**8.4. Predictive scores in CTO PCI**

**8.2. Radial access for CTO PCI**

approach.

54 Interventional Cardiology

referral to CABG [4, 88].

obstacles vanished [99].

Radial access is feasible for contralateral injections in CTO PCI but may be challenging when microcatheters and techniques with additional equipment are used [81, 82]. However, based on the availability of sheathless-guiding catheters with a larger interventional lumen, the radial approach has become more frequently used for both the antegrade and retrograde

In the early days of interventional cardiology, CTO PCI was associated with very low success and relatively high complication rates [83–87]. This leads to a high number of patients undergoing surgery, which was also seen in the SYNTAX and the BARI (Bypass Angioplasty Revascularization Investigation) trial, where the presence of a CTO was a strong predictor for

Procedural failures during CTO are mainly due to the incapacity to pass the lesion with a guidewire, followed by failed balloon crossing, the inability to dilate the lesion, or a vessel perforation [60, 66, 89–91]. Traditional predictors for CTO PCI failure are increasing age of the occlusion, small vessel diameter, presence of calcium or a blunt stump, proximal cap ambiguity, excessive tortuosity, long occlusion length, bridging collaterals, and absent visibility of the distal vessel [72, 89, 92–95]. Furthermore, these lesions show a higher mean Multicenter CTO Registry of Japan (J-CTO) score and have collaterals that are less likely suitable for the retrograde approach [96]. However, additional angiographic features such as multivessel disease, previous CABG, and side branch at the proximal occlusion point seem not to be predic-

Over time, with the improvement of both equipment such as microcatheters and dedicated guidewires with greater torque response [98] and recanalization techniques such as retrograde procedures, safe and effective CTO PCI became possible [60] and most of the prior

Only limited randomized data are available on the outcomes of patients with CTO undergoing CABG [100–102]. CTOs represent a difficult lesion subset also for surgical revascularization, thus leading to incomplete revascularization with 31.9% of CTOs referred for CABG not being surgically revascularized and 7.5% with occluded bypass grafts after 1 year [103].

In SYNTAX, the presence of a CTO was the strongest independent predictor of incomplete revascularization with 51% in the PCI arm and one of the major anatomic predictors for referral to CABG [105]. Interestingly, CABG enhances the progression of atherosclerosis and increases the risk for new CTOs in native coronary arteries, which itself represents an independent predictor of death, MI, and repeat revascularization in these patients [102, 103]. Moreover, long-term patency of saphenous vein grafts (SVG) is limited and is significantly lower than for second-generation DES (70 vs 90% at 5 years, respectively) [106]. Therefore, CABG might only be considered when complete arterial revascularization can be achieved,

At least one CTO is found in more than 50% of patients with CABG [1, 104].

**8.3. Procedural success in patients with CTO undergoing PCI or CABG**

tive for procedural failure with novel guidewire techniques [97].

Scoring systems for CTO PCI are very helpful for case selection as well as to predict procedural efficiency and the probability for success and complications [109, 110]. The SYNTAX score, indeed, highly depends on the presence and specific features of CTO, with a single CTO contributing a substantial 10–15 points but is generally more suitable for diffused triple-vessel disease with and without involvement of the left main.

J-CTO [89] and CT-RECTOR [46] scores predict the likelihood of successful guidewire crossing within 30 minutes. The J-CTO score represents a standardized score of difficulty that predicts successful guidewire crossing within 30 minutes, is simple, easy to remember, and clinically applicable. However, the J-CTO score may be limited in some cases. The CL score considers both clinical and angiographic information, predicts success of a first antegrade attempt, and may be useful in centers where the retrograde or hybrid approach has not yet been implemented [111]. The progress CTO score includes four angiographic characteristics and should be applied when using the hybrid approach [112]. A comparison of these three scores for predicting success of CTO PCI showed a moderate performance in predicting technical outcome, with a favor for antegrade procedures [113]. A novel prediction model including age, ostial location, and collateral filling was also strongly associated with technical failure when using advanced recanalization technologies [70]. The ORA score, however, predicts technical failure by both antegrade and retrograde techniques and categorizes difficulty and success rate of CTO procedures into four groups.

Finally, the Mehran risk score is most widely used as a classic model for CIN after CTO PCI, but it is rather inconvenient in clinical practice because it was established only after contrast media exposure [114, 115].

#### **8.5. Stents in CTO PCI**

The use of bare-metal stents (BMS) after successful CTO PCI has been proven to be superior in terms of immediate angiographic success as well as long-term restenosis and reocclusion when compared with balloon angioplasty (POBA) alone [116–120]. DES in comparison to BMS shows again a significant reduction in TVR and adverse clinical events [121–126] although a trend toward a higher stent thrombosis rate was observed [127–129]. As a consequence, stent implantation following successful CTO PCI increased dramatically over time and reached nearly 100% at the turn of the millennium [130].

#### **8.6. Bioresorbable vascular scaffolds in CTO**

Bioresorbable vascular scaffolds (BVS) have potential long-term benefits compared with DES, thus being particularly reasonable in CTO [131]. A first feasibility analysis in 23 patients with selected and simple CTO lesions demonstrated excellent 6-month and 1-year follow-up after BVS implantation, but these initial results need to be confirmed in larger studies with further long-term follow-up [132].

#### **8.7. Relevance of the target vessel of CTO PCI**

Studies have shown the prognostic importance of the anterior wall of the left ventricle [133, 134]. In accordance with these findings, successful CTO PCI is associated with an improvement in long-term survival as compared to CTO PCI failure in the subpopulation of patients with LAD CTO [76] (cohort from 1980 to 2004, overall stent use < 20%, only three patients received DES).

Results from a contemporary multinational CTO registry suggest that successful PCI of a CTO in only the LAD and the LCX, but not the RCA, is associated with improved long-term survival [135]. Over 90% of patients included in this analysis received a stent, mostly DES, which likely resulted in higher long-term patency. Due to higher anatomical complexity, the LCX is the least commonly attempted target vessel in CTO PCI with a lower rate of procedural success and a trend toward higher MACE rates [89, 95, 97, 98, 136, 137].

#### **8.8. CTO and STEMI**

Patients presenting with acute STEMI show an incidence of CTO up to 13% and tend to suffer poor immediate and long-term prognosis [94, 130, 138–147]. Several trials revealed a concurrent CTO in a non-infarct-related artery (non-IRA) as an independent predictor of short- and long-term mortality in STEMI patients undergoing primary PCI [148–150]. A metaanalysis of seven observational studies including 14,117 patients with a concurrent CTO in a non-IRA artery presenting with STEMI found a three-fold increase in mortality in both single- and multi-vessel disease cases [75]. Furthermore, concurrent CTO in a non-IRA in MVD was significantly associated with residual left ventricular ejection fraction (LVEF) early after STEMI and further decrease of LVEF in the first year after the index STEMI [13], and this seems particularly true for a CTO of the LAD [151].

The acute closure of the donor artery during STEMI leads to extensive myocardial ischemia in a two-vessel area with consecutive hemodynamic instability [144, 148, 152–155]. This is even more pronounced if the culprit vessel has impaired collateral filling itself [156].

#### **8.9. Complete revascularization in CTO PCI**

The most common reason for incomplete revascularization in PCI is the presence of a CTO [157], and incomplete revascularization associated with CTO carries a worse outcome and a higher risk of death compared with complete revascularization [158, 159]. The potential benefit of successful CTO PCI has been derived from retrospective analyses and mainly includes improvement of LVF in preventing heart failure [160], reduction of arrhythmias, and, above all, reduction of mortality, MI, as well as the need for repeating revascularization procedures [161]. Therefore, complete revascularization strategies after the index PCI for STEMI should include CTO procedures.

The EXPLORE (Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infarction) trial was the first randomized controlled trial evaluating whether patients with STEMI and concurrent CTO in a non-IRA benefit from additional CTO PCI shortly after primary PCI [151]. In agreement with earlier registry studies, EXPLORE reported a survival benefit only for successful CTO PCI of the LAD but not for the RCA or LCX [76, 135].

Migliorini et al. studied 330 high surgical risk patients undergoing PCI for unprotected left main disease (ULMD) with more than one-third having at least one CTO [162] and found the presence of a concurrent CTO of the RCA in patients undergoing PCI for ULMD to be a significant predictor for mortality. In contrast to other studies, CTO of both LAD and LCX were not found predictive of worse outcomes. The fact that RCA CTO were attempted less frequently (51%) than CTO of the other two main coronary arteries (79%) may explain the prognostic impact of the RCA in this study.

In the SYNTAX trial, incomplete revascularization was associated with a significant increase in 4-year mortality [105]. The presence of a CTO was less likely to result in complete revascularization in both the PCI and CABG arms and was the strongest independent predictor of incomplete revascularization in the PCI arm. The very low rate of complete revascularization in the PCI arm (34.3%) compared with the CABG arm (64.8%) was mostly related to CTO PCI failure in approximately 50%.

#### **8.10. Restenosis after CTO PCI**

selected and simple CTO lesions demonstrated excellent 6-month and 1-year follow-up after BVS implantation, but these initial results need to be confirmed in larger studies with further

Studies have shown the prognostic importance of the anterior wall of the left ventricle [133, 134]. In accordance with these findings, successful CTO PCI is associated with an improvement in long-term survival as compared to CTO PCI failure in the subpopulation of patients with LAD CTO [76] (cohort from 1980 to 2004, overall stent use < 20%, only three

Results from a contemporary multinational CTO registry suggest that successful PCI of a CTO in only the LAD and the LCX, but not the RCA, is associated with improved long-term survival [135]. Over 90% of patients included in this analysis received a stent, mostly DES, which likely resulted in higher long-term patency. Due to higher anatomical complexity, the LCX is the least commonly attempted target vessel in CTO PCI with a lower rate of procedural

Patients presenting with acute STEMI show an incidence of CTO up to 13% and tend to suffer poor immediate and long-term prognosis [94, 130, 138–147]. Several trials revealed a concurrent CTO in a non-infarct-related artery (non-IRA) as an independent predictor of short- and long-term mortality in STEMI patients undergoing primary PCI [148–150]. A metaanalysis of seven observational studies including 14,117 patients with a concurrent CTO in a non-IRA artery presenting with STEMI found a three-fold increase in mortality in both single- and multi-vessel disease cases [75]. Furthermore, concurrent CTO in a non-IRA in MVD was significantly associated with residual left ventricular ejection fraction (LVEF) early after STEMI and further decrease of LVEF in the first year after the index STEMI [13], and this seems par-

The acute closure of the donor artery during STEMI leads to extensive myocardial ischemia in a two-vessel area with consecutive hemodynamic instability [144, 148, 152–155]. This is even

The most common reason for incomplete revascularization in PCI is the presence of a CTO [157], and incomplete revascularization associated with CTO carries a worse outcome and a higher risk of death compared with complete revascularization [158, 159]. The potential benefit of successful CTO PCI has been derived from retrospective analyses and mainly includes improvement of LVF in preventing heart failure [160], reduction of arrhythmias, and, above all, reduction of mortality, MI, as well as the need for repeating revascularization procedures [161]. Therefore, complete revascularization strategies after the index PCI for STEMI should include CTO procedures.

more pronounced if the culprit vessel has impaired collateral filling itself [156].

success and a trend toward higher MACE rates [89, 95, 97, 98, 136, 137].

long-term follow-up [132].

56 Interventional Cardiology

patients received DES).

**8.8. CTO and STEMI**

ticularly true for a CTO of the LAD [151].

**8.9. Complete revascularization in CTO PCI**

**8.7. Relevance of the target vessel of CTO PCI**

Long subintimally placed stents may attribute to a higher restenosis rate. They are typically seen with the STAR technique [163] and are more frequent after retrograde wire crossing [164]. DES are consistently superior over BMS. Second-generation everolimus-eluting stents have lower rates of restenosis after CTO PCI compared with first-generation DES [165], and PCI of a CTO in stent restenosis shows generally a high success rate with good long-term results [166]. Many studies on restenosis after CTO PCI, however, did not have angiographic follow-up despite the fact that reocclusion can be completely silent after CTO PCI [121, 122, 129, 164, 165, 167–173].
