Multiple myeloma complicated with light chain cast nephropathy with focal amyloidosis: A case report.

This case report describes a rare and interesting case of a patient with multiple myeloma complicated with light chain (LC) cast nephropathy and focal amyloidosis. The patient presented with acute kidney injury, anaemia and bone lesions. The diagnosis was confirmed by bone marrow biopsy, serum and urine electrophoresis and kidney biopsy. The patient was treated with isazomil, pomalidomide and dexamethasone combination chemotherapy, followed by autologous stem cell transplantation. The patient achieved clinical remission, stable renal function and improved serum lambda free LC levels. This case highlights the challenges and advances in the diagnosis and treatment of this condition.

Rare Mutations in CCDC7 Contribute to Early-Onset Preeclampsia by Inhibiting Trophoblast Migration and Invasion.

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.

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.

Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial.

BACKGROUND: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation. METHODS: The study was a prospective, randomized, double-blind, placebo-controlled trial. Forty-one participants were randomly divided into two groups receiving ubiquinol 200 mg daily or placebo orally 14 days before flying to high altitude (3900 m) until the end of the study. Cardiopulmonary exercise testing was performed at baseline (300 m), on the third day after reaching high altitude, and on the seventh day after returning to baseline. RESULTS: Acute high-altitude exposure prolonged resting ventricular repolarization, represented by increased corrected QT interval (455.9 ± 23.4 vs. 427.1 ± 19.1 ms, P < 0.001) and corrected Tpeak-Tend interval (155.5 ± 27.4 vs. 125.3 ± 21.1 ms, P < 0.001), which recovered after returning to low altitude. Ubiquinol supplementation shortened the hypoxia-induced extended Tpeak-Tend interval (-7.7 ms, [95% confidence interval (CI), -13.8 to -1.6], P = 0.014), Tpeak-Tend /QT interval (-0.014 [95% CI, -0.027 to -0.002], P = 0.028), and reserved maximal heart rate (11.9 bpm [95% CI, 3.2 to 20.6], P = 0.013) during exercise at high altitude. Furthermore, the decreased resting amplitude of the ST-segment in the V3 lead was correlated with decreased peak oxygen pulse (R = 0.713, P < 0.001) and maximum oxygen consumption (R = 0.595, P < 0.001). CONCLUSIONS: Our results illustrated the electrophysiology changes during high-altitude acclimatization and de-acclimatization. Similarly, ubiquinol supplementation shortened the prolonged Tpeak-Tend interval and reserved maximal heart rate during exercise at high altitude. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2200059900.

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.

Association between short inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.

OBJECTIVE: To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery. METHODS: This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery. RESULTS: Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26). CONCLUSIONS: The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.

The exploration of genetic aetiology and diagnostic strategy for 321 Chinese individuals with intellectual disability.

BACKGROUND: Intellectual disability is a heterogeneous neurodevelopmental disorder with complex genetic architectures. Different sequential methodologies are usually applied to identify the genetic aetiologies of ID patients. METHODS: We collected 321 consecutive ID patients. All patients underwent karyotyping, while 293 and 164 cases further received copy number variation sequencing (CNV-seq) and whole-exome sequencing (WES). The updated WES technology can detect CNVs simultaneously. The diagnostic data from 137 patients who received WES and CNV-seq were used to define the approach that could be recommended as the first-tier test. RESULTS: WES obtains the highest diagnostic yield of 50% (82/164), compared with karyotyping (7.79%, 25/321) and CNV-seq (19.80%, 58/293). Among the variants detected by WES, 66.67% (44/66) de novo and 57.58% (38/66) novel pathogenic/likely pathogenic (P/LP) variants were identified in patients with ID. Besides, 24 out of 25P/LP CNVs discovered by CNV-seq can also be accurately identified using WES in 137 patients who received WES and CNV-seq. Thus, genetic abnormalities found through karyotyping, CNV-seq, and WES can be completely detected by combined karyotyping and WES. CONCLUSIONS: This study illustrates the genetic aberrations of a Chinese ID cohort and expands the mutation spectrum of ID-related genes. Compared with the conventional diagnostic strategy, a combination of karyotype analysis and WES could be recommended as the first-tier diagnostic strategy for ID patients.

Development and Validation of a Liquid-Liquid Phase Separation-Related Gene Signature as Prognostic Biomarker for Low-Grade Gliomas.

Aim: To explore whether the liquid-liquid phase separation- (LLPS-) related genes were potential prognostic markers that could contribute to the further classification of low-grade gliomas (LGGs). Methods: The LLPS-related genes were subjected to functional enrichment analysis. The univariable, least absolute shrinkage and selection operator, and multivariable stepwise Cox regression analyses were performed to develop an LLPS-related gene signature (GS) in the discovery data set. The biological characteristics of the high-risk LGG were explored using gene set enrichment analysis. Two independent external data sets were used to validate the LLPS-related GS. Results: LLPS-related genes are involved in multiple important cancer-related biological processes and pathways in LGG. Nine LLPS-related genes were identified to construct the LLPS-related GS, which was significantly associated with the prognosis of LGG patients. The LLPS-related GS could successfully divide patients with LGG into high- and low-risk groups, and the high-risk group showed a poorer prognosis than the low-risk group. Furthermore, the LLPS-related GS was independent of IDH and 1p19q status. Several cancer-related pathways may be more active in high-risk LGGs, such as IL6 JAK STAT3 signaling pathway. The LLPS-related GS was successfully validated with two independent external data sets. Conclusion: We developed and validated a novel LLPS-related GS for risk stratification of LGG. Our findings may provide more precise management for LGGs and a useful reference for LLPS mechanism to link LGG studies.

PLXND1-mediated calcium dyshomeostasis impairs endocardial endothelial autophagy in atrial fibrillation.

Left atrial appendage (LAA) thrombus detachment resulting in intracranial embolism is a major complication of atrial fibrillation (AF). Endocardial endothelial cell (EEC) injury leads to thrombosis, whereas autophagy protects against EEC dysfunction. However, the role and underlying mechanisms of autophagy in EECs during AF have not been elucidated. In this study, we isolated EECs from AF model mice and observed reduced autophagic flux and intracellular calcium concentrations in EECs from AF mice. In addition, we detected an increased expression of the mechanosensitive protein PLXND1 in the cytomembranes of EECs. PLXND1 served as a scaffold protein to bind with ORAI1 and further decreased ORAI1-mediated calcium influx. The decrease in the calcium influx-mediated phosphorylation of CAMK2 is associated with the inhibition of autophagy, which results in EEC dysfunction in AF. Our study demonstrated that the change in PLXND1 expression contributes to intracellular calcium dyshomeostasis, which inhibits autophagy flux and results in EEC dysfunction in AF. This study provides a potential intervention target for EEC dysfunction to prevent and treat intracardiac thrombosis in AF and its complications.

Prognostic significance of day-by-day in-hospital blood pressure variability in COVID-19 patients with hypertension.

Hypertension is the most common comorbidity in patients with coronavirus disease 2019 (COVID-19) and increases in-hospital mortality. Day-by-day blood pressure (BP) variability (BPV) is associated with clinical outcomes in hypertensive patients. However, little information is available on the association of BPV with the outcomes of COVID-19 patients with hypertension. This study aimed to demonstrate whether day-by-day in-hospital BPV had prognostic significance in these patients. The authors included 702 COVID-19 patients with hypertension from Huoshenshan Hospital (Wuhan, China), who underwent valid in-hospital BP measurements on at least seven consecutive days. Day-by-day BPV was assessed by standard deviation (SD), coefficient of variation (CV), and variation independent of mean (VIM). Overall, patients with severe COVID-19 and non-survivors had higher BPV than moderate cases and survivors, respectively. Additionally, higher BPV was correlated with greater age and higher levels of C-reactive protein, procalcitonin, high-sensitive cardiac troponin I, and B-type natriuretic peptide. In multivariable Cox regression, SD of systolic BP (SBP) was predictive of mortality [hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.05-1.30] as well as acute respiratory distress syndrome (ARDS) (HR 1.09, 95% CI 1.01-1.16). Similar trends were observed for CV and VIM of SBP, but not indices of diastolic BP variability. The authors demonstrated that day-by-day in-hospital SBP variability can independently predict mortality and ARDS in COVID-19 patients with hypertension. And high BPV might be correlated with severe inflammation and myocardial injury. Further studies are needed to clarify whether early reduction of BPV will improve the prognosis of these patients.

Pitavastatin activates mitophagy to protect EPC proliferation through a calcium-dependent CAMK1-PINK1 pathway in atherosclerotic mice.

Statins play a major role in reducing circulating cholesterol levels and are widely used to prevent coronary artery disease. Although they are recently confirmed to up-regulate mitophagy, little is known about the molecular mechanisms and its effect on endothelial progenitor cell (EPC). Here, we explore the role and mechanism underlying statin (pitavastatin, PTV)-activated mitophagy in EPC proliferation. ApoE-/- mice are fed a high-fat diet for 8 weeks to induce atherosclerosis. In these mice, EPC proliferation decreases and is accompanied by mitochondrial dysfunction and mitophagy impairment via the PINK1-PARK2 pathway. PTV reverses mitophagy and reduction in proliferation. Pink1 knockout or silencing Atg7 blocks PTV-induced proliferation improvement, suggesting that mitophagy contributes to the EPC proliferation increase. PTV elicits mitochondrial calcium release into the cytoplasm and further phosphorylates CAMK1. Phosphorylated CAMK1 contributes to PINK1 phosphorylation as well as mitophagy and mitochondrial function recover in EPCs. Together, our findings describe a molecular mechanism of mitophagy activation, where mitochondrial calcium release promotes CAMK1 phosphorylation of threonine177 before phosphorylation of PINK1 at serine228, which recruits PARK2 and phosphorylates its serine65 to activate mitophagy. Our results further account for the pleiotropic effects of statins on the cardiovascular system and provide a promising and potential therapeutic target for atherosclerosis.

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.

Cardiovascular Indicators of Systemic Circulation and Acute Mountain Sickness: An Observational Cohort Study.

Background: Acute high-altitude (HA) exposure results in blood pressure (BP) and cardiac function variations in most subjects, some of whom suffer from acute mountain sickness (AMS). Several previous studies have found that cardiovascular function indicators are potentially correlated with AMS. Objectives: This study aims to examine HA-induced cardiovascular adaptations in AMS patients and compare them with healthy subjects. It also aims to investigate the relationship between cardiovascular function indicators and AMS, as well as to provide some insightful information about the prevention and treatment of AMS. Methods: Seventy-two subjects were enrolled in this cohort study. All the subjects ascended Litang (4,100 m above sea level). They were monitored by a 24-h ambulatory blood pressure (ABP) device and underwent echocardiography examination within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS. Results: Acute mountain sickness group consisted of more women (17 [60.7%] vs. 10 [22.7%], p = 0.001) and fewer smokers (5 [17.9%] vs. 23 [52.3%], p = 0.003). Compared with subjects without AMS, subjects with AMS had lower pulse pressure (PP) (daytime PP, 45.23 ± 7.88 vs. 52.14 ± 4.75, p < 0.001; nighttime PP, 42.81 ± 5.92 vs. 49.39 ± 7.67, p < 0.001) and lower effective arterial elastance (Ea) (1.53 ± 0.24 vs. 1.73 ± 0.39, p = 0.023). Multivariate regression indicated that female sex (OR = 0.23, p = 0.024), lower daytime PP (OR = 0.86, p = 0.004), and lower Ea (OR = 0.03, p = 0.015) at low altitude (LA) were independent risk factors for AMS. Combined daytime PP and Ea at LA had a high predictive value for AMS (AUC = 0.873; 95% CI: 0.789-0.956). Correlation analysis showed that AMS-induced headache correlated with daytime PP (R = -0.401, p < 0.001) and nighttime PP at LA (R = -0.401, p < 0.001). Conclusion: Our study demonstrated that AMS patients had a lower PP and Ea at LA. These baseline indicators of vasodilation at LA were closely associated with AMS, which may explain the higher headache severity in subjects with higher PP at LA.

Analysis of risk factors for early stent thrombosis in the Chinese population: A multicenter restrospective study.

BACKGROUND: The predictive scoring systems for early stent thrombosis (EST) remains blank in China. The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population. METHODS: EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention (PCI). Patients from ten Chinese hospitals diagnosed as stent thrombosis (ST) from January 2010 to December 2016 were retrospectively included as the study group. A control group (1 case:2 controls) was created by including patients without ST, major adverse cardiovascular events, or cerebrovascular events during follow-up. The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients, who were included to identify factors that predicted EST and to develop a prediction scoring system. The other 171 patients without integrated 1:2 pair were used for external validation. RESULTS: EST was independently associated with a low hemoglobin concentration (adjusted odds ratio [OR] 0.946, 95% confidence interval [95% CI] 0.901-0.993, P=0.026), a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score (OR 1.166, 95% CI 1.049-1.297, P=0.004), and a DAPT (DAPT) duration of <30 days (OR 28.033, 95% CI 5.302-272.834, P<0.001). The simple EST prediction score provided an area under the curve (AUC) of 0.854 (95% CI 0.777-0.932, P<0.001) with 70.0% sensitivity and 90.0% specificity, and 0.742 (95% CI 0.649-0.835, P<0.001) with 54.5% sensitivity and 81.0% specificity for external validation dataset. CONCLUSIONS: EST may be independently associated with DAPT discontinuation within 30 days, a low hemoglobin concentration, and a high SYNTAX score. The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

Sex-Dependent Association Between Early Morning Ambulatory Blood Pressure Variations and Acute Mountain Sickness.

BACKGROUND: Acute high altitude (HA) exposure elicits blood pressure (BP) responses in most subjects, and some of them suffer from acute mountain sickness (AMS). However, a 24-h ambulatory BP (ABP) change and the correlation with the occurrence of AMS in different sexes are still unclear. OBJECTIVES: This prospective study aimed to investigate HA induced BP responses in males and females and the relationship between AMS and 24-h ABP. METHODS: Forty-six subjects were matched according to demographic parameters by propensity score matching with a ratio of 1:1. All the subjects were monitored by a 24-h ABP device; the measurement was one period of 24 h BP. 2018 Lake Louise questionnaire was used to evaluate AMS. RESULTS: Both the incidence of AMS (14 [60.9%] vs. 5 [21.7%], P = 0.007) and headache (18 [78.3%] vs. 8 [34.8%], P = 0.003) were higher in females than in males. All subjects showed an elevated BP in the early morning [morning systolic BP (SBP), 114.72 ± 13.57 vs. 120.67 ± 11.10, P = 0.013]. The elevation of morning SBP variation was more significant in females than in males (11.95 ± 13.19 vs. -0.05 ± 14.49, P = 0.005), and a higher morning BP surge increase (4.69 ± 18.09 vs. -9.66 ± 16.96, P = 0.005) was observed after acute HA exposure in the female group. The increase of morning SBP was associated with AMS occurrence (R = 0.662, P < 0.001) and AMS score (R = 0.664, P = 0.001). Among the AMS symptoms, we further revealed that the incidence (R = 0.786, P < 0.001) and the severity of headache (R = 0.864, P < 0.001) are closely correlated to morning SBP. CONCLUSIONS: Our study demonstrates that females are more likely to suffer from AMS than males. AMS is closely associated with elevated BP in the early morning period, which may be correlated to higher headache incidence in subjects with higher morning SBP.

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.

Probability of severe postpartum hemorrhage in repeat cesarean deliveries: a multicenter retrospective study in China.

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

Sex Differences in the Incidence and Risk Factors of Myocardial Injury in COVID-19 Patients: A Retrospective Cohort Study.

Male novel coronavirus disease (COVID-19) patients tend to have poorer clinical outcomes than female patients, while the myocardial injury is strongly associated with COVID-19-related adverse events. Owing to a lack of corresponding data, we aimed to investigate the sex differences in the incidence of myocardial injury in COVID-19 patients and to identify the potential underlying mechanisms, which may partly account for the sex bias in the incidence of adverse events. This retrospective study included 1,157 COVID-19 patients who were hospitalized in Huoshenshan Hospital from 12 March 2020 to 11 April 2020. Data on the patients' demographic characteristics, initial symptoms, comorbidities and laboratory tests were collected. Totally, 571 (49.4%) female and 586 (50.6%) male COVID-19 patients were enrolled. The incidence of myocardial injury was higher among men than women (9.2 vs. 4.9%, p = 0.004). In the logistic regression analysis, age, and chronic kidney disease were associated with myocardial injury in both sexes. However, hypertension [odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.20-4.22], coronary artery disease (OR = 2.46, 95% CI 1.14-5.34), leucocyte counts (OR = 3.13, 95% CI 1.24-7.86), hs-CRP (OR = 4.45, 95% CI 1.33-14.83), and D-dimer [OR = 3.93 (1.27-12.19), 95% CI 1.27-12.19] were independent risk factors only in the men. The correlations of hs-CRP and D-dimer with hs-cTnI and BNP were stronger in the men. The incidence of myocardial injury in COVID-19 patients is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders in men. Our findings can be used to improve the quality of clinical management in such settings.

Blood pressure and left ventricular function changes in different ambulatory blood pressure patterns at high altitude.

Acute high-altitude (HA) exposure induces physiological responses of the heart and blood pressure (BP). However, few studies have investigated the responses associated with dipper and non-dipper BP patterns. In this prospective study, 72 patients underwent echocardiography and 24-h ambulatory BP testing at sea level and HA. Patients were divided into dipper and non-dipper groups according to BP at sea level. Acute HA exposure elevated 24-h systolic and diastolic BP and increased BP variability, particularly in the morning. Moreover, acute exposure increased left ventricular torsion, end-systolic elastance, effective arterial elastance, and untwisting rate, but reduced peak early diastolic velocity/late diastolic velocity and peak early diastolic velocity/early diastolic velocity, implying enhanced left ventricular systolic function but impaired filling. Dippers showed pronounced increases in night-time BP, while non-dippers showed significant elevation in day-time BP, which blunted differences in nocturnal BP fall, and lowest night-time and evening BP. Dippers had higher global longitudinal strain, torsion, and untwisting rates after acute HA exposure. Variations in night-time systolic BP correlated with variations in torsion and global longitudinal strain. Our study firstly demonstrates BP and cardiac function variations during acute HA exposure in different BP patterns and BP increases in dippers at night, while non-dippers showed day-time increases. Furthermore, enhanced left ventricular torsion and global longitudinal strain are associated with BP changes. Non-dippers showed poor cardiac compensatory and maladaptive to acute HA exposure. However, the exact mechanisms involved need further illumination.

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.