Geographic Diversity in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry

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Background. There is variability in clinical and lesion characteristics as well as techniques in chronic total occlusion (CTO) percutaneous coronary intervention (PCI).  

Methods. We analyzed patient and lesion characteristics, techniques, and outcomes in 11 503 CTO-PCI procedures performed in North America (NA) and in the combined regions of Europe, Asia, and Africa from 2017 to 2023 as documented in the PROGRESS-CTO registry.

Results. Eight thousand four hundred seventy-nine (74%) procedures were performed in NA. Compared with non-NA patients, NA patients were older, with higher body mass index and higher prevalence of diabetes, hypertension, dyslipidemia, family history of coronary artery disease, prior history of PCI, coronary artery bypass graft surgery and heart failure, cerebrovascular disease, and peripheral arterial disease. Their CTOs were more complex, with higher J-CTO (2.56 ± 1.22 vs 1.81 ± 1.24; P < .001) and PROGRESS-CTO (1.29 ± 1.01 vs 1.07 ± 0.95; P < .001) scores, longer length, and higher prevalence of proximal cap ambiguity, blunt/no stump, moderate to severe calcification, and proximal tortuosity. Retrograde (31.0% vs 22.1%; P < .001) and antegrade dissection and re-entry (ADR) (21.2% vs 9.2%; P < .001) were more commonly used in NA centers, along with intravascular ultrasound (69.0% vs 10.1%; P < .001). Procedure and fluoroscopy times were longer in NA, while contrast volume and radiation dose were lower. Technical (86.7% vs 86.8%; P > .90) and procedural (85.4% vs 85.8%; P = .70) success and in-hospital major adverse cardiovascular events (MACE) (1.9% vs 1.7%; P = .40) were similar in NA and non-NA centers.

Conclusions. Compared with non-NA patients, NA patients undergoing CTO PCI have more comorbidities, higher CTO lesion complexity, are more likely to undergo treatment with retrograde and ADR, and have similar technical success and MACE.

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is performed around the world with increasing consensus on techniques and crossing strategies.^1-4 Several CTO-PCI registries have been tracking outcomes, including the Outcomes, Patient Health Status, and Efficiency in CTO Hybrid Procedures (OPEN-CTO),⁵ the European CTO (EuroCTO),⁶ the Asia-Pacific CTO Club (APCTO),⁷ the Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE),⁸ the Japanese CTO PCI Expert Registry (J-CTO),⁹ the Korean Multicenter CTO Registry (K-CTO),¹⁰ the Iberian registry (REBECO),¹¹ the Latin American CTO registry (LATAM),¹² and  the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO).¹³ Data from these registries suggest differences in clinical and lesion characteristics between difference regions.^{5,6,8,12,14,15} However, comparative data on contemporary CTO-PCI practice worldwide are lacking as most registries primarily report data from their respective continents. The PROGRESS-CTO registry started in North America (NA) but expanded over time to include centers from the rest of the world, allowing comparison of patient and lesion characteristics, along with procedural techniques and outcomes, by geography.

We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 11 503 CTO PCIs (11 440 patients) that were performed at 32 NA and 10 non-NA centers between 2017 and 2023 as documented in the PROGRESS-CTO registry (Clinicaltrials.gov identifier: NCT02061436). We compared CTO PCIs performed in NA (USA, Canada) with those performed in Europe, Asia and Africa (Turkey, Egypt, Russia, Lebanon, Greece). We used REDCap (Research Electronic Data Capture) electronic data capture tools, hosted at the Minneapolis Heart Institute Foundation, to collect and manage study data.^16,17 The study was approved by the institutional review board of each center.

We identified coronary CTOs as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-months duration. Estimation of the occlusion duration was clinically based on the first onset of angina, a previous myocardial infarction (MI) in the target vessel territory, or comparison with a prior angiogram.

We assessed calcification by angiography and classified it as mild (spots), moderate (involving ≤ 50% of the reference lesion diameter), or severe (> 50%). Technical success was defined as achievement of a less than 30% residual diameter stenosis in the treated area and TIMI grade 3 antegrade flow.  Procedural success was defined as achieving technical success in the absence of any in-hospital major adverse cardiovascular events (MACE). Any of the following adverse events prior to hospital discharge were included as in-hospital MACE: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft (CABG) surgery, tamponade requiring either pericardiocentesis or surgery, and stroke. MI was characterized according to the Third Universal Definition of Myocardial Infarction (type 4a MI).¹⁸ The Japanese CTO (J-CTO) score was calculated based on the description by Morino et al,¹⁹ the PROGRESS-CTO score based on the description by Christopoulos et al,²⁰ the new PROGRESS-CTO complication scores (acute MI, MACE, mortality, and pericardiocentesis) based on the description by Simsek et al,²¹ and the PROGRESS-CTO perforation score based on the description by Kostantinis et al.²²

Categorical variables were reported as n (percentages) and were analyzed using the Pearson’s chi-square test. Continuous variables were presented as mean ± standard deviation or as median (interquartile range) and were compared using the independent-samples t-test for normally distributed variables and the Mann-Whitney U test for non-parametric variables, as appropriate. These statistical tests were performed using R Statistical Software, version 4.2.2 (R Foundation for Statistical Computing). A P-value of less than 0.05 was considered statistically significant.

During the study period (2017-2023), 8479 (74%) procedures were performed in NA whereas 3024 (26%) were performed in Europe, Asia, and Africa (Figure 1). NA patients were older, with higher body mass index (BMI) and higher prevalence of diabetes, hypertension, dyslipidemia, and family history of coronary artery disease; prior history of PCI, CABG and heart failure; cerebrovascular disease; and peripheral arterial disease (Table 1). Patients from non-NA centers were more likely to be men, current smokers, to have prior MI, and be asymptomatic at presentation.

The angiographic characteristics of the study lesions and procedural techniques are presented in Table 2. In non-NA centers, the target CTO vessel was more likely to be the right coronary artery (55.1% vs 50.8%; P < .001). The lesions of NA patients were more complex, having longer length and higher prevalence of proximal cap ambiguity, blunt/no stump, moderate to severe calcification (53.0% vs 20.6%; P < .001), moderate to severe proximal tortuosity (30.3% vs 20.6%, P < .001), and in-stent restenosis. NA cases had higher J-CTO (2.56 ± 1.22 vs 1.81 ± 1.24; P < .001) and PROGRESS-CTO (1.29 ± 1.01 vs. 1.07 ± 0.95; P < .001) scores. Non-NA cases were more likely to have target lesions with a side branch at the proximal cap, as well as a larger vessel diameter.

Procedural techniques are presented in Table 3. The first crossing strategy was more likely to be antegrade in non-NA centers (88.5% vs 86.0%; P < .001), while primary antegrade dissection and reentry (ADR) (0.9% vs 2.8%; P < .001) and primary retrograde crossing (10.6% vs 11.2%; P < .001) were less common. The retrograde approach (31.0% vs 22.1%; P < .001) and ADR (21.2% vs 9.2%; P < .001) were more commonly used in NA centers that also used a higher number of stents per CTO PCI.  NA cases had higher use of intravascular lithotripsy (IVL), laser/rotational/orbital atherectomy, and scoring balloons; no cases of IVL and laser atherectomy were reported in the non-NA centers. Intravascular ultrasound (IVUS) was more commonly used in NA (69.0% vs 10.1%; P < .001). Radial access only was more common in non-NA centers (17.0% vs 10.0%; P < .001), while femoral access only was more common in NA centers (44.6% vs 32.6%; P < .001). Procedure (121 vs 77 min; P < .001) and fluoroscopy (43.50 vs 36 min; P < .001) times were longer in NA (Figure 2). Contrast volume (250 vs 175 ml; P < .001) and radiation dose (3.51 vs 1.73 Gy; P < .001) were higher in non-NA centers. There was significant variation in X-ray machines; the Innova (GE Healthcare) was the most used in the non-NA centers, and the Allura (Philips) was the most used in the NA centers (Figure 3).

Figure 4 presents the ADR techniques used: the Carlino and scratch-and-go techniques were more commonly used in non-NA centers, while the CrossBoss (Boston Scientific) and knuckle wire techniques were more commonly used in NA centers. Subintimal tracking and re-entry (STAR) (34.8% vs 27.3%; P = .012) and limited antegrade subintimal tracking (LAST) (34.8% vs 6.3%; P < .001) were more commonly used in non-NA centers, while the Stingray (Boston Scientific) was more commonly used in NA centers (41.0% vs 6.1%; P < .001).

Technical (86.7% vs 86.8%; P > .90) and procedural (85.4% vs 85.8%; P = .70) success were similar in the NA and non-NA centers (Table 4). MACE did not differ between groups (1.9% vs 1.7%; P = .4), nor did the rest of the in-hospital complications; the only exception was stroke, which was more common in NA centers (0.2% vs 0.0%; P = .02).  In NA, the technical success rates of the procedures did not significantly change between 2017 and 2023 (2017: 84.4%; 2018: 85.9%; 2019: 86.4%; 2020: 86.2%; 2021: 87.5%; 2022: 86.7%; 2023: 89.5%; P = .068). Conversely, in regions outside of NA, technical success increased during the same time period (2017: 76.4%; 2018: 84.3%; 2019: 86.6%; 2020: 87.1%; 2021: 88.5%; 2022: 88.1%; 2023: 89.4%; P < .001). The NA medium- and high-volume operators, defined as those performing over 30 CTO procedures annually, accounted for 60.3% of the CTO cases. Conversely, in non-NA regions, 53.8% of the CTO cases were performed by medium- and high-volume operators from those areas.

The major findings of our study are that, compared with non-NA patients, those undergoing CTO PCI in NA had (a) a higher comorbidity burden, (b) more complex lesions, (c) higher IVUS use, (d) similar technical and procedural success, and (e) similar MACE rates.

Table 5 shows the variability in population composition observed in various CTO PCI registries worldwide. NA patients were more likely to be obese and to have dyslipidemia (94.4% vs 50.4%; P < .001). The prevalence of dyslipidemia was 70% in the Latin America CTO registry,¹² 33.3% in the Korean CTO registry,¹⁰ 58.4% in the Asia-Pacific CTO registry,⁷ 80.0% in the Japanese CTO registry,⁹  73.8% in the European CTO registry,⁶ and 67.6% in the Iberian CTO registry.¹¹

The proportion of prior CABG patients was much higher in NA centers (32.3% vs 12.9%; P < .001) in our study, similar to the prevalence reported in the US-based OPEN-CTO registry (36.5%).⁵ The prevalence of prior CABG in the LATAM registry was 19%.¹² Prior CABG patients have more complex angiographic characteristics and lower CTO PCI success rates.^23,24

The proportion of women undergoing CTO PCI was higher in NA centers (21.3% vs 16.0%; P < .001). Compared with the NA cohort from our study, the prevalence of women was higher in the Korean CTO registry (26.1%),¹⁰ similar in the Latin America CTO registry (22%)¹² and the OPEN-CTO registry (19.6%),⁵ and lower in the Asia-Pacific CTO registry (11.6%).⁷ Despite high technical and procedural success and acceptable complication rates being reported in women undergoing CTO PCI, women are still underrepresented in CTO PCI registries worldwide.²⁵

The target CTO lesions of NA patients had higher anatomic complexity, as demonstrated by both the J-CTO and PROGRESS-CTO scores, which could reflect differences in the burden of baseline comorbidities and cardiovascular risk factors. The latter could also explain the higher risk of complications (as quantified by the PROGRESS-CTO complications score) observed in the patients treated in NA. Procedure and fluoroscopy times were longer in NA, which is likely related to lesion complexity.²⁶ However, contrast volume and radiation doses were higher in non-NA centers. Contrast volume is usually higher in complex lesions, but IVUS use, which was higher in NA, is associated with lower contrast volume.^27,28 An additional explanation could be the higher reliance on antegrade wiring in non-NA cases. A paradox emerges wherein despite longer procedure times in NA, their radiation dose was lower. This may be attributed to variability in X-ray equipment. Newer X-ray systems (such as the Allura [Philips], Clarity [Philips], and Q-zen [Siemens]) that have been associated with lower median air kerma radiation dose in previous studies^29,30 were more commonly used in NA (Figure 3).

Radial access was more commonly used at the non-NA centers. This could potentially be explained by lower lesion complexity in the non-NA group³¹ and slower adoption of the radial approach in NA.

IVUS use was more common in the NA centers (69.0% vs. 10.1%; P < .001), likely due to the cost of the device. A systematic review and meta-analysis consisting of 2 randomized and 2 observational studies examining the impact of IVUS on the outcomes of CTO PCI reported lower risk of stent thrombosis, with similar in-hospital outcomes.³² IVUS was used in 23.6% of the cases reported by the Korean CTO registry between 2007 and 2019¹⁰ and in 37% of the cases reported by the Asia-Pacific CTO registry in 2016.⁷ The Latin America CTO Registry, between 2008 and 2020, reported IVUS use of 17.7%,³³ while the Iberian CTO registry in Spain and Portugal, between 2015 and 2019, reported IVUS use of 14%.¹¹ The European CTO registry reported IVUS use of 12.8% in 2015,⁶ while, IVUS use was 38% at US centers between 2012 and 2015.²⁷

Despite differences in population composition and lesion characteristics, overall outcomes remained similar. Higher success rates could be expected in the non-NA centers based on lower lesion complexity and fewer comorbidities. However, these centers used the retrograde approach and ADR less often, possibly due to the additional cost of the equipment required for these techniques.³⁴ Alternatively, this could reflect differences in training and/or practice patterns.

Our study underscores the need to consider local variability to enhance CTO PCI outcomes globally. Additional research in diverse patient populations could be beneficial. Fostering a global exchange of knowledge and expertise through collaboration should be a priority, while disparities in resource availability highlighted by the study could guide investment in technology and training, particularly in regions that are lagging in the adoption of newer, safer technologies. The variability in IVUS use and the preference for certain approaches (such as antegrade wiring in the non-NA centers) could probably reflect not only disparities in resource availability but also differing practices and expertise levels. Dedicated training programs could enhance these skills and contribute to the narrowing of practice pattern variations between different regions.

Limitations. The PROGRESS-CTO is an observational registry with all inherent limitations. There was no independent adjudication of clinical events or core laboratory assessment of the study angiograms. The procedures reported in the registry were performed at centers with experienced operators in CTO PCI, potentially limiting the generalizability of the results to centers with limited CTO-PCI expertise. Finally, fewer centers were available for analysis outside NA areas.

Compared with non-NA centers, patients undergoing CTO PCI in NA had more comorbidities and higher CTO lesion complexity, and more common use of ADR and the retrograde approach, but similar success and MACE rates.

From the ¹Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA; ²Texas Health Presbyterian Hospital, Dallas, Texas, USA; ³University Hospitals, Case Western Reserve University, Cleveland, Ohio, USA; ⁴Henry Ford Cardiovascular Division, Detroit, Michigan, USA; ⁵WellSpan York Hospital, York, Pennsylvania, USA; ⁶Massachusetts General Hospital, Boston, Massachusetts, USA; ⁷Oklahoma Heart Institute, Tulsa, Oklahoma, USA; ⁸Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA; ⁹Selcuk University, Konya, Turkey; ¹⁰Aswan Heart Center, Magdi Yacoub Foundation, Cairo, Egypt; ¹¹Tristar Hospitals, Tennessee, USA; ¹²Biruni University Medical School, Istanbul, Turkey; ¹³Cleveland Clinic, Cleveland, Ohio, USA; ¹⁴Meshalkin Novosibirsk Research Institute, Novosibirsk, Russia; ¹⁵St. Vincent Hospital, Indianapolis, Indiana, USA; ¹⁶St. Boniface General Hospital, Winnipeg, Manitoba, Canada; ¹⁷Memorial Bahçelievler Hospital, Istanbul, Turkey; ¹⁸Department of Cardiology, Columbia University Medical Center, New York, USA.

Acknowledgments: The authors are grateful for the philanthropic support of our generous anonymous donors, and the philanthropic support of Drs. Mary Ann and Donald A Sens; Mrs. Diane and Dr. Cline Hickok; Mrs. Wilma and Mr. Dale Johnson; Mrs. Charlotte and Mr. Jerry Golinvaux Family Fund; the Roehl Family Foundation; the Joseph Durda Foundation; Ms. Marilyn and Mr. William Ryerse; Mr. Greg and Mrs. Rhoda Olsen. The generous gifts of these donors to the Minneapolis Heart Institute Foundation’s Science Center for Coronary Artery Disease (CCAD) helped support this research project.

Disclosures: Dr. Choi serves on the Medtronic advisory board. Dr. Poommipanit is a consultant for Asahi Intecc and Abbott Vascular. Dr. Alaswad is a consultant and speaker for Boston Scientific, Abbott Cardiovascular, Teleflex, and Cardiovascular Systems Inc. Dr. Basir is a consultant for Abbott Vascular, Abiomed, Cardiovascular Systems, Inc (CSI), Chiesi, and Zoll. Dr. Davies receives speaker honoraria from Abiomed, Asahi Intec, Boston Scientific, Medtronic, Teleflex and Shockwave Medical. She also serves on advisory boards for Abiomed, Avinger, Boston Scientific, Medtronic and Rampart. Dr. Jaffer has done sponsored research for Canon, Siemens, Shockwave, Teleflex, Mercator, and Boston Scientific; and has been a consultant for Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, and Intravascular Imaging Inc. He has equity interest in Intravascular Imaging Inc, DurVena; and the right to receive royalties through Massachusetts General Hospital licensing arrangements with Terumo, Canon and Spectrawave. Dr. McEntegart has received consultancy fees from Abbott Vascular and Boston Scientific. Dr. Khatri has received personal honoraria for proctoring and speaking from Abbott Vascular, Medtronic, Terumo, and Shockwave Medical. Dr. Azzalini received consulting fees from Teleflex, Abiomed, GE Healthcare, Abbott Vascular, Reflow Medical, and Cardiovascular Systems, Inc.; serves on the advisory board of Abiomed and GE Healthcare; and owns equity in Reflow Medical. Dr. Sandoval: Abbott Diagnostics, Roche Diagnostics, Zoll, Phillips, JACC Advances (associate editor); 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, American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medicure, Medtronic, Siemens, Teleflex, and Terumo; receives research support from Boston Scientific, GE Healthcare; is the owner of Hippocrates LLC; and is a shareholder in 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: @CCAD_MHIF, @esbrilakis, @michaella_alex

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