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BackgroundInappropriately high activated clotting time (ACT) during percutaneous coronary intervention (PCI) is associated with an increased risk of bleeding events. However, whether the prescription of direct oral anticoagulants (DOAC) affects ACT kinetics during heparin use and adverse clinical events in patients undergoing PCI remains unclear. To evaluate the ACT changes during and adverse clinical events after PCI in patients who were prescribed DOAC.MethodsThis observational study included 246 patients undergoing PCI at the two cardiovascular centers who were not receiving warfarin and whose ACT was recorded immediately before and 30 min after injection of unfractionated heparin (UFH). Patients were divided into two groups according to DOAC prescription at the time of the index PCI: DOAC users (n=31) and non-users (n=215). Any bleeding and systemic thromboembolic events were investigated until 30 days after PCI.ResultsThe average age of this population was 70.5 years, and 66.3% were male. Average ACT was significantly higher in DOAC users than non-users both before and 30 min after UFH induction (157.2 ± 30.1 vs. 131.8 ± 25.1 sec, pConclusionPatients receiving DOAC have higher ACTs during PCI and higher incidence of bleeding events than those not receiving DOAC.CONDENSED ABSTRACTChanges in activated clotting time (ACT) and incidence of systemic thromboembolic and bleeding events in patients undergoing percutaneous coronary intervention (PCI) using conventional heparin were compared between those receiving direct oral anticoagulants (DOAC) and those who were not. ACT both before and 30 min after initial heparin injection was higher in patients who received DOAC than in those who did not. DOAC prescription did not affect the incidence of systemic thromboembolic events. Conversely, patients receiving DOAC more frequently experienced post-PCI bleeding events than those not receiving DOAC.

Background: The prescription of inhibitors for renin-angiotensin-aldosterone system (RAAS) is associated with improved prognosis but have respectively different mechanisms of action in patients with coronary artery disease (CAD). We aimed to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI. After excluding 18 patients who received both ACEi and ARB from 2,896 registered patients, we ultimately evaluated 369 patients treated with ACEi, 492 with ARB and 541 without ACEi or ARB. The primary endpoint was a major adverse cardiovascular and cerebrovascular events (MACCE) including death from any cause, acute coronary syndrome, stent thrombosis, stroke and hospitalization for heart failure. The impact of RAAS inhibitors on all-cause mortality alone was also evaluated. Results: During the observation period with 366 days of a median follow-up, Kaplan-Meier analysis revealed that the ARB group had the lowest rate of MACCE than other two groups (Log-rank for trend, p< for < 0.0001, Figure). Regarding all-cause mortality, the ARB group and ACEi group had comparable rates for MACCE, which were lower than the no-ACEi/ARB group (p< for < 0.0001). In a Cox regression analysis, after adjusting with age, gender, comorbidities, multivessel disease, acute myocardial infarction, and medications at discharge including dual antiplatelet therapy and statins, ARB therapy was still had a superiority to ACEi therapy regarding with MACCE (hazard ratio: 0.54, 95% confidence interval: 0.30-0.98). Conclusion: In the multicenter cohort study, ARB therapy was associated with better one-year clinical outcomes compared to ACEi therapy in patients undergoing PCI.

Introduction: The combination of aspirin and P2Y12 receptor antagonist is the standard antiplatelet therapy after percutaneous coronary intervention (PCI). Previous trials reported that prasugrel reduced the risk of ischemic events, but increased bleeding events compared to clopidogrel. Hypothesis: The prognostic impact of low-dose prasugrel (3.75 mg/day), which the dose was determined by phase II trial, is different from that of clopidogrel, depending on patient’s bleeding risk. Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI. We analyzed 1,001 patients who received the combination of aspirin and prasugrel or clopidogrel after PCI. The primary endpoint was a composite of major bleeding event and major adverse cardiovascular and cerebrovascular events (MACCE) including any death, acute coronary syndrome, stent thrombosis, stroke and heart failure hospitalization. Results: There were 490 patients with high bleeding risk (HBR) and 511 patients with low bleeding risk (LBR), based on ARC-HBR criteria. In HBR patients, the Low-dose prasugrel group had significantly lower rates of MACCE (Log-rank, p=0.003) and the composite endpoint than the Clopidogrel group (p=0.001). While, in LBR patients, there was no significant difference in rates of MACCE or the composite endpoint between the groups (p=0.76, p=0.15, respectively), and a higher rate of major bleeding event in the Low-dose prasugrel group (p=0.002). With Cox proportional hazards analysis, low-dose prasugrel has still retained the superiority to clopidogrel regarding with the composite endpoint in HBR patients, even after adjusting with diverse covariates (hazard ratio: 0.33, 95% confidence interval: 0.16-0.65). Conclusion: In the multicenter cohort study in Japan, low-dose prasugrel showed a long-term prognostic superiority to clopidogrel only in HBR patients undergoing contemporary PCI.

Previous reports have focused on cardiovascular and bleeding events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, antithrombotic treatment strategies and clinical outcomes after second-generation drug-eluting stents (DES) implantation in AF patients remain to be determined. We enrolled 244 consecutive AF patients treated with second-generation DES. The study population was derived from multi-center AF registry (including 8 centers in Japan) from 2010 to 2012. Prescription of antithrombotic agents and clinical outcomes were retrospectively examined. Ninety-two patients (37.7%) were prescribed dual antiplatelet therapy (DAPT) at discharge and 152 patients (62.3%) were given DAPT plus oral anticoagulation (OAC) with warfarin. The median follow-up period was 730 days. Kaplan–Meier analysis showed that major adverse cardiac and cerebrovascular events (MACCE) were not significantly different (2-year event rate, 17.6 vs. 13.5%, p = 0.37), but bleeding events were significantly higher in the DAPT plus OAC group than in the DAPT group (2-year event rate, 6.1 vs. 17.9%, p = 0.033). In a sub-analysis of DAPT plus OAC patients, adequate time in the therapeutic range (TTR) group (TTR ≥ 65%) was not significantly different from the suboptimal OAC group (TTR

Background The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. In a recent study, iFR was found to be more closely linked to coronary flow reserve (CFR) than fractional flow reserve (FFR). E/e′ is a surrogate marker of left ventricular (LV) filling pressure and LV diastolic dysfunction. Coronary resting flow was found to be increased in patients with elevated E/e′, and higher coronary resting flow was associated with lower CFR. Higher baseline coronary flow induces a greater loss of translesional pressure and may affect iFR. However, no reports have examined the impact of E/e′ on iFR. The purpose of this study was to assess the relationship between iFR and E/e′ compared with FFR. Methods and results We retrospectively examined 103 consecutive patients (142 with stenosis) whose iFR, FFR, and E/e′ were measured simultaneously. The mean age, LV mass index, and systolic blood pressure of patients with elevated E/e′ were higher than those of patients with normal E/e′. Although no significant differences were observed in mean FFR values and % diameter stenosis, the mean iFR value in patients with elevated E/e′ was significantly lower than that in patients with normal E/e′. The iFR was negatively correlated with E/e′, while there was no correlation between FFR and E/e′. Multivariate analysis showed that E/e′ and % diameter stenosis were independent determinants of iFR. Conclusion E/e′ ratio affects iFR values. Our results suggest that FFR mainly reflects the functional severity of the epicardial stenosis whereas iFR could potentially be influenced by not only epicardial stenosis but also other factors related to LV filling pressure or LV diastolic dysfunction. Further research is needed to understand the underlying mechanisms that influence the evaluation of iFR in patients with elevated E/e′.

We aimed to clarify the relationships between angiographic lesion characteristics and values of fractional flow reserve (FFR) on intermediate coronary artery stenosis. The clinical meaning and assessment for "visual-functional mismatches," including regular-mismatches [defined as angiographic percent diameter stenosis (%DS) ≥50 % and FFR >0.80] and reverse-mismatches (defined as angiographic %DS

A 60-year-old woman presented with ST-elevation myocardial infarction due to extrinsic compression of the left main coronary artery (LMCA) caused by a dilated pulmonary artery (PA) with idiopathic pulmonary hypertension and was successfully treated with intravascular ultrasound- and optical coherence tomography-guided stenting. Continuous subcutaneous epoprostenol infusion therapy was initiated immediately after the procedure and increased aggressively. Imaging modalities were extremely useful in making the diagnosis and providing follow-up of LMCA compression syndrome in this case. Over the one-year observation period, a sufficient hemodynamic improvement was obtained, without exacerbation of the PA dilatation, resulting in the absence of compression of the LMCA.

The aim of this study was to examine the clinical value of iFR for AS patients. Functional evaluation of coronary stenosis in patients with aortic valve stenosis (AS) is challenging because the stress-induced test is often thought to be a contraindication. AS patients have a unique coronary flow pattern dependent on the diastolic phase. The instantaneous wave-free ratio (iFR) is a vasodilator-free, invasive pressure wire index of the functional severity of coronary stenosis and is calculated under resting conditions. And iFR calculated during a specific period of diastole may have the potential benefit to assess the functional severity of coronary stenosis in AS patients. We examined 158 consecutive patients (217 stenoses) whose iFR and fractional flow reserve (FFR) were measured simultaneously. Among the 158 patients, AS was observed in 13 (8.2%). The iFR showed good correlation with FFR in AS patients. The best cut-off value of iFR for the receiver-operator curve analysis to predict FFR of 0.8 was 0.9 for non-AS patients. However, it was 0.73 for AS patients. The present study demonstrated good correlation between iFR and FFR for AS patients. Vasodilator-free assessment using iFR may provide potential benefits when evaluating coronary stenosis in patients with AS. In AS patients, the best cut-off of iFR value predicting FFR value of 0.8 was lower than 0.9 that is the standard predictive value of iFR.

A 55-year-old woman with variant angina was hospitalized for cardiopulmonary arrest because of pulseless electrical activity (PEA). Despite intensive postresuscitation drug therapy, another episode of angina occurred, with complete atrioventricular block and PEA. There was no confirmed ventricular fibrillation or ventricular tachycardia. Coronary arteriography did not show significant stenosis, and acetylcholine-loading test was positive. The patient was diagnosed with coronary spastic angina, and a pacemaker was implanted to stabilize hemodynamics during attacks. The pacemaker settings required some ingenuity: a high output was selected to avert pacing failure, and a rate drop response setting was selected to ensure efficient pacing.

It remains unclear whether there are subgroups of acute heart failure syndromes (AHFS) patients in whom New York Heart Association (NYHA) class IV symptoms at admission is related to a higher risk of mortality because of the heterogeneity of this patient population. The aim of this study was to evaluate the association of NYHA class IV symptoms at baseline with in-hospital mortality in subgroups of patients with AHFS.Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4786 patients were included in this analysis. The primary endpoint was in-hospital all-cause death. NYHA class IV at baseline was detected in 44.3% of the patients. The all-cause death rate was significantly higher in patients with NYHA class IV than in those with NYHA class II or III (9.0% vs. 4.3%, P0.001). To examine the heterogeneity of the association between NYHA class IV symptoms at baseline and in-hospital mortality, subgroup analyses were performed. As a result, the presence of NYHA class IV symptoms on admission was associated with a significantly higher risk of all-cause death in patients aged ≥75years, female patients, patients without an idiopathic dilated etiology, and patients with preserved ejection fraction (EF).This study demonstrated that an age≥75years, female gender, the absence of idiopathic dilated etiology, and a preserved EF should be considered when assessing the clinical significance of NYHA class IV symptoms in relation to the risk of in-hospital mortality in patients hospitalized for AHFS.

Background: Instantaneous wave-free ratio (iFR) is a vasodilator free index calculated using trans-lesional pressure ratio during a specific period of diastole that is called “wave-free period”, and reported to have a good correlation with fractional flow reserve (FFR). In patients with severe aortic valve stenosis (AS), evaluation of intermediate coronary stenosis by FFR using vasodilators is thought to be a contraindication in some situations. Moreover, previous studies reported unique coronary flow pattern during diastolic phase in patients with AS. To date, there is no report claiming the correlation of iFR and FFR in this population. The purpose of the present study was to examine the clinical value of iFR in patients with AS. Method and Results: We examined consecutive 154 patients (with 214 stenosis) whose iFR and FFR were measured simultaneously. The mean age of AS patients (n=10, mean aortic valve area: 0.75 ± 0.42cm2) was higher than non-AS patients (n=144). Other patients’ characteristics are shown in Table 1. The mean iFR value in AS patients was significantly lower than that of non-AS patients, despite no significant difference was observed in the mean FFR value and % diameter stenosis (Table 2). iFR showed a good correlation with FFR in AS patients (Figure 1) and the best cut-off value of iFR in receiver operator curve analysis to predict FFR ≤ 0.8 was 0.73 in AS patients (AUC 0.84, sensitivity 0.8, specificity 0.86, p=0.016; Figure 2), whereas, 0.90 in non-AS patients. Conclusion: The present study demonstrated the good correlation between iFR and FFR in AS patients. Besides, the value below 0.73 of iFR was thought to be a predictor of myocardial ischemia in AS patients, which was lower than standard predictive range of ischemia in iFR. Vasodilator-free assessment by iFR may have potential benefits in evaluating intermediate coronary stenosis in patients with AS.

Backgrounds: Critical limb ischemia (CLI) is a severe clinical presentation of patients with peripheral artery disease, and their limb salvage and survival rates are extremely poor. However, there is still only limited evidence from observational studies for contemporary outcomes in CLI patients who underwent endovascular treatment (EVT) including both above and below the knee lesion. Therefore, this study aimed to evaluate the prognostic and predictive factors for patients with CLI who underwent EVT. Methods: Cumulative total number of 192 patients with CLI who underwent EVT between March 2009 and April 2014 was prospectively enrolled. After the exclusion of patients who were lost to follow-up within 6 months, 175 patients were retrospectively analyzed for clinical and angiographic parameters. The primary endpoints of this study were all-cause death and major amputation above the ankle joint. Results: The study population was typically elderly (average age: 68 year-old) and 76% male with a normal body mass index (BMI: 23 kg/m2) and diverse comorbidities, including 34% diabetes and 72% maintenance hemodialysis. Target lesions consisted of 23% aortoiliac, 56% femoropopliteal and 67% below-the-knee arteries, including 37% isolated below-the-knee lesion. Median follow-up period was 23.9 months. Survival rate and major amputation free rate at 1-year were 87% and 95%, respectively (Figure). Multivariate analysis elucidated that low BMI and cerebrovascular disease were independent predictors for all-cause mortality (Table 1). Interestingly, infection was the leading cause of death (23 patients (46%), and main focus of infection was lower extremities (15 patients (30%)). As for major limb amputation, current smoking was the only independent predictor (Table 2). Conclusion: This study demonstrates that low BMI and cerebrovascular disease predict all-cause mortality, and current smoking does major amputation after EVT in patients with CLI.

BACKGROUND Hemodialysis (HD) patients are reported to show poor clinical outcomes after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) compared with non-HD patients and their long-term prognosis remains unclear. METHODS AND RESULTS We prospectively enrolled 489 consecutive patients undergoing PCI with SES and performed a retrospective analysis focusing on HD patients. Median follow-up was 7.0 years (interquartile range, 4.2-7.9) and the follow-up rate was 100%. At the 7-year follow-up, the cumulative incidences of all-cause death, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were significantly higher in HD patients than in non-HD patients (HD vs. non-HD=34.7% vs. 9.6%, 42.6% vs. 10.2% and 75.3% vs. 24.4%, respectively; log-rank P

In the Journal of Arrhythmia, we previously reported the case of a 55-year-old woman with variant angina who was implanted with a pacemaker to treat cardiopulmonary arrest due to complete atrioventricular block and pulseless electrical activity [1]. In this report, we follow the clinical outcome of the pacemaker implantation in this patient. Upon implantation, we simulated the proper and effective response of the pacemaker to prepare for the possibility that the patient might encounter coronary ischemia-induced bradycardia. A high output setting was selected in order to prevent pacing failure and a rate drop response (RDR) setting was selected both to ensure efficient pacing in the case of an angina attack and to conserve battery power during periods when there was no angina. Three years have passed since the pacemaker was implanted. During this time, the patient appears to have been in remission of vasospastic activity and the patient is doing well without symptomatic angina. We also evaluated the pacemaker data and found that an episode of paroxysmal atrioventricular block occurred asymptomatically and that the RDR response was functioning appropriately (Fig. 1). Finally, the ventricular pacing rate was 0.4% and the average battery longevity was 11.5 years (range, 9.5–13 years), which was longer than that of the ordinary setting. Fig. 1 The pacemaker electrocardiogram; a rate drop response (RDR) was activated after an episode of paroxysmal atrioventricular block.

Background: The benefit of fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) in patients with coronary artery disease compared with angio-guided PCI has shown recently. However, the argument for mismatch (angiographic diameter stenosis ≧ 50% and FFR > 0.80) or reverse-mismatch (angiographic diameter stenosis < 50%, FFR ≦ 0.80), so called, “visual-functional mismatch”, is remains to be solved in contemporary practice. In the present study, we examined the association of the lesion characteristics and “visual-functional mismatch”. Method and Results: We analyzed 140 consecutive patients (157 lesions) undergoing coronary angiography and FFR examination. The mean age of study population was 68.7 years old, 54.3% of them had diabetes, 87.9% of them had hypertension and 77.1% of them had dyslipidemia. In terms of lesion characteristics, ratio of LAD lesion was 58.6%, tandem or diffuse lesion was 48.4%, mean percentage of diameter stenosis was 68.2% and lesion length was 16.3mm. The study population was divided into 4 groups by angiographic stenosis (cut-off: 50%) and FFR (cut-off: 0.80). There were no differences in patients’ background among 4 groups. Mismatches were observed in 28.7% of lesions, whereas, reverse-mismatches were observed in 10.1% of lesions. Lesion characteristics causing “visual-functional mismatch” are shown in Table 1 and ROC curve s of diameter stenosis for functional significance are shown in Figure 1. Conclusion: Specific lesion characteristics are applicable for predicting “visual-functional mismatch”. Angiographic severity seemed to be more reliable in LAD lesions, tandem/diffuse lesions or proximal lesions. FFR measurement should be considered for angiographic 50% stenosis in LAD to perform appropriate PCI, whereas, FFR measurement should be considered for angiographic 75% stenosis in non-LAD to avoid unnecessary PCI.