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Background: Diastolic dysfunction in humans is an age-related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported., Methods: Data from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function., Results: Rhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen-free status., Conclusions: Rhesus macaques share common sex- and age-related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex- and age-matching within future rhesus macaque cardiovascular research., (© 2023 The Authors. Journal of Medical Primatology published by John Wiley & Sons Ltd.)

Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk for impairment in heart failure and diastolic relaxation while preserving ejection fraction (EF). Recently, several sodium glucose cotransporter-2 (SGLT2) inhibitors have demonstrated to decrease cardiovascular disease (CVD) events in elderly diabetic patients, although gender difference in the effect of SGLT2 inhibitors is unknown. The objective of the present study was to evaluate gender difference in the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD function in patients with diabetes mellitus., Methods: This was a retrospective study. Patients received 20 mg of tofogliflozin daily for 3 months. EF, ratio of early filling to atrial filling (E/A), a change in mitral inflow E and mitral e' annular velocities (E/e'), left atrial dimension (LAD) and maximal diameter of inferior vena cava (IVC max ), including various physiological parameters were measured between baseline, 1 month and 3 months after administration of tofogliflozin. Interaction between gender and time after administration was evaluated using mixed effect model., Results: The results showed significant decrease in E/e' (P < 0.01) and significant interaction between time and gender in E/A (P < 0.01), following administration of tofogliflozin for 3 months. EF was constantly higher significantly in women (P < 0.01)., Conclusion: It is concluded that 3-month administration of tofogliflozin decreased E/e' with gender difference in EF and E/A., Competing Interests: None to declare., (Copyright 2020, Higashikawa et al.)

Pulmonary function and arterial stiffness correlate significantly, attributing to the chronic inflammation of atherosclerosis. However, through the pulmonary or systemic circulation, pulmonary and vascular functions associate hemodynamically with cardiac morphology and function. In the present study, we investigated arterial-cardiac-pulmonary interaction by examining how the pulmonary and vascular functions correlate with the heart. This study investigated 55 consecutive subjects not suffering from pulmonary, vascular and cardiac disease who underwent health screening test at our medical center. First, the presence of atherosclerotic disease (hypertension, dyslipidemia and diabetes) and smoking status of the patients were determined. Next, pulmonary function test, vascular function test including cardio-ankle vascular index, and echocardiography were performed. Then, we examined the correlation among the pulmonary, vascular and the heart. Our results revealed many correlations among these three factors. Especially left atrial dimension (LAD) and E/A ratio (E/A) were important cardiac factors associated with both pulmonary and vascular functions independently. Conventionally, inflammatory responses are known to involve in the correlation between pulmonary and vascular functions. Our study demonstrated that cardiac function and morphology were also involved in this correlation, signifying that LAD and E/A plays important roles in the arterial-cardiac-pulmonary interaction.

To detect potential cardiac abnormalities in asymptomatic methamphetamine abusers using three-dimensional speckle tracking echocardiography (3D STE). Fifty-three male methamphetamine abusers, free of cardiac symptoms/signs, were enrolled in this study. A control group of 53 age-matched male normal subjects was studied for comparison. Standard 3D, flow and tissue Doppler echo with measurements of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction (LVEF), the ratio of the early to late diastolic transmitral filling velocity (E/A), the ratio of the early diastolic transmitral filling velocity to the early diastolic septal tissue velocity (E/E') and 3D STE with measurements of global area strain (GAS), global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) were performed, respectively. These echocardiographic parameters were compared between methamphetamine abusers and normal subjects, and receiver operating characteristic curve (ROC) analysis was done to differentiating methamphetamine abusers from normal subjects. LVESV, LVEDV, LVEF, E/A, E/E' ratios and GRS were not significantly different between methamphetamine abusers and normal subjects (p > 0.05). However, GAS, GLS and GCS were significantly less in methamphetamine abusers than in normal subjects (p < 0.05). The areas under ROC (AUC) for GAS were greatest among all the 3D STE derived LV global strains (GAS vs. GLS, GCS and GRS, 0.95 vs. 0.76, 0.69 and 0.61, respectively). The cutoff value with - 30.3% of GAS had sensitivity of 91.8%, specificity of 91.6% and accuracy of 91.3% for differentiating methamphetamine abusers from normal subjects. The potential myocardial function abnormalities can be detected by 3D STE in asymptomatic methamphetamine abusers, and GAS is a good indicator for indentifying methamphetamine abusers from normal population, which can be used to screening and monitor methamphetamine abuse, detect subclinical LV dysfunction, predict potential methamphetamine-related cardiotoxicity, and to initiate early cardioprotective therapy before the onset of overt heart failure in time.

Objectives: The impact of surgical ventricular restoration (SVR) on survival and major adverse cardiac events (MACEs) is still controversial. The purposes of this study were to analyze our surgical experience with SVR for ischemic cardiomyopathy and to determine the effect of preoperative left ventricular diastolic dysfunction on mid-term outcomes after SVR., Methods and Results: Between April 2010 and May 2016, 19 patients underwent SVR. The mean age was 60 ± 11 years and the mean New York Heart Association functional class was 2.9 ± 0.8. Preoperative mean left ventricular end systolic volume index (LVESVI) and ejection fraction (LVEF) were 134 ± 56 mL/m 2 and 24 ± 7%, respectively. The early-to-late mitral valve flow ratio (E/A) on echocardiogram was 2.4 ± 1.8 and 9 patients had E/A ≥2, excluding 2 patients with atrial fibrillation. The mean follow-up period was 29 ± 16 months. One patient died of heart failure at 6 months postoperative; the overall survival rate at 3 years was 95%. MACEs requiring hospitalization occurred in 10 patients; E/A ≥2, or restrictive filling pattern, was the only significant predictor of MACE in multivariate analysis. Reverse remodeling was associated with E/A <2, but not E/A ≥2. There was also a significant difference between patients with E/A <2 vs. ≥2 with respect to MACE-free survival rates at 3 years (100 vs. 10%; p = 0.001)., Conclusion: The degree of preoperative diastolic dysfunction can influence the outcome after SVR. Patients with E/A ≥2 may not be good candidates for SVR.

Key Points: In a rat model of ageing that is free of atherosclerosis or hypertension, E/A, a diagnostic measure of diastolic filling, decreases, and isovolumic relaxation time increases, indicating that both active and passive ventricular relaxation are impaired with advancing age. Resting coronary blood flow and coronary functional hyperaemia are reduced with age, and endothelium-dependent vasodilatation declines with age in coronary resistance arterioles. Exercise training reverses age-induced declines in diastolic and coronary microvascular function. Thus, microvascular dysfunction and inadequate coronary perfusion are likely mechanisms of diastolic dysfunction in aged rats. Exercise training, initiated at an advanced age, reverses age-related diastolic and microvascular dysfunction; these data suggest that late-life exercise training can be implemented to improve coronary perfusion and diastolic function in the elderly., Abstract: The risk for diastolic dysfunction increases with advancing age. Regular exercise training ameliorates age-related diastolic dysfunction; however, the underlying mechanisms have not been identified. We investigated whether (1) microvascular dysfunction contributes to the development of age-related diastolic dysfunction, and (2) initiation of late-life exercise training reverses age-related diastolic and microvascular dysfunction. Young and old rats underwent 10 weeks of exercise training or remained as sedentary, cage-controls. Isovolumic relaxation time (IVRT), early diastolic filling (E/A), myocardial performance index (MPI) and aortic stiffness (pulse wave velocity; PWV) were evaluated before and after exercise training or cage confinement. Coronary blood flow and vasodilatory responses of coronary arterioles were evaluated in all groups at the end of training. In aged sedentary rats, compared to young sedentary rats, a 42% increase in IVRT, a 64% decrease in E/A, and increased aortic stiffness (PWV: 6.36 ± 0.47 vs.4.89 ± 0.41, OSED vs. YSED, P < 0.05) was accompanied by impaired coronary blood flow at rest and during exercise. Endothelium-dependent vasodilatation was impaired in coronary arterioles from aged rats (maximal relaxation to bradykinin: 56.4 ± 5.1% vs. 75.3 ± 5.2%, OSED vs. YSED, P < 0.05). After exercise training, IVRT, a measure of active ventricular relaxation, did not differ between old and young rats. In old rats, exercise training reversed the reduction in E/A, reduced aortic stiffness, and eliminated impairment of coronary blood flow responses and endothelium-dependent vasodilatation. Thus, age-related diastolic and microvascular dysfunction are reversed by late-life exercise training. The restorative effect of exercise training on coronary microvascular function may result from improved endothelial function., (© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.)

Left ventricular (LV) filling impairment is present in patients with chronic obstructive pulmonary disease (COPD). Airflow obstruction is related to reduced LV end-diastolic volume, stroke volume, and cardiac output. The ratio of peak early diastolic filling velocity of the mitral inflow to peak early diastolic velocity of the mitral annulus (E/e'), an echocardiographic parameter, can be applied as a surrogate marker of LV filling pressures. Forty-seven individuals with suspected COPD underwent pulmonary function tests and echocardiography. The ratio of forced expiratory volume in 1s to forced vital capacity (FEV1/FVC) and the E/e' ratio were determined. Multivariate linear regression analysis showed that the FEV1/FVC ratio (β=0.01; 95% confidence interval, 0.001-0.019; p=0.036) independently predicted the log transformed E/e' ratio. An increase of FEV1/FVC ratio (in percentage) by 1 unit was associated with an increase of the E/e' ratio multiplied by 1.01. Airflow obstruction inversely predicts LV filling pressure in suspected COPD cases., (Copyright © 2013 Elsevier B.V. All rights reserved.)

During the life cycle of heterothallic tetrapolar Agaricomycetes such as Lentinula edodes (Berk.) Pegler, the mating type system, composed of unlinked A and B loci, plays a vital role in controlling sexual development and resulting formation of the fruit body. L. edodes is produced worldwide for consumption and medicinal purposes, and understanding its sexual development is therefore of great importance. A considerable amount of mating type factors has been indicated over the past decades but few genes have actually been identified, and no complete genetic structures of L. edodes B mating-type loci are available. In this study, we cloned the matB regions from two mating compatible L. edodes strains, 939P26 and 939P42. Four pheromone receptors were identified on each new matB region, together with three and four pheromone precursor genes in the respective strains. Gene polymorphism, phylogenetic analysis and distribution of pheromone receptors and pheromone precursors clearly indicate a bipartite matB locus, each sublocus containing a pheromone receptor and one or two pheromone precursors. Detailed sequence comparisons of genetic structures between the matB regions of strains 939P42, 939P26 and a previously reported strain SUP2 further supported this model and allowed identification of the B mating type subloci borders. Mating studies confirmed the control of B mating by the identified pheromone receptors and pheromones in L. edodes., (© 2013 Elsevier B.V. All rights reserved.)

Purpose: In acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), a conservative fluid management strategy improves lung function but could jeopardize extrapulmonary organ perfusion. The objective was to evaluate the diagnostic accuracy of echocardiography to predict tolerance of negative fluid balance (NFB) in patients with ARDS/ALI., Materials and Methods: A prospective and observational study in an adult intensive care unit of a university hospital was conducted. All hemodynamically stable patients with ARDS/ALI were included. Echocardiography was performed before NFB and again after 24 hours. Tolerance of NFB was evaluated by the presence of hypotension, acute kidney injury, or need for fluid expansion. The 2 patient groups (tolerating and not tolerating NFB) were compared., Results: Forty-five patients were included. Median age (Q1-Q3) was 58 (52-66) years, and the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen was 205 (163-258) mm Hg. Negative fluid balance was 1950 (1200-2200) mL within 24 hours in the tolerant group. Complications of NFB were observed in 35% cases. After univariate and multivariate logistic regression analyzes, 2 criteria was independently associates with poor tolerance: mitral inflow E wave to early diastolic mitral annulus velocities ratio (E/Ea ratio; odds ratio, 2.02 [1.02-4.02]; P = .04) and weight gain (odds ratio, 1.2 [1.03-1.4]; P = .02). The area under receiver operating characteristic curves was 0.74 for E/Ea and 0.77 for weight gain., Conclusions: The ratio of E/Ea accurately predicted tolerance of NFB in patients with ARDS/ALI., (© 2013.)

Background: Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF., Methods: 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 μg/l or ferritin of 100-299 μg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies., Results: Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency., Conclusion: In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID., (© 2013.)

Background: We assessed the global and regional ventricular septal functions using conventional echocardiography and two-dimensional speckle tracking imaging in children with postoperative multiple ventricular septal defects., Methods: Thirty-six children were studied: 16 with postoperative multiple ventricular septal defects and 20 normal control subjects. In children with multiple ventricular septal defects, 60 ventricular septal defects were closed using one of three different techniques (patch closure, the sandwich technique, direct closure). Speckle tracking imaging was applied to three short-axis echocardiographic images., Results: The total patch area used in the multiple ventricular septal defects group was correlated with the postoperative ejection fraction (r=0.703) and Tei index (r=0.778). The global septal peak systolic radial displacement and global septal peak systolic radial strain in the multiple ventricular septal defects group were significantly lower than those observed in the control subjects. The peak systolic radial strain in the segments closed with patches and the peak systolic radial displacement in the segments closed with the felt sandwich technique were significantly lower than those observed in the intact septal segments. No significant regional functional depressions were identified in the segments that were closed directly., Conclusions: The postoperative ventricular global and septal functions were significantly reduced in children with multiple ventricular septal defects, especially in the cases with complex congenital heart disease and that were closed with large prosthetic materials. These results suggest that an effort to minimize the use of patch materials may lead to preserved postoperative ventricular function., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Kawasaki disease (KD) is a common cause of acquired heart disease in children. Recent studies have focused on the biochemical markers of the myocardium, their high sensitivity and specificity and significance in the diagnosis of KD. This study aimed to determine the serum level of brain natriuretic peptide (BNP) and its relation with the heart function of children with KD and to explore its clinical value in diagnosis of KD., Methods: Forty-three KD children, aged from 5 months to 8 years (mean 2.3±0.6 years), were admitted to Qingdao Children's Hospital from February 2007 to April 2009. Among them 27 were male, and 16 female. The 43 patients served as a KD group. Patients with myocarditis, cardiomyopathy, congenital heart disease and other primary heart diseases were excluded. Thirty healthy children, aged from 3 months to 15 years (mean 2.5±0.8 years) or 17 males and 13 females served as a control group. There were no significant differences in age and gender between the two groups (P>0.05). In the KD group, ELISA was used to measure the levels of serum BNP in acute and convalescent stages; and in the control group, the levels of serum BNP were measured once randomly. Left ventricular ejection fraction (LVEF), left ventricular shorten fraction (LVSF), cardiac index (CI) and left ventricular inflow velocity through the mitral annulus (including E-velocity and A-velocity) were measured by two-dimensional echocardiography in the acute and convalescent stages in the KD group. All data were expressed as mean±SD. The methods of analysis included Student's t test and the linear regression analysis test. P<0.05 was considered statistically significant., Results: The level of serum BNP in the acute stage (517.26±213.40) ng/ml was significantly higher than that in the convalescent stage (91.56±47.97) ng/ml in the control group (37.55±7.56) ng/ml (P<0.01). The levels of LVEF, LVSF and CI in the acute stage were significantly lower than those in the convalescent stage (P<0.05), but the E/A level was not significantly different between the acute and convalescent stages (P>0.05). Linear regression analysis showed that the BNP level was negatively correlated with the levels of LVEF, LVSF and CI(r=-0.63, -0.52, -0.53, P<0.05), but not significantly correlated with the E/A level (r=-0.18, P>0.05)., Conclusion: The levels of serum BNP are significantly increased in KD patients, and are negatively correlated with the levels of LVEF, LVSF, and CI. The detection of serum BNP level is of clinical significance in the diagnosis of KD.