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Aim In-stent neoatherosclerosis (NA) has emerged as an important contributing factor to late stent failure and cardiovascular events. The aim of this study was to investigate whether lipid markers are associated with NA using optical coherence tomography (OCT) after percutaneous coronary intervention (PCI) in patients with coronary artery disease under well-controlled low density lipoprotein cholesterol (LDL-c) on statin treatment. Methods We enrolled consecutive 115 patients under statin treatment who underwent PCI with current-generation drug-eluting stent for acute and chronic coronary syndrome. OCT image and various lipid markers were obtained at 1-year for scheduled research assessment. NA was defined as a lipid laden neointima or calcified neointima. Both small dense LDL-c (sd-LDL-c) and remnant lipoprotein cholesterol (RL-c) were measured using direct homogenous assay. Results During an average follow-up of 13 months, NA was observed in 14 (13.6%) patients. Not LDL-c but sd-LDL-c, Malondialdehyde-modified LDL (MDA-LDL) as oxidized LDL and (RL-c) were significantly higher in patients with NA. The optimal threshold values of sd-LDL-c, MDA-LDL and RL-c for predicting NA according to receiver operating characteristics analysis were 32.3 mg/dl, 91.0 U/L, and 3.3 mg/dL, respectively. On multivariate logistic regression analysis, sd-LDL-c (≥32.3 mg/dL) and MDA (≥91.0 U/L) were significantly associated with NA (odds ratio [OR]:13.62, p=0.016, OR: 12.68, p=0.01, respectively). Conclusions In statin-treated patients, sd-LDL-c and MDA-LDL but not LDL-c might be useful biomarkers to identify the formation of NA at 1 years after PCI. Aggressive reduction of these atherogenic LDL may have a potential to prevent the formation of NA. Funding Acknowledgement Type of funding sources: None.

Background Orsiro ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) might facilitate early vascular healing responses that seems to be associated with improved long-term clinical outcomes. We compared the early vascular healing responses to BP-SES and Xience durable-polymer everolimus-eluting stent (DP-EES) in patients with chronic coronary syndrome (CCS) using optical coherence tomography (OCT). Methods A total of 40 patients with CCS receiving OCT-guided PCI were included. 20 patients were assigned to BP-SES, and 20 to DP-EES. OCT was performed immediately after stent placement (post-procedure) and at 1 month follow-up. Struts were recorded as uncovered if any part was visibly exposed in the lumen or covered if a layer of tissue covered all reflecting surfaces. The incidence of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed. Results At 1 month, the percentage of uncovered struts was significantly lower in the BP-SES compared with the DP-EES (2.8±1.6% vs. 5.8±1.8%, respectively; p Conclusion Early vascular healing response to Orsiro BP-SES implantation was revealed in CCS patients at 1 month compared with Xience DP-EES. Orsiro BP-SES may have a potential to shorten the dual antiplatelet therapy duration. Funding Acknowledgement Type of funding source: None

Background It is known that the early coronary revascularization in patients with non-ST-elevation myocardial infarction (NSTEMI) was associated with favorable clinical outcomes. However, it is still unclear whether this efficacy is equivalent over all the ages of the patients. Methods Patients with NSTEMI were screened from the database of the Tokyo CCU network registry. Of those, the patients treated without revascularization (medical treatment) were matched with the patients receiving revascularization by propensity score matching. The probabilities of in-hospital death were calculated in the logistic regression model. In two subgroups stratified according to median of the age (elderly and non-elderly subgroups), the odds ratios of revascularization for in-hospital death were calculated. Results In the patients registered between 2013 and 2017, 4,851 patients with NSTEMI were identified. After the screening, 370 patients with medical treatment were matched with 370 patients treated with revascularization. The incidence of in-hospital death was significantly higher in the patients with medical treatment (20.3% vs 13.0%, P=0.01). The two probability curves of in-hospital death in patients with and without revascularization converged as age increased. In the elderly subgroup, the revascularization was not significantly associated with favorable outcome of mortality, whereas it had a significant impact on mortality in the non-elderly subgroup (odds ratio: 0.47 [95% CI 0.23–0.95]). Conclusion The impact of revascularization on short-term mortality in patients with NSTEMI tended to be reduced as age increased. Funding Acknowledgement Type of funding source: None

Background Recent clinical study suggests newer-generation drug-eluting stents (DES) that combine ultrathin strut and nano-coating with biodegradable polymers sirolimus-eluting stent (BP-SES) could improve long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) over current generation DES. However, safety profiles in very early phase have not been systematically addressed. Objective and method We exploratory investigate early vascular response following BP-SES implantation in patients with STEMI to reveal mechanism of the favorable clinical outcomes in recent studies using frequency domain-optical coherence tomography (FD-OCT). Consecutive twenty patients with STEMI who underwent FD-OCT immediately after primary PCI and were eligible for follow-up FD-OCT at 2 weeks after implantation were enrolled between June 2018 and November 2019. Results Twenty patients (age 62.7±11.3 years, male 85.0%) were enrolled with frequencies of hypertension (45.0%), diabetes mellitus (35.0%), dyslipidemia (55.0%) and smoking (80.0%). Aspiration catheter were used in all patients, and 1.13±0.34 stents were used. Only one patient (5.0%) received chronic antiplatelet therapy with aspirin prior to the onset of STEMI. All patients started to receive prasugrel as thienopyridine from this event and continued dual antiplatelet therapy for 2 weeks. The percentage of uncovered struts significantly decreased from post-procedure to 2W follow-up (69±18% post-procedure versus 30±11% at 2W follow up, p Conclusion(s) This study firstly elucidated very early vascular responses following ultrathin strut BP-SES implantation in STEMI patients, showing early progression of strut coverage and resolution of athero-thrombotic materials. This technology may have a potential to overcome the current generation DESs in this clinical setting. Thrombus, uncovered and malapposed struts Funding Acknowledgement Type of funding source: None

Background It is known that low diastolic blood pressure (DBP) is associated with long-term cardiovascular events after acute myocardial infarction (AMI). However, the impact of low diastolic blood pressure on short-term outcome has not yet been well investigated. Methods and results We included 15,208 patients who were hospitalized for AMI and registered in the Tokyo CCU network registry between 2013 and 2016. Thirty-day in-hospital mortality rate was 4.8% (728/15,208). To assess the relationship between DBP at the time of admission and 30-day mortality non-linearly, spline regression model was applied with the stratification of the cohort according to tercile of systolic blood pressure (SBP, low:≤122 mmHg, intermediate:123–148 mmHg, high:≥149 mmHg) and J-curve phenomenon was observed in the low and high SBP groups. In multivariate logistic regression analysis, adjusted odds ratio of the lowest quintile of DBP (≤64 mmHg) was 1.65 (95% CI:1.02–2.66) in low SBP group and 4.55 (95% CI:1.72–12.00) in high SBP group. Conclusion Low DBP was associated with increased 30-day in-hospital mortality rate after AMI even in patients with high SBP. Funding Acknowledgement Type of funding source: None

Background Insertable cardiac monitors (ICMs) allow for lengthy monitoring of cardiac rhythm and improve diagnostic yield in patients with unexplained syncope. In most cardiac syncope cases, sick sinus syndrome, atrioventricular block, and paroxysmal supraventricular tachycardia (SVT) are detected using ICMs. On the other hand, epileptic seizures are sometimes diagnosed as unexplained syncope because in these situations, the loss of consciousness is a similar manifestation. Thus, the population of patients with unexplained syncope monitored by ICMs includes epileptic patients. Clinical risk factors for bradycardia, SVT and epilepsy that necessitate therapy in patients with unexplained syncope are not well known. If these risks can be clarified, clinicians could provide more specific targeted monitoring. Purpose We aimed to identify these predictors. Methods We retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope in three medical facilities. We performed Cox's stepwise logistic regression analysis to identify significant independent risk factors for bradycardia, SVT, and epilepsy. Results One hundred thirty-two patients received ICMs to monitor unexplained syncope. During the 17-month follow-up period, 19 patients (10 patients had sick sinus syndrome and 9 had atrioventricular block) needed pacemaker for bradycardia; 8 patients (3 had atrial flutter, 4 had atrial tachycardia, and 1 had paroxysmal atrial fibrillation) needed catheter ablation for SVT; and 9 patients needed antiepileptic agents from the neurologist.Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p=0.02) was an independent risk factor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p=0.008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p=0.006) were identified as significant independent prognostic factors for SVT. Syncope while supine (OR = 11.7; 95% CI, 1.72 to 79.7; p=0.01) or driving (OR = 15.6; 95% CI, 2.10 to 115.3; p=0.007) was an independent factor for epileptic seizure. Conclusions ICMs are useful devices for diagnosing unexplained syncope. Palpitation, atrial fibrillation and syncope during effort were independent risk factors for bradycardia and for SVT. Syncope while supine or driving was an independent risk factor for epilepsy. We should carefully follow up of patients with these risk factors. Funding Acknowledgement Type of funding source: None

Background Micro-bubble test by using transcranial color flow imaging (TCCFI) is important as a screening evaluation for diagnosis of paradoxical cerebral embolism which requires the proof of right to left shunt at atrial septum. In addition, high risk features of patent foramen ovale (PFO) that may allow thrombus to easily pass through the PFO itself were previously reported. However, little is known about the association between the degrees on micro-bubble test by TCCFI and the features of high risk PFO. Purpose Our aim is to clarify the relationship between the degree of micro-bubble test in TCCFI and the morphology of PFO from transesophageal echocardiography (TEE). Methods Seventy-seven patients in whom cardiogenic embolism was strongly suspected by neurologists in Showa University from April to December in 2019 were retrospectively studied. 55 patients underwent both TCCFI and TEE with sufficient Valsalva stress. TCCFI grade of micro-bubble test was classified into 3 groups (A: none, B: small, and C: massive), in which signified “none” is no sign of micro-embolic signals (MES) within 30 seconds, “small” is 1 or more MES, and “massive” is so much MES look like a curtain (Figure). Evaluated high risk characteristics of PFO for cerebral embolism as previously reported were as follows; (1) tunnel height, (2) tunnel length, (3) total excursion distance into right and left atrium, (4) existence of Eustachian valve or Chiari network, (6) angle of PFO from inferior vena cava (7) large shunt (20 or more micro-bubbles). Results Of all TCCFI-positive patients (n=32; Group B=19, Group C=13) with cerebral embolism, PFOs were detected in 23 patients in TEE. Therefore, the sensitivity and specificity of TCCFI to PFO were 87% and 63% (AUC=0.75, p Conclusions Micro-bubble test by using TCCFI may have screening advantages in predicting paradoxical cerebral embolism, high-risk morphology of PFO, and platypnea orthodeoxia syndrome. Figure 1 Funding Acknowledgement Type of funding source: None

Background The appropriate treatment for silent myocardial ischemia (SMI) is controversial. The prognosis of asymptomatic patients after percutaneous coronary intervention (PCI) is unknown. Asymptomatic patients might be sicker and have delay of diagnosis when they have coronary events in clinical course. We, thus, hypothesized SMI are associate with the poor outcomes after PCI for stable coronary artery disease (CAD). Purpose The present study compared the long-term outcomes of patients with SMI vs. stable angina pectoris (SAP) after elective PCI. Methods Our prospective registry database included 923 consecutive patients with CAD who underwent PCI from October 2015 to August 2018. Patients with emergent PCI, acute coronary syndrome at admission, or chronic total occlusion patients were not included. A total 613 patients (71.4±11.2 years, 75.7% male) who underwent elective PCI were studied. The end points included all-cause mortality, non-fatal myocardial infarction, and repeat revascularization. Results They were divided into 2 groups according to symptom status: SMI (n=392) and SAP (n=221). SMI patients were predominantly men, and more frequently had diabetes mellitus (197 [50.4%] vs. 91 [41.2%], p=0.028), previous myocardial infarction (44 [11.3%] vs. 8 [3.6%], p=0.001) and heart failure hospitalization.Echocardiography showed SMI groups had reduced ejection fraction (56.9±12.6 vs 63.3±9.1, P Conclusion In patients with stable CAD undergoing elective PCI, SMI was associated with an increase in mortality. Optimal care for SMI patients after PCI should be clarified in future studies. Funding Acknowledgement Type of funding source: None

Aims Optical frequency domain imaging (OFDI) is a recently developed, light-based, high-resolution intravascular imaging technique. Intravascular ultrasound (IVUS) is a widely used, conventional imaging technique for guiding percutaneous coronary intervention (PCI). We aimed to demonstrate the non-inferiority of OFDI-guided PCI compared with IVUS-guided PCI in terms of clinical outcomes. Methods and results We did a prospective, multicentre, randomized (ratio 1:1), active-controlled, non-inferiority study to compare head-to-head OFDI vs. IVUS in patients undergoing PCI with a second generation drug-eluting stent. The primary endpoint was target vessel failure defined as a composite of cardiac death, target-vessel related myocardial infarction, and ischaemia-driven target vessel revascularization until 12 months after the PCI. The major secondary endpoint was angiographic binary restenosis at 8 months. We randomly allocated 829 patients to receive OFDI-guided PCI (n = 414) or IVUS-guided PCI (n = 415). Target vessel failure occurred in 21 (5.2%) of 401 patients undergoing OFDI-guided PCI, and 19 (4.9%) of 390 patients undergoing IVUS-guided PCI, demonstrating non-inferiority of OFDI-guided PCI to IVUS-guided PCI (hazard ratio 1.07, upper limit of one-sided 95% confidence interval 1.80; Pnon-inferiority = 0.042). With 89.8% angiographic follow-up, the rate of binary restenosis was comparable between OFDI-guided PCI and IVUS-guided PCI (in-stent: 1.6% vs. 1.6%, P = 1.00; and in-segment: 6.2% vs. 6.0%, P = 1.00). Conclusion The 12-month clinical outcome in patients undergoing OFDI-guided PCI was non-inferior to that of patients undergoing IVUS-guided PCI. Both OFDI-guided and IVUS-guided PCI yielded excellent angiographic and clinical results, with very low rates of 8-month angiographic binary restenosis and 12-month target vessel failure. Clinical registration ClinicalTrials.gov, number NCT01873027.

Background Lethal-ventricular-arrhythmia (VA) could be sometimes initiated by idiopathic Premature Ventricular Contractions (PVCs) originated form inferior wall. Furthermore, J-wave elevation in inferior leads was sometimes associated with lethal-VA. However, it was unclear the relationship between these PVCs and J-wave elevation in patients with lethal-VA. Purpose The aim of this study was to investigate the relationship between PVCs and J-wave elevation. Methods and results We studied 32 patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with RBBB and superior axis. These PVCs were originating from inferior wall of left ventricular. Lethal-VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal-VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal-VA. The ratio of J-wave elevation in lethal-VA was significant higher as compared to those with non-lethal-VA (5/5 (100%) vs. 3/27 (11.1%), p Conclusions We speculated that J-wave elevation in inferior leads might be a predictor of lethal-VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs were useful method of treating lethal-VA. Acknowledgement/Funding None

Background Although the patient's characteristics and outcome of acute myocardial infarction (AMI) have been sufficiently investigated and primary percutaneous coronary intervention (PCI) has been recognized as established treatment strategy, those of recent myocardial infarction (RMI) have not been fully evaluated. Purpose The purpose of the present study was to clarify clinical characteristics and in-hospital outcomes of RMI patients from the database of the Tokyo CCU network multicenter registry. Methods In Tokyo CCU network multicenter registry database from 2013 to 2016, 15788 consecutive patients were registered as AMI (within 24 hours from onset) and RMI (within 2–30 days from onset). However 1246 patients were excluded because of inadequate data. And we excluded 66 cases because of out of onset period and 129 cases that strongly suspected of involvement of vasospastic events. Therefore, remaining 14347 patients were categorized to RMI group (n=1853) and AMI group (n=12494), and analyzed. Results Compared with AMI group, average age was older (70.4±12.9 vs 68.0±13.4 years, p Kaplan-Meier analysis Conclusions RMI patients had distinctive clinical features in backgrounds and treatment strategies compared with AMI patients, and the major cause of death of RMI patients was different from that of AMI patients. Furthermore, even though treatment during hospitalization of RMI patients was well done, death due to mechanical complications continued to increase.

Background The most effective approach for long-standing persistent atrial fibrillation (LSPAF) ablation remained undetermined. Here, we hypothesized that selective linear ablation (SLA) according to the type of tachycardia induced by burst atrial pacing (BAP) after pulmonary venous isolation (PVI) in single-procedure reduces the recurrence. Methods A cohort of 66 LSPAF patients (Mean age 71.0±8.2 years, AF duration 40.5±58.8 months) who underwent PVI in single-procedure between April 2016 and November 2018 was evaluated. Results Any sustained atrial tachycardia (AT) or AF were not inducible by BAP after PVI in 21 patients (Non-inducible group, 31.8%, 71.3±7.9 years, 34.4±54.2 months). These patients underwent cavo-tricuspid isthmus (CTI) ablation after PVI. Forty-one patients underwent selective liner ablation according to the type of tachycardia induced by BAP after PVI (SLA group, 62.1%, 71.2±8.3 years, 39.3±55.6 months). Maccroreentry ATs (6 common atrial flutter, 5 AT originating from left atrial anterior wall, 2 peri-mitral atrial flutter, 1 roof-dependent atrial flutter) were induced by BAP in 14 patients of SLA group (73.2±19.7 years, 51.7±83.5 months). RF applications created the complete linear lesions to terminate maccroreentry ATs. Sustained AF was induced by BAP after PVI in 27 patients of SLA group (70.2±9.2 years, 32.9±31.2 months). These patients underwent posterior wall isolation (PWI) and CTI ablation. Unmappable AT was induced by BAP after PVI in 4 patients (Non-SLA group, 6.1%, 67.0±9.7 years, 84.5±105.6 months). These patients underwent PWI, CTI and mitral isthmus ablation on an empirical basis instead of SLA. Using a 90-day blanking period, the single-procedure Kaplan-Meier estimates of AT or AF event-free survival were 79% at 12 months. During follow-up (14.5±8.0 months), although 19 /21 (90.5%) of Non-inducible group patients and 33/41 (80.5%) of SLA group patients did not experience AT or AF recurrence, all of Non-SLA group patients experienced AF recurrence. There was no difference between Non-inducible group and SLA group in predicting recurrence of AT or AF (p=0.3). However, there was a difference when compared with Non-SLA group (each p Kaplan-Meier survival curves Conclusions In LSPAF patients without inducibility of any tachycardia after PVI, sinus rhythm was highly maintained without stepwise ablation other than CTI ablation. SLA reduced recurrence of AF in LSPAF patients with AT and AF induced after PVI. In addition, nonselective liner ablations for unmappable AT after PVI were less effective in LSPAF patients.

Aims To evaluate the feasibility of the combined use of virtual histology (VH)-intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for detecting in vivo thin-cap fibroatheroma (TCFA). Methods and results In 56 patients with angina, 126 plaques identified by IVUS findings were analysed using both VH-IVUS and OCT. IVUS-derived TCFA was defined as an abundant necrotic core (> 10% of the cross-sectional area) in contact with the lumen (NCCL) and %plaque-volume > 40%. OCT-derived TCFA was defined as a fibrous cap thickness of < 65 mu m overlying a low-intensity area with an unclear border. Plaque meeting both TCFA criteria was defined as definite-TCFA. Sixty-one plaques were diagnosed as IVUS-derived TCFA and 36 plaques as OCT-derived TCFA. Twenty-eight plaques were diagnosed as definite-TCFA; the remaining 33 IVUS-derived TCFA had a non-thin-cap and eight OCT-derived TCFA had a non-NCCL (in discord with NCCL visualized by VH-IVUS, mainly due to misreading caused by dense calcium). Based on IVUS findings, definite-TCFA showed a larger plaque and vessel volume, %plaque-volume, higher vessel remodelling index, and greater angle occupied by the NCCL in the lumen circumference than non-thin-cap IVUS-derived TCFA. Conclusion Neither modality alone is sufficient for detecting TCFA. The combined use of OCT and VH-IVUS might be a feasible approach for evaluating TCFA.

Aims Since the intravascular ultrasound (IVUS) cannot detect neointimal layers in the majority of sirolimus-eluting stents (SES) at the chronic phase, it is still controversial to what extent SES remain uncovered. However, optical coherence tomography (OCT) with excellent resolution may be able to detect thinner neointima. Methods and results A total of 34 patients (57 SES) underwent OCT and IVUS evaluations at 6-month follow-up. The thickness of neointima on each SES strut cross-section and strut apposition to the vessel wall was evaluated. By OCT evaluation, the median (25th, 75th percentiles) neointima thickness was 52.5 µm (28.0 µm, 147.6 µm) and the prevalence of struts covered by thin neointima undetectable by IVUS was 64%. The average rate of neointima-covered struts in an individual SES was 89%. Nine SES (16%) showed full coverage by neointima, whereas the remaining stents had partially uncovered strut lesions. Among the 6840 struts visualized by OCT in all of the SES, 79 struts showed malapposition without neointimal coverage, and were frequently observed in the areas of SES overlap. Conclusion At 6 months, most of the SES were covered with thin neointima, but few showed full coverage.

Aims Plasma brain natriuretic peptide (BNP) concentration increases in proportion to heart failure (HF) severity. Although plasma BNP decreases to a certain level by optimal treatment, there is significant heterogeneity in the baseline value among individuals. The underlying mechanism of the steady-state plasma BNP levels remains still controversial. We investigated the hypothesis that myocardial stiffness ( K m) is a major determinant of the plasma BNP level. Methods and results In 19 patients with diastolic HF [DHF; left ventricular ejection fraction (LVEF)≥45%], 18 with systolic HF (SHF; LVEF