Improved identification of left atrial enlargement in patients with obesity.

Accurate standardization of left atrium volume (LAV) in patients with obesity is challenging. The aim of this study was to investigate and to examine the relation between LAV indexed to height2 and left atrial function in patients with moderate to severe obesity. Echocardiograms of patients with moderate to severe obesity (body mass index (BMI) ≥ 35 kg/m2) without known cardiac disease were analyzed. LAV was indexed to body surface area (BSA) and height2, and patients were divided into those with or without left atrial enlargement (LAE) based on normalization using either BSA (LAEbsa) or height2 (LAEh2). Using speckle tracking echocardiography, LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were assessed as a measure of LA function. LA dysfunction was defined as LASct < 14%. A total of 142 patients were included in the analysis of whom 54.2% had LAEh2 and 18.3% LAEBSA. The LAEh2 group had significantly lower LASct (12.2% ± 3.2% vs. 13.6% ± 4.5%, p = 0.019) as compared to the patients without LAEh2. Significantly more patients with LA dysfunction would be correctly identified by LAEh2 than by LAEBSA (41.5% vs. 15.0%, p < 0.001). In patients with moderate to severe obesity, the use of LAEh2 identified significantly more patients with decreased LA function. LAVh2 should be preferred over LAVBSA in patients with moderate to severe obesity.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

AIM: Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. METHODS AND RESULTS: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (ß coefficient -0.404, p = 0.002), and a decrease in LASct (%) (ß coefficient -0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). CONCLUSIONS: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.

Potential role of left atrial strain in estimation of left atrial pressure in patients with chronic heart failure.

AIMS: In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available. METHODS AND RESULTS: Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP. CONCLUSIONS: In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.

The Beneficial Effect of Praeruptorin C on Osteoporotic Bone in Ovariectomized Mice via Suppression of Osteoclast Formation and Bone Resorption.

Being a highly prevalent disease, osteoporosis causes metabolism defects. Low bone density, compromised bone strength, and an increased danger of fragility fracture are its main characteristics. Natural compounds have been considered as potential alternative therapeutic agents for treating osteoporosis. In this study, we demonstrated that a natural compound, praeruptorin C (Pra-C), derived from the dried roots of Peucedanum praeruptorum, has beneficial effects in suppressing osteoclast formation and resorption function via attenuating the activation of nuclear factor kappa B as well as c-Jun N-terminal kinase/mitogen-activated protein kinase signaling pathways. Moreover, Pra-C was tested in the ovariectomized (OVX) mice, a well-established model of post-menopausal bone loss, and the results indicated Pra-C exerted beneficial effects on inhibiting excessive osteoclast activity and increasing bone mass of OVX mice. Therefore, the protective effects of Pra-C on OVX mice bone are related to its inhibition of osteoclast formation and bone resorption, suggesting that Pra-C is a good potential candidate for osteoporosis treatment.

The use of molecular analyses in voided urine for the assessment of patients with hematuria.

INTRODUCTION: Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer. MATERIAL AND METHODS: Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model. RESULTS: Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively. CONCLUSIONS: This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.