Association between evolocumab use and slow progression of aortic valve stenosis.

No medications have been reported to inhibit the progression of aortic valve stenosis (AS). The present study aimed to investigate whether evolocumab use is related to the slow progression of AS evaluated by serial echocardiography. This was a retrospective observational study from 2017 to 2022 at Yokohama City University Medical Center. Patients aged ≥ 18 with moderate AS were included. Exclusion criteria were (1) mild AS; (2) severe AS defined by maximum aortic valve (AV) velocity ≥ 4.0 m/s; and/or (3) no data of annual follow-up echocardiography. The primary endpoint was the association between evolocumab use and annual changes in the maximum AV-velocity or peak AV-pressure gradient (PG). A total of 57 patients were enrolled: 9 patients treated with evolocumab (evolocumab group), and the other 48 patients assigned to a control group. During a median follow-up of 33 months, the cumulative incidence of AS events (a composite of all-cause death, AV intervention, or unplanned hospitalization for heart failure) was 11% in the evolocumab group and 58% in the control group (P = 0.012). Annual change of maximum AV-velocity or peak AV-PG from the baseline to the next year was 0.02 (- 0.18 to 0.22) m/s per year or 0.60 (- 4.20 to 6.44) mmHg per year in the evolocumab group, whereas it was 0.29 (0.04-0.59) m/s per year or 7.61 (1.46-16.48) mmHg per year in the control group (both P < 0.05). Evolocumab use was associated with slow progression of AS and a low incidence of AS events in patients with moderate AS.

Prognostic importance of glycemic variability on left ventricular reverse remodeling after the first episode of ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the effect of glycemic variability (GV), determined using a continuous glucose monitoring system (CGMS), on left ventricular reverse remodeling (LVRR) after ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 201 consecutive patients with STEMI who underwent reperfusion therapy within 12 h of onset were enrolled. GV was measured using a CGMS and determined as the mean amplitude of glycemic excursion (MAGE). Left ventricular volumetric parameters were measured using cardiac magnetic resonance imaging (CMRI). LVRR was defined as an absolute decrease in the LV end-systolic volume index of > 10% from 1 week to 7 months after admission. Associations were also examined between GV and LVRR and between LVRR and the incidence of major adverse cardiovascular events (MACE; cardiovascular death, acute coronary syndrome recurrence, non-fatal stroke, and heart failure hospitalization). RESULTS: The prevalence of LVRR was 28% (n = 57). The MAGE was independent predictor of LVRR (odds ratio [OR] 0.98, p = 0.002). Twenty patients experienced MACE during the follow-up period (median, 65 months). The incidence of MACE was lower in patients with LVRR than in those without (2% vs. 13%, p = 0.016). CONCLUSION: Low GV, determined using a CGMS, was significantly associated with LVRR, which might lead to a good prognosis. Further studies are needed to validate the importance of GV in LVRR in patients with STEMI.

Present and Future Status of Cardiovascular Emergency Care System in Urban Areas of Japan　- Importance of Prehospital 12-Lead Electrocardiogram.

Acute cardiovascular disease, such as acute myocardial infarction and aortic disease, can lead to a serious life-threatening state within minutes to hours, so early accurate diagnosis, and appropriate treatment without delay are essential. To provide high-quality and timely treatment, 24-h availability of medical staff and cardiologists, as well as a cardiac catheterization laboratory are needed. In Japan, the number of patients with acute cardiovascular disease is increasing with the aging population and westernization of lifestyle; however, workstyle reforms for physicians, including a policy to limit overtime work, have been legislated. Under these conditions, it is necessary to centralize hospitals that treat cardiovascular emergency diseases as high-volume centers and build a patient triage system for allocating patients before hospital arrival. The prehospital 12-lead electrocardiogram (ECG) plays a central role in prehospital diagnosis and triage, and its importance will increase in future. We discuss the current and future state of the cardiovascular emergency medical care system utilizing prehospital 12-lead ECG in urban areas of Japan.

A Simple Risk Score to Differentiate Between Coronary Artery Obstruction and Coronary Artery Spasm of Patients With Acute Coronary Syndrome Without Persistent ST-Segment Elevation.

BACKGROUND: 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: age >70 years (6 points), non-STE myocardial infarction (9 points), diabetes mellitus (5 points), B-type natriuretic peptide >90 pg/mL (7 points), neutrophil to lymphocyte ratio >2 (5 points), and high-density lipoprotein cholesterol <50 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) (P<0.001), indicating that a total score of <20 was a potential clinical indicator of CA spasm-induced ACS. CONCLUSIONS: CA spasm-induced ACS should be suspected if a total score of <20, and a spasm provocation test was being considered.

Prognostic Significance of the Combination of Left Atrial Reservoir Strain and Global Longitudinal Strain Immediately After Onset of ST-Elevation Acute Myocardial Infarction.

BACKGROUND: 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 strain <25.8% was a strong predictor (Log rank, χ2=76.7, P<0.0001). Net reclassification improvement (NRI) demonstrated that adding LA reservoir strain had significant incremental effect on the conventional parameters (NRI and 95% CI: 0.24 [0.11-0.44]) . When combined with GLS >-11.5%, the patients with LA reservoir strain <25.8% were found to be at extremely high risk for MACE (Log rank, χ2=126.3, P<0.0001). CONCLUSIONS: LA reservoir strain immediately after STEMI onset was a significant predictor of poor prognosis in patients, especially when combined with GLS.

Effect of Infarction-Related Artery Location on Clinical Outcome of Patients With Acute Myocardial Infarction in the Contemporary Era of Percutaneous Coronary Intervention　- Subanalysis From the Prospective Japan Acute Myocardial Infarction Registry (JAMIR).

BACKGROUND: 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. CONCLUSIONS: 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.

Effect of Low Body Mass Index on the Clinical Outcomes of Japanese Patients With Acute Myocardial Infarction　- Results From the Prospective Japan Acute Myocardial Infarction Registry (JAMIR).

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 <18.5 kg/m2, n=133), Q2 group (18.5≤BMI<25.0 kg/m2, n=1,424), Q3 group (25.0≤BMI<30.0 kg/m2, n=672), and Q4 group (30.0 kg/m2≤BMI, n=144). The primary endpoint was all-cause death, and the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. The median follow-up period was 358 days. Q1 patients were older and had lower prevalence of coronary risk factors. Q1 patients also had higher all-cause mortality and higher incidence of secondary endpoints than normal-weight or obese AMI patients. Multivariate analysis showed that low BMI (Q1 group) was an independent predictor for primary endpoint. CONCLUSIONS: AMI patients with low BMI had fewer coronary risk factors but worse clinical outcomes than normal-weight or obese patients.

Clinical Usefulness of the Serial Examination of Three-Dimensional Global Longitudinal Strain After the Onset of ST-Elevation Acute Myocardial Infarction.

BACKGROUND: 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 χ2=165.5, P<0.0001). The deterioration of 3D-GLS at 1 year was a significant prognosticator (log-rank χ2=36.7, P<0.0001). CONCLUSIONS: The deterioration of 3D-GLS measured by STE at 1 year after the onset of STEMI is the strongest predictor of long-term prognosis.

Admission free-fatty acid level is a predictor of the mid-term worsening renal function in patients with ST-segment elevation myocardial infarction.

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.

Impact of red blood cell distribution width and mean platelet volume in patients with ST-segment elevation myocardial infarction.

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.

Global Strain Measured by Three-Dimensional Speckle Tracking Echocardiography Is a Useful Predictor for 10-Year Prognosis After a First ST-Elevation Acute Myocardial Infarction.

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<0.0001). When combined with 3D-GCS >-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.

Skeletal muscle mass is associated with glycemic variability in patients with ST-segment elevation myocardial infarction.

Skeletal muscle function has been studied to determine its effect on glucose metabolism; however, its effect on glycemic variability (GV), which is a significant glycemic marker in patients with coronary artery disease, is unknown. The aim of the present study was to elucidate the association between skeletal muscle mass and GV. Two hundred and eight consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent continuous glucose monitoring to evaluate mean amplitude of glycemic excursion (MAGE) as GV and a dual-energy X-ray absorptiometry (DEXA) to evaluate skeletal muscle mass were enrolled. Skeletal muscle index (SMI) level was calculated as skeletal muscle mass divided by height squared (kg/m2). SMI level in men had a weak inverse correlation with Log MAGE level by the linear regression model in diabetes mellitus (DM) patients (R2 = 0.139, P = 0.004) and even in non-DM patients (R2 = 0.068, P = 0.004). Multivariate linear regression analysis with a stepwise algorithm (age, male sex, body mass index [BMI], hemoglobin A1c [HbA1c], fasting glucose, HOMA-IR, and SMI; R2 = 0.203, P < 0.001) demonstrated that HbA1c level (B = 0.077, P < 0.001) and SMI level (B = - 0.062, P < 0.001) were both independently associated with Log MAGE level. This association was also confirmed in limited non-DM patients with a subgroup analysis. SMI level was associated with Log MAGE level (B = - 0.055, P = 0.001) independent of BMI or HbA1c level. SMI level was inversely associated with MAGE level independent of glucose metabolism in STEMI patients, suggesting the significance of skeletal muscle mass as blood glucose storage for glucose homeostasis to reduce GV.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

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 < 17.92 ng/mg creatinine. The patients were followed up for a median period of 34 months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

Characteristics and Prognosis of Patients with Vasospastic Angina Diagnosed by a Provocation Test with Secondary Prevention Implantable Cardioverter Defibrillator.

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.

Direct Oral Anticoagulant Therapy for Cancer-Associated Venous Thromboembolism in Routine Clinical Practice.

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.

In-Hospital Mortality in Acute Myocardial Infarction According to Population Density and Primary Angioplasty Procedures Volume.

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<0.001). Patients in less densely populated areas were more often transported to hospitals with a lower primary PCI volume, and they had a longer distance to travel. By using multivariable analysis, primary PCI volume was found to be significantly associated with in-hospital mortality, but distance to hospital was not. When divided into the low- and high-volume hospitals, using the cut-off value of 115 annual primary PCI procedures, the increase in in-hospital mortality associated with low population density was observed only in patients hospitalized in the low-volume hospitals. CONCLUSIONS: Increased in-hospital mortality related to low population density was observed only in AMI patients who were transported to the low primary PCI volume hospitals, but not in those who were transported to high-volume hospitals.

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

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 (ß=0.29, P=0.0006) and poor initial TIMI flow (ß=0.37, P<0.0001) as independent determinants of AUCCK. CONCLUSIONS: T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

Prognostic Significance of a Combination of QRS Score and E/e' Obtained 2 Weeks After the Onset of ST-Elevation Myocardial Infarction.

BACKGROUND: 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; P<0.0001), QRS-2wks (HR 1.153; 95% CI 1.057-1.254; P<0.0001), 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-2wks >4 and mean E/e' >14 were at an extremely high risk of cardiac death or HF (log rank, χ2=116.3, P<0.0001). CONCLUSIONS: In patients with STEMI, a combination of QRS-2wks and mean E/e' was a simple but useful predictor of cardiac death and HF.

Combination of extracellular volume fraction by cardiac magnetic resonance imaging and QRS duration for the risk stratification for patients with non-ischemic dilated cardiomyopathy.

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 â‰¦ 0.30 and QRS â‰¦ 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 < 0.001, log-rank test). No significant difference was found between group 1 and group 2 (p = 0.053), group 2 and group 3 (p = 0.115). The area under the receiver operating characteristic curve (AUC) for predicting adverse events was 0.778 (95% confidence interval CI 0.612-0.939) for ECV, 0.792 (95% CI 0.539-0.924) for QRS duration, 0.822 (95% CI 0.688-0.966) for combination of ECV and QRS duration. NIDCM patients with high ECV and prolonged QRS duration had significantly worse prognosis compared to those with normal ECV and normal QRS duration. The combination of ECV and QRS duration could be useful as a non-invasive method for better risk stratification for patients with NIDCM.

Impact of Total Antithrombotic Effect on Bleeding Complications in Patients Receiving Multiple Antithrombotic Agents.

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.