Collagenase Plaque Digestion for Facilitating Guide Wire Crossing in Chronic Total Occlusions

Abstract

Background-Chronic total occlusions (CTOs) are associated with significant angina, impaired left ventricular function, and worse long-term outcomes. Percutaneous coronary interventions in CTO are unsuccessful in up to 50% of cases, primarily because of inability to cross the lesion with a guide wire. Collagen is the predominant component of the atherosclerotic plaque. The objective of this study was to determine the efficacy and toxicity of local delivery of a collagen-degrading enzyme to facilitate guide wire crossing in CTO. Methods and Results-Type IA collagenase (100 or 450 g) or placebo was locally administered to 45 CTOs in a rabbit femoral artery model. Mean occlusion duration was 16Ϯ5 weeks. Attempts to cross the CTO (mean length, 28Ϯ9 mm) with conventional guide wires were assessed at 72 hours after treatment. An additional 3 arteries per group were assessed for collagenase effects at 24 hours after treatment. Successful guide wire crossings were significantly higher in collagenase-treated arteries (13 of 21, 62%) than in placebo-treated arteries (7 of 24, 29%) (Pϭ0.028). No adverse effects on arterial structure were observed in collagenase-treated arteries.

Percutaneous Recanalization of Chronically Occluded Coronary Arteries

“…Success rates of Ϸ50% to 60% have been reported with this technique in several series of refractory CTOs, with blood transfusions primarily from access site bleeding required in 0% to 15% of patients. 49 -52 Collagenase infusion in experimental models has shown promise in modifying the fibrotic, collagen-rich structure of occlusive plaque to facilitate successful guidewire passage 53 ; human studies are pending. The utility of therapeutic ultrasound in crossing vascular occlusions has been studied for many years, 54,55 although the results with a first-generation system in coronary CTOs were suboptimal because of relatively high device profile and stiffness.…”

Collagenase Total Occlusion-1 (CTO-1) Trial

“…19 Extensive preclinical studies in a rabbit femoral artery chronic occlusion model have previously shown that local delivery of collagenase significantly improved guide wire crossing. 10,11 It is generally acknowledged that success rates are lower in reattempt CTO cases than in first attempts. In the Japanese CTO (J-CTO) registry, reattempts were reported in 54 cases (10.2% of the overall study cases).…”

“…Previous preclinical work has shown that a 72-hour waiting period between delivery and guide wire crossing is also effective and, in some cases, may be more clinically convenient. 10 Whether the collagenase procedure can be shortened into a single-day procedure remains to be determined; however, the time required for collagenase injection seems well suited to chronic occlusions diagnosed at the time of angiography when operators may have limited time to attempt the CTO given the prescheduled list of cases. The patient can then be brought back for revascularization at a more suitable time.…”

“…[7][8][9] Collagenase, a matrix metalloproteinase enzyme that selectively degrades type I collagen, has been shown to facilitate guide wire crossing in an animal model of CTO. 10,11 The objectives of this study were to assess the feasibility, safety, and efficacy of locally delivering collagenase into chronic occlusions to facilitate guide wire crossing in patients with at least 1 previously failed attempt to revascularize CTO.…”

Importância dos estudos pré-clínicos em animais de experimentação para a cardiologia intervencionista

“…Of these, gas-drying with thrombin and a high-cholesterol diet was deemed the most efficacious. Strauss et al subsequently modified the thrombin injection model by infusing collagenase before wire passage 64 . Several characteristics of human CTO were evident in this model, including mature fibrous tissue, multiple small intraluminal vascular channels, occasional extracellular lipid deposits, and disruption of the internal elastic lamina (Fig.6).…”