Update on Chronic Total Occlusion Percutaneous Coronary Intervention

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Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) continues to evolve. This review summarizes recent publications categorized by outcomes, techniques, complications, and ongoing studies in this rapidly growing area.

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) continues to evolve. In this manuscript, we summarize studies on CTO PCI published between November 2022 and September 2023, categorized by outcomes, technique, complications, and ongoing studies.

Optimal medical therapy vs CTO-PCI. The EuroCTO trial assessed the long-term safety and efficacy of PCI with a biolimus-eluting stent plus optimal medical therapy (OMT) compared with OMT alone in patients with coronary CTOs. At 1 year, compared with the OMT group, the CTO PCI group had greater improvement in angina frequency (mean angina frequency score: OMT 86.8 vs PCI 92, P = .003), mean quality of life (QoL) (QoL score: OMT 70.5 vs PCI 77.1, P = .007), and physical limitation (PL) (mean PL score: OMT 75.9 vs PCI 81.1, P = .02), as assessed by the Seattle Angina Questionnaire (SAQ).¹ At 3-year follow-up, there was no difference in the incidence of cardiovascular death or non-fatal myocardial infarction (MI) (OMT 3.7% vs PCI 6.2%; P = .29) in intention to treat analysis. The incidence of major adverse cardiovascular events (MACE) was higher in the OMT group (OMT 21.2% vs PCI 11.2%; P = .008) primarily due to higher incidence of ischemia-driven revascularization (OMT 17.5% vs PCI 3.5%; P = .002). There were no differences in stroke and hospitalization for bleeding (P = .43, P = .27, respectively).²

The randomized controlled comparison of OMT with PCI of CTO (COMET-CTO) trial randomized 100 patients to CTO-PCI + OMT vs OMT alone. At 6-month follow-up, the CTO-PCI group had fewer anginal episodes (mean angina frequency score: OMT 76.8 vs PCI 89.8, P = .006), less PL (mean PL score: OMT 60.5 vs PCI 72.7, P = .014), and better QoL (mean QoL score: OMT 62.5 vs PCI 79.9, P = .001), assessed by SAQ.³ After 56 ± 12 months of follow-up, there was no difference between groups in MACE (P = .363), QoL score (mean QoL score: OMT 66.7 vs PCI 68.5; P = .717), cardiac death (OMT 12% vs PCI 6%; P = .489), MI (OMT 2% vs PCI none; P = 1), and revascularization (OMT 22% vs PCI 9%; P = .093).⁴

Impact of patient characteristics. Two studies (1 prospective study⁵ and 1 registry⁶) investigated the effect of CTO-PCI on quality of life in the elderly. Successful CTO-PCI significantly improved symptoms, including dyspnea, angina, and QoL, in both studies. In the OPEN CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion) registry, CTO PCI had lower technical success (adjusted risk ratio = 0.92; 95% CI, 0.86-0.99; P = .02) and numerically higher in-hospital MACE (9.1% vs 5.9%, P = .10) in patients 75 years old or older (19.8% of the total population) compared with patients less than 75 years old. At 1-year follow-up, SAQ QoL score was not significantly different between adults aged 75 years old or older and adults less than 75 years old (adjusted difference = 0.9; 95% CI, -1.4-3.1; P = .44).⁶ 

In a study of 1076 patients, those who were 75 years old or older (9.4% of the total population) had similar procedural success (P = .375), intraprocedural complications (P = .697), and in-hospital MACE (P = .08). At 1-year follow-up, all-cause mortality (OR 1.37; 95% CI, 0.53-3.55; P = .520), repeat revascularization (OR 1.11; 95% CI, 0.51-2.42; P = .891), and non-fatal MI (OR 2.12; 95% CI, 0.76-5.96; P = .153) were also not significantly different between the 2 groups.⁵

Men and women have different outcomes after CTO PCI. Among 35 449 CTO PCIs performed between 2008 and 2019 in the European Registry of CTO (ERCTO),⁷women (15.2% of the total population) were older (67.9 ± 10.3 vs 64.0 ± 10.5, P < .001) and more likely to have hypertension (80.6% vs 74.1%, P < .001), insulin-dependent diabetes (13.6% vs 9.9%, P < .001), and renal failure (mean estimated glomerular filtration rate [eGFR] [mL/min]: 64.8 ± 26.1 vs 75.7 ± 30.5, P < .001). Women had lower J-CTO scores (mean J-CTO: 2.02 ± 1.26 vs 2.23 ± 1.27, P < .001) and higher procedural success (adjusted OR [aOR] 1.11; 95% CI, 1.011-1.230; P = .030) than men. Although in-hospital MACE (0.9% vs 0.9%, P = .766) was similar in men and women, women had higher risk of coronary perforation (3.7% vs 2.9%, P = .001) and vascular access complications (1.0% vs 0.6%, P = .001).⁷

In-stent vs de novo CTO. A meta-analysis of studies that compared outcomes of PCI of in-stent vs de novo CTOs showed that in-stent CTO PCI is associated with higher MACE (OR 1.57; 95% CI, 1.31-1.89; P < .001), target vessel MI (OR 2.29; 95% CI, 1.7-3.1; P < .001), and ischemia-driven target-vessel revascularization (TVR) (OR 2.66; 95% CI, 2.01-3.53; P < .001). In-stent CTO PCI was associated with lower risk of bleeding and blood transfusion (OR 0.43; 95% CI, 0.19-1.00; P = .05) without significant differences in technical (OR 1.06; 95% CI, 0.78-1.42; P = .72) and procedural (OR 1.0; 95% CI, 0.89-1.13; P = .99) success.⁸

Prior coronary artery bypass graft surgery (CABG). Alexandrou et al reported the 2-year follow-up outcomes of 3475 patients with prior CABG who underwent CTO-PCI in the PROGRESS-CTO registry. Patients with CABG were older (67.7 ± 33.8 vs 63.5 ± 23.2, P < .001), more likely to be men (84.5% vs 79.7%, P < .001), and had lower left ventricular ejection fraction (LVEF) (49.9% vs 50.6%, P=.015) and estimated glomerular filtration rate (67.4 vs 73.46, P < .001). CTOs in prior CABG patients were more likely to have moderate/severe calcification (64.2% vs 38.4%, P < .001), proximal tortuosity (38.2% vs 25.4%, P < .001), proximal cap ambiguity (43.9% vs 31.2%, P < .001), longer lesion length (37.4 ± 25.4 vs 28.6 ± 19.2, P < .001) and higher J-CTO scores (2.81 ± 1.17 vs 2.2 ± 1.27, P < .001). Patients with prior CABG had lower technical (82.1% vs 88.2%, P < .001) and procedural (80.6% vs 86.8%, P < .001) success, and higher in-hospital mortality (0.8% vs 0.3 %, P < .001), acute MI (0.9% vs 0.5%, P = .007), and perforation (7.0% vs 4.2%, P < .001). At 2-year follow-up, prior CABG patients had higher MACE, repeat PCI, and MI, but similar all-cause mortality.⁹

Left anterior descending artery (LAD) CTO-PCI. Megaly et al examined the outcomes of LAD CTO-PCI in a single high-volume center.¹⁰ Overall technical success was 97.4% and the most common crossing strategy was antegrade wiring (53.4%). The incidence of in-hospital MACE and death was 5.5% and 1.2%, respectively. At 2 years, survival was 92.7%, and MACE-free survival was 85%, with no difference between patients with and without ischemic cardiomyopathy (ICM) (defined as LVEF ≤ 40%). At 9 months, the LVEF of ICM patients increased by 10.9% overall, and by 14% in patients who were on OMT at 6 months.

Distal target vessel quality. In an analysis of the PROGRESS-CTO registry, Allana et al demonstrated that 33% of CTOs had poor quality distal vessel, which was associated with lower technical (79.9% vs 86.9%, P < .001) and procedural (79% vs 86.8%, P < .01) success, higher MACE (2.5% vs 1.7%, P < .01) and perforation (6.4% vs 3.7%, P < .001), higher utilization of the retrograde approach (25.2% vs 14.9%, P < .001), lower utilization of antegrade dissection and reentry (ADR) (10.6% vs 13.5%, P < .001), higher radiation dose (2.4 [1.3-4] vs 2 Gray [1.1-3.7], P = .002), and longer procedural time (130 [86-182] vs 105 min [69-156], P < .001) (Figure 1).¹¹

Remaining CTO. A cohort study from the Scandinavian Chronic Total Occlusion (SKEJ-CTO) registry investigated the long-term prognosis of patients with remaining CTO after the final revascularization attempt.¹² During 8-year follow-up, patients with remaining CTOs had higher mortality (unadjusted hazard ratio [HR] 1.65; 95% CI, 1.03-2.47; P = .015; adjusted HR 1.32; 95% CI, 0.88-1.99; P = .18) and major adverse cardiac and cerebrovascular events (MACCE) (unadjusted HR 1.79; 95% CI, 1.34-2.41; P < .001; adjusted HR 1.51; 95% CI, 1.11-2.05; P = .009).¹²

Reattempt CTO-PCI. Among 9560 CTO PCIs in the PROGRESS-CTO registry, 20% had a prior failed attempt.¹³ Prior failed CTO-PCI attempt was associated with higher lesion complexity (J-CTO scores: 3.3 ± 1.16 vs 2.12 ± 1.19, P < .001), longer procedure time (120 vs 111 minutes, P < .001), and higher air kerma radiation dose (2.3 vs 2.1 Gray, P = .013). Operators performing more than 30 CTO PCIs per year had higher technical success (87.4% vs 80.8%, P < .001).

Guelker et al¹⁴ and Li et al¹⁵ reported that reattempt CTO lesions were more complex and had longer duration. Success (initial attempt: 86.9% vs reattempt: 83%, P = .204) and complication rates (initial attempt: 6% vs reattempt: 4%, P = .467) were similar in reattempt CTO PCI.¹⁴ Li et al reported 68% success rate for reattempt CTO PCIs; during a median follow-up of 21.7 months, MACE was higher in patients who had failed reattempt CTO PCI (14.2% vs 38.9%, aHR 0.351; 95% CI, 0.134-0.917; P = .033).¹⁵ CTO PCI can, therefore, still be performed in patients with prior CTO PCI failure with high success rates, especially when performed by experienced operators.

Bifurcation CTO. Konstantinidis et al compared the outcomes of the patients with vs without a bifurcation within the CTO segment.¹⁶ The prevalence of bifurcation CTO PCI was 40.4% and such lesions had higher J-CTO (2.4 ± 1.16 vs 2.2 ± 1.2, P = .025) and PROGRESS-CTO (1.6 ± 0.95 vs 1.2 ± 0.9, P < .001) scores. The most frequently used technique for treating the bifurcation was the provisional approach (93.5%). Overall procedural success (80.4% vs 77.8%, P = .447) and the incidence of complications (MACE: 5.7% vs 5.0%, P = .688) was similar in patients with and without bifurcations.

Same-day discharge. Simsek et al showed significant increase in same-day discharge after CTO PCI from 3% in 2015 to 21% in 2022.¹⁷ Same-day discharge was more common with radial-only access (OR 2.45; 95% CI, 2.03-2.96; P < .001) and lower in patients with prior MI (OR 0.71; 95% CI, 0.59-0.87; P = .001), chronic lung disease (OR 0.64; 95% CI, 0.47-0.88; P = .006), and longer procedure time (OR 0.93; 95% CI, 0.91-0.95; P < .001, per 10-min increase).

Single vs multiple operators. Karacsonyi et al reported that 15% of 9296 CTO PCIs in the PROGRESS-CTO registry were performed by multiple operators.¹⁸ Single operator cases had higher J-CTO (2.38 ± 1.29 vs. 2.28 ± 1.2, P = .005) and PROGRESS-CTO (1.13 ± 1.01 vs 0.97 ± 0.93, P < .001) scores, shorter procedural (112 vs 131 mins, P < .001) and fluoroscopy (42 vs 49 min, P < .001) times, similar technical (86% vs 86%, P = .9) and procedural (84% vs 85%, P = .7) success, and similar periprocedural MACE (2.1% vs 2.4%, P = .6).

Acute coronary syndrome (ACS) and CTO PCI. Although CTO PCI is uncommon in ACS patients, it is sometimes needed, for example, in prior CABG patients with saphenous vein graft failure in whom the graft cannot be recanalized.¹⁹ Among 8826 CTO PCI patients in the PROGRESS-CTO registry, 6.3% presented with ACS. The most common ACS presentation was non-ST-segment elevation MI (54%).²⁰ Technical success (88% vs 86%, P = .12), in-hospital MACE (0.9% vs 2.1%, P = .06), and adverse events after 3 months of follow-up (3.4% vs 7.2%; Kaplan-Meier log-rank P = .16) were similar in patients with and without ACS.²⁰

Contrast volume. Ebisawa et al analyzed 9853 CTO PCIs from the J-CTO expert registry and showed that minimum contrast media volume (≤ 50 mL) was associated with lower incidence of contrast-induced acute kidney injury in patients with chronic kidney disease (CKD) (1.05% vs 4.1%, P = .003).²¹ The retrograde approach was more commonly used in the minimal contrast media volume group, especially in complex CTO lesions (J-CTO score 3-5; 80% vs 44.7%, P = .02).

Procedure time. The duration of CTO PCI can be long, especially in complex cases. Rempakos et al stratified 6442 CTO PCIs from the PROGRESS-CTO registry into successful lesion crossing within 30 minutes, successful crossing after 30 minutes or more, and unsuccessful lesion crossing.²² The mean duration of CTO PCI was 129 ± 76 minutes. CTOs crossed in less than 30 minutes were less complex than those crossed after 30 minutes or more (J-CTO score 1.89 ± 1.19, 2.85 ± 1.13) and those that could not be crossed (2.88 ± 1.22, P < .001). As the time spent for lesion crossing increased, the probability of successful crossing decreased (after 30, 90, and 180 minutes: 76.7%, 60.7%, and 42.7%, respectively). A primary antegrade approach in LAD CTOs (OR 1.24; 95% CI, 1.09-1.42; P = .001), proximal cap ambiguity (OR 1.91; 95% CI, 1.63-2.25; P < .001), blunt/no stump (OR 1.83; 95% CI, 1.58-2.12; P < .001), occlusion length (OR, 1.32; 95% CI, 1.26-1.37; P < .001), prior failed attempt (OR 1.4; 95% CI, 1.19-1.64; P < .001), calcification (OR 1.7; 95% CI, 1.49-1.94; P < .001), and tortuosity (OR 1.84; 95% CI, 1.58-2.15; P < .001) were associated with longer lesion crossing time. Median time required after crossing until the end of the procedure was longer in technical failure with successful crossing than technical success (69.5 vs 52 min, P < .001). Intravascular ultrasound (IVUS) (63 vs 42 min, P < .001) and optical coherence tomography (58 vs 42 min, P < .001) use were associated with longer post-wiring procedure duration.²²

Equipment utilization. Konstantinis et al reported that the more commonly used guidewires for antegrade-only CTO PCI were the Pilot 200 (28%, Abbott Vascular) and the Fielder XT (24%, Asahi Intecc), whereas Corsair (21%, Asahi Intecc) and Turnpike Spiral (20%, Teleflex) were the most commonly used microcatheters. Since 2017, use of the Gladius Mongo wire (Asahi Intecc) has significantly increased from 4% (2017-2019) to 22% (2020-2022). For retrograde cases, the most extensively utilized guidewires were the Sion (32%, Asahi Intecc), Sion black (22%, Asahi Intecc), Pilot 200 (22%), and Suoh 03 (19%, Asahi Intecc), whereas Corsair (16%) and Turnpike LP (11%) were the most commonly used microcatheters. The Sion (32%), Sion Black (15%), and Suoh 03 (11%) were more often successful for collateral crossing.²³

Stents. Two studies (1 retrospective²⁴ and 1 prospective²⁵) examined the outcomes of ultra-thin strut drug-eluting stents (DES) in CTO PCI. In both studies, ultra-thin strut DES had comparable outcomes with standard thickness DES (1-year MACE in the retrospective study: aHR 1.15; 95% CI, 0.41-2.97; P = .85). Five-year follow-up of the PRISON-IV (PRImary Stenting of Occluded Native coronary arteries) study showed no difference between sirolimus-eluting stents (Orsiro, Biotronik) and durable polymer everolimus-eluting stents (Xience, Abbott Vascular) in target lesion revascularization (13.9% vs 7.9%, P = .077) and MACE (18.7% vs 13.3%, P = .177).²⁵ 

The Iberian CTO registry showed that most CTO PCIs (61.5%) required use of overlapping stents,²⁶ especially in more complex CTOs (J-CTO score: 2.9 ± 1 vs 2.75 ± 0.9, P = .007). After 19 months of follow-up, the incidence of MACE was 2% without any difference between single and overlapping stents.

Antegrade approach. Karacsonyi et al analyzed 2177 CTO PCIs performed using ADR to understand the frequency of use and outcomes of the limited antegrade subintimal tracking technique (LAST).²⁷ The most frequently used ADR technique was the Stingray system (Boston Scientific) (66.9%). LAST was used in 11.1% of the ADR cases and was associated with lower procedural success (OR 0.61; 95% CI, 0.41-0.91). Primary LAST (applied as the initial strategy) had higher technical and procedural success rate and similar MACE compared with secondary LAST (other ADR techniques were tried first), suggesting that LAST has a limited role in ADR (Figure 2).²⁷

Proximal cap ambiguity. Proximal cap ambiguity is a key node in every CTO PCI crossing algorithm.^28-31 Among 9498 CTO PCIs from the PROGRESS-CTO registry,³² 35% had proximal cap ambiguity, which was more common in prior CABG patients (37% vs 24%, P < .001). Compared with unambiguous proximal cap lesions, lesions with proximal cap ambiguity had higher J-CTO score, lower technical (79% vs 90%, P < .001) and procedural (77% vs 89%, P < .001) success, and higher MACE (2.5% vs 1.7%, P < .001). Lesions with proximal cap ambiguity were more likely to require use of the retrograde approach (50% vs 21%, P < .001), which was also more often the final successful crossing technique (29% vs 13%, P < .001).

Retrograde approach. The ERCTO retrograde score was developed to predict the likelihood of technical success for retrograde CTO PCI.³³ When the ERCTO score was used in the PROGRESS-CTO registry, it provided modest prediction of procedural success (c-statistic for all cases: 0.636; 95% CI, 0.610-0.662; c-statistic for primary retrograde cases: 0.651; 95% CI, 0.607-0.695).³⁴ Deng et al reported high success (92%) and low complication (4%) rate for retrograde CTO PCI via ipsilateral septal collateral channels (CC) in 25 patients.³⁵

Balloon-uncrossable lesions. Balloon-uncrossable lesions are associated with CTO PCI failure and complications.³⁶ In the PROGRESS-CTO registry, 9.2% of successfully crossed CTOs were balloon-uncrossable. Balloon-uncrossable lesions had a higher prevalence of in-stent restenosis (ISR) (23% vs 16%, P < .001), moderate/severe calcification (68% vs 40%, P < .001), and moderate/severe tortuosity (36% vs 25%, P < .001).³⁷ Balloon-uncrossable lesions had lower technical (91 vs 99%, P < .001) and procedural (88% vs 96%, P < .001) success and higher MACE (3.14% vs 1.49%, P < .001). The most used techniques for these lesions were guide catheter extensions (34%), grenadoplasty (25%), rotational atherectomy (RA) (23%), laser atherectomy (18%), and intravascular lithotripsy (0.6%).³⁷

Calcium. Heavy coronary calcium can hinder CTO PCI.³⁸ Among 13 079 CTO PCIs from the PROGRESS-CTO registry,³⁹ moderate/severe calcification was present in 46.6%. The most common calcium modification techniques were balloon angioplasty (76.6%), RA (7.3%), laser atherectomy (3.4%), and intravascular lithotripsy (3.4%). Moderate/severe calcification was associated with lower technical success (OR 0.73; 95% CI, 0.63-0.84), higher MACE (OR 2.33; 95% CI, 1.66-3.27), higher incidence of perforation (6.5% vs 3.4%, P < .001) and higher use of the retrograde approach (40.3% vs 23.5, P < .001).³⁹ 

Anticoagulation. Verreault-Julien reported that bivalirudin was used in 0.75% of 9723 CTO PCIs in the PROGRESS-CTO registry.⁴⁰ Compared with unfractionated heparin, bivalirudin cases had no significant difference in procedural success, in-hospital net adverse cardiac events (NACE) (OR 0.99; 95% CI, 0.13-7.27), MACE rate, or vascular access complications.⁴⁰

Imaging. Blessing et al published 2 studies examining right atrial (RA) and right ventricular (RV) function after right coronary artery (RCA) CTO PCI with 2-dimensional echocardiography and longitudinal strain imaging.^41,42 Six months after successful revascularization of RCA CTOs, both RA (mean RA reservoir longitudinal strain: baseline: 30.9% [21.1%-43%]; follow up: 33.4% [20.7%-47.7%], P < .001) and RV function (mean RV free wall longitudinal strain: baseline -20.7% [-6.3%-32%]; follow up -23.4% [-8.3% to -39.3%], P < .001) significantly improved.

Preprocedural coronary computed tomography angiography (CCTA) is increasingly being used for planning CTO PCI.⁴³ Simsek et al studied the impact of preprocedural CCTA on CTO PCI outcomes in the PROGRESS-CTO registry.⁴⁴ Preoperative CCTA was performed in 5.3% of all patients, and helped resolve proximal cap ambiguity (27%), identify significant calcium not seen on ICA (18%), and change the estimated CTO length by greater than 5 mm (10%). Technical success (OR 1.18; 95% CI, 0.83-1.67) and MACE (OR 1.47; 95% CI, 0.72-3.00) were similar in cases with and without preprocedural CCTA.⁴⁴

In a prospective observational study comparing myocardial perfusion before and 3 months after successful CTO PCI using computed tomography perfusion, the ischemic burden significantly decreased (5 [5-7] vs 1 [0-2] segments, P < .001),⁴⁵ along with myocardial blood flow improvement (85.3 [71.7-94.1] vs 134.6 [123.8-156.9] mL/min, P < .001) and an increase in the relative flow reserve (0.49 [0.41-0.57] vs 0.88 [0.74-0.95], P < .001).⁴⁵

IVUS can facilitate and optimize CTO PCI.⁴⁶ In an analysis from the PROGRESS-CTO registry, IVUS was used in 44.5% (33.1% for stent optimization, 11.5% for crossing) of 8771 cases.⁴⁷ IVUS was more often used in highly calcified and complex lesions for stent optimization (51.2% vs 34.4%, P < .001). Use of IVUS was associated with lower air kerma radiation dose and contrast volume, and higher technical (99.3% vs 96.3%, P < .001) and procedural (96.1% vs 94.6%, P = .002) success.⁴⁷

Coronary physiology. A prospective, multicenter, observational study measured coronary flow changes after successful CTO PCI using continuous thermodilution immediately after the procedure and at 3-month follow-up.⁴⁸ Immediately after CTO PCI, the CTO artery absolute coronary blood flow increased by 30% (P < .001), microvascular resistance decreased by 16% (P < .001), and fractional flow reserve (FFR) increased by 0.02. These changes remained significant at the 3-month follow-up. Prior CABG and higher eGFR patients had larger change in absolute flow.⁴⁸

Other techniques. Suzuki et al compared the Navifocus WR (Navi) IVUS-based (Terumo) conventional wiring with a novel AnteOwl WR (AO) IVUS-based (Terumo) real-time 3-dimensional wiring.⁴⁹ Navi-IVUS has a small profile and short distance from tip to transducer. AO-IVUS is a boosted version of Navi-IVUS with a pull-back system and tip-detection abilities. Procedural success (93% vs 59%, P = .007) was higher and wiring duration was lower (9 ± 8 min vs 24 ± 26 min, P = .001) with AO-IVUS–guided wiring compared with Navi-IVUS–guided wiring.⁴⁹

In a study of 2789 CTO PCIs performed at a German high-volume center, RA was used in 6.9% of cases and was associated with higher procedural success (93.2% vs 85.1%, P = .0002) and higher need for pericardiocentesis (3.11% vs 0.50%, P < .01), but similar in-hospital and 1-year MACE (18.6% vs 16.72%, P = .485).⁵⁰

Periprocedural mortality. Periprocedural death occurred in 0.4% of 12 928 CTO PCIs in the PROGRESS-CTO registry.⁵¹ Patients with congestive heart failure (43% vs 28%, P = .023) and complex lesions (mean J-CTO scores: 2.8 vs 2.4, P < .001) had higher periprocedural mortality. Mechanical circulatory support (MCS) use (41% vs 3.5%, P < .001) and retrograde crossing (33% vs 13%, P < .001) were also higher. The most common cause of periprocedural death was pericardial tamponade (58%), followed by acute MI (17.3%), and cardiac arrest/shock (7.7%). Non-cardiac causes of death included stroke (5.8%), renal failure (3.8%), respiratory distress (3.8%), and hemorrhagic shock (3.8%).⁵¹

Risk scores. Two studies performed external validation of complication risk scores.^52,53 Azzalini et al applied the PROGRESS-CTO complication risk scores to the OPEN-CTO registry, and found good discrimination for MACE (c-statistic 0.72; 95% CI, 0.66-0.78), mortality (c-statistic 0.79; 95% CI, 0.66-0.95), and pericardiocentesis (c-statistic 0.71; 95% CI, 0.60-0.82), but the acute MI score had inferior performance (c-statistic 0.57; 95% CI, 0.49-0.66).⁵² Khandelwal et al analyzed the validation of the British Cardiovascular Interventional Society (UK-BCIS) Complex High Risk Interventional Procedures (CHIP) score for predicting 1-year outcomes in the Mount Sinai institutional database and demonstrated good discrimination for 1-year MACCE (c-statistic 0.70), however, only 7.7% of the patients had undergone CTO PCI.⁵³

Coronary perforation. One of the most feared complications of CTO PCI is coronary perforation. Konstantinis et al developed the PROGRESS-CTO perforation risk score for predicting the risk of coronary perforation (c-statistic, 0.74; 95% CI, 0.712-0.773). The score uses 5 parameters:⁵⁴ age 65 years or older (+1), moderate/severe calcification (+1), blunt/no stump (+1), use of ADR (+1), and retrograde approach (+2). Simsek et al used the score in a pooled analysis of 3 independent registries and found a c-statistic of 0.76 (95% CI, 0.72-0.79).⁵⁵ Another CTO PCI perforation score, the OPEN-CLEAN (Outcomes After Chronic Total Occlusion Hybrid Procedures, CABG, Length of occlusion, LVEF > 50%, Age, severe calcification) score showed good performance in the PROGRESS-CTO registry (c-statistic 0.74, 95% CI, 0.68-0.79).⁵⁶

Aortocoronary dissection. Konstantinis et al reported 0.2% incidence of aortocoronary dissection among 12 117 CTO PCIs in the PROGRESS-CTO registry.⁵⁷ Aortocoronary dissection was more common in the RCA (96.3%) and with the retrograde approach (59.3%). Most patients were treated with ostial stenting (70.4%), and no patients required emergency surgery.

Mechanical support. Urgent MCS was required in 4.5% of 7171 CTO PCIs in the PROGRESS-CTO registry.⁵⁸ Karacsonyi et al developed a score to predict urgent MCS in CTO PCI using the following parameters: retrograde approach, LVEF, and lesion length greater than 60 mm.⁵⁹ The model had good discrimination (c-statistic 0.79; 95% CI, 0.73-0.86).

Guidewire fracture and loss. Guidewire fracture and/or loss is an uncommon but potentially serious CTO PCI complication. Leibundgut et al developed a new technique called "knuckle-twister" for transcatheter removal of broken guidewires and reported successful application in 7 cases.⁶⁰ The steps of this technique are as follows:

1. Choose a polymer-jacketed tapered guidewire as retrieval wire (Fielder XT-A, etc.).
2. Form a knuckle that is approximately 3- to 6-cm long, depending on how long the vessel is where the wire is lost.
3. Insert the knuckle into the coronary artery until it is parallel to the broken wire.
4. As an alternative, move the retrieval wire slightly away from the lost wire.
5. Start drilling the retrieval wire.
6. Pull back while drilling continually until the wire is totally entangled with the missing wire.
7. To extract the lost wire from the coronary vessel, insert the retrieval wire into the guiding catheter.
8. A guide catheter extension can be added to the method to protect the proximal vessel or prevent further entanglement with a proximal stent.

The ISCHEMIA-CTO (International Randomized Trial on the Effect of Revascularization or Optimal Medical Therapy of Chronic Total Coronary Occlusions with Myocardial Ischemia) trial is an ongoing, randomized, controlled, prospective, superiority, multicenter study evaluating the impact of CTO PCI on patients with a CTO lesion, target vessel diameter of 2.5 mm, and myocardial ischemia. Prior to randomization, all patients undergo 3 months of OMT. Study patients are divided into 3 groups: (1) Group A - asymptomatic (Canadian Cardiovascular Angina Score [CCS] < 2 and self-assessment questionnaire [SAQ] [QoL] > 60) patients with myocardial ischemia (≥ 10% of LV) in a territory supplied by CTO; (2) Group B - symptomatic patients (CCS class ≥ 2 and/or SAQ QoL score ≤ 60 after treating non-CTO lesions and after OMT) with myocardial ischemia (5% of LV) in a territory supplied by a CTO; and (3) Group C - patients enrolled but not randomized in cohort A or B. The plan is to enroll 1560 patients (1200 in cohort A and 360 in cohort B), and the planned completion date is 2028.⁶¹

The INVEST-CTO (Effectiveness and Safety of a Planned Investment Procedure in High-Risk CTO PCI) trial is a prospective, single-arm, international, multicenter study aimed to evaluate the efficacy and safety of a planned investment procedure followed by CTO PCI completion (at 8-12 weeks) in anatomically high-risk CTOs. Planned enrollment is 200 patients and estimated completion date is September 2024.⁶²

The ORBITA-CTO (Comparison of the Impact of CTO PCI Versus Placebo on Angina in Patients with Background Optimal Medical Therapy) pilot trial is a double-blind, placebo-controlled study to compare CTO-PCI vs placebo with OMT. The study will enroll 50 patients with symptoms caused by a CTO, ischemia evidence, and viability within the CTO vessel, and J-CTO score of less than or equal to 3. The planned completion date is June 2024.⁶³

Several studies have examined, or are examining, outcomes, techniques, and complications of CTO PCI during the last year. Implementing the recent study findings into daily clinical practice may enhance the outcomes of patients undergoing CTO PCI.

From the ¹Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA; ²Department of Cardiology, Sayama Hospital, Saitama, Japan; ³Henry Ford Cardiovascular Division, Detroit, Michigan, USA; ⁴Wellspan York Hospital, York, Pennsylvania, USA; ⁵Texas Health Presbyterian Hospital, Dallas, Texas, USA; ⁶Maria Vittoria Hospital, Torino, Italy; ⁷Maria Pia Hospital, Torino, Italy; ⁸Memorial Bahcelievler Hospital, Istanbul, Turkey; ⁹Biruni University Medical School, Istanbul, Turkey; ¹⁰Cleveland Clinic, Cleveland, Ohio, USA; ¹¹Emory University Hospital Midtown, Atlanta, Georgia, USA; ¹²Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK; ¹³Athens Naval and Veterans Hospital, Athens, Greece; ¹⁴Royal Brompton Hospital, London, UK; ¹⁵University Heart Center Freiburg, Bad Krozingen, Germany.

Disclosures: Dr. Alaswad has been a consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and CSI. Dr. Basir receives grant support from Abiomed, Chiesi, and Zoll; and consultant fees/honoraria from Abbott Vascular, Abiomed, Boston Scientific, Cardiovascular Systems, Inc, Chiesi, Seranas, and Zoll. Dr. Davies receives speaking honoraria from Abiomed, Asahi Intec, Boston Scientific, Medtronic, Shockwave and Teleflex; and serves on advisory boards for Abiomed, Avinger, Boston Scientific, Medtronic, and Rampart. Dr. Choi serves on the Medtronic advisory board. Dr. Khatri has received personal honoraria for proctoring and speaking from Abbott Vascular, Medtronic, Terumo, Shockwave, and Boston Scientific. Dr. Nicholson has been a proctor for and on the speaker’s bureau and advisory boards for Abbott Vascular, Boston Scientific, and Asahi Intecc, Inc.; and he reports intellectual property with Vascular Solutions. Dr. Rinfret has received fees from Abbott Vascular, Abiomed, Boston Scientific, and SoundBite Medical, and has been a consultant for Teleflex. Dr. Jaber has received fees from Medtronic and proctoring fees from Abbott. Dr. Egred has a proctorship and receives speaker’s fees and honoraria from Abbott Vascular, Boston Scientific, Philips, Spectranetics, Volcano, Vascular Perspective, Merrill, Svelte, Terumo, EPS Medical, Abiomed, and AstraZeneca. Dr. Mashayekhi received consultancy fees and speaker honoraria from Abbott, Abiomed, Asahi Intecc, Inc., AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi Sankyo, Medtronic, Shockwave, Teleflex, and Terumo S.A. Dr. Sandoval receives consulting/speaker honoraria from Abbott Diagnostics, Roche Diagnostics, Zoll, and Philips; is an associate editor for JACC Advances; and holds Patent 20210401347. Dr. Burke receives consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr. Brilakis receives consulting/speaker honoraria from Abbott Vascular, the American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Inc., Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medicure, Medtronic, Siemens, and Teleflex; receives research support from Boston Scientific, GE Healthcare; is the owner of Hippocrates LLC; and is a shareholder of MHI Ventures, Cleerly Health, and Stallion Medical. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 E 28th Street #300, Minneapolis, MN 55407, USA. Email: esbrilakis@gmail.com; X: @dnzmtlu, @m1chaella_alex, @RempakosT, @AhmedAlOgaili, @yadersandoval, @esbrilakis, @CCAD_MHIF