In-vivo assessment of vascular injury for the prediction of in-stent restenosis.

BACKGROUND: Despite optimizations of coronary stenting technology, a residual risk of in-stent restenosis (ISR) remains. Vessel wall injury has important impact on the development of ISR. While injury can be assessed in histology, there is no injury score available to be used in clinical practice. METHODS: Seven rats underwent abdominal aorta stent implantation. At 4 weeks after implantation, animals were euthanized, and strut indentation, defined as the impression of the strut into the vessel wall, as well as neointimal growth were assessed. Established histological injury scores were assessed to confirm associations between indentation and vessel wall injury. In addition, stent strut indentation was assessed by optical coherence tomography (OCT) in an exemplary clinical case. RESULTS: Stent strut indentation was associated with vessel wall injury in histology. Furthermore, indentation was positively correlated with neointimal thickness, both in the per-strut analysis (r = 0.5579) and in the per-section analysis (r = 0.8620; both p ≤ 0.001). In a clinical case, indentation quantification in OCT was feasible, enabling assessment of injury in vivo. CONCLUSION: Assessing stent strut indentation enables periprocedural assessment of stent-induced damage in vivo and therefore allows for optimization of stent implantation. The assessment of stent strut indentation might become a valuable tool in clinical practice.

Dynamic assessment of the left main-left circumflex bending angle: Implications for ostial left circumflex artery in-stent restenosis after successful two-stent PCI.

BACKGROUND: Two-stent techniques for percutaneous coronary intervention (PCI) on left main (LM) bifurcation (LMB) lesions are associated with an increased risk of in-stent restenosis (ISR) at left circumflex artery (LCx) ostium but the underlying mechanisms are incompletely understood. This study sought to investigate the association between cyclic change of LM-LCx bending angle (BALM-LCx) and the risk of ostial LCx ISR following two-stent techniques. METHODS: In a retrospective cohort of patients undergoing two-stent PCI for LMB lesions, BALM-LCx and distal bifurcation angle (DBA) were computed with 3-dimensional angiographic reconstruction. The analysis was performed both at end-diastole and end-systole, and the angulation change throughout the cardiac cycle was defined as the cardiac motion-induced angulation change (∆CAngle). RESULTS: A total of 101 patients were included. The mean pre-procedural BALM-LCx was 66.8 ± 16.1° at end-diastole and 54.1 ± 13.3° at end-systole with a range of 13.0 ± 7.7°. Pre-procedural ∆CBALM-LCx > 16.4° was the most relevant predictor of ostial LCx ISR (adjusted OR 11.58, 95% CI 4.04-33.19; p < 0.001). Post-procedural ∆CBALM-LCx > 9.8° and stent-induced diastolic BALM-LCx change > 11.6° were also related with ostial LCx ISR. DBA was positively correlated with BALM-LCx and showed a weaker association of pre-procedural ∆CDBA > 14.5° with ostial LCx ISR (adjusted OR 6.87, 95% CI 2.57-18.37; p < 0.001). CONCLUSIONS: Three-dimensional angiographic bending angle is a feasible and reproducible novel method for LMB angulation measurement. A large pre-procedural cyclic change of BALM-LCx was associated with an increased risk of ostial LCx ISR following two-stent techniques.

Prevalence, Management and Outcomes of Percutaneous Coronary Intervention for Coronary In-Stent Restenosis: Insights From the France PCI Registry.

BACKGROUND: Despite the evolution of stent technology, there is a non-negligible risk of in-stent restenosis (ISR) after Percutaneous coronary intervention (PCI). Large-scale registry data on the prevalence and clinical management of ISR is lacking. METHODS: The aim was to describe the epidemiology and management of patients with ≥1 ISR lesions treated with PCI (ISR PCI). Data on characteristics, management and clinical outcomes were analyzed for patients undergoing ISR PCI in the France-PCI all-comers registry. RESULTS: Between January 2014 and December 2018, 31,892 lesions were treated in 22,592 patients, 7.3 % of whom underwent ISR PCI. Patients undergoing ISR PCI were older (68.5 vs 67.8; p < 0.001), and more likely to have diabetes (32.7 % vs 25.4 %, p < 0.001), chronic coronary syndrome or multivessel disease. ISR PCI concerned drug eluting stents (DES) ISR in 48.8 % of cases. Patients with ISR lesions were more frequently treated with DES than drug eluting balloon or balloon angioplasty (74.2 %, 11.6 % and 12.9 %, respectively). Intravascular imaging was rarely used. At 1 year, patients with ISR had higher target lesion revascularization rates (4.3 % vs. 1.6 %; HR 2.24 [1.64-3.06]; p < 0.001). CONCLUSIONS: In a large all-comers registry, ISR PCI was not infrequent and associated with worse prognosis than non-ISR PCI. Further studies and technical improvements are warranted to improve the outcomes of ISR PCI.

The usefulness of subtraction coronary computed tomography angiography for in-stent restenosis assessment of patients with CoCr stent using 320-row area detector CT.

ABSTRACT: The aim of this study was to assess in-stent restenosis (ISR) of coronary artery for patients with CoCr stent using subtraction coronary computed tomography angiography (CCTA) with one-breath-hold scan on 320-row area detector CT, invasive coronary angiography (ICA) as clinical standard.Patients who were referred for CCTA from January 2020 to May 2021 were retrospectively analyzed. Pre-contrast and CCTA was performed with dedicated one-breath-hold subtraction scan protocol and post processing to get subtracted-CCTA image without stent. Subjective image qualities and diagnosable rate were analyzed for CCTA and subtracted-CCTA respectively. The ISR degree of each stent was evaluated both on CCTA and subtracted-CCTA images. The receiver-operating characteristic curve with sensitivity, specificity, accuracy of CCTA, and subtracted-CCTA in the diagnosis of ISR were calculated with ICA as reference.Forty patients with 85 CoCr coronary stents of 3 to 3.5 mm diameter with ICA confirmation within 1 month were finally included. Subtracted-CCTA showed more diagnosable segments of stent (91.76% [78/85]) than those of CCTA (50.59% [43/85]) (P < .001). The subjective image quality score of CCTA was 2.23 ±â€Š1.32 while 3.41 ±â€Š0.90 on subtracted-CCTA (P < .001). Both subtracted-CCTA and CCTA showed high consistency with ICA (Kappa = 0.795 and 0.918 respectively). The area under the curve was 0.607 for CCTA and 0.757 for subtracted-CCTA (P < .001) for stent based diagnose, respectively. The sensitivity, specificity, accuracy of CCTA, and subtracted-CCTA were 90.0%, 97.0%, 95.3%, and 87.5%, 100.0%, 97.43%, respectively.Subtracted-CCTA showed improved diagnose performance for ISR, which potentially reduce further follow-up ICA procedures for patients with CoCr stents.

Cost-effectiveness of stress CTP versus CTA in detecting obstructive CAD or in-stent restenosis in stented patients.

OBJECTIVES: The aim of this retrospective study was to determine cost-effectiveness of stress myocardial CT perfusion (CTP), coronary CT angiography (CTA), and the combination of both in suspected obstructive coronary artery disease (CAD) or in-stent restenosis (ISR) in patients with previous coronary stent implantation. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with CTA, CTP, and CTA + CTP. Model input parameters were obtained from published literature. Probabilistic sensitivity analysis was performed to evaluate overall model uncertainty. A single-variable deterministic sensitivity analysis evaluated the sensitivity of the results to plausible variations in model inputs. Cost-effectiveness was assessed based on a cost-effectiveness threshold of $100,000 per QALY. RESULTS: In the base-case scenario with willingness to pay of $100,000 per QALY, CTA resulted in total costs of $47,013.87 and an expected effectiveness of 6.84 QALYs, whereas CTP resulted in total costs of $46,758.83 with 6.93 QALYs. CTA + CTP reached costs of $47,455.63 with 6.85 QALYs. Therefore, strategies CTA and CTA + CTP were dominated by CTP in the base-case scenario. Deterministic sensitivity analysis demonstrated robustness of the model to variations of diagnostic efficacy parameters and costs in a broad range. CTP was cost-effective in the majority of iterations in the probabilistic sensitivity analysis as compared with CTA. CONCLUSIONS: CTP is cost-effective for the detection of obstructive CAD or ISR in patients with previous stenting and therefore should be considered a feasible approach in daily clinical practice. KEY POINTS: • CTP provides added diagnostic value in patients with previous coronary stents. • CTP is a cost-effective method for the detection of obstructive CAD or ISR in patients with previous stenting.

Angiography and Optical Coherence Tomography Assessment of the Drug-Coated Balloon ESSENTIAL for the Treatment of In-Stent Restenosis.

OBJECTIVES: This study sought to assess the efficacy of the drug-coated balloon (DCB) ESSENTIAL for the treatment of in-stent restenosis (ISR). BACKGROUND: DCBs have proven a valid therapeutic option for the management of ISR in several clinical trials, yet no class effect can be claimed. Accordingly, every new DCB model has to be individually evaluated through clinical studies. METHODS: This is a prospective, multicenter study including consecutive patients undergoing percutaneous coronary intervention for ISR with the ESSENTIAL DCB. A 6-month quantitative coronary angiography (QCA)/optical coherence tomography (OCT) follow-up was scheduled. The primary endpoint was OCT-derived in-segment maximal area stenosis. Secondary endpoints included QCA-derived in-segment late lumen loss (LLL) and target lesion failure (TLF) rates at 6, 12, and 24 months. TLF was defined as the composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS: A total of 31 patients were successfully treated with DCB, with 67% of ISR corresponding to drug-eluting stents (DES). At 6 months, 26 patients underwent the scheduled angiographic follow-up. The mean value for in-segment maximal area stenosis was 51.4 ±â€¯13% and the median value was 53% (IQR 46.4-59.5). In the DES-ISR subgroup, these parameters were 52.6 ±â€¯10% and 55.2% (IQR 49.3-58.5), respectively. In-segment LLL was 0.25 ±â€¯0.43 mm with only 2 (7.7%) patients showing binary restenosis (>50%). The incidence of TLF was 10% at 6 months, 13.3% at 12 months, and 13.3% at 24 months. CONCLUSIONS: In this study, the ESSENTIAL DCB showed sustained efficacy in the prevention of recurrent restenosis after treatment of ISR. SUMMARY: We sought to assess the efficacy of the drug-coated balloon ESSENTIAL for the treatment of in-stent restenosis through a prospective, multicenter study including QCA and OCT assessment at 6-month follow-up. The primary endpoint was in-segment maximal area stenosis. Among the 31 patients successfully treated with the ESSENTIAL DCB, an angiographic follow-up was conducted in 26. Mean in-segment maximal area stenosis was 51.4 ±â€¯13% and the median value was 53% (IQR 46.4-59.5). In the DES-ISR subgroup, corresponding values were 52.6 ±â€¯10% and 55.2% (IQR 49.3-58.5), respectively. The observed in-segment LLL was 0.25 ±â€¯0.43 mm and binary restenosis rate was 7.7%. TLF was 10% at 6 months and 13.3% at 12 and 24 months.

The potential hazard of a non-slip element balloon causing distal longitudinal stent deformation: the first clinical experience and in vitro assessment.

BACKGROUND: A new complication, longitudinal stent deformation (LSD), is increasingly reported with recent intracoronary stent designs. There have been experiences of unusual cases of distal LSD caused by entrapment of a Lacrosse® non-slip element (NSE) balloon (Goodman Co., Ltd., Nagoya, Japan), which has three flexible nylon elements to prevent slippage. Accordingly, the aim of this study is to report the clinical experience of distal LSD caused by the NSE in the documented center and to investigate the incidence and mechanisms involved. METHODS: Coronary intervention cases were retrospectively reviewed using the NSE balloon in hospital between May 2014 and June 2017. In bench testing, distal LSD was reproduced in a silicon tube model to identify its mechanism. RESULTS: A total of 95 patients with 107 lesions underwent coronary interventions with NSE. Of these, 72 lesions (12 de-novo lesions and 60 in-stent restenosis) were treated using in-stent dilatation. Two distal LSD cases occurred, representing an incidence of 2.78% (2/72) among all procedures; 16.7% (2/12) of the de-novo lesions developed LSD. In vitro experimentation allowed indentification of the mechanisms involved and bailout strategies. CONCLUSIONS: This is the first study to evaluate NSE balloon catheter entrapment complicated by distal LSD in which reconstruction of the deformed stent and retrieval of the NSE could be achieved successfully. There is a potential hazard for distal LSD during post-dilatation using the NSE balloon due to its structural characteristics. Careful assessment is needed to prevent this complication.

Incidence, procedural management, and clinical outcomes of coronary in-stent restenosis: Insights from the National VA CART Program.

BACKROUND: In-stent restenosis (ISR) remains a common clinical problem associated with significant morbidity. We sought to evaluate the temporal trends in incidence and procedural management of coronary restenosis as well as evaluate the association between different treatment modalities and clinical outcomes. METHODS: We identified all patients treated for coronary ISR within the Veterans Affairs Healthcare System from October 1, 2006 to September 30, 2014. The temporal trends in incidence as well as intraprocedural management were assessed. Among patients treated for single vessel restenosis, a propensity matched cohort was created for those treated with drug-eluting stents (DES) or other treatment modalities. Target vessel revascularization (TVR) and mortality were compared between the two subpopulations. RESULTS: From 2006 to 2014, 65,443 patients underwent percutaneous coronary intervention and 6,872 patients (10.5%) with 8,921 lesions were treated for ISR. The proportion of patients undergoing revascularization for restenosis increased 0.28% per year (P = 0.055). Among a propensity-matched cohort of 6,231, the rates of TVR (subdistribution HR: 0.623, 95% CI: 0.511-0.760) and mortality (HR: 0.730, 95% CI: 0.641-0.830) were significantly lower among patients treated with a DES compared with other treatments. After adjustment for known risk factors, treatment with DES continued to be associated with a reduction in mortality rate (Adjusted HR: 0.802, 95% CI: 0.704-0.913). CONCLUSIONS: There is a trend toward an increasing proportion of coronary interventions for ISR in a national cohort of Veterans and treatment with a DES is associated with the lowest rate of TVR and overall mortality.

Intravascular ultrasound assessment of minimum lumen area and intimal hyperplasia in in-stent restenosis after drug-eluting or bare-metal stent implantation. The Nordic Intravascular Ultrasound Study (NIVUS).

INTRODUCTION: Drug-eluting stents (DES) reduce the risk of restenosis after percutaneous coronary intervention. The aim of the study was to evaluate, by intravascular ultrasound (IVUS), the minimum lumen area site in the stented segment and the distribution of intimal hyperplasia in patients presenting with a DES or bare-metal stent (BMS) in-stent restenosis. METHODS: The "Nordic Intravascular Ultrasound Study (NIVUS)" study was conducted in Nordic and Baltic countries as a prospective multicenter registry. Two hundred nine patients (DES n=121 and BMS n=88) with in-stent restenosis were enrolled. RESULTS: At the minimum lumen area site in the stented segment, the stent area (5.8±2.2mm2 vs. 7.6±2.4mm2, p<0.001) and intimal hyperplasia area (2.6±2.0mm2 vs. 5.0±2.2mm2, p<0.001) were significantly lower in patients treated with DES compared to BMS. The percentage of stents that did not have a minimum stent area of at least 5.0mm2 (under expansion) was higher in DES (58.7% vs. 37.7%, p=0.008) compared to BMS. Intimal hyperplasia covered 55.4±33.3% of the stent length in the DES compared to 90.7±17.4% in the BMS group, p<0.001. Focal in-stent restenosis was more often seen in DES treated patients compared to BMS treated patients (DES n=84 (59.9%) vs. BMS n=15 (17.0%), p<0.001). CONCLUSION: Stent underexpansion was more often seen in DES than BMS in-stent restenosis. DES more often had focal in-stent restenosis with less intimal hyperplasia.

Impact of stent diameter and length on in-stent restenosis after DES vs BMS implantation in patients needing large coronary stents-A clinical and health-economic evaluation.

AIMS: The British National Institute of Clinical Excellence (NICE) guidelines recommend to use drug-eluting stents (DES) instead of bare-metal stents (BMS) only in lesions >15 mm in length or in vessels <3 mm in diameter. We analyzed the impact of stent length and stent diameter on in-stent restenosis (ISR) in the BASKET-PROVE study population and evaluated the cost-effectiveness of DES compared to BMS. METHODS/RESULTS: The BASKET-PROVE trial compared DES vs BMS in large coronary arteries (≥3 mm). We calculated incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves with regard to quality-adjusted life years (QALYs) gained and target lesion revascularizations (TLRs) avoided. A total of 2278 patients were included in the analysis. A total of 74 ISR in 63 patients were observed. In-stent restenosis was significantly more frequent in segments treated with a BMS compared to segments treated with a DES (5.4% vs 0.76%; P<.001). The benefit of a DES compared to a BMS regarding ISR was consistent among the subgroups of stent length >15 mm and ≤15 mm, respectively. With the use of DES in short lesions, there was only a minimal gain of 0.005 in QALYs. At a threshold of 10 000 CHF per TLR avoided, DES had a high probability of being cost-effective. CONCLUSION: In the BASKET-PROVE study population, the strongest predictor of ISR is the use of a BMS, even in patients in need of stents ≥3.0 mm and ≤15 mm lesion length and DES were cost-effective. This should prompt the NICE to reevaluate its recommendation to use DES instead of BMS only in vessels <3.0 mm and lesions >15 mm length.

A systematic review and meta-analysis of multidetector computed tomography in the assessment of coronary artery bypass grafts.

PURPOSE: The present meta-analysis aimed to compare the diagnostic accuracy of more recent computed tomography coronary angiography (CTCA) with invasive coronary angiography (ICA) in the assessment of graft patency after coronary artery bypass graft surgery (CABG). MATERIAL AND METHODS: A systematic review was performed using nine electronic databases from their dates of inception to July 2015. Predefined inclusion criteria included studies reporting on comparative outcomes using ≥64 slice multidetector computed tomography (MDCT) and ICA. The primary endpoints included graft occlusion and significant graft stenosis ≥50%. Secondary analyses included the comparison of arterial versus venous graft conduits, and the use of different MDCT techniques. RESULTS: Thirty-one studies were identified according to selection criteria, involving 1975 patients with 5364 assessed grafts. Combined assessment of stenosis and occlusion for all grafts demonstrated a sensitivity of 96.1% [95% confidence interval (CI) 94.3-97.4%] and specificity of 96.3% (95% CI 95.1-97.3%). CTCA assessment of venous grafts demonstrated higher sensitivity compared to arterial grafts, when testing for both occlusion and stenosis (97.6% vs 89.2%, p=0.004). CONCLUSION: Results of this study demonstrated that CTCA had a relatively high pooled sensitivity, specificity and negative predictive value compared to ICA. However, patient baseline characteristics varied between studies, and the results should be interpreted with caution. Nonetheless, our results indicate that CTCA should be recognized as an accurate and non-invasive investigation for graft patency in symptomatic patients after CABG.

Optical coherence tomography assessment of in-stent restenosis after percutaneous coronary intervention with two-stent technique in unprotected left main.

BACKGROUND: Optical coherence tomography (OCT) has contributed to a better understanding of in-stent restenosis (ISR); however, studies evaluating ISR pattern after two-stent technique in unprotected left main (ULM) are lacking. We aim to evaluate the ISR pattern of proximal LAD and LCX after two-stent technique in ULM. METHODS: We performed OCT in 26 patients with isolated or combined ISR (identified by angiography as >50%) after two stent implantation in the proximal LCX and LAD. Finally, 13 LAD and 22 LCX ISR lesions underwent OCT assessments. OCT analyses were undertaken in the proximal segments of the LAD and LCX. In addition, we compared OCT findings in the flow divider (FD) and lateral wall (LW). RESULTS: In both the LAD and LCX, the distance from the ostium to the minimum lumen area (MLA; LAD, 2.00mm [1.00, 3.00]; LCX, 1.00mm [0.00, 1.80] distal to ostium) was short. Uncovered struts were more common on the FD side compared with the LW in the LAD (6.25% [0.00, 20.00] vs 0.00% [0.00, 0.00], respectively, p=0.016) and LCX (11.32% [0.00, 19.44] vs 0.00% [0.00, 4.55], respectively, p<0.001). Conversely, neointimal hyperplasia (NIH) was significantly thicker on the FD side compared with the LW in the LCX (0.31mm [0.19, 0.47] vs 0.15mm [0.09, 0.31], p<0.001). CONCLUSIONS: While uncovered struts were more commonly found on the FD side of both arteries, NIH was significantly thicker on the FD side compared with the LW in the LCX. These unique findings might indicate inferior outcomes after two-stent techniques in ULM bifurcation lesions.

Comparative assessment of the antirestenotic efficacy of two paclitaxel drug-eluting balloons with different coatings in the treatment of in-stent restenosis.

BACKGROUND/OBJECTIVES: Preclinical investigations have suggested that coating technology is crucial for the efficacy of drug-eluting balloons (DEB). Aim of this study is to compare the antirestenotic efficacy of two paclitaxel DEB with different coatings in the treatment of in-stent restenosis (ISR) by means of a morphological and functional assessment. METHODS: In a single center, prospective, non-randomized study, the shellac-paclitaxel coated DIOR, and the urea-paclitaxel coated IN.PACT Falcon were compared in the setting of ISR. Quantitative angiography, fractional flow reserve (FFR), and optical coherence tomography (OCT) were performed at baseline, postprocedure and 6-month follow-up. Main endpoints were QCA, FFR and OCT-based parameters of restenosis. RESULTS: Forty-five patients were included, 20 (44 %) received treatment with the DIOR and 25 (56 %) with the IN.PACT Falcon. Angiographic and device success were 100 and 90 % for the DIOR, and 100 and 92 % for the IN.PACT Falcon, respectively. After 6-months, in-segment late lumen loss (-0.03 ± 0.43 vs. 0.36 ± 0.48 mm, p = 0.014) and diameter stenosis (30.7 ± 16.2 vs. 41.3 ± 22.6 %, p = 0.083) were lower for the IN.PACT Falcon. FFR distal of the stent was significantly higher in the IN.PACT Falcon group (0.92 ± 0.07 vs. 0.84 ± 0.13, p = 0.029) and in-stent FFR gradient was lower (0.05 ± 0.05 vs. 0.13 ± 0.12, p = 0.002). Between postprocedure and follow-up, a 16 % decrease in neointimal volume was observed for the IN.PACT Falcon, while a 30 % increase was observed for the DIOR (p = 0.006). CONCLUSIONS: The IN.PACT Falcon DEB showed higher antirestenotic efficacy than the DIOR in the treatment of ISR, demonstrating that DEB with an excipient-based coating is not equally effective.

Assessment of coronary in-stent restenosis: value of subtraction coronary computed tomography angiography.

In conventional coronary computed tomography angiography (CCTA), metal artifacts are frequently observed where stents are located, making it difficult to evaluate in-stent restenosis. This study was conducted to investigate whether subtraction CCTA can improve diagnostic accuracy in the evaluation of in-stent restenosis. Subtraction CCTA was performed using 320-row CT in 398 patients with previously placed stents who were able to hold their breath for 25 s and in whom mid-diastolic prospective one-beat scanning was possible. Among these patients, 126 patients (94 men and 32 women, age 74 ± 8 years) with 370 stents who also underwent invasive coronary angiography (ICA) were selected as the subjects of this study. With ICA findings considered the gold standard, conventional CCTA was compared against subtraction CCTA to determine whether subtraction can improve diagnostic accuracy in the evaluation of in-stent restenosis. When non-assessable stents were considered to be stenotic, the diagnostic accuracy in the evaluation of in-stent restenosis was 62.7 % for conventional CCTA and 89.5 % for subtraction CCTA. When the non-assessable stents were considered to be non-stenotic the diagnostic accuracy was 90.3 % for conventional CCTA and 94.31 % for subtraction CCTA. When subtraction CCTA was used to evaluate only the 138 stents that were judged to be non-assessable by conventional CCTA, 116 of these stents were judged to be assessable, and the findings for 109 of them agreed with those obtained by ICA. Even for stents with an internal diameter of 2.5-3 mm, the lumen can be evaluated in more than 80 % of patients. Subtraction CCTA provides significantly higher diagnostic accuracy than conventional CCTA in the evaluation of in-stent restenosis.

Human recombinant activated protein C-coated stent for the prevention of restenosis in porcine coronary arteries.

Activated protein C (APC), an endogenous protein, inhibits inflammation and thrombosis and interrupts the coagulation cascade. Here, we investigated the effect of human recombinant APC on the development of neointimal hyperplasia in porcine coronary arteries. Yukon Choice bare metal stents were coated with 2.6 µg APC/mm(2). Under general anesthesia, APC-coated and bare stents were implanted in the left anterior descending and circumflex coronary arteries of 10 domestic pigs. During the 4-week follow-up, animals were treated with dual antiplatelet therapy and neointimal hyperplasia was evaluated via histology. Scanning electron microscopy indicated successful but unequal coating of stents with APC; nearly complete drug release occurred within 4 h. Enzyme-linked immunosorbent assay revealed that intracoronary stent implantation rapidly increased the levels of monocyte chemoattractant protein-1, an effect that was inhibited by APC release from the coated stent. Fibrin deposition and adventitial inflammation were significantly decreased 1 month after implanting APC-coated stents versus bare stents, paralleled by significantly smaller neointimal area (0.98 ± 0.92 vs. 1.44 ± 0.91 mm(2), P = 0.028), higher lumen area (3.47 ± 0.94 vs. 3.06 ± 0.91 mm(2), P = 0.046), and lower stenosis area (22.2 ± 21.2% vs. 32.1 ± 20.1%, P = 0.034). Endothelialization was complete with APC-coated but not bare (90%) stents. P-selectin immunostaining revealed significantly fewer activated endothelial cells in the neointima in the APC group (4.6 ± 1.9 vs. 11.6 ± 4.1%, P < 0.001). Thus, short exposure of coronary arteries to APC reduced inflammatory responses, neointimal proliferation, and in-stent restenosis, offering a promising therapy to improve clinical outcomes of coronary stenting. However, coating stents with APC for prolonged, controlled drug release remains technically challenging.

Coronary In-Stent Restenosis: Assessment with Corrected Coronary Opacification Difference across Coronary Stents Measured with CT Angiography.

PURPOSE: To determine whether changes in coronary opacification normalized to the aorta (corrected coronary opacification [CCO]) across stents can help identify in-stent restenosis (ISR) severity with use of invasive coronary angiography as the standard of reference. MATERIALS AND METHODS: This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The authors retrospectively analyzed 106 patients (88 men, 18 women; mean age, 59.6 years ± 10.4; age range, 36-84 years) who had previously undergone stent implantation within 3 months of coronary computed tomographic (CT) angiography. Attenuation values in the coronary lumen were measured proximal and distal to the stents and normalized to the descending aorta. The CCO difference across the stent was compared with the severity of ISR. One-way analysis of variance least significant difference was used for comparison. RESULTS: A total of 141 stents were assessed. Seventy-six stents were normally patent, 18 had ISR of less than 50%, 28 had ISR of 50%-99%, and 19 were fully occluded. The median CCO differences in the four groups were 0.078, 0.163, 0.346, and 0.606, respectively. There was no significant difference between stents with an ISR of at least 50% and those with total occlusion (P = .056), although the other groups had significant differences at pairwise comparison (P < .01 for all). For stents smaller than 3 mm in diameter, the median CCO differences in the four groups were 0.086, 0.136, 0.390, and 0.471, respectively. The CCO differences across normal stents and stents with ISR of less than 50% were significantly less than those across stents with an ISR of at least 50% and those with total occlusion (P < .01 for all). There were no significant differences between stents with no ISR and those with an ISR of less than 50% (P = .821) and between stents with an ISR of at least 50% and those with an ISR of 100% (P = .836). CONCLUSION: The CCO difference across coronary stents is related to ISR severity in obstructive ISR in stents smaller than 3 mm in diameter.

Intravascular ultrasound assessment of optimal stent area to prevent in-stent restenosis after zotarolimus-, everolimus-, and sirolimus-eluting stent implantation.

OBJECTIVES AND BACKGROUND: The impact of underexpansion and minimal stent area (MSA) criteria in the second generation drug-eluting stents (DES) has not been addressed yet. METHODS: Using intravascular ultrasound (IVUS), we assessed the optimal cut-off values of post-stenting MSA to prevent in-stent restenosis (ISR). Poststenting IVUS data and 9-month follow-up angiography were available in 912 patients with 990 lesions: 541 sirolimus-eluting stents (SES), 220 zotarolimus-eluting stents (ZES) and 229 everolimus-eluting stents (EES). RESULTS: For the prediction of angiographic ISR, the MSA of each DES was measured. The poststenting MSA was 6.4 ± 1.8 mm(2) in SES, 6.2 ± 2.1 mm(2) in ZES and 6.2 ± 2.1 mm(2) in EES. At the 9-months follow-up, the incidence of angiographic ISR was similar between SES (3.3%) vs. ZES (4.5%) vs. EES. (4.4%), (P = 0.53). Multivariable logistic regression analysis identified the post-stenting MSA as the only independent predictor of angiographic ISR in ZES (Odds ratio 0.722, 95% confidence interval 0.581-0.897, P = 0.001) and in EES (Odds ratio 0.595, 95% confidence interval 0.392-0.904, P = 0.015). The best MSA cut-off value was 5.5 mm(2) for the prediction of SES restenosis (sensitivity 72.2% and specificity 66.3%). For ZES, the optimal MSA predicting ISR was 5.3 mm(2) (sensitivity 56.7% and specificity 61.8%). For EES, the MSA <5.4 mm(2) predicted ISR (sensitivity 60.0% and specificity 60.0%). CONCLUSIONS: As a preventable mechanism of ISR, smaller stent area predicted angiographic restenosis of the second generation DES as well as the first generation. The optimal cut-off values of post-stenting MSA for preventing restenosis were similar between ZES vs. EES vs. SES.