The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system

Clinical trials have established bosentan, an orally active non-selective endothelin (ET) receptor antagonist, as a beneficial treatment in pulmonary hypertension. Trials have also shown short-term benefits of bosentan in systemic hypertension and congestive heart failure. However, bosentan also increased plasma levels of ET-1, probably by inhibiting the clearance of ET-1 by endothelin type B (ET.) receptors, and this may mean its effectiveness is reduced with long-term clinical use. Preliminary data suggests that selective endothelin type A (ETA) receptor antagonists (BQ-123, sitaxsentan) may be more beneficial than the non-selective ET receptor antagonists in heart failure, especially when the failure is associated with pulmonary hypertension. Experimental evidence in animal disease models suggests that non-selective ET or selective ETA receptor antagonism may have a role in the treatment of athero-sclerosis, restenosis, myocarditis, shock and portal hypertension. In animal models of myocardial infarction and/or reperfusion injury, non-selective ET or selective ETA receptor antagonists have beneficial or detrimental effects depending on the conditions and agents used. Thus clinical trials of the nonselective ET or selective ETA receptor antagonists in these conditions are not presently warranted. Several selective endothelin-converting enzyme inhibitors tors have been synthesised recently, and these are only beginning to be tested in animal models of cardiovascular disease, and thus the clinical potential of these inhibitors is still to be defined.

Eosinophilic heart: Marked left ventricular wall thickening and myocardial dysfunction improving with corticosteroid therapy

We report a case of a 34-year-old male with acute severe heart failure associated with marked concentric left ventricular wall thickening and biopsy evidence of eosinophilic myocardial infiltrate. This appears to be an unusual description of this degree of concentric myocardial thickening in eosinophilic myocarditis coupled with Doppler tissue echocardiography. Following high-dose corticosteroid treatment, wall thickness, systolic and diastolic left ventricular function normalized and the patient experienced a dramatic clinical improvement. (ECHOCARDIOGRAPHY, Volume 20, May 2003).