Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be technically complex. Coronary computed tomography angiography (CTA) is increasingly being used for planning CTO PCI. Coronary CTA can help evaluate cap morphology, lesion length, calcification, and distal vessel quality. The use of coronary CTA for CTO PCI may be enhanced by integration with artificial intelligence and real-time imaging. In a randomized controlled trial, preprocedural coronary CTA increased the success of CTO PCI. In this review, the authors describe how coronary CTA can help diagnose and characterize CTO lesions, estimate the time needed for guidewire crossing time, predict and facilitate CTO PCI technical success, and provide real-time procedural guidance.

BACKGROUND:Epicardial collaterals represent a conduit for retrograde crossing in chronic total occlusion (CTO) percutaneous coronary intervention (PCI), but carry higher procedural risk compared with septal or bypass graft crossing. METHODS:We analyzed 1527 CTO PCI cases attempted via epicardial collaterals between January 2012 and March 2026 from the PROGRESS-CTO multicenter registry (49 centers). Temporal trends were assessed using logistic regression. Technical success, procedural success, and in-hospital major adverse cardiac events (MACE) were evaluated. RESULTS:Mean patient age was 65 ± 10 years; 86.4% were men. Lesion complexity was high (mean J-CTO score 3.16 ± 1.02). Use of the retrograde approach overall and via epicardial collaterals decreased significantly over time (both p < 0.001). Epicardial collateral crossing success increased (p < 0.001), while MACE rates did not change significantly (p = 0.085). Technical and procedural success were 77.0% and 74.4%, respectively. In-hospital MACE occurred in 3.8% of cases. Coronary perforation occurred in 13.8% of procedures and was strongly associated with MACE (15.2% vs. 2.0%, p < 0.001). CONCLUSIONS:In a large contemporary multicenter registry, while use of retrograde CTO PCI via epicardial collaterals declined over time, crossing success improved without a significant increase in complications, suggesting improved case selection and procedural expertise.

BACKGROUND:The safety and efficacy of protamine reversal of heparin anticoagulation during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is unknown. To outline the indications for and outcomes of protamine administration during CTO PCI. METHODS:We conducted a multicenter registry of consecutive patients who underwent CTO PCI between January 2019 and March 2025 at five centers and received protamine. Patients were stratified into bailout (for perforation or access-site bleeding) and non-bailout cohorts. The primary endpoint was major adverse cardiovascular events (all-cause death, myocardial infarction, target vessel revascularization, and pericardiocentesis). Outcomes were reported descriptively by indication for protamine use, without formal comparative analysis. RESULTS:Among 2345 CTO PCI procedures, 672 patients (28.7%) received protamine, including 179 in the bailout cohort and 493 in the non-bailout cohort. The mean J-CTO score was 3.0 ± 1.3 in the bailout cohort and 2.6 ± 1.2 in the non-bailout cohort. Retrograde strategies were used in 31.8% of the bailout cohort and 19.3% of the non-bailout cohort. Overall, there were 126 coronary perforations observed (6.1%), of which 10 cases (0.5%) required pericardiocentesis. In-hospital major adverse cardiovascular events occurred in 20 patients (11.2%) in the bailout cohort and in 10 patients (2.0%) in the non-bailout cohort (reported descriptively without comparative inference). Across both cohorts, there were no reported cases of stent thrombosis or anaphylaxis. CONCLUSION:Protamine use during CTO PCI was variably applied across centers and was associated with acceptable in-hospital outcomes; however, the lack of a non-protamine comparison group limits any inference regarding safety.

Background: Icosapent Ethyl (IPE) is a highly purified ethyl ester of eicosapentaenoic acid (EPA), shown to reduce the risk of major adverse cardiovascular events (MACE) and mortality in patients with atherosclerosis and hypertriglyceridemia. Preclinical investigations of atherosclerosis and arterial thrombosis demonstrate anti-inflammatory and anti-thrombotic properties of IPE in vivo. However, its mechanistic and functional impact on deep venous thrombosis (DVT) and post-thrombotic syndrome (PTS) remains undefined. Here, we investigated the effect of IPE on murine DVT resolution and post-thrombotic vein wall fibrosis, a key driver of PTS. Methods: C57/BL6 male mice (n=57) underwent inferior vena cava (IVC) ligation to induce complete stasis DVT on Day 0. On Day 2, mice were randomized to receive vehicle control (phosphate buffered saline (PBS) with 0.5% Tween80) or IPE (615 mg/kg/day with Tween80 0.5%), via gavage. Treatment continued for six days until D8 sacrifice. Then, thrombus with and without the vein wall were harvested for weight, length, width and normalized thrombus weight (weight/length) measurements and vein wall analysis. D8 vein wall collagen thickness (VWCT) was assessed using picrosirius red (PSR) analysis. Results: IPE reduced VWCT at day 8 (IPE: 28.90 ± 0.69 µm vs. Control: 34.84 ± 4.27 µm, n=16 sections/group; p= 0.029, Fig. 1A), as assessed by PSR analysis. Two-way repeated measures ANOVA revealed a consistent overall treatment effect across thrombus levels (p=0.039, Fig. 1C). In addition, IPE treatment resulted in trend reduction in median thrombus weight (IPE: 13.50 mg, IQR 4.50 vs. Control: 15.00 mg, IQR 4.00; n=12-19/group; p=0.130, Fig. 1D) and normalized thrombus weight (IPE: 19.22 mg/cm, IQR 4.22 vs. Control: 21.46 mg/cm, IQR 3.89; n=12-19/group; p=0.064, Fig. 1E). IPE treatment did not significantly affect median thrombus width or length (IPE: 0.65 cm, IQR 0.18 vs. Control: 0.73 cm, IQR 0.12; n=12-19/group; p=0.435, Fig. 1F). Unless noted, comparisons used the Mann–Whitney U test. Conclusion: IPE attenuates vein wall fibrosis and modestly reduces thrombus burden in complete stasis murine DVT. These findings suggest that IPE favourably influences thrombus resolution and vein wall remodelling and support further mechanistic investigation of IPE’s potential as an adjunct therapy for reducing PTS. Ongoing analyses will further characterize the effect of IPE on inflammatory and collagen synthetic mediators in DVT resolution.

BACKGROUND:Ulnar artery access may provide an alternative access route for chronic total occlusion percutaneous coronary intervention (CTO PCI), but data is limited. AIMS:To assess the utilization, patient characteristics, and in-hospital outcomes of ulnar artery access compared with radial access and non-ulnar access in patients undergoing CTO PCI. METHODS:We analyzed patients who underwent CTO PCI between 2012 and 2024 at 51 centers within the PROGRESS-CTO Registry. Patients were stratified by access: (1) no radial/ulnar, (2) radial without ulnar, and (3) ulnar. The primary endpoint was in-hospital major adverse cardiovascular events (MACE). Secondary endpoints included technical success. Multivariable logistic regression was used to identify independent predictors of outcomes. RESULTS:Among 18,826 patients, 8844 (47.0%) had no radial/ulnar access, 9835 (52.2%) radial without ulnar, and 147 (0.8%) ulnar. Ulnar patients were younger (62.5 ± 10.4 vs. 64.0 ± 10.4 radial and ulnar, 65.1 ± 10.5 no radial/ulnar, p < 0.001) and had higher prevalence of prior PCI (73.6% vs. 59.3% and 64.0%, p < 0.001) and peripheral arterial disease (23.9% vs. 12.1% and 15.1%, p < 0.001). Lesion complexity was lower with ulnar access (J-CTO 2.19 ± 1.27 vs. 2.32 ± 1.27 radial and 2.47 ± 1.21 no radial/ulnar, p < 0.001). In-hospital outcomes were similar: MACE (2.7% ulnar vs. 1.8% radial vs. 2.0% no radial/ulnar, p = 0.315), technical success (83.7% vs. 87.3% vs. 87.2%, p = 0.425), and access complications (0.7% vs. 0.7% vs. 1.2%, p = 0.001). Logistic regression showed no independent association between ulnar access and MACE, technical success, or access-site complications. CONCLUSION:In the largest series to date, ulnar access was used in 0.8% of CTO PCI with similar outcomes to radial and femoral access. Given its use in lower complexity cases, these findings are hypothesis-generating and warrant prospective evaluation.

BACKGROUND:Post thrombotic syndrome is a fibrotic disease related to inflammation resolution. There are no direct therapies that can ameliorate this disease. Monocyte/macrophages (Mo/MØ) are the primary leukocyte involved with later venous resolution, and likely direct vein wall responses and healing. Herein, we explored the vein wall response with Mo/MØ depletion by two methods. METHODS:Using two mouse models of venous thrombosis (VT), complete stasis and a flow restricted model, Mo/MØ depletion was accomplished using CD11b-DTR mice administered diphtheria toxin, and clodronate micelle administration in wild type mice. Tissue assays for structural histology, immunohistochemistry and western blotting were performed. RESULTS:Mo/MØ depletion resulted in significantly less vein wall fibrotic thickness, in the stasis model at day 14 in both the CD11b-DTR mice and those receiving clodronate micelles. No significant effect of Mo/MØ depletion was observed in the flow restricted VT model. The decrease in vein wall fibrosis was associated with fewer DDR2+ vein wall cells in the CD11b-DTR mice, but no difference in endothelial luminal coverage. Decreased cytokine and growth factor expression of IL-6, FSP-1, and VEGFa were associated with Mo/MØ depletion. Lastly, PMN depletion was associated with increased proinflammatory Mo/MØ, and a trend towards increased vein wall fibrosis as compared with controls. CONCLUSION:Mo/MØ direct the post VT late fibrotic response, possibly by affecting fibroblasts and inflammatory cytokine expression. This effect was only found with the complete stasis model and is consistent with worsened PTS in humans with complete venous obstruction.

Background: Atherosclerotic plaque inflammation, driven by activated macrophages, is a major contributor to plaque rupture and acute coronary syndromes. Somatostatin receptor subtype 2 (SSTR2), expressed on activated macrophages, represents an ideal target for molecular imaging, and has been imaged in larger arteries using clinical PET imaging. This study evaluates the potential of a novel near-infrared fluorescence (NIRF) somatostatin-based probe to image macrophage-driven plaque inflammation, with new potential applicability to human coronary sized arteries. Methods: The binding specificity of the NIRF probe was evaluated in vitro using human macrophages with or without activation by lipopolysaccharide (LPS, 100 ng/mL) and imaged at 1, 6, and 24 hours post-incubation. The pharmacokinetics and biodistribution of the probe were assessed in C57BL/6J mice via fluorescence reflectance imaging. Specificity was validated through competitive inhibition with excess unlabeled somatostatin. The probe’s plaque-targeting efficacy was tested in atherosclerotic ApoE-/- mouse model (N=6) using intravital fluorescence microscopy (IVM), followed by FM and immunohistochemical detection of SSTR2 and macrophage CD68 expression Results: The probe demonstrated significant and specific uptake by LPS-stiumlated macrophages, with enhanced NIRF signal intensity on microscopy compared to controls (Fig 1A and B p <0.05). In vivo biodistribution studies revealed rapid clearance, with a calculated blood half-life of 15.79 minutes (Fig 1C), and preferential accumulation in macrophage-rich organs such as the liver and spleen. Competitive inhibition with excess unlabeled somatostatin resulted in a significant reduction in probe uptake in hepatic tissue (p<0.01),. In carotid plaques of ApoE-/- mice (Fig 1D), the probe showed substantial accumulation in macrophage-rich regions on IVM, with NIRF signal peaking at 60 minutes post-injection (Fig 1E; normalized intensity ratio: 4.41, p<0.05). Histological analysis (Fig 1F) demonstrated robust colocalization of the SMT probe signal with SSTR2 (Fig 1G; r=0.71, p=0.001) and CD68 (Fig 1G; r=0.54, p=0.002). Conclusions: This somatostatin-based NIRF probe shows rapid pharmacokinetics, high specificity for SSTR2+ macrophages, and strong efficacy in imaging inflamed plaques. It lays the groundwork for intravascular NIRF imaging to detect high-risk plaques, now under clinical evaluation

The global chronic total occlusion (CTO) crossing algorithm was developed by experts to improve CTO percutaneous coronary intervention (PCI) outcomes but has yet to be validated using real-world data. To evaluate the association between adherence to the global CTO crossing algorithm and outcomes in CTO PCI. We examined the clinical and angiographic characteristics and procedural outcomes of 13,852 CTO PCIs at 43 US and non-US centers between 2012 and 2025. Adherence to the global CTO crossing algorithm was defined using 3 characteristics: proximal cap ambiguity, poor distal vessel quality, and use of primary antegrade dissection/re-entry (ADR). Among 13,852 CTO PCIs, 70% (n = 9,693) followed the global CTO crossing algorithm. Discordant cases more frequently involved the right coronary artery (61.5% vs 49.4%, p < 0.001) and exhibited greater complexity: longer occlusions, proximal cap ambiguity, blunt/no stump, poor distal vessel quality, and calcification (all p < 0.001). Discordant lesions also had a higher J-CTO score (2.55 ± 1.18 vs 2.23 ± 1.27; p < 0.001). Algorithm adherence was associated with higher crossing success with the initially selected technique (72.5% vs 49.4%), technical (87.9% vs 85.6%), and procedural success (86.7% vs 84.2%) (all p < 0.001). The incidence of perforation was lower in concordant cases (4.1% vs 6.1%; p < 0.001), although major adverse cardiovascular events (MACE) were comparable. On multivariable analysis, algorithm adherence was independently associated with technical success (odds ratio 1.22; 95% confidence interval 1.04-1.42; p = 0.014). Adherence to the global CTO crossing algorithm is associated with greater crossing success using the initially selected strategy, higher technical success, and similar in-hospital MACE.

Coronary computed tomography angiography (CCTA) is emerging as a valuable adjunct for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), particularly for lesions in which angiography incompletely defines procedural anatomy. In this systematic review, the authors evaluated the role of CCTA in CTO diagnosis, lesion characterization, prediction of guidewire crossing and procedural success, and procedural guidance. CCTA provides a detailed assessment of key features that directly influence CTO PCI strategy and outcomes. Randomized and observational data suggest that preprocedural CCTA can improve procedural planning, increase technical success in complex lesions, and support safer and more efficient CTO PCI through fluoroscopic co-registration and other real-time guidance applications. These findings highlight the clinical value of CCTA as a tool that can enhance case selection, optimize crossing strategy, and improve procedural success in contemporary CTO PCI.

Objective: The combination of near-infrared fluorescence (NIRF) with intravascular ultrasound (IVUS) has shown promising applications for imaging atherosclerosis in ex vivo human arteries and in vivo animal models. However, long acquisition times, rotational distortion causing inconsistent image quality and poor catheter durability have hampered clinical translation. Technical limitations have included motor drive unit (MDU) instability, and catheter designs with a single-layer drive shaft and long rigid length of the distal tip. Methods: Herein, we present an improved, next-generation NIRF-IVUS system by integrating an aluminum v-block-based high-speed MDU and 3.0 French (∅ = 1.0mm) catheter with a dual-layer drive shaft and reduced rigid tip length. We show a sixfold increase in imaging speed (30 FPS, 6 mm/s pullback) mirroring speed capabilities of standalone, commercial IVUS imaging. Results: In phantoms, we find that key NIRF-IVUS specifications like co-registration, rotational stability and NIRF resolution/sensitivity are preserved. Furthermore, we demonstrate that NIRF-IVUS molecular imaging of cathepsin protease activity can highlight stent-induced arterial inflammation independent of imaging speed, in rabbits in vivo. We calculate similar (not significant, p = 0.65) NIRF target-to-background ratios (TBRs) in stented tissue areas at low-speed (1.88) and high-speed (2.00) imaging. Finally, in vivo NIRF-IVUS imaging of FDA-approved indocyanine green detects early-stage plaques in rabbit aorta not visible on standalone IVUS. Similar NIRF TBRs are calculated in low-speed (4.13) and high-speed (4.08) pullbacks. Conclusion and Significance: Our study demonstrates that NIRF-IVUS can highlight key pathobiological markers of atherosclerosis beyond standalone IVUS at clinical imaging speeds, further supporting the clinical translation of the NIRF-IVUS technology.

Background: Deep vein thrombosis (DVT) leads to post-thrombotic syndrome (PTS) in around 30-50% of patients despite anticoagulation. Catheter-based thrombectomy/ thrombolysis (CDT) lacks consistent efficacy in preventing PTS. Locally delivered steroids such as dexamethasone (DEX), are currently under clinical evaluation as an adjunct to CDT in the DEXTERITY-AFP trial (NCT04862468) with the aim of reducing PTS, but minimal mechanistic data for DEX exists regarding DVT resolution. Here, we hypothesized that perivascular local DEX will improve DVT resolution and reduce vein wall fibrosis in experimental murine DVT. Method: Male C57BL/6J mice (n=146) underwent complete inferior vena cava (IVC) ligation to induce stasis DVT on day 0, followed by surgical de-ligation on day 2 to simulate CDT/MT and spur restoration of blood flow (RBF), as determined by a non-invasive ultrasound (IVC flow velocity > 0 mL/sec). On day 2, periadventitial PBS or DEX (0.05–0.5 mg/mouse) was administered via a 30G needle, followed by serial ultrasonography to evaluate RBF. On day 8, thrombus burden and vein wall remodeling were assessed using immunohistochemistry, RNA sequencing, and qRT-PCR. Results: DEX 0.1mg/mouse significantly reduced day 8 thrombus burden (p=0.0006), thrombus weight (p=0.008), and intra-thrombus CD68+ macrophages (p=0.007) in IVC DVT (Fig. A). Higher (0.2–0.5 mg/mouse) and lower (0.05 mg/mouse) DEX doses also did not worsen thrombus burden. DEX 0.1mg/mouse decreased day 8 vein wall collagen thickness (p=0.0001), DDR2+ fibroblasts (p=0.001) and CD68+ macrophages (p=0.04) in vein wall and perivascular region (Fig. B, C) and improved mean blood flow velocity in thrombosed IVCs on days 4-8. Predictively, the day 4 RBF+ status correlated with reduced day 8 vein wall collagen thickness with DEX reducing VWCT irrespective of RBF status (RBF+PBS; 62.04µm, RBF-PBS; 51.31µm, RBF-DEX; 29.05µm, RBF+DEX; 20.63µm, Fig. D). Further, global transcriptome of DEX/PBS treated vein walls revealed downregulation of collagen synthesis pathways (Fig. E), supporting the antifibrotic effects of DEX. Conclusion: In conclusion, locally delivered DEX improves murine stasis DVT resolution by improving early venous blood flow, and then reducing thrombus burden, vein wall injury, and macrophage content. These findings underscore the potential of targeted perivascular steroid therapy as an adjuvant to CDT in patients undergoing thrombectomy and provide mechanistic support for the DEXTERITY trials.

Background: Real-time assessment of leukocyte subsets in atherosclerosis is limited by gating and motion artifacts in large arteries. We describe a femoral artery ligation–induced model of accelerated atherosclerosis that enables ungated intravital multiphoton microscopy (MPM) of immune cell trafficking in free-breathing mice. Using this, we tracked plaque CD11b+ cells in vivo and evaluated CD11b+ subsets based on uptake of low–molecular weight FITC–dextran (LMW-FD), a feature of M2-slanted pinocytosis-capable macrophages. Aims: To (i) develop an accelerated femoral atherosclerosis model capable of motion-compensated free-breathing MPM (ii) track CD11b+ subsets based on LMW-FD uptake in atheroma in vivo. Methods: Male ApoE-/- mice (N=104) were used to develop a femoral artery double ligation model of accelerated atherosclerosis (Figure, A.) After establishing consistent lesions in 84 mice, MPM cell tracking was performed in 20 mice. On day 14, the femoral artery was surgically exposed, and MPM imaging was performed for 1 hr following intravenous injection of a CD11b–647 ab and 3 kDa LMW-FD. After MPM, femoral plaques were harvested for histological analyses. iNOS immunofluorescence assessed colocalization between CD11b+ cells retaining LMW-FD (CD11b+ LMW-FD+) and iNOS+ cells. MPM analyses focused on CD11b and LMW-FD uptake in intimal plaque regions, with colocalization quantified by Manders’ correlation coefficient (MCC). Results: Day 14 post-ligation plaques harvested from the femoral artery exhibited key features of atherosclerosis, including increased inflammation (CD68+) and lipid deposition (Sudan Black+). The femoral model enabled motion-compensated MPM with stable single-cell tracking, capturing CD11b+ leukocyte deceleration during rolling and firm adhesion, and retention of LMW-FD in a subset of CD11b+ cells. Most plaque CD11b+ cells were also LMW-FD+ in vivo (MCC= 67±22%, n=13) and on ex vivo frozen sections (MCC= 72±10%, n=18). CD11b+LMW-FD+ cells colocalized less often with the inflammatory marker iNOS (MCC= 9.8%±3.7%) compared with CD11b+LMW-FD- cells (MCC= 33.1%±16.4%) (Figure). Conclusion: An accelerated femoral atherosclerosis model enables simplified, free-breathing, non-cardiac gated MPM tracking of CD11b+ leukocytes in vivo. MPM revealed a subset of CD11b+ cells that can retain 3kDa LMW-FD. These cells show reduced iNOS colocalization, indicating the potential to further investigate this M2-slanted macrophage subset in atheroma progression.

Background: The impact of prior myocardial infarction (MI) on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains understudied. Methods: We compared the characteristics and outcomes of 15,461 patients with versus without history of prior MI who underwent 15,478 CTO PCIs between 2012-2025 at 58 US and non-US centers (PROGRESS-CTO registry). Results: 43.2% (n=6,677) of the patients had history of prior MI. Prior MI patients were younger and more likely to be men, to have hypertension, lower left ventricular ejection fraction, cerebrovascular and peripheral arterial disease. Patients with prior MI that did not have prior PCI (22.8%), were more likely to have a myocardial viability test performed (32.6% vs 27.3%, p<0.001). The lesions of patients with prior MI had higher J-CTO (2.41 vs 2.34, p<0.001) and PROGRESS-CTO (1.25 vs 1.16, p<0.001) scores, higher lesion diameter, longer lesion length, were more likely to have proximal cap ambiguity (35.5% vs 33.8%, p=0.035), side branch at the proximal cap (58.3% vs 56.2%, p=0.014) and moderate/severe tortuosity (28.8% vs 24.6%, p<0.001). They had higher use of the retrograde wiring technique (33.3% vs 29.4%, p<0.001), longer procedural and fluoroscopy times and higher contrast and radiation use. Prior MI cases had lower technical (85.6% vs 88.8%, p<0.001) and procedural (84.3% vs 87.7%, p<0.001) success, but similar major adverse cardiac events (MACE) (2.1% vs 1.7%, p=0.113). They were more likely to experience in-hospital acute MI (0.6% vs 0.4%, p=0.046), coronary perforation (5.0% vs 4.3%, p=0.039) and have elective peripheral ventricular assist device use (2.3% vs 1.7%, p=0.006). In multivariable analysis, prior MI was independently associated with lower technical success (odds ratio (OR) 0.79, 95%CI 0.70-0.89). For 3,546 prior MI cases (53.1%) data regarding the location of the prior MI was available. Most (53.6%) had prior MI in the area that was perfused by the totally occluded vessel. These cases were more likely to have a prior myocardial viability test (29.6% vs 19.7%, p<0.001), had lower technical (83.9% vs 86.3%, p=0.052), with the association persisting in the multivariable analysis (OR 0.62, 95%CI 0.47-0.83), but similar procedural success (82.9% vs 85.2%, p=0.063) and MACE (1.7% vs 1.5%, p=0.712). Conclusions: Patients with prior MI undergoing CTO PCI have more comorbidities and higher lesion complexity, achieve lower technical success but have similar MACE.

BACKGROUND:Coronary microvascular dysfunction (CMD) and vasospastic angina (VSA) are common, yet underdiagnosed. Existing studies of invasive CMD/VSA assessment have specified patient selection and procedural technique, with little known about testing use in real-world practice. OBJECTIVES:The purpose of the study was to observe procedural and therapeutic decision-making for patients undergoing invasive CMD/VSA assessment. METHODS:FlowLab was a multicenter, prospective study of patients with possible CMD in whom the treating physician used the CoroFlow bolus thermodilution system to measure coronary flow reserve and index of microcirculatory resistance (IMR). As the purpose was to observe how testing is performed in current practice, procedural technique, including whether to perform vasospasm testing, was at operator discretion. Procedural data were collected in real-time. RESULTS:A total of 253 procedures were performed at 14 U.S. sites. The most common presenting symptoms were chest pain (222/253; 88%) and dyspnea (93/253; 37%). The median CoroFlow duration was 10 (IQR: 7-14) minutes and provocative vasospasm testing was performed in 50% (124/246). Forty-three percent (110/253) of patients had abnormal coronary flow reserve (<2.5) and 28% (72/253) had abnormal IMR (≥25). CMD/VSA was identified in 53% (135/253) of patients, with a final diagnosis of CMD in 59% (19/32) of these and VSA in 28% (9/32). Anginal therapy addition was more common in those with elevated IMR (61% [44/72] vs 29% [53/181]; P < 0.0001). CONCLUSIONS:In a prospective assessment of invasive testing for CMD/VSA, we observed varied procedural and technical approaches. Testing was rapid, and a final diagnosis of CMD or VSA was common with immediate implications for patient management. Further integration of CMD/VSA evaluation may help address current gaps in diagnosis and treatment.

Background: Chronic total occlusion (CTO) modification procedures are defined as intentional balloon dilatation (diameter ≥2.0 mm) of the entire CTO, including the proximal and distal caps and the CTO body. The outcomes of CTO modification procedures have received limited study. Methods: We analyzed the baseline clinical and angiographic characteristics and outcomes of 2,829 patients, with a total of 2,869 CTOs who underwent a CTO percutaneous coronary intervention (PCI) after a previous failure attempt from the PROGRESS-CTO registry. Results: Of these 2,869 CTO lesions, 600 (20.9%) had undergone modification procedures during the index procedure. Patients who underwent CTO modification were older with higher prevalence of hypertension (92.0% vs 87.6, p=0.005) and dyslipidemia (94.0% vs 83.4%, p<0.001), lower rate of interventional collaterals (49.2 vs 57.5, p<001), higher angiographic complexity, including more moderate/severe calcification (59.4% vs 48.5%, p<0.001) and moderate/severe proximal tortuosity (43.6% vs 30.4%, p<0.001). The most common CTO target vessel in both groups was the Right Coronary Artery (RCA). CTO modification lesions were longer (38.35 vs 30.58 mm, p<0.001) and had higher prevalence of blunt/no stump (63.9% vs 54.5%, p<0.001) and in-stent restenosis (24.6% vs 20.2%, p=0.031), but lower prevalence of side branch at the proximal cap (51.9% vs 61.2%, p<0.001). Lesions that underwent modification had higher J-CTO scores. There was no statistically significant difference in technical (84.1% vs 85.4%, p=0.478) and procedural success (82.7% vs 84.3%, p=0.403) or MACE (1.7% vs 1.8%, p=1.000), between patients who had undergone modification procedures and those who had not. Conclusions: Despite higher lesion complexity CTOs that underwent modification after an unsuccessful initial attempt were recanalized at equally high success and equally low complication rates during the repeat attempt.

OBJECTIVES:The impact of contrast type in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains controversial. The authors sought to evaluate the impact of contrast medium selection on patients undergoing CTO PCI. METHODS:The authors examined the outcomes of patients who underwent CTO PCI using iso-osmolar (iodixanol) vs pooled low-osmolar contrast media (LOCM) using data from the PROGRESS-CTO registry. RESULTS:Iodixanol was used in 1007 (18.1%) of 5558 CTO PCIs. Compared with pooled LOCM, iodixanol-treated patients were more likely to be women, were older, and more likely to have diabetes, dyslipidemia, hypertension, history of heart failure, myocardial infarction, coronary artery bypass graft surgery, and stroke. Iodixanol cases had higher complexity, with longer lesion length (35.25 ± 25.16 vs 28.91 ± 19.46 mm, P less than .001), higher prevalence of moderate or severe calcification (43% vs 37%, P less than .001) and moderate or severe proximal tortuosity (30% vs 24%, P less than .001), and higher Japanese-CTO (2.52 vs 2.17, P less than .001) and PROGRESS-CTO scores (1.30 vs 1.16, P less than .001). Iodixanol cases required longer procedure times but similar contrast volumes. Technical (85.3% vs 89.2%, P = .001) and procedural success (83.4% vs 87.3%, P = .001) were lower in iodixanol cases. Acute kidney injury (AKI) occurred in 6.4% of cases. After propensity score matching, the patients who received iodixanol had lower incidence of AKI (odds ratio [OR]: 0.67; 95% CI, 0.47, 0.97; P = .032) and a trend for lower incidence of major adverse renal or cardiovascular events (OR: 0.75; 95% CI, 0.56, 1.0; P = .061). CONCLUSIONS:AKI occurred in approximately 6% of CTO PCI cases. Iodixanol use was associated with a lower incidence of AKI, despite being used in more complex patients.

Background: Acetylsalicylic acid (ASA) has been shown to reduce recurrent deep venous thrombosis (DVT) rates. However, limited mechanistic data is available regarding the efficacy of ASA on DVT resolution and measures of post-thrombotic syndrome (PTS), particularly in female subjects. Furthermore, real-world sex-specific data on ASA prescription and withdrawal rates in secondary DVT prevention patients are sparse. Methods: First the effects of ASA pretreatment on thrombogenesis were assessed in both female and male C57BL/6 mice (n=149) utilizing serial intravital microscopy in an extended murine DVT model. Next the effects of ASA on DVT resolution and vein wall inflammation were evaluated in male mice with IVC stasis DVT using histopathological and scanning electron microscopy analyses. Next, in a single-center clinical study, secondary DVT prevention patients with a history of unprovoked lower extremity DVT were assessed for ASA and anticoagulant prescription and withdrawal rates over 24 months. Results: In murine stasis DVT, utilizing serial IVM for 24 hours (n=82), ASA pretreatment (3 mg/kg/day) significantly reduced thrombogenesis and accelerated DVT resolution in males (Fig 1A p<0.05), with a higher ASA dose (15 mg/kg/day) required in females for efficacy (Fig 1B p>0.05 all, Fig 1C p<0.05 all). In complete-stasis DVT (n=67), ASA pretreatment reduced day 8 thrombus (Fig 1D-E, p<0.001), fibrin-rich area and fibrin fibril density, and increased plasminogen expression. ASA further reduced vein wall fibrosis and fibroblasts (Fig 1F-H, p<0.05), as well as vein wall MMP activity. Next, in a cohort of 131 patients with unprovoked DVT followed over 24 months, 13.3% of patients discontinued anticoagulation therapy (Fig 1I-J, p trend <0.001). Discontinuation occurred more often in females (19.5% vs. 9.7% in males, p interaction =0.047). ASA was infrequently prescribed in patients who stopped anticoagulation (3/7 males, 0/8 females). Conclusions: Preventative ASA treatment reduced murine thrombogenesis and improved DVT resolution, with females requiring a higher ASA dose to achieve efficacy. ASA further reduced vein wall injury and inflammation. Clinically, patients with unprovoked DVT showed increasing rates of anticoagulant withdrawal over 24 months, especially in female patients. Such patients further infrequently receive ASA. These results may motivate reconsideration of preventative ASA to reduce recurrent DVT and PTS in patients ineligible for anticoagulant therapy.