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Introduction: To assess the efficacy of Shakuyaku-Kanzo-to, a Japanese herbal medicine, for prophylaxis against paclitaxel-induced myalgia and arthralgia, a comparative study was conducted with 50 patients treated with carboplatin and paclitaxel.Patients and Methods: Patients were alternatively assigned to receive either the intervention group (with Shakuyaku-Kanzo-to) or the control group (without Shakuyaku-Kanzo-to). We assessed the grade and the duration of myalgia and arthralgia.Results: The grades of myalgia and arthralgia in the control group were significantly higher than the grades determined in the intervention group (p = 0.018). The mean duration of myalgia and arthralgia was 2.78 +/- 2.09 days for the intervention group and 5.08 +/- 2.89 days for the control group. The duration was significantly shorter in the intervention group than in the control group (p = 0.002).Discussion: This study shows that prophylactic administration of Shakuyaku-Kanzo-to was effective against paclitaxel-induced myalgia and arthralgia. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to define the independent determinants of left atrial appendage (LAA) thrombus among various echocardiographic parameters measured by Velocity Vector Imaging (VVI) in patients with nonvalvular atrial fibrillation (AF) receiving warfarin, particularly in patients with a low CHADS2 score. Methods LAA emptying fraction (EF) and LAA peak longitudinal strain were measured by VVI using transesophageal echocardiography in 260 consecutive patients with nonvalvular persistent AF receiving warfarin. The patients were divided into two groups according to the presence (n=43) or absence (n=217) of LAA thrombus. Moreover, the patients within each group were further divided into subgroups according to a CHADS2 score ≤1. Results Multivariate logistic regression analysis showed that LAAEF was an independent determinant of LAA thrombus in the subgroup of 140 with a low CHADS2 score. Receiver operating characteristics curve analysis showed that an LAAEF of 21% was the optimal cutoff value for predicting LAA thrombus. Conclusions LAA thrombus formation depended on LAA contractility. AF patients with reduced LAA contractile fraction (LAAEF ≤21%) require strong anticoagulant therapy to avoid thromboembolic events regardless of a low CHADS2 score (≤1).

Abstract Background The purpose of this study was to determine the cut-off values of Hounsfield units (HU) for the discrimination of plaque components and to evaluate the feasibility of measurement of the volume of plaque components using multi-detector row computed tomography (MDCT). Methods Coronary lesions (125 lesions in 125 patients) were visualized by both integrated backscatter intravascular ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used as a gold standard to determine the cut off values of HU for the discrimination of plaque components. Results Plaques were classified as lipid pool (n =50), fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool, fibrosis and calcification were 18 ± 18 HU (−19 to 58 HU), 95 ± 24 HU (46 to 154 HU) and 378 ± 99 HU (188 to 605 HU), respectively. Using receiver operating characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was correlated with that measured by IB-IVUS (r =0.66, p Conclusion Lipid volume measured by MDCT was moderately correlated with that measured by IB-IVUS. MDCT may be useful for volumetric assessment of the lipid volume of coronary plaques, whereas the assessment of fibrosis volume was unstable.

Abstract Background The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS). Methods Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification ≤10°) in 36 patients and 22 plaques (moderately calcified group: 10° Results In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r = 0.456, p = 0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p = 0.032, r = −0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 ± 1.49 vs. 2.47 ± 1.79%/10 mmHg, p =0.014 and 28.3 ± 26.0 vs. 15.7 ± 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 ± 0.68 vs. 1.57 ± 0.95%/10 mmHg, p =0.012 and 26.5 ± 24.3 vs. 13.0 ± 16.7, p =0.020). These relationships were not seen in the moderately calcified group. Conclusion The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.

Abstract Background It is recognized that one of the causes of atrial fibrillation (AF) is pathological degeneration of the left atrium (LA). However, prospective study that elucidated the relationship between the incidence of persistent AF and pathological degeneration has not been performed. The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) values for the prediction of progression from paroxysmal AF (PAF) to persistent AF. Methods We measured IBS values of the entire LA wall at 5 mm intervals (except the posterior wall) in 27 patients with paroxysmal AF and evaluated progression to persistent AF for three years. IBS values were acquired with transesophageal echocardiography (TEE) using a 4–7 MHz transducer. IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). Each IBS value was color-coded to construct three dimensional maps. Results Average IBS values of total voxels in color-coded maps in the persistent AF group were significantly greater than those in the non-persistent AF group (25.8 ± 5.0 dB vs. 17.4 ± 10.2 dB, p = 0.047), whereas there was no significant difference in LA diameter between the persistent AF and the non-persistent AF group. There was significant difference in persistent AF-free survival after the baseline measurements in the subjects stratified by IBS value ( Conclusion Using IBS values measured by TEE, we can identify an increase in atrial degeneration that may predict the occurrence of persistent AF before LA dilation.

Background: Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated., Objective: We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients., Method and Result: Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase., Conclusion: The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Minatoguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The optimal treatment strategy for coronary calcified nodules (CN) remains uncertain. We aimed to evaluate the efficacy and safety of different calcium modification strategies, including rotational atherectomy (RA), orbital atherectomy (OA), and intravascular lithotripsy (IVL) for managing CN with optical coherence tomography (OCT) guidance., Methods: Consecutive patients undergoing OCT-guided percutaneous coronary intervention (PCI) for severely calcified lesions using RA, OA, or IVL between January 2017 and December 2022 were included. Primary endpoint was minimum stent area (MSA) post-PCI. Secondary endpoints included MSA at CN site and 1-year target vessel failure (TVF), defined as a composite of cardiac death, target-vessel myocardial infarction, or target vessel revascularization., Results: Among 154 patients and 158 lesions, CN was identified in 54 lesions (34.2%) and managed with RA (39%, n = 21), OA (33%, n = 18), or IVL (28%, n = 15). The IVL group exhibited a larger minimal lumen diameter, maximum calcium arc, and maximum calcium thickness. Post-PCI OCT demonstrated comparable MSA (RA: 6.23 ± 0.34 mm², OA: 5.75 ± 0.39 mm², IVL: 6.24 ± 0.46 mm²; p = 0.62) and MSA at CN site (7.17 ± 0.43 mm², 6.46 ± 0.49 mm², 7.86 ± 0.56 mm², respectively; p = 0.55) after adjusting for morphologic factors. The incidence of TVF at 1 year was similar among the group (RA: 19.0%, OA: 22.2%, IVL: 13.3%, p = 0.81)., Conclusions: In patients undergoing PCI for CN, similar procedural and clinical outcomes can be achieved using RA, OA, or IVL. These findings warrant further investigation in larger, prospective trials., (© 2024 Wiley Periodicals LLC.)

MicroRNA(miR)-143 and miR-145 are mainly expressed in vascular smooth muscle cells. However, the relationship between plasma miR-143 or miR-145 levels and the left ventricular (LV) function in patients with heart diseases remains unclear. Blood samples were taken from the antecubital vein in patients with heart diseases (n = 52), such as coronary artery disease, old myocardial infarction, cardiomyopathy, and valvular heart disease, and controls without heart diseases (n = 22). We measured plasma miR-143 and -145 levels by quantitative RT-PCR using TaqMan MicroRNA Assays and THUNDERBIRD Probe qPCR Mix. Plasma BNP levels were also measured. Echocardiography was performed to measure the LV ejection fraction (LVEF) and LV dilation. Plasma miR-143 and miR-145 levels were significantly higher in patients with heart diseases than in controls, respectively. Plasma miR-143 and miR-145 levels were significantly higher in patients with LVEF < 50% than in those with LVEF ≧ 50%, respectively. Plasma miR-143 and miR-145 levels were inversely correlated with LVEF, respectively. Plasma miR-143 and miR-145 levels were positively correlated with LV end-systolic dimension, respectively. Plasma miR-143 and -145 levels were positively correlated with plasma BNP levels, respectively. Plasma BNP levels were inversely correlated with LVEF. Plasma miR-143 and miR-145 levels are elevated in patients with LV dysfunction and may counteract LV dysfunction., (© 2024. The Author(s).)

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease. However, the effect of SGLT2i in patients with ADPKD have not been fully elucidated. Herein, we report the case of a patient with ADPKD on tolvaptan who was administered the SGLT2i dapagliflozin. The patient was a Japanese woman diagnosed with ADPKD at age 30. Despite the treatment with tolvaptan, eGFR was gradually declined from 79.8 to 50 ml/min/1.73 m 2 in almost 5 years and 10 mg of dapagliflozin was initiated in the hope of renoprotective effects. Although a small increase in vasopressin levels was observed, eGFR decline rate was moderated after dapagliflozin initiation. This case suggested an additional renoprotective effect of dapagliflozin in patient with ADPKD receiving tolvaptan. Although there is no evidence about the renal protective effect of SGLT2i in patients with ADPKD, we hereby report a case successfully treated with dapagliflozin for approximately 2 years. Further research, including clinical trials, is needed to evaluate whether SGLT2i are effective in patients with ADPKD., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The German word "kurort" means cure (kur) and area (ort), whereby a patient's health improves through walking in areas full of nature. A single session of kurort health walking (kurort) decreased high blood pressure and improved mental health. However, its continuing effect with repeat sessions remains unclear., Methods and Results: The subjects participated twice in kurort health walking in specially designated courses in Gifu City (n=242). Systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured before and after kurort health walking. Mental health was assessed using a 10-item checklist after kurort health walking. Both basal SBP and DBP before walking were significantly decreased more in the second session than in the first. In both the first and second sessions SBP and DBP decreased, but the decrease in SBP (∆SBP) by kurort was significantly greater in the SBP ≥140- than in the SBP <140-mmHg group, SBP inversely correlated with ∆SBP, the decrease in DBP (∆DBP) was significantly greater in the DBP ≥90- than in the DBP <90-mmHg group, and DBP inversely correlated with ∆DBP. Mental health was similarly improved after both the first and second kurort., Conclusions: Basal SBP and DBP decreased more in the second than in the first kurort. The decrease in SBP and DBP, and improvement of mental health was noted after both sessions., Competing Interests: S.M. is a member of Circulation Reports’ Editorial Team. The other authors declare that no conflicts of interest exist., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Since it is widely accepted that there is a positive correlation between the salt intake and hypertension or cerebro-cardiovascular-renal events, salt intake restriction is currently widely recommended, especially in patients with hypertension. However, salt intake restriction does not always have beneficial effects. Indeed, an excessively low salt intake has been reported to be harmful to health. While a reasonable vegetable and fruit intake reportedly decreases blood pressure, whether or not vegetable and fruit intake truly leads to reductions in cerebro-cardiovascular-renal events or all-cause mortality remains unclear. We reviewed the importance of vegetable and fruit intake for health, focusing on the relationship between urinary potassium excretion, a marker of vegetable and fruit intake, and cerebro-cardiovascular-renal events or all-cause mortality. In conclusion, vegetable and fruit intake may be essential for reducing cerebro-cardiovascular-renal events and all-cause mortality.

Background: Sodium zirconium cyclosilicate, a non-absorbed non-polymer zirconium silicate, is a new potassium binder for hyperkalemia. A previous report showed that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows a higher continuation rate of renin-angiotensin-aldosterone system inhibitors. However, no studies have compared sodium zirconium cyclosilicate with existing potassium binders for renin-angiotensin-aldosterone system inhibitor continuity. The purpose of this study was to evaluate the effect of sodium zirconium cyclosilicate on angiotensin-converting enzyme inhibitor /angiotensin receptor blocker continuation in patients with hyperkalemia compared to that of calcium polystyrene sulfonate., Methods: Patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly prescribed sodium zirconium cyclosilicate or calcium polystyrene sulfonate to treat hyperkalemia at a tertiary referral hospital between August 2020 and April 2022 were enrolled in this single-center, retrospective observational study. The primary outcome measure was angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription three months after initiating potassium binders., Results: In total, 174 patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly administered sodium zirconium cyclosilicate (n = 62) or calcium polystyrene sulfonate (n = 112) were analyzed. The prescription rate of angiotensin-converting enzyme inhibitors /angiotensin receptor blockers at 3 months was significantly higher in the sodium zirconium cyclosilicate group than in the calcium polystyrene sulfonate group (89 vs. 72%). Multivariate logistic regression models showed that sodium zirconium cyclosilicate was independently associated with the primary outcome (odds ratio 2.66, 95% confidence interval 1.05-7.43). The propensity score-matched comparison also showed a significant association between sodium zirconium cyclosilicate and the primary outcome., Conclusions: Our study suggests that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows for a higher continuation rate of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than calcium polystyrene sulfonate. These findings suggest that sodium zirconium cyclosilicate has potential benefits for patients with chronic kidney disease receiving renin-angiotensin-aldosterone system inhibitors., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Pancreatic stellate cells (PSCs) are stromal cells in the pancreas that play an important role in pancreatic pathology. In chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), PSCs are known to get activated to form myofibroblasts or cancer-associated fibroblasts (CAFs) that promote stromal fibroinflammatory reactions. However, previous studies on PSCs were mainly based on the findings obtained using ex vivo expanded PSCs, with few studies that addressed the significance of in situ tissue-resident PSCs using animal models. Their contributions to fibrotic reactions in CP and PDAC are also lesser-known. These limitations in our understanding of PSC biology have been attributed to the lack of specific molecular markers of PSCs. Herein, we established Meflin (Islr), a glycosylphosphatidylinositol-anchored membrane protein, as a PSC-specific marker in both mouse and human by using human pancreatic tissue samples and Meflin reporter mice. Meflin-positive (Meflin + ) cells contain lipid droplets and express the conventional PSC marker Desmin in normal mouse pancreas, with some cells also positive for Gli1, the marker of pancreatic tissue-resident fibroblasts. Three-dimensional analysis of the cleared pancreas of Meflin reporter mice showed that Meflin + PSCs have long and thin cytoplasmic protrusions, and are localised on the abluminal side of vessels in the normal pancreas. Lineage tracing experiments revealed that Meflin + PSCs constitute one of the origins of fibroblasts and CAFs in CP and PDAC, respectively. In these diseases, Meflin + PSC-derived fibroblasts showed a distinctive morphology and distribution from Meflin + PSCs in the normal pancreas. Furthermore, we showed that the genetic depletion of Meflin + PSCs accelerated fibrosis and attenuated epithelial regeneration and stromal R-spondin 3 expression, thereby implying that Meflin + PSCs and their lineage cells may support tissue recovery and Wnt/R-spondin signalling after pancreatic injury and PDAC development. Together, these data indicate that Meflin may be a marker specific to tissue-resident PSCs and useful for studying their biology in both health and disease. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Background: Percutaneous coronary intervention (PCI) of calcified lesions remains challenging for interventionalists., Aims: We aimed to investigate whether combining rotational atherectomy (RA) with cutting balloon angioplasty (RA+CBA) results in more optimal stent expansion compared with RA followed by non-compliant balloon angioplasty (RA+NCBA)., Methods: ROTA-CUT is a prospective, multicentre, randomised trial of 60 patients with coronary artery disease undergoing PCI of moderately or severely calcified lesions with drug-eluting stent implantation. Patients were randomised 1:1 to either RA+CBA or RA+NCBA. The primary endpoint was the minimum stent area on intravascular ultrasound (IVUS). Secondary endpoints included minimum lumen area and stent expansion assessed by IVUS and acute lumen gain, final residual diameter stenosis and minimum lumen diameter assessed by angiography. Clinical endpoints were obtained at 30 days., Results: The mean age was 71.1±9.4 years, and 22% were women. The procedural details of RA were similar between groups, as were procedure duration and contrast use. Minimum stent area was similar with RA+CBA versus RA+NCBA (6.7±1.7 mm 2 vs 6.9±1.8 mm 2 ; p=0.685). Furthermore, there were no significant differences regarding the other IVUS and angiographic endpoints. Procedural complications were rare, and 30-day clinical events included 2 myocardial infarctions and 1 target vessel revascularisation in the RA+CBA group and 1 myocardial infarction in the RA+NCBA group., Conclusions: Combining RA with CBA resulted in a similar minimum stent area compared with RA followed by NCBA in patients undergoing PCI of moderately or severely calcified lesions. RA followed by CBA was safe with rare procedural complications and few clinical adverse events at 30 days.

Objective The objective of this study was to estimate the humoral immune response evaluated by immunoglobulin G (IgG) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD-IgG) following the third mRNA coronavirus disease 2019 (COVID-19) vaccination in patients with kidney disease who received immunosuppressive treatment. Methods The primary outcome was RBD-IgG levels after the third SARS-CoV-2 vaccination. The primary comparison was the RBD-IgG levels between patients with kidney disease who received immunosuppressive treatment (n=124) and those who did not (n=33). Results The RBD-IgG levels were significantly lower in the patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. The RBD-IgG levels were lower in patients treated with glucocorticoid monotherapy than in those who did not receive immunosuppressive treatment. Even in patients who received ≤5 mg prednisolone, the RBD-IgG levels were significantly lower. Nine of the 10 patients who received rituximab within one year before the first vaccination did not experience seroconversion after the third vaccination. Meanwhile, all nine patients who received rituximab only after the second vaccination experienced seroconversion, even if B cell recovery was insufficient. Patients treated with mycophenolate mofetil plus glucocorticoid plus belimumab had significantly lower RBD-IgG levels than those treated with mycophenolate mofetil plus glucocorticoid. Conclusion The RBD-IgG levels were lower in patients with kidney disease who received immunosuppressive treatment than in those who did not receive immunosuppressive treatment. Low-dose glucocorticoid monotherapy affected the humoral immune response following the third mRNA COVID-19 vaccination.

Background: MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified., Methods and results: Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase., Conclusions: An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients.

High-risk coronary plaques have certain morphological characteristics. Thus, comprehensive assessment is needed for the risk stratification of plaques in patients with coronary artery disease. Integrated backscatter intravascular ultrasound (IB-IVUS) has been used successfully used to evaluate the tissue characteristics of coronary plaques; however, the mechanical properties of plaques have been rarely assessed. Therefore, we developed Speckle-tracking IVUS (ST-IVUS) to evaluate the mechanical properties of coronary plaque. This study aimed to evaluate the relation between the tissue characteristics of coronary plaques using IB-IVUS and their mechanical properties using ST-IVUS. We evaluated 95 non-targeted plaques in 95 patients undergoing elective percutaneous coronary intervention to the left anterior descending artery. We set regions of interest (ROIs) in the cross-sectional images of coronary plaques where we divided 120 degree plaques into four quadrants (every 30 degrees), with the center at the area of maximum atheroma thickness. We measured relative calcification area (%CA, relative fibrous area (%FI) and relative lipid pool area (%LP) in a total of 380 ROIs. In ST-IVUS analysis, we measured strain in the circumferential direction of the lumen area (LA strain: %), the external elastic membrane area strain (EEM strain: %), and strain in the radial direction (radial strain: %). On global cross-sectional area IB-IVUS analysis, the %CA was 1.2 ± 1.2%; the %FI was 49.0 ± 15.9%, and the %LP was 49.7 ± 16.5%. In ST-IVUS analysis, the LA strain was 0.67 ± 0.43%; the EEM strain was 0.49 ± 0.33%, and the radial strain was 2.02 ± 1.66%. On regional analysis, the %LP was not associated with the LA strain (r = - 0.002 p = 0.97), the EEM strain (r = - 0.05 p = 0.35), or with the radial strain (r = - 0.04 p = 0.45). These trends were seen between the %FI and the LA strain (r = 0.02 p = 0.74), the %FI and the EEM strain (r = 0.05 p = 0.35), and the %FI and the radial strain (r = 0.04 p = 0.50). A significant correlation was only observed between the %CA and the LA strain (r = - 0.15 p = 0.0038). Our findings indicate that the associations between mechanical properties and tissue characteristics lacked statistical significance, more often than not, and that it is necessary to evaluate the mechanical properties as well as plaque characteristics for risk stratification of coronary plaques., (© 2022. Springer Japan KK, part of Springer Nature.)

Tissue characterization plays an important role in the development of acute coronary syndromes. iMap is an intravascular ultrasound (IVUS) tissue characterization system that provides useful information by reconstructing color-coded maps. Mechanical properties due to dynamic mechanical stress during a cardiac cycle may also trigger vulnerable plaque. Speckle tracking IVUS (ST-IVUS) has been introduced to observe plaque behavior in relation to mechanical properties. We report the case of an 84-year-old woman with stable coronary artery disease who underwent percutaneous coronary intervention, at which time IVUS demonstrated mainly three low echoic areas like lipid pools with thick fibrous caps. Pathological evaluation with iMap revealed that one low echoic area was occupied with necrotic tissue and that the other two areas occupied fibrotic. Although those tissue characterizations were different, they showed similar stretching behavior at systole by ST-IVUS which depicted plaque behavior from IVUS images using a color mapping. The mechanical properties of individual coronary plaques may differ depending on the tissue disposition. It is necessary to consider mechanical properties using ST-IVUS as well as to evaluate tissue characterization in plaque risk stratification., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Hypertension is one of the risk factors for cerebro-cardiovascular and renal (CCR) diseases. High blood pressure is affected by the amount of salt (NaCl) and potassium (K) intake. There are many studies reporting the relationship between urinary sodium or potassium excretion and CCR events or all-cause mortality in general populations. Thus, it is necessary to investigate the relationship between urinary NaCl or K excretion and CCR events or all-cause mortality in hypertensive patients under control with anti-hypertensive drugs., Methods: A prospective, multi-center cohort study was performed in 3210 hypertensives under treatment with anti-hypertensive drugs for 5 years. The primary outcome was the CCR events, and the secondary outcome was all-cause mortality. A time-dependent Cox proportional hazards regression analysis was performed to assess the association between outcomes and urinary NaCl and K excretion, blood pressure, or heart rate., Results: During the follow-up period, 61 CCR events and 110 all-cause deaths occurred. There was no association between urinary NaCl excretion and CCR events or all-cause mortality. Lower urinary K excretion and higher Na/K ratio were associated with higher risk of CCR events or all-cause mortality. The CCR events were not associated with systolic, diastolic blood pressure, or heart rate., Conclusion: Lower urinary K excretion was associated with higher risk of CCR events or all-cause mortality in hypertensive patients under treatment with anti-hypertensive drugs., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Technetium-99m-sestamibi ( 99m Tc-sestamibi) single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in patients with acute coronary syndrome (ACS) could be used to assess area-at-risks, as well as myocardial infarct or saved sizes. In patients with ACS, accelerated washout of 99m Tc-sestamibi during early and delayed imaging in the acute phase may suggest mitochondrial dysfunction in the injured but salvaged myocardium. However, the link between 99m Tc-sestamibi accelerated washout and exercise tolerance is unknown. The purpose of this study was to investigate a possible association between 99m Tc-sestamibi accelerated washout and exercise tolerance in acute ACS patients as they progressed into the chronic phase. One hundred and sixty-five patients with ACS who underwent 99m Tc-sestamibi SPECT MPI during the acute phase were recruited. On this basis, we calculated the total perfusion deficits (TPDs) for early (1 h after tracer injection) and delayed (4 h after tracer injection) images using automated quantification software. We then subtracted the early TPDs from the delayed TPDs to calculate the ΔTPD. We conducted a cardiopulmonary exercise test in acute and chronic phases. We divided two groups according to the median ΔTPD (the ΔTPD ≥ 4 group and the ΔTPD < 4 group) and compared anaerobic threshold (AT; ml/kg/min) between the groups. For anaerobic threshold (AT) improvement in data analysis, we employed multivariate logistic regression analysis. A total of 101 ST-segment elevation myocardial infarctions, 36 non-ST-elevation myocardial infarctions, and 28 unstable angina pectoris events were reported as ACS. From acute phase (10.8 ± 4.2 ml/kg/min) to chronic phase (11.9 ± 2.3 ml/kg/min), the AT in the ΔTPD ≥ 4 group was significantly increased (p < 0.0001). This trend was also seen in the ΔTPD < 4 group from acute (11.4 ± 1.8 ml/kg/min) to chronic phase (12.1 ± 2.2 ml/kg/min, p = 0.015). AT was lower in the ΔTPD ≥ 4 group in the acute phase (p = 0.027), but there was no difference in AT between the two groups in the chronic phase (p = 0.60). ΔTPD and the absence of diabetes were both independent predictors of AT improvement in multivariate logistic regression analysis. Receiver-operating characteristic curve analysis determined that ΔTPD = 6 was the best cut-off value, with 60.0% sensitivity and 71.4% specificity, respectively. The accelerated washout of 99m Tc-sestamibi in patients with ACS during the acute phase could help to predict improvement in exercise tolerance in the chronic phase., (© 2022. Springer Japan KK, part of Springer Nature.)

Adipose-derived mesenchymal stem cells (ASCs) have shown therapeutic potentials against refractory diseases. However, the detailed therapeutic mechanisms remain unclear. Here, we report the therapeutic actions of human ASCs in nephritis, focusing on cellular dynamics and multi-organ networks. Intravenously-administered ASCs accumulated in spleen but not kidneys. Nevertheless, ASCs increased M2 macrophages and Tregs in kidneys and drove strong renoprotection. Splenectomy abolished these therapeutic effects. ASC-derived extracellular vesicles (EVs) were transferred to M2 macrophages, which entered the bloodstream from spleen. EVs induced the transcriptomic signatures of hyperpolarization and PGE2 stimulation in M2 macrophages and ameliorated glomerulonephritis. ASCs, ASC-derived EVs, and EV-transferred M2 macrophages enhanced Treg induction. These findings suggest that EV transfer from spleen-accumulated ASCs to M2 macrophages and subsequent modulation of renal immune-environment underlie the renoprotective effects of ASCs. Our results provide insights into the therapeutic actions of ASCs, focusing on EV-mediated modulation of macrophages and the spleen-kidney immune network., (© 2022. The Author(s).)

Rapid percutaneous coronary intervention for acute myocardial infarction (AMI) reduces acute mortality, but there is an urgent need for treatment of left ventricular dysfunction and remodeling after AMI to improve the prognosis. The myocardium itself does not have a high regenerative capacity, and it is important to minimize the loss of cardiomyocytes and maintain the cardiac function after AMI. To overcome these problems, attention has been focused on myocardial regeneration therapy using cells derived from bone marrow. The clinical use of bone marrow stem cells is considered to have low safety concerns based on the experience of using bone marrow transplantation for blood diseases in clinical practice. It has been reported that bone marrow mononuclear cells (BM-MNC) and mesenchymal stem cells (BM-MSC) differentiate into cardiomyocytes both in vitro and in vivo, and they have been considered a promising source for stem cell therapy. To prevent heart failure after human AMI, studies have been conducted to regenerate myocardial tissue by transplanting bone marrow stem cells, such as BM-MSCs and BM-MNCs. Therapies using those cells have been administered to animal models of AMI, and were effective to some extent, but the effect in clinical trials was limited. Recently, it was reported that multilineage-differentiating stress enduring cells (Muse cells), which are endogenous pluripotent stem cells obtainable from various tissues including the bone marrow, more markedly reduced the myocardial infarct size and improved the cardiac function via regeneration of cardiomyocytes and vessels and paracrine effects compared with BM-MSCs. Here, we describe stem cell therapies using conventional BM-MNCs and BM-MSCs, and Muse cells which have potential for clinical use for the treatment of AMI., (Copyright © 2021. Published by Elsevier Ltd.)

Heart failure is the end-stage phenotype of several cardiac diseases. The number of heart failure patients is increasing in accordance with an increase in the number of elderly people. The prognosis of heart failure is poor and its 5-year death rate is comparable to that of stage III cancer. It is important to understand the essential mechanism of the worsening prognosis of heart failure and to practice effective treatment from the perspective of improving the prognosis of heart failure based on its essential mechanism. Plasma noradrenaline level is a good predictor of the survival rate of heart failure patients, and sympathetic nerve activity is augmented in patients with heart failure as evidenced by a higher noradrenaline release rate (spillover) from the sympathetic nerve endings especially in the heart and kidney. Noradrenaline release is regulated by presynaptic receptors at the sympathetic nerve endings, and the kidney affects the sympathetic nerve activity. Although the short-term reflex augmentation of sympathetic nerve activity caused by reduced cardiac function may help to improve cardiac function, long-term augmentation of sympathetic nerve activity damages the heart and deteriorates the prognosis of heart failure. Currently, drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, mineralocorticoid antagonists, ivabradine, angiotensin receptor-neprilysin inhibitor, and sodium-glucose transport protein 2 inhibitors, are used for the treatment of heart failure, and had a good prognosis in large randomized, controlled clinical trials. Interestingly, the same characteristics in common of these drugs is the ability to optimize excessively augmented sympathetic nerve activity. This review discusses insights into essential mechanism of heart failure that determines the prognosis of heart failure, focusing on the interaction between sympathetic nerve activity and anti-heart failure drugs currently recommended by the 2021 guidelines of the Japanese Circulation Society and the Japanese Heart Failure Society for heart failure treatment., Competing Interests: Declaration of Competing Interest There is no conflict of interest to be declared., (Copyright © 2021. Published by Elsevier Ltd.)

Perivascular mesenchymal cells (PMCs), which include pericytes, give rise to myofibroblasts that contribute to chronic kidney disease progression. Several PMC markers have been identified; however, PMC heterogeneity and functions are not fully understood. Here, we describe a novel subset of renal PMCs that express Meflin, a glycosylphosphatidylinositol-anchored protein that was recently identified as a marker of fibroblasts essential for cardiac tissue repair. Tracing the lineage of Meflin + PMCs, which are found in perivascular and periglomerular areas and exhibit renin-producing potential, showed that they detach from the vasculature and proliferate under disease conditions. Although the contribution of Meflin + PMCs to conventional α-SMA + myofibroblasts is low, they give rise to fibroblasts with heterogeneous α-SMA expression patterns. Genetic ablation of Meflin + PMCs in a renal fibrosis mouse model revealed their essential role in collagen production. Consistent with this, human biopsy samples showed that progressive renal diseases exhibit high Meflin expression. Furthermore, Meflin overexpression in kidney fibroblasts promoted bone morphogenetic protein 7 signals and suppressed myofibroblastic differentiation, implicating the roles of Meflin in suppressing tissue fibrosis. These findings demonstrate that Meflin marks a PMC subset that is functionally distinct from classic pericytes and myofibroblasts, highlighting the importance of elucidating PMC heterogeneity., (© 2022. The Author(s).)

Background: We recently reported that multilineage-differentiating stress enduring (Muse) cells intravenously administered after acute myocardial infarction (AMI), selectively engrafted to the infarct area, spontaneously differentiated into cardiomyocytes and vessels, reduced the infarct size, improved the left ventricular (LV) function and remodeling in rabbits. We aimed to clarify the efficiency of Muse cells in a larger animal AMI model of mini-pigs using a semi-clinical grade human Muse cell product., Method and Result: Mini-pigs underwent 30 min of coronary artery occlusion followed by 2 weeks of reperfusion. Semi-clinical grade human Muse cell product (1x107, Muse group, n = 5) or saline (Vehicle group, n = 7) were intravenously administered at 24 h after reperfusion. The infarct size, LV function and remodeling were evaluated by echocardiography. Arrhythmias were evaluated by an implantable loop recorder. The infarct size was significantly smaller in the Muse group (10.5±3.3%) than in the Vehicle group (21.0±2.0%). Both the LV ejection fraction and fractional shortening were significantly greater in the Muse group than in the Vehicle group. The LV end-systolic and end-diastolic dimensions were significantly smaller in the Muse group than in the Vehicle group. Human Muse cells homed into the infarct border area and expressed cardiac troponin I and vascular endothelial CD31. No arrhythmias and no blood test abnormality were observed., Conclusion: Muse cell product might be promising for AMI therapy based on the efficiency and safety in a mini-pig AMI., Competing Interests: The authors have declared that no competing interests exist.

Background: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM)., Objectives: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart., Methods: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy., Results: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period., Conclusions: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart., Competing Interests: Funding Support and Author Disclosures This study was supported in part by JSPS KAKENHI grant no. JP21K08077 from the Japan Society for the Promotion of Science and a research grant from Gifu University School of Medicine. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the Cardiac Rehabilitation Gifu Network (CR-GNet) feasibility in managing diseases and assisting patients in attaining physical fitness, and its impact on long-term outcomes after acute coronary syndrome (ACS)., Methods: In this prospective observational study, we enrolled 47 patients with ACS registered in the CR-GNet between February 2016 and September 2019. 37, 29, and 21 patients underwent follow-up assessments for exercise capacity (peak oxygen uptake) at 3 months, 6 months, and 1 year after discharge, respectively. Major adverse cardiac events (MACE) were compared with controls not registered in the CR-GNet., Results: The coronary risk factors, except blood pressure, improved at 3 and 6 months, and 1 year after discharge. These risk factors in each patient significantly reduced from 2.9 at admission to 1.6, 1.4, and 1.9 at 3 months, 6 months, and 1 year after discharge (p<0.05), respectively. Peak oxygen uptake was significantly higher at 3 months (17.5±4.9 ml/kg/min), 6 months (17.9±5.1 ml/kg/min), and 1 year (17.5±5.5 ml/kg/min) after discharge than that at discharge (14.7±3.6 ml/kg/min) (p<0.05). During follow-up, there was no significant difference; MACE did not occur in any patients in the CR-GNet but occurred in controls., Conclusion: CR-GNet is a feasible option for the long-term management of ACS patients., Competing Interests: The authors have no conflicts of interest to declare, (2022, JAPANESE PHYSICAL THERAPY ASSOCIATION.)

Background: Kurort is a German term from the words kur (cure) and ort (area), and refers to improvements in patients' health in areas full of nature. We investigated the effect of kurort health walking in the 2 urban-style kurort health walking courses opened in Gifu City on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, and mood. Methods and Results: The subjects were 454 people (136 males, 318 females; mean [±SD] age 61.7±9.9 years) taking part in kurort health walking for the first time. SBP, DBP, and heart rate were measured before and after kurort health walking. Mood was assessed using a 10-item checklist after kurort health walking. Kurort health walking significantly decreased SBP and DBP and increased heart rate. The decrease in SBP was significantly greater in the SBP ≥140 than <140 mmHg group, indicating that SBP before Kurort health walking was inversely correlated with the change in SBP. Similarly, the decrease in DBP was significantly greater in the DBP ≥90 than <90 mmHg group, indicating that DBP before kurort health walking was also inversely correlated with the change in DBP. All 10 items on the mood assessment were significantly improved after kurort health walking. Conclusions: Kurort health walking preferentially decreases higher blood pressure and improves mood., Competing Interests: S.M. is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)