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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Use of Coils and a Pulmonary Vasodilator to Reduce Pulmonary Hypertension in a Patient with Interstitial Pneumonia and Scleroderma.

Fistulas between systemic and pulmonary arteries are associated with various underlying etiologies and cause pulmonary hypertension (PH). Diagnosis of this condition requires several imaging studies and the exclusion of other possible causes of PH. We herein report a case of a patient with interstitial pneumonia and scleroderma. The imaging revealed multiple fistulas involving the inferior phrenic and left lower pulmonary arteries. The fistulas were closed using coils, but the PH remained presumably due to other undiagnosed fistulas. The improvement of symptoms following use of a supplementary pulmonary vasodilator provides the hope that the chosen treatment could be a viable alternative approach for other similar cases.

Serial Optical Coherence Tomography Evaluation at 6, 12, and 24 Months After Biolimus A9-Eluting Biodegradable Polymer-Coated Stent Implantation.

BACKGROUND: The Nobori (Terumo Corporation, Tokyo, Japan) is a biolimus A9-eluting stent (BES) featured with a biodegradable polymer coated on the abluminal side only. We previously reported that favourable vessel healing was achieved at 6-12 months after BES implantation. However, detailed long-term vessel reaction after BES deployment is unclear. METHODS: Twenty-two BESs were serially evaluated using optical coherence tomography (OCT) at 6, 12, and 24 months after stenting. Average neointimal thickness, uncovered struts, and neointimal unevenness score (each cross-section as maximum neointimal thickness in 1 cross section divided by the average neointimal thickness of the same cross-section) were manually measured. In addition, we evaluated the percentage of struts with peri-strut low-intensity area (a region around stent struts that homogenously showed less intensity than the surrounding tissue, which suggests fibrin deposition or impaired neointima maturation), thrombi, and atherogenic neointimas (neointimas containing a diffuse border and poor-signal region with invisible struts due to marked signal attenuation). RESULTS: Serial OCT observation revealed a small gradual increase in neointimal thickness from 6 to 24 months (73 ± 24 µm; 81 ± 26 µm; and 108 ± 35 µm, respectively, P = 0.001) with a nonsignificant decrease in the lumen area (6.36 ± 1.98 mm(2); 6.18 ± 2.04 mm(2); and 5.87 ± 2.06 mm(2); P = 0.72). Frequency of uncovered struts (3.89 ± 3.91%; 1.55 ± 1.63%; and 0.23 ± 0.67%; P = 0.001), neointimal unevenness score (1.95 ± 0.18% to 1.86 ± 0.19% to 1.78 ± 0.17; P = 0.012), percentage of thrombi (5%, 0%, and 0%; P = 0.37) and peri-strut low-intensity area (6.8%, 5.1%, and 1.6%; P = 0.017) decreased from 6 to 12 and 24 months. Atherogenic neointima was not observed in the event-free OCT cohort. CONCLUSIONS: The Nobori stent achieved acceptable long-term vessel healing, mostly without adverse vessel reactions.

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.

Effect of daily glucose fluctuation on coronary plaque vulnerability in patients pre-treated with lipid-lowering therapy: a prospective observational study.

OBJECTIVES: This study sought to investigate the effect of daily glucose fluctuation on coronary plaque properties in patients with coronary artery disease (CAD) pre-treated with lipid-lowering therapy. BACKGROUND: There is growing evidence that glucose fluctuation, as a residual risk apart from dyslipidemia, is an important factor contributing to the development of CAD. METHODS: This prospective study enrolled 70 consecutive CAD patients who were referred for percutaneous coronary intervention and whose low-density lipoprotein cholesterol level was <120 mg/dl under statin treatment or <100 mg/dl without statins. Daily glucose fluctuation was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). The plaque properties in the culprit and nonculprit lesions were assessed by virtual histology intravascular ultrasound, and the volume percentage of necrotic core within the plaque (%NC) and the presence of thin-cap fibroatheroma were evaluated. RESULTS: In total, 165 lesions were evaluated in 70 patients (40 diabetic and 30 nondiabetic patients). %NC was well correlated with MAGE (r = 0.490, p <0.001). A linear mixed effect model showed that MAGE had the strongest effect on %NC (coefficient ß = 0.080 ± 0.020 [standard error], p < 0.001). The generalized linear mixed effect model revealed that MAGE was the only independent predictor of the presence of thin-cap fibroatheroma (odds ratio: 1.037; 95% confidence interval: 1.010 to 1.065; p = 0.007). CONCLUSIONS: Daily glucose fluctuation may have an effect on coronary plaque vulnerability in patients with CAD pre-treated with lipid-lowering therapy. Further investigations should address the rationale for the early detection and control of glucose fluctuation in the era of universal statin use for CAD patients.

Two-year vessel healing after everolimus-eluting stent implantation: serial assessment by optical coherence tomography.

BACKGROUND: Previous reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES). METHODS: We evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus. RESULTS: Although the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, -0.06±0.36 vs. -0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups. CONCLUSION: Although both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation.

Impact of cytochrome P450 2C19 loss-of-function polymorphism on intra-stent thrombi and lesion outcome after everolimus-eluting stent implantation compared to that after first-generation drug-eluting stent implantation.

BACKGROUND: The contribution of clopidogrel response due to cytochrome P450 (CYP) 2C19 loss-of-function polymorphism after drug-eluting stent (DES) implantation is unclear. METHODS: A total of 196 patients who had undergone optical coherence tomography (OCT) at 8 months following first-generation DES (120 lesions) and current-generation everolimus-eluting stent (EES) implantation (127 lesions) were enrolled. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs). OCT findings were compared among the 3 groups. Responsiveness to clopidogrel was assessed by VerifyNow platelet reactivity unit (PRU). RESULTS: The incidence of intra-stent thrombi was significantly higher after first-generation DES implantation compared with EES implantation (35% vs 13%, respectively; p=0.0001). In the first-generation DES group, the incidence of intra-stent thrombi significantly increased among EMs, IMs, and PMs (21% vs 36% vs 63%, respectively; p=0.007), while there was no significant difference among the 3 groups after EES implantation (10% vs 13% vs 20%, respectively; p=0.55). The PRU significantly increased among EMs, IMs, and PMs in each stent group. In multivariate analyses, although PMs had a 3-fold higher risk of thrombi formation compared with non-PMs after first-generation DES implantation, there were no significant differences in thrombi formation between the 2 groups after EES implantation. The optimal PRU cutoff values for the prediction of intra-stent thrombi with first-generation DES and EES were 234 and 256, respectively. CONCLUSION: CYP2C19 loss-of-function polymorphism is associated with a higher incidence of intra-stent thrombi after first-generation DES implantation, while the impact is attenuated following EES implantation.

Balloon pulmonary angioplasty: an additional treatment option to improve the prognosis of patients with chronic thromboembolic pulmonary hypertension.

AIMS: To evaluate the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) using the results of pulmonary endarterectomy (PEA) for operable patients as a reference, and annotate the role of BPA in the management of CTEPH. METHODS AND RESULTS: Data from 53 CTEPH patients were collected retrospectively. Twenty-four operable patients underwent PEA, and 29 non-operable patients underwent BPA. Patients who underwent BPA showed improved mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (39.4±6.9 to 21.3±5.6 mmHg, 763±308 to 284±128 dyn·s-1·cm-5, 3.47±0.80 to 4.26±1.15 L/min, respectively); patients who received PEA showed similar efficacy (44.4±11.0 to 21.6±6.7 mmHg, 781±278 to 258±125 dyn·s-1·cm-5, 3.35±1.11 to 4.44±1.58 L/min, respectively). The mortality rates of BPA and PEA patients were 3.4% and 8.3%, respectively. CONCLUSIONS: The efficacy and safety of BPA for non-operable cases were similar to those achieved using PEA for operable cases. BPA could be an additional treatment option for non-operable CTEPH patients, and most CTEPH patients can be satisfactorily treated by BPA or PEA.

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.

Analysis by optical coherence tomography of long-term arterial healing after implantation of different types of stents.

BACKGROUND: Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs. METHODS: We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima. RESULTS: At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents. CONCLUSIONS: Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs.