Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Impact of Hemodialysis on Left Ventricular-Arterial Coupling in End-Stage Renal Disease Patients.

INTRODUCTION: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. METHODS: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. RESULTS: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. CONCLUSIONS: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings.

Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus.

BACKGROUND: International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice. OBJECTIVE: To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM). METHOD: A prospective screening study at the DM complication screening centre was performed. RESULTS: Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3-5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged <50 years to 7.14% in those aged 70-79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47-9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38-7.69), p = 0.007*), CKD (p<0.001*) and newly detected AF (OR: 7.02 (2.65-18.57), p<0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF <50%. CONCLUSION: NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.

Protocol for Home-Based Solution for Remote Atrial Fibrillation Screening to Prevent Recurrence Stroke (HUA-TUO AF Trial): a randomised controlled trial.

INTRODUCTION: Current international guidelines recommend ECG monitoring after an ischaemic stroke to detect atrial fibrillation (AF) in order to prevent stroke recurrence. However, optimal strategies to detect AF and the downstream management to prevent stroke recurrence remain to be established. The objective of the study was to explore the use of long-term home-based ECG monitoring for AF detection and stroke prevention in patients with a history of stroke. METHODS AND ANALYSIS: This prospective, randomised, open-label trial with blinded endpoint adjudication aimed to evaluate the efficacy of long-term home-based ECG monitoring for AF detection and stroke prevention in a 24-month period. Patients aged >18 years with a history of ischaemic stroke will be stratified according to the time from the index ischaemic stroke: <1, 1-3 and >3 years and then randomised in 1:1 to (1) home-based AF screening and (2) control. The home-based AF screening system comprises (1) a handheld single-lead ECG recorder (Comfit Healthcare Devices, Hong Kong SAR, China) and (2) a patient-facing smartphone application specially designed for the study. Patients randomised to the home-based AF group will record a 30 s single-lead ECG using a specially designed handheld ECG device every morning or when symptomatic. All remotely obtained data will be automatically transmitted in real-time through the study smartphone application to a secured cloud hosting and analysed using an artificial intelligence-based diagnostic system. When a diagnosis of AF is made with the system, the patients will be called back for a formal cardiology consultation within 1 week. The primary endpoint is the time to first detection of AF at 24 months of follow-up. Secondary endpoints include recurrent stroke or transient ischaemic attack, initiation of long-term anticoagulation therapy, hospitalisation for heart failure, cardiovascular death and all-cause death. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of The University of Hong Kong, and Hong Kong West Cluster, Hospital Authority, Hong Kong SAR, China. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04523649.

Antithrombotic therapy and the risk of new-onset dementia in elderly patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of dementia. Little is known about the relationship of antithrombotic therapy and the risk of dementia in patients with AF without clinical stroke. METHOD: This was an observational study based on a hospital AF registry. Patients aged 65-85 years at the time of AF diagnosis were identified via the computerised database of the clinical management system. Patients with prior stroke or known cognitive dysfunction were excluded. The primary outcome was newly diagnosed dementia during the follow-up period. RESULTS: 3284 patients (mean age 76.4±5.3 years, 51.6% male) were included for analysis. The mean CHA2DS2-VASc score was 3.94±1.44. 18.5% patients were prescribed warfarin, 39.8% were prescribed aspirin and 41.7% were prescribed no antithrombotic therapy. After a mean follow-up of 3.6 years, 71 patients (2.2%) developed dementia, giving rise to an incidence of 0.61%/year. The incidence of dementia were 1.04%/year, 0.69%/year and 0.14%/year for patients on no therapy, aspirin and warfarin, respectively. Both univariate and multivariate analyses showed that age ≥75 years, female gender and high CHA2DS2-VASc score were associated with significantly higher risk of dementia; warfarin use was associated with significantly lower risk of dementia (HR: 0.14%, 95% CI 0.05 to 0.36, p<0.001). Patients on warfarin with time in therapeutic range (TTR) ≥65% had a non-significant trend towards a lower risk of dementia compared with those with TTR <65%. CONCLUSION: In elderly AF patients, warfarin therapy was associated with a significantly lower risk of new-onset dementia compared those with no therapy or aspirin.

Body volume is the major determinant of worsening renal function in acutely decompensated heart failure with reduced left ventricular ejection fraction.

AIMS: Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. METHODS AND RESULTS: This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p<0.01), and brain natriuretic peptide (BNP) reduced from 1380±901 pg/mL to 797±738 pg/mL (p<0.01). Nonetheless serum creatinine (SCr) increased from 134±46 µmol/L to 151±53 µmol/L (p<0.01), and 35% of patients developed worsening of renal function. The change in SCr was positively correlated with age (r=0.34, p=0.017); and negatively with the ratio of extracellular water to total body water, a parameter of body volume status (r=-0.58, p<0.001); E:E' ratio (r=-0.36, p=0.01); right ventricular systolic pressure (r=-0.40, p=0.009); and BNP (r=-0.40, p=0.004). Counterintuitively, no correlation was observed between SCr and cardiac output, or total peripheral vascular resistance. Regression analysis revealed that normal body volume and lower BNP independently predicted worsening of renal function. CONCLUSIONS: Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

Daily ambulatory remote monitoring system for drug escalation in chronic heart failure with reduced ejection fraction: pilot phase of DAVID-HF study.

Aims: Underutilization of guideline-directed heart failure with reduced ejection fraction (HFrEF) medications contributes to poor outcomes. Methods and results: A pilot study to evaluate the safety and efficacy of a home-based remote monitoring system for HFrEF management was performed. The system included wearable armband monitors paired with the smartphone application. An HFrEF medication titration algorithm was used to adjust medication daily. The primary endpoint was HFrEF medication utilization at 120 days. Twenty patients (60.5 ± 8.2 years, men: 85%) with HFrEF were recruited. All received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) at recruitment; 45% received ≥50% maximal targeted dose (MTD) with % MTD of 44.4 ± 31.7%. At baseline, 90 and 70% received beta-adrenergic blocker and mineralocorticoid receptor antagonist (MRA), 35% received ≥50% MTD beta-adrenergic blocker with % MTD of 34.1 ± 29.6%, and 25% received ≥50% MTD MRA with % MTD of 25.0 ± 19.9%. At 120 days, 70% received ≥50% MTD ACEI/ARB/ARNI (P = 0.110) with % MTD increased to 64.4 ± 33.5% (P = 0.060). The proportion receiving ≥50% MTD ARNI increased from 15 to 55% (P = 0.089) with % MTD ARNI increased from 20.6 ± 30.9 to 53.1 ± 39.5% (P = 0.006*). More patients received ≥50% MTD MRA (65 vs. 25%, P = 0.011*) with % MTD MRA increased from 25.0 ± 19.9 to 46.2 ± 28.8% (P = 0.009*). Ninety-five per cent of patients had reduced NT-proBNP with the percentage reduction of 26.7 ± 19.7%. Conclusion: Heart failure with reduced ejection fraction medication escalation with remote monitoring appeared feasible.

Reference Values of Carotid Ultrafast Pulse-Wave Velocity: A Prospective, Multicenter, Population-Based Study.

BACKGROUND: Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse-wave velocity (PWV) with high reproducibility, but a lack of reference values has precluded its widespread use in clinical practice. The aims of this study were to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV. METHODS: A total of 1,544 healthy Han Chinese volunteers (581 men [38%]; age range, 18-95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). Basic clinical parameters and carotid PWV at the beginning of systole (BS) and at end-systole (ES) were measured using ultrafast ultrasound imaging techniques. RESULTS: PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. PWV at BS was significantly higher in men than in women; however, no significant difference was noted in PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with PWV at both BS and ES. PWV at BS and ES progressively increased with increases in age, BP, and BMI. Furthermore, age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established. CONCLUSIONS: Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness.

The impact of cigarette smoking in predicting stroke using CHADS2 and CHA2DS2-VASc schemas.

OBJECTIVE: To determine the impact of smoking status in the prediction of stroke using CHADS2 and CHA2DS2-VASc schemes. METHODS: Five hundred twenty-eight consecutive patients with arrhythmic symptoms and without any documented arrhythmia from Queen Mary Hospital, Hong Kong, were followed up to determine the incidence of ischemic stroke, new-onset atrial fibrillation (AF), or all-cause mortality. Smoking status was classified into nonsmokers and smokers. The pairwise comparisons of C-statistics for outcomes were performed. RESULTS: During a median follow-up period of 6.2 years, 65 (12.3%) individuals developed ischemic stroke. Smokers experienced higher annual incidence of stroke, a new-onset AF, and all-cause death compare to nonsmokers, with corresponding hazard ratio (HR) of stroke, AF, and all-cause death being 2.51 (95% confidence intervals, CI 1.36als, CIse death bein 1.15a3.24), and 1.95 (95% CI 1.161.95 (95% CIath being 2.51 (95% confidence corr2 and CHA2DS2-VASc for stroke were 0.60 (95% CI 0.51 for stp = 0.09) and 0.59 (95% CI 0.50 (95%, p = 0.15) respectively, whereas the C-statistics of CHADS2 and CHA2DS2-VASc were 0.66 (95% CI 0.61 were 0p = 0.005), 0.75 (95% CI 0.7 CI 0.7p < 0.0001), respectively among nonsmokers. After incorporating smoking, both the CHADS2-smoking and CHA2DS2-VASc-smoking achieved better C-statistics for new-onset ischemic stroke prediction superior to baseline score systems in male groups. CONCLUSION: Cigarette smoking status has impact on stroke stratification using CHADS2 and CHA2DS2-VASc scheme. The discrimination of the CHADS2 and CHA2DS2-VASc scheme for stroke can be significantly improved if smoking status is additionally considered.

Point-of-care ultrasound augments physical examination learning by undergraduate medical students.

BACKGROUND: Little is known about the impact of the provision of handheld point-of-care ultrasound (POCUS) devices on physical examination skills of medical students. METHODS: We describe an educational initiative that comprised a POCUS workshop followed by allocation of a POCUS device to medical students for use over the subsequent 8 weeks. They were encouraged to scan patients and correlate their physical examination findings. A mobile instant messaging group discussion platform was set to provide feedback from instructors. Physical examination skills were assessed by means of clinical examination. RESULTS: 210 final-year medical students from the University of Hong Kong participated in the programme. 46.3% completed the end of programme electronic survey: 74.6% enjoyed using the POCUS device, 50.0% found POCUS useful to validate physical examination findings and 47.7% agreed that POCUS increased their confidence with physical examination. 93.9% agreed that the programme should be incorporated into the medical curriculum and 81.9% would prefer keeping the device for longer time from 16 weeks (45.6%) to over 49 weeks (35.3%). Medical students who participated in the POCUS programme had a higher mean score for abdominal examination compared with those from the previous academic year with no POCUS programme (3.65±0.52 vs 3.21±0.80, p=0.014), but there was no statistically significant difference in their mean score for cardiovascular examination (3.62±0.64 vs 3.36±0.93, p=0.203). CONCLUSION: The POCUS programme that included provision of a personal handheld POCUS device improved students' attitude, confidence and ability to perform a physical examination.

Can Combined Screening of Ultrasound and Elastography Improve Breast Cancer Identification Compared with MRI in Women with Dense Breasts-a Multicenter Prospective Study.

Objectives: To assess the performance of elastography (ES) and ultrasound (US) in predicting the malignancy of breast lesions and to compare their combined diagnostic value with that of magnetic resonance imaging (MRI). Materials and Methods: The study prospectively enrolled 242 female patients with dense breasts treated in 35 heath care facilities in China between November 2018 and October 2019. Based on conventional US and elastography, radiologists classified the degree of suspicion of breast lesions according to the US Breast Imaging Reporting and Data System (BI-RADS) criteria. The diagnostic value was compared between US BI-RADS and MRI BI-RADS, with pathological results used as the reference standard. Results: The results demonstrated that irregular tumor shape, a nonparallel growth orientation, indistinct margins, angular contours, microcalcifications, color Doppler flow and ES score on US imaging were significantly related to breast cancer in dense breasts (P=0.001; P=0.001; P=0.008; P<0.001; P=0.019; P=0.008; P=0.002, respectively). The sensitivity, specificity, PPV, NPV, accuracy and AUC of US BI-RADS category were 94.7%, 90.7%, 95.8%, 88.0%, 93.4% and 0.93 (95%CI, 0.88-0.97), respectively, while those of MRI BI-RADS category were 98.2%, 57.5%, 84.3%, 83.3%, 86.0% and 0.78 (95%CI, 0.71-0.85), respectively. MRI BI-RADS showed a significantly higher sensitivity than US BI-RADS (98.2% vs 94.7%, P=0.043), whereas US BI-RADS showed significantly higher specificity (90.7% vs 57.5%, P<0.001). US BI-RADS showed better diagnostic efficiency in differentiating nodules in dense breasts than MRI BI-RADS (AUC 0.93 vs 0.78, P<0.001). Conclusion: By combining the use of ES and conventional US, US BI-RADS had better diagnostic efficiency in differentiating nodules in dense breasts than MRI. For the diagnosis of malignant tumors in patients with dense breasts, MRI and US BI-RADS can be used as supplemental diagnostic tools to detect lesions, with US BI-RADS considered the preferred adjunctive resource.

PAK1 promotes proliferation, migration and invasion of hepatocellular carcinoma by facilitating EMT via directly up-regulating Snail.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary cause of cancer mortality. PAK1 plays key roles in many types of cancers. However, the role of PAK1 in HCC is not clear. METHODS: qRT-PCR and Western blotting were used to determine expressions of PAK1, Snail and epithelial mesenchymal transition (EMT)-related proteins. Luciferase reporter assay was used to measure the interaction between PAK1 and Snail. Wound healing, transwell, colony formation assays and flow cytometry were used to assess cell migration, invasion, proliferation and apoptosis. Mouse tumor xenograft model was used to determine the effect of PAK1 on tumor growth in vivo. RESULTS: PAK1 and Snail were up-regulated in HCC cells. PAK1 knockdown suppressed cell proliferation, migration and invasion, and increased apoptosis of HCC cells. PAK1 knockdown also inhibited tumor growth in vivo. Mechanistically, PAK1 promoted EMT by targeting Snail. Knockdown of PAK1 could up-regulate pro-apoptotic proteins but down-regulate proliferation-related proteins via suppressing ß-catenin signaling pathway. CONCLUSION: PAK1 promotes EMT process by increasing Snail, and facilitates progression of HCC by activating ß-catenin pathway.

Changes in left ventricular function and contractile homogeneity in young adults with newly diagnosed hyperthyroidism due to Graves' disease.

PURPOSE: The aim of this study was to investigate myocardial dysfunction and mechanical abnormalities in young patients with Graves' disease before therapy, using two-dimensional speckle tracking echocardiography. METHODS: We performed a comprehensive transthoracic echocardiographic examination, including segmental and global radial strain, and time-to-peak radial strain, in 47 young patients with hyperthyroidism and 34 healthy adults. The time-to-peak radial strain was corrected by RR interval. The variables derived from radial myocardial deformation by the six-basal, six-mid, and six-apical segmental model were compared to investigate the difference of the myocardial function between the two groups. RESULTS: Early diastolic mitral inflow velocity, E/A ratio, early diastolic mitral annular velocity, and e'/a' ratio were lower in patients with Graves' disease than in controls. The left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume, cardiac output, heart rate, late diastolic mitral inflow velocity, and late diastolic mitral annular velocity were slightly higher in patients than in controls. Radial strain, global radial strain, and corrected time-to-peak radial strain were lower in the patient group. CONCLUSIONS: The decreased radial strain, global radial strain, and corrected time-to-peak radial strain in young patients with newly diagnosed hyperthyroidism due to Graves' disease could serve as an early sign of subclinical cardiac involvement.

Risk of venous thromboembolism in Chinese pregnant women: Hong Kong venous thromboembolism study.

BACKGROUND: Previous Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum period in the Chinese population. We investigated the risk of venous thromboembolism in a "real-world" cohort of pregnant Chinese women with no prior history of venous thromboembolism. METHODS: In this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed. RESULTS: The mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29-36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester. CONCLUSION: Chinese women had a substantially lower risk of venous thromboembolism during pregnancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early pregnancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.

A Novel Mathematical Model for Correcting the Physiologic Variance of Two-Dimensional Echocardiographic Measurements in Healthy Chinese Adults.

BACKGROUND: To facilitate differentiation between normal and abnormal values, it is necessary to correct echocardiographic measurements for physiologic variance induced by age, gender, and body size variables. METHODS: A total of 34 two-dimensional echocardiographic parameters were measured in 1,224 healthy Chinese adults with body mass index < 25.0 kg/m2. An optimized multivariate allometric model and scaling equations were first developed in 858 subjects (group A), and their reliability was then verified in the remaining 366 subjects (group B). The traditional single-variable isometric model in which parameters are linearly corrected by a single body size variable (height, weight, body mass index, or body surface area) was used for comparison. The success of correction was defined as the absence of significant correlations (r > 0.20, P < .05) between the corrected values and age or any body size variables, while maintaining high correlations (r > 0.80) between the corrected and uncorrected values. RESULTS: Before correction, all 34 parameters correlated significantly with one or more of the physiologic variables of age and body size and differed significantly between men and women on 29 parameters (85.3%) in both groups. The success rate of correction with the single-variable isometric model was only 11.0% (15 of 136 corrections due to four variable corrections used for each parameter), while use of the optimized multivariate allometric model successfully corrected all 34 parameters (100%) for physiologic variance induced by age and body size variables and eliminated the gender differences in 32 parameters (94.1%). A new set of reference values for corrected echocardiographic measurements independent of age, gender, and body size variables were established. CONCLUSIONS: The novel optimized multivariate allometric model developed in this study is superior to traditional the single-variable isometric model in the correction of echocardiographic parameters for physiologic effects of age, gender, and body size variables and thus should be encouraged in both scientific research and clinical practice.

miR-122 enhances sensitivity of hepatocellular carcinoma to oxaliplatin via inhibiting MDR1 by targeting Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the primary causes of cancer-related death and resistance to cytotoxic chemotherapy is the major cause of mortality in HCC patients. miR-122 is a liver specific miRNA and is found to be reduced in HCC, however, the function of miR-122 in HCC chemosensitivity remains elusive. METHODS: We used qRT-PCR to measure expressions of miR-122, ß-catenin and MDR1 in four HCC cell lines. And we assessed the effects of miR-122 or ß-catenin on cell viability and apoptosis upon oxaliplatin (OXA) treatment by MTT assay and flow cytometry. In addition, we validated the interactions of miR-122/ß-catenin and ß-catenin/MDR1 by dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). Western blotting was used to determine the protein levels of ß-catenin, Wnt1 and MDR1. In the end, we verified the anti-tumor effect of miR-122 in vivo by using mouse tumor xenograft model. RESULTS: We found that miR-122 was down-regulated in HCC cells. Up-regulation of miR-122 or inhibition of Wnt/ß-catenin signaling promoted HCC cells apoptosis and increased the sensitivity of HCC cells to OXA. On the molecular level, we showed that miR-122 directly targeted and suppressed Wnt/ß-catenin pathway while ß-catenin bound with MDR1 promoter and activated its transcription. Overexpression of miR-122 inhibited MDR1 expression via directly suppressing Wnt/ß-catenin pathway. CONCLUSION: Our study fully demonstrated that miR-122 inhibits MDR1 expression via suppression of Wnt/ß-catenin pathway, thereby enhancing HCC sensitivity to OXA. Therefore, miR-122 could serve as a novel potential therapeutic target for HCC.

Rationale and design of the screening of pulmonary hypertension in systemic lupus erythematosus (SOPHIE) study.

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

Four-dimensional echocardiography area strain combined with exercise stress echocardiography to evaluate left ventricular regional systolic function in patients with mild single vessel coronary artery stenosis.

BACKGROUND: The aim of this prospective study was to assess the diagnosis value of four-dimensional echocardiography area strain (AS) combined with exercise stress echocardiography to evaluate left ventricular regional systolic function in patients with mild single vessel coronary artery stenosis. METHODS: Based on treadmill exercise load status, two-dimensional conventional echocardiography and four-dimensional echocardiography area strain were performed on patients suspected coronary artery disease before coronary angiogram. Thirty patients (case group) with mild left anterior descending coronary artery stenosis (stenosis <50%) and thirty gender- and age-matched patients (control group) without coronary artery stenosis according to the coronary angiogram results were prospectively enrolled. RESULTS: All the patients had no left ventricular regional wall motion abnormality in two-dimensional echocardiography at rest and exercise stress. There was no significant difference in the 16 segmental systolic peak AS at rest between two groups. After exercise stress, the peak systolic ASrest-stress at mid anterior wall (-7.00%±10.90% vs 2.80%±23.69%) and mid anterolateral wall (-4.40%±18.81% vs 8.80%±19.16%) were decreased, while increased at basal inferolateral wall (14.00%±19.27% vs -5.60%±15.94%) in case group compared with control group (P<.05). CONCLUSIONS: In patients with mild single vessel coronary artery stenosis, the area strain was decreased at involved segments, while compensatory increased at noninvolved segments after exercise stress. Four-dimensional echocardiography area strain combined with exercise stress echocardiography could sensitively find left ventricular regional systolic function abnormality in patients with mild single vessel coronary artery stenosis, and locate stenosis coronary artery accordingly.

Prediction of Thromboembolic Events in Heart Failure Patients in Sinus Rhythm: The Hong Kong Heart Failure Registry.

AIM: Heart failure (HF) increases the risk of thromboembolic events (TE). Study in a Caucasian population has shown that the CHA2DS2-VASc score predicts TE among HF patients without atrial fibrillation. We sought to assess the usefulness of the CHA2DS2-VASc score in predicting TE in an Asian population and refine the scoring system to improve its predictability of TE among HF patients in sinus rhythm. METHODS: A total of 1,202 consecutive patients who were admitted to our institution for new-onset HF from 2005 to 2012 and without atrial fibrillation or anticoagulation were retrospectively reviewed. RESULTS: The mean age was 77.6 ± 12.2 years and 51.7% were female. After 36.2 ± 30.1 months, 113 (9.4%) developed TE. The annual incidence was 0.54%, 1.54%, 2.98% and 5.04% per year in those who had a CHA2DS2-VASc score of 1, 2-3, 4-5 and ≥6, respectively. In multivariate analysis, age ≥75 years [Hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.23-5.46, p = 0.012), chronic ischemic heart disease (HR 1.54, 95% CI 1.02-2.31, p = 0.040) and chronic kidney disease (HR 1.66, 95% CI 1.09-2.53, p = 0.018) independently predicted TE. Incorporation of chronic ischemic heart disease and chronic kidney disease into the CHA2DS2-VASc score significantly increased the area under the Receiver Operating Curve from 0.57 (95% CI 0.54-0.59) to 0.61 (95% CI 0.55-0.66; p = 0.022). CONCLUSION: The CHA2DS2-VASc score is useful for stratification of the risk of TE among HF patients in sinus rhythm. Incorporation of chronic ischemic heart disease and chronic kidney disease into the score modestly improves its predictive value.