Chronic total occlusion (CTO) of coronary arteries represents an advanced form of atherosclerotic coronary artery disease, which is currently prevalent in almost one-fifth of patients presenting for diagnostic coronary angiography [13]. Revascularization of CTO using PCI has several clinical benefits, including ischemic symptom relief and quality of life improvement. These findings are supported to date by limited randomized controlled studies, yet it is still unclear whether revascularization provides a survival benefit or long-term freedom from cardiac events [14].

The mean age of our patients was 56 ± 9.6 years and 91% of the patients were men. The mean age seen in international registries was found to be to be around 10 years higher than our study as seen in the OPEN-CTO (65 years), RECHARGE (66 years) and EURO-CTO (62 years). This could be explained by the very high prevalence of atherosclerotic cardiovascular disease in our region and its consequences appearing at an earlier age in our patients. The very high percentage of male patients in our study is also consistent with these large registries where the percentage of males ranged from 80 to 88% [15,16,17].

Seventy-seven % of patients were done via an antegrade approach and 23% were done via a retrograde approach with an overall procedural success rate of 91.25% (Antegrade 93.5%, Retrograde 83.3%).

All the procedures done in this study were by expert high volume CTO operators which explains why the procedural success rate in our center was comparable to large international CTO registries such as the OPEN CTO registry [14] which has a 90% procedural success rate, the PROGRESS-CTO registry [18] with 87% and the EURO-CTO with 88% [19].

Our success rate was higher than all-comer registries where multiple operators with variable levels of experience are involved such as the NCDR (National Cardiovascular data registry) [20] in the USA which showed a 59% procedural success rate and the BCIS (British cardiovascular society) registry [21] which showed a 67% procedural success rate. Therefore, it is vital to have your most experienced CTO operators performing the procedure to maintain the high standards required in your CTO program [22].

As in most registries, the procedural success rate in retrograde procedures in our study was lower (83.33%) than those involving an antegrade only approach (93.55%) and it was driven mainly by an increase in peri-procedural myocardial injury. Other factors that may lower the procedural success rate are the need for urgent repeat PCI or CABG, development of acute neurological deficit or an acute myocardial infarction during the hospital stay.

Having an 83.33% procedural success rate in retrograde procedures is a testament to the adequate training & experience of operators at our center as it is comparable to the results achieved in the European RECHARGE registry (86%) and the Japanese CTO PCI Expert Registry (88%) and higher than the results seen in the OPEN-CTO (74.7%), the PROGRESS-CTO (75.4%) and the EURO-CTO (75.3%) registries [16, 17, 23,24,25,26].

In a recent update from the PROGRESS-CTO registry antegrade-only cases, Pilot 200 (28%; Abbott Vascular) and Fielder XT (24%; Asahi Intecc) were the most commonly used guidewires, with a recent increase in the use of GLADIUS MONGO wire from 4 to 22% in the time period from 2020 to 2022 while Corsair (21%; Asahi Intecc) and Turnpike Spiral (20%; Vascular Solutions) were the most frequently used microcatheters. In retrograde cases, Sion (32%; Asahi Intecc) was the most frequent guidewire used, followed by Sion Black (22%; Asahi Intecc), Pilot 200 (22%), and Suoh 03 (19%; Asahi Intecc), while Corsair (16%) and Turnpike LP (11%) were the most commonly used microcatheters with a recent increase in the use of CORSAIR Pro XS [27].

In our study, the most commonly used guidewires in the antegrade cases were the GAIA 2nd (61.29%), GAIA 3rd (29.03%), CP12 (29.03%) and the Fielder XT (25.8%) while the most frequently used microcatheters was the Caravel (30.65%). The GLADIUS MONGO guidewire was only used in 7.5% of all cases due to its limited availability in our region despite its increased use internationally. In the retrograde group the most frequently used guidewires were the Sion Black (66.6%), Fielder XT-R (66.6%) and Sion (50%) while the most commonly used micro-catheter was the CORSAIR Pro in 72% of cases.

The retrograde group required longer procedure times than the antegrade group (136 min vs 92 min), larger volumes of contrast were used (Mean contrast volume 486 ml vs 338 ml) and higher exposure to radiation doses was found (Mean cumulative AK 9.8 Gy vs 6.4 Gy) which were statistically significant.

Regarding the retrograde procedures, the long procedure time was comparable to those seen in the Euro-CTO (159 min), the J-CTO (160 min), the PROGRESS-CTO (168 min) registries but higher than the procedure times seen in the OPEN-CTO (107 min) and the RECHARGE registries (90 min).

The average contrast volume used was much higher than those seen in Euro-CTO (387 ml), the J-CTO (241 ml), OPEN-CTO (278 min), PROGRESS-CTO (215 ml) and the RECHARGE registries (250 ml). This could be explained by a liberal use of contrast in our center with the under-utilization of IVUS (6.25% of procedures in our study) to guide the procedure due to the financial limitations limiting its availability and preventing its routine use in our cases.

In our study there was also a much higher average exposure to radiation doses compared to those seen in the OPEN-CTO (2.5 GY), the RECHARGE (1.6 GY) and PROGRESS-CTO (2.2 GY) registries. This could be explained by our extensive usage of cine, long fluoroscopy times, limited use of IVUS and not utilizing a reduced 7.5 FPS frame rate [16, 17, 24,25,26].

The in-hospital MACE rate is similar to results seen in the OPEN-CTO [15] registry (7%) but it is higher than MACE results seen in the PROGRESS-CTO (3.5%) [28], RECHARGE (2.6%) [16] and the LATAM registry (3%) [29]. This could be explained due to the relatively small number of patients in our study compared to these large international registries so the percentage of MACE in our study would appear larger than usual.

In-hospital mortality was 1.25% in our study which is similar to the registries previously mentioned and a testament to the very low levels of cardiovascular death associated with CTO procedures worldwide.

Three out of the 7 patients (42.86%) in our study who suffered from in-hospital MACE developed another Major adverse cardiac event during the 6-month follow-up period. This was a higher percentage than the patients who did not suffer from in-hospital MACE and was statistically significant.

In a recent meta-analysis, CTO patients undergoing PCI who developed peri-procedural myocardial injury faced a significantly higher risk of major adverse cardiac events, all-cause death, cardiac death, myocardial infarction, and target vessel revascularization during long-term follow-up which makes it an important marker for prognosis in these patients [30].

A recent study showed that multivessel artery disease, retrograde approach, and the presence of procedural complications were predictors of Peri-procedural myocardial injury (PMI) after CTO-PCI and that patients who develop PMI tend to have a poorer clinical prognosis and more MACE than those who do not develop PMI [31].

81.25% of patients in our study showed an improvement in the grade of their exertional dyspnea or angina within the 6-month follow-up period. The percentage of cases who showed improvement of symptoms after a 6-month period was similar between the 2 groups.

Several randomized clinical trials have yielded valuable insights into the effectiveness of CTO PCI. In the large DECISION-CTO trial where 834 patients were randomly assigned to either CTO or non-CTO PCI. The study revealed a high success rate of 90.6% for CTO PCI, but no significant differences were observed in the occurrence of death, MI, stroke, and target vessel revascularization between the two groups during the 4-year follow-up period and it did not report improved quality of life in the PCI arm [32].

However, careful examination of the study design and results reveals several limitations that need to be taken into consideration when interpreting the study results such as its underpowered nature due to early termination, a relatively high crossover rate from non-CTO PCI to CTO PCI (19%), a significant proportion of patients experiencing either no symptoms or mild symptoms, lack of information regarding the proportion of patients who underwent prior functional evaluation and its outcomes, and the study's non-inferiority design.

Other trials demonstrated enhancements in quality of life measures, but also did not exhibit significant differences in major adverse event rates such as the EURO-CTO trial where 396 patients were randomly assigned to CTO PCI or non-CTO PCI in a 2:1 ratio. After 12 months, patients who underwent CTO PCI achieved an 86% success rate, with notable improvements in angina frequency and quality of life. dimensions according to the Seattle Angina Questionnaire [33].

In a study conducted by Obedinskiy et al. (IMPACTOR-CTO trial) 94 patients with isolated right coronary artery chronic total occlusion (CTO) were randomly assigned to either CTO percutaneous coronary intervention (PCI) or non-CTO PCI at a single center. The results revealed that CTO PCI led to a greater reduction in ischemia and improvements in 6-min walk distance and quality of life, as assessed by the SF-36 health survey [34].

However, two other randomized clinical trials yielded different findings. One trial focused on patients with ST-segment elevation myocardial infarction (MI) (EXPLORE trial) assessing left ventricular systolic function and diastolic volume at 4 months. The other trial (REVASC trial) involved patients with stable angina evaluating segmental wall thickening in CTO territory and global and regional left ventricular function at 6 months [35, 36].

Both trials showed no significant differences between CTO PCI and non-CTO PCI in terms of hard outcomes such as MACE or improvement in left ventricular function. In contrast to the EXPLORE trial, REVASC showed a reduction in the combined clinical endpoint favoring CTO PCI, which was driven largely by a reduced need for clinically driven revascularization, with no difference in fatal outcomes [37].

A recent comprehensive meta-analysis was conducted, encompassing all existing prospective randomized and observational studies, to evaluate the correlation between successful CTO-PCI and patient life quality. The findings revealed a notable enhancement in SAQ scores among patients with CTO who underwent successful revascularization. Interestingly, a significant difference in scores was observed as early as 30 days after PCI and this improvement persisted throughout the longest follow-up period of 48 months. The results indicate that there is evidence to support the utilization of PCI as a treatment option for symptomatic patients with CTO who do not respond to medical treatment [38].

16.25% of patients in our study needed re-hospitalization within a 6-month period after PCI. The overall TLR rate at 6 months was 8.75%, the overall TVR rate at 6 months was 1.25%.

This was similar to the rates seen in the OPEN-CTO registry (14.8% re-hospitalization) [15] and in the EURO-CTO [19] with an average of 23 months of follow-up where re-hospitalization rate was 14.2% and the overall MACE including revascularization was 13.6%.

A study reviewing the one-year outcomes of the RECHARGE registry demonstrated a favorable overall MACE rate of 8% at 12 months post-discharge. Furthermore, similar to our study there was a low TLR rate (5.5%) and TVR rate (5.2%) seen 12 months after a technically successful procedure [39].

Our results are comparable with a large published study by Wilson et al. [40] who reported an 8.6% MACE rate, a TLR rate of 4.5% and a TVR rate of 5.0% 12 months after technically successful procedures. Previous reports from CTO cohorts report TLR of 6.3–10.7% with second generation DES [41, 42].

Regarding the effectiveness and safety of the antegrade vs retrograde approaches, a recent study by Eugene et al. [43] compared antegrade and retrograde approaches in 485 CTO patients where Procedural success for antegrade and retrograde was 94.4% and 84.6%, respectively. This was similar to success rates in our study. In-hospital MACE occurred in 19 (3.8%) CTO episodes and was more common in the retrograde group (6.6% vs 1.5%). The majority of these were myocardial infarction (17 of 19). There were nine coronary perforations, seven retrograde (3.1%), two antegrade (0.7%, p = 0.09), and one required pericardiocentesis (0.2%). Our study had a higher in-hospital MACE rate in the retrograde group (16.6%) compared to this study owing to the higher prevalence of peri-procedural Myocardial injury compared to the antegrade group while having no patients who required pericardiocentesis due to perforation.

Another recent study, the PROGRESS-MENATA registry demonstrated that high success and acceptable complication rates are currently achieved at experienced centers in the MENATA region using a combination of crossing strategies. Mean J-CTO score was 2.1 ± 1.2 and overall procedural success rates were high (92%) which was similar to our study. They had a low incidence (1.8%) of in-hospital major adverse cardiac events. Antegrade wire escalation was the most common crossing strategy used (followed by retrograde approach [44].

These high success rates and relatively low complication rates in multiple studies and registries further emphasize the increasing safety of these procedures when utilizing modern techniques and equipment.

Regarding the clinical implications of the results of our study, it should influence clinical practice in encouraging the development of CTO training programs in multiple centers across the country with the guidance of a proctor expert CTO operator to be able to help thousands of symptomatic CTO patients across the country with limited access to high quality care to be able to have a procedure done which is proven to improve their symptoms.

While maintaining high success rates and low complication rates, patient safety is ensured when carefully chosen patients with clear indications are operated upon under the guidance of expert operators in a well-equipped center and the stigma around the complication rates surrounding complex CTO procedures could be eventually decreased with increasing confidence in the success of CTO procedures.

Future research directions should be aiming to recruit a large number of patients across these multiple centers and aim to reproduce these results on a wider scale to be able to further emphasize the safety of CTO procedures when done in a carefully selected population under the guidance of expert operators.

The current study was a prospective cohort study in which all study participants were recruited from a single center (Ain Shams University Hospitals) which may not be representative of the different centers in Egypt with a wide variability in CTO training programs and availability of high-volume CTO operators.

The implications regarding this is that not all PCI centers should be allowed to operate on complex CTO patients without having expert operators with a pre-defined yearly minimum number of patients operated on, while also having all the equipment needed for both crossing and also equipment to ensure bail-out and safety in case of occurrence of complications such as coils and graft stents. The results of this study should only be reciprocated and applied upon in centers with similar capabilities and operators with similar expertise in order to be able to generalize these results and reach success rates and safety from complications in similar rates.

A large sample size would help in better assessment of success rates and complication rates as well as recruiting larger number of patients in retrograde group for better accuracy in comparison with antegrade group. A longer follow-up period may help in detecting long-term MACE that may otherwise not be detected during the first 6 months.

The study did not evaluate the technical success rate between the different CTO techniques and did not compare short-term MACE between successful and failed CTO PCI procedures where patients continued on optimal medical therapy only.