European Heart Journal Supplements - current issue

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.