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Anti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined.In a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs).Baseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (-0.3 ± 0.6 vs. -0.04 ± 0.7 mmsup3/sup/mm, p = 0.03) and %PV (-0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (-0.1 ± 0.7 vs. -0.4 ± 0.8 mmsup3/sup/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (-1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. -0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (β = -0.33, p = 0.004) and %NV (β = -0.28, p = 0.03) at 10 months.Alogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients' subset.

Reduced skeletal muscle mass is a major component of sarcopenia, associated with impaired exercise capacity and poor prognosis in patients with heart failure (HF). Measurement of skeletal muscle mass by dual-energy X-ray absorptiometry may be affected by fluid retention, typically in the patients' lower extremities. The aim of the present study was to elucidate the association between upper and lower extremity skeletal muscle mass (USM and LSM) and all-cause mortality in hospitalized patients with HF, after discharge.This was a single-centre observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years), with a left ventricular ejection fraction of 39 ± 16%. USM and LSM were measured by dual-energy X-ray absorptiometry with patients in a stable state after decongestion therapy.The USM and LSM were 5.29 ± 1.18 and 13.78 ± 3.20 kg for men and 3.37 ± 0.68 and 9.19 ± 1.80 kg for women. A positive correlation was obtained between USM and LSM with mid-upper arm circumference (r = 0.684, P 0.001) and calf circumference (r = 0.822, P 0.001), respectively. During a median follow-up of 37 months, 92 (22.0%) of the 418 patients died. A Kaplan-Meier analysis revealed that sex-specific quartiles of USM/heightBoth USM and LSM had a prognostic implication on mortality after discharge in HF, even though LSM may have been affected by leg oedema. These findings indicate that clinicians should not ignore a patient's USM or LSM in the prognostication of patients with HF.

The role of left atrial (LA) function in the long-term prognosis of ST-elevation acute myocardial infarction (STEMI) is still unclear.Methods and Results: Percutaneous coronary intervention (PCI) was performed in 433 patients with the first episode of STEMI within 12 h of onset. The patients underwent echocardiography 24 h after admission. LA reservoir strain and other echocardiographic parameters were analyzed. Follow up was performed for up to 10 years (mean duration, 91 months). The primary endpoint was major adverse cardiovascular events (MACE): cardiac death or hospitalization due to heart failure (HF). MACE occurred in 90 patients (20%) during the follow-up period. Multivariate Cox hazard analyses showed LA reservoir strain, global longitudinal strain (GLS), age and maximum B-type natriuretic peptide (BNP) were the significant predictors of MACE. Kaplan-Meier curves demonstrated that LA reservoir strain25.8% was a strong predictor (Log rank, χLA reservoir strain immediately after STEMI onset was a significant predictor of poor prognosis in patients, especially when combined with GLS.

The aim of this study was to create a risk scoring model to differentiate obstructive coronary artery (CA) from CA spasm in the etioology of acute coronary syndrome (ACS).Methods and Results: We included 753 consecutive patients with ACS without persistent ST-segment elevation (p-STE). The exclusion criteria were: (1) out-of-hospital cardiac arrest; (2) cardiogenic shock; (3) hemodialysis; (4) atrial fibrillation/flutter; (5) severe valvular disease; (6) no coronary angiography; (7) non-obstructive coronary artery without "definite" vasospastic angina definition; and/or (8) missing data. From the multivariate logistic regression analysis for prediction of obstructive CA, an integer score of 2 to each 0.5 increment in odds ratio was given, and values were divided into quartiles according to the total score. The scores were as follows: age70 years (6 points), non-STE myocardial infarction (9 points), diabetes mellitus (5 points), B-type natriuretic peptide90 pg/mL (7 points), neutrophil to lymphocyte ratio2 (5 points), and high-density lipoprotein cholesterol50 mg/dL (5 points). CA spasm-induced ACS occurred in 50.0% in Quartile 1 (total score: 0-13), 20.5% in Quartile 2 (total score: 14-19), 4.9% in Quartile 3 (total score: 20-26), and 2.2% in Quartile 4 (total score: 27-37) (P0.001), indicating that a total score of20 was a potential clinical indicator of CA spasm-induced ACS.CA spasm-induced ACS should be suspected if a total score of20, and a spasm provocation test was being considered.

This study aimed to investigate the possible influence of arterial stiffness assessed by the cardio-ankle vascular index (CAVI) on chronic-phase left ventricular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI).A total of 208 consecutive patients with first STEMI (age, 64 ± 11 years; 86% men) who underwent reperfusion therapy within 12 h of onset were enrolled. We analysed arterial stiffness by measuring CAVI in a stable phase after admission and performed two-dimensional echocardiography at baseline and 7 months' follow-up. Subsequently, we assessed left ventricular global longitudinal strain (LV-GLS) to evaluate left ventricular function. A total of 158 (75.9%) patients underwent baseline cardiac magnetic resonance (CMR). We estimated left ventricular infarct size by measuring peak levels of creatine kinase-myocardial band (CK-MB), and CMR-late gadolinium enhancement (LGE).On the basis of the median CAVI value, the patients were allocated into high CAVI (CAVI ≥ 8.575) and low CAVI (CAVI8.575) groups. The groups showed no statistically significant differences in LV-GLS at baseline (-13.5% ± 3.1 vs. -13.9% ± 2.7%, P = 0.324). However, LV-GLS was significantly worse in the high CAVI group than in the low-CAVI group at 7 months (-14.0% ± 2.9 vs. -15.6% ± 3.0%, P 0.001). Stratified by CAVI and peak CK-MB or LGE, the four groups showed significant differences in LV-GLS at 7 months after STEMI (both P 0.001). Multivariate linear regression analysis with the forced inclusion model showed that CAVI was an independent predictor of LV-GLS at 7 months ( P = 0.015).CAVI early after STEMI onset was significantly associated with chronic-phase LV-GLS. In addition, combining CAVI with CK-MB or LGE improves its predictive ability for evaluation of chronic-phase LV-GLS. Thus, the arterial stiffness assessment by CAVI was an important factor related to chronic-phase left ventricular dysfunction after the first STEMI.

A 78-year-old man suffering from epigastric discomfort presented with an initial electrocardiogram showing complete right bundle branch block (RBBB) and ST-segment depression continuing to positive symmetrical T waves in leads V2 to V4, suggestive of de Winter's pattern. Emergent coronary angiography demonstrated 2-vessel disease with 90% stenosis in the proximal segment of the left anterior descending artery (LAD) with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, and 75% in the mid portion and 90% in the distal portion of the right coronary artery, without collateral flow to LAD. A drug-eluting stent was deployed at the proximal LAD, and the flow of the diagonal branch deteriorated to TIMI grade 1 flow on the final angiogram. De Winter's pattern temporarily disappeared, and the procedure was finished. However, when the patient was admitted to the coronary care unit, de Winter's pattern emerged again with less severe epigastric discomfort. Subsequently, chest X-ray showed pulmonary edema in both lungs. Repeat angiography revealed acute stent thrombosis of LAD with TIMI grade 1 flow. De Winter's pattern with the combination of RBBB can be observed not only on admission but also at the time of occurrence of stent thrombosis.

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

In this prospective observational study, we investigated the effects of the severity and classification of sleep-disordered breathing (SDB) (obstructive, central, or mixed apnea predominant) on left ventricular (LV) dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). In total, 115 patients with STEMI underwent a sleep study using a multichannel frontopolar electroencephalography recording device (Sleep Profiler®︎) 1 week after STEMI onset. We evaluated LV global longitudinal strain (LV-GLS) measured using two-dimensional echocardiography (2DE) as a parameter for LV function at 1 week and 7 months. The obstructive apnea index was significantly associated with the LV-GLS at 1 week and 7 months (r = 0.27, p = 0.002; and r = 0.23, p = 0.013, respectively). However, central and mixed apnea indices were not. Multivariate linear regression analysis showed that the obstructive apnea index was independently associated with LV-GLS at 1 week and 7 months (β = 0.27, p < 0.001; and β = 0.19, p = 0.016, respectively). However, the three-type SDB classification was not significantly associated with LV-GLS. In examination of the influence of SDB on STEMI, it may be useful to focus on the obstructive apnea index rather than focusing only on the SDB classification and apnea-hypopnea index.

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.

Background: Rapidly progressive, extensive myocardial injury/infarction (RPEMI) beyond the concept of wave-front phenomenon can be observed even when achieving timely reperfusion; however, the pathogenesis of RPEMI remains unknown. This retrospective study investigated clinical and lesion characteristics of RPEMI, focusing on culprit-lesion morphology (CLM). Methods: Among patients with extensive anterior-wall ST-segment elevation myocardial infarction due to proximal left anterior descending artery lesions who had reperfusion within 3 hours of symptom onset, 60 patients undergoing both intravascular ultrasound and cardiac magnetic resonance imaging were enrolled. Myocardial injury/infarction before reperfusion therapy was assessed by QRS scores at hospitalization electrocardiogram, and the extent of myocardial injury/infarction was evaluated by cardiac magnetic resonance imaging, which measured area at risk, infarct size, myocardial salvage index, microvascular obstruction, and left ventricular ejection fraction. RPEMI was defined as lower left ventricular ejection fraction (less median value) with microvascular obstruction. Results: Despite comparable onset-to-door and onset-to-reperfusion times and area at risk, patients with RPEMI showed higher QRS scores at hospitalization (5 [4.3–6] versus 3 [2–4], P P =0.04), and a tendency toward lower myocardial salvage index (0.27±0.14 versus 0.36±0.20, P =0.10) compared with those without. Patients with versus without RPEMI more frequently observed specific CLM on intravascular ultrasound, characterized by the combination of vulnerable plaques, plaque ruptures, and/or large thrombi. When stratified by CLM-score composed of these 3 criteria, higher CLM-scores were or tended to be associated with higher QRS scores and incidence of RPEMI. In multivariate analyses including no-reflow phenomenon and final coronary-flow deterioration, increased CLM-score (≥2) was independently associated with high QRS scores and RPEMI (odd ratio 11.25 [95% CI, 2.43–52.00]; P =0.002). Conclusions: Vulnerable CLM was a consistent determinant of advanced myocardial injury/infarction both before and after reperfusion therapy and may play a pivotal role in the development of RPEMI.

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

Background Balloon angioplasty, including drug-coated balloon (DCB), is an important option of percutaneous coronary interventions (PCI), even in the drug-eluting stent era. Although quantitative coronary angiography (QCA) has been frequently used to determine the optimal endpoint of balloon angioplasty, physiological assessment may add incremental prognostic values. Quantitative flow ratio (QFR) has evolved as a novel 3D QCA-based physiological index to estimate fractional flow reserve without hyperemia nor pressure guidewire, offering both anatomical and functional lesion assessments. This study aimed to characterize post-procedural anatomical and physiological indexes by QFR and to compare their prognostic impacts on long-term clinical outcomes. Methods This retrospective study included 98 patients with de novo (n=39) or in-stent restenosis (n=59) lesions who underwent PCI with DCB (n=69) or plain-old balloon angioplasty (POBA, n=29). All lesions were analyzed by QCA and QFR. QCA analysis measured lesion length, reference lumen diameter (RLD), minimum lumen diameter (MLD) and percent diameter stenosis (%DS) at pre- and post-procedures as anatomical indexes. QFR analysis measured post-procedural QFR of target vessel (QFR-vessel) and QFR-gradient (ΔQFR between proximal and distal segments of the lesion) as physiological indexes. Primary endpoint was target lesion revascularization (TLR) within 1-year post-procedure. Results Target lesion profiles were as follows: lesion length 26.3±16.6 mm, RLD 2.90±0.70 mm, MLD 0.94±0.32 mm and %DS 79.3±18.6%. At post-procedure, MLD, residual %DS, QFR-vessel and QFR-gradient of target lesions were 1.88±0.49 mm, 34.7±10.6%, 0.84±0.13 and 0.06±0.04, respectively. During 1 year post-procedure, TLR occurred in 19 (19%) patients. Patients with TLR showed smaller MLD (1.66±0.45 mm vs. 1.93±0.49 mm, p=0.028) and QFR-vessel (0.79±0.03 vs. 0.85±0.01, p=0.06), and greater residual %DS (42.7±11.3% vs. 32.8±9.5%, p=0.0002) and QFR-gradient (0.12±0.06 vs. 0.04±0.02, p Conclusions Post-procedural QFR-gradient within the lesion was an independent and stronger predictor of subsequent TLR, compared with anatomical indexes. Further studies are warranted to investigate whether QFR guidance to optimize PCI procedure could improve clinical outcomes in patients with balloon angioplasty. Figure 1 Funding Acknowledgement Type of funding source: None

Previous studies have reported that acute myocardial infarction (AMI) related to left anterior descending (LAD) lesion is associated with worse outcomes than left circumflex artery (LCX) or right coronary artery (RCA) lesions. However, it is unknown whether those relationships are still present in the contemporary era of primary percutaneous coronary intervention (PCI), using newer generation drug-eluting stents and potent antiplatelet agents.Methods and Results:This study is a sub-analysis of the Japan AMI Registry (JAMIR), a multicenter, prospective registry enrolling 3,411 AMI patients between December 2015 and May 2017. Among them, 2,780 patients undergoing primary PCI for only a culprit vessel were included and stratified based on infarction-related artery type (LAD, LCX, and RCA). The primary outcome was 1-year cardiovascular death. The overall incidence of cardiovascular death was 3.4%. Patients with LAD infarction had highest incidence of cardiovascular death compared to patients with LCX and RCA infarction (4.8%, 1.3%, and 2.4%, respectively); however, landmark analysis showed that culprit vessel had no significant effect on cardiovascular death if a patient survived 30 days after primary PCI. LAD lesion infarction was an independent risk factor for cardiovascular death in adjusted Cox regression analysis.The present sub-analysis of the JAMIR demonstrated that LAD infarction is still associated with worse outcomes, especially during the first 30 days, even in the contemporary era of PCI.

Two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) can predict the prognosis. This study investigated the clinical significance of a serial 3D-STE can predict the prognosis after onset of STEMI.Methods and Results:This study enrolled 272 patients (mean age, 65 years) with first-time STEMI treated with reperfusion therapy. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Within 1 year, 19 patients who experienced major adverse cardiac events (MACE; cardiac death, heart failure requiring hospitalization) were excluded. Among the 253 patients, 248 were examined with follow-up echocardiography. The patients were followed up for a median of 108 months (interquartile range: 96-129 months). The primary endpoint was the occurrence of a MACE; 45 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 2D-global longitudinal strain (GLS) and 3D-GLS at 1-year indices were significant predictors of MACE. The Kaplan-Meier curve demonstrated that a 3D-GLS of-13.1 was an independent predictor for MACE (log-rank χThe deterioration of 3D-GLS measured by STE at 1 year after the onset of STEMI is the strongest predictor of long-term prognosis.

The role of left ventricular (LV) mechanical dispersion estimated after an ST elevation acute myocardial infarction (STEMI) remains unclear.The study participants were 208 consecutive patients (152 men, age = 72 years) presenting with STEMI for the first time who underwent primary percutaneous coronary intervention (PCI) within 12 h of STEMI onset. Within 48 h of PCI (mean = 24 h), 2D and 3D speckle-tracking echocardiography were performed. The global longitudinal strain (GLS) was calculated using 3D (3D-GLS) and 2D (2D-GLS) speckle tracking. Mechanical dispersion was defined using the standard deviation (SD) of the time to regional peak longitudinal strain (LS) for all 16 segments for both 2D-STE and 3D-STE (2D-LS-SD, 3D-LS-SD). Infarct size was estimated by Tc99m-sestamibi as the total area of 50% of the uptake area at 2 weeks. The patients were followed up for a longer period of time (median118months) and checked for major adverse cardiac events (MACE: cardiac death, heart failure).During follow-up, 55 patients experienced MACE. The cut-off values were determined using receiver operating characteristic curves. The multivariate analysis revealed that a 3D-LS-SD 56.7 ms was a significant predictor of MACEs (hazard ratio = 1.991, 95% confidence interval 1.033-3.613, p = 0.03), but 2D-LS-SD 58.1 ms was not an independent predictor of MACEs (hazard ratio = 1.577, 95% confidence interval 0.815-3.042, p = 0.1). Furthermore, the combination of 3D-GLS and 3D-LS-SD had accurate predictability for MACE, as shown by the Kaplan-Meier curves (log rank, χLV mechanical dispersion besides 3D-GLS assessed by 3D-STE immediately after PCI can predict long-term prognosis.

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