Angiogenesis in chronically ischaemic human heart following percutaneous myocardial revascularisation.

Patients with intractable angina and severe diffuse coronary artery disease not amenable to conventional revascularisation therapy have relatively few treatment options. A number of studies suggest myocardial laser revascularisation is of clinical benefit in such patients.1, 2 Percutaneous myocardial revascularisation (PMR) involves the use of an intravascular catheter, positioned within the left ventricular cavity under fluoroscopic guidance, to deliver controlled bursts of holmium:YAG laser energy. PMR results in the formation of small channels (~1.75 mm diameter) that extend from the endocardial surface partly into the myocardial wall. Many uncontrolled studies suggest that PMR provides symptomatic relief, although the first randomised controlled trial demonstrated no benefit over a sham procedure.3 It has been suggested that PMR induces angiogenesis, although many other mechanisms of action have been suggested. To determine whether PMR has any effects on angiogenesis in the human ischaemic myocardium we have undertaken a detailed histological and immunohistochemical examination of the hearts of two patients who died eight weeks and 52 weeks after apparently symptomatically successful PMR therapy. In this first detailed study of human myocardium subjected to percutaneous myocardial laser revascularisation, we report evidence of sustained myocardial neovascularisation in treated areas and of the presence of vascular endothelial growth factor (VEGF). Unexpectedly, most of the neovessels are abnormal and immature, lacking a smooth muscle coat. Furthermore, neovessels are largely confined to scar tissue. Both the above factors are likely to limit the extent to which angiogenesis following PMR could improve perfusion. In a broader context, our findings that, once formed, immature and abnormal neovessels are sustained long term in human myocardium, may be relevant to the general design of strategies for therapeutic angiogenesis in patients���for example, the direct application of angiogenic factors (or genes)