Showing papers in "the british journal of cardiology in 2002"

The National Service Framework for Coronary Heart Disease

Abstract: Cardiovascular disease is the most important cause of illness in Britain. The focus of the National Service Framework for Coronary Heart Disease (NSF for CHD) is appropriate since the burden of CHD is high in the UK. Interventions for primary and secondary prevention include advice on reducing modifiable risk factors, smoking, maintaining blood pressure < 140/85 mmHg and using statins and dietary advice to lower serum cholesterol. Identification of those at greatest risk will require practice-based registers. Audits will be needed to ensure that the stipulated interventions are offered to those on the disease registers. The biggest implication for primary prevention will be selection of patients at increased risk of CHD. Implementation of the NSF will increase GPs' workload.

The pathophysiology of primary pulmonary hypertension

Abstract: Primary pulmonary hypertension (PPH) is a progressive disease with a poor prognosis. It is characterised by an elevated pulmonary artery pressure and pulmonary vascular resistance that ultimately lead to right ventricular failure and death. PPH is a relatively rare and neglected disease which, until recently, had been poorly understood and had no effective form of therapy. This, however, is changing with the rapid accumulation of knowledge relating to the disease and its management. In this article, we review the possible mechanisms that may have a pivotal role in the development of the disease.

The role of orlistat in the treatment of obese patients with mild to moderate hypercholesterolaemia: consequences for coronary risk

Abstract: This study investigated the effect of orlistat on weight loss and serum lipid parameters in obese patients with hypercholesterolaemia. A total of 215 adult obese patients (body mass index >30 kg/m 2 ) with hypercholesterolaemia (total plasma cholesterol >6.5 mmol/L or plasma low density lipoprotein cholesterol ≥4.2 mmol/L) were recruited for screening at 12 out-patient clinics in the UK. Of these, 142 patients were randomised to receive double-blind treatment for 24 weeks with orlistat 120 mg (n=71) or placebo (n=71) three times daily in combination with a mildly hypocaloric diet. Patients completing the double-blind phase (orlistat n=42, placebo n=55) were eligible to enter a further 28-week open-label phase and received orlistat 120 mg three times daily in combination with the hypocaloric diet. Mean weight loss after 24 weeks was 4.4 kg (4.4%) in the orlistat group vs. 2.6 kg (2.5%) with placebo (p 5% of their initial body weight (p 10% (p=NS). Patients who continued on orlistat during the open-label phase had a mean weight loss of 4.97 kg (4.86%) after 52 weeks. Patients who switched to orlistat had a mean weight loss of 4.28 kg (4.23%). Orlistat was associated with significantly greater reductions than placebo in plasma total cholesterol (-10.88 ′ 1.36% vs. -3.25 ′ 1.33%; p<0.001) and LDL-cholesterol (-14.14 ′ 2.68% vs. -3.68 ′ 3.61%; p<0.05) during the double-blind phase. Despite similar weight loss at the end of the 52-week period, patients who remained on orlistat throughout the study had greater improvements in plasma lipid concentrations than patients who switched to orlistat after 24 weeks. Orlistat, in combination with a mildly hypocaloric diet, promotes clinically meaningful weight loss and improvements in lipid concentrations in obese patients with hypercholesterolaemia.

Rapid appraisal of clinicians' reactions to guidance from the National Institute of clinical Excellence on use of glycoprotein IIb/IIIa antagonists for acute coronary syndromes

Abstract: Introduction We conducted a postal survey of UK consultant cardiologists to assess reaction to the guidance issued by the National Institute of Clinical Excellence (NICE) on the use of glycoprotein IIb/IIIa antagonists (GPAs) for acute coronary syndromes.

Transradial coronary angioplasty

Abstract: The most commonly used access sites for interventional cardiology are the femoral, brachial and radial arteries. The selection of arterial approach significantly influences the cost of the procedure and the patient's quality of life as well as vascular access site complication rates, affecting procedural morbidity and mortality figures. 1 The exponential rise in stent deployment combined with more aggressive antiplatelet and anticoagulant therapy has exacerbated femoral vascular complications, with major bleeding rates of 23% following rescue angioplasty with concurrent use of glycoprotein (GP) IIb/IIIa inhibitors.2 A safer route of arterial access would therefore be highly desirable. The radial artery has been safely used for many years to provide haemodynamic monitoring. The vessel is superficial and is usually not an end artery, such that occlusion does not result in ischaemic complications. Haemostasis is easily achieved by pressure over the point of arterial puncture; any bleeding is soon recognised, allowing prompt action. Campeau first described the use of the radial artery for coronary angiography in 1989 and subsequently Kiemeneij and colleagues in Amsterdam have pioneered the percutaneous transradial approach for interventional procedures.

A case study from a Sussex Primary Care Group: Improving secondary prevention in coronary heart disease using an educational intervention

Abstract: An educational intervention was developed to try to raise both data quality standards and those of clinical care in the secondary prevention of coronary heart disease. The intervention was used within primary care organisations utilising their own clinical data and with primary care professionals learning from each other. A special tool (MIQUEST) was used to extract the clinical data. Anonymised data were then shared with the whole primary care organisation at six-monthly data quality workshops. Patients needing interventions were identified in individual practices and these practice visits were also used as learning opportunities. At the end of the study there was an increase in the recording of the diagnosis of ischaemic heart disease (IHD). The recording of blood pressure and its control also improved. The number of IHD patients not on aspirin was reduced. Measurement of cholesterol, prescription of statins and the giving of advice to smokers all increased. The increase was largest in the practices with the lowest baseline data. The study concluded that this primary care data quality programme could provide an educational environment within which primary care organisations could improve secondary prevention in coronary heart disease.

Brugada syndrome: a review

Abstract: Brugada syndrome was described 10 years ago. It is a syndrome of sudden cardiac death associated with partial right bundle branch block and ST segment elevation in the right precordial leads V1-V3 on the resting ECG. Those affected have structurally normal hearts (as demonstrated by standard techniques) but they have a mortality rate of 10% a year, whether they are symptomatic or asymptomatic. It is thought to be primarily a disease of cardiac conduction and has been linked to abnormalities in the sodium channel (SCN5A). Differential diagnoses include arrhythmogenic right ventricular dysplasia, idiopathic ventricular fibrillation and polymorphic ventricular tachycardia. Brugada et al. suggest that the Brugada shift pattern on 12-lead ECG is a specific marker for those at risk of sudden death. They recommend that symptomatic individuals be protected with an implantable cardiac defibrillator. Asymptomatic individuals remain a diagnostic dilemma.

Serious interaction between digoxin and warfarin

Abstract: Drug interaction with warfarin is a common cause of loss of anticoagulant control. An interaction between warfarin and digoxin has not previously been documented in the British National Formulary or datasheet. We report acase of digoxin toxicity responsible for prolongation of the INR to more than 10.

Prognosis, outcome and recurrence of stroke

Abstract: Defining prognosis may be helpful in planning acute treatment of stroke, setting rehabilitation goals and setting resource priorities. Case fatality is 12% within the first seven days of a first-ever stroke. Late deaths are usually due to the consequences of immobilisation and stroke recurrence. Long-term outcome is difficult to predict but older age, significant pre-stroke co-morbidity and severe stroke are generally associated with poor physical recovery. Stroke patients have a risk of recurrence 15 times that of an age- and sex-matched population. Stroke type may influence recurrence. Early stroke recurrence may be prevented by antiplatelet drugs. Patients in atrial fibrillation and with recently symptomatic high-grade carotid stenosis are at particular risk of stroke.

The effect of nifedipine GITS on outcomes in patients with previous myocardial infarction: A subgroup analysis of the INSIGHT study

Abstract: Post-myocardial infarction (Ml) patients have a higher risk for subsequent cardiovascular and cerebrovascular events than the average population. This study was to test the effects on outcomes of nifedipine GITS compared to the diuretic combination co-amilozide in hypertensive patients with a history of Ml on outcomes (subset of the INSIGHT study). The multinational, randomised, double-blind International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study compared the treatment effects of nifedipine GITS 30 mg and co-amilozide (hydrochlorothiazide 25 mg plus amiloride 2.5 mg) in hypertensive patients aged 55-80 years with a blood pressure of 150/95 mmHg (or 160 mmHg systolic). This pre-specified subanalysis was performed in patients with a history of Ml. The primary outcome was a composite of cardiovascular death, non-fatal stroke, Ml, and heart failure. Of 6,321 randomised patients, 383 (6.1%) had a previous Ml. The percentage of primary outcomes in post-MI patients did not differ between the two treatment groups (14.9%). The number of post-MI patients with composite secondary outcomes was 53 (27.2%) in the nifedipine GITS group and 60 (31.9%) in the co-amilozide group. The incidence rates of primary and secondary outcomes were higher in patients with a previous Ml than in patients without a history of Ml. For the randomised use of nifedipine GITS and co-amilozide in hypertensive patients with a previous Ml, the choice seemed unimportant for outcomes and blood pressure lowering. The results of this subgroup analysis are consistent with INSIGHT's overall findings of no significant differences in efficacy, suggesting that post-MI hypertensive patients are no more likely to suffer further events when treated with long-acting nifedipine than on co-amilozide.

Clopidogrel in coronary artery disease

Abstract: latelets play a central role in both acute coronary syndromes and the ischaemic complications following percutaneous coronary intervention (PCI). Aspirin is a relatively weak antiplatelet agent and only inhibits one of many pathways leading to platelet activation. The thienopyridines, ticlopidine and clopidogrel inhibit platelet activation via the adenosine diphosphate (ADP) pathway. Ticlopidine, the first generation thienopyridine, is effective in reducing cardiovascular events but is associated with serious haematological toxicity that has limited its use. Clopidogrel, the second generation thienopyridine has improved tolerability and safety. The CAPRIE trial demonstrated that treatment with clopidogrel in patients with vascular disease is associated with a modest reduction in vascular events when compared to aspirin therapy. The CURE trial found that the addition of clopidogrel to aspirin in patients with non-ST segment elevation acute coronary syndromes resulted in a 20% relative risk reduction in the combined end point of cardiovascular death, myocardial infarction or stroke. This benefit was at the cost of a 1% increase in major bleeding. In addition the combination of clopidogrel and aspirin is effective in preventing periprocedural ischaemic events in patients undergoing PCI.

Hypertension trials: the current evidence base and forthcoming trials

Abstract: Recently reported and ongoing morbidity and mortality trials in hypertensive patients are addressing important unanswered questions in hypertension management. What is the optimal first-line treatment for hypertension, what is the ideal combination of antihypertensive drugs, how are these influenced in particular patient subgroups, and what are the treatment thresholds and blood pressure goals of treatment for optimal prevention of cardiovascular disease? Limitations of some recent trials are highlighted and emphasise the need for further prospective metaanalyses of studies to provide adequate power to address some of these important questions. Current ongoing large scale studies, including ALLHAT and ASCOT, will shortly be reporting results to the scientific community and are likely to influence management decisions across a wide range of patient subgroups.

United Kingdom prospective Diabetes study: implications for metformin

Abstract: One of the purposes of the United Kingdom Prospective Diabetes Study (UKPDS) was to compare the efficacy of different antidiabetic drugs in the long-term treatment of type 2 diabetes. In overweight type 2 patients, use of metformin as the initial antidiabetic drug therapy reduced overall mortality and reduced various long-term complications to a greater extent than other first-line treatments tested (sulphonylureas and insulin) whilst controlling hyperglycaemia to a similar extent. The benefit of early intervention with metformin may be due, at least in part, to its actions against insulin resistance and associated cardiovascular risk factors. Thus the UKPDS has provided evidence that early intensive glucose control with metformin in overweight type 2 diabetic patients is a particularly effective approach to reduce vascular complications and improve survival.

The electronic health record and the management of cardiovascular disease

Abstract: A dvanced web-based clinical Advanced web-based clinical care applications as part of an electronic health record can assist clinicians to meet Government targets for the management of cardiovascular disease. A clinical module of the Tayside electronic health record collects electronic data automatically from a variety of sources and holds this data in a central regional repository. It identifies those patients with existing cardiovascular disease and also those high priority patients at risk of developing clinical atherosclerosis. It allows the clinician to effectively manage these patients in line with national evidence-based guidelines. Real time audit of patient management is instantly available at the point of direct patient contact, as well as benchmarking to agreed performance criteria. Demonstrating improvement in clinical outcomes remains the eventual goal.

Management of overweight and obesity in patients with cardiovascular disease

Abstract: Overweight and obesity affect around half of the UK population, and are a serious public health problem. Obesity is associated with hypertension, dyslipidaemia, type 2 diabetes and a sedentary lifestyle, and has been shown to be an independent risk factor for development of cardiovascular disease. There are characteristic structural changes of the heart and vasculature in obesity. There is strong evidence that even modest weight reduction lowers cardiovascular risk. Dietary intervention, lifestyle advice and increased exercise are the initial strategy, but selected patients will require adjunctive treatment with anti-obesity drugs. In the absence of contraindications, orlistat is appropriate to use in obese patients with established cardiovascular disease, though sibutramine use is contraindicated in this population. Surgical intervention, such as gastric restrictive procedures, may be needed in severe obesity but there is a high complication rate among the morbidly obese and particularly in those who are also diabetic.

Therapeutic potential of the natriuretic peptide system

Abstract: Neurohormonal activation has a central role in the pathophysiology of various cardiovascular disorders. Despite recent therapeutic advances, potential exists to further manipulate these activated systems. The natriureticpeptide family consists of at least four structurally related peptides, with varying degrees of biological similarity. In the context of cardiovascular disease, the vast majority of data relates to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP).

Delivering evidence-based care to patients with heart failure: results of a structured programme. Commentary

Abstract: The Omada programme, a nurse-delivered model of care, has achieved improved levels of evidence-based intervention for patients with chronic heart failure in nine secondary care centres in the UK. It may provide an appropriate model for audit and delivery of care, in line with the requirements of the National Service Framework for Coronary Heart Disease.

Amlodipine treatment in patients undergoing PTCA in the UK: a cost-effectiveness analysis

Abstract: The objective of this analysis was to assess the health economic outcomes of treating patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with amlodipine over a four-month time period in the UK. Thetotal expected costs were determined and compared for patients using amlodipine versus those on placebo following an initial angioplasty. A decision tree model was constructed to estimate these total expected costs. Clinical data for the model were obtained from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES). Clinical outcomes in the model included myocardial infarction (MI), repeat PTCA, coronary artery bypass grafting (CABG) and all-cause mortality. Resource usage and economic data for the model were produced through the use of a modified Delphi panel and various economic literature and databases. The adjunctive use of amlodipine with PTCA decreased the rate of all adverse clinical outcomes by 9.4%. This improved clinical outcome led to a decrease in overall four-month costs per patient using amlodipine of £204. The total expected cost per patient using amlodipine was £3,833 and the total expected cost per patient not using amlodipine was £4,037.

The role of platelets and antiplatelet therapy in atherothrombotic disease

Abstract: Platelet-initiated thrombus plays a central role in the pathogenesis of arterial thrombotic disease. Platelets are activated by a range of physiological agonists including thrombin, ADP, thromboxane and collagen, acting in co-operation. ADP, though a weak agonist on its own, is important in enhancing platelet activation induced by other agents. Activation results in platelet adhesion, aggregation and degranulation leading to thrombus growth. Platelets also reinforce thrombus formation through platelet-mediated thrombin generation and the release of PAI-1 that inhibits fibrinolysis. Antiplatelet therapy is therefore of potential benefit both prior to and during a thrombotic episode. The commonly used antiplatelet drugs inhibit specific, single pathways of platelet activation but have overall benefit. Inhibition of intracellular activation pathways can be achieved with aspirin (which inhibits platelet cyclo-oxygenase) and dipyridamole (which inhibits phosphodiesterase). Two related thienopyridine derivatives, ticlopidine and clopidogrel, are specific inhibitors of the P2Y 1 2 ADP receptor. They have comparable pharmacological activity but clopidogrel has a better safety profile. A number of potent glycoprotein IIb/IIIa antagonists have been developed for therapeutic use. They are effective in percutaneous coronary intervention, though data from primary stenting trials are less positive. The recent update of the meta-analysis of trials of antiplatelet therapy by the Antithrombotic Trialists' Collaboration has confirmed the benefit of antiplatelet therapy in secondary prevention.

Patients of Southern Asian descent treated with valsartan (POSATIV) study

Abstract: Southern Asians in the UK have a substantially increased (50%) risk of coronary heart disease compared with the general population, in part due to a high prevalence of hypertension and diabetes. This patient group has not been specifically studied in a clinical trial using modern antihypertensive therapy such as the angiotensin II receptor antagonists (AIIRAs). A multi-centre, double-blind, randomised, parallel-group study compared the effects of treatment with valsartan 80 mg once daily (o.d.) with control therapy (bendrofluazide 2.5 mg o.d.) in 116 patients with mild hypertension (diastolic blood pressure [DBP] > 90 mmHg and < 105 mmHg) after a four-week run-in period. Sitting blood pressure was measured at baseline (end of run-in) and after four and eight weeks of treatment using the OMRON automatic oscillometric blood pressure monitor. The study medication dosage was doubled if patients had < 4 mmHg decrease in DBP after four weeks. Compared with the control group (n=62), the addition of valsartan 80/160 mg o.d. (n=51) resulted in a significantly greater reduction in blood pressure at eight weeks (mean change in blood pressure -15.6 mmHg [95% Cl -19.9 to -11.2 mmHg] for systolic blood pressure [SBP] and -9.3 mmHg [95% Cl -11.8 to -6.8 mmHg] for DBP; p<0.001). Both treatments were well tolerated. Valsartan is effective and well tolerated, and would be an appropriate treatment option in Southern Asian hypertensive patients.

Grown-up congenital heart disease: experience in a district general hospital

Abstract: Some 340 adult patients (186 male, 154 female; average age 36 years) with congenital heart disease are now seen in a dedicated clinic at a district general hospital. Septal defects and aortic pathology account for 48% ofcases seen and 21% have complex congenital heart disease. A first operation has been performed in 55%, a second operation in 13.3% and a third operation in 3.2%. Pulmonary hypertension is present in 7%. Eighty two of the 154 women have had 123 pregnancies. Care issues relating to the pregnant grown-up congenital heart disease (GUCH) patient are discussed. The growth of this population is highlighted, as is the requirement for more structured care. Issues relating to the establishment of a dedicated GUCH clinic are discussed, including training of cardiologists in this sub-speciality.

Complications associated with 64 temporary pacing wires implanted at a district general hospital: should this procedure be reserved for specialist centres?

Abstract: This study assessed complication rates in 64 emergency temporary pacing procedures, of which atrioventricular block formed the largest group (72%). Of the in-hospital deaths, most (76%) were due to myocardial infarction,and none due to the procedure. Immediate complications occurred in 22%: arrhythmia or arterial puncture, and one hemiparesis. Late complications occurred in 34%: loss of capture, infection including one instance of staphylococcal septicaemia. No complications occurred in 59%. Involvement of a consultant in the procedure did not reduce complication rates. In such potentially unstable patients, the risks of not pacing or delaying pacing probably far outweigh those of immediate intervention.

The HEARTS collaboration - Delivering improved secondary prevention of CHD for patients with heart disease

Abstract: Full implementation of the available evidence on secondary prevention should ensure that all patients after myocardial infarction should be offered both effective treatment and be maintained on treatment. This article describes the Heart disease Evidence-based Audit and Research in Tayside Scotland (HEARTS) collaboration which has been set up to try and achieve this. HEARTS can collect electronic data from many sources; prioritise data from multiple sources, such as hospital and general practice; process and link patient records; and, allow manual validation of electronic data. It can also facilitate clinical governance issues in general practice and hospital plus disseminate information to patients. It is hoped that, in addition to secondary prevention, it will be able to extend its focus to other aspects of cardiovascular disease in the future as well as being used for epidemiological and qualitative projects. The system maintains the security and rights of patients at all times.

The cost-effectiveness of amlodipine treatment in patients with coronary artery disease

Abstract: The objective of this paper was to quantify the impact on overall cardiovascular disease treatment costs resulting from the use of amlodipine in the coronary artery disease (CAD) population in the UK. A Markov cohort simulation model was developed to estimate the overall average healthcare costs of patients with CAD in the UK and to determine the cost-effectiveness of the use of amlodipine as part of their treatment regimen. Outcome probabilities used in the model were based on patient-level data from the Prospective Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). Cost estimates for in-patient and outpatient care associated with each outcome were applied to quantify the overall average healthcare cost for each arm of the study. The hospitalisation rate per patient in the placebo cohort was 61.8% while that in the amlodipine cohort was 44.3%. This corresponds to an average cost per patient for cardiovascular disease (CVD) treatment of £1,858.64 for amlodipine patients and £1,800.49 for placebo patients over three years of follow-up. Calculations yield a cost per hospitalisation avoided of £331.67. In conclusion, the inclusion of amlodipine in the treatment regimen for patients with CAD is expected to result in improved clinical outcomes through a marginal investment in cost.

Biphasic positive pressure ventilation in acute cardiogenic pulmonary oedema

Abstract: Non-invasive positive pressure ventilation (NIPPV) may be used in the treatment of acute cardiogenic pulmonary oedema. It has been shown to reduce the need for intubation and to improve left ventricular function. Patients do not need to be admitted to intensive care but can be managed in a coronary care unit. Two cases are described in this article. The indications, contraindications and complications of NIPPV are described and a practical guide to its use is given.

Pleuritic chest pain and hypoxia: a diagnostic dilemma

Abstract: Introduction Pulmonary thromboembolism (PE) is notoriously difficult to diagnose since it commonly presents in a non-specific manner. Only 15-30% of the patients identified at post-mortem as having a massive PE have been diagnosed correctly prior to death. 1 , 2 However, large studies have shown that certain clinical symptoms and features such as dyspnoea, tachypnoea, pleuritic chest pain with a normal chest radiograph and a low Pa O 2 are present in more than 90% of patients with PE. 2 Clinicians in a district hospital setting have to rely on these features, especially when facilities for detailed imaging such as computerised tomography (CT) or pulmonary angiography are not available. Occasionally, certain other diseases can mimic the clinical picture of PE and lead to delay in instituting appropriate treatment. We present two patients with symptoms and clinical investigations which were highly suggestive of acute PE but who turned out to have very different diagnoses in the end.

Extended-release fluvastatin 80 mg shows greater efficacy, with comparable tolerability, versus immediate-release fluvastatin 40 mg for once daily treatment of primary hypercholesterolaemia

Abstract: Anew extended-release (XL) formulation of fluvastatin has been developed for once daily treatment of primary hypercholesterolaemia. This study was designed to determine the safety and effect of fluvastatin XL 80 mg on a range of lipid parameters compared with the immediate-release (IR) formulation of fluvastatin 40 mg. In a multicentre, double-blind study, 555 patients with primary hypercholesterolaemia (Fredrickson types IIa or IIb) were randomised to 24 weeks treatment with fluvastatin XL 80 mg or IR 40 mg, each given once daily at bedtime. The study found the least square mean reduction in LDL-C after 24 weeks treatment was 32.6% in the fluvastatin XL 80 mg group (n=312) and 23.9% in the fluvastatin IR 40 mg group (n=165), an 8.7% between-treatment difference (95% confidence interval: 6.5%, 10.9%) in favour of the XL formulation (p 35% reductions in low-density lipoprotein cholesterol (42.3% vs. 13.3%). High-density lipoprotein cholesterol levels were increased by 9.1% and 7.0%, respectively in the XL and IR groups; median triglyceride levels fell by 19% and 13%, respectively. Tolerability was comparable in the two groups, and there were no laboratory safety concerns. The study concluded that fluvastatin XL 80 mg once daily is safe as a starting dose and effectively lowers low-density lipoprotein cholesterol and triglyceride levels in patients with primary hypercholesterolaemia.

Angiotensin II receptor antagonists in the treatment of heart failure: Background to and design of the CHARM study

Abstract: While angiotensin-converting enzyme (ACE) inhibitors are established agents for the treatment of hypertension and heart failure, in contrast the angiotensin II receptor antagonists (AIIRAs) have failed to demonstrate more than equivalence in randomised clinical trials. Trials such as ELITE II are criticised on the grounds that the dose used of losartan (50 mg) may have been sub-optimal. In ValHeFT, valsartan was shown to be superior to placebo only in patients who did not also receive a beta blocker. The ambiguity of response of AIIRAs in such trials will hopefully be clarified in CHARM, a large, placebo-controlled study which will assess the effects of candesartan in heart failure patients with either reduced ejection fractions in addition to an ACE inhibitor, and in those intolerant to an ACE inhibitor, as well as in patients with preserved ventricular function (diastolic heart failure) not on an ACE inhibitor. The design of the study is discussed.