Toru Inami

Late Vascular Responses From 2 to 4 Years After Implantation of Sirolimus-Eluting Stents: Serial Observations by Intracoronary Optical Coherence Tomography

Background—Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results—Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 &mgr;m versus 123.0±102.5 &mgr;m; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions—The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.Background— Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results— Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P <0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P =0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P =1.0), the cross sections with ESL increased (9.6% versus 15.2%; P =0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P <0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P =1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions— The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

Impact of Prediabetic Status on Coronary Atherosclerosis A multivessel angioscopic study

OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Six-month follow-up evaluation for everolimus-eluting stents by intracoronary optical coherence tomography: comparison with paclitaxel-eluting stents.

BACKGROUND Although several clinical trials have shown the superior efficacy and safety of second-generation everolimus-eluting stents (EES) in comparison with first-generation paclitaxel-eluting stents (PES), the differences in the vascular healing process between EES and PES in a human coronary artery during an early stage are unknown. METHODS A prospective optical coherence tomography (OCT) observation was performed for 25 EES in 21 patients and 27 PES in 21 patients at 6 months after implantation. Cross-sections within single-stent segments were analyzed at intervals of 1mm. The neointimal (NI) thickness on each strut was measured. Uncovered struts (NI thickness=0 μm), malapposed struts, NI area (%), uncovered strut ratio >0.3 (UCSR; number of uncovered struts/number of total struts) per cross-section, and in-stent thrombus were evaluated. RESULTS A total of 5198 EES struts in 514 cross-sections and 4243 PES struts in 469 cross-sections were identified. NI thickness and its area were smaller for EES than PES (80.0 ± 84.8 μm vs. 117.9 ± 140.0 μm and 19.1 ± 8.9% vs. 23.7 ± 11.5%, respectively; P<0.001). The frequencies of uncovered struts and malapposed struts were lower in EES compared to PES (2.3% vs. 5.2% and 2.1% vs. 5.7%, respectively; P<0.001). Patients who had cross-sections of UCSR >0.3 and thrombi were identified less frequently in EES than in PES group (5% vs. 57%; P<0.001, and 19% vs. 48%; P=0.05, respectively). CONCLUSIONS Six-month OCT examination showed a favorable vessel healing response after the implantation of EES, demonstrating less in-stent late loss as well as fewer uncovered struts and better stent apposition to the vessel wall in comparison with PES.

Late Vascular Responses From 2 to 4 Years After Implantation of Sirolimus-Eluting StentsClinical Perspective

Background—Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results—Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 &mgr;m versus 123.0±102.5 &mgr;m; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions—The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.Background— Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings. Methods and Results— Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P <0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P =0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P =1.0), the cross sections with ESL increased (9.6% versus 15.2%; P =0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm2 versus 0.62±0.68 mm2 and 16.6±5.4° versus 65.1±38.4°; P <0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P =1.0). All thrombi were identified in patients who had cross sections with ESL. Conclusions— The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

Links between sleep disordered breathing, coronary atherosclerotic burden, and cardiac biomarkers in patients with stable coronary artery disease.

BACKGROUND Sleep disordered breathing (SDB) is highly prevalent in patients with cardiovascular disease, although it is not clear whether SDB has any link to coronary atherosclerotic burden in patients with stable coronary artery disease (CAD). This study sought to analyze the links between SDB, coronary atherosclerotic burden, and cardiac biomarkers in stable CAD patients. METHODS AND RESULTS We studied 83 consecutive patients who underwent coronary angiography or scheduled percutaneous coronary intervention. SDB was evaluated by an ambulatory polysomnographic monitoring device. Coronary atherosclerotic burden was evaluated by the Gensini score, and myocardial stress/injury were assessed by measuring plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hs-TnT). Patients with an apnea hypopnea index (AHI)≧15 events/h (n=32) showed significantly higher Gensini score (35.7±38.0 vs 20.1±19.7, p=0.033) than those with AHI<15. The higher AHI group showed significantly higher NT-proBNP (275.8±402.6 pg/ml vs 131.9±146.3 pg/ml, p=0.047) and hs-TnT levels (0.011±0.005 ng/ml vs 0.008±0.003 ng/ml, p=0.015). Furthermore it was revealed that AHI significantly correlated with the Gensini score (r=0.253, p=0.036), NT-proBNP (r=0.266, p=0.027), and hs-TnT (r=0.274, p=0.023), and multiple stepwise linear regression analysis revealed that AHI (β=0.257, p=0.029) and history of smoking (β=0.244, p=0.038) were independently correlated with Gensini score among clinical and SDB-related parameters. CONCLUSIONS Severity of SDB has a significant link to the severity of coronary atherosclerotic burden, which also reflected elevated NT-proBNP and hs-TnT as silent myocardial ischemia and minute myocardial injury even in stable CAD patients.

The possibility of delayed arterial healing 5 years after implantation of sirolimus-eluting stents: serial observations by coronary angioscopy.

BACKGROUND Although very late stent thrombosis occurs several years after implantation of sirolimus-eluting stent (SES), the morphologic changes of the stent beyond 2 years have not yet been systematically studied in living patients. The late vascular response to SES was therefore evaluated by serial angioscopic studies at 2 and 5 years after stent implantation. METHODS A total of 17 patients with 17 SES underwent a repeated angioscopy procedure at 2 and 5 years. Neointimal stent coverage (NSC) was classified as follows: grade 0, presence of uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, complete neointimal coverage without visible struts. For each patient, the minimum and maximum NSC grade and the existence of in-stent thrombus were recorded. RESULTS The minimum and maximum NSC grade did not increase between the 2 and 5 years (0.59 ± 0.51 vs 0.88 ± 0.70, P = .17, and 1.82 ± 0.39 vs 1.94 ± 0.24, P = .30, respectively). The prevalence of patients with uncovered struts did not significantly decrease from 2 to 5 years (41% vs 29%, P = .49). During the follow-up period, 3 of 6 thrombi disappeared, whereas new thrombus formation was found in 3 patients without any clinical symptoms. In-stent thrombus did not decrease (35% vs 35%, P > .99). CONCLUSIONS The current serial angioscopic study suggests that incomplete NSC and the prevalence of latent thrombus within the SES segments did not decrease from 2 to 5 years. The risk of stent thrombosis related to incomplete healing of SES may continue for an extended period.

Detection of acute aortic dissection by extremely high soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and low troponin T levels in blood

Detection of acute aortic dissection by extremely high soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and low troponin T levels in blood Nobuaki Kobayashi ⁎, Noritake Hata , Noriaki Kume , Shinya Yokoyama , Masamichi Takano , Takuro Shinada , Kazunori Tomita , Akihiro Shirakabe , Toru Inami , Yoshihiko Seino , Kyoichi Mizuno d a Division of Intensive Care Unit, Chiba-Hokusoh Hospital, Nippon Medical School, Chiba, Japan b Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan c Cardiovascular Center, Chiba-Hokusoh Hospital, Nippon Medical School, Chiba, Japan d Division of Cardiology, Nippon Medical School, Tokyo, Japan

Impact of small thrombus formation in restenotic bare-metal stent lesions associated with acute coronary syndrome: Identification by optical coherence tomography

BACKGROUND Although in-stent restenosis (ISR) after bare-metal stent (BMS) implantation is considered to be clinically benign, ISR is often associated with adverse complications, such as acute coronary syndrome (ACS). The frequency, type, and location of thrombi in ISR lesions and their clinical presentation have not yet been precisely validated. METHODS Thirty angiographic ISR lesions occurring within 3 to 8 months after stenting were evaluated by optical coherence tomography (OCT). A thrombus was defined as a mass protruding into the lumen with an irregular surface, and its type was divided into red or white. The maximum size of a thrombus and the longitudinal distance from the thrombus to the narrowest lumen were measured. RESULTS A thrombus was identified in 2 patients by angiography and in 10 patients by OCT (7% vs. 33%; P=0.01). OCT showed that 9 patients had white thrombus and another patient had both types of thrombi. ACS relevant to ISR was seen in 6 patients, and the frequency of ACS was significantly higher in patients with thrombus than in those without thrombus [50% (5/10) vs. 5% (1/20); P=0.003]. The maximum size of the thrombus was 412 ± 220 µm in height, 424 ± 251 µm in width, and the longitudinal distance between the thrombus and the minimum lumen area was 0.3 ± 0.7 mm. CONCLUSIONS One third of ISR lesions following BMS deployment dominantly contained a white thrombus, and half of them were associated with ACS. A small thrombus formation adjacent to the narrowest lumen in an ISR lesion may therefore contribute to the clinical presentation of ACS.

Switching to Pitavastatin in Statin-Treated Low HDL-C Patients Further Improves the Lipid Profile and Attenuates Minute Myocardial Damage.

Background The aim of this study is to determine the prevalence of minute myocardial damage (MMD) in already statin-treated dyslipidemic patients with a low high-density lipoprotein-cholesterol (HDL-C) level, and to evaluate whether pitavastatin could affect the lipid profiles and biomarkers reflecting myocardial stress and injury. Methods Twenty patients (15 men; age 66 ± 8) being treated with any statin but who had HDL-C < 40 mg/dL, were switched to pitavastatin (2 mg/day) treatment. The patient lipid profiles and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), and high-sensitive C-reactive protein (hs-CRP) were evaluated for six months. Results At three months after the statin replacement, the HDL-C significantly increased from 37 ± 3 mg/dL to 40 ± 5 mg/dL (P < 0.05), and the low-density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio significantly reduced (100 ± 28 mg/dL to 86 ± 22 mg/dL, P < 0.05; 2.68 ± 0.67 to 2.17 ± 0.64, P < 0.05, respectively), and these changes were sustained for six months. In the whole study population, no significant changes were observed in the NT-proBNP, hsTnT, or hsCRP for six months. However, in 11 cases who showed a positive (> 0.003 ng/mL) hsTnT at baseline, a significant reduction in the hsTnT was observed (0.016 ± 0.020 ng/mL to 0.014 ± 0.020 ng/mL, P < 0.05), and its percent reduction significantly correlated with the percent increase in HDL-C (r = -0.68, P < 0.05). Conclusions MMD (positive hsTnT) was observed in more than half of patients with low HDL-C despite the administration of any statin, and the replacement of their previous statin with pitavastatin further improved their lipid profiles and led to better myocardial protection, possibly mediated via the elevation of the HDL-C level.

Management of Coronary Artery Disease in Patients Undergoing Elective Abdominal Aortic Aneurysm Open Repair

The efficacy of prophylactic coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in patients with abdominal aortic aneurysm (AAA) scheduled for open repair surgery remains controversial.