Katsuya Miura

Smoking Cessation Reverses DNA Double-Strand Breaks in Human Mononuclear Cells

Objective Cigarette smoking is a major risk factor for atherosclerotic cardiovascular disease, which is responsible for a significant proportion of smoking-related deaths. However, the precise mechanism whereby smoking induces this pathology has not been fully delineated. Based on observation of DNA double-strand breaks (DSBs), the most harmful type of DNA damage, in atherosclerotic lesions, we hypothesized that there is a direct association between smoking and DSBs. The goal of this study was to investigate whether smoking induces DSBs and smoking cessation reverses DSBs in vivo through examination of peripheral mononuclear cells (MNCs). Approach and Results Immunoreactivity of oxidative modification of DNA and DSBs were increased in human atherosclerotic lesions but not in the adjacent normal area. DSBs in human MNCs isolated from the blood of volunteers can be detected as cytologically visible “foci” using an antibody against the phosphorylated form of the histone H2AX (γ-H2AX). Young healthy active smokers (n = 15) showed increased γ-H2AX foci number when compared with non-smokers (n = 12) (foci number/cell: median, 0.37/cell; interquartile range [IQR], 0.31–0.58 vs. 4.36/cell; IQR, 3.09–7.39, p<0.0001). Smoking cessation for 1 month reduced the γ-H2AX foci number (median, 4.44/cell; IQR, 4.36–5.24 to 0.28/cell; IQR, 0.12–0.53, p<0.05). A positive correlation was noted between γ-H2AX foci number and exhaled carbon monoxide levels (r = 0.75, p<0.01). Conclusions Smoking induces DSBs in human MNCs in vivo, and importantly, smoking cessation for 1 month resulted in a decrease in DSBs to a level comparable to that seen in non-smokers. These data reinforce the notion that the cigarette smoking induces DSBs and highlight the importance of smoking cessation.

Ten-year clinical outcomes after sirolimus- eluting stent implantation: Impact of an in-stent restenosis target lesion

UNLABELLED Little is known about the long-term outcomes after first-generation sirolimus-eluting stent (SES) implantation. We aimed to investigate the clinical outcomes up to 10 years after SES implantation. METHODS The study population comprised 342 patients (504 lesions) who underwent SES implantation between January 2002 and December 2004. The median duration of follow-up was 3816 days (interquartile range [Q1-Q3], 3,705-3,883 days). RESULTS The cumulative event rate of definite stent thrombosis was 3.9%. The cumulative rate of target lesion revascularization (TLR) at 1, 5, and 10 years was 8.7%, 18.8%, and 31.1%, respectively, and the annual rate of TLR was 3.1%. Clinically driven TLR occurred at relatively constant rate during 10 years (2.0% per year). In a multivariate analysis, higher body mass index, hemodialysis, in-stent restenosis (ISR) target lesion, and total stent length >30 mm were independent risk factors of TLR within 5 years. An independent risk factor of TLR beyond 5 years was ISR target lesion. CONCLUSIONS Late TLR after SES implantation is a long-term hazard, lasting up to 10 years. The ISR target lesion is a risk factor of TLR during 10 years.

Association of nonculprit plaque characteristics with transient slow flow phenomenon during percutaneous coronary intervention

BACKGROUND The slow flow (SF) phenomenon is more prevalent in patients with acute coronary syndrome (ACS), who frequently exhibit vulnerable plaques in remote coronary arteries. We aimed to clarify the impact of nonculprit plaque characteristics on the occurrence of SF using multidetector computed tomography (MDCT). METHODS The study population comprised 180 consecutive patients with non-ST-segment elevation ACS (NSTE-ACS) who underwent MDCT before intervention. The characteristics of culprit and nonculprit lesions were compared between patients with and without SF. RESULTS SF was observed in 43 (23.8%) of the 180 patients. The prevalence of positive remodeling (PR), low-attenuation plaque (LAP), and napkin-ring sign (NRS) in culprit lesion was significantly higher in the SF group than in the non-SF group (86.1% vs. 39.4%; p<0.001, 81.4% vs. 18.3%; p<0.001, and 65.1% vs. 16.1%; p<0.001, respectively). The same result was observed for nonculprit lesions (58.1% vs. 14.6%; p<0.001, 45.2% vs. 6.6%; p<0.001, and 14.3% vs. 4.9%; p<0.04, respectively). Multivariate analysis revealed LAP [odds ratio (OR), 12.8; 95% confidence interval (CI), 3.7-54.7; p<0.001], and NRS (OR, 5.1; 95% CI, 1.3-25.3; p=0.03) in culprit lesions and PR (OR, 4.7; 95% CI, 1.1-22.2; p=0.04) in nonculprit lesions were independently associated with SF. CONCLUSIONS The plaque characteristics of nonculprit lesions are associated with the occurrence of SF during percutaneous coronary intervention. Assessment of plaque characteristics of both culprit and nonculprit lesions using MDCT may be useful for the prediction of SF.

Late Restenosis After Both First-Generation and Second-Generation Drug-Eluting Stent Implantations Occurs in Patients With Drug-Eluting Stent Restenosis

Background—There are currently inadequate data about whether late restenosis occurs after drug-eluting stent (DES) implantation in patients with DES restenosis. Methods and Results—We collected data for 608 patients who received revascularization for DES restenosis between 2004 and 2012 and analyzed 688 lesions: 359 lesions treated with a first-generation DES (first DES) and 329 lesions treated with a second-generation DES (second DES). Two serial angiographic follow-ups were routinely planned for the patients (at 8 and 20 months after the procedure). Early follow-up angiography was performed for 620 lesions (90.1%), and recurrent restenosis occurred in 84 lesions (25.8%) in the first DES group and in 72 lesions (24.5%) in the second DES group (P=0.78). Target lesion revascularization was performed for 69 lesions (21.2%) in the first DES group and for 48 lesions (16.3%) in the second DES group (P=0.15). Late follow-up angiography was performed for 438 (87.1%) of the remaining 503 lesions (excluding target lesion revascularization lesions), and late restenosis was found in 35 lesions (15.8%) in the first DES group and in 28 lesions (14.7%) in the second DES group (P=0.79). Nonfocal-type restenosis, percentage diameter stenosis after the procedure, previous stent size ⩽2.5 mm, and right coronary artery ostial lesion were independent predictors of early restenosis. Nonfocal-type restenosis, percentage diameter stenosis at early follow-up, and stent fracture were independent predictors of late restenosis. Conclusions—Late restenosis occurs after both first DES implantation and second DES implantation for DES restenosis.

Do lower target temperatures or prolonged cooling provide improved outcomes for comatose survivors of cardiac arrest treated with hypothermia

Background Optimal protocols for targeted temperature management are still unclear. This study investigated whether lower target temperatures and/or prolonged cooling could provide improved outcomes in comatose survivors of cardiac arrest. Methods and Results This observational study was conducted using the prospectively collected targeted temperature management database in Hiroshima, Japan. Between September 2003 and September 2014, 237 patients treated with TTM after cardiac arrest were enrolled in this study. The target temperatures and durations were assigned by the treating physicians regardless of the patients’ conditions. Favorable outcomes were defined as a cerebral performance category scale of 1 or 2 at the 90-day follow-up time point. The rate of favorable outcomes were similar between the patients whose protocols of target temperature were <34°C and ≥34°C (40% versus 35%, P=0.41), cooling durations were <28 and ≥28 hours (33% versus 44%, P=0.11), and rewarming durations were <28 and ≥28 hours (35% versus 41%, P=0.39). However, in patients treated with extracorporeal cardiopulmonary resuscitation, target temperatures <34°C were associated with more favorable outcomes (29% versus 8%, P=0.01). The cooling and rewarming durations >28 hours and target temperatures <34°C were associated with more frequent lethal arrhythmia, pneumonia, and/or bleedings. Conclusions Prolonged durations of cooling and rewarming ≥28 hours may not improve outcomes and may increase complications. Further studies are necessary to assess the hypothesis that target temperatures <34°C provide improved outcomes in patients treated with extracorporeal cardiopulmonary resuscitation.

Long-term (8–10 years) outcomes after biodegradable polymer-coated biolimus-eluting stent implantation

Objective Efficacy and safety data on biodegradable polymer-coated biolimus-eluting stent (BP-BES) are currently limited to 5 years. We evaluated longer term (8–10 years) clinical and angiographic outcomes after BP-BES implantation. Methods Between 2005 and 2008, 243 patients (301 lesions) underwent BP-BES implantation. The primary clinical outcome measure was defined as any target lesion revascularisation (TLR). Absolute serial angiographic studies without any concomitant TLR within 2 years after the procedure were performed in 55 patients (65 lesions) at postprocedure, mid-term (within 1 year), late term (between 1 and 2 years) and very late term (beyond 2 years). Results The median follow-up duration was 9.4 years (IQR 8.2–10.2 years). The 8-year cumulative incidence of any TLR was 20.3%. The increase rate was approximately 7% per year in the first 2 years, but decelerated to approximately 1.2% per year beyond 2 years after the procedure. The minimal lumen diameter significantly decreased from postprocedure (2.63±0.44 mm) to mid-term (2.43±0.59 mm, p=0.002) and from late term (2.27±0.63 mm) to very late term (1.98±0.73 mm, p=0.002). The 8-year cumulative incidences of definite or probable stent thrombosis (ST) and major bleeding (Bleeding Academic Research Consortium (BARC) ≥3) were 0.5% and 12.0%, respectively. Definite ST was none within 10 years in the entire cohort. Conclusions The long-term clinical outcomes after BP-BES implantation were favourable, although angiographic late progression of luminal narrowing did not reach a plateau. The incidence of ST remained notably low, whereas that of major bleeding gradually increased.

Impact of Stent Type and Presence of Vasospastic Angina on Long-Term Prognosis

BACKGROUND Little is known about the impact of stent type on the prognosis of vasospastic angina (VSA) in patients who undergo stent implantation.Methods and Results:We evaluated consecutive patients undergoing coronary angiography with positive (n=650; VSA) and negative (n=2,872; non-VSA) ergonovine testing. Among them, 304 patients undergoing stent implantation for organic stenosis were classified for comparison into 3 respective VSA and non-VSA groups based on stent type (68 and 78 with bare-metal stent [BMS]; 21 and 49 with sirolimus-eluting stent [SES]; 26 and 62 with newer generation drug-eluting stent [N-DES]). The primary outcome was defined as target lesion revascularization, target vessel revascularization, emergency coronary angiography, and cardiac death. The 2-year cumulative incidence of the primary outcome was significantly higher in the VSA group than non-VSA group after SES implantation (38.1% vs. 16.1%, P=0.03), whereas there were no differences between the 2 groups after both BMS implantation and N-DES implantation. The difference in the percent diameter stenosis from mid-term to late-term follow-up was significantly higher in the VSA group than non-VSA group (10.0% vs. 2.3%, P=0.045) after SES implantation, whereas there were no differences between the 2 groups after both BMS implantation and N-DES implantation. CONCLUSIONS The impact of VSA on clinical and angiographic outcomes was observed only in SES implantation, but not after N-DES or BMS implantation.

Optical Coherence Tomography Predictors for Recurrent Restenosis After Paclitaxel-Coated Balloon Angioplasty for Drug-Eluting Stent Restenosis

BACKGROUND Little is known of the relationship between optical coherence tomography (OCT) findings and recurrent restenosis after paclitaxel-coated balloon (PCB) angioplasty for drug-eluting stent in-stent restenosis (DES-ISR). To identify the predictors of recurrent restenosis after PCB angioplasty, we investigated quantitative and qualitative OCT findings during PCB angioplasty for DES-ISR. Methods and Results: In all, 222 DES-ISR lesions treated by PCB angioplasty with OCT assessment and followed-up angiographically at 6 months were divided into restenotic and non-restenotic lesions on the basis of the presence or absence of restenosis at follow-up. There was a significantly higher proportion of the heterogeneous tissue pattern in restenotic than non-restenotic lesions (26.5% vs. 11.0%, respectively; P=0.02). The OCT-derived post-procedural minimal lumen and stent areas were significantly smaller in restenotic lesions, but the intima area was similar in both groups. Post-procedural stent underexpansion, defined as a stent diameter : size of the previous stent ratio <1.0, was more frequently observed in restenotic than non-restenotic lesions (33.3% vs. 17.4%, respectively; P=0.02). Multivariate analysis identified a heterogeneous tissue pattern (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.32-6.47; P=0.006) and post-procedural stent underexpansion (OR 2.36; 95% CI 1.15-4.85; P=0.04) as independent predictors of recurrent restenosis. CONCLUSIONS The heterogeneous tissue pattern and insufficient post-procedural minimal lumen area, caused primarily by stent underexpansion, may be associated with restenosis after PCB angioplasty for DES-ISR.

TCT-720 Impact of stent underexpansion and tissue patterns on recurrent restenosis after paclitaxel-coated balloon angioplasty for drug-eluting stent restenosis assessed with optical coherence tomography

Residual stenosis and the heterogeneous tissue pattern are reported to be the risk factors of recurrent restenosis after paclitaxel-coated balloon (PCB) angioplasty for drug-eluting stent (DES) in-stent restenosis (ISR). Optimal coherence tomography (OCT) can assess the mechanism of restenosis. We

TCTAP A-088 Quantitative Optical Coherence Tomographic Findings After Paclitaxel-coated Balloon Angioplasty for Drug-eluting Stent Restenosis

Residual stenosis after paclitaxel-coated balloon (PCB) angioplasty for drug-eluting stent (DES) in-stent restenosis (ISR) was one of the risk factors of recurrent restenosis. Optimal coherence tomography (OCT) and optical frequency domain imaging (OFDI) enables to assess the neointimal tissue and