Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: A necropsy study of 20 patients

Abstract

This report describes clinical, morphologic and histologic findings at necropsy late (range 1.6 to 24.1 months [average 8.2 months]) after clinically successful coronary balloon angioplasty in 20 patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 patients (70%), including 6 patients with sudden coronary death. Of the 20 patients, 14 (70%) had a cardiac cause of death and 6 (30%) had a noncardiac cause of death. Two major subgroups of histologic findings were observed: 1) intimal proliferation (60%), and 2) atherosclerotic plaque only (40%). Of the eight sites with atherosclerotic plaque only, six were eccentric lesions and two were concentric lesions. No morphologic evidence of previous angioplasty injury (cracks, breaks, tears) was observed in the eight patients with atherosclerotic plaque only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphologic findings at angioplasty restenosis sites, specific treatment strategies for restenosis after coronary artery balloon angioplasty are proposed.

Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat.

“…Intimal VSMC hyperplasia is the primary cause of vascular reocclusion and restenosis after angioplasty (5,40). If the endothelial cell barrier in vivo is altered, the factor Xa-mediated VSMC mitogenesis that we observed in vitro could contribute, after angioplasty, to the high rate of arterial restenosis and even to atherogenesis.…”

Gene Transfer of Human Prostacyclin Synthase Prevents Neointimal Formation After Carotid Balloon Injury in Rats

“…34 -36 The main cause of restenosis is neointimal formation, which has been observed in 60% of necropsy cases after successful coronary angioplasty. 37 A derangement in vascular eicosanoid metabolism has been implicated in the development of thrombosis and the atherogenic process. 17 The balance between the productions of TXA 2 from platelets and PGI 2 from vessel walls (principally by endothelium and, to a lesser extent, by medial smooth-muscle cells) is an important maintenance factor of vascular integrity.…”

Molecular atherectomy for restenosis

“…As inferred from animal models, the sequence of SMC division, migration, and matrix synthesis is initiated by (1) removal of much of the endothelium and associated basal lamina, which function as semipermeable selective barriers to plasma mitogens and which, furthermore, contain heparin, transforming growth factor β (TGFβ), and other growth inhibitors; (2) rupture of the internal elastic laminae, which exposes SMCs to serum factors and monocytes; (3) exposure of thrombogenic factors such as subendothelial collagens, lipids, tissue factor, and macrophages; (4) stretching of SMCs, thereby directly activating ion channels and proto-oncogenes; (5) separation of adjacent SMCs, thereby disrupting contact inhibition, as well as bathing SMCs in serum mitogens; (6) release of mitogens from ruptured endothelial cells and SMCs; (7) release of chemoattractants from monocytes and expression of intercellular adhesion molecules for monocytes; and (8) stimulation of SMCs (and regenerating endothelial cells) to synthesize and release their own growth factors (Schwartz et al 1990b). It has not yet been possible to corroborate all of these findings in human tissue, but the descriptions of a few specimens obtained within the first few days after PTCA are broadly consistent with features common to the various animal models (Waller et al 1991, Farb et al 1990, Correa et al 1991, Nobuyoshi et al 1991. In brief, there are enough similarities with the animal models to justify their continued use, despite the fact that several experimental therapies effective in rat or rabbit models have not shown benefit in pig and baboon models, or in randomized clinical trials.…”

“…Samples obtained by atherectomy performed 2-6 months after PTCA reveal maturing scar, with foci of activated and quiescent smooth muscle cells (SMCs), and little thrombus or lipid (Waller et al 1991, Gordon et al 1990, Potkin and Roberts 1988, Correa et al 1991, Nobuyoshi et al 1991. Unfortunately, there is almost no available histology from the first hours to days after angioplasty, and even this is more relevant to the pathogenesis of early fatality than of restenosis.…”