SIDAMI - Sildenafil and Diastolic Dysfunction After AMI

Background:

Acute myocardial infarction (AMI) is characterized by regional myocardial damage which may lead to systolic and diastolic dysfunction with a subsequent risk of left ventricular (LV) remodeling, local and systemic neurohormonal activation, vascular dysfunction and development of heart failure. The pathophysiology and prognosis of LV systolic dysfunction after AMI has been the focus of research for several decades. Insights from these studies have led to several therapeutic interventions that improve outcome. In addition to depressed systolic function, clinical or radiographic evidence of heart failure is a consistent and powerful predictor of outcome in patients following AMI. Pulmonary congestion after AMI reflects raised LV filling pressures but is frequently seen after what appears to be only minor myocardial damage. The pathophysiological mechanism for this is incompletely understood but may involve impaired active relaxation of the myocardium and increased LV chamber stiffness, hence, abnormalities in diastolic function. Abnormal LV diastolic function especially when chamber stiffness is increased is characterized by a disproportionate increase in filling pressure during exercise and an inadequate increase of cardiac output. During ventricular diastole the left atrium acts as a conduit between the left ventricle and the pulmonary veins. Thus in case of increased filling pressures left atrial pressure is elevated exposing the pulmonary vascular bed to increased pressures. In accordance pulmonary artery pressure is frequently increased after AMI, even when systolic function is preserved.

Several recent studies have demonstrated that Doppler echocardiographic indices suggestive of increased filling pressure and increased pulmonary arterial pressure are associated with excess mortality and morbidity after AMI . The optimal management of this large group of patients is unknown, but in theory lowered preload improved cardiac output especially during exercise and lowering of pulmonary arterial pressure could relive symptoms and improve exercise capacity.

Sildenafil is a potent selective phosphodiesterase inhibitor that suppresses degradation of cyclic GMP. In the pulmonary bed this leads to pulmonary vasodilation, in addition sildenafil has been shown to improve endothelium dependent vasodilation thus augmenting abnormal vascular tone . In patients with systolic heart failure sildenafil has been demonstrated to lower pulmonary wedge pressure, improve cardiac index and lower pulmonary arterial pressure without causing systemic hypotension . Thus in theory sildenafil may have beneficial effects in patients at high risk of heart failure.

Hypothesis: