Abstract Background Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases. Materials and methods NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein–protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model. Results A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2 , PTPRC , CXCR2 , MNDA , S100A9 , NCF2 , S100A12 , and S100A8 . Conclusions In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.
Studies show that the ratio of echocardiographic tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) is a non-invasive substitute for measuring right ventricle (RV) to pulmonary circulation coupling. RV failure indicates deteriorating prognosis in patients with amyloid light-chain cardiac amyloidosis (AL-CA). The aim of this study was to assess the association between the TAPSE/PASP ratio and short-term outcome in patients with AL-CA. Seventy-one patients (mean age, 62 ± 8 years, 69% male) diagnosed with AL-CA were enrolled in the study. Short-term outcome was defined as 6-month all-cause mortality. Among the patients, 17 (24%) died within the first 6 months (mean follow-up period 55 ± 48 days). Linear regression analysis indicated that the TAPSE/PASP ratio was strongly correlated with RV global longitudinal strain (r = –0.655, p < 0.001), RV free wall thickness (r = –0.599, p < 0.001), and left atrial reservoir strain (r = 0.770, p < 0.001). The time-dependent receiver operating characteristic and the area under the curve (AUC) showed that the TAPSE/PASP ratio was a better predictor (AUC = 0.798; 95% confidence interval (CI): 0.677–0.929) of short-term outcome than TAPSE (AUC = 0.734; 95% CI: 0.585–0.882) and PASP (AUC: 0.730; 95% CI: 0.587–0.874). Multivariate logistic regression showed that patients with the worse TAPSE/PASP (< 0.47 mm/mmHg) and lower systolic blood pressure (< 100 mmHg) had the highest risk of dying.
Abstract Aims Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models. Methods and results Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1β were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models. Conclusion LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.
Reports show that the left ventricular myocardial work index (LVMWI) is a novel parameter for evaluating cardiac function. Decompensated heart failure leads to a high rate of early mortality in advanced patients with light-chain cardiac amyloidosis (AL-CA) and prevents them from a relatively delayed response to chemotherapy. This study aimed to assess the association of the LVMWI with short-term outcomes and to construct a simple model for risk stratification.A total of 79 patients with an initial diagnosis of AL-CA were included in this retrospective cohort study. LVMWI was calculated by integrating brachial artery cuff blood pressure and left ventricular longitudinal strain (LVLS). The short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study.The median follow-up time was 21 months (3-36 months), and 23 (29%) patients died in the first 6 months. The time-dependent ROC and the area under the curve (AUC) showed that the LVMWI had the best predictive potential at the 6-month time point [AUC =0.805; 95% confidence interval (CI): 0.690-0.920]. A bivariate prognostic model based on the LVMWI was constructed, and D-dimer showed a synergistic effect with optimum predicted potential (AUC =0.877; 95% CI: 0.791-0.964). Kaplan-Meier analysis demonstrated that patients with two, one, and none of the variates beyond the cut-off value bore a different risk of 6-month all-cause mortality (accumulated mortality was 86%, 30%, 3%, respectively; log-rank, P<0.001). Multivariate nested logistic regression showed that the level of D-dimer provided an incremental prognostic value (Δχ2=10.3; P=0.001) to the value determined from New York Heart Association (NYHA) classification and the LVMWI.The LVMWI is associated with the short-term outcome of patients with AL-CA. The D-dimer test provides additional prognostic information for the LVMWI.
<b><i>Introduction:</i></b> Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for its use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. <b><i>Methods:</i></b> Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses were utilized to verify the prognostic potential of CA125. <b><i>Results:</i></b> The mean age was 61 ± 8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e’, and left ventricular ejection fraction showed acceptable prognostic potential (C-index = 0.829, 95% CI: 0.749–0.909). CA125 remained an independent prognostic factor (HR = 1.018, 95% CI: 1.005–1.031, <i>p</i> = 0.008, per 10 U/mL increase) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs. 0.784, <i>p</i> = 0.037). <b><i>Conclusion:</i></b> Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.
Background To facilitate the clinical use of cardiac T1ρ, it is important to understand the impact of age and sex on T1ρ values of the myocardium. Purpose To investigate the impact of age and gender on myocardial T1ρ values. Study Type Cross‐sectional. Population Two hundred ten healthy Han Chinese volunteers without cardiovascular risk factors (85 males, mean age 34.4 ± 12.5 years; 125 females, mean age 37.9 ± 14.8 years). Field Strength/Sequence 1.5 T; T1ρ‐prepared steady‐state free precession (T1ρ mapping) sequence. Assessment Basal, mid, and apical short‐axis left ventricular T1ρ maps were acquired. T1ρ maps acquired with spin‐lock frequencies of 5 and 400 Hz were subtracted to create a myocardial fibrosis index (mFI) map. T1ρ and mFI values across different age decades, sex, and slice locations were compared. Statistical Tests Shapiro–Wilk test, Student's t test, Mann–Whitney U test, linear regression analysis, one‐way analysis of variance and intraclass correlation coefficient. Significance: P value <0.05. Results Women had significantly higher T1ρ and mFI values than men (50.3 ± 2.0 msec vs. 47.7 ± 2.4 msec and 4.7 ± 1.0 msec vs. 4.3 ± 1.1 msec, respectively). Additionally, in males and females combined, there was a significant positive but weak correlation between T1ρ values and age ( r = 0.27), while no correlation was observed between the mFI values and age ( P = 0.969). Data Conclusion We report potential reference values for cardiac T1ρ by sex, age distribution, and slice location in a Chinese population. T1ρ was significantly correlated with age and sex, while mFI was only associated with sex. Evidence Level 2 Technical Efficacy Stage 1
Background: To investigate the relationship between red blood cell (RBC) folate and congestive heart failure (CHF). Methods: We extracted the concentrations of RBC folate and collated CHF information from the National Health and Nutrition Examination Survey (NHANES) survey (12820 individuals). Weighted univariate logistic regression, weighted multivariate logistic regression, and restrictive cubic spline (RCS) were used to assess the relationship between RBC folate concentrations and CHF. Results: The unadjusted model showed that the highest tertile group of RBC folate concentration was significantly associated with a higher risk of CHF compared to the lowest tertile group of RBC folate levels (odds ratio [OR] = 3.09; 95% confidence interval [CI], 2.14–4.46). Similar trends were seen in the multivariate-adjusted analysis (OR = 1.98; 95% CI: 1.27–3.09). The OR was >1.0 when the predicted RBC folate exceeded 2757 nmol/L in the RCS model, indicating that the risk of CHF was low and relatively stable up to a predicted RBC folate level of 2757 nmol/L, but began to increase rapidly thereafter (p = 0.001). Conclusions: The risk of CHF may be increased either by high RBC folate concentrations (highest tertile of RBC folate or >2637 nmol/L) or by folate deficiency. Considering the two sides of the association between RBC folate and CHF, there is a need for large-scale clinical research to better investigate if the association between RBC folate and CHF is a cause-effect relationship, what are the underlying pathophysiological basis, as well as to identify optimal dietary folate equivalent (DFE) and RBC folate concentration intervals.
ABSTRACT Background Cardiovascular disease prevalence remains high among chronic kidney disease (CKD) patients. Mechanisms and treatments to improve prognosis remain of paramount importance, and imaging biomarkers of left ventricular myocardial structure and function have better defined the phenotype of renal cardiomyopathy. The left atrial function and right heart remain are less well reported in CKD. This study used cardiac magnetic resonance imaging (CMR) to assess the interplay of left atrial and right ventricular function. Methods In a cross-sectional study, we examined 58 CKD patients (Group I: stages 2–3, n = 25; Group II: stages 4–5, n = 33). Additionally, 26 age-matched healthy controls were included. Comprehensive CMR protocols (1.5T) were employed, encompassing cine imaging, native T1 and T2 mapping, and tissue tracking strain analysis. Left ventricular (LV), right ventricular (RV) and left atrial (LA) structure, function and strain parameters were assessed. Results Compared with healthy controls, both Groups I and II exhibited impaired RV and LA function. right ventricular end-diastolic volume index and right ventricular end-systolic volume index showed significant increases in both Groups I and II (P < .001). All LV, RV and LA strain parameters were reduced in the patient groups (all P < .001). In the univariate binary logistic regression, several parameters, including age, blood pressure, RV volumes and LV/RV strain, were found to have a statistically significant association with CKD. In a multivariable model adjusted for other confounders, RV GLS and left atrial strain remained as independent significant predictors. Conclusions RV size, LA strain and volume assessed by CMR serve as markers of RV and LA cardiac dysfunction in CKD patients with preserved LVEF. Greater attention should be given to RV and LA dysfunction for early identification of cardiac dysfunction in CKD patients.
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