Lower on-treatment platelet reactivity during everolimus-eluting stent implantation contributes to the resolution of post-procedural intra-stent thrombus: serial OCT observation in the PRASFIT-Elective study.

Intra-stent thrombus (IS-Th) formed immediately after percutaneous coronary intervention (PCI) is associated with subsequent adverse coronary events. However, the impact of on-treatment platelet reactivity on IS-Th is unknown. PRASFIT-Elective is a multicenter study of PCI patients receiving prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg), with aspirin (100 mg). Among the 742 study patients, 111 were pre-specified for the OCT sub-study. Of these, 82 underwent OCT immediately after PCI to assess IS-Th and at an 8-month follow-up to evaluate the fate of the IS-Th. Lesions were considered resolved when IS-Th were detected after PCI but not on the follow-up or persistent when IS-Th were observed on both scans. The P2Y12 Reactive Unit (PRU) value was determined at the initial PCI and 4 and 48 weeks post-PCI. In 76 patients (86 lesions), we detected 230 IS-Th initially, and 196 IS-Th (85.2%) were resolved at the 8-month OCT. At PCI, but not 4 or 48 weeks after, the resolved IS-Th group had a lower PRU than the persistent IS-Th group (199 ± 101 vs. 266 ± 102, p = 0.008). Multivariate logistic regression analyses revealed that lower PRU at PCI and less calcified lesions were independent predictive factors for the resolution of IS-Th. Local lesion-related factors and lower on-treatment platelet reactivity at the time of PCI may contribute to the resolution of IS-Th after EES implantation, potentially improving clinical outcome.

Vascular response to biolimus A-9 eluting stent in patients with shorter and prolonged dual antiplatelet therapy: optical coherence tomography sub-study of the NIPPON trial.

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point.

Association between daily glucose fluctuation and coronary plaque properties in patients receiving adequate lipid-lowering therapy assessed by continuous glucose monitoring and optical coherence tomography.

BACKGROUND: Glucose fluctuation has been recognized as a residual risk apart from dyslipidemia for the development of coronary artery disease (CAD). This study aimed to investigate the association between glucose fluctuation and coronary plaque morphology in CAD patients. METHODS: This prospective study enrolled 72 consecutive CAD patients receiving adequate lipid-lowering therapy. They were divided into 3 tertiles according to the mean amplitude of glycemic excursions (MAGE), which represents glucose fluctuation, measured by continuous glucose monitoring (tertile 1; < 49.1, tertile 2; 49.1 ~ 85.3, tertile 3; >85.3). Morphological feature of plaques were evaluated by optical coherence tomography. Lipid index (LI) (mean lipid arc × length), fibrous cap thickness (FCT), and the prevalence of thin-cap fibroatheroma (TCFA) were assessed in both culprit and non-culprit lesions. RESULTS: In total, 166 lesions were evaluated. LI was stepwisely increased according to the tertile of MAGE (1958 ± 974 [tertile 1] vs. 2653 ± 1400 [tertile 2] vs. 4362 ± 1858 [tertile 3], p < 0.001), whereas FCT was the thinnest in the tertile 3 (157.3 ± 73.0 µm vs. 104.0 ± 64.1 µm vs. 83.1 ± 34.7 µm, p < 0.001, respectively). The tertile 3 had the highest prevalence of TCFA. Multiple linear regression analysis showed that MAGE had the strongest effect on LI and FCT (standardized coefficient ß = 0.527 and -0.392, respectively, both P < 0.001). Multiple logistic analysis identified MAGE as the only independent predictor of the presence of TCFA (odds ratio 1.034; P < 0.001). CONCLUSIONS: Glucose fluctuation and hypoglycemia may impact the formation of lipid-rich plaques and thinning of fibrous cap in CAD patients with lipid-lowering therapy.

Vascular responses in patients with and without diabetes mellitus after everolimus-eluting stent implantation.

BACKGROUND: Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM). METHODS AND RESULTS: We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients. CONCLUSIONS: Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients.

Favorable vessel healing after nobori biolimus A9-eluting stent implantation-6- and 12-month follow-up by optical coherence tomography.

BACKGROUND: Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6-9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear. METHODS AND RESULTS: We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72 ± 23 to 82 ± 25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96 ± 3.97% to 1.51 ± 1.63%, P=0.001, and 0.50 ± 1.84% to 0.06 ± 0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24). CONCLUSIONS: Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months.

Neoatherosclerosis and mural thrombus detection after sirolimus-eluting stent implantation.

BACKGROUND: Although both optical coherence tomography (OCT) and angioscopy are robust tools for detecting intrastent thrombi and neoatherosclerosis in vivo, whether OCT findings are comparable with angioscopy findings remains unclear. METHODS AND RESULTS: 22 patients presenting with de novo lesions underwent 26 sirolimus-eluting stent (SES) implantations, with follow-up OCT and angioscopy at 10 months post-implantation for segmental assessment of the proximal, mid-, and distal SES segments (66 segments). The mean signal intensity index (signal intensity of the neointima/signal intensity of fibrous intimal hyperplasia) was quantified for angioscopically detected in-stent yellow and white segments. The detection rate for red thrombi was numerically higher with angioscopy than with OCT (17% vs. 9%; P=0.053). Angioscopically detected in-stent yellow segments were categorized into 3 OCT patterns: "high-attenuation tissue covering struts" (OCT-defined neoatherosclerosis), "high-attenuation tissue underneath struts," and "low-attenuation and low-intensity tissue covering struts"; further, macrophage-like appearance was most frequently observed with OCT-defined neoatherosclerosis (56%, 6.3%, and 0%, respectively, P<0.001). The mean signal intensity index of neoatherosclerosis was significantly lower than that of angioscopically detected in-stent white segments (0.929 vs. 0.997, P=0.004). CONCLUSIONS: Current OCT-based definitions for thrombus detection may underestimate the presence of subclinical red thrombi. Qualitative and quantitative OCT assessments of the neointima may enhance the detection of neoatherosclerosis over SES in vivo.

Subsequent shunt closure after targeted medical therapy can be an effective strategy for secundum atrial septal defect with severe pulmonary arterial hypertension: two case reports : strategy for ASD with severe PAH.

Secundum atrial septal defect (ASD) is the most common form of congenital heart disease in adults. Surgical and transcatheter closures of ASD are widely accepted therapeutic approaches. In patients with severe pulmonary arterial hypertension (PAH), however, the closure of the defect is still controversial. We report two cases of ASD patients with severe PAH successfully repaired subsequent to effective medical therapy. Subsequent shunt closure after targeted medical therapy can be an effective strategy in selected ASD patients with severe PAH.

Noninvasive and simple assessment of cardiac output and pulmonary vascular resistance with whole-body impedance cardiography is useful for monitoring patients with pulmonary hypertension.

BACKGROUND: Right heart catheterization (RHC) is the gold standard for the diagnosis of pulmonary hypertension (PH) and a useful tool for monitoring PH. However, there are some disadvantages in the regular use of RHC because it is invasive. Noninvasive methods for monitoring hemodynamics are needed to manage patients with PH. In this study, we aimed to evaluate the reliability of noninvasive hemodynamic assessment with whole-body impedance cardiography (Non-Invasive Cardiac System [NICaS]) for PH. METHODS AND RESULTS: We investigated 65 consecutive patients undergoing RHC. Two-thirds of them had pulmonary arterial hypertension and one-third had chronic thromboembolic PH; 25% of the patients were receiving medical therapy. Cardiac output (CO) was estimated by NICaS (NI-CO), thermodilution (TD-CO), and the Fick method (Fick-CO). There was a strong correlation between NI-CO and TD-CO (r=0.715, P<0.0001) and Fick-CO (r=0.653, P<0.0001). Noninvasive pulmonary vascular resistance (PVR) was estimated using a conventional invasive equation with NI-CO, mean pulmonary arterial pressure was calculated by echocardiographic measurement, and pulmonary capillary wedge pressure was estimated at 10mmHg in all cases. NICaS-derived PVR was very strongly correlated with invasive PVR (TD-PVR: r=0.704, P<0.0001; Fick-PVR: r=0.702, P<0.0001). CONCLUSIONS: Noninvasive measurement of CO and PVR using NICaS and echocardiography is a useful tool for the assessment of PH.

Potential benefit of final kissing balloon inflation after single stenting for the treatment of bifurcation lesions--insights from optical coherence tomography observations.

BACKGROUND: Treatment of coronary bifurcation lesions using a single stenting strategy is preferable over that using a 2-stent technique. The benefit of final kissing inflation (FKI), however, has not been established. METHODS AND RESULTS: Seventy-two patients (76 lesions) with true bifurcation lesions treated with a single drug-eluting stent with FKI (n=33 lesions) or without FKI (non-FKI, n=43 lesions) were enrolled in this study. Optical coherence tomography (OCT) was performed at 6-12 months after implantation. Based on the OCT findings, the percentage of jailing struts (number of jailing struts/total number of struts at the bifurcation lesion) was calculated. Percentage of uncovered struts and frequency of thrombus attachment were each evaluated at the proximal, bifurcation, and distal segments. Major adverse cardiac events (MACE) were also evaluated. The percentage of jailing struts was significantly lower in the FKI than in the non-FKI group (5.8±6.2% vs. 17.3±6.1%, P<0.01). Thrombus attachment was less frequent in the FKI group (24.2% vs. 46.5%, P=0.046), especially at side-branch orifices (3.0% vs. 27.9%, P<0.001). The percentage of uncovered struts was lower in the FKI than non-FKI group at the proximal, bifurcation, and distal segments. The incidence of MACE was not different in this small cohort. CONCLUSIONS: FKI might reduce the frequency of subclinical thrombus possibly by reducing the number of jailing struts.

Qualitative and quantitative assessment of stent restenosis by optical coherence tomography: comparison between drug-eluting and bare-metal stents.

BACKGROUND: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. METHODS AND RESULTS: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01). CONCLUSIONS: The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies.

Impact of stent platform of paclitaxel-eluting stents: assessment of neointimal distribution on optical coherence tomography.

BACKGROUND: The Taxus Express™ paclitaxel-eluting stent (Express-PES) and Taxus Liberté™ PES (Liberté-PES) have identical drugs, drug doses, and polymers, but different stent platforms. The Liberté-PES platform has thinner struts, specifically designed for more uniform drug elution. METHODS AND RESULTS: Fifty-four patients who underwent 6-month follow-up optical coherence tomography (OCT) after Express-PES (n=27) or Liberté-PES (n=27) implantation were enrolled. Longitudinal and circumferential uniformity of neointimal distribution was evaluated in 3-D by computing mean neointimal thickness (NIT) within 360 equally spaced radial sectors for every 1-mm cross-section. After stenting, intravascular ultrasound showed that Liberté-PES had a significantly smaller maximum angle between adjacent struts, with a tendency toward a lower incidence of % length of the segment with maximum angle >90° than Express-PES. Liberté-PES had a significantly thinner mean NIT than the Express-PES with comparable frequency of uncovered struts. Longitudinal and circumferential absolute variation of NIT expressed by standard deviation of NIT from each sector was significantly smaller for Liberté-PES than for Express-PES. Liberté-PES had a tendency toward a decreased incidence of thrombus and peri-strut low-intensity areas (findings suggestive of delayed arterial healing), compared to Express-PES. CONCLUSIONS: Stent design and thickness appeared to affect neointima suppression of PES. The stent platform of the Liberté-PES may offer greater and more homogeneous reduction of neointimal proliferation spatially across the full length of the PES.

Effect of cytochrome P450 2C19 polymorphism on target lesion outcome after drug-eluting stent implantation in japanese patients receiving clopidogrel.

BACKGROUND: Cytochrome P450 (CYP) 2C19 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after drug-eluting stent (DES) implantation, but its contribution to lesion outcome after DES implantation is unclear. METHODS AND RESULTS: The study included 160 Japanese patients who received clopidogrel and underwent DES implantation with follow-up angiography. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The incidence of major adverse cardiac events (MACE) and target lesion revascularization (TLR) were compared among the 3 groups. Optical coherence tomography (OCT) was performed for 120 patients to evaluate the incidence of intra-stent thrombi. Of the 160 patients, the proportion of EM, IM, and PM was 37.5%, 48.1%, and 14.4%, respectively. The incidence of TLR and MACE was more frequent in IM and PM than EM (TLR: 18.2% and 26.1% vs. 3.3%, P=0.008, MACE: 22.1% and 30.4% vs. 5.0%, P=0.005). Among the 120 patients who underwent follow-up OCT, intra-stent thrombi were more frequently detected in IM and PM than in EM (45.6% and 63.2% vs. 20.5%, P=0.005). The incidence of TLR was significantly higher in patients with than in those without intra-stent thrombi (27.7% vs. 6.8%, P=0.003). CONCLUSIONS: CYP2C19 loss-of-function polymorphism might be associated with the incidence of MACE and TLR in association with intra-stent thrombi.

Pulmonary Endarterectomy and Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension　- Similar Effects on Health-Related Quality of Life.

Background: While hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) can be improved by invasive therapy such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), there has been little data on the health-related quality of life (HRQOL) in such patients. Methods and Results: This single-center and observational study compared the impact of invasive therapy on HRQOL. We utilized the Medical Outcome Study 36-Item Short Health Survey (SF-36) to measure HRQOL and compared HRQOL changes after PEA and BPA. A total of 48 patients were diagnosed with CTEPH. Of these, 39 patients completed questionnaires before and after invasive therapy. The PEA group (n=15) and the BPA group (n=24) had similar improvements in clinical parameters. With regard to HRQOL score, both groups had fairly low scores in physical functioning (PF), role physical (RP), general health (GH), social functioning (SF), role emotional (RE), and physical component summary (PCS) at baseline. PF, GH, vitality (VT), mental health (MH), and PCS had significant improvements in the PEA group while PCS and all subscales except for bodily pain (BP) had significant improvements in the BPA group. Furthermore, changes between baseline and follow-up were not significantly different between the 2 groups. Conclusions: BPA for patients who are ineligible for PEA can recover HRQOL to a similar level to that achieved by PEA.

Extensive revascularisation by balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension beyond haemodynamic normalisation.

AIMS: Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, even after BPA many patients still suffered from exertional dyspnea. Our purpose is to clarify the clinical validity of extensive revascularization by BPA (ERBPA) beyond hemodynamic normalization. METHODS AND RESULTS: 35 CTEPH patients with normalized or borderline mean pulmonary arterial pressure (mPAP) after BPA were retrospectively analyzed. We evaluated the clinical efficacy of ERBPA strategy in 15 patients (ERBPA group) by comparing with the natural course of 20 patients who could be followed without additional BPA (conventional BPA group). ERBPA reduced the number of pulmonary arterial segments with residual stenoses from 11.7±0.4 to 5.3±0.5 segments. Symptoms, six-minute walking distance, and VE/VCO2 slope were significantly improved in the ERBPA group but not the conventional BPA group, which indicated that this improvement was due to ERBPA and not merely a natural progression after hemodynamic normalization. Complications accompanied with ERBPA were fewer than that of the initial BPA therapy. CONCLUSION: ERBPA targeting residual stenoses can safely ameliorate symptoms and exercise capacity by additional improvement of hemodynamics. The results encourage us to optimize the current BPA goal to be more aggressive.

Favorable early vessel healing after everolimus-eluting stent implantation: 3-, 6-, and 12-month follow-up of optical coherence tomography.

BACKGROUND: Although a prospective randomized control study revealed that 3-month dual anti-platelet therapy (DAPT) is safe and does not compromise the efficacy of everolimus-eluting stent (EES) in selected patients, detailed vessel healing at early phase after EES implantation has yet to be investigated in Japanese patients. METHODS AND RESULTS: A total of 27 lesions in 19 patients treated with EES were serially evaluated by using optical coherence tomography (OCT) at 3, 6, and 12 months after stent implantation. In addition to standard quantitative OCT parameters, the percentage of stents with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (63±17µm; 83±30µm; and 111±44µm, respectively; p=0.006) and small decrease in average lumen area (6.80±2.57mm2, 6.62±2.58mm2, 6.33±2.58mm2, p=0.038) from the 3- to the 12-month follow-up. The incidences of uncovered and malapposed struts were low at 3 months and did not significantly change at 6 months and 12 months (3.01±4.43; 2.45±3.75; and 1.47±3.16, p=0.143, and 0.75±0.65; 0.63±0.73; and 0.58±1.42, p=0.162, respectively). Also, frequency of struts with PLIA was already low at three months and significantly decreased during the follow-up (6.4±6.5; 4.6±5.4; and 2.3±3.3, respectively; p=0.001). CONCLUSION: Favorable vessel healing was achieved at 3 months after EES implantation without neointimal hyperplasia which was persistently suppressed up to 12 months.

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Residual symptoms after pulmonary endarterectomy (PEA) remain as the clinical issues to be solved. Additional balloon pulmonary angioplasty (BPA) after PEA showed its efficacy with symptoms in a case series, although long-term spontaneous recovery of exercise ability after PEA was also reported. However, no studies have validated the clinical efficacy of additional BPA by directly comparing PEA with and without BPA. The aim of this study was to retrospectively evaluate the efficacy of additional BPA as a sequential hybrid therapy for chronic thromboembolic pulmonary hypertension after PEA. METHODS AND RESULTS: Among 44 patients with chronic thromboembolic pulmonary hypertension, 20 patients had residual symptoms after PEA. Of those, 10 patients underwent additional BPA (hybrid group) and were compared with the other 10 patients, who were followed up without BPA (PEA group). The period from PEA to additional BPA was 7.3±2.3 months. In hybrid group, mean pulmonary arterial pressure was significantly improved by PEA (40.6±1.8 to 26.9±3.1 mm Hg, P=0.001) and improved further (to 16.7±1.8 mm Hg, P=0.002) with additional BPA, which resulted in remarkable improvement in World Health Organization (WHO) functional class (pre- to post-BPA: class I/II/III/IV, 0/5/4/1 to 7/3/0/0; P<0.001). Compared with the PEA group at follow-up, the hybrid group achieved better mean pulmonary arterial pressure (18.7±1.7 versus 30.2±3.2 mm Hg, P=0.008), WHO functional class (class I/II/III/IV, 7/3/0/0 versus 0/8/2/0; P=0.001), and 6-minute walking distance (429±38 versus 319±22 m, P=0.028). CONCLUSIONS: A sequential hybrid strategy improved residual symptoms and exercise capacity compared with single-PEA therapy.

Morphological and pharmacological determinants of peri-procedural myocardial infarction following elective stent implantation: Optical coherence tomography sub-analysis of the PRASFIT-Elective study.

BACKGROUND: Previous studies have suggested that peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) is associated with adverse short- and long-term outcomes, and several morphological predictors of PMI have been studied. However, the determinants of PMI under novel anti-platelet therapy are not fully elucidated. METHODS AND RESULTS: PRASFIT-Elective is a multicenter, parallel-group study of PCI patients in non-acute settings receiving either prasugrel or clopidogrel in addition to aspirin. Among 742 study patients, 94 (116 lesions) underwent optical coherence tomography (OCT) to evaluate the area of intra-stent tissue (IST, which comprises tissue protrusion and thrombus) after stenting in addition to standard parameters. We investigated the relationship between the peak creatine kinase (CK)-MB fraction levels after PCI and post-stent OCT findings, as well as on-treatment platelet reactivity determined by the P2Y12 reaction units (PRU) at PCI, in a post hoc manner. The multivariate linear analysis revealed that a larger total IST area (standardized coefficient: 0.370, p<0.001) and smaller minimal stent diameter (standardized coefficient: -0.242, p<0.014), but not the PRU value (p=0.988), were independently associated with CK-MB leakage. The IST area after stenting was mainly determined by the target lesion lipid index (averaged lipid arc×lipid length) (r=0.583, p<0.001). CONCLUSION: Following elective PCI, a large IST area originating from a lipid-rich plaque and a smaller minimal stent diameter were associated with PMI.

High perfusion pressure as a predictor of reperfusion pulmonary injury after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Clinical efficacy of balloon pulmonary angioplasty (BPA) to the patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) for improving pulmonary hemodynamics and exercise tolerance has been reported in these several years. However, reperfusion pulmonary injury (RPI) remains to be a major complication of BPA to overcome. This study elucidated the local predictor of RPI. METHODS: Twenty-eight consecutive patients with non-operable CTEPH underwent BPA for lesions in the segmental or sub-segmental vessels. Pre- and post-BPA pulmonary arterial pressures at proximal (Pp) and distal (Pd) to the stenosis were measured by a 0.014-in. pressure wire. Positive or negative RPI was evaluated by chest computed tomography in each re-perfused segment separately 4 h after BPA. RESULTS: Pressure measurements pre- and post-BPA were obtained from 110 lesions, where Pd and pressure ratio (Pd/Pp) increased after BPA in all lesions. Among them, RPI was observed in 49 lesions (44.5%). In the RPI-positive lesions, post-BPA Pd and post-BPA Pd/Pp were higher compared with the RPI-negative lesions. Multivariate logistic analysis revealed that the post-BPA Pd was independently associated with RPI incidence. Receiver operating characteristic curve analysis demonstrated the best cut-off value of 19.5 mm Hg for post-BPA Pd to predict RPI. CONCLUSIONS: High reperfusion pressure after BPA could be a predictor of RPI. Monitoring local pressure during BPA procedure may have a potential to reduce the incidence of RPI.

The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry.

AIMS: Although pathological studies have indicated the development of neoatherosclerosis (NA) after stenting, its risk factors and impact on future clinical events remain unclear. We aimed to clarify the possible risk factors for NA development and to evaluate the impact of NA in a large Japanese observational OCT database of patients with coronary heart disease. METHODS AND RESULTS: One hundred and seventy-five consecutive patients (314 lesions) who underwent OCT examination >1 year after bare metal or drug-eluting stent implantation were enrolled. We assessed the presence of NA by follow-up OCT and compared adverse clinical events between NA+ and NA- patients. Forty-six patients had NA at the follow-up OCT. These patients had higher low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) levels at follow-up. In multivariate logistic analysis, LDL cholesterol and CRP levels at follow-up were independently associated with the presence of NA (odds ratio [OR]: 1.022, p=0.008, OR 1.022, p=0.001, respectively). Moreover, patients with NA had a higher incidence of major adverse cardiac events (MACE) at follow-up. Multivariate Cox hazard analysis showed that the presence of NA was an independent risk factor for MACE (hazard ratio: 2.909, p=0.012). CONCLUSIONS: High LDL cholesterol and CRP levels may be risk factors for NA development in patients treated with coronary stents. Moreover, the presence of NA was independently associated with MACE, suggesting the need for careful clinical follow-up of these patients.

Impact of residual platelet reactivity under clopidogrel treatment for lesions and the clinical outcome after drug-eluting stent implantation in patients with hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are at high risk for adverse clinical outcomes after drug-eluting stent (DES) implantation. However, the impact of residual platelet reactivity under dual anti-platelet therapy in this subset of patients remains unclear. METHODS: We enrolled 142 stable angina patients (194 lesions) treated with DES, who were taking aspirin and 75mg clopidogrel and had undergone 8-month angiography with optical coherence tomography (OCT). OCT findings and major adverse cardiac events (MACEs) at 1 year (cardiac death, acute coronary syndrome, target lesion and vessel revascularization, and stent thrombosis) were compared between 28 HD patients and 114 non-HD patients. Responsiveness to clopidogrel was assessed by measuring P2Y12 reaction unit (PRU) at 8 months. RESULTS: PRU was significantly higher in HD patients than in non-HD patients (p=0.006), even though proportion of cytochrome P450 2C19 genotype was equivalent. HD patients had a significantly higher rate of thrombi formation (assessed using OCT) and MACEs than non-HD patients (thrombi: p=0.001; MACEs: p=0.0001). The PRU value was independently associated with MACEs in both groups. The optimal cutoff values of PRU for predicting MACEs were 235 for HD patients and 259 for non-HD patients. CONCLUSIONS: HD was associated with a high residual platelet reactivity, which may contribute to the higher incidence of MACEs after DES implantation in HD patients. HD may be a patient profile that merits a more potent anti-platelet regimen.