Interaction of AI-Enabled Quantitative Coronary Plaque Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry.

BACKGROUND: Luminal stenosis, computed tomography-derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography are all known to be associated with adverse clinical outcomes. The interactions between these variables, patient outcomes, and quantitative plaque volumes have not been previously described. METHODS: Patients with coronary computed tomography angiography (n=4430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry underwent artificial intelligence-enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume and each plaque subtype were derived using receiver-operator characteristic curve analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events, late revascularization, a composite of the two, and cardiovascular death and myocardial infarction. RESULTS: At one year, 55 patients (1.2%) had experienced major adverse cardiac events, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis, and FFRCT, total plaque volume above the receiver-operator characteristic curve-derived optimal cutoff (total plaque volume >564 mm3) was associated with the major adverse cardiac event/late revascularization composite (adjusted hazard ratio, 1.515 [95% CI, 1.093-2.099]; P=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both major adverse cardiac event/late revascularization (total percent atheroma volume >24.4%; hazard ratio, 2.046 [95% CI, 1.474-2.839]; P<0.0001) and cardiovascular death/myocardial infarction (total percent atheroma volume >37.17%, hazard ratio, 4.53 [95% CI, 1.943-10.576]; P=0.0005). Calcified, noncalcified, and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/myocardial infarction in analyses stratified by median plaque volumes. CONCLUSIONS: Analysis of the ADVANCE registry using artificial intelligence-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02499679.

Impact of Smoking on Coronary Volume-to-Myocardial Mass Ratio: An ADVANCE Registry Substudy.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm3 ± 934.0 [SD]; never-smokers, 2967.6 mm3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm3/g ± 7.9; former smokers, 24.9 mm3/g ± 7.1; never-smokers, 25.8 mm3/g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article. © RSNA, 2024.

Coronary computed tomography angiography-based SYNTAX score for comprehensive assessment of advanced coronary artery disease.

BACKGROUND: Since the initial attempt to adapt the anatomical SYNTAX score (aSS) to coronary computed tomography angiography (CCTA), CCTA imaging technology has evolved, and is currently used as a "decision-maker" for revascularization strategy in complex coronary artery disease (CAD) and has rendered necessary some updating of the aSS to the CCTA modality. OBJECTIVES: The aim is to provide updated definitions of the aSS derived from CCTA in patients with complex CAD undergoing CABG. METHODS: The modifications of CCTA-aSS are the following; (i) updated definition and detection criteria of total occlusion (TO) in CCTA based on length assessment, (ii) inclusion of scoring points for serial bifurcations located in one single coronary segment. (iii) inclusion of weighing score points for lesions located distal to a TO, not visualized on conventional coronary angiography, but visible in CCTA, (iv) removal of thrombus and bridging collateral items from the weighing score, considering the limited diagnostic capability of CCTA in detecting these specific lesion characteristics. RESULTS: the updated CCTA-aSS was tested in a first-in-man study using the sole guidance of CCTA for the planning and performance of bypass surgery in complex CAD (n â€‹= â€‹114). An interobserver analysis showed excellent reproducibility (ICC â€‹= â€‹0.96, 95 â€‹% confidence interval 0.94-0.97). CONCLUSION: The updated CCTA-aSS was implemented in a cohort of patients with complex CAD undergoing CABG with the sole guidance of CCTA and FFRCT and the Inter-reproducibility of the analysis of the updated score was found excellent. The prognostic value of the modified CCTA-aSS will be examined in future studies.

Safety and feasibility evaluation of planning and execution of surgical revascularisation solely based on coronary CTA and FFRCT in patients with complex coronary artery disease: study protocol of the FASTTRACK CABG study.

INTRODUCTION: The previously published SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention based on coronary CT angiography (CCTA) had a very high agreement with the treatment decision derived from invasive coronary angiography (ICA). The study objective of the FASTTRACK CABG is to assess the feasibility of CCTA and fractional flow reserve derived from CTA (FFRCT) to replace ICA as a surgical guidance method for planning and execution of CABG in patients with three-vessel disease with or without left main disease. METHODS AND ANALYSIS: The FASTTRACK CABG is an investigator-initiated single-arm, multicentre, prospective, proof-of-concept and first-in-man study with feasibility and safety analysis. Surgical revascularisation strategy and treatment planning will be solely based on CCTA and FFRCT without knowledge of the anatomy defined by ICA. Clinical follow-up visit including CCTA will be performed 30 days after CABG in order to assess graft patency and adequacy of the revascularisation with respect to the surgical planning based on non-invasive imaging (CCTA) with functional assessment (FFRCT) and compared with ICA. Primary feasibility endpoint is CABG planning and execution solely based on CCTA and FFRCT in 114 patients. Primary safety endpoint based on 30 day CCTA is graft assessment and topographical adequacy of the revascularisation procedure. Automatic non-invasive assessment of functional coronary anatomy complexity is also evaluated with FFRCT for functional Synergy Between percutaneous coronary intervention With Taxus and Cardiac Surgery Score assessment on CCTA. CCTA with FFRCT might provide better anatomical and functional analysis of the coronary circulation leading to appropriate anatomical and functional revascularisation, and thereby contributing to a better outcome. ETHICS AND DISSEMINATION: Each patient has to provide written informed consent as approved by the ethical committee of the respective clinical site. Results will be submitted for publication in peer-reviewed journals and will be disseminated at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04142021.

Rationale, design and goals of the HeartFlow assessing diagnostic value of non-invasive FFRCT in Coronary Care (ADVANCE) registry.

BACKGROUND: Coronary CT angiography (CTA) is a reliable tool for the detection of coronary artery disease (CAD) that conveys significant prognostic information. It does not provide data on the hemodynamic significance of a given lesion, particularly in intermediate-grade stenosis. Fractional flow reserve by CT (FFRCT) can accurately predict the hemodynamic significance of coronary lesions. The primary objective of this registry is to determine whether the integration of FFRCT as an adjunct to coronary CTA will lead to a significant change in the management of CAD in patients with stable angina. METHODS: The ADVANCE Registry is a multi-center, prospective registry designed to evaluate utility, clinical outcomes and resource utilization following FFRCT-guided treatment in clinically stable, symptomatic patients diagnosed with CAD by coronary CTA. Approximately 5000 patients will be enrolled from up to 50 sites in Europe, USA, Canada and Asia. Requirement for enrollment is the presence of atherosclerosis on coronary CTA. For each enrolled patient, a clinical management review committee will use data from coronary CTA and FFRCT to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The primary endpoint of the registry is the reclassification rate between the management plan based on coronary CTA alone versus CTA plus FFRCT. The secondary endpoints of the registry include the evaluation of the rate of invasive coronary angiography (ICA), revascularization, major adverse coronary events, resource utilization, cumulative radiation dose exposure and the rate of ICA without obstructive CAD at 3-year follow-up. CONCLUSIONS: The ADVANCE registry is designed to assess the real-world impact of FFRCT on the clinical management of stable CAD when used along with coronary CTA.

Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study.

AIMS: In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. METHODS AND RESULTS: At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFR(CT) (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFR(CT)-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFR(CT) arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53-69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFR(CT) results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFR(CT)) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFR(CT) arms. CONCLUSIONS: Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

The PROXIMAL trial: proximal protection during saphenous vein graft intervention using the Proxis Embolic Protection System: a randomized, prospective, multicenter clinical trial.

OBJECTIVES: To determine if outcomes could be further improved, we investigated an embolic protection device placed proximal to the target lesion that could provide protection before lesion instrumentation, allow the use of conventional guidewires, and permit embolic protection in anatomy unfavorable for distal devices. BACKGROUND: Embolic complications during stenting of degenerated saphenous vein coronary bypass grafts are reduced, but not eliminated, by distal protection. METHODS: A total of 594 patients undergoing stenting of 639 saphenous vein grafts were prospectively randomized, using a noninferiority design, to compare 2 treatment strategies: control (distal protection whenever possible) or test (proximal protection when possible, distal when not). RESULTS: The primary composite end point of death, myocardial infarction, or target vessel revascularization at 30 days by intention to treat analysis occurred in 10.0% of control and 9.2% of test patients; difference = -0.8% (95% confidence interval [CI] -5.5% to 4.0%); p for noninferiority = 0.0061. In device specific analysis, this composite end point occurred in 11.7% of distal protection patients and 7.1% of proximal protection patients (difference = -4.6% [95% CI -9.6% to 0.3%]; p for superiority = 0.10, p for noninferiority = 0.001). Finally, in the subset of patients with lesions amenable to treatment with either proximal or distal protection devices (n = 410), the primary composite end point occurred in 12.2% of distal protection patients and 7.4% of proximal protection patients; difference = -4.7% (95% CI -10.4% to 1.0%), p for superiority = 0.14, p for noninferiority = 0.001. CONCLUSIONS: Using proximal embolic protection whenever possible during treatment of diseased saphenous vein grafts produced outcomes similar to those with distal embolic protection.

Effectiveness of same day percutaneous coronary intervention followed by minimally invasive aortic valve replacement for aortic stenosis and moderate coronary disease ("hybrid approach").

In 2005, the investigators described a "hybrid" cardiovascular interventional strategy combining percutaneous coronary intervention (PCI) for coronary artery disease (CAD) followed by valve surgery for patients with urgent complex CAD and valve disease to reduce morbidity and mortality. This hybrid approach has been extended prospectively in elderly, high-risk patients with aortic stenosis scheduled for elective minimally invasive aortic valve replacement (MI-AVR) who, on preoperative coronary angiography, were found to have moderate CAD amenable to PCI. In this prospective, observational series, 18 patients (mean age 76 years) underwent elective hybrid MI-AVR with PCI from May 2003 to February 2006. Five patients had undergone previous coronary artery bypass grafting. Patients underwent coronary angiography the day of (n = 12) or evening before (n = 6) MI-AVR, and after identifying moderately severe CAD, all 18 underwent the implantation of drug-eluting stents to the affected coronary arteries, followed by MI-AVR. Although all patients received standard doses of antiplatelet medications, including acetylsalicylic acid (325 mg before PCI and 325 mg/day thereafter) and clopidogrel (300 mg after PCI, 75 mg/day thereafter for 90 days for the Cypher stent), there were no reoperations for bleeding; only 8 of 18 patients required postoperative blood transfusions. One patient died postoperatively from a colonic perforation, and there were no late mortalities after a mean follow-up of 19 months. In conclusion, this hybrid strategy has low morbidity and mortality and may be a new therapeutic option for older, high-risk patients with combined CAD and aortic valve disease.

High-density lipoproteins enhance progenitor-mediated endothelium repair in mice.

OBJECTIVE: We quantified endothelial progenitor cell (EPC) engraftment into the endothelial layer as an index of progenitor-mediated endothelial repair. Studies were conducted in C57BL/6J and in apolipoprotein E-deficient (apoE(-/-)) mice. We also investigated the possibility that high-density lipoproteins (HDL) may promote progenitor-mediated endothelial repair. METHODS AND RESULTS: Thoracic aortic sections from C57BL/6J and apoE(-/-) mice were analyzed for evidence of progenitor-derived endothelium as determined by the number of stem cell antigen-1-positive (Sca-1+) cells in the endothelial layer. EPCs (Sca-1+ cells) were significantly increased after endothelial damage induced by lipopolysaccharide (LPS) administration in C57BL/6J mice. The number of EPCs was greater in the aortic endothelium of untreated apoE(-/-) than in untreated C57BL/6J mice and was similar to the number observed in LPS-treated C57BL/6J mice. The number of EPCs in the aortic endothelium of apoE(-/-) mice more than doubled after intravenous infusion of reconstituted HDL. CONCLUSIONS: EPCs are recruited into the aortic endothelial layer of mice in response to an inflammatory insult. EPCs are also increased in the aortic endothelium of untreated apoE(-/-) mice. The observation that number is further increased in apoE(-/-) mice after injection of HDL suggests a role for HDL in promoting progenitor-mediated endothelial repair.

Vascular neointimal formation and signaling pathway activation in response to stent injury in insulin-resistant and diabetic animals.

Diabetes and insulin resistance are associated with increased disease risk and poor outcomes from cardiovascular interventions. Even drug-eluting stents exhibit reduced efficacy in patients with diabetes. We now report the first study of vascular response to stent injury in insulin-resistant and diabetic animal models. Endovascular stents were expanded in the aortae of obese insulin-resistant and type 2 diabetic Zucker rats, in streptozotocin-induced type 1 diabetic Sprague-Dawley rats, and in matched controls. Insulin-resistant rats developed thicker neointima (0.46+/-0.08 versus 0.37+/-0.06 mm2, P=0.05), with decreased lumen area (2.95+/-0.26 versus 3.29+/-0.15 mm2, P=0.03) 14 days after stenting compared with controls, but without increased vascular inflammation (ED1+ tissue macrophages). Insulin-resistant and diabetic rat vessels did exhibit markedly altered signaling pathway activation 1 and 2 weeks after stenting, with up to a 98% increase in p-ERK (anti-phospho ERK) and a 54% reduction in p-Akt (anti-phospho Akt) stained cells. Western blotting confirmed a profound effect of insulin resistance and diabetes on Akt and ERK signaling in stented segments. p-ERK/p-Akt ratio in stented segments uniquely correlated with neointimal response (R2=0.888, P=0.04) in insulin-resistant and type 1 and 2 diabetic rats, but not in lean controls. Transfemoral aortic stenting in rats provides insight into vascular responses in insulin resistance and diabetes. Shifts in ERK and Akt signaling related to insulin resistance may reflect altered tissue repair in diabetes accompanied by a shift in metabolic:proliferative balance. These findings may help explain the increased vascular morbidity in diabetes and suggest specific therapies for patients with insulin resistance and diabetes.

Morphometric analysis of particulate debris extracted by four different embolic protection devices from coronary arteries, aortocoronary saphenous vein conduits, and carotid arteries.

Different embolic protection devices have been introduced for endovascular interventions: filters or balloon occlusion and aspiration systems. Despite widening use in a variety of vascular beds and clinical syndromes, little is known about the particulate burden liberated from different vascular beds and caught by different protection devices. We performed histologic and morphometric analyses of particulate debris captured during stenting of degenerated saphenous vein bypass grafts and native coronary arteries during acute myocardial infarction or during elective intervention and carotid arteries to assess the relative performance of different protection devices. We analyzed 232 interventions (90 saphenous vein bypass grafts, 77 native coronary arteries, and 65 carotid arteries) with 4 different devices (65 FilterWires, 99 Interceptors, 41 GuardWires, and 27 Proxis catheters) using the RapidVue particle analyzer. No difference in embolic volume retrieved was demonstrated between devices in saphenous vein bypass grafts and carotid interventions. A smaller volume of particulate debris was retrieved by the GuardWire compared with the FilterWire and the Proxis catheter in native coronary artery interventions. The Interceptor and the GuardWire captured more smaller particles than did the FilterWire or Proxis catheter. During saphenous vein bypass graft or carotid intervention, different embolic protection strategies were performed similarly. In native coronary artery stenting, however, proximal embolic protection retrieved larger amounts of debris than did distal filters or occlusion devices. These data may allow greater tailoring of embolic protection device development and application in specific anatomic locales.

Influence of vessel diameter on the efficacy of distal protection devices during saphenous vein graft intervention.

We sought to determine the influence of vessel diameter on the efficacy of distal protection devices during saphenous vein graft intervention. From the Filterwire EX Randomized Evaluation trial, in which patients who underwent saphenous vein graft stenting were randomized to distal protection with the GuardWire or FilterWire EX, outcomes in 572 patients were examined in vessel size tertiles. The 30-day composite incidence of major adverse cardiac events (MACEs) increased with vessel size and was 6.9%, 9.7%, and 14.9% in the smallest, middle, and largest tertiles, respectively (p = 0.04). MACE rates were relatively vessel size independent for the GuardWire but increased steadily with vessel size with the FilterWire EX. In the smallest tertile, MACEs were reduced by 71% with the FilterWire EX compared with the GuardWire (p = 0.05), with the devices showing similar event rates in the other tertiles.

Coronary artery perforation by cutting balloon resulting in dissecting subepicardial hematoma and avulsion of the vasculature.

We report a case of perforation caused by cutting balloon angioplasty of in-stent restenosis in a saphenous vein coronary bypass graft. This was complicated by a subepicardial hematoma leading to avulsion of the penetrating arteries and cardiogenic shock. Despite surgical evacuation and percutaneous left ventricular assist-device support, death ensued.

Staged initial percutaneous coronary intervention followed by valve surgery ("hybrid approach") for patients with complex coronary and valve disease.

OBJECTIVES: The goal of this study was to determine if a "hybrid" approach to the treatment of complex combined coronary and valve disease is superior to the results predicted by a Society of Thoracic Surgeons' (STS) algorithm with conventional coronary artery bypass graft (CABG)/valve surgery in high-risk patients. BACKGROUND: With advancements in percutaneous coronary interventions (PCIs), some patients requiring coronary revascularization and valve surgery may benefit from a hybrid approach involving initial planned PCI followed by valve surgery, rather than conventional CABG/valve surgery. METHODS: We retrospectively analyzed 26 consecutive patients with coronary artery and valve disease who underwent planned initial PCI followed by valve surgery during the same hospital stay between September 1997 and August 2003. We calculated the predicted mortality at the time of PCI and compared it with the observed mortality. RESULTS: There were 12 male and 14 female patients with a median age of 72 years (range 53 to 91 years). Balloon angioplasty was performed in all patients, followed by stenting in 22 (85%) patients. Within a median of 5 days (range 0 to 14 days), 15 patients (58%) underwent primary and 11 patients (42%) underwent re-operative valve surgery. Operative mortality was 1 of 26 patients (3.8%), dramatically lower than the STS-predicted mortality of 22%. Median blood loss was 900 ml, and 22 patients (85%) required blood transfusions. Survival at 1, 3, and 5 years was 78%, 56%, and 44%, respectively. CONCLUSIONS: Hybrid initial PCI followed by staged valve surgery represents an excellent alternative to conventional CABG/valve surgery in some high-risk patients, particularly those who present in shock after myocardial infarction. Lower mortality rates come at the cost of more bleeding and transfusion requirements.

Embolic protection with filtering or occlusion balloons during saphenous vein graft stenting retrieves identical volumes and sizes of particulate debris.

BACKGROUND: Distal embolization of plaque particulate liberated during stenting may cause periprocedural complications. The number, size, and volume of debris released during stenting, however, have not been quantified, rendering embolic protection approaches empiric. We used a novel method of microparticle size assessment to measure volume and characterize individual sizes of particles captured by the PercuSurge GuardWire balloon or a vascular filter during saphenous vein graft stenting. METHODS AND RESULTS: Braided nitinol filters (average distal pore size 100 microns) were used in 47 saphenous vein grafts in 44 patients. The PercuSurge GuardWire was used in 17 saphenous vein grafts in 16 patients. Particulate debris was subjected to microparticle size analysis (RapidVue, Beckman Coulter). All samples contained particulate debris. For both filter and GuardWire populations, most particles were <100 microm in longest dimension (87% and 90% of particles, respectively), and the distribution of particle sizes was identical. Total embolic load per lesion for both filters and GuardWire aspirates was also similar: median embolic load per filter was 16 mm3 (range 2 to 84 mm3). Median embolic load per GuardWire was also 16 mm3 (range 7 to 42 mm3). Histopathologic analysis demonstrated that most samples contained plaque elements and platelet-rich thrombus. CONCLUSIONS: During saphenous vein graft interventions, particulate retrieved with a vascular filtering device or an occlusion balloon was similar in amount and character. This supports the notion that unless soluble mediators play an important role in adverse acute clinical events after stenting, the clinical efficacy of filtering devices may be equal to that of occlusion devices.

Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.

BACKGROUND: Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment. METHODS AND RESULTS: An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy. CONCLUSIONS: This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Randomized comparison of distal protection with a filter-based catheter and a balloon occlusion and aspiration system during percutaneous intervention of diseased saphenous vein aorto-coronary bypass grafts.

BACKGROUND: The high rate of periprocedural complications resulting from atherothrombotic embolization after percutaneous intervention in diseased saphenous vein grafts is reduced by distal microcirculatory protection using a balloon occlusion and aspiration system. Whether filter-based catheters, which offer the inherent advantages of maintained perfusion and ease of use, are as effective for this purpose has not been established. METHODS AND RESULTS: A total of 651 patients undergoing percutaneous intervention of 682 saphenous vein graft lesions were prospectively randomized to distal protection with the filter-based FilterWire EX versus the GuardWire balloon occlusion and aspiration system. Device success was 95.5% and 97.2% with the FilterWire EX and GuardWire, respectively (P=0.25). Postprocedural measures of epicardial flow and angiographic complications were similar between the 2 groups, although bailout IIb/IIIa inhibitors were required slightly less frequently in the FilterWire EX group (0% versus 1.5%, P=0.03). The primary end point, the composite incidence of death, myocardial infarction, or target vessel revascularization at 30 days, occurred in 9.9% of FilterWire EX patients and 11.6% of GuardWire patients (difference [95% CI]=-1.7% [-6.4%, 3.1%]; P for superiority=0.53, P for noninferiority=0.0008). CONCLUSIONS: Distal protection with the FilterWire EX may be safely used as an adjunct to percutaneous intervention of diseased saphenous vein grafts and, compared with distal protection with the GuardWire balloon occlusion and aspiration system, results in similar rates of major adverse cardiac events at 30 days.

Targeting CCR2 or CD18 inhibits experimental in-stent restenosis in primates: inhibitory potential depends on type of injury and leukocytes targeted.

A central role for leukocytes in neointimal hyperplasia after arterial injury is suspected. However, the relative importance of neutrophils and monocytes in balloon or stent-induced injury are not well understood, and mechanistic targeting of leukocyte recruitment or function is crude. We determined the temporal and spatial distribution of different leukocytes after balloon and stent-induced injury in primate iliac arteries. Based on these data, we targeted neutrophil and monocyte recruitment selectively after angioplasty or stent implantation and demonstrated that monocyte-specific blockade achieved via blockade of the MCP-1 receptor CCR2, was effective at reducing neointimal hyperplasia after stenting. In contrast, combined neutrophil and monocyte blockade achieved by targeting the leukocyte beta(2)-integrin beta-subunit CD18 was required to reduce neointimal hyperplasia after balloon injury. Distinct patterns of leukocyte infiltration in balloon versus stent-injured arteries predict distinct mechanisms for antiinflammatory strategies targeting neutrophils or monocytes in primates and may assist design of effective clinical strategies for optimizing vascular interventions.