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Little evidence is available regarding the long-term outcome in elderly patients after deferral of revascularization based on fractional flow reserve (FFR).Methods and Results: From the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicenter registry), 1,262 patients were divided into 2 groups according to age: elderly and younger patients (aged ≥75 or75 years, respectively). The primary endpoint was the cumulative 5-year incidence of target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). Cumulative 5-year incidence of TVF was not significantly different between elderly and younger patients (14.3% vs. 10.8%, P=0.12). Cardiac death occurred more frequently in elderly patients than younger patients (4.4% vs. 0.8%, P0.001), whereas TVMI and CDTVR did not differ between groups (1.3% vs. 0.9%, P=0.80; 10.7% vs. 10.1%, P=0.80, respectively). FFR values in lesions with diameter stenosis50% were significantly higher in elderly patients than in younger patients (0.88±0.07 vs. 0.85±0.07, P=0.01), whereas this relationship was not observed in those with diameter stenosis ≥50%.Elderly patients had no excess risk of ischemic events related to the deferred coronary lesions by FFR, although FFR values in mild coronary artery stenosis were modestly different between elderly and younger patients.

The aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements.Deferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time.From J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated.FFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P 0.001) than those without HTR, even when they had negative FFR.Assessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473).

Diabetes was reported to be associated with an impaired response to clopidogrel.The aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).A subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.There were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; PClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498).

Background: Cerebrovascular disease often coexists with coronary artery disease (CAD), and it has been associated with worse clinical outcomes in CAD patients. However, the prognostic effect of prior stroke on long-term outcomes in patients with acute coronary syndrome (ACS) is still unclear. Methods and Results: An observational cohort study of ACS patients who underwent emergency percutaneous coronary intervention (PCI) between January 1999 and May 2015 was conducted. Patients were divided into 2 groups according to their history of stroke. We evaluated both all-cause death and cardiac death. Of the 2,548 consecutive ACS patients in the current cohort, 268 (10.5%) had a history of stroke at the onset of ACS. Patients with a history of stroke were older and had a higher prevalence of comorbidities such as hypertension or renal deficiency. The cumulative incidences of all-cause death and cardiac death were significantly higher in patients with a history of stroke (both log-rank P

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-C) predicted reduced risk of cardiovascular-related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single-center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow-up period between the index PCI and latest follow-up were 5.9 and 0-17.8 years, respectively. Consequently, Kaplan-Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL-C. Multivariable Cox proportional hazard regression analysis adjusted by cancer-related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.

Background: The effect of symptoms on clinical outcomes after deferral of revascularization based on fractional flow reserve (FFR) remains poorly understood. Methods and Results: From the J-CONFIRM (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter) Registry, this study evaluated 1,215 patients with stable coronary artery disease, including symptomatic and asymptomatic patients (n=571 and 644, respectively). The primary endpoint was the cumulative 2-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). An inverse probability weighted analysis was performed to adjust for the differences in baseline clinical characteristics between the 2 groups. At 2 years, the TVF rate did not differ significantly between symptomatic and asymptomatic patients (6.5% vs. 4.9%, respectively; P=0.15) or between symptomatic and asymptomatic patients with lesions with an FFR ≤0.80 (8.0% vs. 12.3%, respectively; P=0.20). Conversely, symptomatic patients showed significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) than asymptomatic patients, regardless of negative FFR values (>0.80). Conclusions: Despite negative FFR values, symptomatic patients were at higher risk of TVF than asymptomatic patients, driven primarily by a higher rate of CDTVR. Conversely, those with a positive FFR were likely to develop TVF regardless of their symptoms.

Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.

Although an elevated neutrophil to lymphocyte ratio (NLR) has been associated with the adverse outcomes of coronary artery disease (CAD), less is known about its prognostic value among patients with low high-sensitivity C-reactive protein (hs-CRP) levels. We enrolled 2,591 consecutive patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) and had available data on preprocedural hs-CRP and NLR between 2000 and 2016. Of these patients, 1,951 with low-grade hs-CRP levels (< 2.0 mg/L) were divided into quartiles based on the NLR values. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke after the index PCI. Clinical follow-up data were obtained up to 5 years. The median NLR was 1.9 (interquartile range: 1.5-2.5). During the follow-up, 102 events occurred (5.2%), with a cumulative incidence that was significantly higher in the highest NLR group than in the other groups (log-rank, P = 0.02). After adjusting for the other cardiovascular risk factors, the risk for the primary endpoint was significantly higher for the highest than in the lowest NLR group (HR 1.97, 95% CI 1.09-3.54, P = 0.02). Increasing NLR as a continuous variable was associated with the incidence of adverse cardiovascular events (HR 1.85 per log 1 NLR increase, 95% CI 1.19-2.88, P = 0.007). In conclusion, the adverse long-term clinical outcomes of CAD patients with low-grade hs-CRP levels has been independently predicted by increased NLR level. NLR could be useful for risk stratification of CAD patients with increased inflammatory marker levels.

Discordant results have been reported on outcomes of acute myocardial infarction (AMI) patients who present during off-hours.We investigated 3283 consecutive patients with AMI who were selected from the prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation (defined as weekends, holidays, and weekdays from 8:01 PM to 7:59 AM) at hospitals on long-term clinical outcomes. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina for up to 3 years from the index event.During off-hours, 52% of patients presented. Primary percutaneous coronary intervention was performed in 85% of patients, and the door-to-balloon time was comparable between off-hours and regular hours (74, interquartile range [IQR] 52 to 113 versus 75, IQR 52 to 126 minutes, P = 0.34). Rate of overall primary endpoint overall did not overall significantly differ (25.3% versus 23.5%, log-rank P = 0.26), in patients with ST-elevation myocardial infarction (STEMI) (log-rank P = 0.93) and in patients with non-ST-elevation myocardial infarction (NSTEMI) (log-rank P = 0.14). Multivariate Cox regression analysis showed that off-hours presentation was not significantly associated with long-term clinical events in all cohorts.The impact of presentation during off-hours or regular hours on the long-term clinical outcomes of Japanese patients with AMI is comparable in contemporary practice.

Aims Living alone is reported as an independent risk factor for cardiovascular disease. However, little is known about the association between clinical outcomes and living alone in patients with acute coronary syndrome (ACS). The aim of this study was to determine whether living alone is an independent prognostic risk factor for long-term mortality stratified by age in patients with ACS who were treated with primary percutaneous coronary intervention (PCI). Methods and results We conducted an observational cohort study of ACS patients who underwent PCI between January 1999 and May 2015 at Juntendo University Shizuoka Hospital, Japan. The primary endpoint was all-cause death. Among 2547 ACS patients, 381 (15.0%) patients were living alone at the onset of ACS. The cumulative incidence of all-cause death was comparable between living alone and living together (34.8% vs. 34.4%, log-rank P = 0.63). However, among younger population (aged Conclusion Although living alone was not significantly associated with long-term clinical outcomes in patients with ACS, it was a predictive risk factor among younger ACS patients. Careful attention should be paid to patients’ lifestyle, especially younger patients with ACS.

Background: Little large-scale data is available about the long-term (beyond 3 years) clinical outcomes after fractional flow reserve (FFR)–based deferral of revascularization in clinical practice. We sought to assess the 5-year outcomes after deferral of revascularization based on FFR. Methods: The J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry) prospectively enrolled 1263 patients with 1447 lesions in whom revascularization was deferred based on FFR from 28 Japanese centers. The primary study end point was the cumulative 5-year incidence of target vessel failure (TVF), including cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. Results: Five-year follow-up was completed in 92.2% of patients. The 5-year TVF rate was 11.6% in deferred lesions, mainly driven by clinically driven target vessel revascularization (9.8%). Cardiac death and target vessel–related myocardial infarction were 1.9% and 0.95%, respectively. Cumulative 5-year incidence of TVF was similar between the FFR 0.75 to 0.80 and 0.81 to 0.85 groups even after adjustment for baseline characteristics (12.2% versus 13.0%, inverse probability–weighted hazard ratio, 0.86 [95% CI, 0.46–1.60]; P =0.63). Compared with the almost normal FFR (0.86–1.00) group, the significant (P Conclusions: The 5-year TVF rate was 11.6% in deferred lesions, mainly driven by clinically driven target vessel revascularization. Notably, cardiac death and target vessel–related myocardial infarction rarely occurred during the follow-up. Our findings highlight the long-term safety of FFR-based deferral of revascularization in patients with chronic coronary syndrome. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000014473.

Guideline-directed medical therapy (GDMT) is essential to prevent future cardiovascular events in chronic coronary syndrome (CCS) patients. However, whether achieving optimal GDMT could improve clinical outcomes in CCS patients with deferred lesions based on fraction flow reserve (FFR) remains thoroughly investigated. We sought to evaluate the association of GDMT adherence with long-term outcomes after FFR-based deferral of revascularization in a real-world registry.This is a post-hoc analysis of the J-CONFIRM registry (long-term outcomes of Japanese patients with deferral of coronary intervention based on fractional flow reserve in multicentre registry). Optimal GDMT was defined as combining four types of medications: antiplatelet drug, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, beta-blocker, and statin. After stratifying patients by the number of individual GDMT agents at 2 years, landmark analysis was conducted to assess the relationship between GDMT adherence at 2 years and 5-year major adverse cardiac events (MACEs), defined as a composite of all-cause death, target vessel-related myocardial infarction, clinically driven target vessel revascularization. Compared with the suboptimal GDMT group (continuing ≤3 types of medications, n = 974), the optimal GDMT group (n = 139) showed a lower 5-year incidence of MACE (5.2% vs. 12.4%, P = 0.02). The optimal GDMT was associated with a lower risk of MACE (hazard ratio: 0.41; 95% confidence interval: 0.18 to 0.92; P = 0.03).Patients with optimal GDMT were associated with better outcomes, suggesting the importance of achieving optimal GDMT on long-term prognosis in CCS patients after FFR-guided deferral of revascularization.

Background: Although short-term mortality of acute myocardial infarction (AMI) has decreased dramatically, sudden cardiac arrest is still one of serious complication. We assessed the clinical characteristics and prognosis’ predictors of AMI patients with out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively analyzed consecutive patients with AMI who were treated with emergency percutaneous coronary intervention between 2004 and 2017. Patients with OHCA were compared with those without OHCA. Results: Among 2,101 AMI patients, 95 (4.7%) presented OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93-0.97; p Conclusions: About 1 of 20 AMI patients presented with OHCA and younger age, absence of coronary risk factors, and anterior wall infarction were associated with OHCA occurrence.

Introduction: The evidence-based optimal medical therapy has been encouraged in the treatment of patients with coronary artery disease. However, as follow-up periods are limited (-5 years) in the most of randomized trials, prognostic efficacy of drugs in longer time period has not been fully evaluated. Therefore, this registry-based study aimed to simultaneously address the long-term prognostic impact of 6 major classes of cardiovascular (CV) drugs, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), Statins and Non-aspirin antiplatelets following percutaneous coronary intervention (PCI). Methods and Results: This is an analyses of single center prospective registry with lengthy history launched in 1984. Consecutive 6,299 patients underwent first PCI between 1984 and 2018 were included and CV mortality was set as the endpoint. Median and the range of follow-up period is 8.8, 0-28.9 years, respectively. Cox proportional hazard analyses adjusted by age, gender, BMI, diabetes and cardiac and renal function simultaneously evaluated the prognostic impacts of 6 major CV drugs in the entire population and patients with acute coronary syndrome (ACS). Among 6 drugs, ARBs (Hazard Ratio (HR): 0.72, 95% confidence interval (95% CI): 0.55-0.93, p=0.01), Non-aspirin antiplatelets (0.67, 0.53-0.86, p=0.002) and Statins (0.56, 0.44-0.7, pFigure A ). In ACS patients (n=1,790), only Statins at PCI predicted the reduced risk of CV mortality (HR: 0.44, 95%CI 0.28-0.68 pFigure B ). Conclusions: This long-term PCI registry-based analyses demonstrated the significant prognostic efficacy of ARBs, antiplatelets other than aspirin and statins. In ACS patients, only Statins, not other 5 classes of major CV drugs, were associated with reduced risk of CV mortality.

Background and Objective: Living alone is reported as an independent risk factor for worse clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Manifestations of psychological stress in patients living alone is reported to be associated with subsequent cardiovascular events. The impact of living alone on the psychological factors of patients may be differ depending on their living environment. However, comparison of the effects of living alone in different living environment on the prognosis of patients with ACS has not been reported. Purpose: The aim of the study was to compare the effect of living alone on clinical outcomes in patients with ACS between urban and rural area. Methods: Data from a multi-center, observational study of consecutive ACS patients who underwent emergency PCI between January 2012 and December 2016 were analyzed. The clinical endpoint was major adverse cardiovascular events (MACE) which defined as composite of cardiovascular death, ACS, and stroke. Results: In this study, 1349 patients were enrolled and divided into two population according to their living environment; urban area (n=417), and rural area (n=932). 87 patients (20.9 %) in urban area, and 169 patients (18.1 %) in rural were living alone. There were no significant differences in baseline characteristics between the living alone and the living together group in both urban and rural area. During a median follow-up period of 2.1 years, Kaplan-Meier curves showed the living alone group had higher risk of MACE than the living together group in urban area (log-rank, p=0.01). On the other hands, no significant differences were shown in the incidences of MACE between two groups in rural area (p=0.86). After adjustment for other covariates, the living alone was significantly associated with MACE (hazard ratio [HR], 2.83; 95 % confidential interval [CI], 1.16-6.91; p=0.02) compared with the living together in urban area. However, in rural area, the living alone group was not significantly associated with MACE (HR, 1.02; 95 % CI, 0.66-1.57; p=0.92) compared with the living together group. Conclusion: Living alone was significantly associated with worse clinical outcomes after emergency PCI of ACS in urban area but not in rural area.

The left intermammary artery (LIMA) graft is commonly used in coronary artery bypass grafting (CABG) to left anterior descending (LAD) because of its superior long-term patency. Acute occlusion of the LIMA causing ST-elevation myocardial infarction (STEMI) in the late postoperative period is rare, and its pathological mechanism is unclear. We present a case of acute occlusion of the LIMA in a 87-year-old woman who underwent CABG surgery 13 years previously. She was transferred to our hospital because of acute chest pain. Electrocardiography showed ST-elevation in anterior leads. Emergency coronary angiography revealed total occlusion of proximal LAD segment and the ostial LIMA (Figure). Therefore, we judged that the LIMA occlusion was causing anterior STEMI, and performed emergency percutaneous intervention. We successfully implanted a drug eluting stent at the culprit lesion and final angiography showed good reperfusion. Although the LIMA graft is expected long-term patency, early recognition of the possibility of LIMA occlusion might be necessary in patients with AMI after CABG surgery.

The association between lipoprotein(a) (Lp[a]) levels and cardiovascular disease has been reported. However, it is still uncertain whether Lp(a) concentration could be a residual risk factor for cardiovascular events after acute coronary syndrome (ACS). The aim of the present study is to evaluate the impact of Lp(a) on long-term cardiovascular outcomes in patients with ACS treated with statins. We studied 1,758 consecutive patients with ACS who underwent emergency percutaneous coronary intervention between 2008 and 2017. We finally enrolled 1,131 patients for whom Lp(a) data were available and who were treated with statins at discharge. Patients were divided into 2 groups according to Lp(a) levels (median Lp(a) 15.0 mg/100 ml). The primary end points were major adverse cardiac events (MACEs), composite of all-cause death, and myocardial infarction up to 5 years. Overall, 107 MACEs (9.5%) were identified. The cumulative incidence of MACE was significantly higher in the high Lp(a) group than the low Lp(a) group (log-rank p = 0.01). After adjustment for other cardiovascular risk factors, the high Lp(a) group had a significantly higher risk of MACE (hazard ratio 1.66, 95% confidence interval 1.05 to 2.61, p = 0.03). Multivariate Cox hazard analysis also showed that increasing Lp(a) as a continuous variable was associated with the incidence of MACE (hazard ratio 1.35 per log Lp[a] 1 increase, 95% confidence interval 1.07 to 1.72, p = 0.01). In conclusion, high Lp(a) level is significantly associated with long-term cardiovascular outcomes in patients with ACS treated with statins after primary percutaneous coronary intervention and is likely to be a potential biomarker for residual risk prediction of future clinical events.

Background and objective Living alone is reported as an independent risk factor for worse clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Manifestations of psychological stress such as depression and anxiety in patients living alone is thought to be associated with subsequent cardiovascular events. The impact of living alone on the psychological factors of patients may be differ depending on their living environment. However, comparison of the effects of living alone in different living environment on the prognosis of patients with ACS has not been reported. Purpose The aim of the present study was to compare the clinical effect of living alone on clinical outcomes in patients with ACS between urban area and rural area. Methods Data from a multi-center, observational study of consecutive patients who underwent emergency PCI for ACS between January 2012 and December 2016 were analyzed. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE). MACCE was defined as composite of cardiovascular death, ACS, and stroke. Results In this study, 1349 patients were enrolled and divided into two population according to their living environment: urban area population (n=417), and rural area population (n=932). In urban area population, 87 patients (20.9%) were living alone, and 330 (79.1%) were living together. In rural area population, 169 (18.1%) were living alone, and 763 (81.9%) were living together. There are no significant differences in baseline characteristics between the living alone group and the living together group in both urban area population and rural area population. During a median follow-up period of 2.1 years, Kaplan-Meier curves showed the living alone group had higher risk of MACCE than the living together group in urban area population (log-rank, p=0.01). On the other hands, there are no significant differences in the incidences of MACCE between two groups in rural area population (p=0.86). After adjustment for other covariates, the living alone was significantly associated with MACCE (hazard ratio [HR], 2.83; 95% confidential interval [CI], 1.16–6.91; p=0.02) compared with the living together group in urban area population. However, in rural area population, the living alone group was not significantly associated with MACCE (HR, 1.02; 95% CI, 0.66–1.57; p=0.92) compared with the living together group. Conclusion Living alone was significantly associated with worse clinical outcomes after emergency PCI of ACS in urban area but not in rural area. Funding Acknowledgement Type of funding sources: None. Figure 1

Left ventricular thrombus (LVT) is known as a life-threatening complication of acute myocardial infarction, in terms of sequential systemic embolization. When an LVT is found to be sufficiently large or mobile, not only anticoagulation therapy but also surgical thrombectomy should be administered immediately to prevent embolic events. Generally, since infarcted myocardium is comparatively fragile, ventriculotomy may result in anastomotic failure or further deterioration of LV function. We report herein a case of transmitral removal of LVT by which we successfully avoided ventriculotomy. A 50-year-old Japanese man was hospitalized due to ST-segment elevation myocardial infarction and emergency coronary angiography revealed total occlusion at the proximal left anterior descending artery. On hospital day 9, transthoracic echocardiography detected a massive LVT at the apex, protruding into the left ventricle. Considering the risk of embolization, urgent thrombectomy via a transmitral approach was performed. The LVT was easily removed through the mitral valve under endoscopic support, without any embolic events or postoperative complications.

Background: Dipeptidyl-peptidase-4 inhibitors (DPP4i) have become one of the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, no large cardiovascular outcome trials (CVOTs) have shown any significant superiority with respect to reducing cardiovascular risk. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. Therefore, the aim of this study was to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4 and it is relevant for the cardiovascular system.Methods: This single-center analysis involved consecutive Japanese diabetic patients who underwent percutaneous coronary intervention (PCI) for the first time between 2008 and 2018 (n=885). Primary and secondary endpoints were set as cardiovascular (CV)-death and the composite of CV-death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (IGF- binding protein 3: IGFBP-3) were measured by ELISA.Results: Unadjusted Kaplan-Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV-death by DPP4i at PCI (hazard ratio (HR): 0.39, 95% confidence interval (CI): 0.16–0.82, p=0.01) and 3P-MACE (HR: 0.47, 95% CI: 0.25–0.84, p=0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (pConclusion: The findings of the present study indicate that DPP4i improved outcomes in Japanese diabetic patients following PCI, in which the beneficial effects might be mediated by DPP4-IGF-1 axis. Trial registration: This study reports the retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan - Clinical Trials Registry, UMIN-CTR 000035587).

Background Although short-term mortality of acute myocardial infarction (AMI) has decreased dramatically in the past few decades, sudden cardiac arrest remains a serious complication. The aim of the study was to assess the clinical characteristics and predictors of prognosis in AMI patients who experienced out-of-hospital cardiac arrest (OHCA). Methods We retrospectively registered consecutive AMI patients who were treated with emergency percutaneous coronary intervention (PCI) between 2004 and 2017. Clinical characteristics and outcomes were compared between patients with OHCA and those without OHCA. Results Among 2101 AMI patients, 95 (4.7%) presented with OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93–0.97; p p = 0.01) or dyslipidemia (OR, 0.56; 95% CI, 0.36–0.88; p = 0.01), left main trunk (LMT) or left anterior descending artery (LAD) as the culprit lesion (OR, 3.26; 95% CI, 1.99–5.33; p p p = 0.004), glucose level (OR, 1.01; 95% CI, 1.00–1.01; p = 0.01), and renal deficiency (OR, 3.35; 95% CI, 1.07–10.53; p = 0.04) as independent predictors of 30-day mortality among AMI patients with OHCA. Conclusions In patients with AMI who underwent emergency PCI, 30-day mortality was six times greater in those having presented initially with OHCA compared with those without OHCA. Younger age, absence of diabetes mellitus or dyslipidemia, LMT or LAD as the culprit lesion, and renal deficiency were independent predictors of OHCA. OHCA patient with higher blood glucose level on admission, LMT or LAD as the culprit lesion, or renal deficiency showed worse clinical outcomes.

IntroductionPacing-induced cardiomyopathy occasionally occurs in patients undergoing pacemaker implantation. Although compared with right ventricular (RV) apical pacing, RV septal pacing can attenuate left ventricular dyssynchrony; the success rate of lead placement on the RV septum using the stylet system is low. Additionally, no randomised controlled trial has addressed the issue regarding the accuracy of RV lead placement on the RV septum using the stylet and delivery catheter systems. This study hypothesises that a newly available delivery catheter system can improve the accuracy of RV lead placement on the RV septum.Methods and analysisIn a multicentre, prospective, randomised, single-blind, controlled trial, 70 patients with pacemaker indication owing to atrioventricular block will be randomised to either the delivery catheter or stylet group before the pacemaker implantation procedure. The position of the RV lead tip will be assessed using ECG-gated cardiac CT in all patients within 4 weeks after pacemaker implantation. Lead tip positions are classified into three groups: (1) RV septum, (2) anterior/posterior edge of the RV septal wall and (3) RV free wall. The primary endpoint will be the success rate of RV lead tip placement on the RV septum, which will be evaluated using cardiac CT.Ethics and disseminationThis study will be conducted according to the stipulations of the Helsinki Declaration and the institutional review board of Hamamatsu University School of Medicine. The results of the study will be disseminated at several research conferences and will be published in peer-reviewed journals.Trial registration numberjRCTs042200014; Pre-results.

Introduction C-reactive protein (CRP) is an established marker for vascular inflammation and predictor of adverse cardiovascular events, but the prognostic value of preprocedural CRP in coronary artery disease (CAD) patients who have undergone percutaneous coronary intervention (PCI) remains controversial. Furthermore, the impact of CRP levels during follow-up in CAD patients after PCI on long-term adverse clinical outcomes is uncertain. We evaluated the association between high-sensitivity (hs)-CRP values at follow-up angiography and long-term clinical outcomes in CAD patients after coronary intervention. Methods We prospectively enrolled 3507 consecutive CAD patients who underwent first PCI between 1997 and 2011 at our institution. We identified 2509 patients (71.5%) who underwent follow-up angiography (6–8 months after PCI). Of those, 1605 patients (45.8%) who had data available for hs-CRP at follow-up angiography were stratified into three groups according to tertiles of hs-CRP level at the time of follow-up angiography. The primary endpoint was composite of all-cause death and non-fatal acute coronary syndrome (ACS). Results Median follow-up was 1716 days. The cumulative incidence of all-cause death and ACS differed significantly among groups (log-rank, p = 0.0002). Multivariate Cox regression analysis showed that a higher hs-CRP level at follow-up angiography was associated with a greater risk of all-cause death and ACS [adjusted hazard ratio (HR) for all-cause death and ACS 2.14, 95% confidence interval (CI) 1.43–3.27, p = 0.0002. Conclusion Elevated hs-CRP levels during follow-up were significantly associated with higher frequencies of adverse long-term clinical outcomes in patients with CAD after PCI.

Long-term clinical outcomes among patients with cardiogenic shock (CS) and heart failure (HF) who survive the early phase of acute myocardial infarction (AMI) remain uncertain. We investigated 3283 consecutive patients with AMI, selected from a prospective, nation-wide multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014. The 3263 eligible patients were divided into the following three groups: CS-/HF- group (n = 2467, 75.6%); CS-/HF+ group (n = 479, 14.7%); and CS+ group (n = 317, 9.7%). The thirty-day mortality rate in CS+ patients was 32.8%, significantly higher than in CS- patients. Among CS+ patients, multivariate logistic regression analysis identified statin use before admission (Odds ratio (OR) 0.32, 95% confidence interval (CI) 0.14-0.66, P = 0.002), renal deficiency (OR 8.72, 95%CI 2.81-38.67, P0.0001) and final thrombolysis in myocardial infarction flow grade (OR 0.42, 95%CI 0.18-0.99, P = 0.046) were associated with 30-day mortality. Landmark Kaplan-Meier analysis showed that mortality rates after 30 days were comparable between CS+ and CS-/HF+ groups but were lower in the CS-/HF- group. Multivariate Cox hazard analysis also showed that hazard risk of mortality after 30 days was comparable between the CS+ and CS-/HF+ groups (Hazard ratio (HR) 1.03, 95%CI 0.63-1.68, P = 0.90), and significantly lower in the CS-/HF- group (HR 0.44, 95%CI 0.32-059, P0.0001). In conclusion, AMI patients with CS who survived 30 days experienced worse long-term outcomes compared with those without CS up to 3 years. Attention is required for patients who show HF on admission without CS to improve long-term AMI outcomes.

Background: Safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) is uncertain in patients undergoing complex percutaneous coronary intervention (PCI). Methods: We conducted a post hoc subgroup analysis based on the complexity of PCI in the STOPDAPT-2 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-2), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT after cobalt-chromium everolimus-eluting stent implantation. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents, >60 mm total stent lengths, and target of chronic total occlusion. The primary end point was the composite of cardiovascular (cardiovascular death/myocardial infarction/definite stent thrombosis/stroke) and bleeding (TIMI [Thrombolysis in Myocardial Infarction] major/minor) end points. The major secondary end points were the cardiovascular and bleeding end points. Results: Among the 3009 study patients, there were 509 patients (16.9%) with complex PCI (1-month DAPT: N=245, and 12-month DAPT: N=264) and 2500 patients (83.1%) without complex PCI (1-month DAPT: N=1255, and 12-month DAPT: N=1245). There were no significant interactions between the complexity of PCI and the effects of 1-month DAPT versus 12-month DAPT on the primary end point (complex PCI: 1.67% versus 5.32%, hazard ratio, 0.30 [95% CI, 0.10–0.92], P =0.04, and noncomplex PCI: 2.50% versus 3.35%, hazard ratio, 0.75 [95% CI, 0.47–1.20], P =0.23; P interaction =0.14), and on the major secondary cardiovascular end point (complex PCI: 1.67% versus 3.04%, hazard ratio, 0.54 [95% CI, 0.16–1.79], P =0.31, and noncomplex PCI: 2.02% versus 2.39%, hazard ratio, 0.86 [95% CI, 0.50–1.47], P =0.58; P interaction =0.49). The cumulative 1-year incidence of the major secondary bleeding end point was significantly lower in the 1-month DAPT group than in the 12-month DAPT group regardless of the complexity of PCI (complex PCI: 0% versus 2.29%, log-rank P =0.02, and noncomplex PCI: 0.48% versus 1.38%, log-rank P =0.02). Conclusions: The effects of clopidogrel monotherapy after 1-month DAPT relative to 12-month DAPT for the primary and major secondary end points were comparable in complex PCI and noncomplex PCI without significant interactions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02619760.

Background The aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF). Methods Data were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40–49%) and 201 patients with rEF (EF Results The median follow-up period was 5.5 years in mrEF patients and 4.3 years in rEF patients. Cumulative event-free survival was significantly lower in the group with beta-blockers than in the group without beta-blockers in rEF (p = 0.003), whereas no difference was observed in mrEF (p = 0.137) between those with and without beta-blockers. In the multivariate analysis, use of beta-blockers was associated with reduction in clinical outcomes in patients with rEF (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36–0.97; p = 0.036), whereas no association was observed among those with mrEF (HR 0.74; 95% CI 0.49–1.10; p = 0.137). Conclusions Our observational study showed that use of beta-blockers was not associated with long-term clinical outcomes in IHD patients with mrEF, whereas a significant association was observed in those with rEF.

Background: Insulin-like growth factor-1 (IGF-1) is a protein which plays protective roles against cardiovascular disorders, including the endothelial dysfunction and the instability of atherosclerotic plaque. However, prognostic implication of serum IGF-1 level has been rarely evaluated in diabetic patients with established coronary artery disease. Methods: This single center observational study involved consecutive 819 diabetic patients underwent percutaneous coronary intervention (PCI) since 2008 to 2018. In frozen-stocked (-80°C) serum, IGF-1 was measured by ELISA assay. Endpoints were set as cardiovascular (CV) death and the composite of CV death, myocardial infarction and ischemic stroke (3-point MACE). The median and the range of follow-up period was 4.0 and 0-10.4 years, respectively. Results: Participants were divided by the median of IGF-1 (75 ng/ml) (low (n=412) and high IGF-1 group (n=407)). Unadjusted Kaplan-Meier analyses with log-rank test showed the significantly higher incidences of CV death and 3P-MACE in low IGF-1 group ( Figures ). Moreover, multivariate Cox proportional hazard analysis adjusted by covariates including age, sex, PCI for acute coronary syndrome, multivessel disease, renal function (eGFR, ml/min/1.73m 2 ) and glycated hemoglobin (HbA1c, %) demonstrated that low IGF-1≤75 ng/ml was associated with substantially increased risk of CV death (Hazard Ratio (HR): 1.9, 95% confidence interval (95%CI): 1.1-3.6, p=0.03) and 3P-MACE (HR 1.7, 95%CI:1.0-2.7, p=0.04), respectively. Conclusion: Findings in this study suggest that serum IGF-1 levels are a useful and independent prognostic indicator in diabetic patients following PCI.

Background Inflammatory status pre-percutaneous coronary intervention (PCI) and post-PCI has been reported not only associated with poor prognosis, but also to impair renal function. Statins reduce cardiovascular events by lowering lipids and have anti-inflammatory impacts, but residual inflammatory risk (RIR) exists. It remains unclear that the synergistic effect of RIR and chronic kidney disease (CKD) on long-term clinical outcome in stable coronary artery disease (CAD) patients undergoing PCI in statin era. Aim The aim of this study was to investigate the long-term combined impact of RIR evaluating hs-CRP at follow-up and CKD among stable CAD patients undergoing PCI in statin era. Methods This is a single-center, observational, retrospective cohort study assessing consecutive 2,984 stable CAD patients who underwent first PCI from 2000 to 2016. We analyzed 2,087 patients for whom hs-CRP at follow-up (6–9 months later) was available. High residual inflammatory risk was defined as hs-CRP >0.6 mg/L according to the median value at follow up. Patients were assigned to four groups as Group1 (high RIR and CKD), Group2 (low RIR and CKD), Group3 (high RIR and non-CKD) or Group4 (low RIR and non-CKD). We evaluated all-cause death and major adverse cardiac events (MACE), defined as a composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke. Results Of patients (83% men; mean age 67 years), there were 299 (14.3%) patients in group 1, 201 (9.6%) patients in group 2, 754 (36.1%) patients in group 3, and 833 (39.9%) patients in group 4. The median follow-up period was 5.2 years (IQR, 1.9–9.9 years). In total, 189 (frequency, 16.1%) cases of all-cause death and 128 (11.2%) MACE were identified during follow-up, including 53 (4.6%) CV deaths, 27 (2.4%) MIs and 52 (4.8%) strokes. The rate of all-cause death and MACE in group 1 was significantly higher than other groups (p Conclusion The presence of both high RIR and CKD conferred a synergistic adverse effect on the risk for long-term adverse cardiac events in patients undergoing PCI. Kaplan-Meier curve Funding Acknowledgement Type of funding source: None

BackgroundPeroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that has key roles of lipid metabolism and inflammation. The PPARα may affects the initiation and progression of atherosclerosis by reducing inflammatory responses. Pemafibrate (K-877) is a novel selective PPARα modulator (SPPARMα), which was designed to possess higher PPARα potency and selectivity than existing PPARα agonists. The aim of this study is to evaluate the effect of pemafibrate on vascular response in coronary atherosclerosis model using low density lipoprotein receptor knock-out (LDLR-KO) pigs with balloon injury.Methods and resultsTen LDLR-KO pigs were randomly allocated to two groups [pemafibrate (n = 5) and control (n = 5)] and fed with a diet containing 2.0% cholesterol and 20% lard throughout the study. Balloon injury was created in 40 coronary segments two weeks after starting the oral administration of pemafibrate or placebo. Necropsy was conducted 8 weeks later. Coronary artery sections were reviewed to evaluate lesion progression and the mRNA expression levels for C-Jun, NFκ B, CCL2, CCR7, CD163 and MMP9 determined using real-time RT-PCR. LDL cholesterol at baseline was about 700 mg/dL. The mean ratio of macrophages to plaque area was significantly lower in pemafibrate group compared with control one (7.63±1.16 vs 14.04±4.51, P = 0.02) whereas no differences were observed in intimal area between groups. The mRNA levels of C-Jun, NFκB and MMP9 were significantly decreased in pemafibrate group.ConclusionsPemafibrate was associated with inhibition of inflammatory responses in coronary artery atherosclerosis model using LDLR-KO swine with balloon injury.

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.

The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y

The aim of this study was to investigate the long-term clinical impact of residual inflammatory risk (RIR) by evaluating serial high-sensitivity C-reactive protein (hs-CRP) in Asian patients with coronary artery disease (CAD). We evaluated 2032 patients with stable CAD undergoing percutaneous coronary intervention (PCI) with serial hs-CRP measurements (2 measurements, 6&ndash, 9 months apart) from the period 2000 to 2016. A high-RIR was defined as hs-CRP &gt, 0.9 mg/L according to the median value. Patients were assigned to four groups: persistent-high-RIR, increased-RIR, attenuated-RIR, or persistent-low-RIR. Major adverse cardiac events (MACE) and all-cause death were evaluated. MACE rates in patients with persistent high, increased and attenuated RIR were significantly higher than in patients with persistent low RIR (p &lt, 0.001). Moreover, the rate of all-cause death was significantly higher among patients with persistent high and increased RIR than among patients with attenuated and persistent low RIR (p &lt, 0.001). After adjustment, the presence of persistent high RIR (hazard ratio (HR) 2.22, 95% confidence interval (CI) 1.37&ndash, 3.67, p = 0.001), increased RIR (HR 2.25, 95%CI 1.09&ndash, 4.37, p = 0.029), and attenuated RIR (HR 1.94, 95%CI 1.14&ndash, 3.32, p = 0.015) were predictive for MACE. In addition, presence of persistent high RIR (HR 2.07, 95%CI 1.41&ndash, 3.08, p &lt, 0.001) and increased RIR (HR 1.94, 95%CI 1.07&ndash, 3.36, p = 0.029) were predictive for all-cause death. A high RIR was significantly associated with MACE and all-cause death among Japanese CAD patients. An evaluation of changes in inflammation may carry important prognostic information and may guide the therapeutic approach.

Discordant results have been reported on outcomes of acute myocardial infarction (AMI) patients who present during off-hours.We investigated 3283 consecutive patients with AMI who were selected from the prospective, nationwide, multicenter registry (J-MINUET) database comprising 28 institutions in Japan between July 2012 and March 2014 to determine the current impact of off-hours presentation (defined as weekends, holidays, and weekdays from 8:01 PM to 7:59 AM) at hospitals on long-term clinical outcomes. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina for up to 3 years from the index event.During off-hours, 52% of patients presented. Primary percutaneous coronary intervention was performed in 85% of patients, and the door-to-balloon time was comparable between off-hours and regular hours (74, interquartile range [IQR] 52 to 113 versus 75, IQR 52 to 126 minutes, P = 0.34). Rate of overall primary endpoint overall did not overall significantly differ (25.3% versus 23.5%, log-rank P = 0.26), in patients with ST-elevation myocardial infarction (STEMI) (log-rank P = 0.93) and in patients with non-ST-elevation myocardial infarction (NSTEMI) (log-rank P = 0.14). Multivariate Cox regression analysis showed that off-hours presentation was not significantly associated with long-term clinical events in all cohorts.The impact of presentation during off-hours or regular hours on the long-term clinical outcomes of Japanese patients with AMI is comparable in contemporary practice.