.0001), larger chest size (P =.0001), and history of smoking (P =.004). The inability to estimate LVM in 20% of subjects has important implications to our understanding the strength of association between potential risk factors and LVM, an independent measure of cardiovascular risk. LVM is more likely to be missing in older subjects who have a large chest and a history of smoking. The effects of such a selection bias should be considered in any analysis, and a characterization of the excluded subjects should be developed.

Adult↗
PubMed1998

Efficacy and safety of carvedilol in patients with chronic heart failure receiving concomitant amiodarone therapy. Australia/New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: The beta-blocker/vasodilator carvedilol is found to have beneficial effects in patients with chronic heart failure. However, the safety and efficacy of this agent in the presence of concomitant amiodarone therapy has not been previously determined. METHODS AND RESULTS: We retrospectively analyzed the Australia/New Zealand Carvedilol Heart Failure Research Collaborative Group study of 415 patients with mild to moderate ischemic heart failure where amiodarone was administered as part of the treatment therapy (in 52 patients). After the open-label carvedilol run-in, patients received carvedilol (target dose 25 mg twice daily) or placebo for an average of 19 months. The main adverse events during this double-blind period were worsened heart failure, hypotension/dizziness, bradycardia/atrioventricular block, and aggravation of angina. By Chi square analysis, carvedilol and amiodarone together were not associated with a greater overall incidence of adverse effects than either drug alone. The beneficial effects of carvedilol on left ventricular ejection that were observed in the main trial were preserved in the presence of amiodarone. CONCLUSIONS: Carvedilol is a useful additional therapy for patients with chronic heart failure already receiving amiodarone. Carvedilol can be added to amiodarone in these patients without expectation of increased adverse effects or loss of clinical efficacy.

Adrenergic beta-Antagonists↗
PubMed1998

Atherosclerosis and left ventricular hypertrophy: persisting problems in treated hypertensive patients.

OBJECTIVES: First, to determine whether hypertensive patients managed in general practice have more advanced atherosclerosis and left ventricular hypertrophy than matched normotensive patients from the same practices. Second, to investigate the associations of several potentially modifiable factors with these vascular and cardiac outcomes. DESIGN AND METHODS: We performed a case-control study of 500 hypertensive cases (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or receiving treatment) and 506 age- (mean 61 years) and sex- (54% female) matched normotensive controls recruited from general practices. Carotid artery far wall thickness (CWT), assessed by B-mode ultrasound, and left ventricular mass (LVM), assessed by M-mode echocardiography, were the main study outcome measures. RESULTS: Mean systolic/diastolic blood pressure levels in the 399 treated cases (145/87 mmHg) were lower than those in untreated cases (158/94 mmHg) but higher than those in controls (133/82 mmHg, all P < 0.0001). Mean body mass index (BMI) and total triglyceride levels were higher and high-density lipoprotein cholesterol was lower in cases than in controls (all P < 0.0004). Mean CWT was 10% greater in cases than in controls and LVM was 14% greater (both P < 0.001), but both were similar in treated and untreated cases (P > 0.05). In multivariate analyses, blood pressure and BMI were both directly and independently related to CWT and LVM (both P < 0.0001). CONCLUSIONS: In this study, hypertensive patients managed in general practice - whether treated with antihypertensive drugs or not - had more advanced atherosclerosis and left ventricular hypertrophy than did matched normotensive patients. Efforts to lower blood pressure further and to reduce BMI could potentially reduce these differences, and this might lead to a reduction in the risk of major cardiovascular events.

Aged↗
PubMed1998

Left ventricular remodelling and improved long-term outcomes in chronic heart failure.

Several targets for heart failure therapy may be met through different mechanisms which are not necessarily associated. In the Australia/New Zealand Heart Failure Research Collaborative Group Study, patients with chronic stable heart failure of ischaemic aetiology on treatment including ACE inhibitors were randomized to treatment with either the vasodilator beta-blocking drug carvedilol or placebo. At 12 months, symptoms and exercise performance were unchanged, but ejection fraction increased significantly with carvedilol treatment; at 20 months, the rate of death and hospitalization was also significantly reduced in the carvedilol-treated group. In a sub-study using two dimensional echocardiography, progressive left ventricular (LV) dilatation occurred in the placebo group, compared with significant reductions in LV volumes with the carvedilol treatment group. An overview of all available carvedilol trial data showed the odds of death reduced by one-half with treatment (OR 0.51, 95% CI 0.33-0.77, 2P = 0.0014). Thus, improved LV remodelling occurs with carvedilol treatment in heart failure and is associated with improved long-term outcomes including survival. Improved LV function may, in part, mediate the survival benefit of carvedilol and provide a reliable surrogate for long-term outcomes.

Adrenergic beta-Antagonists↗
PubMed1998

Translation of clinical trial results into practice.

Angiotensin-converting enzyme (ACE) inhibitors have been shown in several large studies to prolong life and prevent disease progression in patients with heart failure and to prevent progression of left ventricular dysfunction following myocardial infarction. Despite this, it appears that a significant proportion of eligible patients are not receiving these agents and not obtaining their benefits. Patients in clinical trials are generally more selected and homogeneous than heart failure patients in the community. Clinicians may often feel that the typical clinical trial patient is not representative of many patients in their own practices and that trial results are often not generalizable to practice. It is only with the emergence of evidence from trials which more closely represent community practice and the promotion of agreed management guidelines that ACE inhibitors will be used more widely. Specialists and primary care practitioners need to provide an integrated approach to heart failure management to achieve optimal outcomes for patients.

Age Distribution↗
PubMed1998

Towards 2001: will ACE inhibitors have a role in atherosclerosis treatment?

Angiotensin-converting enzyme (ACE) inhibitors have been in clinical use for 20 years, during which time their application has been extended from the treatment of hypertension and heart failure to left ventricular dysfunction after myocardial infarction. They are also being used today for the treatment of diabetic nephropathy. More recently, the rationale for an antiatherosclerotic effect of ACE inhibition has emerged, based on more detailed understanding of the renin-angiotensin-aldosterone system and the role of this system in atherogenesis, in addition to supportive experimental animal and preliminary clinical data. The possible clinical benefit of ACE inhibition in atherosclerosis is currently being assessed in several large-scale trials with both surrogate and clinical outcome measures in high-risk patients with clinically manifest atherosclerosis, principally coronary artery disease. The trials should further elucidate the mechanisms of benefit from ACE inhibition and further define their role in therapy of patients with coronary disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

OBJECTIVES: The aim of this study, a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure due to ischemic heart disease, was to determine the effects of this treatment on left ventricular size and function with the use of quantitative two-dimensional (2D) echocardiography. BACKGROUND: Beta-adrenergic blocking drugs have been shown to improve left ventricular ejection fraction in patients with heart failure due to either ischemic heart disease or idiopathic dilated cardiomyopathy. However, the effects of such treatment on left ventricular size remain uncertain. METHODS: One hundred twenty-three patients from 10 centers in New Zealand and Australia participated in the 2D echocardiographic substudy. Echocardiography was performed before randomization and was repeated after 6 and 12 months of treatment. Left ventricular end-diastolic and end-systolic volumes were measured from apical four- and two-chamber views with the use of a modified Simpson's rule method. RESULTS: After 12 months, heart rate was 8 beats/min lower in the carvedilol than in the placebo group, whereas left ventricular end-diastolic and end-systolic volumes were increased in the placebo group but reduced in the carvedilol group. At 12 months, left ventricular end-diastolic volume index was 14 ml/m2 less in the carvedilol than in the placebo group (p = 0.0015); left ventricular end-systolic volume index was 15.3 ml/m2 less (p = 0.0001), and left ventricular ejection fraction was 5.8% greater (p = 0.0015). CONCLUSIONS: In patients with heart failure due to ischemic heart disease, carvedilol therapy for 12 months reduced left ventricular volumes, increased left ventricular ejection fraction and prevented progressive left ventricular dilation. These changes demonstrate a beneficial effect of carvedilol on left ventricular remodeling in heart failure. The observed changes may explain in part the improved clinical outcomes produced by treatment with carvedilol.

Adrenergic beta-Antagonists↗
PubMed1997

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

AIMS: Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. METHODS AND RESULTS: Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. CONCLUSIONS: Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Administration, Oral↗
PubMed1997

Massive nitrogen loss in critical surgical illness: effect on cardiac mass and function.

OBJECTIVE: The authors measured cardiac mass and function to determine whether these changed in patients who were critically ill who were losing large amounts of nitrogen from the body. SUMMARY BACKGROUND DATA: The large losses of body nitrogen that occur in patients with protein-energy malnutrition are associated with a loss of cardiac mass and function. It is not known if this also occurs in patients who were critically ill who are losing massive amounts of nitrogen. METHODS: Once hemodynamically stable, 13 patients who were critically ill underwent sequential measurements of left ventricular mass (LVM) and function, total body nitrogen (TBN), total body potassium, body weight, fat-free mass, and limb muscle mass. RESULTS: Over a 21-day study period, there was no change in LVM or function despite falls of 14% and 21% in TBN and total body potassium, respectively, a 21% fall in limb muscle mass, and a deterioration in skeletal muscle function by approximately 40%. CONCLUSIONS: In patients who were critically ill, cardiac mass does not decrease and function does not deteriorate after hemodynamic stability has been achieved despite massive losses of protein from the body.

Adolescent↗
PubMed1997

Beta-adrenergic blocking agents in the treatment of congestive heart failure: mechanisms and clinical results.

Congestive heart failure is a major public health problem in Western countries. Despite current treatment including angiotensin converting enzyme inhibitors, mortality and morbidity remain high. The sympathetic nervous system is markedly activated in heart failure, and inhibition of this system with the beta-adrenergic blocking agents may provide further benefit. Several clinical trials involving over 3,000 patients have shown that beta-blocker therapy improves left ventricular function in patients with heart failure. However, the effects of such therapy on symptoms and exercise tolerance have been variable. Recent reports have suggested that survival is improved with the beta-blocker carvedilol. Large-scale, long-term clinical trials are required to confirm these findings and to clearly define the role of this promising therapy for patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed1997

Optimal treatment of heart failure in the elderly.

Heart failure is a common condition in the elderly and one that is likely to become more prevalent as the population ages. Many drugs have been developed for the treatment of heart failure, but because clinical trials of these agents have often not included elderly patients their results need to be extrapolated from younger to older patients. Age-related physiological changes that affect how the available treatments are used occur in many organ systems. Effective management strategies can be implemented in elderly patients as well as in younger age groups, and these can improve both functional status and quality of life as well as reducing hospital admission and improving survival. This article reviews the physiological changes that occur in the elderly and the treatment approach that can be taken in elderly patients with heart failure.

Aged↗
PubMed1996

Management of acute myocardial infarction in Auckland.

AIM: To analyse the utilisation of therapies in coronary care units for patients with acute myocardial infarction. METHODS: An evaluation form was completed prospectively by a designated nurse in each coronary care unit of the four Auckland hospitals in 1993. RESULTS: One thousand and eighty one patients who were admitted with definite or probable acute myocardial infarction had a coronary care unit stay of 63.4 (SD 49.3) hours, and hospital stay of 7.3 (5.1) days. The mortality for definite myocardial infarction was 13.7% (< 70 years 7.1%). Coronary angiography was performed on 10% of patients during their hospital admission, and 4.9% underwent revascularisation. Thrombolytic therapy was administered to 52% (495/948) of patients with definite infarction and 4% had contraindications. Patients aged > or = 70 years (47% vs 55% p = 0.02) or diabetics (46% vs 56%, p = 0.04) were less likely to receive thrombolysis. The utilisation of aspirin and oral beta-blockers was 86% and 40%, respectively, in patients with definite infarction and both were used less frequently in patients > or = 70 years. Intravenous beta-blockers were administered to < 1% of patients. Angiotensin converting enzyme (ACE) inhibitors were prescribed in 21%, intravenous or long acting nitrates in 41% and calcium antagonists in 14%; the latter two therapies were used more frequently in patients > or = 70 years. There was no evidence of gender or ethnic bias for either investigation or treatment. CONCLUSION: On the basis of results of recent clinical trials, there may be under utilisation of some treatments for acute myocardial infarction including aspirin, thrombolytic therapy, beta-blockers and ACE inhibitors, while calcium antagonists may be over used.

Adrenergic beta-Antagonists↗