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Constipation has been reported to increase the risk of cardiovascular mortality. Patients with atrial fibrillation (AF) and heart failure (HF) have more comorbidities and an increased bleeding risk. However, it remains unclear whether constipation is associated with an increased risk of incident bleeding complications in AF with HF. Here, we investigated the association between constipation requiring laxatives and major bleeding in AF and HF. We retrospectively analyzed the medical records of 370 consecutive patients hospitalized for AF and congestive HF. Constipation was defined as regularly taking laxatives or having at least two prescriptions for a ≥ 30-day supply of laxatives. Sixty patients experienced major bleeding events during a median follow-up of 318 days. The most common sites of bleeding were lower gastrointestinal (28%, 17/60), upper gastrointestinal (27%, 16/60), and intracranial (20%, 12/60). There were 33 (55%) patients with constipation in the bleeding group and 107 (35%) in the non-bleeding group (P = 0.004). Multivariate Cox regression analysis adjusted for HAS-BLED score, hemoglobin, and direct oral anticoagulant use showed that constipation (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.11–3.08; p = 0.019) was a significant risk factor for major bleeding. We found a significant association between constipation requiring laxatives and major bleeding in patients with AF and HF. These findings indicate the need for constipation prevention in these patients to avoid reliance on invasive defecation management, including laxatives.

BackgroundSpontaneous left atrial intramural hematoma (LAIH) is extremely rare and there are only two cases of spontaneous LAIH involving cardiac amyloidosis (CA) reported in literature. In both cases, LAIH rapidly compromised hemodynamic stability proving to be a rare yet fatal complication.Case summaryAn 83-year-old man presented with cardiogenic shock. Electrocardiogram showed complete atrioventricular block, and echocardiogram revealed severe hypokinesis and left ventricular hypertrophy. Coronary angiography revealed no significant coronary stenosis and tissue biopsy was taken from the left ventricle. The patient was intubated, placed on extracorporeal membrane oxygenation with intra-aortic balloon pump and temporary pacemaker, and admitted to ICU. Day 6 of admission, he became hemodynamically unstable, and presented with atrial fibrillation. Transesophageal echocardiography showed a newly formed large mass in the left atrium. Day 11 of admission, the patient passed away. Autopsy revealed cardiac amyloidosis and showed the mass to be a left atrial intramural hematoma. Diffuse amyloid deposits were found in the myocardium as well as the blood vessel walls of the region surrounding the LAIH.ConclusionLAIH is a rare yet fatal complication of CA. Autopsy revealed diffuse amyloid deposits within the left atrium may lead to left atrial fragility and contribute to development of LAIH. LAIH should be considered as an important differential diagnosis in the setting of a rapidly growing left atrial mass, and in hemodynamic instability in patients with CA.

Several non-invasive methods for pulmonary vascular resistance (PVR) measurement are proposed, but none are sufficiently accurate for use in clinical practice. This study proposes a new echocardiographic method of pulmonary artery wave reflection and investigates its efficacy in managing patients with pulmonary hypertension.Methods and Results:In total, 83 patients with left heart disease, pulmonary arterial hypertension, and chronic thromboembolic pulmonary hypertension (CTEPH), who underwent Doppler echocardiography and right heart catheterization, were included in the study. Pulmonary artery wave reflection was characterized by separating the pulmonary artery pressure waveform into forward and backward (Pb) waves, based on wave intensity. Pulmonary artery pressure waveforms were estimated from continuous Doppler tracings of tricuspid regurgitation velocity, and flow velocity was measured using pulsed Doppler of the right ventricular outflow tract. Pb-peak was compared with catheter hemodynamic indices, and with PVR by Abbas 2003, 2013 and Haddad in relation to increased catheter PVR. Catheter PVR and Pb were strongly correlated (r=0.77, P0.001). The areas under the receiver operator characteristic curve for Pb-peak, PVR by Abbas 2003, 2013 and Haddad were 0.91, 0.72, 0.80, and 0.80, respectively, and were used to detect an increase in PVR (3 Woods units).This study describes a novel, simple, and non-invasive echocardiography method to assess pulmonary wave reflected pressure to identify patients with pulmonary hypertension due to increased PVR.

The COVID-19 pandemic is continuing to have drastic consequences for patients, healthcare workers, and the health system. Its cardiovascular implications have been well described in previous studies, but original reports from Japan are sparse. Validating overseas findings in the Japanese clinical settings is crucial to improve local COVID-19 care and to clarify the pandemic's impacts in the country. This review of available literature demonstrates that in Japanese patients and clinical settings too, there is a close relationship between COVID-19 and the cardiovascular system including cardiovascular complications. On the contrary, secondary effects on cardiovascular practice including service disruptions, telemedicine, and epidemiological changes in Japan have been relatively small.

Left ventricular noncompaction cardiomyopathy (LVNC) is a heart muscle disorder morphologically characterized by reticulated trabeculations and intertrabecular recesses in the left ventricular (LV) cavity. LVNC is a genetically and phenotypically heterogeneous condition, which has been increasingly recognized with the accumulation of evidence provided by genotype-phenotype correlation analyses. Here, we report 2 sporadic adult cases of LVNC; both developed acute heart failure as an initial clinical manifestation and harbored causal sarcomere gene mutations. One case was a 57-year-old male with digenic heterozygote mutations, p.R1344Q in myosin heavy chain 7 (MYH7) and p.R144W in troponin T2, cardiac type (TNNT2), who showed morphological characteristics of LVNC in the lateral to apical regions of the LV together with a comorbidity of non-transmural myocardial infarction, resulting from a coronary artery stenosis. After the removal of ischemic insult and standard heart failure treatment, LVNC became less clear, and LV function gradually improved. The other case was a 36-year-old male with a heterozygote mutation, p.E334K in myosin binding protein C3 (MYBPC3), who exhibited cardiogenic shock on admission with morphological characteristics of LVNC being most prominent in the apical segment of the LV. The dosage of beta-blocker was deliberately increased in an outpatient clinic over 6 months following hospitalization, which remarkably improved the LV ejection fraction from 21% to 54.3%. Via a combination of imaging and histopathological and genetic tests, we have found that these cases are not compatible with a persistent phenotype of primary cardiomyopathy, but their morphological features are changeable in response to treatment. Thus, we point out phenotypic plasticity or undulation as a noticeable element of LVNC in this case report.

To compare the characteristics and clinical course of patients with coronavirus disease (COVID-19) according to the healthcare level of the admitted hospital, to provide an insight into determining the appropriate level of care for each patient.This retrospective, observational study utilized data from the COVID-19 Registry Japan (COVIREGI-JP), the largest Japanese registry of hospitalized patients with COVID-19. Datasets were obtained from reports filed as of May 31, 2022.A total of 59,707 patients (2004 in the primary care group, 41,420 in the secondary care group, and 16,283 in the tertiary care group) from 585 facilities were included in the analysis. Patients with established risk factors for severe disease, such as old age and the presence of comorbidities, were treated at higher care facilities and had poorer initial conditions and in-hospital clinical course, as well as higher mortality. Analysis of the fatality rates for each complication suggested that patients with complications requiring procedures (e.g. pleural effusions, myocardial ischemia, and arrhythmia) may have better survival rates in facilities with specialist availability. The number of deaths and severe COVID-19 cases in this study were notably less than those reported overseas.Our results showed that more difficult COVID-19 cases with poor outcomes were treated at higher care level facilities in Japan. Attending to possible complications may be useful for selecting an appropriate treatment hospital. Healthcare providers need to maintain a broad perspective on the distribution of medical resources.

Coronavirus disease (COVID-19) causes myocardial injury by inducing a cytokine storm in severe cases. Studies have reported that myocardial injury persists for a prolonged period during COVID-19 recovery, and cardiac troponin is a useful indicator of myocardial injury. The interleukin-6 (IL-6) level is known to be associated with the morbidity and mortality of COVID-19, but this association has not been studied during recovery. The current study examined the association between IL-6 levels and myocardial damage during COVID-19 recovery. Four of 209 patients (1.9%) who recovered from COVID-19 had elevated IL-6 levels. All 4 patients tested positive for high-sensitivity troponin T, and 3 patients had subclinical left ventricular (LV) dysfunction according to echocardiography. Positivity for IL-6 during COVID-19 recovery suggests ongoing myocardial damage due to inflammation.

The aim of this study is to investigate myocardial damage in recovering coronavirus disease 2019 (COVID-19) patients with high-sensitivity troponin levels (hsTnT) and echocardiography. In this single-center cohort study, 215 COVID-19 recovered patients were recruited from all over Japan between April and September 2020. Demographic characteristics, hsTnT levels, and echocardiography data were collected for 209 patients, after excluding those without serum samples or good-quality echocardiographic images. The mean (± standard deviation) age was 44 (± 12) years (range: 36-55 years), and 50.7% of the patients were males. The median time interval (interquartile range) from COVID-19 onset to post-recovery examination was 56 days (34-96 days). Seventy-four recovered patients (35.4%) had hsTnT less than detection sensitivity (< 3 pg/mL) and 135 recovered patients (64.6%) had hsTnT ≥ 3 pg/mL. Ejection fraction was more than 50% in all cases. Left ventricular global longitudinal strain (LVGLS) and right ventricular free-wall longitudinal strain (RVFWLS) were reduced in 62 (29.7%) and 8 patients (3.8%), respectively. They were significantly associated with elevated hsTnT levels. In cases with hsTnT above 5 pg/mL, the LVGLS was greatly reduced to 19.0 ± 2.2% (p < 0.001). Multivariate linear regression analysis showed that elevated hsTnT level was an independent predictor of reduced LVGLS (standardized β = -0.34; p < 0.001). In recovered COVID-19 patients, even a slight increase in hsTnT above detection sensitivity was associated with decreased LVGLS. hsTnT and echocardiography may be useful tools to detect myocardial injury in recovered COVID-19 patients.

To determine the prevalence of coronary artery stenosis (CAS) in Japanese hemophiliacs living with HIV- 1 (JHLH), a prospective study at AIDS Clinical Center, Tokyo, which provides care and treatment to nearly 10% of the JHLH was conducted. The study subjects were 76 JHLH who visited our clinic and received coronary computed tomography angiography (CCTA) between January through December 2019. CCTA with radiographic contrast media was used for CAS screening. Coronary artery calcium score (CACS) by CCTA, pulse wave velocity (PWV), electrocardiography, echocardiography, and chest radiography were also included to the screening process. Stenosis of 50% or more by CCTA was defined as moderate to severe CAS. All patients diagnosed with moderate to severe CAS were recommended to undergo coronary angiography (CAG). Among the 76 JHLH, 19 were excluded. Among the enrolled 57 patients, only 5 had complained of chest symptoms. Their median age was 47 years (interquartile range: 44-55 years), prevalence of hypertension 42.1%, diabetes mellitus 14.0%, dyslipidemia 38.6%, and smoking history 52.6%. Moderate to severe CAS was diagnosed in 14 patients by CCTA (24.6% of CCTA tested). Twelve patients agreed to undergo CAG. Seven patients were diagnosed as severe CAS by CAG (12.3% of CCTA received), although only 2 (28.6%) had chest symptoms. PWV and CACS were useful and significant non-invasive markers of moderate to severe CAS (p = 0.016, p < 0.001, respectively). In conclusions, our study identified high prevalence of severe CAS among JHLH. We recommend screening of all HIV-1-infected hemophiliacs with PWV and CACS, regardless of chest symptoms.

A 19-year-old man presented with chest pain after a trans-Pacific flight. Venous thromboembolism was diagnosed and treated with catheter-directed thrombolysis. Genetic testing revealed factor V Leiden mutation. In addition to the flight history and genetic hypercoagulability, a renal abnormality causing an external compression over the inferior vena cava was suspected to be a contributing factor. (Level of Difficulty: Intermediate.), Graphical abstract

Immune checkpoint inhibitors (ICIs) are widely used in various types of cancers and patients. Recently, it has been reported that ICIs aggravate atherosclerosis. This study aimed to identify characteristics that are related to the progression of atherosclerosis.This study was conducted in a single medical center and included 32 patients who were grouped based on the presence of an immune-related adverse event (IRAE). There were 16 IRAE patients and 16 non-IRAE patients. Atherosclerosis was measured as the volume of calcified plaque at the aortic arch on a computed tomography (CT) scan. We measured the volume on CT at 3 time points as follows: before treatment, at ICI initiation, and after 180 days or more.After the first ICI administration, the IRAE group showed significant exacerbation of atherosclerosis compared to the non-IRAE group (P = 0.002). A high volume of plaque was observed in IRAE patients after ICI treatment as compared to before ICI administration (P = 0.058).ICIs tend to hasten atherosclerosis progression in IRAE patients, indicating that high-risk cardiovascular patients should be concerned about cardiovascular events. Moreover, this study suggests the possibility of predicting IRAEs based on the volume of calcified plaques.

A 52-year-old woman presented with a continuous heart murmur at an annual health examination. Coronary computed tomography angiography showed confluent coronary artery fistulas meeting to form a large aneurysm fistulizing to the pulmonary artery. Percutaneous coil embolization was performed, resulting in the disappearance of the coronary artery fistulas and aneurysms. (Level of Difficulty: Intermediate.), Central Illustration, A 52-year-old woman presented with a continuous heart murmur at an annual health examination. Coronary computed tomography angiography showed confluent…

Tobacco smoking is a leading preventable cause of morbidity and mortality worldwide; still, the success rate of smoking cessation is low in general. From the viewpoint of public health and clinical care, an objective biomarker of long-term smoking behavior is sought.Methods and Results: This study assessed DNA methylation as a biomarker of smoking in a hospital setting through a combination of molecular approaches including genetic, DNA methylation and mRNA expression analyses. First, in an epigenome-wide association study involving Japanese individuals with chronic cardiovascular disease (n=94), genome-wide significant smoking association was identified at 2 CpG sites on chromosome 5, with the strongest signal at cg05575921 located in intron 3 of the aryl-hydrocarbon receptor repressor (AHRR) gene. Highly significant (P1×10The present study results support that reversion of AHRR hypomethylation can be a quantifiable biomarker for progress in and observance of smoking cessation, although some methodological points need to be considered.

Cardiovascular complications of coronavirus disease 2019 (COVID-19) are critical for prognosis but have not been elucidated in Japan.Methods and Results:The COVID-19 Registry Japan, which included data from 19,853 individuals at the end of 2020, was analyzed. The incidences of cardiovascular complications were 0.098% for myocarditis/pericarditis/cardiomyopathy, 0.48% for ventricular tachycardia/fibrillation, 0.17% for myocardial ischemia, 0.062% for endocarditis, 0.59% for deep vein thrombosis, 0.19% for pulmonary embolism, and 0.37% for cerebral infarction/hemorrhage. Excluding endocarditis, all complications were associated with increased in-hospital mortality.Cardiovascular complications of COVID-19 were infrequent in Japan but were associated with poor prognosis.

The serum 1,5-anhydro-d-glucitol (1,5-AG) level rapidly decreases concomitantly with urinary glucose excretion in hyperglycemia. 1,5-AG is a sensitive clinical marker of short-term glycemic control, postprandial hyperglycemia and glucose fluctuation. Increasing evidence about the relationship between cardiovascular disease (CVD) and glucose fluctuations have been published. In this review, we summarize the possibilities and limitations of 1,5-AG as a marker of CVD. Research showed that 1,5-AG level is associated with prevalence of CVD and is also a predictive value for cardiovascular (CV) events. Especially in a high risk population, the predictive value of 1,5-AG for CV events becomes more effective. Besides, 1,5-AG is an effective glycometabolic marker that complements HbA1c in terms of glucose fluctuation. Appropriate use of 1,5-AG might lead to improved prognosis for patients or decrease medical financial burden of the population through early detection of glucose disorder and quality glucose control.

A 27-year-old Caucasian male traveler with well-controlled asthma was admitted to our hospital because of severe heart failure (HF). He had a history of cocaine use. Transthoracic echocardiography (TTE) showed severe diffuse hypokinesis of the left ventricle (LV) and a large mobile thrombus in the LV. He was treated with diuretics, inotropes and anticoagulants which led to small improvements in the HF and LV thrombus, however, he needed to undergo left ventricular assist device (LVAD) implantation and surgical removal of a residual LV thrombus due to inotrope-dependency.It is necessary to consider the possibility of cocaine or illicit drug use in a young individual with cardiovascular disease or sudden death even in Japan where cocaine and drugs are prohibited by law, as recreational drug use has been increasing in many countries around the world.

The COVID-19 pandemic has rapidly emerged as one of the biggest public health concerns of the 21st century. Although it was initially reported as a cluster of pneumonia cases, it quickly became apparent that COVID-19 is not merely a respiratory tract infection. Its clinical course is often complicated by cardiovascular manifestations including venous and arterial thrombosis, electrical disturbances, and myocardial damage. In addition, the cardiovascular system is involved not only during infection but also preceding the contraction of the virus; having cardiovascular comorbidities indicates significant vulnerability to the pathogen. As longer-term data continue to accumulate, we now have concerns over its lasting cardiovascular effects after recovery. Moreover, there have been substantial collateral effects on the epidemiology of cardiovascular diseases. Reports of adverse cardiovascular events from vaccination have emerged as new hurdles to our efforts to bring an end to the pandemic. As such, the association between COVID-19 and the cardiovascular system and cardiovascular practice in general is expansive. In this review, we provide an overview of the knowledge and considerations in this field, based on the evidence available at the time of this writing., Graphic abstract Effects of COVID-19 on the Cardiovascular System and Practice Graphic abstract Image, graphical abstract Effects of COVID-19 on the Cardiovascular System and Practice

BACKGROUND: Several studies have reported elevated troponin levels in coronavirus disease 2019 (COVID-19) patients, so we investigated myocardial damage by measuring high-sensitivity troponin T (hsTnT) levels and analyzed the relationship with comorbidities.Methods and Results:Of 209 patients who recently recovered from COVID-19, 65% had an elevated hsTnT level that was higher than levels in patients with acute phase infection despite most patients (79%) having a mild illness. The hsTnT levels correlated with disease severity, sex, comorbidities, and ACEi and ARB use. CONCLUSIONS: Myocardial damage occurs in the recovery phase of COVID-19, and its evaluation, regardless of patient age, should be considered.

The prognosis has improved remarkably in recent years with the development of cancer treatment. With the increase in the number of cancer survivors, complications of cardiovascular disease have become a problem. Therefore, the field of onco-cardiology has been attracting attention. The field of onco-cardiology covers a wide range of areas. In the past, cardiac dysfunction caused by cardiotoxic drug therapies such as doxorubicin (Adriamycin) was the most common cause of cardiac dysfunction, but nowadays, cardiovascular complications caused by aging cancer survivors, atherosclerotic disease in cardiovascular risk carriers, thromboembolism, and new drugs (e.g., myocarditis caused by immune checkpoint inhibitors and hypertension caused by angiogenesis) are becoming more common. In this review, we summarize the latest findings of cardiotoxicity of cancer therapy, appropriate treatment and prevention, and cardiovascular complications of novel chemotherapy, which will increase in demand in the near future.

Balloon pulmonary angioplasty (BPA) has improved the survival rate of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The resolution of symptoms is one of the remaining goals of BPA. Frailty affects the outcome of cardiovascular diseases or treatments. The aim of this study is to assess the association between frailty and outcome of BPA. The resolution of symptoms is evaluated by the post-BPA World Health Organization functional class (WHO-FC). A total of 54 patients with CTEPH were divided into 2 groups by post-BPA WHO-FC (WHO-FC I group; n = 34 vs. WHO-FC ≥ II group; n = 20). Frailty was assessed by physicians using the clinical frailty scale (CFS) at the point of patient admission for their first BPA sessions. Compared to the WHO-FC ≥ II group, the WHO-FC I group was younger (65.6 ± 13.9 years vs. 74.3 ± 8.0 years) and had a lower CFS (3 [3, 4] vs. 4 [4, 6]) (median [25th, 75th percentiles]). The WHO-FC I achievement rates for each CFS score were CFS 3: 82.8%; 4: 53.8%; 5: 25.0%; 6: 33.3%; and 7: 20.0%. Logistic regression analysis showed that CFS was an independent predictor of WHO-FC I achievement (odds ratio 0.50, p = 0.012), but pre-BPA hemodynamic parameters and age were not independent predictors. Whether WHO-FC I can be achieved is predicted by pre-BPA patient frailty but not by pre-BPA hemodynamic parameters and age.

Venous thromboembolism (VTE) is a multifactorial disease. Because low-frequency variants and rare mutations have been found to predispose carriers toward VTE, there is a need for variant discovery in clinical settings. Therefore, we used a whole-exome approach for a young VTE patient with a positive family history. We identified in the proband and his affected mother a rare, functional missense variant of prothrombin, p.Arg541Trp, which contributes to the clinical picture of VTE.

The coronavirus disease 2019 (COVID-19) pandemic has affected presentations of conditions unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself. We investigated the pandemic's effect on incidence and characteristics of pulmonary embolism (PE) cases without the infection. We retrospectively compared non-COVID PE patients during January 16-August 31, 2020 (COVID period) with PE patients during the same period in 2017-2019 (Pre-COVID period). The number of out-of-hospital onset cases was significantly higher during the pandemic than during each of the pre-COVID years. Also, the patients in the COVID period were older, more likely to be free of thrombotic predispositions, had higher mortality risks of PE, and were more likely to arrive at the hospital on emergency transport. Sedentary lifestyles during the pandemic seem to have had considerable effects on presentations of PE.

Amyloidosis and sarcoidosis are systemic diseases that affect multiple organ systems. Accurate diagnosis of cardiac amyloidosis and sarcoidosis is particularly important because cardiac involvement can be fatal. Amyloidosis is characterized by the deposition of amyloid fibrils, and cardiac amyloidosis is classified into amyloid immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) types. Radionuclide tracers for amyloidosis include (a) bone tracers, (b) amyloid-directed molecules, and (c) PET amyloid agents. Bone tracers are particularly sensitive in detection of ATTR type amyloidosis, whereas PET amyloid agents show a higher affinity for the AL type. In sarcoidosis, gallium 67 (67Ga) citrate scintigraphy and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET are pivotal to diagnosis of cardiac sarcoidosis, and 18F-FDG PET/CT has particularly high efficacy in detection of sarcoidosis and monitoring of response to therapy. A major limitation of 18F-FDG is physiologic uptake in the myocardium, which can remain in approximately 20% of patients even after elaborate preparation (eg, prolonged fasting >12-18 hours, modification to a high-fat and low-carbohydrate diet, and injection of unfractionated heparin). This limitation has led to a search for potential new tracers. Recently introduced tracers that show promise include those used in somatostatin receptor imaging and cellular proliferation imaging, which provide detectability as high as that for 18F-FDG without requiring dietary restrictions and have potential for monitoring disease activity. ©RSNA, 2020.

Coronavirus disease (COVID-19) is associated with pulmonary hypertension due to pulmonary embolism, which affects subsequent outcomes. However, definitive diagnosis of pulmonary hypertension is difficult because of the risk of spreading the infection. Here, we assess the utility of plane computed tomography in noninvasively predicting the clinical severity of COVID-19.

The "on-therapy range" of direct oral anticoagulants is the 90% interval of drug concentration. Previously, we reported the on-therapy range of rivaroxaban in a single-center cohort. The present study aimed to confirm the range and intraindividual reproducibility in a multicenter cohort.Eligible patients with non-valvular atrial fibrillation under rivaroxaban treatment for prevention of ischemic stroke were enrolled from nine institutes in Tokyo, Japan, between June 2016 and May 2017 (n = 324). The first and second (three months later) blood samples both taken within 1-5 hours after rivaroxaban intake were analyzed (n = 219). Plasma concentration of rivaroxaban (PC-Riv) and prothrombin time (PT) with five reagents were measured.The 90% interval of PC-Riv was 47.3-532.9 ng/mL. The 90% interval of PT measured with RecombiPlasTin 2G was 11.8-22.3 seconds, the widest range among the five reagents examined. PC-Riv reproducibility within a 90% interval was evaluated bidirectionally (first-to-second and second-to-first), and 92.4% of samples were reproducible. The change rate (CR) of PC-Riv between two samplings ranged widely, and high CR (≥54.3%, cutoff for predicting non-reproducibility) was predicted by concomitant drugs (non-dihydropyridine calcium antagonist and thiazide) and mitral regurgitation.We reported the on-therapy range of rivaroxaban in a multicenter cohort. This range was consistent with that of a single-center cohort and was highly reproducible within three months in daily clinical practice. However, caution is necessary regarding several factors that may affect the intraindividual variation of PC-Riv.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

A 50-year-old man with a dual-chamber pacemaker was admitted to our hospital complaining of chest pain. Anterior ST segment elevation myocardial infarction (STEMI) was diagnosed. Emergency coronary angiography revealed total occlusion of the proximal left anterior descending artery (LAD), and primary percutaneous coronary intervention was performed. Angiograms showed that the LAD was wrapped around the apex of both ventricles. On day 8, ventricular fibrillation and cardiopulmonary arrest occurred due to elevation of the pacing threshold because of pacemaker malfunction. The pacemaker was upgraded to an implantable cardioverter-defibrillator and the lead was inserted into the right ventricular septum. Myocardial scintigraphy with thallium-201 and technetium-99m pyrophosphate located the infarct zone around the apex of both ventricles. We conclude that pacing failure of the right ventricular lead occurred in this case of LAD occlusion due to a LAD supplying the right ventricular apex. Clinicians should be aware of the possibility of pacemaker failure in patients presenting with anterior STEMI due to a wrap-around LAD. .

Background: Estrogen plays a significant role in cardiovascular benefits. As one of its beneficial pathways, ERα non-nuclear signaling is known to be protective for the vascular system, but its role for cardiac remodeling is unknown thus far. We previously reported cGMP pathways are one of the critical therapeutic targets for heart failure and ERα non-nuclear signaling played a pivotal role in cardioprotection and was indispensable to the therapeutic efficacy of cGMP-PDE5 inhibition. However, it is still remaining undetermined which cells are playing the key role in cardioprotective effects via ERα non-nuclear signaling. Methods: We generated genetically modified mouse lacking ERα in cardiomyocytes (ERα f/f /αMHC Cre/+ ) or endothelial cells (ERα f/f /Tie2 Cre/+ ) and assessed the effects of chronic pressure-overload (TAC) and the efficacy of PDE5 inhibitor (PDE5i) sildenafil after TAC. In addition, for the first time we generated endothelial cell specific genet-modified mouse lacking interactions between p85α and ERα which are critical for non-nuclear signaling (ERα KI/KI /Tie2 Cre/+ ). Cardiac functions were assessed for evaluating the effects of endothelial ERα non-nuclear singlaing to failing hearts. Results: Under physiological E2 status, PDE5i’s anti-remodeling effects after TAC were abrogated in ERα f/f /Tie2 Cre/+ (FS(%) ± SEM with vs without PDE5i 28.16 ± 3.43 vs 31.87 ± 2.30) but not in ERα f/f /αMHC Cre/+ (FS(%) ± SEM with PDE5i vs without PDE5i 54.57 ± 3.418 vs 43.3 ± 1.21) consistent with hemodynamic analysis. Assessment with ERα KI/KI /Tie2 Cre/+ showed decreased cardiac functions even with physiological E2. Hemodynamic analysis also supported the cardioprotective effects of ERα non-nuclear signaling in endothelial cells. Conclusion: ERα non-nuclear reaction in endothelial cells plays an important role in cardio-protective mechanism, and endothelial estrogen signals are indispensable to the therapeutic efficacy of cGMP-PDE5 inhibition. Our results clarified one of the cardioprotective signals of estrogen and highlighted the new strategy for heart failure treatment.

Background: Estrogen exerts complex physiological effects via its rapid (non-genomic) and genomic actions. In particular, rapid signaling of estrogen receptor alpha (ERα) has been implicated in the vasculo-protective effects, in which both endothelial and smooth muscle cells might be involved. However, no prior studies have determined the role of ERα rapid signaling in the endothelium. This study aims to clarify the impact of ERα rapid signaling in the vasculo-protection, using a novel mouse model lacking endotheilal-specific ERα rapid signaling. Methods and Results: In immunoblotting, p85α and pGSK3β, non-genomic pathway downstream signals, were reduced in ERα mutants RR259/260AA with estradiol (E2) stimulation at concentrations of 10 -11 and 10 -10 M . ERE-luciferase assay demonstrated E2 induced genomic pathway activity was preserved even in ERα mutants RR259/260AA. We generated a mouse model in which rapid signaling of ERα was ablated in the endothelium by crossing Tie2-Cre transgenic mice with floxed ERα mutants (RR 259/260 AA) in which p85α and ERα interaction was disrupted. In endothelial cells isolated from ERα KI/KI Tie2 cre/+ animals, E2 at a concentration of 10 -8 M failed to induce phosphorylation of Akt, confirming the absence of ERα rapid signaling. Baseline characteristics at 8 to 12 weeks of age were undistinguishable between the genotypes, including body weight (KI:19.2±0.366 g vs WT: 18.9±0.356 g ) systolic blood pressure (KI:106.1±3.336 vs WT: 103.5±2.133 mmHg) and echocardiographic fractional shortening (KI:54.4±0.751 vs WT: 55.19±0.947 %). We then assessed how vascular remodeling process was impacted in a carotid artery wire injury model. Histological analyses with Elastica van Gieson staining two weeks after induction of injury revealed that wall thickness and area of medial layer composed mainly of smooth muscle cells were significantly increased in ERα KI/KI Tie2 cre/+ mouse, as compared to wild types (KI:44.85±1.948 μm vs WT: 29.32±1.753 μm , KI:42,047±1,560 μm 2 vs WT: 32,815±1,211 μm 2 , respectively ). Conclusions: Our results demonstrate that the rapid signaling of ERα in the endothelium critically regulates vascular smooth muscle cell growth after vascular injury, suggesting the essential role to vascular remodeling.

BACKGROUND Rho-associated kinases (ROCK1 and ROCK2) are important regulators of the actin cytoskeleton and endothelial nitric oxide synthase (eNOS). Because the phosphorylation of eukaryotic elongation factor-1A1 (eEF1A1) by ROCK2 is critical for eNOS expression, we hypothesized that this molecular pathway may play a critical role in neuroprotection following focal cerebral ischemia.Methods and Results:Adult male wild-type (WT) and mutant ROCK2 and eNOS-/-mice were subjected to middle cerebral artery occlusion (MCAO), and cerebral infarct size, neurological deficit and absolute cerebral blood flow were measured. In addition, aortic endothelium-dependent response to acetylcholine, NG-nitro-L-arginine methyl ester (L-NAME) and sodium nitroprusside were assessed ex vivo. Endothelial cells from mouse brain or heart were used to measure eNOS and eEF1A activity, as well as NO production and eNOS mRNA half-life. In global hemizygous ROCK2+/-and endothelial-specific EC-ROCK2-/-mice, eNOS mRNA stability and eNOS expression were increased, which correlated with enhanced endothelium-dependent relaxation and neuroprotection following focal cerebral ischemia. Indeed, when ROCK2+/-mice were place on an eNOS-/-background, the neuroprotective effects observed in ROCK2+/-mice were abolished. CONCLUSIONS These findings indicate that the phosphorylation of eEF1A1 by ROCK2 is physiologically important for eNOS expression and NO-mediated neuroprotection, and suggest that targeting endothelial ROCK2 and eEF1A may have therapeutic benefits in ischemic stroke and cardiovascular disease.

ObjectiveParoxysmal atrial fibrillation could progress to permanent atrial fibrillation. Whether the transmitral inflow waves could be used to predict progression from paroxysmal atrial fibrillation to permanent atrial fibrillation is unknown. Therefore, we investigated the association between the transmitral inflow waves and progression of paroxysmal atrial fibrillation.MethodWe performed a retrospective study by analysing clinical and echocardiographic data from 88 patients with paroxysmal atrial fibrillation. We excluded patients who had structural heart disease, significant valvular disease, cardiomyopathy, cardiac device implantation or a left ventricular ejection fraction ResultThe patients with progression to permanent atrial fibrillation were more likely to be male and had lower peak A velocity than those without progression. After adjusting for covariates, lower peak A velocity remained the independent predictor of progression to permanent atrial fibrillation (p=0.025).ConclusionThe A velocity could be useful for predicting progression to permanent atrial fibrillation in Asian people.