Shinjo Sonoda

Six- and Twelve-Month Results From First Human Experience Using Everolimus-Eluting Stents With Bioabsorbable Polymer

Background—Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS). Methods and Results—FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P =NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P =NS), with an associated late loss of 0.11 mm versus 0.85 mm (P <0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P =NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9±1.9 mm3 /mm versus 22.4±9.4 mm3 /mm, P <0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months. Conclusions—In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.

Seasonal variation in metabolic syndrome prevalence

Accumulating evidence has shown that seasonal variations can exist within metabolic syndrome parameters. The aim of this study was to examine the hypothesis that there are seasonal variations in the prevalence of metabolic syndrome in Japanese subjects. We investigated a total of 1202 male workers in our institution (44±10 years) who underwent health checkups in both June (summer) and December (winter) 2008. In this study, metabolic syndrome was defined according to the criteria proposed by the National Cholesterol Education Program (NCEP), the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine (JSIM). Serum levels of high-density lipoprotein-cholesterol and fasting glucose, as well as blood pressure (BP), were significantly higher in winter than in summer, whereas waist circumference and serum levels of triglyceride exhibited little change. The prevalence rates of NCEP, IDF, and JSIM metabolic syndrome in this study were 3.8, 15.1 and 12.4% in winter and 3.2, 10.7 and 8.4% in summer, respectively. Of all metabolic syndrome components, an elevated BP was most significantly correlated with the seasonal variation of metabolic syndrome prevalence. This study demonstrated seasonal variations in metabolic syndrome prevalence in Japanese male workers. These results indicate that the season of health checkups may affect the clinical diagnosis and management of metabolic syndrome.

Outcomes of everolimus-eluting stent incomplete stent apposition: a serial optical coherence tomography analysis.

AIM The aim of the present study was to evaluate the natural course of acute incomplete stent apposition (ISA) after second-generation everolimus-eluting stent (EES) when compared with first-generation sirolimus-eluting stent (SES) by using optical coherence tomography (OCT). METHODS AND RESULTS From the OCT substudy of the RESET trial, we identified 77 patients (EES = 38 and SES = 39) who successfully underwent serial OCT examination at post-stenting and 8-12-month follow-up. The presence of ISA was assessed in the OCT images, and ISA distance was measured from the centre of the strut blooming to the adjacent lumen border. Incomplete stent apposition was observed in all EES and SES at post-stenting, and it was persistent in 26% of EES and 38% of SES at 8-12-month follow-up. Maximum ISA distance was significantly decreased during the follow-up period in both EES (315 ± 94-110 ± 165 μm, P < 0.001) and SES (308 ± 119-143 ± 195 μm, P < 0.001). Receiver-operating curve analysis identified that the best cut-off value of OCT-estimated ISA distance at post-stenting for predicting late-persistent ISA at 8-12-month follow-up in EES and SES was >355 and >285 μm, respectively. CONCLUSIONS The second-generation EES showed better healing of acute ISA in comparison with the first-generation SES. Optical coherence tomography can predict late-persistent ISA after DES implantation and provide useful information to optimize PCI.

Incidence and Clinical Impact of Stent Fracture After the Nobori Biolimus-Eluting Stent Implantation

Background Stent fracture (SF) after drug‐eluting stent implantation has become an important concern. The aim of this study was to assess the incidence, predictors, and clinical impact of SF after biolimus‐eluting stent. Methods and Results A total of 1026 patients with 1407 lesions undergoing the Nobori biolimus‐eluting stent implantation and follow‐up angiography within 9 months after index procedure were analyzed. SF was defined as complete or partial separation of the stent, as assessed by using plain fluoroscopy, intravascular ultrasound, or optical coherence tomography during the follow‐up. We assessed the rate of SF and the cumulative incidence of clinically driven target lesion revascularization and definite stent thrombosis within 9 months. SF was observed in 58 (4.1%) of 1407 lesions and 57 (5.5%) of 1026 patients. Lesions with hinge motion (OR 8.90, 95% CI 3.84 to 20.6, P<0.001), tortuosity (OR 4.16, 95% CI 1.75 to 9.88, P=0.001), and overlapping stents (OR 2.41, 95% CI 0.95 to 6.10, P=0.06) were predictors of SF. Cumulative incidence of clinically driven target lesion revascularization within 9 months was numerically higher in the SF group than that in the non‐SF group (12.0% versus 1.0%). Cumulative incidence of definite stent thrombosis within 9 months tended to be higher in the SF group than that in the non‐SF group (1.7% versus 0.5%). Conclusions SF after biolimus‐eluting stent occurs in 4.1% of lesions and appears to be associated with clinically driven target lesion revascularization.

Vascular response to bioresorbable polymer sirolimus-eluting stent vs. permanent polymer everolimus-eluting stent at 9-month follow-up: an optical coherence tomography sub-study from the CENTURY II trial

Aims The Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES) is a newly developed drug-eluting stent (DES) that consists of a thin-strut, cobalt chromium with bioresorbable polymer coated only albuminally. We sought to compare tissue coverage in coronary lesions treated with BP-SES with the XIENCE permanent polymer everolimus-eluting stent (PP-EES) using optical coherence tomography (OCT). Methods and results A total of 36 patients participated in the CENTURY II trial in our institution and were randomly assigned to BP-SES (n = 15) and PP-EES (n = 21). Of these, 27 patients (13 BP-SES and 14 PP-EES) underwent OCT at 9-month follow-up. Tissue coverage and apposition were assessed on each strut, and the results in both groups were compared using multilevel logistic or linear regression models with random effects at three levels: patient, lesion, and struts. A total of 6450 struts (BP-SES, n = 2951; PP-EES, n = 3499) were analysed. Thirty and 79 uncovered struts (1.02 and 2.26%, P = 0.35), and 3 and 4 malapposed struts (0.10 and 0.11%, P = 0.94) were found in BP-SES and PP-EES groups, respectively. Mean neointimal thickness did not significantly differ between both groups (110 ± 10 vs. 93 ± 10 µm, P = 0.22). No significant differences in per cent neointimal volume obstruction (13.2 ± 4.6 vs. 10.5 ± 4.9%, P = 0.14) or other areas-volumetric parameters were detected between both groups. Conclusion BP-SES shows an excellent vascular healing response at 9-month follow-up, which is similar to PP-EES.

Association of seasonal variation in the prevalence of metabolic syndrome with insulin resistance

The aim of this study was to examine the hypothesis that seasonal variation in the prevalence of metabolic syndrome (MetS) is associated with increased insulin resistance. Among 840 Japanese male workers who were evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR) in June (summer) 2010, we prospectively studied a total of 758 subjects (40–65 years of age) who underwent an assessment in December (winter) 2010. MetS was defined according to the criteria proposed by the International Diabetes Federation (IDF) and the Japanese Society of Internal Medicine (JSIM). The median level of HOMA-IR in the study subjects was 0.84 (interquartile range: 0.60–1.19). The prevalence rates of IDF- and JSIM-MetS significantly increased from 12.4 and 9.6% in the summer to 16.6 and 13.3% in the winter, respectively (each P<0.05). Our data suggest that these increases are mainly due to increases in blood pressure (BP) and glucose during the winter assessment. The prevalence rates of IDF-MetS in the first, second, third and fourth quartiles of HOMA-IR were 1.1, 5.8, 14.3 and 29.1% in the summer and 3.1, 10.6, 21.9, and 31.3% in the winter, respectively. Similar results were obtained when using the JSIM criteria. In the third quartile, the frequency of elevated BP increased from 42.4% in the summer to 61.2% in the winter (P<0.05), and these values were mainly correlated with significant variations in IDF- and JSIM-MetS prevalence rates. This study demonstrates that seasonal variation in MetS prevalence is associated with mildly to moderately increased insulin resistance in middle-aged Japanese men.

Long-term coronary arterial response to biodegradable polymer biolimus-eluting stents in comparison with durable polymer sirolimus-eluting stents and bare-metal stents: Five-year follow-up optical coherence tomography study

OBJECTIVE The long-term coronary arterial response of biodegradable polymer biolimus-eluting stents (BES) remains unclear. We sought to evaluate the coronary arterial response of biodegradable polymer BES at 5 years after stent implantation using optical coherence tomography (OCT) as compared with that of durable polymer sirolimus-eluting stents (SES) and bare-metal stents (BMS). METHODS Five-year follow-up OCT was performed in 30 patients with 33 stents (10 with 12 BES; 10 with 11 SES; 10 with 10 BMS). Quantitative parameters and qualitative characteristics of the neointima were evaluated. A total of 5178 struts (BES, n = 2056; SES, n = 1410; BMS, n = 1712) were analyzed. RESULTS Uncovered struts were found in 15 out of 2055 struts in the BES (weighted estimate 0.01%, 95% confidence intervals [CI]: 0.00-0.33%) and 54 out of 1410 struts in the SES (0.11%, 95% CI: 0.00-3.33%) (odds ratio [OR] 0.12, 95% CI: 0.01-1.95, p = 0.13). None of 1712 struts were uncovered in the BMS. Cross-sectional qualitative analysis of neointimal tissue showed that the frequency of lipid-laden neointima tended to be lower in the BES (2.26%, 95% CI: 0.38-12.3%) compared with the SES (9.90%, 95% CI: 4.37-20.9%; OR 0.21, 95% CI 0.03-1.16, p = 0.07), and was similar to the BMS (2.23%, 95% CI: 0.54-8.74%; OR 0.98, 95% CI 0.13-7.14, p = 0.98). CONCLUSIONS Biodegradable polymer BES shows a favorable coronary arterial response compared with SES, but different response with BMS at 5 years follow-up. The observed frequency of in-stent neoatherosclerosis within BES was similar to BMS and tended to be lower than SES.

Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.

To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future.

Plasma Levels of Nitric Oxide Metabolites Are Markedly Reduced in Normotensive Men With Electrocardiographically Determined Left Ventricular Hypertrophy

Recent studies have revealed that electrocardiographically determined left ventricular hypertrophy (ECG-LVH) is a risk factor for cardiovascular death not only in hypertensive patients but also in normotensive subjects. However, the underlying mechanisms remain to be elucidated. In this study, we tested our hypothesis that normotensive subjects with ECG-LVH have reduced nitric oxide production. A total of 840 Japanese male workers were enrolled, and 579 eligible subjects were studied. ECG-LVH was assessed according to the Sokolow–Lyon voltage criteria and the Cornell voltage–duration product. The median level of plasma NOx (nitrite plus nitrate), a marker of systemic nitric oxide production, was markedly lower in the normotensive subjects with ECG-LVH (n=73) than in those without (n=506), and the clinical characteristics were significantly different between the 2 groups (each P<0.05). Importantly, a one-to-one propensity score matching analysis showed similar markedly lower median plasma NOx level in the normotensive subjects with ECG-LVH compared with that observed in the matched normotensive subjects without ECG-LVH (P<0.05). Furthermore, the tertiles of the plasma NOx levels were inversely correlated with the prevalence and severity of ECG-LVH (both P<0.05). The lower plasma NOx levels were associated with significantly higher plasma 8-isoprostane levels, a marker of systemic lipid peroxidation (P<0.05). These results provide the first evidence that normotensive subjects with ECG-LVH exhibit defective nitric oxide production, along with increased oxidative stress. Our findings may thus explain, at least in part, a potential mechanism underlying the increased risk of cardiovascular death in normotensive individuals with ECG-LVH.

Basal Left Ventricular Dilatation and Reduced Contraction in Patients With Mitral Valve Prolapse Can Be Secondary to Annular Dilatation Preoperative and Postoperative Speckle-Tracking Echocardiographic Study on Left Ventricle and Mitral Valve Annulus Interaction

Background—Prominent mitral valve (MV) annular dilatation with only modest left ventricular (LV) dilatation in patients with MV prolapse (MVP) suggests predominant dilatation in adjacent basal LV, which may augment regional wall tension and attenuate contraction by Laplace’s law. We hypothesized that MV annular dilatation in patients with MVP is associated with the basal predominance of LV dilatation and attenuated contraction, which can be altered by surgical MV plasty with annulus reduction. Methods and Results—Echocardiography with speckle-tracking analysis to assess regional cross-sectional short-axis area and longitudinal contraction (strain) of basal, middle, and apical LV was performed in 30 controls and 130 patients with MVP. The basal value/averaged middle and apical values (B/M·A ratio) of LV cross-sectional area and strain were obtained. Patients with MVP showed significantly greater MV annular area (6.4±1.6 versus 3.7±0.6 cm2/m2), increased B/M·A LV area ratio (2.4±0.5 versus 1.8±0.2), and reduced B/M·A LV strain ratio (0.83±0.14 versus 0.96±0.09) than controls (P<0.001). Multivariable analyses identified that MV annular dilatation was independently associated with increased B/M·A LV area ratio (&bgr;=0.60, P<0.001), which was associated with reduced B/M·A LV strain ratio (&bgr;=−0.32, P<0.001). In 35 patients with MVP, B/M·A LV area and strain ratio significantly altered after surgical MV plasty with annulus reduction (2.5±0.5–1.8±0.3 and 0.73±0.10–0.89±0.17, P<0.001, respectively). Conclusions—In patients with MVP, MV annular dilatation was associated with the basal predominance of LV dilatation and reduced contraction, which can be altered by surgical MV plasty with annulus reduction, suggesting unfavorable influence from MV annular dilatation on basal LV.Background— Prominent mitral valve (MV) annular dilatation with only modest left ventricular (LV) dilatation in patients with MV prolapse (MVP) suggests predominant dilatation in adjacent basal LV, which may augment regional wall tension and attenuate contraction by Laplace’s law. We hypothesized that MV annular dilatation in patients with MVP is associated with the basal predominance of LV dilatation and attenuated contraction, which can be altered by surgical MV plasty with annulus reduction. Methods and Results— Echocardiography with speckle-tracking analysis to assess regional cross-sectional short-axis area and longitudinal contraction (strain) of basal, middle, and apical LV was performed in 30 controls and 130 patients with MVP. The basal value/averaged middle and apical values (B/M·A ratio) of LV cross-sectional area and strain were obtained. Patients with MVP showed significantly greater MV annular area (6.4±1.6 versus 3.7±0.6 cm2/m2), increased B/M·A LV area ratio (2.4±0.5 versus 1.8±0.2), and reduced B/M·A LV strain ratio (0.83±0.14 versus 0.96±0.09) than controls ( P <0.001). Multivariable analyses identified that MV annular dilatation was independently associated with increased B/M·A LV area ratio (β=0.60, P <0.001), which was associated with reduced B/M·A LV strain ratio (β=−0.32, P <0.001). In 35 patients with MVP, B/M·A LV area and strain ratio significantly altered after surgical MV plasty with annulus reduction (2.5±0.5–1.8±0.3 and 0.73±0.10–0.89±0.17, P <0.001, respectively). Conclusions— In patients with MVP, MV annular dilatation was associated with the basal predominance of LV dilatation and reduced contraction, which can be altered by surgical MV plasty with annulus reduction, suggesting unfavorable influence from MV annular dilatation on basal LV.