RNA methylation patterns, immune characteristics, and autophagy-related mechanisms mediated by N6-methyladenosine (m6A) regulatory factors in venous thromboembolism.

Recent studies have found a link between deep vein thrombosis and inflammatory reactions. N6-methyladenosine (m6A), a crucial element in immunological regulation, is believed to contribute to the pathophysiology of venous thromboembolism (VTE). However, how the m6A-modified immune microenvironment is involved in VTE remains unclear. In the present study, we identified a relationship between VTE and the expression of several m6A regulatory elements by analyzing peripheral blood samples from 177 patients with VTE and 88 healthy controls from public GEO databases GSE19151 and GSE48000. We used machine learning to identify essential genes and constructed a diagnostic model for VTE using multivariate logistic regression. Unsupervised cluster analysis revealed a marked difference between m6A modification patterns in terms of immune cell infiltration, inflammatory reactivity, and autophagy. We identified two m6A-related autophagy genes (i.e., CHMP2B and SIRT1) and the crucial m6A regulator YTHDF3 using bioinformatics. We also examined two potential mechanisms through which YTHDF3 may affect VTE. m6A modification, immunity, and autophagy are closely linked in VTE, offering novel mechanistic and therapeutic insights.

Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Integrative Analysis of N6-methyladenosine RNA modifications related genes and their Influences on Immunoreaction or fibrosis in myocardial infarction.

Increasing studies have shown that N6-methyladenosine (m6A) modification plays an important role in cardiovascular diseases. In this study, we systematically investigated the regulatory mode of m6A genes in myocardial infarction (MI) by combining bioinformatics analysis of clinical samples with animal experiments. We utilized gene expression data of clinical samples from public databases to examine the expression of m6A genes in heart tissues and found a large difference between the healthy control group and MI group. Subsequently, we established an MI diagnosis model based on the differentially expressed m6A genes using the random forest method. Next, unsupervised clustering method was used to classify all MI samples into two clusters, and the differences in immune infiltration and gene expression between different clusters were compared. We found LRPPRC to be the predominant gene in m6A clustering, and it was negatively correlated with immunoreaction. Through GO enrichment analysis, we found that most differentially expressed genes between the two clusters were profibrotic. By means of WGCNA, we inferred that GJA4 might be a core molecule in the m6A regulatory network of MI. This study demonstrates that m6A regulators probably affects the immune-inflammatory response and fibrosis to regulate the process of MI, which provides a potential therapeutic target.

Evaluation of metal pollution characteristics using water and moss in the Luanchuan molybdenum mining area, China.

Luanchuan is rich in molybdenum resources, and mining activities are frequent, but over-mining can cause serious metal pollution to the local environment. To explore the degree of metal pollution caused by mining activities, the content characteristics and spatial distribution of metals in mining areas were studied by measuring the concentrations of Fe, Mn, Zn, Ba, Mo, Cu, Cr, Co, V, and W in surface water and mosses of mining areas. In addition, the metal pollution index (HPI), contamination factor (CF), and pollution load index (PLI) were used to evaluate metal pollution, and factor analysis was used to analyze the sources of metals. The results of the analysis of surface water at the mine site indicate the most abundant element in surface water, with a maximum concentration of 3713.8 µg/L, and its content far exceeds the water quality standard of Class III of the Environmental Quality Standard for Surface Water. The results of the HPI analysis showed that nearly 90% of the surface water was moderately contaminated (HPI ≥ 15). The results of the analysis of atmospheric deposition at the mine site confirm that the metal elements with a high threat to the atmospheric environment are Mo and W. The results of PLI indicate that the level of atmospheric deposition pollution in the study area is severe (PLI > 4). Factor analysis indicated that rock weathering and mining activities were the main sources of metals. This study provides a theoretical basis for the investigation and control of metal pollution in similar metal mining areas.

Electrical Synchrony Optimization for Left Bundle Branch Area Pacing in Patients With Bradycardia and Heart Failure.

Left bundle branch area pacing (LBBAP) has emerged as a promising physiological pacing modality. This study was designed to investigate the acute impact of the atrioventricular delay (AVD) on cardiac electrical characteristics and identify an optimal range of AVDs for LBBAP to achieve electrical atrioventricular and interventricular synchrony. Patients indicated for ventricular or biventricular pacing were studied during routine follow-ups at least 3 months after LBBAP implantation. Patients were excluded if they had a complete AV block or persistent atrial fibrillation. AVD was programed from 40 to 240 ms or until intrinsic conduction occurred. Optimal AVD was determined by the electrocardiography criteria, including QRS duration, reduced R-wave in lead V1, reduced notching or slurring in lateral leads, and more desirable precordial QRS transition. A total of 38 patients (age 68.7 ± 10.3 years; 16 male (42%); 18 dual-chamber pacemakers and 20 cardiac resynchronization therapy devices; average follow-up period 15.1 ± 10.2 months) were included. The fusion of LBBAP and intrinsic right ventricular conduction occurred in 21 patients with corresponding optimal AVD determined. A great proportion (∼85%) of the optimal AVDs ranged from 50% to 80% of the observed atrium-to-left bundle branch-sensing (A-LBBS) intervals. The linear correlation between the optimal AVD and corresponding A-LBBS interval (optimal AVD = 0.84 × [A-LBSs interval] - 36 ms) produced R = 0.86 and p <0.0001. In conclusion, AVD selection during LBBAP greatly impacted the ventricular electrical characteristics and the optimal AVD was linearly correlated with the corresponding A-LBBS interval.

An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction.

The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. In addition, an upstreaming acute interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte Il6 receptor deficiency and Stat3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL-6/STAT3/MR/FGF21 signaling axis that mediates heart-liver cross-talk during MI. Targeting the signaling axis and the cross-talk could provide new strategies to treat MI and heart failure.

T-Cell Mineralocorticoid Receptor Deficiency Attenuates Pathologic Ventricular Remodelling After Myocardial Infarction.

BACKGROUND: Mineralocorticoid receptor (MR) antagonists have been widely used to treat heart failure (HF). Studies have shown that MR in T cells plays important roles in hypertension and myocardial hypertrophy. However, the function of T-cell MR in myocardial infarction (MI) has not been elucidated. METHODS: In this study, we used T-cell MR knockout (TMRKO) mouse to investigate the effects of T-cell MR deficiency on MI and to explore the underlying mechanisms. Echocardiography and tissue staining were used to assess cardiac function, fibrosis, and myocardial apoptosis after MI. Flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect immune cell infiltration and inflammation. RESULTS: T-cell MR deficiency significantly improved cardiac function, promoted myocardial repair, and inhibited myocardial apoptosis, fibrosis, and inflammation after MI. Luminex assays revealed that TMRKO mice had significantly lower levels of interferon-gamma (IFN-γ) and interleukin-6 (IL-6) in serum and infarcted myocardium than littermate control mice. In cultured splenic T cells, MR deficiency suppressed IL-6 expression, whereas MR overexpression enhanced IL-6 expression. Chromatin immunoprecipitation (ChIP) assay demonstrated that MR bound to the MR response element on the promoter of IL-6 gene. Finally, T-cell MR deficiency significantly suppressed accumulation of macrophages in infarcted myocardium and differentiation of proinflammatory macrophages, thereby alleviating the consequences of MI. CONCLUSIONS: T-cell MR deficiency improved pathologic ventricular remodelling after MI, likely through inhibition of accumulation and differentiation of proinflammatory macrophages. At the molecular level, MR may work through IFN-γ and IL-6 in T cells to exert functions in MI.

Resynchronization effects and clinical outcomes during left bundle branch area pacing with and without conduction system capture.

BACKGROUND: Left bundle branch area pacing (LBBAP) includes left bundle branch pacing (LBBP) and left ventricular (LV) septal myocardial pacing (LVSP). HYPOTHESIS: The study aimed to assess resynchronization effects and clinical outcomes by LBBAP in heart failure (HF) patients with cardiac resynchronization therapy (CRT) indications. METHODS: LBBAP was successfully performed in 29 consecutive patients and further classified as the LBBP-group (N = 15) and LVSP-group (N = 14) based on the LBBP criteria and novel LV conduction time measurement (LV CT, between LBBAP site and LV pacing (LVP) site). AV-interval optimized LBBP or LVSP, or LVSP combined with LVP (LVSP-LVP) was applied. LV electrical and mechanical synchrony and clinical outcomes were assessed. RESULTS: All 15 patients in the LBBP-group received optimized LBBP while 14 patients in the LVSP-group received either optimized LVSP (5) or LVSP-LVP (9). The LV CT during LBBP was significantly faster than that during LVP (p < .001), while LV CT during LVSP were similar to LVP (p = .226). The stimulus to peak LV activation time (Stim-LVAT, 71.2 ± 8.3 ms) and LV mechanical synchrony (TSI-SD, 35.3 ± 9.5 ms) during LBBP were significantly shorter than those during LVSP (Stim-LVAT 89.1 ± 19.5 ms, TSI-SD 49.8 ± 14.4 ms, both p < .05). Following 17(IQR 8) months of follow-up, the improvement of LVEF (26.0%(IQR 16.0)) in the LBBP-group was significantly greater than that in the LVSP-group (6.0%(IQR 20.8), p = .001). CONCLUSIONS: LV activation in LBBP propagated significantly faster than that of LVSP. LBBP generated superior electrical and mechanical resynchronization and better LVEF improvement over LVSP in HF patients with CRT indications.

NCOR1 maintains the homeostasis of vascular smooth muscle cells and protects against aortic aneurysm.

Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays critical roles in the pathogenesis of aortic aneurysm (AA). The function of nuclear receptor corepressor1 (NCOR1) in regulation of VSMC phenotype and AA is unclear. Herein, using smooth muscle NCOR1 knockout mice, we demonstrated that smooth muscle NCOR1 deficiency decreased both mRNA and protein levels of contractile genes, impaired stress fibers formation and RhoA pathway activation, reduced synthesis of elastin and collagens, and induced the expression and activity of MMPs, manifesting a switch from contractile to degradative phenotype of VSMCs. NCOR1 modulated VSMC phenotype through 3 different mechanisms. First, NCOR1 deficiency increased acetylated FOXO3a to inhibit the expression of Myocd, which downregulated contractile genes. Second, deletion of NCOR1 derepressed NFAT5 to induce the expression of Rgs1, thus impeding RhoA activation. Third, NCOR1 deficiency increased the expression of Mmp12 and Mmp13 by derepressing ATF3. Finally, a mouse model combined apoE knockout mice with angiotensin II was used to study the role of smooth muscle NCOR1 in the development of AA. The results showed that smooth muscle NCOR1 deficiency increased the incidence of aortic aneurysms and exacerbated medial degeneration in angiotensin II-induced AA mouse model. Collectively, our data illustrated that NCOR1 interacts with FOXO3a, NFAT5, and ATF3 to maintain contractile phenotype of VSMCs and suppress AA development. Manipulation of smooth muscle NCOR1 may be a potential approach for AA treatment.

Noninvasive evaluation of pulmonary hypertension using the second heart sound parameters collected by a mobile cardiac acoustic monitoring system.

Background: Pulmonary hypertension (PH) is linked to higher rates of morbidity and mortality worldwide. Early diagnosis of PH is important for clinical treatment. The estimated pulmonary artery systolic pressure (ePASP ≥ 35 mmHg) measured by echocardiography helps screen PH patients. In this paper, we report a novel PH screening method through a mobile cardiac acoustic monitoring system. Methods: In the retrospective study, patients admitted to our hospital between January 2022 and April 2023 were classified into PH and control groups using ePASP and compared with acoustic cardiographic parameters. According to ePASP, PH severity was classified as mild, moderate, and severe. We analyzed the first and second heart sound (S1, S2) characteristics, including amplitude (S1A, S2A), energy (S1E, S2E), and frequency (S1F, S2F). Results: The study included 209 subjects, divided into PH (n = 121) and control (n = 88) groups. Pearson correlation analysis confirmed the positive correlation between S2F and ePASP. The diagnostic performance of S2F as assessed by the area under the ROC curve was 0.775 for PH. The sensitivity and specificity of diagnosing ePASP ≥ 35 mmHg when S2F ≥ 36 Hz were found to be 79.34% and 67.05%, respectively, according to ROC analysis. Severity classification was performed using S2F, the area under the ROC curve was 0.712-0.838 for mild PH, 0.774-0.888 for moderate PH, and 0.826-0.940 for severe PH. Conclusions: S2F collected by the mobile cardiac acoustic monitoring system offers a convenient method for remote PH screening, potentially improving PH management and outcomes.

Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure.

BACKGROUND: Left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block. METHODS: LBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation. Electrical synchrony was assessed by QRS duration and area, mechanical synchrony by the SD of time to peak velocity of 12 left ventricular segments (Ts-SD) and interventricular mechanical delay, and hemodynamics by the maximum rate of left ventricular pressure rise (dP/dtmax). RESULTS: Twenty-one patient with heart failure and left bundle branch block (mean age 67±10 years, 48% male, and 90% nonischemic cause) were included. Both LBBP and BVP provided significant improvements in electrical and mechanical synchrony, and hemodynamics compared to the baseline. Compared with BVP, LBBP achieved a larger reduction in QRS duration (-11 ms [95% CI, -17 to -4 ms]; P=0.003) and QRS area (-85 µVs [95% CI, -113 to -56 µVs]; P<0.001); LBBP achieved a greater decrease in Ts-SD (-14 ms [95% CI, -21 to -7 ms]; P=0.001), with no significant difference in interventricular mechanical delay (-2 ms [95% CI, -13 to 8 ms]; P=0.63). The increase in dP/dtmax from LBBP was significantly higher than that from BVP (6% [95% CI, 2%-9%]; P=0.002). CONCLUSIONS: LBBP delivers greater acute electrical and mechanical resynchronization and hemodynamic improvement than BVP in predominantly nonischemic heart failure patients with left bundle branch block. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04505384.

Vitamin D intakes and health outcomes in infants and preschool children: Summary of an evidence report.

BACKGROUND: A systematic review was commissioned to support an international expert group charged to update the Food and Agriculture Organisation of the United Nations (FAO)/World Health Organisation (WHO)'s vitamin D intake recommendations for children aged 0-4 years. MATERIALS AND METHODS: Multiple electronic databases were searched to capture studies published from database inception to the 2nd week of June 2020 according to key questions formulated by the FAO/WHO. Relevant studies were summarised and synthesised by key questions and by health outcomes using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The 146 included studies examined the effects of different vitamin D intake levels on a variety of health outcomes (e.g. infectious disease, growth, neurodevelopment, rickets, and bone mineral density), and on outcomes for setting vitamin D upper limits (e.g. hypercalcemia, hypercalciuria, and nephrocalcinosis). For most outcomes, the strength of evidence was low or very low. Evidence was rated moderate for the effect of daily vitamin D supplementation on raising serum 25(OH)D concentrations, and a random-effects meta-regression analysis of 28 randomised controlled trials (mostly in infants 0-12 months) showed that each 100 IU/d increase in vitamin D supplementation was associated with an average of 1.92 (95% CI 0.28, 3.56) nmol/L increase in achieved 25-hydroxy-vitaminn D (25[OH]D) concentration (n = 53 intervention arms; p = .022) with large residual heterogeneity (I2 = 99.39%). Evidence was very low on two of the upper limit outcomes - hypercalcemia and hypercalciuria. CONCLUSIONS: The evidence report provided the expert group with a foundation and core set of data to begin their work to set vitamin D nutrient reference values. To move the field forward, future studies should use standardised 25(OH)D assay measurements and should examine the relationship between long-term vitamin D status and health outcomes.Key MessagesResults of a large complex systematic review suggest the current totality of evidence from trials and prospective observational studies do not reach sufficient certainty level to support a causal relationship between vitamin D intake and asthma, wheeze, eczema, infectious diseases, or rickets (most trials reported no rickets) in generally healthy infants and young children.In this systematic review, the only body of evidence that reached a moderate level of certainty was regarding the effect of daily vitamin D supplementation (vitamin D3 or D2 supplements to infants/children) on increasing serum 25(OH)D concentrations. However, currently there is no consensus on the definitions of vitamin D status, e.g. deficiency, insufficiency, sufficiency and toxicity, based on serum 25(OH)D concentrations.This systematic review provided an international expert group a foundation and core set of data through intake-response modelling to help set vitamin D nutrient reference values for infants and children up to 4 years of age.

Left bundle branch potential predicts better electrical synchrony in bradycardia patients receiving left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is a novel physiological pacing technology. We aim to explore the relation between LBB potential (LBB Po) and left ventricular (LV) electrical/mechanical synchrony in bradycardia patients without heart failure (HF) receiving LBBP. METHODS: A total of 62 patients undergoing LBBP were categorized by LBB Po: the LBB Po positive (+) group and the LBB Po negative (-) group. The perioperative electrocardiographic and echocardiography parameters related to cardiac synchrony were analyzed. RESULTS: There were 42 (67.74%) patients in the LBB Po (+) group and 20 patients in the LBB Po (-) group. Paced QRS duration (113.50 ± 17.65 ms vs. 123.40 ± 13.18 ms, P = 0.031) and stimulus left ventricular activation time (71.76 ± 3.53 ms vs. 74.45 ± 3.12 ms, P = 0.005) were shorter in the LBB Po (+) group than in the LBB Po (-) group. No significant differences in the LV mechanical synchrony (Ts-SD-12, 36.55 ± 19.76 vs. 39.95 ± 16.04, P = 0.505; PSD, 51.14 ± 17.69 vs. 45.65 ± 10.55, P = 0.205) between the two groups. There was not statistically difference in ventricular lead parameters measured intraoperative between the two groups. Compared with the LBB Po (-) group, the LBB Po (+) group showed a dramatically higher total procedure duration time (93.52 ± 9.18 min vs. 86.25 ± 10.54 min, p = 0.007) and fluoroscopy time for ventricle lead implantation (18.95 ± 3.43 min vs. 14.00 ± 3.16 min, p < 0.001). CONCLUSIONS: The appearance of LBB Po may suggest better electrical synchrony during LBBP, but similar in LV mechanical synchrony. However, the total operation duration and fluoroscopy time of ventricular lead implantation in the LBB Po (+) group were longer. Therefore, it may be unnecessary to deliberately recognize the LBB Po when it is difficult to detect LBB Po and meet the LBBP criterion.

Predictive effect of J waves on cardiac compression and clinical prognosis of esophageal tumors: a retrospective study.

Background: The J wave syndromes (JWS) could be observed in patients with mediastinal tumors, though few studies have verified the statistical correlation between J waves and cardiac compression by tumors. This study aimed to investigate the relationship between J waves and cardiac compression by esophageal tumor and to compare the prediction of J waves on clinical prognosis with that of cardiac compression by esophageal tumor. Methods: We enrolled 273 patients (228 males, 45 females; mean 63.8±7.5 years) with esophageal tumors admitted to Shanghai Chest Hospital between August 2016 and November 2020. The J wave was defined as a J-point elevation of ≥0.1 mV in a 12-lead electrocardiogram (ECG) and classified into multiple types. Chest computed tomography (CT) was reviewed to clarify the anatomical relationship between the heart and the esophageal tumor. The prognosis of severe cardiac events and survival status were followed up through medical history, examination records and telephone records. Results: J waves were present in 141 patients among all 273 cases. The sensitivity and specificity of cardiac compression by the tumor for J waves were 78.1% and 67.3%, respectively. The odds ratio (OR) of cardiac compression by the tumor to J waves was 7.33 [95% confidence interval (CI): 4.21-12.74; P<0.001]. The Kappa coefficient between J waves and cardiac compression was 0.44±0.05. The significance association between J waves and cardiac compression was independent from other clinical variables (P<0.001). Decreased J wave amplitude was correlated with the disappearance of cardiac compression during follow-up (P=0.03). Patients with J waves had a higher risk of severe cardiac events than those without J waves (OR =2.84, 95% CI: 1.22-6.63; P=0.01). During the follow-up period, we found that the presence of J waves [hazard ratio (HR) =2.28; 95% CI: 1.35-3.84; P=0.002] and cardiac compression by the tumor (HR =2.51; 95% CI: 1.51-4.17; P<0.001) were both negatively correlated with the survival time of patients. Conclusions: The presence of J waves could be used as an effective mean to predict the mechanical impact of esophageal tumor on the heart, and played an important role in predicting the survival of patients.

Mobile Cardiac Acoustic Monitoring System to Evaluate Left Ventricular Systolic Function in Pacemaker Patients.

The mobile cardiac acoustic monitoring system is a promising tool to enable detection and assist the diagnosis of left ventricular systolic dysfunction (LVSD). The objective of the study was to evaluate the diagnostic value of electromechanical activation time (EMAT), an important cardiac acoustic biomarker, in quantifying LVSD among left bundle branch pacing (LBBP) and right ventricular apical pacing (RVAP) patients using a mobile acoustic cardiography monitoring system. In this prospective single-center observational study, pacemaker-dependent patients were consecutively enrolled. EMAT, the time from the start of the pacing QRS wave to first heart sound (S1) peak; left ventricular systolic time (LVST), the time from S1 peak to S2 peak; and ECG were recorded simultaneously by the mobile cardiac acoustic monitoring system. LVEF was measured by echocardiography. A logistic regression model was applied to evaluate the association between EMAT and reduced EF (LVEF < 50%). A total of 105 pacemaker-dependent patients participated. The RVAP group (n = 58) displayed a significantly higher EMAT than the LBBP group (n = 47) (150.95 ± 19.46 vs. 108.23 ± 12.26 ms, p < 0.001). Pearson correlation analysis revealed a statistically significant negative correlation between EMAT and LVEF (p < 0.001). Survival analysis showed the sensitivity and specificity of detecting LVEF to be < 50% when EMAT ≥ 151 ms were 96.00% and 96.97% in the RVAP group. In LBBP patients, the sensitivity and specificity of using EMAT ≥ 110 ms as the cutoff value for the detection of LVEF < 50% were 75.00% and 100.00%. There was no significant difference in LVST with or without LVSD in the RVAP group (p = 0.823) and LBBP group (p = 0.086). Compared to LVST, EMAT was more helpful to identify LVSD in pacemaker-dependent patients. The cutoff point of EMAT for diagnosing LVEF < 50% differed regarding the pacing type. Therefore, the mobile cardiac acoustic monitoring system can be used to identify the progress of LVSD in pacemaker patients.

Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction.

RATIONALE: Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS: Using osteoblast MR knockout (MRobko) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MRobko mice compared to littermate control (MRfl/fl) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MRobko mice compared to MRfl/fl mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS: MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients.

Diagnostic performance of a wearing dynamic ECG recorder for atrial fibrillation screening: the HUAMI heart study.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia with high morbidity and mortality rate. Evidence shows that in every three patients with AF, one is asymptomatic. The asymptomatic and paroxysmal nature of AF is the reason for unsatisfactory and delayed detection using traditional instruments. Research indicates that wearing a dynamic electrocardiogram (ECG) recorder can guide accurate and safe analysis, interpretation, and distinction of AF from normal sinus rhythm. This is also achievable in an upright position and after exercises, assisted by an artificial intelligence (AI) algorithm. METHODS: This study enrolled 114 participants from the outpatient registry of our institution from June 24, 2020 to July 24, 2020. Participants were tested with a wearable dynamic ECG recorder and 12-lead ECG in a supine, an upright position and after exercises for 60 s. RESULTS: Of the 114 subjects enrolled in the study, 61 had normal sinus rhythm and 53 had AF. The number of cases that could not be determined by the wristband of dynamic ECG recorder was two, one and one respectively. Case results that were not clinically objective were defined as false-negative or false-positive. Results for diagnostic accuracy, sensitivity, and specificity tested by wearable dynamic ECG recorders in a supine position were 94.74% (95% CI% 88.76-97.80%), 88.68% (95% CI 77.06-95.07%), and 100% (95% CI 92.91-100%), respectively. Meanwhile, the diagnostic accuracy, sensitivity and specificity in an upright position were 97.37% (95% CI 92.21-99.44%), 94.34% (95% CI 84.03-98.65%), and 100% (95% CI 92.91-100%), respectively. Similar results as those of the upright position were obtained after exercise. CONCLUSION: The widely accessible wearable dynamic ECG recorder integrated with an AI algorithm can efficiently detect AF in different postures and after exercises. As such, this tool holds great promise as a useful and user-friendly screening method for timely AF diagnosis in at-risk individuals.

Lipid goal attainment in post-acute coronary syndrome patients in China: Results from the 6-month real-world dyslipidemia international study II.

BACKGROUND: Dyslipidemia International Study II (DYSIS II)-China was conducted to determine the low-density lipoprotein cholesterol (LDL-C) goal (<1.8 mmol/L) attainment rate in patients with post-acute coronary syndrome (ACS). HYPOTHESIS: Compliance with treatment guideline recommendations improves the LDL-C goal attainment rate in post-ACS patients. METHODS: This multicenter prospective observational study conducted at 28 tertiary hospitals determined the LDL-C goal attainment rates at admission and 6-month follow-up in patients on lipid-lowering treatment (LLT) for ≥3 months and those not on LLT (LLT-naive or off LLT for ≥3 months) at admission. Predictors of goal attainment at 6 months were identified using multivariate logistic regression. RESULTS: The LDL-C goal attainment rate at admission in 1102/1103 enrolled patients was 17.1%; it was 41.2% among 752 patients with available lipid results at 6 months. The distance to goal was 0.7 mmol/L at 6 months. Statin monotherapy was the most prescribed LLT. Only 7.7% of patients were receiving statin + ezetimibe and 8.4% of patients were receiving an atorvastatin-equivalent dose of ≥40 mg/day at 6 months. Being male (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.6) and undergoing percutaneous coronary intervention during index hospitalization (OR 1.5, 95% CI 1.1 to 2.1) were the independent predictors for LDL-C goal attainment. CONCLUSIONS: This real-world DYSIS II study in China reports a low LDL-C goal attainment rate in post-ACS patients even after 6 months of LLT. Lack of intensification of statin therapy and underutilization of combinations suggest gaps between real-world treatment practices and guideline recommendations.