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BACKGROUND Acute myocardial infarction (AMI) patients with low body mass index (BMI) exhibit worse clinical outcomes than obese patients; however, to our knowledge, no prospective, nationwide study has assessed the effect of BMI on the clinical outcomes of AMI patients.Methods and Results:In this multi-center, prospective, nationwide Japanese trial, 2,373 AMI patients who underwent emergent percutaneous coronary intervention within 12 h of onset from the Japanese AMI Registry (JAMIR) were identified. Patients were divided into the following 4 groups based on their BMI at admission: Q1 group (BMI

Background Landiolol enables us to treat the patients with rapid atrial fibrillation (AF) with acute decompensated heart failure (ADHF) efficiently. We sought to determine the role of echocardiography in predicting the prognosis. Methods Among 314 patients, a total 115 ADHF patients with reduced ejection fraction and rapid AF were enrolled. They received landiolol treatment to decrease the heart rate (HR) to 20% within 24 h. The dose of landiolol was increased every 2 h; then, we performed echocardiography repeatedly, at baseline, 2 h, and 24h. We followed the patients after discharge for 180 days, and checked cardiac death and HF hospitalization as major adverse cardiac events (MACE). Results During initial hospitalization, 5 patients (4%) died. During 180 days after discharge, 19 (16%) out of 115 patients experienced MACE (2 cardiac death, 17 HF rehospitalization, 5 in-hospital death). Multivariate analysis showed that the change in left ventricular outflow tract-velocity time integral (LVOT-VTI) at 2 h was the most significant predictor for MACE (hazard ratio =1.21, 95% confidence interval: 1.10-1.83, p=0.0001). Kaplan-Meier curves demonstrated the patients with deteriorated LVOT-VTI at minimum dose landiolol suggested the high-risk patients for MACE (χ2=30.9, p Conclusions During landiolol treatment, the patients with deteriorated LVOT-VTI predicted the poor prognosis. We may detect the high-risk patients by two-point echocardiography. UMIN000020084. Registered 1 November 2013 – prospective study https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000023203

Whether free fatty acids (FFAs), which are generators of reactive oxygen species and substrates of cytotoxic lipid peroxidation products in proximal tubules of the kidney, can be a predictor of worsening renal function (WRF) is not fully elucidated. A total of 110 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h after symptom onset were included. The exclusion criteria were out-of-hospital cardiac arrest, vasospastic angina, hemodialysis, and/or lack of data. FFAs and serum cystatin C were measured on admission, and urinary liver-type fatty acid-binding protein (L-FABP) was measured 3 h after admission. WRF, defined as an increase in serum creatinine by ≥ 0.3 mg/dL for 2-year follow-up, was observed in 16 patients (15%). A multivariate logistic regression analysis (a stepwise algorithm) revealed that the FFA level was an independent predictor of WRF (P = 0.024). The FFA level was associated with WRF adjusted after serum cystatin C (odds ratio [OR]: 1.378 per 1 mEq/L, P = 0.017), L-FABP (OR: 1.370 per 1 mEq/L, P = 0.016), or the Mehran contrast-induced nephropathy (CIN) risk score (OR: 1.362 per 1 mEq/L, P = 0.021). The FFA level was inversely associated with the change in estimated glomerular filtration rate level for 2 years (R2 = 0.051, P = 0.018). The FFA level on admission was associated with the mid-term WRF in patients with STEMI.

Both low appendicular skeletal muscle index (ASMI) and specific abdominal fat composition [i.e., increased visceral to subcutaneous (V/S) fat ratio] have been associated with cardiovascular events. However, the combined impact of these 2 components on long-term outcomes remains unclear, especially in patients with ST-segment elevation myocardial infarction (STEMI).In 303 patients with STEMI, ASMI and V/S fat ratio were assessed using dual-energy X-ray absorptiometry and abdominal computed tomography. Based on the criteria of the Asian Working Group for Sarcopenia and median of V/S fat ratio, sarcopenic obesity (SO) pattern was defined as low ASMI with high V/S fat ratio. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for heart failure and unplanned revascularization.During a median follow-up of 3.9 years, primary endpoint occurred in 67 patients. Patients with an SO pattern showed significantly lower event-free survival rate compared with those without (p=0.006 by log-rank). Notably, when stratified by median age (67 years), this trend was particularly prominent in the younger-age group (p0.001), but not significant in the older-age group (p=0.38). In the younger-age group, the multivariate analysis revealed that patients with SO pattern had a 2.97 (1.10-7.53) fold higher risk for primary endpoints compared with those without.Low ASMI with high V/S fat ratio, or so-called sarcopenic obesity, was associated with poor prognosis after STEMI, particularly in younger-age patients. The combined assessment of skeletal muscle with abdominal fat distribution may help stratify the risk among patients with STEMI, rather than each component alone.

Background Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI.Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96-129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >-11.0 was an independent predictor for MACE (log-rank χ2=132.2, P -18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. Conclusions Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.

The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n = 229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67 years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528 days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ≧ 13.7% had more deaths or MACCEs with marginal significance (p = 0.0799). Patients with MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0283). Patients with RDW ≧ 13.7% and MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.

Background: The significance of late diastolic velocity (a′) obtained by tissue Doppler imaging (TDI), which reveals atrial function, in ST-elevation myocardial infarction (STEMI) remains unclear. This study evaluated the association of TDI parameters determined either immediately or 2 weeks after percutaneous coronary intervention (PCI) with long-term outcomes. Methods and Results: In all, 740 patients with first-time STEMI underwent immediate PCI (i.e., within 12 h of onset). Echocardiography was performed in 307 patients 2 weeks after onset (Group A; mean age 64 years, 249 males), in 277 patients immediately after PCI (Group B; mean age 65 years, 229 males), and in 156 patients twice (i.e., immediately and 2 weeks after PCI; Group C; mean age 65 years, 135 males). Patients were followed-up for up to 10 years (mean 81 months). The primary endpoints were cardiac death or heart failure hospitalization. Major adverse cardiovascular events (MACE) occurred in 143 patients (19%) during the follow-up period. Both univariate and multivariate Cox hazard analyses were used to determine predictors of MACE. At 24 h and 2 weeks after STEMI onset, a′ and E/e′ were the strongest predictors of MACE, respectively. Conclusions: TDI parameters have different implications depending on the timing of echocardiography after a first-time STEMI. Based on the results of this study, atrial dysfunction measured by TDI 24 h after STEMI onset may indicate a poor prognosis.

Background Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF. Methods This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid‐range LVEF (40–50%), and reduced (

Aims Acute myocardial infarction complicated by cardiogenic shock (AMICS) is associated with substantial mortality, although there are limited data available on bleeding in this critical condition. This study sought to investigate the incidence and impact of major in-hospital bleeding on all-cause mortality in patients with AMICS who undergo percutaneous coronary intervention (PCI). Methods and results Between 2015 and 2017, a total of 3411 patients hospitalized within 24 h after symptom onset were prospectively enrolled in the Japan Acute Myocardial Infarction Registry (JAMIR) and followed up for a median of 293 (interquartile range, 22–375) days. AMICS developed in 335 (9.8%) patients (mean age, 71.3 ± 13.6 years). Overall, the rate of major in-hospital bleeding (Bleeding Academic Research Consortium types 3 and 5) and in-hospital mortality was 14.6% and 28.7%, respectively. The majority of major in-hospital bleeding (73.5%) occurred within 48 h after PCI. Compared to patients without major in-hospital bleeding, those with it had higher rates of renal failure, left main coronary artery culprit lesion, and intra-aortic balloon pump or extracorporeal membrane oxygenation support, and had longer door-to-device time. The cumulative incidence of 1-year all-cause mortality was significantly higher in the major bleeding group compared to the non-major bleeding group (63.8% vs. 25.5%; log-rank P Conclusions These findings of JAMIR indicate that major in-hospital bleeding is associated with all-cause mortality in patients with AMICS who undergo PCI.

This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

Aim: The importance of sarcopenia in cardiovascular diseases has been recently demonstrated. This study aims to examine whether skeletal muscle mass (SMM), an important component of sarcopenia, is associated with an increased risk of poor outcome in patients after ST-segment elevation myocardial infarction (STEMI). Methods: We measured SMM in 387 patients with STEMI using dual-energy X-ray absorptiometry. Patients were divided into low- and high-appendicular skeletal mass index (ASMI: appendicular SMM divided by height squared (kg/m2)) groups using the first quartile of ASMI (≤ 6.64 kg/m2 for men and ≤ 5.06 kg/m2 for women). All patients were followed up for the primary composite outcome of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for congestive heart failure, and unplanned revascularization. Results: Low-ASMI group was older and had a more complex coronary lesion, a lower left ventricular ejection fraction, and a higher prevalence of Killip classification ≥ 2 than high-ASMI group. During a median follow-up of 33 months, the event rate was significantly higher in low-ASMI group than in high-ASMI group (24.7% vs 13.4%, log-rank p = 0.001). Even after adjustment for patients' background, low ASMI was independently associated with the high risk of primary composite events (adjusted hazard ratio 2.06, 95% confidence interval 1.01–4.19, p = 0.04). In the subgroup analyses of male patients (n = 315), the optimal cutoff point of ASMI for predicting primary composite outcome was 6.75 kg/m2, which was close to its first quartile value. Conclusions: Low ASMI is independently associated with poor outcome in patients with STEMI.

Background The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for cancer-associated venous thromboembolism (VTE) in routine clinical practice remain unclear. Moreover, data on long-term outcomes in patients with cancer-associated VTE who received DOAC therapy are limited.Methods and Results:This retrospective study enrolled 1,096 consecutive patients with acute VTE who received warfarin or DOAC therapy between April 2014 and May 2017. The mean follow-up period was 665±490 days. The number of cancer-associated VTE patients who received DOAC therapy was 334. Patients who could not be followed up and those prescribed off-label under-dose DOAC were excluded. Finally, 303 patients with cancer-associated VTE were evaluated. The number of cases of major bleeding and VTE recurrence was 54 (17.8%) and 26 (8.6%), respectively. In the multivariate analysis, the factors correlated with major bleeding were high cancer stage, high performance status, liver dysfunction, diabetes mellitus, and stomach cancer; those correlated with recurrent VTE were initial diagnosis of pulmonary embolism, uterine cancer, and previous cerebral infarction. Major bleeding was an independent risk factor of all-cause death. In the Kaplan-Meier analysis, those who received prolonged DOAC therapy had lower composite major bleeding and recurrent VTE risks than those who did not. Conclusions In DOAC therapy for cancer-associated VTE, major bleeding prevention is important because it is an independent risk factor of death.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92 ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG

Aim: The purpose of this study is to investigate the impact of arterial stiffness assessed using Cardio-ankle Vascular Index (CAVI) on long-term outcome after acute coronary syndrome (ACS). Methods: A total of 387 consecutive patients (324 males; age, 64 ± 11 years) with ACS were enrolled. We examined CAVI and brachial-ankle pulse wave velocity (ba PWV) as the parameters of arterial stiffness. The patients were divided into two groups according to the cut-off value of CAVI determined using the receiver operating characteristic curve for the prediction of major adverse cardiovascular events (MACE): low-CAVI group, 177 patients with CAVI < 8.35; high-CAVI group, 210 patients with CAVI ≥ 8.35. The primary endpoint was the incidence of MACE (cardiovascular death, recurrence of ACS, heart failure requiring hospitalization, or stroke). Results: A total of 62 patients had MACE. Kaplan-Meier analysis demonstrated a significantly higher probability of MACE in the high-CAVI group than in the low-CAVI group (median follow-up: 62 months; log-rank, p < 0.001). Multivariate analysis suggested that CAVI was an independent predictor of MACE (hazard ratio [HR], 1.496; p = 0.02) and cardiovascular death (HR, 2.204; p = 0.025), but ba PWV was not. We investigated the incremental predictive value of adding CAVI to the GRACE score (GRS), a validated scoring system for risk assessment in ACS. Stratified by CAVI and GRS, a significantly higher rate of MACE was seen in patients with both higher CAVI and higher GRS than the other groups (p < 0.001). Furthermore, the addition of CAVI to GRS enhanced net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.337, p = 0.034; and IDI, 0.028, p = 0.004). Conclusion: CAVI was an independent long-term predictor of MACE, especially cardiovascular death, adding incremental clinical significance for risk stratification in patients with ACS.

Background Lipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS). Methods The Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available. Results The patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (−6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test). Conclusions Lp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients.

BACKGROUND Low population density may be associated with high mortality in acute myocardial infarction (AMI) patients. The purpose of this study was to investigate the effect of population density and hospital primary percutaneous coronary intervention (PCI) volume on AMI in-hospital mortality in Japan.Methods and Results:This is a retrospective study of 64,414 AMI patients transported to hospital by ambulances. The main outcome measure was in-hospital mortality. The median population density was 1,147 (interquartile range, 342-5,210) persons/km2. There was a significant negative relationship between population density and in-hospital mortality (OR for a quartile down in population density 1.086, 95% CI 1.042-1.132, P

The extracellular volume fraction (ECV) by T1 mapping can quantify diffuse myocardial fibrosis, and useful as a non-invasive marker for risk stratification for patients with non-ischemic dilated cardiomyopathy (NIDCM). Prolonged QRS interval on electrocardiogram is related to worse clinical outcome for heart failure patients. The purpose of this study was to evaluate the prognostic value of the combination of ECV and QRS duration for NIDCM patients. A total of 60 NIDCM patients (mean age 61 ± 12 years, mean left ventricular ejection fraction 37 ± 10%, mean QRS duration 110 ± 19 ms) were enrolled. Using a 1.5-T MR scanner and 32-channel cardiac coils, the mean ECV value of six myocardial segments at the mid-ventricular level was measured by the modified look-locker inversion recovery method. Adverse events were defined as follows: cardiac death; recurrent hospitalization due to heart failure. Patients were allocated into three groups based on ECV value and QRS duration (group 1: ECV ≦ 0.30 and QRS ≦ 120 ms; group 2: ECV > 0.30 or QRS > 120 ms; group 3: ECV > 0.30 and QRS > 120 ms). During a median follow-up duration of 370 days, 7 of 60 (12%) NIDCM patients experienced adverse events. NIDCM patients with events had longer QRS duration (134 ± 31 ms vs. 106 ± 14 ms, p = 0.01) and higher ECV (0.34 ± 0.07 vs 0.29 ± 0.05, p = 0.026) compared with those without events. On Kaplan–Meier curve analysis, significant difference was found between group 1 and group 3 (p

Introduction Chronic inflammation has been receiving considerable attention as an emerging risk factor for cardiovascular disease. In contrast, with the aging of the population, frailty has been also attracting a great deal of attention as the residual risk for cardiovascular disease. Although inflammation and frailty exacerbate each other and have an adverse effect on many diseases, the relationship between chronic inflammation and frailty and the impact of these combination on long-term prognosis in patients with acute coronary syndrome (ACS) are not elucidated. Purpose The aims of this study were to determine the association between chronic inflammation and frailty and its impact on long-term cardiovascular outcomes in patients with ACS. Methods A total of 482 consecutive ACS patients with obstructive coronary artery disease (age 66±12 years, male 81%) were enrolled in this observational study. We evaluated patients' gait speed as a measure of frailty before discharge. C-reactive protein (CRP) levels at 1 month after discharge were also evaluated as inflammation in the chronic phase. According to commonly used criteria of the residual inflammation (CRP>0.2 mg/dL) and the definition of the European Working Group for Sarcopenia (gait speed ≤0.8 m/sec), patients were stratified by 4 subgroups: low/high CRP with slow/normal gait speed. The primary endpoint was composite outcomes of cardiovascular death, myocardial infarction and ischemic stroke. Results While there was no significant association between CRP levels and gait speed in all patients, a significant negative association between two variables was observed in the high CRP group (Spearman's ρ = −0.31, p=0.001). During the median follow-up of 6 years, primary endpoints have occurred in 82 patients. Overall, event-free rates differed significantly among the 4 groups, demonstrating the lowest event-free rate in the patients with high CRP and slow gait speed (p Conclusion In the patients with ACS, CRP levels and gait speed were negatively associated in the high CRP group. Chronic inflammation and frailty were both associated with poor prognosis in ACS and in particular, the combination of these factors was strongly associated with poor prognosis. Funding Acknowledgement Type of funding sources: None. Figure 1

Background: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for isolated distal deep vein thrombosis (IDDVT) associated with cancer in routine clinical practice remain unclear. Moreover, prior studies on prolonged therapy for IDDVT are limited. Methods: This retrospective study enrolled 1641 consecutive patients with acute venous thromboembolism (VTE) who had received oral anticoagulant therapy, including warfarin or DOAC, between April 2014 and September 2018 in our institutions. In these patients, 200 patients with cancer-associated IDDVT were evaluated. Results: Mean follow-up period was 780 ± 593 days. Major bleeding and VTE recurrence were observed in 22 (11.0%) and 11 (5.5%) patients, respectively. In multivariate analysis, statistically significant factors correlated with major bleeding were advanced cancer stage, high performance status, stomach cancer, and gallbladder cancer; those correlated with all-cause death were advanced cancer stage, high performance status, liver dysfunction, pancreatic cancer, and major bleeding. Cumulative events of major bleeding and recurrence between patients with prolonged DOAC therapy (≥90 days) and those with nonprolonged therapy were not significantly different. Conclusions: Preventing major bleeding is important because it is a significant risk factor for all-cause death. Major bleeding and recurrent events were comparable between prolonged and nonprolonged therapy.

Background: We investigated the clinical usefulness of landiolol for rapid atrial fibrillation (AF) in patients with acute decompensated heart failure (ADHF) and identify the patients eligible for landiolol. Methods and Results: A total of 101 ADHF patients with reduced ejection fraction (HFrEF) with rapid AF were enrolled. Immediately after admission, an initial dose of landiolol was given (1 μg/kg−1/min−1), and then the dose was increased to decrease heart rate (HR) to 20% in ≤24 h. Thirty-seven were monitored using right heart catheterization at 3 points (baseline, 1 μg/kg−1/min−1, and maximum dose). We checked the major adverse events (MAE) during initial hospitalization, which included cardiac death, HF prolongation (required i.v. treatment at 30 days), and worsening renal function. The average maximum dose of landiolol was 3.8±2.3 μg/kg−1/min−1. HR (P97 mmHg had less frequent MAE (P

Objectives Doppler echocardiography is a well-recognized technique for noninvasive evaluation; however, little is known about its efficacy in patients with rapid atrial fibrillation (AF) accompanied by acute decompensated heart failure (ADHF). The aim of this study was to explore the usefulness of serial echocardiographical assessment for rapid AF patients with ADHF. Patients A total of 110 ADHF patients with reduced ejection fraction (HFrEF) and rapid AF who were admitted to the CCU unit and received landiolol treatmentto decrease the heart rate (HR) to 20% within 24 hours were enrolled. Interventions Immediately after admission, the patients (n=110) received landiolol, and its dose was increased to the maximum; then, we repeatedly performed echocardiography. Among them, 39 patients were monitored using invasive right heart catheterization (RHC) simultaneously with echocardiography. Measurements and main results There were significant relationships between Doppler and RHC parameters through the landiolol treatment (Figure, baseline–max HR treatment). We observed for the major adverse events (MAE) during initial hospitalization, which included cardiac death, HF prolongation (required intravenous treatment at 30 days), and worsening renal function (WRF). MAE occurred in 44 patients, and logistic regression analyses showed that the mean left atrial pressure (mLAP)-Doppler (odds ratio = 1.132, 95% confidence interval [CI]: 1.05–1.23, p=0.0004) and stroke volume (SV)-Doppler (odds ratio = 0.93, 95% confidence interval [CI]: 0.89–0.97, p=0.001) at 24 hours were the significant predictors for MAE, and multivariate analysis showed that mLAP-Doppler was the strongest predictor (odds ratio = 1.16, 95% CI: 0.107–1.27, p=0.0005) (Table). Conclusions During the control of the rapid AF in HFrEF patients withADHF, echocardiography was useful to assess their hemodynamic condition, even at bedside. Doppler for rapid AF of ADHF Funding Acknowledgement Type of funding source: None

Background Although the prognostic value of non-invasive endothelial function test has been reported in several populations including heart failure patients and angina pectoris patients, it is unknown in patients with acute coronary syndrome (ACS). Furthermore, the role of endothelial dysfunction in increased risk for specific causes of death has not been investigated. Purpose To study the relation between endothelial dysfunction and the risk of death in ACS patients, both overall and with regard to the main causes of death. Method Six hundred and ninety-two patients who were hospitalized for ACS from 2010 to 2014 were enrolled. Reactive hyoeremia index (RHI) was measured to assess endothelial function non-invasively in all patients using the peripheral arterial tonometry. RHI values below 1.67 were interpreted as signs of endothelial dysfunction in accordance with the manufacturer. Patients were followed up for a median of 6.5 years. Result A mean age (standard deviation) was 66 (12) years, and 542 patients (78%) were male. The patients in this study consist of 377 ST-elevation myocardial infarction (54%), and 263 non ST-elevation myocardial infarction (38%), and 52 unstable angina (8%). Endothelial dysfunction was detected in 276 patients (40%). During the follow-up period, 84 patients (12%) died (48 from cardiovascular disease, 36 from other causes). Patients with endothelial dysfunction had an increased risk of death (hazard ratio (HR) 1.83, 95% confidence interval (95% CI): 1.19–2.83, p=0.006) compared with those without endothelial dysfunction. Analyses for specific causes of death showed that patients with endothelial dysfunction had a 2.4-fold higher increased risk of cardiovascular death (HR: 2.44, 95% CI: 1.35 ro 4.59, p=0.003) after multivariate adjustment. However there was no significant relation between endothelial dysfunction and non-cardiovascular mortality (HR: 0.69, 95% CI: 0.34 to 1.36, p=0.29). Conclusion Endothelial dysfunction is strongly associated with an increased risk of cardiovascular mortality in ACS patients. Figure 1 Funding Acknowledgement Type of funding source: None

Background The early transmitral flow velocity (E) divided by the early diastolic velocity of the mitral valve annulus (e') is referred to as the “E/e' ratio,” is useful even for ST elevation acute myocardial infarction (STEMI). However, the role of late diastolic velocity (a') which reveals the atrial function for STEMI is still unclear. Objectives We evaluated the clinical usefulness of tissue Doppler including atrial function for a first-time STEMI by long time follow up. Furthermore, we evaluated the meaning of each parameters by performing immediately after PCI or 2 weeks later. Methods We treated consecutive 571 first-time STEMI patients by immediate PCI within 12 hours after onset, and we examined 270 patients at immediately after PCI (GroupA, 65 years, 250 male) and 301 patients at 2 weeks after onset (GroupB, 64 years, 243 male). We examined trans mitral flow and TDI, then defined E/e' as LV filling pressure and A/a' as left atrial function. We followed them for a long time (>5 years). The primary end point (PE) was cardiac death or re-admission for heart failure (HF). Results We followed the patients in Group A for 10 years, Group B for 5 years. PE occurred in 64 patients in GroupA during 10 years, and 45 patients in GroupB during 5 years. We analyzed the univariate and multivariate Cox hazard analyses and we compared e' and a', E/e' and A/a' (Table). In GroupA, a' and A/a' were the independent predictors, on the other hand neither a' nor A/a' were the predictors in GroupB. E/e' was an independent predictor both in GroupA and B. Conclusion TDI parameters have different meanings by the timing of echocardiography after onset of a first-time STEMI. These results demonstrated that atrial dysfunction immediately after onset of STEMI suggests the poor prognosis after STEMI. Cox Hazard Proportional Analysis Funding Acknowledgement Type of funding source: None

Introduction Dyslipidemia, especially an increase in the low-density lipoprotein cholesterol (LDL-C) has been established as one of the most important risk factors for atherosclerotic cardiovascular diseases. In contrast, some recent studies have shown that the low LDL-C level was associated with short-term poor prognosis in patients with cardiovascular disease, and this is so-called “cholesterol paradox”. However, there is few data evaluating the effects on long-term outcome of “cholesterol paradox” in patients with acute coronary syndrome (ACS). Purpose The purpose of this study was to examine whether the low LDL-C level on admission affect long-term prognosis in patients with ACS. Methods A total of 434 ACS patients who survived to hospital discharge were enrolled in this study. All patients were statin-naïve on admission, and were received statin therapy after hospitalization. Patients were divided into the low LDL-C (≤114 mg/dl) and high LDL-C (>114 mg/dl) groups using the first tertile of the LDL-C level on admission. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for congestive heart failure and unplanned revascularization. Results During a median follow-up period of 5.5 years, primary endpoint occurred in 117 patients. Overall, event-free rates differed significantly between the low and high LDL-C groups, demonstrating the lower event-free rate in patients with the low LDL-C group (38.9% in low LDL-C group versus 20.7% in high LDL-C group, p=0.0002; Figure). Even after adjustment for age, sex, body mass index, and various classical risk factors, the low LDL-C group was significantly at higher risk for primary composite outcomes compared to the high LDL-C group (adjusted hazard ratio 1.65, 95%-confidence interval 1.10–2.49, p=0.02). Conclusion In patients with ACS, the low LDL-C level on admission was significantly associated with long-term worse prognosis, regardless of statin therapy at discharge. In ACS patients with low LDL-C level, it might be necessary for elucidating the residual risk for secondary adverse event to improve their prognosis. Funding Acknowledgement Type of funding source: None

Background Shortening of onset to admission time (OAT) and door-to-balloon time (DBT) is associated with lower adverse cardiac event after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Bleeding event also results in poor outcome in patients with AMI after primary PCI. Little is known about sex differences in DBT and ischemic, bleeding events after AMI. Purpose This study aimed to assess the sex differences of OAT, DTB and adverse cardiac event, incident of bleeding event after primary PCI in patients with AMI. Methods The Japan AMI Registry (JAMIR) is a multicenter, nationwide, prospective registry enrolling patients with AMI from 50 institutes between December 2015 and May 2017. Primary endpoints of this study were ischemic event (composite of cardiovascular death, myocardial infarction and ischemic stroke) and bleeding event (BARC type 3 or 5,).Median follow-up period was 12 months. Results A total of 3,411 patients were enrolled at first. Among them, 329 patients without treated with PCI and 199 patients missing OAT time were excluded from this study. A total 2883 patients of men (n=2240, 77.7%) and women (n=643, 22.3%) were enrolled. OAT and DBT of women were significantly longer than that of men (OAT: 130min, interquartile range 62–300 min vs. 155 min, interquartile range 69–350 min, p=0.040, DBT: 67 min, interquartile range 50–95 min vs. 75 min, interquartile range 53–120 min, p Conclusion The real-world database of the JAMIR showed that the female sex was significant factor for the delay in primary percutaneous coronary intervention and high incident of bleeding, however, ischemic event was lower than that of male sex. Sex difference appears to be associated with ischemic and bleeding event after acute myocardial infarction. Funding Acknowledgement Type of funding source: None

Background De-escalation of P2Y12 inhibitor may occur for various clinical reasons in patients with acute myocardial infarction (AMI). We aimed to assess the characteristics and outcomes of patients who underwent a de-escalation strategy in real-world clinical practice. Methods and Results We studied 2604 AMI patients initially treated with prasugrel using the Japan Acute Myocardial Infarction Registry (JAMIR) database. Of these, 110 (4%) were discharged on clopidogrel [de-escalation group; switching 4 days after admission (median)] and the remaining 2494 continued prasugrel at discharge (continuation group). The de-escalation group had higher incidence of heart failure or history of cerebrovascular disease, and were more likely to receive mechanical circulatory support, and oral anticoagulation than the continuation group. During mean follow-up of 309±133 days post-discharge, no significant differences were observed in ischemic events (2.2% vs. 2.8%, p = 0.74) or major bleeding (1.1% vs. 1.6%, p = 0.72) between the de-escalation and continuation groups. Conclusions Although, patients with de-escalation from prasugrel to clopidogrel had higher bleeding risk profile than those continued on prasugrel, post discharge ischemic and bleeding events were similar between patients with and without de-escalation. De-escalation strategy may be an option for AMI patients with high risk for bleeding.

The early mitral inflow velocity to mitral early diastolic velocity ratio (E/e') and electrocardiogram (ECG) determination of QRS score are useful for risk stratification in patients with ST-elevation myocardial infarction (STEMI).Methods and Results:In this study, 420 consecutive patients (357 male; mean [±SD] age 63.6±12.2 years) with first-time STEMI who successfully underwent primary percutaneous coronary intervention within 12 h of symptom onset were followed-up for 5 years (median follow-up 67 months). Echocardiography, ECG, and blood samples were obtained 2 weeks after onset. Infarct size was estimated by the QRS score after 2 weeks (QRS-2wks) and creatine phosphokinase-MB concentrations (peak and area under the curve). The primary endpoint was death from cardiac causes or rehospitalization for heart failure (HF). During follow-up, 21 patients died of cardiac causes and 62 had HF. Multivariate Cox proportional hazard analysis showed that mean E/e' (hazard ratio [HR] 1.152; 95% confidence interval [CI] 1.088-1.215; P0.0001), QRS-2wks (HR 1.153; 95% CI 1.057-1.254; P0.0001), and hypertension (HR 1.702; 95% CI 1.040-2.888; P=0.03) were independent predictors of the primary endpoint. Kaplan-Meier curve analysis showed that patients with QRS-2wks4 and mean E/e'14 were at an extremely high risk of cardiac death or HF (log rank, χIn patients with STEMI, a combination of QRS-2wks and mean E/e' was a simple but useful predictor of cardiac death and HF.

Background Myocardial bridge (MB), common anatomic variant, is generally considered benign, while previous studies have shown associations between MB and various cardiovascular pathologies. This study aimed to investigate for the first time possible impact of MB on long‐term outcomes in patients with implantable cardioverter defibrillator, focusing on life‐threatening ventricular arrhythmia (LTVA). Methods and Results This retrospective analysis included 140 patients with implantable cardioverter defibrillator implantation for primary (n=23) or secondary (n=117) prevention of sudden cardiac death. Angiographically apparent MB was identified on coronary angiography as systolic milking appearance with significant arterial compression. The primary end point was the first episode(s) of LTVA defined as appropriate implantable cardioverter defibrillator treatments (antitachyarrhythmia pacing and/or shock) or sudden cardiac death, assessed for a median of 4.5 (2.2–7.1) years. During the follow‐up period, LTVA occurred in 37.9% of patients. Angiographically apparent MB was present in 22.1% of patients; this group showed younger age, lower rates of coronary risk factors and ischemic cardiomyopathy, higher prevalence of vasospastic angina and greater left ventricular ejection fraction compared with those without. Despite its lower risk profiles above, Kaplan–Meier analysis revealed significantly lower event‐free rates in patients with versus without angiographically apparent MB. In multivariate analysis, presence of angiographically apparent MB was independently associated with LTVA (hazard ratio, 4.24; 95% CI, 2.39–7.55; P Conclusions Angiographically apparent MB was the independent determinant of LTVA in patients with implantable cardioverter defibrillator. Although further studies will need to confirm our findings, assessment of MB appears to enhance identification of high‐risk patients who may benefit from closer follow‐up and targeted therapies.

Aims In patients with ST-segment elevation myocardial infarction (STEMI), predicting left ventricular (LV) remodelling (LVR) and prognosis is important. We explored the clinical usefulness of three-dimensional (3D) speckle-tracking echocardiography to predict LVR and prognosis in STEMI. Methods and results The study group comprised 255 first STEMI patients (65 years; 210 men) treated with primary percutaneous coronary intervention between April 2008 and May 2012 at Yokohama City University Medical Center. Baseline global longitudinal strain (GLS) was measured with two-dimensional (2D) and 3D speckle-tracking echocardiography. Within 48 of admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-GLS and 3D-GLS were calculated. Infarct size was estimated by 99mTc-sestamibi single-photon emission computed tomography. Echocardiography was performed at 1 year repeatedly in 239 patients. The primary endpoint was LVR, defined as an increase of 20% of LV end-diastolic volume index and major adverse cardiac and cerebrovascular events (MACE: cardiac death, non-fatal MI, heart failure, and ischaemic stroke) at 1 year, and the secondary endpoint was cardiac death and heart failure. Patients were followed for 1 year; 64, 25, and 16 patients experienced LVR, MACE, and the secondary endpoint, respectively. Multivariate analysis revealed that 3D-GLS was the strongest predictor of LVR (odds ratio = 1.437, 95% CI: 1.047–2.257, P = 0.02), MACE (odds ratio = 1.443, 95% CI: 1.240–1.743, P = 0.0002), and the secondary end point (odds ratio = 1.596, 95% CI: 1.17–1.56, P Conclusion 3D-GLS obtained immediately after STEMI is independently associated with LVR and 1-year prognosis.

This study aimed to simultaneously investigate diagnostic performance and limitation of quantitative flow reserve (QFR) for assessing functionally significant coronary stenosis, focusing on factors affecting diagnostic accuracy of QFR.This study evaluated 1) QFR diagnostic accuracy compared with fractional flow reserve (FFR) in patients with stable coronary artery disease (Cohort-A, n = 95) and 2) QFR reproducibility for non-culprit lesions (NCLs) assessment between acute and staged (14±5 days later) procedures in patients with ST-segment elevation myocardial infarction (STEMI) (Cohort-B, n = 65). All coronary angiography image acquisition was performed before the introduction of QFR system into our institution.Cohort-A showed good correlation (r = 0.80, p0.0001) between QFR and FFR; diagnostic accuracy of QFR for FFR ≤0.80 was 85.2% (sensitivity 80.4%, specificity 91.0%, positive predictive value 91.1%, negative predictive value 80.0%). There were 14 lesions showing discordance between QFR and FFR, which was primarily attributable to inadequate lesion visualization due to vessel overlap/tortuosity and/or insufficient intra-coronary contrast-media injection. In Cohort-B, there was also excellent correlation between acute and staged QFR; classification agreement of acute and staged QFR was 92.3%. Five lesions showed discordance between acute and staged QFR, 4 were due to limited image acquisition and/or high coronary flow velocity at acute phase of STEMI and 1 was borderline ischemia.QFR-derived physiological assessment of intermediate coronary stenosis is feasible, even in the acute setting of STEMI. Adjusting some technical factors may further improve the diagnostic performance of QFR.

Background: The aim of this study was to clarify the clinical impact of activities of daily living (ADL) using the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database. Methods and Results: From April 2012 to March 2014, the JROAD-DPC database included 206,643 patients with acute coronary syndrome (ACS; n=49,784), heart failure (HF; n=136,878), or aortic aneurysm/dissection (Aorta; n=19,981). We divided them into 3 categories with regard to age (low, 20–59 years; middle, 60–79 years; high, ≥80 years) and admission ADL (low, Barthel index [BI] 0–70; middle, BI 75–95; high, BI 100). ACS, HF, and Aorta patients with low ADL had higher in-hospital mortality rates (18.3%, 16.7%, and 33.4%) than those with middle or high ADL (P

BACKGROUND Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (β=0.29, P=0.0006) and poor initial TIMI flow (β=0.37, P

Background Antiplatelet therapy is a cornerstone of treatment following acute myocardial infarction (AMI). Recently, prasugrel, a new and potent antiplatelet agent, has been introduced in clinical practice. To date, however, real-world in-hospital and follow-up data in Japanese patients with AMI remain limited. Objectives To examine ischemic and bleeding events in Japanese patients with AMI and the association between these events and antiplatelet therapy. Methods The Japan AMI Registry (JAMIR) is a multicenter, nationwide, prospective registry enrolling patients with AMI from 50 institutions. The inclusion criterion is spontaneous onset of AMI diagnosed based on either the universal definition or Monitoring Trends and Determinants in Cardiovascular disease (MONICA) criteria. The major exclusion criteria are hospital admission ≥ 24 h after onset, no return of spontaneous circulation on admission following out-of-hospital cardiopulmonary arrest, and AMI as a complication of percutaneous coronary intervention or coronary artery bypass grafting. The primary end point of the study is the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Major safety end points include major bleeding based on Thrombolysis in Myocardial Infarction (TIMI) criteria and type 3 or type 5 bleeding based on Bleeding Academic Research Consortium (BARC) criteria. Between December 2015 and May 2017, a total of 3411 patients (mean age 68.1 ± 13.2 years, 23.4% female) were enrolled in the study. Patients will be followed for 1 year. Conclusions JAMIR will provide important information regarding contemporary practice patterns in the management of Japanese patients with AMI, their demographic and clinical characteristics, in-hospital and post-discharge outcomes, and how they are related to antiplatelet therapy. Electronic supplementary material The online version of this article (10.1007/s10557-018-6839-1) contains supplementary material, which is available to authorized users.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy. ispartof: EUROPEAN HEART JOURNAL vol:39 issue:22 pages:2032-2046 ispartof: location:England status: published

Background Sleep-disordered breathing (SDB) is associated with cardiovascular complications. However, the effect of SDB on renal function in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI) remains unclear. Methods We enrolled 154 consecutive ACS patients without heart failure. A sleep study was performed immediately after PCI. Results The mean apnea-hypopnea index (AHI) was 16.4 ± 13.1, and 33 patients (21%) had severe SDB, defined as AHI ≥ 25. Estimated glomerular filtration rate (eGFR) values on admission (60 ± 12 mL/min/1.73 m2 vs. 67 ± 17 mL/min/1.73 m2, p = 0.046) and at discharge (54 ± 15 mL/min/1.73 m2 vs. 63 ± 15 mL/min/1.73 m2, p = 0.002) were lower in patients with severe SDB than in those patients without severe SDB. Multiple linear regression analysis showed that AHIs were significantly correlated with absolute changes in eGFR values from admission to discharge (β = 0.201, p = 0.004). Median 24-h urinary noradrenaline excretion measured on the same day of the sleep study was higher [297 (interquartile range {IQR}: 232–472) vs. 174 (IQR: 107–318) μg/day, p = 0.021] in patients with severe SDB. On multivariate logistic regression analysis, the presence of severe SDB was a significant predictor (adjusted odds ratio 3.76, 95% confidence interval 1.06–13.9, p = 0.047) for eGFR of less than 45 mL/min/1.73 m2 at discharge. This association was independent of age, eGFR on admission, and a presentation of ST-segment elevation myocardial infarction. Conclusion In patients with ACS who undergo PCI, severe SDB is associated with impaired renal function on admission and its deterioration during hospitalization. Further studies will be needed to conclude that SDB would be a therapeutic target in ACS.

Background: As percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) gains wider acceptance as a therapeutic option for coronary artery disease, the importance of appropriate patient selection has increased. Although cardiovascular magnetic resonance imaging (MRI) allows segmental and quantitative analyses of myocardial ischemia and scar transmurality, it has limitations, including contraindications, cost, and accessibility. This study established a non-invasive method to evaluate patients undergoing CTO-PCI using two-dimensional speckle-tracking echocardiography (2D-STE). Methods: Overall, we studied 55 patients who underwent successful CTO-PCI. Cardiovascular MRI and 2D-STE were performed before and 8 ± 2 months after CTO-PCI. Segmental findings of strain parameters were compared with those obtained with late gadolinium enhancement and stress-perfusion MRI. Results: With a cutoff of −10.7, pre-procedural circumferential strain (CS) showed reasonable sensitivity (71%) and specificity (73%) for detecting segments with transmural scar. The discriminatory ability of longitudinal strain (LS) for segments with transmural scar significantly improved during follow-up after successful CTO-PCI in the territory of the recanalized artery (area under the curve (AUC) 0.70 vs. 0.80, p &lt, 0.001). LS accuracy was lower than that of CS at baseline (AUC 0.70 vs. 0.79, p = 0.048), and was increased at follow-up (AUC 0.80 vs. 0.82, p = 0.81). Changes in myocardial perfusion reserve from baseline to follow-up were significantly associated with those in LS but not in CS. Conclusions: Use of 2D-STE may allow the non-invasive evaluation of patients undergoing CTO-PCI to assess the indication before the procedure and treatment effects at follow-up.

Objectives The differential diagnosis between precapillary and postcapillary pulmonary hypertension (PH) is important for deciding on the appropriate therapeutic strategy. The aim of this study was to assess whether the atrial volume ratio can differentiate precapillary and post-capillary PH. Methods Seventy-seven patients with PH who underwent transthoracic echocardiography (TTE) and right heart catheterization were retrospectively studied. Pulmonary hypertension was defined as a mean pulmonary arterial pressure of 25 mm Hg or higher by right heart catheterization. Patients with a pulmonary capillary wedge pressure higher than 15 mm Hg were classified as having postcapillary PH, and patients with a pulmonary capillary wedge pressure of 15 mm Hg or lower were classified as having precapillary PH. The atrial volume ratio derived from TTE was defined as right atrial volume divided by left atrial volume. Results Forty-four (57%) of 77 patients had precapillary PH by the right heart catheterization classification. The atrial volume ratio was significantly higher in precapillary PH than in postcapillary PH (1.03 ± 0.69 versus 0.50 ± 0.19; P

Background Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus is a noninvasive method to quantify coronary flow reserve (CFR). Objectives This study sought to compare the prognostic value of CFR by cardiac magnetic resonance (CMR) and stress perfusion CMR to predict major adverse cardiac events (MACE). Methods Participants included 276 patients with known coronary artery disease (CAD) and 400 with suspected CAD. CFR was calculated as myocardial blood flow during adenosine triphosphate infusion divided by myocardial blood flow at rest using PC cine MRI of the coronary sinus. Results During a median follow-up of 2.3 years, 47 patients (7%) experienced MACE. Impaired CFR ( 10% ischemia on stress perfusion CMR were significantly associated with MACE in patients with known CAD (hazard ratio [HR]: 5.17 and HR: 5.10, respectively) and suspected CAD (HR: 14.16 and HR: 6.50, respectively). The area under the curve for predicting MACE was 0.773 for CFR and 0.731 for stress perfusion CMR (p = 0.58) for patients with known CAD, and 0.885 for CFR and 0.776 for stress perfusion CMR (p = 0.059) in the group with suspected CAD. In patients with known CAD, sensitivity, specificity, and positive and negative predictive values to predict MACE were 64%, 91%, 38%, and 97%, respectively, for CFR, and 82%, 59%, 15%, and 97%, respectively, for stress perfusion CMR. In the suspected CAD group, these values were 65%, 99%, 80%, and 97%, respectively, for CFR, and 72%, 83%, 22%, and 98%, respectively, for stress perfusion CMR. Conclusions The predictive values of CFR and stress perfusion CMR for MACE were comparable in patients with known CAD. In patients with suspected CAD, CFR showed higher HRs and areas under the curve than stress perfusion CMR, suggesting that CFR assessment by PC cine MRI might provide better risk stratification for patients with suspected CAD.

Limited data are available regarding the prediction for functional recovery using late gadolinium enhanced magnetic resonance imaging (LGE MRI) after coronary revascularization for chronic total occlusion (CTO PCI).We studied 59 patients (mean age, 66±11 years) who underwent successful CTO PCI. Two-dimensional echocardiography and strain measurements were performed before and 8±2 months after CTO PCI. The findings of segmental assessment were compared with the extent of LGE MRI using a 16-segment model.From baseline to follow-up, ejection fraction (54.2±12.1% to 56.1±10.6%, p=0.010), global longitudinal strain (LS) (-15.1±5.1 to -16.7±5.1, p0.001), global circumferential strain (CS) (-14.0±4.9 to -15.9±4.9, p0.001), and wall motion score (WMS) index (1.45±0.53 to 1.33±0.39, p=0.014) significantly improved. In the territory of the CTO vessel, LS and CS significantly improved in segments of LGE ≤50%, but not in segments of LGE50%. However, WMS improved only in segments of LGE 1-25%. At baseline and at follow-up, CS allowed better discrimination of segments of LGE50% than WMS [at baseline; area under the curve (AUC) 0.79 vs. 0.68, respectively, p=0.001: at follow-up; AUC 0.84 vs. 0.69, respectively, p0.001). Discriminatory ability of LS for segments of LGE50% significantly improved from baseline to follow-up (AUC 0.73 vs. 0.83, p0.001).The cut-off value of the extent of LGE MRI is 50% to detect segments that will functionally recover after CTO PCI. Change in LS was more sensitive for removal of ischemia by CTO PCI, indicating the utility of LS to monitor the therapeutic effects of CTO recanalization.

Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400 mg/day or placebo for 3 months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39–1.80], post-RHI 1.74 [IQR 1.63–2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53–1.85], post-RHI 1.51 [IQR 1.39–2.11], p = 0.198). Ubiquinol 400 mg/day for 3 months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

Introduction Sarcopenia, characterized by the loss of skeletal muscle mass and muscle strength, has been demonstrated the importance in cardiovascular diseases including ST-segment elevation myocardial infarction (STEMI). However, there is few data comparing the effects on the prognosis of skeletal muscle mass of upper and lower extremities in STEMI patients. Purpose Our purpose was to examine whether skeletal muscle mass of upper and lower extremities affect the prognosis after STEMI. Methods A total of 432 patients with STEMI were enrolled in this study. Dual-energy X-ray absorptiometry scan was performed before discharge. Each of upper and lower extremity skeletal muscle masses was indexed by height squared (kg/m2), and divided into two groups using the first quartile value for each sex. All patients were followed up for the primary composite outcome of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for congestive heart failure, and unplanned revascularization. Results During a median follow-up of 32 months, 68 patients experienced primary composite outcome. The event rate was significantly higher in patients with low-lower extremity skeletal muscle mass index (LESMI) than in those with high-LESMI (24.3% vs 12.9%, log-rank p Conclusions Decreased muscle mass of lower extremity, rather than upper extremity, might have prognostic impact in patients with STEMI.

Background Low muscle mass with or without fat mass is a main component of cachexia in heart failure (HF) and associated with poor prognosis. There is a paucity of data, however, regarding prognostic impact of each component of body composition (i.e., muscle, fat, and bone mass). Purpose We hypothesized that muscle, fat, and bone mass have different impact on prognosis in HF. Methods We retrospectively analyzed 418 patients admitted with a diagnosis of HF (71±13 years, 59% male, 46 and 54% with preserved/mid-range (left ventricular ejection fraction (LVEF) ≥40%) and reduced ( Results Mean appendicular skeletal mass index (ASMI) was 6.9±1.2 kg/m2 in men and 5.6±0.9 in women, so that 55% of patients had low muscle mass categorized by the Asian Working Group of Sarcopenia. During median follow-up of 502 days, 163 (39.0%) patients experienced primary outcome defined as death or heart failure hospitalization. Using optimal cut-off of each body component chosen on the basis of a receiver operating characteristic curve and the Youden method, we demonstrated that lower ASMI defined by the cut-off of 6.5 kg/m2 in male and 5.2 in female (adjusted hazard ratio (HR): 1.768, 95% CI: 1.210–2.581, p=0.003) and bone mass (adjusted HR: 1.498, 95% CI: 1.051–2.152, p=0.025), but not lower fat mass (p=0.34), were associated with elevated risk of primary outcome after multivariate adjustment. Kaplan-Meier curves with p value by Log-rank test were shown in figure. In subgroup analysis, negative impact of lower ASMI was significant regardless of sex and LVEF category, whereas negative impact of low bone mass was significant only in 78 female patients with reduced LVEF. Figure 1 Conclusions Indices about muscle and bone mass rather than fat mass had prognostic impact in HF. The impact of each body component may different according to sex and LVEF.

Introduction Muscle, fat and bone mass may play some roles to keep physical activity and favorable outcome in patients with cardiovascular diseases. However, there is a paucity of data regarding the effects on the prognosis of skeletal muscle, fat, and bone mass in patients with ST-segment elevation myocardial infarction (STEMI). Purpose Our purpose was to examine whether skeletal muscle, fat, and bone mass each affect the prognosis after STEMI. Methods A total of 354 male patients with STEMI were enrolled in this study. Dual-energy X-ray absorptiometry scan was performed before discharge. All patients were followed up for the primary composite outcome of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for congestive heart failure, and unplanned revascularization. Results During a median follow-up of 32 months, 57 patients experienced primary composite outcome. Each of skeletal muscle, fat, and bone mass were indexed by height squared (kg/m2) and divided into two groups using the cut-off value obtained from the maximum Youden index to predict the primary composite outcome. The event rate was significantly higher in patients with low appendicular skeletal muscle mass index (ASMI) (29.2% vs 11.7%, p Conclusions Index about muscle mass rather than fat and bone mass have prognostic impact in male patients with STEMI.

Background: Both native T1 time and extracellular volume (ECV) fraction have been shown to be important measures for the detection of myocardial fibrosis. However, ECV determination requires the administration of an intravenous contrast agent, whereas native T1 mapping can be performed without a contrast agent. Methods: Here, we conducted a meta-analysis of myocardial native T1 data obtained for non-ischemic cardiomyopathy (NIC) patients and controls. A literature review included studies that applied T1 mapping using modified Look–Locker inversion recovery to measure myocardial fibrosis, and the results were validated by comparing datasets for dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) patients and healthy controls (HCs). Results: We identified 16 eligible studies. Pooled mean differences (MDs) and 95% confidence intervals (CIs) were estimated as follows. Native T1 at 1.5-T, DCM vs. HC: MD = 45.26 (95% CI: 30.92–59.59); HCM vs. HC: MD = 47.09 (95% CI: 32.42–61.76). Native T1 at 3.0-T, DCM vs. HC: MD = 82.52 (95% CI: 47.60–117.44); HCM vs. HC: MD = 115.87 (95% CI: 50.71–181.04). ECV at 1.5-T, DCM vs. HC: MD = 4.26 (95% CI: 3.06–5.46); HCM vs. HC: MD = 1.49 (95% CI: −1.45–4.43). ECV at 3.0-T, DCM vs. HC: MD = 8.40 (95% CI: 2.94–13.86); HCM vs. HC: MD = 8.02 (95% CI: 5.45–1–0.59). Conclusion: In conclusion, native T1 values were significantly different between NIC patients and controls. Native T1 mapping may be a useful noninvasive method to detect diffuse myocardial fibrosis in NIC patients. Keywords: Native T1 mapping, Extracellular volume fraction, Dilated cardiomyopathy, Hypertrophic cardiomyopathy, Systematic review, Meta-analysis

Background Antiplatelet therapy is the corner stone of treatment following acute myocardial infarction (AMI). Prasugrel, a new and potent antiplatelet agent, was recently introduced to clinical practice. We compared the clinical outcomes of patients with AMI treated with prasugrel with those treated with clopidogrel in real-world clinical practice in Japan.Methods and Results:The Japan AMI Registry (JAMIR) is a multicenter, nationwide, prospective registry enrolling patients with AMI from 50 institutes. Between December 2015 and May 2017, a total of 3,411 patients were enrolled. Among them, 3,069 patients were treated with either prasugrel (n=2,607) or clopidogrel (n=462) during hospitalization. Median follow-up period was 12 months. Prasugrel-treated patients were predominantly male, younger, more often showed ST-elevation AMI, and had fewer comorbidities. After adjustment using inverse probability of treatment weighting, the primary endpoint, defined as a composite of cardiovascular death, non-fatal MI and non-fatal stroke, was comparable between the prasugrel and clopidogrel groups (adjusted hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.67-1.72), whereas the risk of major bleeding (BARC type 3 or 5 bleeding) was significantly lower in the prasugrel group (adjusted HR 0.62, 95% CI 0.39-0.99). Conclusions The present real-world database of the JAMIR demonstrated that the potent P2Y12-inhibitor prasugrel showed comparable rates of 1-year ischemic events to clopidogrel, but the risk of bleeding was lower with prasugrel than with clopidogrel.

Background Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents. Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single- or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30was significantly lower in patients with bleeding events than in those without (584 [96-993] vs. 1,028 [756-1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30(odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10was not significantly related to bleeding events. Conclusions A lower AR4-AUC30level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.

Yasushi Matsuzawa,1 Kiyoshi Hibi,1 Kenichiro Saka,1 Masaaki Konishi,1 Eiichi Akiyama,1 Naoki Nakayama,1 Toshiaki Ebina,1 Masami Kosuge,1 Noriaki Iwahashi,1 Nobuhiko Maejima,1 Kouichi Tamura,2 Kazuo Kimura1 1Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, Japan Background: Thinning of the fibrous cap of atherosclerotic plaque is a major component of plaque vulnerability. The high resolution of optical coherence tomography (OCT) provides an accurate measurement of fibrous-cap thickness. Endothelial dysfunction is associated with inflammation and enhanced local expression of matrix metalloproteinases. We investigated the association between endothelial dysfunction and OCT-derived thin-cap fibroatheroma (TCFA) in patients with acute coronary syndromes (ACS). Methods: Seventy-four patients with ACS, who underwent both OCT examinations of the culprit lesion before percutaneous coronary intervention and peripheral endothelial function assessment as assessed by logarithmic value of reactive hyperemia index (Ln_RHI), were enrolled. Age-, sex-, hypertension-, and diabetes-matched non-coronary artery disease (non-CAD) patients were also enrolled (n=15). Results: Ln_RHI levels were significantly lower in ACS patients compared with non-CAD patients (0.56±0.26 vs 0.74±0.22, P=0.01). Furthermore, the Ln_RHIs of ACS patients with TCFA (n=44) were significantly lower than those of ACS patients without TCFA (n=30) (0.50±0.24 vs 0.65±0.26, P=0.01). There was a weak but significant positive correlation between Ln_RHI and fibrous-cap thickness (Spearman’s ρ=0.25, P=0.03). Multivariate logistic regression analysis identified lower Ln_RHI as an independent factor associated with TCFA in ACS patients (OR per 0.1 increase in Ln_RHI: 0.78 [95% CI: 0.62–0.98], P=0.03). Conclusion: Advanced endothelial dysfunction significantly correlates with a thin fibrous cap of coronary plaques in patients with ACS. Keywords: peripheral endothelial function, optical coherence tomography, thin-cap fibroatheroma, plaque vulnerability