Clinical Differences of Recent Myocardial Infarction Compared With Acute Myocardial Infarction　- Insights From the Tokyo CCU Network Multicenter Registry.

BACKGROUND: Characteristics and treatment outcomes of acute myocardial infarction (AMI) patients have been studied; however, those of recent myocardial infarction (RMI) patients remain unclear. This study aimed to clarify characteristics, treatment strategy, and in-hospital outcomes of RMI patients in the Tokyo CCU network database.Methods and Results:In total, 1,853 RMI and 12,494 AMI patients from the Tokyo CCU network database during 2013-2016 were compared. Both RMI and AMI were redefined by onset times of 2-28 days and ≤24 h, respectively. The RMI group had a higher average age (70.4±12.9 vs. 68.0±13.4 years, P<0.001), more women (27.6% vs. 23.6%, P<0.001), lower proportion of patients with chest pain as the chief complaint (75.2% vs. 83.6%, P<0.001), higher prevalence of diabetes mellitus (35.9% vs. 31.0%, P<0.001), and higher mechanical complication incidence (3.0% vs. 1.5%, P<0.001) than did the AMI group. Thirty-day mortality was comparable (5.3% vs. 5.8%, P=0.360); major causes of death were cardiogenic shock and mechanical complications in the AMI and RMI groups, respectively. Death from mechanical complications (not onset time) in the AMI group plateaued almost 1 week after hospitalization, whereas it continued to increase in the RMI group. CONCLUSIONS: Both RMI and AMI patients have distinctive clinical features, sequelae, and causes of death. Although treatment of RMI patients adhered to guidelines, it was insufficient, and death from mechanical complications continues to increase.

New non-invasive indexes of arterial stiffness are significantly correlated with severity and complexity of coronary atherosclerosis.

BACKGROUND: Endothelial dysfunction and increased arterial stiffness gradually develop before the manifestation of catastrophic cardiovascular events. Therefore, detection and assessment of vascular function are required to address pre-existing pathological conditions. However, the currently available diagnostic devices and methods are insufficient due to variability among investigators and the time-consuming nature of manual procedures. METHODS: Recently, novel devices were developed for the detection of both arterial stiffness and endothelial dysfunction in a single blood pressure measurement using a cuff-oscillometric technique (AVE-1500, Shisei Datum, Japan). API (arterial pressure volume index) is defined as the reciprocal of the slope of the tangent of the brachial artery pressure-volume curve, and AVI (arterial velocity pulse index) is defined as the ratio of the difference between the ejection and reflection waves. In the present study, we performed retrospective, cross-sectional analyses of subjects (n = 102; mean age = 70.5 ± 10.4 years) with detailed coronary angiographic examinations and clinical background parameters. RESULTS: After adjusting for various variables using multiple linear regression analyses, we found that API, but not AVI, was significantly correlated with coronary artery severity and complexity scores. CONCLUSIONS: We propose that API may be a new vascular index useful for monitoring and assessing the severity and complexity of atherosclerosis in subjects with coronary artery disease and for evaluating atherosclerotic diseases.

Anti-interleukin-5 and multiple autoantibodies are associated with human atherosclerotic diseases and serum interleukin-5 levels.

Atherosclerotic diseases, such as coronary artery disease and peripheral artery disease, are systemic disorders and among the leading causes of mortality and morbidity throughout the world. However, the exact pathophysiological mechanisms underlying the development of atherosclerosis remain unknown; currently, atherosclerosis is thought to involve an inflammatory process. Systemic inflammatory reactions and accumulation of immune cells in atherosclerotic lesions in situ are considered essential. We have comprehensively analyzed autoantibodies in patients with atherosclerosis by means of a newly developed high-throughput autoantibody analysis system. A wide range of autoantibodies was found in sera from patients with atherosclerosis. After we statistically analyzed the titers of each autoantibody with conventional techniques, the results underwent text-mining analyses based on natural language processing. Combinatory analysis revealed a close association between anti-interleukin (IL)-5 antibody and atherosclerosis. Titers of anti-IL-5 antibodies and serum IL-5 concentrations were also closely associated with other risk factors, such as low-density lipoprotein cholesterol, serum creatinine, fasting plasma glucose, gender, and age, suggesting that suppressed IL-5 function mediated by autoantibodies in patients with atherosclerosis plays an important role in the disease process. To validate the clinical significance of these findings, we computed the specificity and sensitivity of titers of anti-IL-5 autoantibodies for human atherosclerosis. When antibody titers of 1.49 were assumed to predict the presence of atherosclerosis, the sensitivity was 95.0% and the specificity 91.0%, with an area under the curve of 0.940. Our results provide important clues to understanding the role of autoantibody-mediated immune reactions in human atherosclerosis and suggest novel therapeutic opportunities for management of the disease.

Clinical features and predictors of non-cardiac death in patients hospitalised for acute myocardial infarction: Insights from the Tokyo CCU network multicentre registry.

BACKGROUND: Patients with acute myocardial infarction (AMI) commonly have multiple comorbidities, and some die in hospitals due to causes other than cardiac complications. However, limited information is available on noncardiac death in patients hospitalised for AMI. Therefore, the present study was performed to determine the incidence, annual trend, clinical characteristics, and predictors of in-hospital non-cardiac death in patients with AMI using the Tokyo Cardiovascular Care Unit (CCU) network registry. METHODS: The registry included 38,589 consecutive patients with AMI who were admitted to the CCU between 2010 and 2019. The primary endpoint was in-hospital noncardiac death. Further, predictors of cardiac and non-cardiac death were identified. RESULTS: The incidence of all-cause in-hospital mortality was 7.0% (n = 2700), and the proportion of mortality was 15.6% (n = 420) and 84.4% (n = 2280) for noncardiac and cardiac causes, respectively. The proportion of noncardiac deaths did not change annually over the last decade (p = 0.66). After adjusting for all variables, age, Killip classification grade, peak creatine kinase, hemoglobin, serum creatinine, and C-reactive protein were common predictors of cardiac and non-cardiac deaths. Indicators of malnutrition, such as lower body mass index (kg/m2) [odds 0.94, 95%CI (0.90-0.97), p < 0.001] and serum low-density lipoprotein cholesterol level (per 10 mg/dl) [odds 0.92, 95%CI (0.89-0.96), p < 0.001] were the specific predictors for non-cardiac deaths. CONCLUSIONS: The incidence of in-hospital noncardiac death was significant in patients with AMI, accounting for 15.6% of all in-hospital mortalities. Thus, prevention and management of non-cardiac complications are vital to improve acute-phase outcomes, especially those with predictors of non-cardiac death.

Analysis of interferon-beta mRNA stability control after poly(I:C) stimulation using RNA metabolic labeling by ethynyluridine.

Interferon-beta (IFN-ß) is a critical antiviral cytokine and is essential for innate and acquired immune responses to pathogens. Treatment with polyinosinic:polycytidylic acid (poly(I:C)) induces transient accumulation of IFN-ß mRNA, which involves an increase and a decrease of IFN-ß mRNA. This phenomenon has been extensively analyzed as a model for understanding the mechanisms of transient gene induction in response to external stimuli. Using a new RNA metabolic labeling method with ethynyluridine to directly measure de novo RNA synthesis and RNA stability, we reassessed both de novo synthesis and degradation of IFN-ß mRNA. We found that transcriptional activity is maintained after the maximum accumulation of IFN-ß mRNA following poly(I:C) treatment on immortalized human bronchial epithelial cells. We also observed an unexpected change in the stability of IFN-ß mRNA before and after the maximum accumulation. The results indicate that this method of RNA metabolic labeling provides a general approach for the simultaneous analysis of transcriptional activity and mRNA stability coupled with transcriptional timing.

Upper-Arm SBP Decline Associated with Repeated Cuff-Oscillometric Inflation Significantly Correlated with the Arterial Stiffness Index.

We evaluated the clinical significance of the new non-invasive vascular indices to explore their potential utility using repeated cuff-oscillometric inflation. In 250 consecutive outpatients, we performed a cross-sectional, retrospective, single-center, observational study to investigate sequential differences in arterial stiffness using blood pressure, arterial velocity pulse index (AVI), and arterial pressure volume index (API) with repeated measurements. Males accounted for 62.7% of the patients, and the mean age was 68.1 ± 12.1 years. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the first reading in repeated measurements were 133.07 ± 21.20 mmHg and 73.94 ± 13.56 mmHg, respectively. The mean AVI and API were 23.83 ± 8.30 and 31.12 ± 7.86, respectively. In each measurement of these parameters, although DBP and AVI did not show significant changes throughout repeated measurements, SBP and API decreased significantly according to the measurement orders. Furthermore, changes in SBP and API were significantly correlated in several of the models. In this study, it was concluded that upper-arm SBP decline associated with repeated cuff-oscillometric inflation was significantly correlated with the arterial stiffness index. The findings of this study will allow clinicians to easily recognize the progression of atherosclerosis through regular, routine practice. In conclusion, this study suggests that changes in repeated SBP measurements may be predictive of arterial stiffness and atherosclerosis.

10-Year Temporal Trends of In-Hospital Mortality and Emergency Percutaneous Coronary Intervention for Acute Myocardial Infarction.

Background: The mortality rate of acute myocardial infarction (AMI) has improved dramatically because of reperfusion therapy during the last 40 years; however, recent temporal trends for AMI have not been fully clarified in Japan. Objectives: The purpose of this study was to elucidate the temporary trend in in-hospital mortality and treatment of AMI for the last decade in the Tokyo Metropolitan area. Methods: We enrolled 30,553 patients from the Tokyo Cardiovascular Care Unit Network Registry, diagnosed with AMI from 2007 to 2016, as part of an ongoing, multicenter, cohort study. We analyzed the temporal trends in basic characteristics, treatment, and in-hospital mortality of AMI. Results: The overall emergency percutaneous coronary intervention (PCI) rate significantly increased (P < 0.001). In particular, it remarkably increased in patients older than 80 years of age (58.3% to 70.3%, P < 0.001) and patients with Killip III or IV (Killip III, 46.9% to 65.7%; Killip IV, 65.2% to 76.6%, P < 0.001 for both). The crude and age-adjusted in-hospital mortality remained low (5.2% to 8.2% and 3.4% to 5.5%, respectively) and significantly decreased during the decade (P < 0.001). The in-hospital mortality remarkably decreased in patients older than 80 years of age (17.3% to 12.7%, P < 0.001) and in those with cardiogenic shock (38.5% to 27.3%, P < 0.001). Conclusions: This large cohort study from Tokyo revealed that in-hospital mortality of AMI significantly decreased with the increase in emergency percutaneous coronary intervention rate over the decade, particularly for high-risk patients such as older patients and those with cardiogenic shock.

Subclavian artery pseudoaneurysm in vascular Behcet's disease repaired using endovascular treatment: A case report of the clinical course over 10 years.

The vascular involvement in patients with Behcet's disease is defined as vascular Behcet's disease, which can greatly influence the prognosis. However, there are few reports on endovascular treatment (EVT) for subclavian pseudoaneurysms with long-term prognosis over 10 years. We present the case of a 42-year-old man with left subclavian artery pseudoaneurysm due to vascular Behcet's disease who was treated with EVT along with immunosuppressive therapies. Subsequently, 8 years after, the aneurysm recurred in the stent with stent fracture. Therefore, additional EVT was performed. We present the details of the patient's clinical course over 10 years after the EVT. .

Severity by National Institute of Health Stroke Scale Score and Clinical Features of Stroke Patients with Patent Foramen Ovale Stroke and Atrial Fibrillation.

The comparative severity of patent foramen ovale (PFO)-related stroke in patients without atrial fibrillation (AF) and AF-related stroke in patients without PFO is unknown. Therefore, we compared the severity of PFO-related stroke and AF-related stroke. Twenty-six patients who underwent transesophageal echocardiography (TEE) were diagnosed with cardioembolic stroke from July 2018 to March 2020. Cases with AF detected by electrocardiograms or thrombus in the left atrium or left atrial appendage on TEE were included in the AF-related stroke group. Cases with a positive microbubble test on the Valsalva maneuver during TEE, and with no other factors that could cause stroke, were included in the PFO-related stroke group. This study was designed as a single-center, small population pilot study. The stroke severity of the two groups by the National Institute of Health Stroke Scale (NIHSS) score was compared by statistical analysis. Of the 26 cases, five PFO-related stroke patients and 21 AF-related stroke patients were analyzed. The NIHSS score was 2.2 ± 2.8 and 11.5 ± 9.2 (p-value < 0.01), the rate of hypertension was 20.0% and 85.7% (p-value = 0.01), and the HbA1c value was 5.5 ± 0.2% and 6.3 ± 1.3% (p-value = 0.02) in the PFO-related and AF-related stroke groups, respectively. Compared with AF-related stroke patients, stroke severity was low in PFO-related stroke patients.

Successful prediction of cardiovascular risk by new non-invasive vascular indexes using suprasystolic cuff oscillometric waveform analysis.

BACKGROUND: Recently, new non-invasive vascular indexes named arterial velocity pulse index (AVI) and arterial pressure volume index (API), which is evaluated by a multifunctional blood pressure monitoring device, were developed using cuff oscillometric technologies and suprasystolic cuff oscillometric wave measurement. However, although a few studies including a computational model have been performed, data on subjects with cardiovascular diseases in actual outpatient clinics remain scant. METHODS: We examined a total 252 consecutive outpatients and analyzed two vascular indexes with various clinical parameters to explore potential utilities of these two indexes in actual clinical settings. RESULTS: Although we found that two indexes were correlated with each other, the clinical implications of these indexes seemed to differ. Our analyses showed that AVI significantly correlated with augmentation index, but not with flow-mediated dilatation, and multivariate analyses suggested that enhanced AVI represents increased workload on the heart with elevated central blood pressure. In contrast, although the results of analyses performed to identify clinical parameters independently related to API were obscure and non-specific, after adjustment for multiple clinical variables, API was found to be significantly and independently associated with both Framingham Cardiovascular Risk Score and the Suita Score, suggesting that API is a useful predictor of future cardiovascular events. CONCLUSIONS: These two new vascular indexes might be useful in actual clinical settings to evaluate cardiovascular risks with various clinical backgrounds.

Identification of bona fide alternative renin transcripts expressed along cortical tubules and potential roles in promoting insulin resistance in vivo without significant plasma renin activity elevation.

Renin belongs to a family of aspartyl proteases and is the rate-limiting enzyme in the synthesis of the potent vasoactive peptide angiotensin II. Processing of renal renin has been extensively investigated in juxtaglomerular granular cells, in which prorenin and active renin are present in secretory condensed granules. Previous studies demonstrated alternative renin transcription in rat adrenal glands. Different studies reported novel intracellular forms of renin deduced from novel 5' variants derived from renin mRNA in both mice and humans. Comprehensive detailed studies in genetically engineered mice showed that both a secreted and an intracellular form of renin plays divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system; however, the presence, regulation, and functions of these renin isoforms in kidney and adrenal gland are not fully understood in mice. To investigate the characteristics of renin isoforms in mice, we performed a systematic inventory of renin transcripts of mice with and without a duplication of the renin gene alternatively from previous studies. We discovered a novel isoform of renin of the Ren2 gene, which conserved functionally important residues of the prosegment and incomplete isoforms of the Ren1C/D gene lacking a pre-pro segment. In situ hybridization assays revealed alternative renin isoforms expressed along cortical tubules. Newly generated transgenic mice with systemic overexpression of alternative renin transcript showed enhanced local angiotensin II generation without elevation of plasma renin activity and systemic insulin resistance in vivo, providing new pathophysiological insights into insulin resistance exaggerated by bona fide renin isoform.