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Dissection and re-entry techniques are essential to achieve safe and effective chronic total occlusion recanalization. Several studies have demonstrated similar outcomes following extraplaque stenting compared with intraplaque stenting. Dissection techniques most often involve the use of knuckled wires to progress within and beyond the chronic total occlusion segment. In this expert consensus document, the authors compare the properties of different polymer-jacketed wires for their use in dissection techniques. The authors also describe 2 principal knuckle wire behaviors, the rolling and the traveling knuckles. Finally, several adjunctive techniques for safer dissection are described. [Display omitted] • DARTs are advocated for long and calcified CTO segments to avoid perforation. • We describe 2 fundamental knuckle behaviors, the rolling and traveling knuckles, and their use. • Better description of knuckle behavior should enhance communication and knowledge transfer. [ABSTRACT FROM AUTHOR]

PCI for aorto-ostial CTO remains challenging. The techniques for guidewire in aorto-ostial CTO may differ from those used in non–aorto-ostial CTOs, influenced by clinical and angiographic characteristics. This study aimed to assess the technical aspects and outcomes of percutaneous coronary intervention (PCI) in patients with aorto-ostial chronic total occlusion (CTO). This analysis included 420 patients with ostial CTO from the Japanese CTO-PCI Expert Registry, spanning January 2014 to December 2022. It examined the strategies and procedural outcomes of CTO PCI. Ostial CTO represented 420 of 10,814 (3.9%) of all CTO PCI cases. Within this subset, aorto-ostial CTO accounted for 218 of 420 (52%) cases. The technical success rate for aorto-ostial CTO was 88% (191/218). Aorto-ostial CTOs exhibited longer lesion lengths and were more likely to present with challenges such as distal target lumen ambiguity, calcification, and tortuosity compared with non–aorto-ostial CTOs. The retrograde approach was more commonly used in aorto-ostial CTO, with retrograde direct crossing being the most successful technique, especially in cases of flush CTO. A multivariate logistic analysis identified several factors significantly associated with unsuccessful aorto-ostial CTO PCI, including difficulties in engaging a guiding catheter, estimating the collateral channel (as assessed by the J-Channel score), and tortuosity. Aorto-ostial CTOs are more complex and frequently require a retrograde approach. The availability of suitable interventional collateral channels is crucial for the success of these procedures. [Display omitted] [ABSTRACT FROM AUTHOR]

We sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H 2 O positron-emission tomography (PET) perfusion imaging. CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. A total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H 2 O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. This study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). The present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H 2 O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. What is new? • CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. • We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H 2 O PET imaging, whereas coronary flow reserve was comparable between sexes. • The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI. What are the clinical implications? • Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients. • These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes. • Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI. • CTO PCI is associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. • We found a greater recovery of stress perfusion in females after CTO PCI as measured by serial [15O]H 2 O PET imaging. • Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients. • These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes. • Studies with preprocedural imaging are warranted to increase our understanding of the impact of sex on MBF after CTO PCI. [ABSTRACT FROM AUTHOR]

Purpose: Chronic total occlusion (CTO) remains as a major target for endovascular treatment (EVT) in improving symptomatic lower-extremity artery disease (LEAD). However, despite the technical demand and learning curve for the procedure, volume-outcome relationship of EVT targeted for CTO in symptomatic LEAD remains unclear. Materials and Methods: Data were obtained from a nationwide registry for EVT procedures limited to the Japanese Association of Cardiovascular Intervention and Therapeutics between January 2018 and December 2020 from 660 cardiovascular centers in Japan. In total, 96 099 patients underwent EVT for symptomatic LEAD, and 41 900 (43.6%) underwent CTO-targeted EVTs during the study period. Institutional volume was classified into quartiles. The association of institutional volumes with short-term outcomes was explored using the generalized linear mixed model using a logit link function, in which, interinstitution variability was used as a random effect. Results: The median institutional volume for all EVT cases per quartile was 29, 68, 125, and 299 cases/year for the first, second, third, and fourth quartiles, respectively. With each model analysis, the adjusted odds ratios (ORs) for technical success were significantly lower in patients who underwent EVT in institutions within the first quartile (<52 cases/year) than in the other quartiles (P <.01, respectively). On the contrary, the adjusted ORs for procedural complications were significantly higher in the first and second quartiles than in the third and fourth quartiles (P <.01, respectively). Conclusion: In contemporary Japanese EVT practice, a higher institutional volume but not operator volume was associated with a higher technical success rate and a lower procedural complication rate in patients with symptomatic LEAD involving CTO lesions. Clinical Impact: EVT for CTO lesions is still challenging for clinicians because of difficulties of wire/devise crossing or high procedural complications rate. Our study demonstrated that a higher institutional volume but not operator volume was associated with a higher technical success rate and a lower procedural complication rate in patients with symptomatic LEAD involving CTO lesions. In contemporary Japanese practice, a higher institutional experience has better impacts on short-term clinical outcomes. Future research should determine the relationship between institutional volume and long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Percutaneous coronary intervention (PCI) to chronic total occlusion (CTO) is still a subject of debate. The primary goal of revascularization is to provide symptomatic relief and enhance left ventricular (LV) functions. Global longitudinal strain (GLS) is proven to be more sensitive than the ejection fraction (EF), especially for subtle ischemic changes. The purpose of this study was to investigate the improvement in LV GLS after revascularization of symptomatic stable coronary patients with single-vessel CTO, categorized according to their collateral supply grades. Sixty-nine patients with successful CTO-PCI were grouped, according to their collateral supply grades, as well-developed (WD) and poor collateral groups and followed-up for 3 months. Basal characteristics were similar for both groups, except for a lower EF (p = 0.04) and impaired GLS (p < 0.0001) in the poor collateral group. At the end of 3 months follow-up, symptomatic relief was similar in both groups (p = 0.101). GLS improvement reached statistical significance only for the poor collateral, not for the WD group (p < 0.0001 and p = 0.054, respectively). The EF did not change significantly in both groups. Poorly collateralized CTO lesions may not only result in baseline LV dysfunction, but also appear to carry potential for recovery after revascularization. This may not be the case for WD collaterals. [ABSTRACT FROM AUTHOR]

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI. [ABSTRACT FROM AUTHOR]

Aim: This systematic review evaluated the impact of a chronic total occlusion (CTO) in a non-infarct-related artery (non-IRA) on clinical outcomes in acute coronary syndrome (ACS) patients and assessed the benefits of staged revascularization. Methods: We performed a comprehensive systematic review to provide further insight into the impact of a CTO in a non-IRA on clinical outcomes after ACS. Moreover, we review the currently available evidence on the clinical significance of staged revascularization for a CTO in a non-IRA patients with ACS and propose whether prophylactic CTO percutaneous coronary intervention (PCI) could improve outcomes in patients who subsequently develop an ACS. Results: Our search identified 999 studies, from which 30 were selected and ten were included in the analysis. The results showed a trend of higher all-cause mortality and major adverse cardiac event rates in the culprit-only-PCI group compared with the multivessel (MV)-PC I group in ST elevation myocardial infarction patients, with varying statistical significance across different outcomes. Conclusion: This review highlights the significant impact of non-IRA CTOs in ACS. Successful CTO revascularization may provide benefits, particularly in ST elevation myocardial infarction, but the optimal management approach remains uncertain. The presence of a non-IRA CTO, especially in cardiogenic shock, predicts worse outcomes. Further research is warranted to determine the effective strategies to improve survival. Plain Language Summary Heart attacks occur when blood flow to the heart is blocked. Some people have a long-standing complete blockage in a heart artery, called a chronic total occlusion (CTO). This review examined studies on heart attack patients, who also had a CTO in a different artery. The review found that having a CTO makes heart attacks more dangerous, increasing the risk of serious complications or death. Treating the CTO might benefit some patients, potentially reducing future heart problems. However, the optimal timing for CTO treatment remains unclear, some doctors prefer immediate treatment, while others advocate waiting. For very sick heart attack patients in cardiogenic shock, a CTO further increases risks. These patients may require specialized treatments to support heart function. Although fixing CTOs might help, more research is needed to determine their effectiveness for all patients. Currently, treatment decisions are made based on each patient's situation. In conclusion, CTOs pose a significant challenge in heart attack treatment. Further studies are necessary to establish the safest and most effective approach for managing heart attack patients with CTOs. Article highlights What we know The presence of a chronic total occlusion (CTO) is associated with higher mortality and adverse events compared with no CTO. Some studies showed the benefit of CTO revascularization on outcomes like mortality, myocardial infarction and the need for coronary artery bypass grafting. Large, randomized trials failed to demonstrate significant benefits of routine CTO percutaneous coronary intervention during index acute coronary syndrome admission. Study implications The pooled estimates failed to show statistically significant differences for most outcomes across studies except in the major adverse cardiac event aspect. Adequately powered randomized trials are still needed to determine if prophylactic CTO percutaneous coronary intervention improves long-term prognosis in acute coronary syndrome patients with concurrent CTOs. [ABSTRACT FROM AUTHOR]

Cigarette smoking is a significant risk factor for coronary artery disease. However, there is insufficient evidence regarding the long-term clinical effects of smoking in Asian populations with chronic total occlusion (CTO). This study aimed to assess the effects of smoking on 5-year (median follow-up period, 4.2 ± 1.5 [interquartile range, 4.06–5.0] years) clinical outcomes in patients with CTO lesions who underwent percutaneous coronary intervention (PCI) or medical treatment (MT). We enrolled 681 consecutive patients with CTO who underwent diagnostic coronary angiography and subsequent PCI or MT. The patients were categorized into smokers (n = 304) and nonsmokers (n = 377). The primary endpoint was major adverse cardiovascular events (MACE), including a composite of all-cause death, myocardial infarction, and revascularization over a 5-year period. Propensity score matching (PSM) analysis was performed to adjust for potential baseline confounders. After PSM analysis, two propensity-matched groups (200 pairs, n = 400) were generated, and the baseline characteristics of both groups were balanced. The smokers exhibited a higher cardiovascular risk of MACE (29.5% vs. 18.5%, p = 0.010) and non-TVR (17.5 vs. 10.5%, p = 0.044) than the nonsmokers. In a landmark analysis using Kaplan–Meier curves at 1 year, the smokers had a significantly higher rate of MACE in the early period (up to 1 year) (18.8% and 9.2%, respectively; p = 0.008) compared with the nonsmokers. The Cox hazard regression analysis with propensity score adjustment revealed that smoking was independently associated with an increased risk of MACE. These findings indicate that smoking is a strong cardiovascular risk factor in patients with CTO, regardless of the treatment strategy (PCI or MT). In addition, in the subgroup analysis, the risk of MACE was most prominently elevated in the group of smokers who underwent PCI. [ABSTRACT FROM AUTHOR]

Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach. Clinical Trial Registration: NCT02748226. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single‐photon emission computed tomography (SPECT) and 18F‐FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). Methods: A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). Results: After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008–1.052, p =.007). The cut‐off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p =.035). A sensitivity analysis restricting patients with single‐vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008–1.043, p =.005). Conclusion: HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO‐PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large‐scale studies. [ABSTRACT FROM AUTHOR]

Background: Macrophage-mediated cleaning up of dead cells is a crucial determinant in reducing coronary artery inflammation and maintaining vascular homeostasis. However, this process also leads to programmed death of macrophages. So far, the role of macrophage death in the progression of atherosclerosis remains controversial. Also, the underlying mechanism by which transcriptional regulation and reprogramming triggered by macrophage death pathways lead to changes in vascular inflammation and remodeling are still largely unknown. TRIM25-mediated RIG-I signaling plays a key role in regulation of macrophages fate, however the role of TRIM25 in macrophage death-mediated atherosclerotic progression remains unclear. This study aims to investigate the relationship between TRIM25 and macrophage death in atherosclerosis. Methods: A total of 34 blood samples of patients with coronary stent implantation, including chronic total occlusion (CTO) leisions (n = 14) or with more than 50% stenosis of a coronary artery but without CTO leisions (n = 20), were collected, and the serum level of TRIM25 was detected by ELISA. Apoe−/− mice with or without TRIM25 gene deletion were fed with the high-fat diet (HFD) for 12 weeks and the plaque areas, necrotic core size, aortic fibrosis and inflammation were investigated. TRIM25 wild-type and deficient macrophages were isolated, cultured and stimulated with ox-LDL, RNA-seq, real-time PCR, western blot and FACS experiments were used to screen and validate signaling pathways caused by TRIM25 deletion. Results: Downregulation of TRIM25 was observed in circulating blood of CTO patients and also in HFD-induced mouse aortas. After HFD for 12 weeks, TRIM25−/−ApoeE−/− mice developed smaller atherosclerotic plaques, less inflammation, lower collagen content and aortic fibrosis compared with TRIM25+/+ApoeE−/− mice. By RNA-seq and KEGG enrichment analysis, we revealed that deletion of TRIM25 mainly affected pyroptosis and necroptosis pathways in ox-LDL-induced macrophages, and the expressions of PARP1 and RIPK3, were significantly decreased in TRIM25 deficient macrophages. Overexpression of TRIM25 promoted M1 polarization and necroptosis of macrophages, while inhibition of PARP1 reversed this process. Further, we observed that XRCC1, a repairer of DNA damage, was significantly upregulated in TRIM25 deficient macrophages, inhibiting PARP1 activity and PARP1-mediated pro-inflammatory change, M1 polarization and necroptosis of macrophages. By contrast, TRIM25 overexpression mediated ubiquitination of XRCC1, and the inhibition of XRCC1 released PARP1, and activated macrophage M1 polarization and necroptosis, which accelerated aortic inflammation and atherosclerotic plaque progression. Conclusions: Our study has uncovered a crucial role of the TRIM25-XRCC1Ub-PARP1-RIPK3 axis in regulating macrophage death during atherosclerosis, and we highlight the potential therapeutic significance of macrophage reprogramming regulation in preventing the development of atherosclerosis. [ABSTRACT FROM AUTHOR]

A bidirectional approach is necessary for treating critical limb ischemia with complex, multiple lesions. We report an ultrasound-guided bidirectional puncture through an occluded vessel to treat an obstruction extending from the anterior tibial artery to the dorsal foot artery in a patient with toe gangrene and rest pain. This technique effectively restored arterial patency and is a promising approach for managing challenging critical limb ischemia occlusions.

Abstract Purpose The conundrum of limited resources in developing countries leads to the abonnement and underutilization of percutaneous coronary intervention for chronic total occlusion, in addition to lack of expertise, limited supplies, and success rates. We embraced this challenge by initiating a dedicated program in a tertiary academic center in Egypt, aiming for optimum utilization of resources, limit cost, and gaining experience. We present our outcomes and the proficiency in establishing the program. Methods We enrolled all patients undergoing percutaneous coronary intervention for chronic total occlusion during the first year of initiating our dedicated program. Analysis of clinical data, angiographic findings, and procedural features were evaluated, aiming to evaluate outcomes. Our primary outcome was successful recanalization achievement, utilization of available resources and cost. Secondary outcomes such as peri-procedural myocardial infarction, coronary perforation, urgent need of coronary artery bypass grafting, cerebrovascular stroke, and mortality were assessed. Results Our study enrolled 64 patients electively admitted to the Critical Care Department, Cairo University, undergoing percutaneous coronary intervention for chronic total occlusion. The median J-CTO score was 2 (0–5). We achieved successful recanalization in 47 patients (73%). The mean procedural time was 123 ± 48.8 min, mean contrast volume was 359.03 ± 151.9 ml, and mean radiation dose was 9.4 ± 4.2 Gy. The mean number of wires per patient was 2.69 ± 1.32, and the most successful crossing strategy was antegrade wiring (56.3%). The commonest cause of failure was failure of re-entry (46.7%). One patient had peri-procedural MI (1.6%), and one patient required urgent CABG. There was no in-hospital mortality or cerebrovascular stroke. The cost ranged from 6520 Egyptian Pounds (EP) ($415) to 63,720 EP ($4058), with a mean of 26,213 EP ($1670). Conclusions Establishing a dedicated program for percutaneous coronary intervention for chronic total occlusion proved to be feasible and proficient, achieving high success rates with limited complications in view of limited resources, rationalized utilization of equipment, and limitation of hospital costs.

Abstract Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach. Clinical Trial Registration: NCT02748226.

Although percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has been increasing in recent years, CTO PCI is still one of the most challenging procedures with relatively higher rates of procedural complications and adverse clinical events after PCI. Due to the innate limitations of invasive coronary angiography, intravascular imaging (IVI) has been used as an adjunctive tool to complement PCI, especially in complex coronary artery disease. Considering the complexity of CTO lesions, the role of IVI is particularly important in CTO intervention. IVI has been a useful adjunctive tool in every step of CTO PCI including assisted wire crossing, confirmation of wire location within CTO segment, and stent optimization. The meticulous use of IVI has been one of the greatest contributors to recent progress of CTO PCI. Nevertheless, studies evaluating the role of IVI during CTO PCI are limited. The current review provides a comprehensive overview of the mechanistic advantages of IVI in CTO PCI, summarizes previous studies and trials, and presents future perspective of IVI in CTO PCI.

Abstract Objectives Patients undergoing a prior failed attempt of chronic total occlusion‐percutaneous coronary intervention (CTO‐PCI) represent a challenging subgroup across all patients undergoing CTO‐PCI. There are limited data on the effects of a prior failed attempt on the outcomes of subsequent CTO‐PCI. We aimed to compare the procedural results and 24‐month outcomes of prior‐failed‐attempt CTO‐PCI with those of initial‐attempt CTO‐PCI. Methods Patients who underwent attempted CTO‐PCI between January 2017 and December 2019 were prospectively enrolled. We analyzed the procedural results and 24‐month major adverse cardiac events (MACE) between patients who underwent prior‐failed‐attempt and initial‐attempt CTO‐PCI. MACE was defined as a composite of cardiac death, target vessel‐related myocardial infarction, and ischemia‐driven target vessel revascularization (TVR) during follow‐up. Results In total, 484 patients who underwent CTO‐PCI (prior‐failed‐attempt, n = 49; initial‐attempt, n = 435) were enrolled during the study period. After propensity score matching (1:3), 147 patients were included in the initial‐attempt group. The proportion of the Japanese‐CTO (J‐CTO) score ≥2 was higher in the patients who underwent prior failed attempt than in those who underwent initial attempt (77.5% vs. 38.8%, p

Abstract Background Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). Methods This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2–3) and poor CCC formation group (Rentrop grade 0–1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. Results A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose–response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584–0.651, P

Xi Wu, Qin Li, Mingxing Wu, Haobo Huang, Zhe Liu, He Huang, Lei Wang Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, 411100, People’s Republic of China, Email heartwl@126.comObjective: The research was carried out to determine and compare the efficiency of completely transradial access (cTRA) and transfemoral access (TFA) in retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI).Background: The cases of retrograde chronic total occlusion (CTO) percutaneous coronary intervention usually need the dual access. The transradial method is now used more frequently in CTO PCI, and improves the safety of CTO PCI.Methods: This retrospective, observational study was carried out in a single center. Participants were patients who underwent dual-access retrograde CTO PCI from January 2017 to October 2023, categorized into two groups: cTRA (biradial access) and TFA (bifemoral, or combined radial and femoral access). All patients in the cTRA group received conventional radial access. All punctures of the femoral artery were performed without fluoroscopic or ultrasound guidance. None of the patients in the TFA group accepted any arterial closure devices. Clinical, angiographic and procedural characteristics and the occurrence of in-hospital major adverse cardiovascular events (MACE) of the cTRA and TFA procedures were recorded.Results: This research involved 187 CTO PCI procedures with dual access, of which 88 were done using cTRA and the rest (99) were carried out through TFA. The J-CTO (Multicenter Chronic Total Occlusion Registry of Japan) score was lower in the cTRA group than TFA group (2.1± 0.6 vs 3.0± 0.8; P < 0.001). The technical success (84.1% vs 82.8%; P= 0.817), procedural success (80.7% vs 79.8%; P= 0.906) and in-hospital MACE rates (5.7% vs 4.0%; P= 0.510) were the same for both groups. For a J-CTO score of 3 or higher, technical success rate was significantly lower in the cTRA group than the TFA group (58.1% vs 74.2%; P < 0.001).Conclusion: In the retrograde CTO PCI, the percentages of success and in-hospital MACE were similar for both cTRA and TFA. Meanwhile, cTRA may be used for simpler lesions (J-CTO score < 3) as compared to TFA.Keywords: transradial approach, transfemoral approach, chronic total occlusion, retrograde, percutaneous coronary intervention

Abstract Background The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). Methods This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. Results Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p

Abstract Background The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. Case presentation A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. Conclusions The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions.

Introduction Methods Results Conclusions Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA‐2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta‐analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS.Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all‐cause mortality, stroke, major bleeding and angina severity.Nineteen RCTs involving 8616 patients were included. Median follow‐up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62–.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow‐up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005).PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow‐up duration beyond 3 years. [ABSTRACT FROM AUTHOR]

Key Clinical Message: With increased complexity in both medical comorbidities and coronary anatomy, the proportion of surgically turndown patients and high‐risk PCI will continue to rise. Impella‐assisted complex PCI can be performed with high technical success and can improve quality of life, angina score, and potentially left ventricular ejection fraction. [ABSTRACT FROM AUTHOR]

Introduction: The safety and effectiveness of the GORE VIABAHN Endoprosthesis for treatment of symptomatic patients with peripheral artery disease (PAD) and complex femoropopliteal (FP) lesions was assessed in a real-world Japanese practice setting. Methods : A prospective, multicenter, postmarket surveillance study was conducted from 2016 to 2017 at 64 sites in Japan. Symptomatic patients with PAD and FP lesions ⩾ 10 cm and reference vessel diameters ranging from 4.0 to 7.5 mm were eligible for enrollment. Outcome measures evaluated at 5 years were primary patency (PP), primary-assisted patency (PAP), secondary patency (SP), freedom from target lesion revascularization (fTLR), occurrence of device- or procedure-related serious adverse events (SAEs), and stent fractures. Results : A total of 321 patients were enrolled and were a mean age of 73.9 ± 8.7 years; 77.3% were men and 26.5% had chronic limb-threatening ischemia (CLTI). The mean lesion length was 23.6 ± 6.6 cm and the frequency with TASC II C/D lesions and chronic total occlusions was 86.6% and 70.4%, respectively. The Kaplan–Meier estimated PP, PAP, SP, and fTLR at 5 years was 62.4%, 74.1%, 82.3%, and 75.9%, respectively. The mean ankle–brachial index was 0.92 ± 0.15 and the mean improvement in Rutherford class was 2.3 ± 1.4, which was maintained through 5 years. The rate of cumulative device- or procedure-related SAEs through 5 years was 19.9% with only 9.3% of those occurring after the first year. No stent fractures were observed through 5 years by x-ray evaluation. Conclusion : The 5-year safety and efficacy outcomes of the endoprosthesis were clinically acceptable for treating complex FP lesions in a real-world cohort of Japanese patients with PAD. (ClinicalTrials.gov Identifier: NCT04706273) [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the peri- and postprocedural outcomes of atherectomy-assisted endovascular treatment of the common femoral (CFA) and popliteal arteries. Methods: Phoenix atherectomy was used for the treatment of 73 and 53 de novo CFA and popliteal artery lesions, respectively, in 122 consecutive patients. Safety endpoints encompassed perforation and peripheral embolization. Postprocedural endpoints included freedom from clinically driven target lesion revascularization (CD-TLR) and clinical success (an improvement of ⩾ 2 Rutherford category [RC]). In addition, 531 patients treated for popliteal artery stenosis or occlusion without atherectomy were used as a comparator group. Results: Procedural success (residual stenosis < 30% after treatment) was 99.2%. The need for bail-out stenting was 2 (2.7%) and 3 (5.7%) in CFA and popliteal artery lesions, respectively. Only one (1.4%) embolization occurred in the CFA, which was treated by catheter aspiration. No perforations occurred. After 1.50 (IQR = 1.17–2.20) years, CD-TLR occurred in seven (9.2%) and six (14.6%) patients with CFA and popliteal artery lesions, respectively, whereas clinical success was achieved in 62 (91.2%) and 31 (75.6%), respectively. Patients treated with atherectomy and DCB in the popliteal artery after matching for baseline RC, lesion calcification, length, and the presence of chronic total occlusion, exhibited higher freedom from CD-TLR compared to the nondebulking group (HR = 3.1; 95% CI = 1.1–8.5, p = 0.03). Conclusion: Atherectomy can be used safely and is associated with low rates of bail-out stenting in CFA and popliteal arteries. CD-TLR and clinical success rates are clinically acceptable. In addition, for the popliteal artery, atherectomy combined with DCB demonstrates lower CD-TLR rates compared to a DCB alone strategy. (German Clinical Trials Register: DRKS00016708) [ABSTRACT FROM AUTHOR]

Objectives: Patients undergoing a prior failed attempt of chronic total occlusion‐percutaneous coronary intervention (CTO‐PCI) represent a challenging subgroup across all patients undergoing CTO‐PCI. There are limited data on the effects of a prior failed attempt on the outcomes of subsequent CTO‐PCI. We aimed to compare the procedural results and 24‐month outcomes of prior‐failed‐attempt CTO‐PCI with those of initial‐attempt CTO‐PCI. Methods: Patients who underwent attempted CTO‐PCI between January 2017 and December 2019 were prospectively enrolled. We analyzed the procedural results and 24‐month major adverse cardiac events (MACE) between patients who underwent prior‐failed‐attempt and initial‐attempt CTO‐PCI. MACE was defined as a composite of cardiac death, target vessel‐related myocardial infarction, and ischemia‐driven target vessel revascularization (TVR) during follow‐up. Results: In total, 484 patients who underwent CTO‐PCI (prior‐failed‐attempt, n = 49; initial‐attempt, n = 435) were enrolled during the study period. After propensity score matching (1:3), 147 patients were included in the initial‐attempt group. The proportion of the Japanese‐CTO (J‐CTO) score ≥2 was higher in the patients who underwent prior failed attempt than in those who underwent initial attempt (77.5% vs. 38.8%, p < 0.001). The retrograde approach was more often adopted in the prior‐failed‐attempt group than in the initial‐attempt group (32.7% vs. 3.4%, [P< 0.001). Successful CTO revascularization rates were significantly lower in the prior‐failed attempt‐group than in the initial attempt group (53.1% vs. 83.3%, P < 0.001). The multivariate analysis revealed that J‐CTO score ≥2 [odds ratio (OR), 0.359; 95% confidence interval (CI), 0.159–0.812; P = 0.014], intravascular ultrasound procedure (OR, 4.640; 95% CI, 1.380–15.603; P = 0.013), and prior failed attempt (OR, 0.285; 95% CI, 0.125–0.648; P = 0.003) were the independent predictors for successful CTO revascularization. There were no significant differences in major procedural complications (2.0% vs. 0.7%, p = 0.438) and MACE rates (4.1% vs. 8.8%, p = 0.438) between the groups, mainly due to the TVR rate (4.1% vs. 8.2%, P = 0.522). Conclusions: Compared with initial‐attempt CTO‐PCI, prior‐failed‐attempt CTO‐PCI deserves more attention, since it is associated with a lower successful CTO revascularization rate. Prior failed attempt, J‐CTO score ≥2, and IVUS procedure are the determining factors for predicting successful CTO revascularization. There are no significantly different unfavorable outcomes between patients who undergo prior‐failed‐attempt and initial‐attempt CTO‐PCI. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to describe a bailout technical strategy to prevent below-the-knee (BTK) distal embolization during procedures with increased inherent risk using universally-available "off-the-shelf" devices. Technique: A conventional retrograde access is obtained of the BTK target vessel where embolization protection is sought. Before starting any potential proximal maneuver with an associated significant risk of distal embolization (eg, atherectomy and mechanical thrombectomy), a low-profile balloon is inserted and inflated through the distal retrograde access, so that any debris resulting from the recanalization procedure is blocked by the stagnant column of blood generated by the inflated balloon. Once the revascularization procedure has been completed, a 4F curved catheter is antegradely advanced down to the distally-inflated balloon, and in case of distal embolization the debris is aspirated in a standard fashion way. Conclusion: A retrograde balloon-assisted "off-the-shelf" embolic protection approach may be considered for BTK revascularization procedures where there is an inherent increased risk of distal trash, especially in the presence of distal single-vessel runoff. Clinical Impact: Distal embolization following endovascular procedures can have devastating consequences and there is a general recommendation for selective use of EPDs in high-risk-scenarios. The increased cost and low availability of the current EPD devices for BTK/BTA arteries have prohibited their widespread use. The retrograde balloon-assisted "off-the-shelf" EPD prevents distal embolization during procedures with increased risk of distal trash using inexpensive, nonspecific equipment available in any basic endovascular suite. [ABSTRACT FROM AUTHOR]

Background and Objectives: Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is often associated with longer total stent length. Our aim was to evaluate the long-term safety and effectiveness of bioresorbable scaffold (BRS) implantation in CTO to avoid using a full metal jacket. Materials and Methods: We conducted a single-center prospective longitudinal case study including 34 patients who underwent PCI of CTO with at least one BRS and drug-eluting stent (DES) implantation (n = 27) or BRS-only at the Latvian Centre of Cardiology between 2016 and 2018. Quantitative coronary angiography (QCA) and intravascular ultrasound were performed during the index procedure and long-term follow-up. Results: Of 34 patients with a mean age of 60.6 ± 9.5 years, 76.5% were male. The most common CTO artery was the right coronary artery (73.5%, n = 25). The median length of occlusion was 23.0 mm (interquartile range (IQR) = 13.9–32.7), with a total mean BRS/DES length of 49.6 ± 20.4 mm. During the median follow-up of 5.6 years (IQR = 5.0–5.9), the primary endpoint of target vessel re-occlusion occurred in 5.9% (n = 2) of patients. Target lesion revascularization (TLR) was performed in 35.3% (n = 12) of patients, with a mean time to TLR of 62.5 (95% confidence interval (CI), 53.9–71.2) months. Through QCA, there was a statistically significant increase in median residual diameter stenosis (20.1–31.4%, p < 0.01) and residual length of stenosis (5.2–7.1%, p = 0.04) compared with the index procedure. Conclusions: Our study demonstrates that BRS is a safe and feasible option for PCI of CTO, allowing for the avoidance of long segment stenting and ensuring long-term patency of the coronary artery. [ABSTRACT FROM AUTHOR]

Background Tip detection-antegrade dissection and re-entry (TD-ADR) technique allows operators to accurately observe both guidewire tip direction and a true lumen in chronic total occlusion (CTO) lesions, while the torque direction of the guidewire on IVUS images does not invariably correspond to that on fluoroscopic images. Case summary A 41-year-old man with hypertension who smokes presented with sudden onset of dyspnoea, acute heart failure, and ischaemic findings on electrocardiogram; we performed percutaneous coronary intervention (PCI) for a sub-totally occluded mid-left anterior descending artery lesion. All antegrade wiring attempts failed to enter the distal true lumen followed by subintimal tracking and re-entry technique. Since the lesion re-occluded the next day, we treated the lesion using a novel TD-ADR technique, termed the 'integrated TD-ADR', because of no interventional retrograde channel. This method integrates fluoroscopic and intravascular ultrasound (IVUS) images, ensuring congruence in the torque direction of the guidewire across both modalities and enabling vertical puncture of the stiff guidewire from the extraplaque space to the distal true lumen quickly and precisely. Final angiography showed good results. Five months later, coronary angiography showed that the lesion remained open. Discussion The integrated TD-ADR technique merges fluoroscopic and IVUS images, allowing operators to torque the guidewire in the same direction on both images. This approach might be more user-friendly than the original technique and has the potential to enhance the success rate of PCI in complex CTO cases. However, further investigations are warranted to address the clinical feasibility and applicability of this technique. [ABSTRACT FROM AUTHOR]

ILUMIEN IV was the first large-scale, multicenter, randomized trial comparing optical coherence tomography (OCT)-guided vs angiography-guided stent implantation in patients with high-risk clinical characteristics and/or complex angiographic lesions. The authors aimed to specifically examine outcomes in the complex angiographic lesions subgroup. From the original trial population (N = 2,487), high-risk patients without complex angiographic lesions were excluded (n = 514). Complex angiographic lesion characteristics included: 1) long or multiple lesions with intended total stent length ≥28 mm; 2) bifurcation lesion with intended 2-stent strategy; 3) severely calcified lesion; 4) chronic total occlusion; or 5) in-stent restenosis. The study endpoints were: 1) final minimal stent area (MSA); 2) 2-year composite of serious major adverse cardiovascular events (MACEs) (cardiac death, target-vessel myocardial infarction [MI], or stent thrombosis); and 3) 2-year effectiveness, defined as target-vessel failure (TVF), a composite of cardiac death, target-vessel MI, or ischemia-driven target-vessel revascularization. The postpercutaneous coronary intervention (PCI) MSA was larger in the OCT-guided (n = 992) vs angiography-guided (n = 981) group (5.56 ± 1.95 mm2 vs 5.26 ± 1.81 mm2; difference, 0.30; 95% CI: 0.14-0.47; P < 0.001). Compared with angiography-guided PCI, OCT-guided PCI resulted in a lower risk of serious MACE (3.1% vs 4.9%; HR: 0.63; 95% CI: 0.40-0.99; P = 0.04). TVF was not significantly different between groups (7.3% vs 8.8%; HR: 0.82; 95% CI: 0.59-1.12; P = 0.20). In complex angiographic lesions, OCT-guided PCI led to a larger MSA and reduced the serious MACE, the composite of cardiac death, target-vessel MI, or stent thrombosis, compared with angiography-guided PCI at 2 years, but did not significantly improve TVF. (Optical Coherence Tomography Guided Coronary Stent Implantation Compared to Angiography: A Multicenter Randomized Trial in PCI; NCT03507777) [Display omitted] [ABSTRACT FROM AUTHOR]

The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height. The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3–positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies. [Display omitted] [ABSTRACT FROM AUTHOR]

There is limited data on predicting successful chronic total occlusion crossing using primary antegrade wiring (AW). The aim of this study was to develop and validate a machine learning (ML) prognostic model for successful chronic total occlusion crossing using primary AW. We used data from 12,136 primary AW cases performed between 2012 and 2023 at 48 centers in the PROGRESS CTO registry (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) to develop 5 ML models. Hyperparameter tuning was performed for the model with the best performance, and the SHAP (SHapley Additive exPlanations) explainer was implemented to estimate feature importance. Primary AW was successful in 6,965 cases (57.4%). Extreme gradient boosting was the best performing ML model with an average area under the receiver-operating characteristic curve of 0.775 (± 0.010). After hyperparameter tuning, the average area under the receiver-operating characteristic curve of the extreme gradient boosting model was 0.782 in the training set and 0.780 in the testing set. Among the factors examined, occlusion length had the most significant impact on predicting successful primary AW crossing followed by blunt/no stump, presence of interventional collaterals, vessel diameter, and proximal cap ambiguity. In contrast, aorto-ostial lesion location had the least impact on the outcome. A web-based application for predicting successful primary AW wiring crossing is available online (PROGRESS-CTO website) (https://www.progresscto.org/predict-aw-success). We developed an ML model with 14 features and high predictive capacity for successful primary AW in chronic total occlusion percutaneous coronary intervention. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Understanding the prognostic impact of percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) is crucial for patient management. Previous studies have primarily been studying prognostic impact of successful versus unsuccessful CTO PCI. This study investigated the prognostic impact of successful and unsuccessful percutaneous coronary intervention (PCI) of chronic total occluded coronary arteries (CTO) with non-CTO PCI as reference. Methods: Patients treated with PCI from 2009 to 2019 in the Central Region of Denmark were included in a population-based cohort study. We compared successful and unsuccessful CTO PCI with non-CTO PCI. Exclusion criteria was myocardial infarction within 30 days. Primary outcome was difference in a composite major adverse cardio- and cerebrovascular events (MACCE) encompassing all-cause death, any myocardial infarction, stroke, hospitalization for heart failure or revascularization tracked via nationwide registries. Results: Of 21,141 screened patients, 10,638 were enrolled: 9,065 underwent non-CTO PCI, 1,300 had successful CTO PCI, and 273 had unsuccessful CTO PCI. Median follow-up time was 5.9 [3.5;9.0] years and 4,750 MACCEs were recorded. Compared to non-CTO PCI, the adjusted MACCE rate for successful CTO PCI was equivalent (Hazard Ratio (HR): 0.98, 95% Confidence Interval (CI): 0.90–1.07, p = 0.71). In contrast, unsuccessful CTO PCI was associated with a higher MACCE rate (HR: 1.22, 95% CI: 1.04–1.43, p<0.01). HR was adjusted for age, body-mass index, previous revascularization, smoking, kidney disease, two or three-vessel disease, left ventricular ejection fraction, diabetes and comorbidities. Conclusions: The pre-specified hypothesis was accepted. Successful CTO PCI was associated with equivalent long-term outcomes as non-CTO PCI, and unsuccessful CTO PCI was identified as a high-risk group associated to worse outcomes. [ABSTRACT FROM AUTHOR]

Background. Chronic total occlusion (CTO) plaque modification (CTO‐PM) is often used for unsuccessful CTO interventions. Methods. A multicenter, prospective study included consecutive patients with failed CTO recanalization. At the end of the failed procedure, patients received either a conventional (CB) or drug‐coated balloon (DCB) for CTO‐PM at the operator's discretion and underwent a new attempt of CTO recanalization ∼3 months later. Results. A total of 55 patients were enrolled (DCB: 22; CB: 33), with a median age of 66 years. The median J‐score was 3, and CCS angina classes III–IV were present in 45% of the patients. After the first CTO‐PCI attempt, no in‐hospital cardiac deaths were registered. The overall rate of in‐hospital myocardial infarction was 3.6%, without significant differences between the DCB and CB groups (4.5% after DCB vs 3.0% after CB, p = 0.999). The success rate of the second CTO‐PCI attempt was 86.8%, with a periprocedural complication rate of 5.7% and with an overall rate of in‐hospital complications of 24.5%, without significant differences between the 2 groups (13.6% in the DCB group vs 32.2% in the CB group, p = 0.195). Compared with CB, in the DCB group, the second CTO‐PCI required a shorter median fluoroscopy time (33 vs 60 min, p < 0.001), a lower contrast volume (170 vs 321 cc, p < 0.001), and a lower radiation dose (1.7 vs 3.3 Gy, p < 0.001). At 1‐year follow‐up, outcomes were comparable between the 2 strategies, target vessel failure occurred in 5.7% and major adverse cardiovascular events in 18.2% (13.6% in the DCB group vs 21.2% in the CB group, p = 0.494). Conclusions. PM after CTO recanalization failure is safe and warrants high success rates when a second attempt is performed. A DCB strategy for CTO‐PM does not seem to ensure higher success or better clinical outcomes, but its use was associated with simpler staged procedures. This trial is registered with NCT05158686. [ABSTRACT FROM AUTHOR]

Background: The optimal endovascular treatment (EVT) for chronic total occlusion (CTO) lesions in patients with peripheral artery disease (PAD) has remained unestablished. We encountered a patient with PAD in whom CTO was successfully treated using a novel technique that involved intravascular ultrasound (IVUS) and angled guiding catheter: IVUS Preceding with Angled guiDing catheter (I-PAD) technique. Case presentation: A 74-year-old male presented with intermittent claudication attributed to CTO of the right external iliac artery. EVT was performed via the right common femoral artery. We retrogradely advanced the I-PAD system (i.e. partially extending the IVUS transducer portion from the tip of the angled guiding catheter) in the CTO lesion under the real-time guidance of IVUS imaging. We successfully traversed the CTO lesion without the use of a guidewire in approximately three minutes. The procedure concluded successfully without any procedure-related complications, following optimal stenting. Conclusions: The I-PAD might be an effective technique to accurately, quickly, and safely pass through CTO lesions. [ABSTRACT FROM AUTHOR]

Background: For ischemic patients, left ventricular function is essential to their quality of life, and the major goal of coronary interventions is to keep the myocardium's blood supply productive. Thus, the complete cessation of blood flow to the myocardium for a prolonged duration is the obstacle to chronic total occlusion (CTO). Effective CTO coronary interventions improve the quality of life for the patient by improving LV systolic function, reducing angina, and increasing exercise capacity. Aim: This study aimed to compare the immediate changes that occur in the left ventricular systolic function in patients with CTO after successful revascularization in presence or absence of collateral circulation. Subjects and methods: This was an analytical cross-sectional study that was conducted at the Military Hospitals (Air Force, Maadi and Kobri El Koba Hospitals). Patients were recruited from the Cardiology Department from January 2023 to December 2023. Two groups were included: Group 1 included forty patients with CTO in any coronary artery more than 2.5 mm in its diameter with presence of ipsilateral or contralateral collateral circulation based on coronary angiography. Group 2 included other forty patients with CTO in any coronary artery more than 2.5 mm in its diameter with no collateral circulation based on the coronary angiography. Trans- thoracic echocardiography was done for all patients including both conventional (M-mode and 2D) and tissue Doppler strain rate studies 24 hours before PCI and two weeks after successful CTO PCI with final TIMI III flow. Results: Strain rate statistically significantly improved in group 1 compared to group 2 in terms of the septal and inferior wall segments 2 weeks after CTO opening. Conclusion: In CTO interventions, the presence of collateral circulation predicts immediate improvement in left ventricular systolic function as assessed by tissue Doppler intervention (TDI) using strain rate technique despite the lack of significant effect on conventional left ventricular systolic parameters as wall motion score index measurements. [ABSTRACT FROM AUTHOR]

Safety is of critical importance to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). This global consensus statement provides guidance on how to optimise the safety of CTO) PCI, addressing the following 12 areas: 1. Set-up for safe CTO PCI; 2. Guide catheter-–associated vessel injuries; 3. Hydraulic dissection, extraplaque haematoma expansion, and aortic dissections; 4. Haemodynamic collapse during CTO PCI; 5. Side branch occlusion; 6. Perforations; 7. Equipment entrapment; 8. Vascular access considerations; 9. Contrast-induced acute kidney injury; 10. Radiation injury; 11 When to stop; and, 12. Proctorship. This statement complements the global CTO crossing algorithm; by advising how to prevent and deal with complications, this statement aims to facilitate clinical practice, research, and education relating to CTO PCI. [ABSTRACT FROM AUTHOR]

To evaluate the characteristics and outcomes of patients with a chronic total occlusion (CTO) in a Non-ST Elevation Myocardial Infarction (NSTEMI) cohort. There is limited data on the clinical characteristics, revascularisation strategies and outcomes of patients presenting with a NSTEMI and a CTO. Retrospective analysis of a six-centre percutaneous coronary intervention (PCI) registry in the UK between January 2015 and December 2020 was performed. Patients with a NSTEMI with and without a CTO were compared for baseline characteristics and outcomes. There were 17,355 NSTEMI patients in total of whom 1813 patients had a CTO (10.4 %). Patients with a CTO were more likely to be older (CTO: 67.8 (±11.5) years vs. no CTO: 67.2 (±12) years, p = 0.04), male (CTO: 81.1 % vs.71.9 %, p < 0.0001) with a greater prevalence of cardiovascular risk factors. All-cause mortality at 30 days: HR 2.63, 95 % CI 1.42–4.84, p = 0.002 and at 1 year: HR: 1.87, 95 % CI 1.25–2.81, p = 0.003 was higher in the CTO cohort. CTO patients who underwent revascularisation were younger (Revascularisation 66.4 [±11.7] years vs. no revascularisation 68.4 [±11.4] years, p = 0.001). Patients with failed CTO revascularisation had lower survival (HR 0.21, 95 % CI 0.10–0.42, p < 0.0001). The mean time to revascularisation was 13.4 days. There was variation in attempt at CTO revascularisation between the 6 centres for (16 % to 100 %) with success rates ranging from 65 to 100 %. In conclusion, the presence of a CTO in NSTEMI patients undergoing PCI was associated with worse in-hospital and long-term outcomes. [Display omitted] • We assessed the clinical characteristics and outcomes of patients with a NSTEMI and a co-existing CTO from six UK centres. • Patients with a NSTEMI and CTO were likely to be older, male with increased prevalence of cardiovascular risk factors. • There was large variation in practice of attempted revascularisation of the CTO between centres. • Failed revascularisation of the CTO was associated with lower long term survival. [ABSTRACT FROM AUTHOR]

Aims Current assessment of myocardial ischaemia from stress perfusion cardiovascular magnetic resonance (SP-CMR) largely relies on visual interpretation. This study investigated the use of high-resolution free-breathing SP-CMR with automated quantitative mapping in the diagnosis of coronary artery disease (CAD). Diagnostic performance was evaluated against invasive coronary angiography (ICA) with fractional flow reserve (FFR) measurement. Methods and results Seven hundred and three patients were recruited for SP-CMR using the research sequence at 3 Tesla. Of those receiving ICA within 6 months, 80 patients had either FFR measurement or identification of a chronic total occlusion (CTO) with inducible perfusion defects seen on SP-CMR. Myocardial blood flow (MBF) maps were automatically generated in-line on the scanner following image acquisition at hyperaemic stress and rest, allowing myocardial perfusion reserve (MPR) calculation. Seventy-five coronary vessels assessed by FFR and 28 vessels with CTO were evaluated at both segmental and coronary territory level. Coronary territory stress MBF and MPR were reduced in FFR-positive (≤0.80) regions [median stress MBF: 1.74 (0.90–2.17) mL/min/g; MPR: 1.67 (1.10–1.89)] compared with FFR-negative regions [stress MBF: 2.50 (2.15–2.95) mL/min/g; MPR 2.35 (2.06–2.54) P < 0.001 for both]. Stress MBF ≤ 1.94 mL/min/g and MPR ≤ 1.97 accurately detected FFR-positive CAD on a per-vessel basis (area under the curve: 0.85 and 0.96, respectively; P < 0.001 for both). Conclusion A novel scanner-integrated high-resolution free-breathing SP-CMR sequence with automated in-line perfusion mapping is presented which accurately detects functionally significant CAD. [ABSTRACT FROM AUTHOR]

Identifying the detailed anatomies of the coronary microvasculature remains an area of research; one needs to develop methods for non-destructive, high-resolution, three-dimensional imaging of these vessels for computational modeling. Currently employed Micro-Computed Tomography (Micro-CT) protocols for vasa vasorum analyses require organ dissection and, in most cases, non-clearable contrast agents. Here, we describe a method developed for a non-destructive, economical means to achieve high-resolution images of the human coronary microvasculature without organ dissection. Formalin-fixed human hearts were cannulated using venogram balloon catheters, which were then fixed into the specimen's aortic root. The canulated hearts, protected by a polyethylene bag, were placed in radiolucent containers filled with insulating polyurethane foam to reduce movement. For vasculature staining, iodine potassium iodide (IKI, Lugol's solution; 6.3% Potassium Iodide, 4.1% Iodide) was injected. Contrast distributions were monitored using a North Star Imaging X3000 micro-CT scanner with low-radiation settings, followed by high-radiation scanning (3600 rad, 60 kV, 900 mA) for the final high-resolution imaging. We successfully imaged four intact human hearts presenting with chronic total coronary occlusions of the right coronary artery. This imaging enabled detailed analyses of the vasa vasorum surrounding stenosed and occluded segments. After imaging, the hearts were cleared of iodine and excess polyurethane foam and returned to their initial formalin-fixed state for indefinite storage. Conclusions: the described methodologies allow for the non-destructive, high-resolution micro-CT imaging of coronary microvasculature in intact human hearts, paving the way for detailed computational 3D microvascular reconstructions with a macrovascular context. [ABSTRACT FROM AUTHOR]

Background: Quantitative flow ratio (QFR) and target-vessel SYNTAX score (tvSS) are novel indices used to assess lesion physiology and morphology in percutaneous coronary intervention (PCI). Their prognostic implication after successful recanalization of coronary chronic total occlusion (CTO) is unknown. Objectives: To investigate the prognostic value of QFR measured immediately after successful CTO-recanalization in predicting vessel-oriented adverse events, and to compare it with the pre-procedural morphological tvSS. Methods: QFR was measured offline after successful CTO-PCIs in a single center. We grouped the patients according to a cut-off value of post-PCI QFR (0.91). The primary outcome was target-vessel failure (TVF) at 2 years. Results: Among 470 CTO lesions performed during the study period, 324 were eligible for QFR analysis (258 with QFR ≥ 0.91 and 66 with QFR < 0.91). The mean age of the study population was 68.3 ± 10.7 years. The low QFR group had a lower left ventricular ejection fraction (45.8 ± 13.9% vs. 49.8 ± 12.4%, p = 0.025) and a higher rate of atrial fibrillation (19.7% vs. 11.2%, p = 0.020). The mean tvSS was 12.8 ± 4.8, and it showed no significant difference in both groups (13.6 ± 5.1 vs. 12.6 ± 4.6, p = 0.122). Patients with low post-CTO QFR had a trend to develop more TVF at 2 years (21.2% vs. 12.4%, HR 1.74; 95% CI 0.93–3.25, p = 0.086). Low post-CTO QFR failed to predict 2-year TVF (aHR 1.67; 95% CI 0.85–3.29, p = 0.136), while pre-procedural tvSS was an independent predictor for 2-year TVF (aHR 1.06; 95% CI 1.01–1.13, p = 0.030). Conclusion: We found a limited prognostic value of immediate physiological assessment using QFR after successful CTO intervention. Pre-procedure morphological characteristics of CTO lesions using tvSS can play a role in predicting long-term adverse events. [ABSTRACT FROM AUTHOR]

Background: With advancements in chronic total coronary occlusion (CTO) recanalization techniques and concepts, the success rate of recanalization has been steadily increasing. However, the current data are too limited to draw any reliable conclusions about the efficacy and safety of drug-coated balloons (DCBs) in CTO percutaneous coronary intervention (PCI). Herein, we conducted a meta-analysis to confirm the efficacy of DCB in CTO PCI. Methods: We systematically searched PubMed, Web of Science and Embase from inception to July 25, 2023. The primary outcome was major advent cardiovascular events (MACE), including cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR). The follow-up angiographic endpoints were late lumen enlargement (LLE), reocclusion and restenosis. Results: Five studies with a total of 511 patients were included in the meta-analysis. Across studies, patients were predominantly male (72.9-85.7%) and over fifty years old. The summary estimate rate of MACE was 13.0% (95% CI 10.1%-15.9%, I2 = 0%, p = 0.428). The summary estimate rates of cardiac death and MI were 2.2% (95% CI 0.7%-3.7%, I2 = 0%, p = 0.873) and 1.2% (95% CI -0.2-2.6%, I2 = 13.7%, p = 0.314), respectively. Finally, the pooled incidences of TLR and TVR were 10.1% (95% CI 5.7%-14.5%, I2 = 51.7%, p = 0.082) and 7.1% (95% CI 3.0%-11.2%, I2 = 57.6%, p = 0.070), respectively. Finally, the summary estimate rates of LLE, reocclusion and restenosis were 59.4% (95% CI 53.5–65.3%, I2 = 0%, p = 0.742), 3.3% (95% CI 1.1–5.4%, I2 = 0%, p = 0.865) and 17.5% (95% CI 12.9–22.0%, I2 = 0%, p = 0.623), respectively. Conclusion: Accordingly, DCB has the potential to be used as a treatment for CTO in suitable patients. [ABSTRACT FROM AUTHOR]

Background: Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) for chronic total coronary occlusions (CTOs) improves clinical symptoms and quality of life. However, data on drug-coated balloon (DCB)-based PCI in CTO lesions are limited. Methods: A total of 200 patients were successfully treated for CTO lesions, either with DCB alone or in combination with DES (DCB-based PCI). They were compared with 661 patients who underwent second-generation DES implantation for CTO from the PTRG-DES registry (DES-only PCI). The endpoint was major adverse cardiovascular events (MACEs), which included a composite of cardiac death, myocardial infarction, stent or target lesion thrombosis, target vessel revascularization, and major bleeding at 2 years. Results: In the DCB-based PCI group, 49.0% of patients were treated with DCB only and 51.0% underwent the hybrid approach combining DCB with DES. Bailout stenting was performed in seven patients (3.5%). The DCB-based PCI group exhibited fewer stents (1.0; IQR: 0.0–1.0 and 2.0; IQR: 1.0–3.0, p < 0.001), shorter stent lengths (6.5 mm; IQR: 0.0–38.0 mm and 42.0 mm; IQR: 28.0–67.0 mm, p < 0.001), and lower usage of small stents with a diameter of 2.5 mm or less (9.8% and 36.5%, p < 0.001). Moreover, the DCB-based PCI group had a lower rate of MACEs than the DES-only PCI group (3.1% and 13.2%, p = 0.001) at 2-year follow-up. Conclusions: The DCB-based PCI approach significantly reduced the stent burden, particularly in the usage of small stent diameters, and resulted in a lower risk of MACEs compared to DES-only PCI in CTO lesions. [ABSTRACT FROM AUTHOR]

Despite the effectiveness of the retrograde approach for chronic total occlusion (CTO) lesions, there are no standardized tools to predict the success of retrograde percutaneous coronary intervention (PCI). The aim of this study was to develop a prediction tool to identify CTO lesions that will achieve successful retrograde PCI. This study evaluated data from 2,374 patients who underwent primary retrograde CTO-PCI and were enrolled in the Japanese CTO-PCI Expert Registry between January 2016 and December 2022 (NCT01889459). All observations were randomly assigned to the derivation and validation cohorts at a 2:1 ratio. The prediction score for guidewire failure in retrograde CTO-PCI was determined by assigning 1 point for each factor and summing all accrued points. The JR-CTO score (moderate–severe calcification, tortuosity, Werner collateral connection grade ≤1, and nonseptal collateral channel) demonstrated a C-statistic for guidewire failure of 0.72 (95% CI: 0.67-0.76) and 0.71 (95% CI: 0.64-0.77) in the derivation and validation cohorts, respectively. Patients with lower scores had higher guidewire and technical success rates and decreased guidewire crossing time and procedural time (P < 0.01). The JR-CTO (Japanese Retrograde Chronic Total Occlusion) score, a simple 4-item score that predicts successful guidewire crossing in patients undergoing retrograde CTO-PCI, has the potential to support clinical decision-making for the retrograde approach. [Display omitted] [ABSTRACT FROM AUTHOR]

The percutaneous management of chronic total occlusions (CTO) is a well-established sub-specialty of Interventional Cardiology, requiring specialist equipment, training, and techniques. The heterogeneity of approaches in CTO has led to the generation of multiple algorithms to guide operators in their management. The evidence base for management of CTOs has suffered from inconsistent descriptive and quantitative terminology in defining the nature of lesions and techniques utilised, as well as seemingly contradictory data about improvement in ventricular function, symptoms of angina, and mortality from large-scale registries and randomised controlled trials. Through this review, we explore the history of CTO management and its supporting evidence in detail, with an outline of limitations of CTO-percutaneous coronary intervention and a look at the future of this growing field within cardiology. [ABSTRACT FROM AUTHOR]

Objectives: To systematically investigate and summarize the utility of coronary computed tomographic angiography (CCTA) in the management of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). Methods: The authors searched the four databases between 2005 and 2023 for studies investigating the role of CCTA and invasive coronary angiograms (ICA) images when used as the pre-procedural tool for CTO-PCI. Efficacy and safety of CCTA in CTO-PCI treatment as a pre-procedural assessment tool was evaluated. Results: Forty-seven studies were finally chosen for this systematic review. CCTA had a high degree of agreement with ICA when applied for J-CTO scoring system. A J-CTO (Multicenter CTO Registry in Japan) score > 3, together with calcification, occlusion length ≥ 20 mm, blunt stump, and bending > 45° were shared imaging risk factors on both ICA and CCTA for technique failure and guidewire crossing over 30 min. Additionally, negative remodeling and multiple diseased vessel were significant indicators on CCTA. Although patients with pre-procedural CCTA showed a trend of higher success rate and easier guidewire crossing, and CCTA showed a slightly higher predictive accuracy for process success, no significant improvement in post-PCI major adverse cardiac events of using CCTA for assessment has been achieved. Conclusions: CCTA is a safe and effective pre-operative tool of CTO-PCI. Except for the shared imaging risk factors with ICA for a hard CTO-PCI including calcification, occlusion length ≥ 20 mm, blunt stump, bending > 45°, and J-CTO score > 3, factors like negative remodeling and multiple diseased vessel were also recognized as significant pre-operative assessment indicators on CCTA. Clinical relevance statement: A pre-procedural assessment based on coronary computed tomographic angiography has the potential to aid in the management of chronic total occlusion percutaneous coronary intervention. Key Points: • A coronary computed tomographic angiography–based pre-procedural assessment can help chronic total occlusion-percutaneous coronary intervention management. • The recognized high-risk features detected via coronary computed tomographic angiography and invasive coronary angiograms are comparable in detecting difficult lesions and chronic total occlusion-percutaneous coronary intervention failure. • Coronary computed tomographic angiography has an additional value to be a safe and effective pre-procedural assessment tool for chronic total occlusion-percutaneous coronary intervention. [ABSTRACT FROM AUTHOR]

There is a need for improved outcomes in the endovascular treatment of patients suffering from chronic limb threatening ischaemia (CLTI), highly calcified lesions, and chronic total occlusions (CTOs). The helical centreline self expanding BioMimics 3D stent might be particularly useful in these high risk subsets, combining flexibility and fracture resistance with radial strength. Herein, the performance of the BioMimics 3D stent was assessed in these high risk subsets. MIMICS-3D is a prospective, multicentre, European real world registry. This was a post hoc analysis, comparing patients with CLTI vs. intermittent claudication (IC), lesions with bilateral calcification vs. those without (peripheral arterial calcium scoring system [PACSS] 3,4 vs. PACSS 0 – 2), and CTO vs. no CTO. Propensity score matching was performed to reduce the impact of baseline variables. The 36 month endpoints were clinically driven target lesion revascularisation (CD-TLR), death, major target limb amputation, and stent patency. A total of 507 patients were enrolled. At 36 months, patients with CLTI had lower freedom from major amputation than patients with IC (92.6% vs. 100%, p <.001). In terms of primary patency, patients with CTO had lower patency rates than those without (63.9% vs. 77.8%, p =.003), but the difference reduced after propensity score matching (70.5% vs. 76.8%, p =.43). Primary patency was not impaired for patients with PACSS 3,4 or patients with CLTI. Freedom from CD-TLR was not significantly different among the groups and was 73.8% for CLTI vs. 78.9% for IC (p =.15), 77.6% for PACSS 3,4 vs. 78.7% for PACSS 0 – 2 (p =.55), and 75.6% for CTO vs. 81.0% for no CTO (p =.11). The outcome of the MIMICS-3D registry suggests that the BioMimics 3D stent is effective in the endovascular treatment of complex femoropopliteal lesions and in CLTI. Future randomised controlled trials should confirm its non-inferiority or superiority compared with existing alternatives. [ABSTRACT FROM AUTHOR]

Purpose: In the present trial, the 24-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and proximal popliteal artery (PA) were evaluated in Japanese patients. Methods: This was a prospective, multicenter, core laboratory-adjudicated, single-arm trial. From 2019 to 2020, 121 patients with symptomatic peripheral artery disease were enrolled. The primary effectiveness outcome measure was primary patency. The safety outcome measure was the major adverse event (MAE) rate. Results: Age was 74.5 ± 7.3 years, and diabetes mellitus was present in 67.5%. Lesion length and reference vessel diameter (RVD) were 106.0 ± 52.6 mm and 5.2 ± 0.8 mm, respectively. Chronic total occlusion (CTO) and bilateral calcification rate (Grade 3 and 4 by peripheral arterial calcium scoring system (PACSS)) were 17.5% and 50.8%, respectively. The 24-month primary patency rate by duplex ultrasound was 71.3%, while freedom from clinically driven target lesion revascularization (CD-TLR) was 87.0%. The MAE rate was 13.2% and all events consisted of CD-TLR. There were no instances of device- or procedure-related deaths major amputations throughout the 24 months. Multivariate Cox proportional hazards regression analysis revealed significant differences associated with loss of primary patency in the following characteristics: CTO, restenotic lesion and RVD. Conclusion: This trial confirmed the safety and effectiveness of TCD-17187 DCB for atherosclerotic lesions of the SFA and/or proximal PA for up to 24 months. Level of Evidence: Level 3, Cohort study. Clinical Trial Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000038612&type=summary&language=J:Registration ID: UMIN000034122. Registration Date: September 13, 2018. [ABSTRACT FROM AUTHOR]