**3.2. Remodeling in CTO**

**3. Histopathology**

46 Interventional Cardiology

on the coronary vessel [17].

circulation [20].

in their size.

**3.1. Collaterals and microchannels in CTO**

well understood in terms of CTO recanalization [21].

Wang et al. demonstrated that acute coronary occlusions leading to segment elevation myocardial infarction (STEMI) seem to predominately occur in predictable spots within the proximal third of the coronary arteries and that for each 10 mm increase in distance from the ostium, the risk of an acute coronary occlusion significantly decreased by 13–30%, depending

In contrast to this, sparse information exists concerning the genesis of CTO and its regional distribution in terms of recanalization. In some publications, soft plaque rupture during acute coronary syndrome (ACS) with rapid thrombotic occlusion followed by its organization is described as the main cause of CTO and only a few appear to derive from atheroma progression [18]. Furthermore, it seems that once thrombotic occlusion occurs the thrombus tends to disseminate retrograde from the site of occlusion to the proximal segments of the vessel with a major side branch [19]. It is known that due to increased chronic hypoxic induction of neovasculature, the affected vessel segment stays biologically active and shows a marked heterogeneity in compensatory angiogenesis with an unpredictable wide range of coronary collateral

Successful guidewire crossing may be facilitated by the presence of intravascular microchannels, but structural changes over time with variable localization of these microvessels are not

In a post-mortem study of 96 CTO lesions, 49% exhibited residual <99% lumen stenosis by histologic criteria despite angiographically documented total occlusions [22]. In this cohort, adventitia and intimal plaque of total occlusions were the prevalent zones of inflammation and neovascularization. Furthermore, the results revealed in CTOs of all ages a close relation between cellular inflammation and vessel wall neovascularization in terms of location and intensity with an increase in numbers of neovascular channels rather than with an increase

Munce et al. found two histological types of microvessels in a rabbit model with induced femoral occlusion: a circumferentially oriented "extravascular" and a longitudinally oriented "intravascular" one. Interestingly, extravascular vessels around the occluded artery developed to a maximum at an early time point, followed by a slow regression over time, while intravascular vessel formation within the central body of the occlusion was delayed, and these vessels became thinner and more tortuous over time. Strongly angulated connections between the intra and extravascular microvessels were constantly present, which could explain devia-

Katsuragawa et al. found different histomorphological features in CTOs with tapering of the proximal occlusion point compared to those with a blunt proximal cap [19]. A total of 80% of the tapering-type lesions had shorter occluded segments and showed small recanalized

tion of the guidewire into extravascular channels during CTO recanalization [21].

As atherosclerotic lesions develop in arteries, two types of remodeling can occur [23]. Positive remodeling is a compensatory process in which the arterial wall grows outward in an attempt to maintain a constant lumen diameter. Negative remodeling is angiographically defined as the ratio of the occluded vessel diameter to the diameter of the contiguous normal vessel <1 and was found to be the strongest predictor of failed antegrade CTO PCI [24, 25]. In negative remodeling, an early phase where fibrin-rich organizing thrombus becomes a proteoglycanrich thrombus and a late phase where proteoglycan-rich thrombus within the CTO body is replaced by dense collagen, thus complicating antegrade wiring, were found [15].
