Pretransfer Aspirin Administration and Its Impact on Angiographic Outcomes for Patients with ST-Elevation Myocardial Infarction.

Although guidelines recommend early aspirin administration after diagnosis of ST-elevation myocardial infarction (STEMI), the decision of pretransfer aspirin administration is at the discretion of the primary physicians. Therefore, this study aimed to determine whether pretransfer aspirin administration was associated with better angiographical outcomes in patients with STEMI. This study compared the angiographic findings of thrombolysis in myocardial infarction (TIMI) flow grade in the infarct-related artery before percutaneous coronary intervention (PCI) between patients who received pretransfer aspirin and those who did not. In total, 28 patients (11.2%) were administered aspirin before transfer and 219 (88.8%) were administered aspirin upon arrival at the hospital. Propensity score matching yielded 135 patients [27 patients (20%) who were administered aspirin before transfer and 108 patients (80%) who were administered aspirin upon arrival at the hospital]. Patients who received pretransfer aspirin had a higher rate of TIMI-3 flow before PCI compared to those who did not receive pretransfer aspirin [8 (28.6%) versus 15 (6.8%), P < 0.01, in all study patients; 8 (26.6%) versus 7 (6.5%), P < 0.01, in propensity-score-matched patients]. Multivariable logistic regression analysis revealed that pretransfer aspirin administration was significantly associated with the presence of TIMI-3 flow before PCI, independent of age, gender, transfer time, and statin use (OR: 5.43, 95% CI: 1.94-15.2, P < 0.01, in all study patients; OR: 6.17, 95% CI: 1.86-20.46, P < 0.01, in propensity-score-matched patients). Pretransfer aspirin administration could lead to the early restoration of coronary blood flow in patients with STEMI, supporting its active use in STEMI care.

Impact of atherothrombotic risk stratification in patients with heavily calcified lesions following rotational atherectomy.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. METHODS: We conducted a study with 196 patients who underwent PCI with RA out of 7391 patients who underwent PCI using a multicenter, prospective cohort registry. Patients were divided into three groups according to the tertiles of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P): 65 patients in the T1 group (TRS 2°P < 3), 66 patients in the T2 group (TRS 2°P = 3), and 65 patients in the T3 group (TRS 2°P > 3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. RESULTS: Cumulative 2-year MACCE occurred in 41 patients (24 %) during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in the T1 group (log-rank test, p = 0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to that of the T1 group (adjusted hazard ratio, 2.66; 95 % confidence interval, 1.04-6.77; p = 0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, p = 0.027; IDI 0.072, p < 0.001). CONCLUSIONS: Atherothrombotic risk stratification using TRS 2°P was useful in identifying high-risk patients with heavily calcified lesions following RA.

A new training model using the self-healing properties of supramolecular hydrogels for endoscopic combined intrarenal surgery.

The combination of hydronephrosis formation, ureteroscopic imaging, and ultrasound delineation has not been included in any non-biological training model of percutaneous nephrolithotomy or endoscopic combined intrarenal surgery. We aimed to develop a realistic kidney phantom using the self-healing properties of supramolecular hydrogels for percutaneous nephrolithotomy and endoscopic combined intrarenal surgery and evaluate its suitability as a training model.Expert and resident urologists performed ultrasound-guided renal pelvic punctures and flexible ureteroscopies for endoscopic combined intrarenal surgery using a training model. Subsequently, the training model was evaluated using a 17-item Likert scale questionnaire (range, 1-5 points). After being filled with carrageenan, the collecting system was inflated, and the relationship between the collecting system volume and collecting system pressure was determined. The durability of the model was verified by repeatedly inserting a 16-Fr access sheath. Five novices and seven urology experts performed the procedure. The mean questionnaire score was 4.25 (standard deviation, 0.37). The model was able to hold 50 mL of air, and the pressure in the collecting system ranged from 6 to 33 mmHg. Repeated punctures were possible even when a 16-Fr access sheath was inserted. Our new training model included the self-healing properties of supramolecular hydrogels, which are tough and flexible and can be evaluated using ultrasonography. According to the questionnaire score, the model was highly satisfactory and has potential as a new educational tool.

Prognostic Value of Novel Natriuretic Peptide Index After Percutaneous Coronary Intervention.

BACKGROUND: The predictive value of both atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is well known. This study evaluated the prognostic value of a novel natriuretic peptide index (NPI) combining ANP and BNP. Methods and Results: This study included 849 consecutive patients with coronary artery disease who underwent successful percutaneous coronary intervention (PCI). Patients were followed up clinically for up to 3 years or until the occurrence of major adverse cardiac events (MACE). The primary endpoint was a composite of all-cause death and non-fatal myocardial infarction. The NPI (pg/mL) was defined as √ANP×BNP. MACE occurred in 73 patients (8.6%) during the follow-up period. Receiver operating characteristic curve analysis showed the highest area under the curve for NPI (0.779) compared with ANP and BNP (0.773 and 0.755, respectively). A risk analysis of MACE occurrence adjusted for the multivariable model showed the highest hazard ratio (HR) for NPI (1.33; 95% confidence interval [CI] 1.18-1.51; P<0.001) compared with ANP and BNP (HR 1.25 [95% CI 1.13-1.39] and 1.30 [95% CI 1.13-1.49], respectively; P<0.001). The NPI was a significant independent predictor of MACE, among other clinical parameters, in the multivariable analysis. CONCLUSIONS: Compared with ANP and BNP, the NPI was more effective in predicting future adverse events after PCI.

Optimal medical therapy after percutaneous coronary intervention in very elderly patients with coronary artery disease.

BACKGROUND: It is still unclear whether optimal medical therapy (OMT) after percutaneous coronary intervention (PCI) has beneficial effects on long-term clinical outcomes in patients aged ≥80 years with coronary artery disease (CAD). METHODS: This study analyzed the time to the first major adverse clinical event including death or nonfatal myocardial infarction (MI), for up to 3 years after PCI using multicenter registry data. Data for 1056 patients aged > 80 years successfully treated with PCI were included in the analysis. OMT was defined as a combination of antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. RESULTS: In total, 204 (19%) patients in this study received OMT and 852 (81%)　received sub-OMT. During a median follow-up of 725 days, adverse clinical events occurred in 183 patients (death, n=177; nonfatal MI, n=6). Kaplan-Meier analysis showed that patients who received OMT had a lower probability of adverse clinical events than those who received sub-OMT (p<0.01, log-rank test). Propensity score matching yielded 202 patient-pairs treated with OMT or sub-OMT, in whom 64 adverse clinical events (death, n=56, nonfatal MI, n=4) occurred during follow-up. OMT remained significant in the reduction of the risk of adverse clinical events in a multivariate Cox proportional hazards model (hazard ratio 0.44; 95% confidence interval 0.26-0.75; p=0.003). CONCLUSIONS: OMT after PCI was associated with significantly fewer adverse clinical events, including all-cause death and nonfatal MI, in patients aged ≥ 80 years with CAD. OMT might be safe and effective for these very elderly patients.

Effect of smartphone-based cognitive behavioral therapy app on insomnia: a randomized, double-blind study.

STUDY OBJECTIVES: This study assessed the effects and safety of the smartphone-based cognitive behavioral therapy for insomnia (CBT-I) app compared with the sham app. METHODS: In this multicenter, double-blind, and parallel-group study, 175 patients with insomnia were randomized to a smartphone-based CBT-I app (Active, n = 87) or a sham app (Sham, n = 88) group. The primary endpoint was the change in Athens Insomnia Score (AIS) from baseline after 8 weeks of treatment. RESULTS: The change in AIS (mean ± standard deviation) from baseline, assessed using a modified-intent-to-treat analysis, was -6.7 ± 4.4 in the Active group and -3.3 ± 4.0 in the Sham group. The difference in the mean change between the groups was -3.4 (p < .001), indicating a greater change in the Active group. The change in CGI-I from the baseline was 1.3 ± 0.8 in the Active group and 0.7 ± 0.8 in the Sham group (p < .001). The proportion of patients with an AIS less than 6 was 37.9% in the Active group and 10.2% in the Sham group (p < .001). As for the safety assessment, no adverse reactions or device failures were detected in the Active group. CONCLUSIONS: This study demonstrated the effectiveness of a smartphone-based CBT-I system for treating insomnia. CLINICAL TRIAL REGISTRATION: ID: jRCT2032210071; trial name: Sham (software)-controlled, multicenter, dynamic allocation, double-blinded study of non-medication therapy with a software Yukumi in patients with insomnia disorders (verification study); URL: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210071.

A Stratified Analysis of the Risk Associated With Low Body Mass Index for Patients After Percutaneous Coronary Intervention.

AIMS: The relationship between low body mass index (BMI) and prognostic factors for patients with coronary artery disease, commonly observed in elderly individuals in Japan, is important. Few studies have evaluated the prognosis for patients with low BMI after percutaneous coronary intervention (PCI). Using a multivariable-adjusted model and data from a prospective cohort registry, we analyzed the risk associated with low BMI for patients after PCI. METHODS: This prospective, multicenter registry included 5965 consecutive patients with coronary artery disease who underwent successful PCI. The patients were followed-up clinically for up to 3 years or until the occurrence of major adverse cardiac events. The primary endpoint was all-cause death and nonfatal myocardial infarction composite. RESULTS: Primary events occurred in 639 (10.7%) patients during the follow-up period. A risk analysis of the primary endpoint adjusted for the multivariable model showed a significant increase in risk for elderly individuals, underweight individuals [HR 1.43 (95% confidence interval (CI), 1.10-1.85), P＜0.001], those with diabetes mellitus (DM), peripheral artery disease, low left ventricular ejection fraction or acute coronary syndrome (ACS), and smokers. A stratified adjusted risk analysis based on BMI levels showed that the risk associated with underweight status was significantly pronounced for male patients, those aged 60-74 years, and those with DM or ACS. CONCLUSION: Underweight patients with several risk factors significantly increased risk after PCI. Furthermore, the risk associated with low BMI was significantly more pronounced for men, individuals aged 60-74 years, and patients with DM or ACS.

A Propensity Score Matched Analysis of Statin Effects on Major Adverse Cardiac Events after Percutaneous Coronary Intervention in Patients Over 75 Years Old.

Objective In an extremely aging society, it is beneficial to reconsider the value of medical treatment for extremely elderly patients. We therefore focused on the efficacy of statin therapy in extremely elderly patients. This study investigated the efficacy of statins for secondary prevention in patients over 75 years old. Methods This prospective multicenter registry included 1,676 consecutive extremely elderly patients with coronary artery disease who underwent successful percutaneous coronary intervention (PCI). The patients were followed up clinically for up to three years or until the occurrence of major adverse cardiac events (MACEs), defined as a composite of all-cause death and non-fatal myocardial infarction. Using propensity score methodology to eliminate selection bias, in a 1:1 matching ratio, we selected 466 pairs of patients for the analysis. Results During the median follow-up period of 25 months, MACEs occurred in 176 patients. The Kaplan-Meier analysis showed that statin treatment correlated with a lower probability of initial MACE occurrences within 30 days compared with no statin treatment (log-rank test, p<0.001). According to a landmark analysis at day 30, statin treatment still showed consistent effectiveness for reducing MACE occurrence during the follow up period (p=0.04). A multivariable Cox hazard analysis showed that statin therapy significantly reduced MACE occurrence (hazard ratio 0.55 [0.40-0.75], p<0.001). In the stratification analysis, statin therapy was especially beneficial in patients without symptomatic heart failure. Conclusion Statins were effective in preventing MACEs in extremely elderly patients after PCI.

Group V Secretory Phospholipase A2 Regulates Endocytosis of Acetylated LDL by Transcriptional Activation of PGK1 in RAW264.7 Macrophage Cell Line.

AIMS: It was suggested that group V secretory phospholipase A2 (sPLA2-V) existed in the nucleus. This study examined whether nuclear sPLA2-V plays a role in endocytosis of acetylated low-density lipoprotein (AcLDL) in monocyte/macrophage-like cell line RAW264.7 cells. METHODS: RAW264.7 cells were transfected with shRNA vector targeting sPLA2-V (sPLA2-V-knockdown [KD] cells) or empty vector (sPLA2-V-wild-type [WT] cells). AcLDL endocytosis was assessed by incubation with 125I-AcLDL or AcLDL conjugated with pHrodo. Actin polymerization was assessed by flow cytometry using Alexa Fluor 546-phalloidin. RESULTS: In immunofluorescence microscopic studies, sPLA2-V was detected in the nucleus. ChIP-Seq and ChIP-qPCR analyses showed binding of sPLA2-V to the promoter region of the phosphoglycerate kinase 1 (Pgk1) gene. In the promoter assay, sPLA2-V-KD cells had lower promoter activity of the Pgk1 gene than sPLA2-V-WT cells, and this decrease could be reversed by transfection with a vector encoding sPLA2-V-H48Q that lacks enzymatic activity. Compared with sPLA2-V-WT cells, sPLA2-V-KD cells had decreased PGK1 protein expression, beclin 1 (Beclin1) phosphorylation at S30, and class III PI3-kinase activity that could also be restored by transfection with sPLA2-V-H48Q. sPLA2-V-KD cells had impaired actin polymerization and endocytosis, which was reversed by introduction of sPLA2-V-H48Q or PGK1 overexpression. In sPLA2-V-WT cells, siRNA-mediated depletion of PGK1 suppressed Beclin1 phosphorylation and impaired actin polymerization and intracellular trafficking of pHrodo-conjugated AcLDL. CONCLUSIONS: Nuclear sPLA2-V binds to the Pgk1 gene promoter region and increases its transcriptional activity. sPLA2-V regulates AcLDL endocytosis through PGK1-Beclin1 in a manner that is independent of its enzymatic activity in RAW264.7 cells.

Synergic Effects of Surfactant and Chelating Agent on Stubborn Keratin Grime for Easy Cleaning.

We report on the synergic effect of surfactants and chelating agents on the mechanism to remove stubborn keratin grime (keratin-Ca), which is bound with calcium ions and one of the most difficult grimes to remove, in order to make it easier to clean bathtubs in less time and with less scrubbing. Our approach was to focus on keratin swelling, which we achieved by applying aqueous solutions with chelating agents and anionic surfactants, the combination of which greatly improved the swelling ratio, resulting in quick, easy removal of keratin-Ca with water rinsing and little scrubbing. For the swelling process, we added chelating agents and anionic surfactants to swell the keratin-Ca by both capturing calcium ions and improving solution permeation. Furthermore, we measured the structural change of the keratin-Ca during swelling by TD-NMR and confirmed that a certain combination of chelating agent and anionic surfactant improved swelling by affecting not only the amorphous part such as the keratin matrix, but also the crystalline part such as the intermediate filaments (IFs).

Glutaredoxin-1 levels in plasma can predict future events in patients with cardiovascular diseases.

Reactive oxygen species that increase during cardiovascular disease (CVD) react with protein cysteine residues to form a glutathione adduct by S-glutathionylation, which is selectively removed by glutaredoxin-1 (Glrx). We previously showed that S-glutathionylation and Glrx play important roles in mouse models of CVD, such as heart failure and peripheral artery disease models. However, there are few clinical studies on Glrx in CVD. Although Glrx is a cytosolic protein expressed in various organs, it is detectable in human plasma. Studies have reported that Glrx in plasma is a potential disease maker, such as CVD and chronic kidney disease and diabetes, however, it remains unclear whether Glrx is related to the prognosis of patients with CVD. The purpose of this study was to elucidate whether Glrx levels in plasma are associated with future events in patients with CVD. Plasma levels of Glrx were measured in 555 patients with CVD who underwent cardiac catheterization using enzyme-linked immunosorbent assay. All patients were followed prospectively for ≤36 months or until occurrence of adverse events, including all-cause death, non-fatal myocardial infarction, and worsening heart failure. During a mean follow-up period of 33 months, 54 adverse events occurred. Kaplan-Meier analysis showed that higher levels of Glrx (>0.622 ng/mL, determined by receiver-operating characteristic curve) resulted in a higher probability for adverse events compared with lower levels of Glrx (≤0.622 ng/mL) (P < 0.01, log-rank test). Multivariate Cox proportional hazards analysis showed that Glrx was a significant predictor of adverse events after adjustment for known risk factors. In conclusion, levels of plasma Glrx >0.662 ng/mL can predict future events in patients with CVD.

Effects on physical performance of high protein intake for critically ill adult patients admitted to the intensive care unit: A retrospective propensity-matched analysis.

OBJECTIVES: This study aimed to examine the effects of protein intake on physical performance in critically ill adult patients admitted to the intensive care unit (ICU). METHODS: This was a retrospective cohort study of adult patients mechanically ventilated over 48 h in the ICU who were classified into two groups based on the amount of protein intake: >1.0 g/kg/d (high-protein group) or <1.0 g/kg/d (low-protein group). After adjustment for possible confounding factors with propensity score matching, we compared muscle strength at the time of ICU discharge and the rate of recovery to independent walking between the two groups. RESULTS: One-to-one propensity score matching created 20 pairs. The high-protein group had significantly higher muscle strength than the low-protein group at the time of discharge from the ICU. In addition, the rate of recovery to independent walking before hospital discharge was higher in the high-protein group than the low-protein group (16 of 20 patients [80%] vs. 8 of 20 patients [40%]; P = 0.032). CONCLUSIONS: Our findings indicate that a sufficient amount of protein intake may lead to a higher rate of recovery to independent walking before discharge from the hospital in critically ill patients admitted to the ICU. This finding is likely related to preserved muscle strength at the time of ICU discharge.

The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation.

Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase-like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage. Conclusions Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with myocardial infarction.

BACKGROUND: Renal dysfunction, defined as a lower estimated glomerular filtration rate (eGFR), has been shown to be related to cardiovascular events in patients with myocardial infarction (MI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of cardiac death and recurrence of MI in patients who have had MI. METHODS AND RESULTS: Urinary ß2-microglobulin (ß2MG) was measured in 681 consecutive patients with MI in our hospital. All patients were followed up for <12 years or until the occurrence of cardiac death and MI. During a median follow-up period of 6 years, the cumulative cardiac death rate was 5.4%, and the MI rate was 3.1%. When outcomes were divided into two groups according to the ß2MG levels, cardiac death and MI rates were lower in patients with lower levels of ß2MG (<0.319 mg/gCre: determined by receiver operating characteristic analyses) than in those with ß2MG ≥0.319 mg/gCre (5.9% versus 17.1%, p<0.01). When outcomes were stratified according to the ß2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that cardiac death and MI rates increased depending on an increase in the ß2MG levels (p<0.05). Moreover, multivariate Cox analyses revealed that high levels of ß2MG were a significant independent predictor of adverse events (hazard ratio: 1.956; 95% confidence interval: 1.014-3.774; p = 0.045). The addition of high levels of ß2MG to conventional risk factors, including eGFR and urinary albumin, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.5447, p = 0.0002; IDI 0.0126, p = 0.0454). CONCLUSION: Renal tubulointerstitial damage, as assessed by urinary ß2MG, is associated with the occurrence of cardiac death and recurrence of MI independent of renal glomerular function in patients with MI.

Echolucency of carotid plaque is useful for selecting high-risk patients with chronic coronary artery disease who benefit from intensive lipid-lowering therapy.

BACKGROUND: Ultrasound assessment of the carotid artery provides prognostic information on coronary events. This study examined whether ultrasound assessments of plaque echolucency of the carotid artery are useful for identifying patients with coronary artery disease (CAD) who are at high risk but could benefit from lipid-lowering therapy for secondary prevention. METHODS: Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis was performed in 393 chronic CAD patients with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL on statin therapy. All patients were prospectively followed up for a maximum of 96 months or until the occurrence of one of the following coronary events: cardiac death, nonfatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. RESULTS: During the follow-up period, 45 coronary events occurred. Patients were stratified by IBS (≤-16.3 or >-16.3 dB, median value) and LDL-C level (<70 or 70-99 mg/dL). Multivariate Cox proportional hazards analysis showed that patients with lower IBS and LDL-C 70-99 mg/dL had significantly higher probabilities of coronary events compared with those with higher IBS and LDL-C <70 mg/dL, after adjustment for a baseline model of risk factors (hazard ratio 5.15; 95% confidence interval 1.21-22.0, p = 0.03). In contrast, patients with lower IBS and LDL-C <70 mg/dL had an improved prognosis comparable with those with higher IBS. Addition of LDL-C levels to the baseline model of risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) in patients with lower IBS (NRI, 0.44, p = 0.04; and IDI, 0.035, p < 0.01), but not in those with higher IBS. CONCLUSIONS: Evaluation of echolucency of the carotid artery was useful for selecting CAD patients at high risk of secondary coronary events but who could benefit from lipid-lowering therapy.

Subarachnoid Hemorrhage Related to a Ruptured Anterior Spinal Artery Aneurysm Associated with Bilateral Vertebral Artery Occlusion.

Objective: We report a rare case of a ruptured anterior spinal artery (ASA) aneurysm caused by bilateral vertebral artery (VA) occlusion. Case Presentations: A 78-year-old man suddenly developed severe headache and slight hemiparesis, and was admitted to our hospital. Computed tomography (CT) revealed subarachnoid hemorrhage, mainly in the posterior fossa. On emergency angiography, the right VA terminated at the origin of the posterior inferior cerebellar artery (PICA), and anastomoses between the PICA and the anterior inferior cerebellar artery (AICA) were observed, in addition to a saccular 3-mm aneurysm with bleb originating from the PICA-AICA anastomosis. Left vertebral arteriography demonstrated that the left VA was occluded segmentally at the V4 level and revealed a tortuous arterial network filling the distal VA. Based on the location of the bleeding, the right VA aneurysm was considered to have ruptured. After balloon test occlusion of the right VA, parent artery occlusion was performed without complications. The patient had no neurological changes immediately after surgery, but several hours later, he stopped breathing. Retrospective analysis revealed an ASA aneurysm, which was determined to be the bleeding source. Although conservative treatment was performed, he died the fourth day after onset without neurological improvement. Conclusion: In cases of subarachnoid hemorrhage associated with bilateral VA occlusion, an aneurysm formed by hemodynamic stress may be the source of hemorrhage. It is important to suspect aneurysms in the extracranial collaterals, such as the ASA, and intracranial collaterals such as the PICA-AICA anastomosis.

Improvement in Brachial Endothelial Vasomotor Function and Brachial-Ankle Pulse Wave Velocity Reduces the Residual Risk for Cardiovascular Events after Optimal Medical Treatment in Patients with Coronary Artery Disease.

AIM: To examine whether improvement in flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery and brachial-ankle pulse wave velocity (baPWV) has an additive effect on achieving optimal goals of traditional risk factors to reduce cardiovascular risk in patients with coronary artery disease (CAD). METHODS: We assessed 323 patients with CAD and impaired vascular function, defined as an impaired FMD of the brachial artery (＜5.5%) and increased baPWV (＞1,440 cm/sec). After FMD and baPWV measurements at 24 weeks of optimal medical treatment (OMT), the study patients were followed up for ＜60 months or until a composite of cardiac death, nonfatal myocardial infarction (MI), unstable angina, or ischemic stroke occurs. RESULTS: During the median follow-up period of 35 months, cardiovascular events occurred in 72 patients. Multivariate Cox hazards analysis showed that patients with an improvement in FMD and baPWV had the lowest probability of future cardiovascular events. In addition, the improvement in FMD and baPWV had a significant incremental effect on the predictive value of the achievement of optimal goals for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). CONCLUSIONS: The improvement in FMD and baPWV had additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD. Thus, serial measurements of FMD and baPWV may be useful for identifying CAD patients at residual risk for adverse cardiovascular events following OMT.

Impact of persistent endothelial dysfunction in an infarct-related coronary artery on future major adverse cardiovascular event occurrence in STEMI survivors.

Although coronary endothelial vasomotor dysfunction predicts future coronary events, few human studies have shown the relationship between persistent endothelial vasomotor dysfunction and major adverse cardiovascular events (MACE) using serial assessments in the same coronary artery. This study examined whether persistent endothelial vasomotor dysfunction is related to MACE occurrence in the infarct-related coronary artery (IRA) of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessments of the coronary vasomotor response to acetylcholine (ACh). This study included 169 consecutive patients with a first acute STEMI due to left anterior descending coronary artery (LAD) occlusion and successful reperfusion therapy with percutaneous coronary intervention. Vasomotor response to ACh in the LAD was measured within 2 weeks of acute myocardial infarction (AMI) (first test) and repeated 6 months (second test) after AMI under optimal anti-atherosclerotic therapy. MACE was defined as the composite of all-cause death, non-fatal MI, angina recurrence requiring percutaneous intervention or surgical bypass, and hospitalization for heart failure. We followed up 126 patients for a period of ≤ 60 months until MACE occurrence after second test. Nineteen MACEs occurred during the follow-up. The log-rank test, Kaplan-Meier curves and univariate Cox proportional hazards regression analysis showed that MACE occurrence was significantly associated with the persistent impairment of epicardial coronary artery dilation and coronary blood flow increases in response to ACh (log-rank test, p < 0.001 and p < 0.001, respectively) (Hazard ratio, p = 0.001 and p = 0.002, respectively). Persistent impairment of endothelial vasomotor function in the infarct-related conduit arterial segment and resistance arteriole were the significant predictor of future MACE occurrence in STEMI survivors.