We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 13,852 CTO PCIs performed at 43 US and non-US centers between 2012 and 2025. Cases without data on proximal cap ambiguity, presence of side branch at the proximal cap, distal landing zone quality, presence of bifurcation at the distal cap, occlusion length, tortuosity, and calcification were excluded from the analysis. Data collection was recorded in a dedicated online database (PROGRESS CTO: Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; Clinicaltrials.gov identifier: NCT02061436). Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the Minneapolis Heart Institute Foundation. ^, The study was approved by the institutional review board of each center.

Adherence to the global CTO crossing algorithm was determined retrospectively based on documented angiographic characteristics and the initial crossing strategy selected. Prospective documentation of algorithm use at the time of decision-making was not available in the registry.

The study cases were categorized into 2 groups based on adherence to the global algorithm for primary strategy selection. Whether the global algorithm was followed was determined based on the presence and approach to the following case characteristics: (1) presence of proximal cap ambiguity, (2) presence of poor distal vessel quality, and (3) use of primary antegrade dissection and re-entry (ADR) in appropriately selected cases ( Figure 1 ). Three examples of cases that followed (example cases 1 and 2) and didn’t follow (example case 3) the global algorithm are provided in Figure 2 .

Global chronic total occlusion crossing algorithm adherence criteria. ADR: Antegrade dissection and re-entry.

Examples of adherence vs non-adherence to the global chronic total occlusion crossing algorithm. ADR: Antegrade dissection and re-entry.

In cases with proximal cap ambiguity, 2 options were considered as following the algorithm: (a) assessment for side branches, and (b) assessment for interventional collaterals. For cases with a side branch, using intravascular ultrasound was considered as following the algorithm, while for cases without a side branch, using a “move the cap” technique, such as the balloon assisted subintimal entry (BASE) technique and the “scratch and go” technique, was considered as following the algorithm. For cases with interventional collaterals, using a primary retrograde crossing strategy was considered as following the algorithm, while for cases without collaterals, using a primary antegrade wiring crossing strategy was considered as following the algorithm.

In cases with poor distal vessel quality, interventional collaterals were assessed. For cases with interventional collaterals, using the primary retrograde crossing strategy was considered as following the algorithm, while for cases without collaterals, using a primary antegrade wiring crossing strategy was considered to follow the algorithm.

For cases in which primary ADR was used 2 out of the following 4 characteristics had to be present for the case to be considered as following the global algorithm: (a) ≥20 mm occlusion length, (b) lack of calcification, (c) lack of tortuosity, and (d) presence of an appropriate re-entry zone of large caliber and without major side branches.

Coronary CTOs were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration. Estimation of the duration of occlusion was clinical, based on the first onset of angina, prior history of myocardial infarction (MI) in the target vessel territory, or comparison with a prior angiogram.

Calcification was assessed by angiography and classified as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (>50%). Technical success was defined as successful CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as the achievement of technical success without any in-hospital major adverse cardiac events (MACE). In-hospital MACE included any of the following adverse events prior to hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft (CABG) surgery, cardiac tamponade requiring either pericardiocentesis or surgery, and stroke. MI was defined using the Third Universal Definition of Myocardial Infarction (type 4a MI). In patients presenting with ST-elevation myocardial infarction (STEMI), the CTO lesion represented a nonculprit lesion treated during the index hospitalization. The Japanese CTO (J-CTO) score was calculated as described by Morino et al., the PROGRESS-CTO score as described by Christopoulos et al., the new PROGRESS-CTO complication scores (Acute MI, MACE, Mortality, and Pericardiocentesis) as described by Simsek et al., and the PROGRESS-CTO perforation score as described by Kostantinis et al.

Categorical variables were expressed as percentages and compared using the Pearson’s chi-square test. Continuous variables are presented as mean ± standard deviation or as median (interquartile range) unless otherwise specified and were compared using the independent-samples t-test for normally distributed variables and the Mann-Whitney U test for nonparametric variables, as appropriate. Univariable logistic regression was performed to identify variables that might be associated with technical success; variables that had p < 0.10 and were deemed clinically/angiographically significant were included in the multivariate analysis. All statistical analysis was performed using R Statistical Software, version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria). A p-value of <0.05 was considered to indicate statistical significance.

Of the 13,852 CTO PCIs performed during the study period, 9,693 (70%) successfully followed the steps of the global CTO crossing algorithm for initial strategy selection. There was no change in adherence to the global algorithm over time. The baseline clinical characteristics of the study patients are presented in Table 1 . Patients in the discordant group were slightly younger and were more likely to have a history of prior MI. Patients in the concordant group were more likely to present with unstable angina and to undergo ad hoc CTO PCI compared with patients in the discordant group.

The angiographic characteristics of the study lesions are shown in Table 2 . The right coronary artery was more commonly the CTO target vessel in cases that followed the global algorithm versus those that did not (61.5% versus 49.4%; p < 0.001). Patients in the discordant group were more likely to have complex angiographic characteristics, including longer occlusion length, proximal cap ambiguity, side branch at the proximal cap, blunt or no stump, poor distal vessel quality, and moderate to severe calcification. They were also more likely to have “interventional” collaterals. The mean J-CTO and PROGRESS-CTO complications (MACE, acute MI, mortality, pericardiocentesis, perforation) scores were also higher in the discordant group. Lesions in the concordant group were more likely to be in-stent and had a higher mean PROGRESS-CTO score.

The retrograde approach was the primary crossing strategy in 15.3% of cases that did versus 4.4% of cases that did not follow the algorithm (p < 0.001). However, the retrograde crossing strategy was less commonly the successful crossing strategy in the concordant group (14.9% versus 28.1%, p < 0.001). Retrograde wiring was used in 45.1% of cases that followed the global algorithm versus 25.0% of cases that did not. Procedures that deviated from the global algorithm were associated with more stents, and higher procedure time, contrast volume, fluoroscopy time, and patient air kerma radiation dose ( Table 3 ).

Table 3

Comparison of procedural techniques used in cases that did vs those that did not follow the global algorithm

Variables	Did not follow the global algorithm ( n = 4052)	Followed the global algorithm ( n = 9693)	p-value
First crossing strategy			<0.001
Antegrade wiring	91.5% (3708)	82.0% (7947)
Antegrade dissection and re-entry	4.1% (165)	2.7% (262)
Retrograde wiring	4.4% (179)	15.3% (1484)
Successful crossing strategy			<0.001
Antegrade wiring	47.3% (1917)	61.1% (5919)
Antegrade dissection and re-entry	10.8% (439)	11.7% (1134)
Retrograde wiring	28.1% (1139)	14.9% (1442)
None	13.7% (555)	12.3% (1186)
Retrograde wiring attempted	45.1% (1827)	25.0% (2428)	<0.001
Balloon uncrossable CTO lesion	9.3% (323)	9.2% (772)	0.87
Balloon undilatable CTO lesion	7.8% (247)	7.0% (533)	0.155
Number of stents	2.40 ± 1.06	2.12 ± 1.02	<0.001
Procedure time (minutes)	128.00 [87.00, 178.00]	105.00 [69.00, 152.00]	<0.001
Contrast volume (mL)	210.00 [150.00, 300.00]	200.00 [145.00, 282.00]	<0.001
Fluoroscopy time (minutes)	51.00 [32.75, 75.45]	38.90 [24.00, 60.60]	<0.001
Patient air kerma radiation dose (Gy)	2.24 [1.20, 3.80]	2.10 [1.13, 3.63]	0.003

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