Evaluation of the effectiveness and safety of a novel substrate-based radiofrequency ablation for persistent atrial fibrillation: a prospective, randomised, parallel-controlled, single-blinded study protocol.

INTRODUCTION: Pulmonary vein isolation (PVI) is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF). However, a single ablation strategy does not always achieve the desired therapeutic effect in all patients with persistent AF, and individualised strategies are required for different clinical characteristics. METHODS AND ANALYSIS: This study aimed to determine the optimal catheter ablation strategy for persistent AF by comparing the efficacy of PVI and BCXL (BC: big circles encircling pulmonary vein isolation; XL: unfixed number of lines based on the left atrial substrate). The BCXL-AF study (clinical trial no. ChiCTR2200067081) was designed as a prospective, randomised, parallel-controlled, single-blinded clinical trial. Overall, 400 patients with persistent AF were randomised in a 1:1 ratio into PVI-only and BCXL-individualised ablation groups. Patients randomised to the individualised ablation group will be further categorised into risk strata according to their clinical condition using the actual ablation method determined by the strata. Seven postoperative visits were conducted from discharge to 24 months of age. The primary observation endpoint will be the incidence of atrial tachyarrhythmia (including AF, atrial flutter and atrial tachycardia with a duration of ≥30 s) without using antiarrhythmic drugs after a blank period of 3 months following a single ablation procedure. The BCXL-AF study will assess an optimal approach for persistent AF RF ablation and evaluate the effectiveness of individualised RF ablation strategies in reducing the recurrence rate of AF. ETHICS AND DISSEMINATION: The study protocol was reviewed, and ethical approval was obtained from the Army Medical University Human Ethics Committee (approval number: 2022-484-01). All the participants provided written informed consent. This study was conducted according to the principles of the Declaration of Helsinki and its amendments. The results of this study will be disseminated through manuscript publication and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200067081.

Single-cell RNA sequencing reveals a mechanism underlying the susceptibility of the left atrial appendage to intracardiac thrombogenesis during atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of thrombosis of the left atrial appendage (LAA). However, the molecular mechanisms underlying this site-specificity remain poorly understood. Here, we present a comparative single-cell transcriptional profile of paired atrial appendages from patients with AF and illustrate the chamber-specific properties of the main cell types. METHODS: Single-cell RNA sequencing analysis of matched atrial appendage samples from three patients with persistent AF was evaluated by 10× genomics. The AF mice model was created using Tbx5 knockout mice. Validation experiments were performed by glutathione S-transferase pull-down assays, coimmunoprecipitation (Co-IP), cleavage assays and shear stress experiments in vitro. RESULTS: In LAA, phenotype switching from endothelial cells to fibroblasts and inflammation associated with proinflammatory macrophage infiltration were observed. Importantly, the coagulation cascade is highly enriched in LAA endocardial endothelial cells (EECs), accompanying the up-regulation of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) and the down-regulation of the tissue factor pathway inhibitor (TFPI) and TFPI2. Similar alterations were verified in an AF mouse model (Tbx5+/- ) and EECs treated with simulated AF shear stress in vitro. Furthermore, we revealed that the cleavage of both TFPI and TFPI2 based on their interaction with ADAMTS1 would lead to loss of anticoagulant activities of EECs. CONCLUSIONS: This study highlights the decrease in the anticoagulant status of EECs in LAA as a potential mechanism underlying the propensity for thrombosis, which may aid the development of anticoagulation therapeutic approaches targeting functionally distinct cell subsets or molecules during AF.

Effect of social app-assisted education and support on glucose control in patients with coronary heart disease and diabetes mellitus.

Background: Social app-assisted education and support may facilitate diabetes self-management. We aim to evaluate the effect of WeChat, a popular social app, on glycemic control in patients with coronary heart disease (CHD) and diabetes mellitus (DM). Methods: We conducted a parallel-group, open-label, randomized clinical trial that included 160 patients with both CHD and diabetes mellitus from a tertiary hospital in China. The intervention group (n = 80) received educational materials (information on glucose monitoring, drug usage, medication, and lifestyle) and reminders in response to individual blood glucose values via WeChat. The control group (n = 80) received usual care. The primary outcome was a change in glycated hemoglobin (HbA1C) levels over 3 months. Secondary outcomes included fasting blood glucose (FBG), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol from baseline to 3 months. Analysis was conducted using a linear mixed model. Results: The intervention group had a greater reduction in HbA1C (-0.85 vs. 0.15%, between-group difference: -1.00%; 95% CI -1.31 to -0.69%; p < 0.001) compared with the control group. Change in fasting blood glucose was larger in the intervention group (-1.53 mmol/L; 95% CI -1.90 to -1.17; p < 0.001) and systolic blood pressure (-9.06 mmHg; 95% CI -12.38 to -5.73; p < 0.001), but not LDL (between-group difference, -0.08 mmol/L; 95% CI -0.22 to 0.05; p = 0.227). Conclusion: The combination of social app with education and support resulted in better glycemic control in patients with CHD and DM. These results suggest that education and support interaction via social app may benefit self-management in CHD and DM.

Systemic Blood Predictors of Elevated Pulmonary Artery Pressure Assessed by Non-invasive Echocardiography After Acute Exposure to High Altitude: A Prospective Cohort Study.

Aim: Elevated pulmonary artery pressure (ePAP) in response to high-altitude hypoxia is a critical physiopathological factor in the hypoxic adaptation that may lead to high-altitude pulmonary edema in the acute phase or high-altitude pulmonary hypertension in the long term. However, the sea-level predictors of risk factors for altitude-induced ePAP have not been examined. Thus, we aimed to identify the baseline systemic blood predictors of ePAP after acute high-altitude exposure. Materials and Methods: A total of 154 participants were transported to a high altitude 3,700 m from sea level within 2 h. Echocardiography examinations were performed to assess the mean pulmonary artery pressure (mPAP) and hemodynamics at both altitudes. All the individuals underwent blood tests to determine the concentrations of vascular regulatory factors. Univariate and adjusted logistic regression analyses were performed to identify the independent predictors of ePAP and factors related to ePAP. Results: The mPAP increased significantly from sea level to high altitude (19.79 ± 6.53-27.16 ± 7.16 mmHg, p < 0.05). Increased levels of endothelin (ET-1), Ang (1-7), Ang II, and bradykinin were found after high-altitude exposure, while the levels of nitric oxide (NO), prostaglandin E2 (PEG2), and serotonin decreased sharply (all p-values < 0.05). At high altitude, 52.6% of the subjects exhibited ePAP, and the mPAP was closely correlated with the baseline Ang II level (r = 0.170, p = 0.036) and follow-up levels of NO (r = -0.209, p = 0.009), Ang II (r = 0.246, p = 0.002), and Ang (1-7) (r = -0.222, p = 0.006) and the left atrial inner diameter (LAD, r = 0.270, p < 0.001). Both the baseline and follow-up NO and Ang II levels were significantly different between the ePAP and non-ePAP groups. Finally, we identified the baseline Ang II and NO concentrations as two independent predictors of ePAP (p < 0.05). We also found that two vascular regulatory factors with inverse roles, namely, Ang (1-7) and Ang II, at high altitudes were independently associated with ePAP. Additionally, ET-1, NO, PEG2, and LAD were associated with ePAP. Conclusion: The baseline concentrations of Ang II and NO at sea level are two independent predictors of ePAP after acute high-altitude exposure. Furthermore, Ang (1-7) and Ang II combined with ET-1, NO, PEG2, and LAD at high altitudes may contribute to the development of ePAP.

Baseline Ratio of Soluble Fas/FasL Predicts Onset of Pulmonary Hypertension in Elder Patients Undergoing Maintenance Hemodialysis: A Prospective Cohort Study.

Background: Pulmonary hypertension (PH) is one of the most common complications associated with end-stage renal disease (ESRD). Though numerous risk factors have been founded, other risk factors remain unidentified, particularly in patients undergoing maintenance hemodialysis with elder age. Soluble Fas (sFas) and its ligand FasL (sFasL) have been reported in chronic renal disease patients; however, they have not been identified in the PH patients of elder hemodialysis patients. We aimed to determine the roles of sFas/sFasL in onset of PH in elder patients undergoing maintenance hemodialysis with ESRD. Methods: Altogether, 163 patients aged 68.00 ± 10.51 years with ESRD who undergoing maintenance hemodialysis in a prospective cohort and were followed-up for a median of 5.5 years. They underwent echocardiography examinations, liver function assessments, residual renal function, and serum ion examinations, before and after dialysis. Furthermore, levels of sFas and sFasL at baseline had also been measured. We compared demographic data, echocardiographic parameters, liver function, ions, and residual renal function as well as serum sFas and sFasL between the PH and non-PH groups. These parameters were correlated with systolic pulmonary artery pressure (sPAP) using Spearman's correlation. Moreover, univariate and adjusted logistic regression analyses have also been conducted. Results: The incidence of PH in the elder dialysis patients was 39.1%. PH populations were demonstrated with significantly higher end-diastolic internal diameters of the left atrium, left ventricle, right ventricle (RV), and pulmonary artery, as well as the left ventricular posterior wall thickness (LVWP; all p < 0.05). A higher baseline serum sFas and sFasL levels have also been identified ( p < 0.001). They also showed lower fractional shortening and left ventricular ejection fraction (LVEF; p < 0.05). Following dialysis, the post-dialysis serum potassium concentration (K+) was significantly higher in the PH group ( p = 0.013). Furthermore, the adjusted regression identified that ratio of sFas/FasL (OR: 1.587, p = 0.004), RV (OR: 1.184, p = 0.014), LVPW (OR: 1.517, p = 0.007), and post-dialysis K+ (OR: 2.717, p = 0.040) was the independent risk factors for PH while LVEF (OR: 0.875, p = 0.040) protects patients from PH. Conclusion: The baseline ratio of sFas/sFasL, RV, LVPW, and post-dialysis K+ was independent risk factors for PH onset, while LVEF was a protective factor for PH.

A novel echocardiographic parameter to identify individuals susceptible to acute mountain sickness.

BACKGROUND: Acute mountain sickness (AMS) may cause life-threatening conditions. This study aimed to screen echocardiographic parameters at sea level (SL) to identify predictors of AMS development. METHODS: Overall, 106 healthy men were recruited at SL and ascended to 4100 m within 7 days by bus. Basic characteristics, physiological data, and echocardiographic parameters were collected both at SL and 4100 m above SL. AMS was identified by 2018 Lake Louise Questionnaire Score. RESULTS: After acute high altitude exposure (AHAE), 33 subjects were diagnosed with AMS and exhibited lower lateral mitral valve tissue motion annular displacement (MV TMADlateral) at SL than AMS-free subjects (13.09 vs. 13.89 mm, p = 0.022). MV TMADlateral at SL was significantly correlated with AMS occurrence (OR = 0.717, 95% CI: 0.534-0.964, p = 0.028). The MV TMADlateral<13.30-mm group showed over 4-fold risk for AMS development versus the MV TMADlateral≥13.30-mm group. After AHAE, the MV TMADlateral<13.30-mm group had increased HR (64 vs. 74 bpm, p = 0.001) and right-ventricular myocardial performance index (0.54 vs. 0.69, p = 0.009) and decreased left ventricular global longitudinal strain (-21.50 vs. -20.23%, p = 0.002), tricuspid valve E/A ratio (2.11 vs. 1.89, p = 0.019), and MV E-wave deceleration time (169.60 vs. 156.90 ms, p = 0.035). CONCLUSION: MV TMADlateral at SL was a potential predictor of AMS occurrence and might be associated with differential alterations of ventricular systolic and diastolic functions in subjects with different MV TMADlateral levels at SL after AHAE.

Echocardiographic Right Ventricular Outflow Track Notch Formation and the Incidence of Acute Mountain Sickness.

Yuan, Fangzhengyuan, Zhexue Qin, Chuan Liu, Shiyong Yu, Jie Yang, Jun Jin, Shizhu Bian, Xubin Gao, Jihang Zhang, Chen Zhang, Mingdong Hu, Jingbin Ke, Yuanqi Yang, Jingdu Tian, Chunyan He, Wenzhu Gu, Chun Li, Rongsheng Rao, and Lan Huang. Echocardiographic right ventricular outflow track notch formation and the incidence of acute mountain sickness. High Alt Med Biol. 22:263-273, 2021. Background: High-altitude exposure causes acute mountain sickness (AMS) and increases pulmonary arterial pressure (PAP). The notching of echocardiographic right ventricular outflow tract flow velocity envelope (right ventricular outflow tract [RVOT] notching), is related to increased PAP. We speculate that acute high-altitude exposure may trigger RVOT notching, which may be associated with AMS. Methods: All 130 subjects, ascended to 4,100 m from low altitude by bus within 7 days, underwent physiological and echocardiographic testing. The subjects with a total score of 3 or above and in the presence of a headache were diagnosed with AMS according to Lake Louise criteria. Results: After high-altitude exposure, the incidence of RVOT notching and AMS was 20% and 28.5%, respectively. The subjects with AMS had a higher incidence (37.8%) of RVOT notching than those without AMS (12.9%). Multivariate logistic regression analysis showed that RVOT notching was associated with systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.05-1.17; p < 0.001) and the occurrence of AMS (OR, 5.48; 95% CI, 1.96-15.35; p = 0.001). Although linear regression analysis showed a weak correlation between SPAP and Lake Louise AMS score in the overall population (r = 0.20, p = 0.020), this correlation was more pronounced in the subpopulation with RVOT notching (r = 0.44, p = 0.023) and SPAP was not related to Lake Louise AMS score in the subpopulation without RVOT notching (r = 0.03, p = 0.698). Among AMS symptoms, the incidence of headache and fatigue were higher in subjects with RVOT notching than those in subjects without RVOT notching. Conclusions: We first observe that high-altitude exposure triggers RVOT notching formation, which is associated with AMS occurrence. Clinical Trials.gov ID: ChiCTR-RCS-12002232.

The Association Between Notching of the Right Ventricular Outflow Tract Flow Velocity Doppler Envelope and Impaired Right Ventricular Function After Acute High-Altitude Exposure.

INTRODUCTION: Pulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear. METHODS: A total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 ± 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 × (maximum tricuspid regurgitation velocity)2+5 and mean PAP (mPAP) = 0.61 × SPAP+2. Cardiac output was calculated as stroke volume × heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 × mitral E/e'. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)/CO. RESULTS: After HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (-)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s') at the mitral/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO2), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO2, RV GLS, and TAPSE/SPAP were more pronounced in the notch (+) group than in the notch (-) group. Additionally, increased tricuspid ICV and mitral/tricuspid s' were found only in the notch (-) group. CONCLUSION: HA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s', reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.

Assessment of right atrial dyssynchrony by 2D speckle-tracking in healthy young men following high altitude exposure at 4100 m.

BACKGROUND: High altitude exposure induces overload of right-sided heart and may further predispose to supraventricular arrhythmia. It has been reported that atrial mechanical dyssynchrony is associated with atrial arrhythmia. Whether high altitude exposure causes higher right atrial (RA) dyssynchrony is still unknown. The aim of study was to investigate the effect of high altitude exposure on right atrial mechanical synchrony. METHODS: In this study, 98 healthy young men underwent clinical examination and echocardiography at sea level (400 m) and high altitude (4100 m) after an ascent within 7 days. RA dyssynchrony was defined as inhomogeneous timing to peak strain and strain rate using 2D speckle-tracking echocardiography. RESULTS: Following high altitude exposure, standard deviation of the time to peak strain (SD-TPS) [36.2 (24.5, 48.6) ms vs. 21.7 (12.9, 32.1) ms, p<0.001] and SD-TPS as percentage of R-R' interval (4.6 ± 2.1% vs. 2.5 ± 1.8%, p<0.001) significantly increased. Additionally, subjects with higher SD-TPS (%) at high altitude presented decreased right ventricular global longitudinal strain and RA active emptying fraction, but increased RA minimal volume index, which were not observed in lower group. Multivariable analysis showed that mean pulmonary arterial pressure and tricuspid E/A were independently associated with SD-TPS (%) at high altitude. CONCLUSION: Our data for the first time demonstrated that high altitude exposure causes RA dyssynchrony in healthy young men, which may be secondary to increased pulmonary arterial pressure. In addition, subjects with higher RA dyssynchrony presented worse RA contractile function and right ventricular performance.

Atrial performance in healthy subjects following high altitude exposure at 4100 m: 2D speckle-tracking strain analysis.

High altitude (HA) exposure has been considered as a cardiac stress and might impair ventricular diastolic function. Atrial contraction is involved in ventricular passive filling, however the atrial performance to HA exposure is poorly understood. This study aimed to evaluate the effect of short-term HA exposure on bi-atrial function. Physiological and 2D-echocardiographic data were collected in 82 healthy men at sea level (SL, 400 m) and 4100 m after an ascent within 7 days. Atrial function was measured using volumetric and speckle-tracking analyses during reservoir, conduit and contractile phases of cardiac cycle. Following HA exposure, significant decreases of reservoir and conduit function indexes were observed in bi-atria, whereas decreases of contractile function indexes were observed in right atrium (RA), estimated via RA active emptying fraction (SL 41.7 ± 13.9% vs. HA 35.4 ± 12.2%, p = 0.001), strain during the contractile phase [SL 13.5 (11.4, 17.8) % vs. HA 12.3 (9.3, 15.9) %, p = 0.003], and peak strain rate during the contractile phase [SL - 1.76 (- 2.24, - 1.48) s-1 vs. HA - 1.57 (- 2.01, - 1.23) s-1, p = 0.002], but not in left atrium (LA). In conclusion, short-term HA exposure of healthy individuals impairs bi-atrial performance, mostly observed in RA. Especially, atrial contractile function decreases in RA rather than LA, which seems not to compensate for decreased ventricular filling after HA exposure. Our findings may provide a novel evidence for right-sided heart dysfunction to HA exposure.

The Prevalence of Pulmonary Hypertension Among Maintenance Dialysis Patients With ESRD and Its Associated Factors: A Retrospective Study.

Aim: To determine the prevalence of pulmonary hypertension (PH) and its associated factors among end-stage renal disease (ESRD) patients who underwent maintenance dialysis. Methods: A total of 491 patients received echocardiography examinations and underwent pulmonary artery systolic pressure (PASP) assessments. A subgroup of 283 patients were subjected to plasma creatinine (Cr) and blood urea nitrogen concentration (BUN) tests, routine blood examinations and electrolyte analysis. First, we compared the differences in echocardiographic, Cr and BUN, blood routine and electrolyte parameters between PH and non-PH groups. The correlations between PASP and the parameters mentioned above were also analyzed. Furthermore, univariate and adjusted logistic regression analyses were performed to identify the independent associated factors. Results: The incidence of PH among ESRD patients who were treated with maintenance dialysis was 34.6%. Most of the echocardiographic parameters, including end-diastolic internal diameters of the left atrium, left ventricle, right atrium, and pulmonary artery, as well as interventricular septum mobility, left ventricular posterior wall mobility, fractional shortening, stroke volume and left ventricle ejection fraction (LVEF), were associated with PH. Furthermore, Mg2+ (p = 0.037) and Cl- (p = 0.043) were significantly associated with PASP. However, after adjustments were made in the regression analysis, only internal diameters of the left atrium, right atrium, and LVEF were independently associated with PH. Conclusion: PH is prevalent, with a relatively high incidence among ESRD patients who undergo maintenance dialysis. The sizes of the left and right atria as well as LVEF were independently associated with PH, but further cohort and basic mechanistic studies are needed to confirm this finding.

Low Stroke Volume Index in Healthy Young Men Is Associated with the Incidence of Acute Mountain Sickness after an Ascent by Airplane: A Case-Control Study.

BACKGROUND: The aims of this study were to explore the characteristics of left ventricular (LV) functional changes in subjects with or without acute mountain sickness (AMS) and their associations with AMS incidence. METHODS: A total of 589 healthy men were enrolled and took a trip from Chengdu (500 m, above sea level (asl)) to Lhasa (3700 m, asl) by airplane. Basic characteristics, physiological data, and echocardiographic parameters were collected both at Chengdu and Lhasa, respectively. AMS was identified by the Lake Louise Questionnaire Score. RESULTS: The oxygen saturation (SpO2), end-systolic volume index, end-diastolic volume index (EDVi), stroke volume index (SVi), E-wave velocity, and E/A ratio were decreased, whereas the heart rate (HR), ejection fraction, cardiac index (CI), and A-wave velocity were increased at the third day after arrival, as evaluated by an oximeter and echocardiography. However, AMS patients showed higher HR and lower EDVi, SVi, CI, E-wave velocity, and E/A ratio than AMS-free subjects. Among them, SVi, which is mainly correlated with the changes of EDVi and altered LV filling pattern, was the most valuable factor associated with AMS incidence following receiver-operator characteristic curves and linear and Poisson regression. Compared with subjects in the highest SVi tertile, subjects in the middle SVi tertile showed higher multivariable Incidence Rate Ratios (IRR) for AMS with higher incidences of mild headache and gastrointestinal symptoms, whereas subjects in the lowest SVi tertile showed even higher multivariable IRR with higher incidences of all the symptoms. CONCLUSIONS: This relatively large-scale case-control study revealed that the reduction of SVi correlated with the altered LV filling pattern was associated with the incidence and clinical severity of AMS.

Pulmonary function tests at low altitude predict pulmonary pressure response to short-term high altitude exposure.

BACKGROUND: Travelling to high altitude (HA) presents a risk of the high levels of pulmonary artery pressure (PAP) at altitude, which is associated with impaired exercise capacity and fatal HA pulmonary oedema. However, prediction of high levels of PAP at altitude is still unclear. METHODS: Echocardiography and pulmonary function tests were performed on 121 healthy men at low altitude (LA) and 4100 m (5 ± 2 h after a 7 day ascent). RESULTS: HA exposure increased the levels of FEV1/FVC ratio, FEF25%, 50%, 75%, MMEF, mPAP, total pulmonary vascular resistance (PVR) and systolic pulmonary arterial pressure (SPAP). More smokers and lower forced expiratory flow at 25% of forced vital capacity (FEF25%) at LA were observed in subjects with mPAP≥30 mmHg than those with mPAP<30 mmHg at HA. Multivariate logistic regression identified that FEF25% at LA [odds ratio (OR) 0.50, 95%CI 0.33-0.76, p = 0.001] and smoking (OR 3.09, 95%CI 1.31-7.27, p = 0.010) were the independent predictors for identifying subjects with mPAP≥30 mmHg at HA. Moreover, FEF25% at LA was linearly correlated with mPAP at HA (r = -0.31, p < 0.001), which mainly existed in smokers. Compared to subjects with FEF25% ≥7.55 L/sec at LA, those with FEF25% <7.55 L/sec at LA showed higher levels of mPAP, and total PVR, and a multivariable OR of 11.16 (95%CI, 3.48-35.81) for developing mPAP ≥ 30 mmHg at HA. However, there was no significant difference in the incidences of AMS and its related clinical symptoms in subjects with different levels of FEF25%. CONCLUSIONS: Thus, these findings suggest that subjects with low FEF25% values at LA are susceptible to high levels of PAP at altitude but not the incidence of AMS following short-term HA exposure, especially in smokers.

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study.

BACKGROUND: More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified. METHODS: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18-24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status). RESULTS: In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO2 was significantly lower in the AMS group than that in the non-AMS group (P = 0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 (EPAS1) was associated with mild gastrointestinal symptoms (P = 0.013), while rs3025039 (VEGFA) was related to mild headache (P = 0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS (OR = 2.70, P < 0.001). CONCLUSIONS: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR-RCS-12002232 . Registered 31 May 2012.

Preliminary Study of Right Ventricular Dyssynchrony Under High-Altitude Exposure: Determinants and Impacts.

The aims of this study were to explore the effect of high-altitude (HA) exposure on the incidence, determinants, and impacts of right ventricular dyssynchrony (RVD). In our study, 108 healthy young men were enrolled, and physiological and echocardiographic variables were recorded at both sea level and 4,100 m. By using two-dimensional speckle-tracking echocardiography, RVD was evaluated by calculating the R-R interval-corrected standard deviation of the time-to-peak systolic strain for the four mid-basal RV segments (RVSD4) and defined by RVSD4 > 18.7 ms. After HA exposure, RVSD4 was significantly increased, and the incidence of RVD was approximately 32.4%. Subjects with RVD showed lower oxygen saturation (SaO2) and RV global longitudinal strain and higher systolic pulmonary artery pressure than those without RVD. Moreover, myocardial acceleration during isovolumic contraction was increased in all subjects and those without RVD, but not in those with RVD. Multivariate logistic regression revealed that SaO2 is an independent determinant of RVD at HA (odds ratio: 0.72, 95% CI: 0.56-0.92; P = 0.009). However, the mean pulmonary artery pressure was linearly correlated with the magnitude of RVD in the presence of Notch. No changes were found in RV fractional area change, tricuspid annular motion, or tricuspid s' velocity between subjects with and without RVD. Collectively, we demonstrated for the first time that HA exposure could induce RVD in healthy subjects, which may be mainly attributed to the decline in SaO2 as well as RV overload; the incidence of RVD was associated with reduced RV regional function and blunted myocardial acceleration.

Baseline Soluble Anti-erythropoietin Antibody Level Is an Independent Associated Factor for Follow-Up Erythropoietin Demand in Maintenance Dialysis Patients With End-Stage Renal Disease: A Prospective Cohort Study.

Aims: The aim of this study was to identify the predictive role of baseline anti-erythropoietin (anti-EPO) antibody levels in follow-up EPO demand in maintenance dialysis patients with end-stage renal disease (ESRD). Methods: Baseline routine blood parameters, clinical data, dialysis-related parameters, EPO, anti-EPO antibody, and anti-EPO-receptor antibody were also measured. Differences in the abovementioned variables were compared among four intervals of the EPO demand index (EDI). Further univariate and adjusted logistic regression analyses were performed to identify the independent predictors for higher EPO demand. Results: The predialysis potassium ion concentration was significantly higher in the fourth quartile (Q4) population than in the other three populations (p < 0.05). Furthermore, the anti-EPO antibody level showed significant differences among the four intervals (p = 0.006). The baseline anti-EPO antibody level was correlated with the follow-up EDI (r 2 = 0.0377, p = 0.030). Furthermore, the follow-up EDI was significantly higher in the anti-EPO antibody-positive group (p = 0.02). Age (OR = 1.071, p = 0.005), ferritin (OR = 1.001, p = 0.038), potassium ion concentration before dialysis (OR = 2.781, p = 0.012), dialysis duration (OR = 1.025, p = 0.030), and anti-EPO antibody level (OR = 7.694, p = 0.004) were potential predictors for higher EPO demand. After adjustment, age (OR = 1.072, p = 0.026), potassium ion concentration before dialysis (OR = 3.425, p = 0.013), and EPO level (OR = 5.27, p = 0.007) were independent predictors for higher EDI demand. Conclusion: The baseline anti-EPO antibody level combined with an older age and a higher predialysis potassium ion concentration are independent predictors for a higher follow-up EPO demand in maintenance dialysis patients with ESRD.

EDN1 gene potentially involved in the development of acute mountain sickness.

Previous investigations have indicated that environmental and genetic factors collectively contribute to the development of acute mountain sickness (AMS), but whether the EDN1 gene is involved in AMS remains to be elucidated. A total of 356 healthy male soldiers who had not traveled to high altitudes in the previous 12 months were enrolled in our study. All participants were taken by plane from 500 m (Chengdu in Sichuan Province) to a 3700 m highland (Lhasa) within 2 hours. Clinical data were collected within 24 hours, and pulmonary function parameters were completed simultaneously. Genotypes were obtained by using iMLDR genotyping assays. A total of 237 soldiers (66.57%) presented AMS symptoms, including headache, dizziness, gastrointestinal upset and fatigue. Soldiers with AMS showed an increase in heart rate (HR), plasma tryptophan and serotonin, and a decrease in SaO2, FEV1, PEF, FVC, V75, V50, V25 and MMF (all P < 0.01). Notably, allele T in single nucleotide polymorphism (SNP) rs2070699 showed a positive correlation with the occurrence of AMS. A general linear regression analysis showed that rs2060799, Mean Arterial Pressure (MAP), SaO2, FVC, tryptophan and serotonin were independent predictors for the occurrence of AMS. Importantly, the area under the curve (AUC) values for tryptophan (0.998), serotonin (0.912) and FVC (0.86) had diagnostic specificity and sensitivity. Our results demonstrated that AMS is accompanied by changes in lung function parameters, increased plasma tryptophan and serotonin levels, and that the EDN1 polymorphism is a potential risk factor for AMS.

Association of EPAS1 and PPARA Gene Polymorphisms with High-Altitude Headache in Chinese Han Population.

BACKGROUND: High-altitude headache (HAH) is the most common complication after high-altitude exposure. Hypoxia-inducible factor- (HIF-) related genes have been confirmed to contribute to high-altitude acclimatization. We aim to investigate a possible association between HIF-related genes and HAH in the Chinese Han population. METHODS: In total, 580 healthy Chinese Han volunteers were recruited in Chengdu (500 m) and carried to Lhasa (3700 m) by plane in 2 hours. HAH scores and basic physiological parameters were collected within 18-24 hours after the arrival. Thirty-five single nucleotide polymorphisms (SNPs) in HIF-related genes were genotyped, and linkage disequilibrium (LD) was evaluated by Haploview software. The functions of SNPs/haplotypes for HAH were developed by using logistic regression analysis. RESULTS: In comparison with wild types, the rs4953354 "G" allele (P=0.013), rs6756667 "A" allele (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (PPARA (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (. CONCLUSIONS: EPAS1 and PPARA polymorphisms were associated with HAH in the Chinese Han population. Our findings pointed out potentially predictive gene markers, provided new insights into understanding pathogenesis, and may further provide prophylaxis and treatment strategies for HAH.EPAS1, and rs6520015 "C" allele in PPARA (.

The Prevalence and Independent Risk Factors of Significant Tricuspid Regurgitation Jets in Maintenance Hemodialysis Patients With ESRD.

BACKGROUND AND AIM: Tricuspid regurgitation (TR) is a frequent complication in various cardiovascular diseases. However, few studies have reported the prevalence of TR especially the moderate to severe or significant TR (ms-TR) maintenance dialysis patients. Thus, we aimed to identify the prevalence of ms-TR and its associated factors. METHODS: A total of 491 maintenance dialysis patients underwent echocardiographic examinations, while a subgroup (n = 283) also received routine blood tests, renal function examinations, and electrolyte analysis. We first compared the differences in abovementioned parameters among groups with various TR areas (TRAs). Finally, univariate and adjusted regression were also used to identify factors that were independently associated with ms-TR. RESULTS: The incidence of TR jets was 62.6%, which included a mildly increased TRA (47.8%), moderately increased TRA (10.4%), and severely increased TRA (3.5%). Most of the cardiac structures and functional parameters, such as the end-diastolic internal diameters of the left atrium (LA), left ventricle (LVDD), right atrium (RA), right ventricle (RV), left ventricular ejection fraction (LVEF), and fractional shortening (FS), were significantly associated with ms-TR. Among serum ions, only total CO2 (TCO2; r = -0.141, p = 0.047) was negatively correlated with TRA. After adjusted, only Na+ [odds ratio (OR): 0.871 0.888, p = 0.048], RA (OR: 1.370, p < 0.001), and FS (OR: 0.887, p < 0.001) were independently associated with ms-TR. CONCLUSION: Tricuspid regurgitation occurs in maintenance hemodialysis patients with ESRD. Na+ FS and RA were independently associated with ms-TR, and these parameters may be potential risk factors/predictors for ms-TR.

The onset of sleep disturbances and their associations with anxiety after acute high-altitude exposure at 3700 m.

Sleep disturbances and psychiatric repercussions pose great challenges at high altitude; however, few studies have investigated sleep disturbance and anxiety profiles and their associations after acute exposure in consecutive patients. Thus, we aimed to study the profiles of sleep disturbances in consecutive patients after high-altitude exposure and the association of such disturbances with anxiety. A total of 668 participants were recruited at sea level and 3700 m. The trials were performed at sea level (1 week prior to a 2-h flight to a high-altitude destination) and at 3700 m (24, 72, and 168 h). Sleep disturbances were assessed by self-reported sleep patterns and scores on the Athens Insomnia Scale (AIS). State anxiety was assessed using the Self-Rating Anxiety Scale (SAS). In our study, the incidence of sleep disturbances increased significantly after acute high-altitude exposure (65.3%, 434/668) and then gradually decreased after 72 h (50%, 141/282) and 168 h (44%, 124/282). The sleep assessments AIS [2.0 (4.0) vs. 4.0 (5.0)] and ESS [4.0 (4.0) vs. 5.0 (5.0)] increased significantly (p < 0.05). Also, the SAS increased significantly from 26.25 (3.75) to 28.75 (7.5). The SAS was significantly high in sleep disturbance group [31.25 (7.5) vs. 27.5 (5), p < 0.001] than in the non-sleep- disturbance group. The baseline SAS and AIS scores were significantly higher in participants with sleep disturbances than in those without (p < 0.01). Age, baseline insomnia, sleepiness, fatigue, and higher SAS were predictors of sleep disturbances in univariate regression (all p values < 0.05). However, only an older age (p = 0.045) and a higher baseline SAS (p = 0.018) remained independent predictors of sleep disturbances. Our findings indicated that acute high-altitude exposure triggers the onset of sleep disturbances, which are closely associated with anxiety. Furthermore, baseline state anxiety and age are independent predictors of sleep disturbances at high altitude.