European Heart Journal Supplements - recent issues

Preface

Fernandez-Aviles, F. — 2006-01-25

(No abstract is available for this citation)

The need to identify new targets for therapeutic intervention in angina

Tavazzi, L. — 2006-01-25

Therapy to reduce the occurrence and symptoms of angina have been less well investigated than drugs to prevent myocardial infarction and death. This article summarizes the current options for anti-anginal and anti-ischaemic drugs and explains why new therapeutic options are needed.

Role of [Na+]i and the emerging involvement of the late sodium current in the pathophysiology of cardiovascular disease

Maier, L. S., Hasenfuss, G. — 2006-01-25

In recent years, it has become increasingly clear that, as well as abnormal intracellular calcium handling, changes in intracellular sodium homeostasis play an important role in the pathophysiology of heart failure. One key source of altered sodium homeostasis may be the slow inactivating sodium current. Altered intracellular sodium promotes alterations in intracellular calcium mainly through the sarcolemmal Na⁺/Ca²⁺ exchanger that can transport Ca²⁺ vs. Na⁺ in both directions. Changes in both calcium and sodium handling are the main factors associated with cardiac dysfunction and the propensity for cardiac arrhythmias. This article gives insight into the mechanisms involved in the pathophysiology of sodium homeostasis in heart failure.

The mechanism of ranolazine action to reduce ischemia-induced diastolic dysfunction

Belardinelli, L., Shryock, J. C., Fraser, H. — 2006-01-25

Ischaemia of myocardium is associated with increases in the late sodium current (I_Na), intracellular sodium and calcium concentrations, calcium overload, and impairment of contractile relaxation (i.e. increased diastolic wall tension). An increase in diastolic wall tension compresses the vasculature and reduces nutritive blood flow, creating a positive feedback system that further impairs myocardial oxygenation and contractile function. Ranolazine reduces the late I_Na and, is expected to decrease sodium entry into ischaemic myocardial cells. As a consequence, ranolazine is proposed to reduce calcium uptake indirectly via the sodium/calcium exchanger and to preserve ionic homeostasis and reverse ischaemia-induced contractile dysfunction.

Clinical implications of inhibition of the late sodium current: ranolazine

Bassand, J.-P. — 2006-01-25

Ranolazine is a unique anti-ischaemic drug that does not significantly affect haemodynamic parameters such as heart rate and blood pressure. Ranolazine has been shown in clinical trials to significantly prolong exercise duration and time to angina, as monotherapy or when administered with conventional anti-anginal therapy. It also reduces angina attacks and consumption of nitroglycerin and is well tolerated at therapeutic doses.

Treatment of angina: a commentary on new therapeutic approaches

Poole-Wilson, P. A., Jacques, A., Lyon, A. — 2006-01-25

Medical treatment of angina has changed little in recent years, with nitrates, beta-blockers, and calcium antagonists being used to control symptoms and aspirin and statins to improve prognosis. However, data on long-term outcomes with these drugs are scarce, and it is clear that the treatment of angina pectoris with current drugs or with invasive interventions does not resolve the clinical problem of continuing symptoms of angina. Several new agents, with innovative mechanisms of action, are now becoming available, making this an area of considerable medical interest.

Preface

Fernandez-Aviles, F. — 2005-11-03

(No abstract is available for this citation)

Obesity management: the cardiovascular benefits

James, W. P. T., Van de Werf, F. — 2005-11-03

(No abstract is available for this citation)

Guidelines on cardiovascular risk assessment and management

Wood, D. A. — 2005-11-03

Cardiovascular disease is the major cause of premature death in most European populations. The underlying pathology is usually atherosclerosis. Cardiovascular disease is closely related to lifestyle and modifiable physiological factors, and risk factor modification has been shown to reduce cardiovascular morbidity and mortality. The current joint European Guidelines differ from previous ones in that the emphasis has moved from coronary heart disease prevention to cardiovascular disease prevention. The Systematic Coronary Risk Evaluation system is recommended to assess an individual's total cardiovascular risk. The guidelines define priorities for intervention and address lifestyle change and management of major cardiovascular risk factors to reduce cardiovascular events. Reduction of overweight and obesity is an important component in reducing cardiovascular risk.

Managing cardiovascular risk: reality vs. perception

Erhardt, L. R. — 2005-11-03

Clinical practice guidelines attempt to bridge the gap between the generation of scientific evidence and its application. For cardiovascular risk reduction, the implementation of knowledge into practice, both with respect to lifestyle change and pharmacological treatment, has been shown to be poor. There are several reasons for this ‘guidelines gap’, with physician factors including insufficient time and underestimation of a patient's cardiovascular risk and patient factors including lack of adherence to lifestyle modification and lack of awareness about cardiovascular risk. Survey data indicate that physicians believe that they are implementing guidelines, but the majority of patients remains undertreated. There is a need for better physician and patient education and also for simplified guidelines to encourage their use by physicians. Cardiologists should work with primary care physicians to adapt national guidelines to ensure local acceptance.

Impact of lipid treatment on cardiovascular risk reduction: new therapeutic targets

Bruckert, E. — 2005-11-03

High levels of LDL cholesterol (LDL-c) are causally related to the development of atherosclerosis. A large body of epidemiological evidence supports a direct relationship between the level of serum LDL-c and the risk of cardiovascular disease, and clinical trials have shown that lowering LDL-c with statins leads to a 30% decrease in the risk of cardiovascular events. However, many patients taking statins continue to suffer cardiovascular disease, highlighting the need both to improve the number of patients reaching LDL-c therapeutic goals and to develop new therapeutic targets. The apoB/apoA-I ratio has been shown to be a major contributor to the risk of myocardial infarction and hence increasing HDL-cholesterol (HDL-c) offers a promising approach to further decrease cardiovascular risk. Clinical trial data with fibrates and nicotinic acid, together with preliminary data on potent new treatments, support HDL-c as a therapeutic target. The cardioprotective effect of HDL-c may not solely be related to its role in reverse cholesterol transport.

What is the relationship between risk factor reduction and degree of weight loss?

Van Gaal, L. F., Mertens, I. L., Ballaux, D. — 2005-11-03

Moderate weight loss achieved through lifestyle interventions positively impacts on a number of metabolic and cardiovascular risk factors. Clinical studies have shown that sustained moderate weight loss lowers blood pressure, improves glucose control, and improves dyslipidaemia as well as inflammatory, haemostatic, and fibrinolytic factors. In addition, it is associated with the prevention of progression to Type 2 diabetes in at-risk subjects. Furthermore, increasing physical fitness is associated with increases in HDL cholesterol and reductions in all-cause mortality. However, there is, as yet, only indirect evidence that modification of risk factors through weight loss will reduce mortality.

Risks and benefits of weight loss: challenges to obesity research

Ryan, D. — 2005-11-03

It is well accepted that being overweight or obese carries risks to health, but there is less agreement as to whether weight loss produces benefits on mortality and on cardiovascular event rates. The evidence from observational studies is conflicting: some studies have shown weight loss to be associated with increased mortality, but this could be because differentiation was not made between intentional and unintentional weight loss. Mechanistic hypotheses can be raised for both beneficial and harmful effects of weight loss. Randomized controlled clinical trials are needed to establish the effect of intentional weight loss and two large outcome studies are now under way: SCOUT and Look AHEAD. These trials are assessing the effect of weight loss on cardiovascular endpoints. Such trials are complex and expensive to undertake, but are important if we are to establish whether weight loss is truly associated with a reduction in mortality.

Does pharmacologically induced weight loss improve cardiovascular outcome? Impact of anti-obesity agents on cardiovascular risk factors

Finer, N. — 2005-11-03

Currently available anti-obesity drugs sibutramine and orlistat, and the soon to be available rimonabant, all produce similar degrees of clinically meaningful weight loss and weight loss maintenance, even though they differ considerably in their mode of action. Pharmacologically induced weight loss has a beneficial impact on a number of metabolic and cardiovascular risk factors, such as glucose homeostasis, blood pressure, central adiposity, and dyslipidaemia. In some cases, these effects appear to be over and above that explained by weight loss. These effects are important if obese patients are to be treated not just for their weight but also to reduce co-existing metabolic and cardiovascular risk factors.

Does pharmacologically induced weight loss improve cardiovascular outcome? Sibutramine pharmacology and the cardiovascular system

Sharma, A. M. — 2005-11-03

The serotonin and noradrenaline re-uptake inhibitor, sibutramine, is a widely used anti-obesity drug that promotes weight loss by increasing satiety, although a mild increase in energy expenditure may also contribute. Noradrenaline re-uptake inhibition with sibutramine in peripheral tissues could theoretically exacerbate arterial hypertension through an increase in synaptic noradrenaline concentrations. This has led to a widespread perception that sibutramine contributes to hypertension and should not be used in patients at high risk of cardiovascular disease. However, neither published trials nor post hoc re-analysis of randomized trial data support this notion; the incidence of sustained blood pressure (BP) increase with sibutramine is not significantly different from control. Indeed, post-marketing surveillance data suggest a significant decrease in BP with sibutramine in obese hypertensives. The biological basis of this effect is underpinned by detailed consideration of adrenergic receptor pharmacology and confirmed by mechanistic studies.

The SCOUT study: risk-benefit profile of sibutramine in overweight high-risk cardiovascular patients

James, W. P. T. — 2005-11-03

Moderate weight loss improves metabolic and cardiovascular risk factors and prevents the progression to Type 2 diabetes. Furthermore, a healthy lifestyle is associated with lower cardiovascular mortality, whereas sustained weight loss and increased fitness are both associated with reduced cardiovascular mortality. Currently available anti-obesity drugs have been shown to deliver moderate weight loss in more patients and for longer than diet and exercise alone. In addition, these anti-obesity agents impact positively on multiple cardiovascular risk factors. The question of whether the use of weight loss agents can prevent cardiovascular morbidity and mortality has not been studied so far. The Sibutramine Cardiovascular Outcome Trial (SCOUT) has been designed to determine whether weight management in cardiovascular high-risk overweight and obese patients can impact upon cardiovascular endpoints. Patient enrolment for the SCOUT trial began in December 2002 with the first patient randomized in February 2003. The study will involve ~9000 patients in 16 countries. They will be treated with a novel lifestyle intervention programme and randomized in a double-blind fashion to receive either sibutramine or placebo.

Questions

2005-11-03

(No abstract is available for this citation)

Preface

Fernandez-Aviles, F. — 2005-10-06

(No abstract is available for this citation)

Foreword

Bolognese, L., Ferrari, R. — 2005-10-06

(No abstract is available for this citation)

Percutaneous coronary intervention guidelines: new aspects for the interventional treatment of acute coronary syndromes

Elsasser, A., Hamm, C. W. — 2005-10-06

In March 2005, the European Society of Cardiology (ESC) guidelines on percutaneous coronary intervention (PCI) were published, in which the management of patients with acute coronary syndromes (ACSs) was presented in detail for the interventional cardiologist. These guidelines supplement previous guidelines from the ESC on ACS with and without ST-elevation. Patients presenting with non-ST-segment elevation ACS should be treated according to the risk of progressing to myocardial infarction (MI) or death. Immediate (<2.5 h) or early (<48 h) coronary angiography and PCI are advised, particularly in patients with elevated troponin levels or diabetes mellitus. Coronary intervention in high-risk patients should be performed with triple antiplatelet therapy (aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors). In patients with ST-segment elevation MI, primary PCI is the preferred treatment option, particularly >3 h after onset of clinical symptoms. Adjunctive therapy should include abciximab. Patients treated with thrombolysis should undergo invasive evaluation within 24 h. If this cannot be achieved, ischaemia-driven angiography is recommended.

Non-ST-elevation acute coronary syndromes management: a fresh look at glycoprotein IIb/IIIa inhibitors

Cavallini, C., Chirillo, F. — 2005-10-06

Several randomized clinical trials have shown glycoprotein (GP) IIb/IIIa inhibition to be beneficial in non-ST-segment elevation acute coronary syndromes (NSTE-ACSs), producing a significant reduction in the risk of death and myocardial infarction. The greatest benefit was found in high-risk patients, such as those with diabetes, those with a positive troponin value at baseline or those undergoing early percutaneous coronary intervention. Data from large national registries have shown that early use of GP IIb/IIIa inhibitors is associated with a benefit consistent with that reported in clinical trials, the lowest adjusted rate of in-hospital mortality was found for hospitals with the highest rate of early use of these drugs. Upstream treatment with small-molecule GP IIb/IIIa inhibitors, in combination with an early aggressive interventional approach, is clearly beneficial and is strongly recommended by international guidelines in high-risk patients with NSTE-ACS. However, GP IIb/IIIa inhibitors appear to be markedly underused in current practice. Potential reasons for this inconsistency are discussed.

Myocardial damage during percutaneous interventions for non-ST-elevation acute coronary syndromes

Bolognese, L., Falsini, G., Liistro, F., Angioli, P. — 2005-10-06

The prognostic significance and pathophysiological mechanisms underlying elevations in cardiac enzymes in patients with non-ST-segment elevation acute coronary syndromes (ACS) post-percutaneous coronary intervention (PCI) is a matter of debate. The few available data, derived mainly from sub-analyses of large randomized trials and from small prospective observational studies, suggest that patients with ACS who undergo PCI have an increased risk for procedural myocardial damage which, in turn, is associated with an adverse clinical outcome. Although the pathophysiology of post-PCI myocardial damage is multifactorial, the embolization of debris or calcified plaque material, or exposure of thrombogenic material at intravascular sites seems to play a key role, as shown by mechanistic studies that demonstrate a close relationship between post-procedural enzyme release and abnormal tissue perfusion. Several pre-procedural treatment strategies using antithrombotic therapies have evolved in an attempt to lower the rate of myocardial damage related to the performance of PCI in ACS patients. Major trials that evaluated the use of glycoprotein (GP) IIb/IIIa inhibitors during PCI in patients with ACS have suggested that maximum benefit is obtained in patients with increased troponin levels and in patients undergoing PCI, reducing the incidence of cardiac enzyme release after the procedure. However, a number of lingering unsolved issues concerning which agent should be used and the most appropriate timing and dosage remain to be explored. Mechanistic and clinical findings suggest that an early invasive strategy with upstream GP IIb/IIIa inhibitors may yield more favourable outcomes than downstream strategies.

Early invasive strategy in the diabetic patient with non-ST-segment elevation acute coronary syndromes

Roffi, M. — 2005-10-06

Diabetic patients with non-ST-segment elevation acute coronary syndromes are at high risk for subsequent cardiovascular events. At the same time, however, they derive greater benefit than non-diabetic counterparts from an aggressive acute-phase management based on platelet glycoprotein IIb/IIIa receptor antagonists and an early invasive strategy. Despite the benefit, these treatment modalities remain underutilized among patients with diabetes mellitus. The widespread use of drug-eluting stents will further improve outcomes in patients with diabetes undergoing early percutaneous revascularization. In this patient population, the sirolimus-eluting stent appears to be superior to the paclitaxel-coated one.

Early invasive strategy in elderly patients with non-ST-elevation acute coronary syndromes

Liistro, F., Ducci, K., Falsini, G., Bolognese, L. — 2005-10-06

The clinical impact of an early invasive strategy (EIS) on elderly patients with acute coronary syndromes (ACSs) has yet to be completely defined because of the poor enrolment of elderly patients in randomized trials in this setting. The reluctance to treat elderly ACS patients is mainly due to the higher risk profile of these patients when percutaneous or surgical revascularization is planned. However, recent clinical data from different centres strongly support the use of an EIS in the elderly, showing a significantly larger absolute reduction in 30-day major adverse clinical events in elderly patients than that in younger patients, and prompt the need for dedicated randomized trials.

Percutaneous coronary intervention and beyond for ST-elevation acute myocardial infarction

Danzi, G. B., Mauri, L., Sozzi, F. — 2005-10-06

The short- and long-term prognosis of acute myocardial infarction (MI) has markedly improved over the past 20 years, from 19% in 1986 to the current 5–6%. One of the reasons for this decrease is the introduction of more effective myocardial reperfusion techniques, as it has been clearly demonstrated that the rapidity, extent, and durability of reperfusion are an important prognostic determinant. Primary percutaneous coronary intervention has been shown to be superior to fibrinolytic treatment because it leads to a higher reperfusion rate. Myocardial salvage after the timely revascularization of an infarct-related artery critically depends on coronary blood flow to the area at risk, and therefore the adequacy of arterial reperfusion in acute MI depends not only on the persistent arterial patency, but also on the integrity of the distal circulation. At the microcirculatory level, distal embolization from the lesion site, the release of vasoconstrictive platelet mediators, and vascular reperfusion injury due to cardiac inflammatory responses may all compromise recovery, and therefore efficacious treatment of acute MI requires the restoration of patent epicardial flow and the preservation of microvascular integrity. The various techniques currently being evaluated for their ability to reduce final infarct size will be discussed.

New and old strategies to afford the liberal use of drug-eluting stents in real-life scenarios

2005-10-06

Drug-eluting stents represent one of the most important improvements in interventional cardiology by decreasing the rate of restenosis dramatically. However, at present, cost constraints and a lack of incremental reimbursement have limited their utilization in daily practice in many countries, including Europe. Strategies to implement the liberal use of sirolimus-eluting stents (SES), especially in the primary percutaneous coronary intervention setting where the cost-effectiveness profile could be less favourable, without affecting medical expenditure are presented and discussed. To project the potential cost-effectiveness of SES-supported multivessel treatment compared with that of coronary artery bypass grafting, a decision- analytical model was developed from a payer's perspective on the basis of data derived from the current Italian health-care system.

A quantitative analysis of the benefits of pre-hospital infarct angioplasty triage on outcome in patients undergoing primary angioplasty for acute myocardial infarction

2005-10-06

Primary coronary angioplasty has been shown to be a very effective reperfusion modality in patients with acute myocardial infarction (MI). However, the time from diagnosis to therapy is often very long, often due to interhospital transfer of the patient. This study evaluates the effect of improving logistics by early infarct diagnosis in the ambulance (ambulance group) and subsequent transportation to a percutaneous coronary intervention (PCI) centre without visiting a nearby non-PCI clinic (referred group). Pre-hospital infarct diagnosis and triage in the ambulance (n=209) were compared with triage at a referral non-PCI centre (n=258) in patients included in the On-TIME (Ongoing Tirofiban In Myocardial infarction Evaluation) study. Baseline characteristics of the two patient groups did not differ significantly, with the exception of a higher prevalence of males in the ambulance group. The ambulance group had a significantly shorter time to treatment (177 vs. 208 min; P<0.01), a higher initial patency rate (44 vs. 35%; P=0.045), a better extent of myocardial reperfusion (myocardial blush grade 3: 59 vs. 47%; P=0.02), a trend toward a higher prevalence of aborted MI (15 vs. 10%; P=0.08), and a significantly lower rate of death or re-MI at 1 year of follow-up (3 vs. 10%; P=0.004). It was concluded that early, pre-hospital infarct diagnosis in the ambulance with immediate transportation to the nearest PCI centre is associated with a shorter time to treatment and improved angiographic and clinical outcomes compared with referral from a non-PCI centre in patients who are candidates to undergo primary angioplasty for acute MI.