Activation of PKC affects the ventricular restitution properties and arrhythmogenesis through L-type Ca+ current.

OBJECTIVE: To investigate the role of protein kinase C (PKC) in action potential duration (APD) restitution and ventricular tachyarrhythmias (VAs). METHODS AND RESULTS: Rabbits hearts were isolated and prepared for Langendorff perfusion technique. The stimuli-extra-stimulus (S1-S2) method and dynamic S1 pacing protocol were performed to construct APD restitution and to induce APD alternans or VA, respectively, at 10 sites throughout the ventricular chamber. Administration of phorbol-12-myristate-13-acetate (PMA) (100 nM) (n = 15) greatly steepened the restitution curves (Smax > 1) (p < .01) at each site compared to the control group (n = 15). Furthermore, treatment with PMA also induced larger spatial dispersions of Smax (p < .05) and decreased the thresholds of the VA and APD alternans (p < .01). However, perfused with the PKC inhibitor, bisindolylmaleimide (BIM) (500 nM) (n = 10), reversibly flattened the APD restitution curves at each site (Smax < 1), decreased the spatial dispersions of Smax, and increased the thresholds of APD alternans and VA. According to the results of patch-clamp, peak amplitude of L-type Ca2+ current was significantly increased by addition of PMA compared with control (CTL) group (p < .05). Antagonize this current with verapamil (n = 10) can fully inhibited the PMA induced increasing of Smax and inducibility of VA and alternans. CONCLUSION: PKC activation increased the dispersion of APD restitution and thus led to occurrence of VA, which possibly related to the increased Ca2+ influx.

Mechanisms and Risk Factors for Premature Ventricular Contraction Induced Cardiomyopathy.

Frequent premature ventricular contractions (PVCs) can cause a reversible form of cardiomyopathy in patients without structural heart disease. Because of the challenging nature of PVC-induced cardiomyopathy (PVICM), the mechanisms and risk factors for PVICM are still unclear. Based on the evidence from retrospective and observational studies, the risk factors for the development of PVICM, in addition to PVC exposure, include QRS duration, coupling interval and male sex. Based on animal models, abnormal calcium handling and cardiac remodeling may be the crucial mechanism underlying the development of cardiomyopathy. We have summarized the current knowledge on PVICM in this review. Understanding these mechanisms and risk factors is important for the diagnosis and management of this condition, which can lead to heart failure if left untreated.

Rotor mechanism and its mapping in atrial fibrillation.

Treatment of atrial fibrillation (AF) remains challenging despite significant progress in understanding its underlying mechanisms. The first detailed, quantitative theory of functional re-entry, the 'leading circle' model, was developed more than 40 years ago. Subsequently, in decades of study, an alternative paradigm based on spiral waves has long been postulated to drive AF. The rotor as a 'spiral wave generator' is a curved 'vortex' formed by spin motion in the two-dimensional plane, identified using advanced mapping methods in experimental and clinical AF. However, it is challenging to achieve complementary results between experimental results and clinical studies due to the limitation in research methods and the complexity of the rotor mechanism. Here, we review knowledge garnered over decades on generation, electrophysiological properties, and three-dimensional (3D) structure diversity of the rotor mechanism and make a comparison among recent clinical approaches to identify rotors. Although initial studies of rotor ablation at many independent centres have achieved promising results, some inconclusive outcomes exist in others. We propose that the clinical rotor identification might be substantially influenced by (i) non-identical surface activation patterns, which resulted from a diverse 3D form of scroll wave, and (ii) inadequate resolution of mapping techniques. With rapidly advancing theoretical and technological developments, future work is required to resolve clinically relevant limitations in current basic and clinical research methodology, translate from one to the other, and resolve available mapping techniques.

Multi-centre, prospective randomized comparison of three different substrate ablation strategies for persistent atrial fibrillation.

AIMS: The optimal strategy for persistent atrial fibrillation (PerAF) is poorly defined. We conducted a multicentre, randomized, prospective trial to compare the outcomes of different ablation strategies for PerAF. METHODS AND RESULTS: We enrolled 450 patients and randomly assigned them in a 1:1:1 ratio to undergo pulmonary vein isolation and subsequently undergo the following three different ablation strategies: anatomical guided ablation (ANAT group, n = 150), electrogram guided ablation (EGM group, n = 150), and extensive electro-anatomical guided ablation (EXT group, n = 150). The primary endpoint was freedom from atrial fibrillation (AF) lasting longer than 30 s at 12 months after a single ablation procedure. After 12 months of follow-up, 72% (108) of patients in the EXT group were free from AF recurrence, as compared with the 64% (96) in the EGM group (P = 0.116), and 54% (81) in the ANAT group (P = 0.002). The EXT group showed less AF/atrial tachycardia recurrence than the EGM group (60% vs. 50%, P = 0.064) and the ANAT group (60% vs. 37.3%, P < 0.001). The EXT group showed the highest rate of AF termination (66.7%), followed by 56.7% in the EGM group, and 20.7% in the ANAT group. The AF termination signified less AF recurrence at 12 months compared to patients without AF termination (30.1% vs. 42.7%, P = 0.008). Safety endpoints did not differ significantly between the three groups (P = 0.924). CONCLUSIONS: Electro-anatomical guided ablation achieved the most favourable outcomes among the three ablation strategies. The AF termination is a reliable ablation endpoint.

Value of estimated pulse wave velocity to identify left ventricular hypertrophy prevalence: insights from a general population.

BACKGROUND: Aortic stiffness shares a similar profile of risk factors with left ventricular hypertrophy (LVH) and can also lead to LVH by itself. Published data have demonstrated the correlation between aortic stiffness and LVH. Recent data have revealed estimated pulse wave velocity (ePWV) to be a simple and cost-effective marker of the severity of aortic stiffness. Our analysis aimed to explore the association between ePWV and LVH prevalence, and to investigate the incremental value of ePWV for the identification of LVH prevalence. METHODS: The present analysis based on a cross-sectional survey which included 11,597 participants from rural areas of southeastern China between Sep 2020 and Feb 2021. ePWV was formulated based on mean blood pressure and age according to a published algorithm. RESULTS: The prevalence of LVH was 14.56%. With the adjustment of age, sex, education, income and physical activity level, current drinking and smoking status, BMI, waist circumference, serum creatinine, total cholesterol, high density cholesterol, mean blood pressure, fasting plasma glucose, anti-hypertensive therapy, anti-diabetic therapy, lipid-lowering therapy, and cardiovascular disease history, every standard deviation increment of ePWV associated with a 2.993 times risk of LVH prevalence. When dividing ePWV into quartiles, the top quartile had a 4.520 times risk of LVH prevalence when compared with the bottom quartile. Furthermore, smooth spline analysis displayed that the association was linear in the whole range of ePWV (p for non-linearity = 0.073). Additionally, subgroup analysis revealed the association was robust to sex, obesity and diabetes, and younger people and hypertensive population were more vulnerable to the increase of ePWV than their corresponding counterparts. Finally, ROC analysis showed a significant advancement when introducing ePWV into established risk factors (0.787 vs. 0.810, p for comparison < 0.001), and reclassification analysis also confirmed significant improvement from ePWV to identify LVH prevalence (category-free net reclassification analysis = 0.421, p < 0.001; integrated discrimination index = 0.023, p < 0.001). CONCLUSION: Our analysis demonstrated a linear association between ePWV and LVH prevalence. Furthermore, our results suggest younger people and hypertensive population are more likely to have LVH prevalence with the increase of ePWV. More importantly, our findings implicate the incremental value of ePWV to optimize the identification of LVH prevalence in a general Chinese population.

Extra-pulmonary vein driver mapping and ablation for persistent atrial fibrillation in obese patients.

AIMS: The aim of this study was to determine whether driver ablation effectively treats persistent atrial fibrillation (AF) in obese patients. METHODS AND RESULTS: We randomly assigned 124 persistent AF obese patients to two groups, one undergoing conventional ablation (n = 62) and the other undergoing driver ablation (n = 62). Sixty-two non-obese patients with persistent AF undergoing driver ablation served as matched controls. Bipolar electrogram dispersion was analysed for driver mapping. Epicardial adipose tissue (EAT) volume was measured using cardiac computed tomography. Obese patients had a higher proportion of driver regions in the posterior wall (56.5% vs. 32.3%, P = 0.007). Driver complexity, measured as the average number and area of driver regions, was higher in the obese group than in the non-obese group (3.5 ± 1.0 vs. 2.9 ± 0.9, P < 0.001; 15.5% ± 4.2% vs. 9.8 ± 2.6%, P < 0.001, respectively). Left atrial EAT volume correlated better with the proportion of area of driver regions than did body mass index (BMI) and total EAT (BMI: r2 = 0.250, P < 0.001; total EAT: r2 = 0.379, P < 0.001; and left atrial EAT: r2 = 0.439, P < 0.001). The rate of AF termination was significantly higher in the driver ablation group than in the conventional ablation group (82.9% vs. 22.8%, P < 0.001). During the follow-up period of 16.9 ± 6.5 months, patients in the driver ablation group had significantly better AF-free survival (91.91% vs. 79.0%, log rank test, P = 0.026) and AF/atrial tachycardia-free survival (83.9% vs. 64.5%, log rank test, P = 0.011) than did patients in the conventional ablation group. CONCLUSION: Obesity is associated with increased driver complexity. Driver ablation improves long-term outcomes in obese patients with persistent AF.

Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019.

AIMS: To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001]. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury. CONCLUSION: The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.

Electrogram dispersion-guided driver ablation adjunctive to high-quality pulmonary vein isolation in atrial fibrillation of varying durations.

OBJECTIVE: To investigate the role of driver mechanism and the effect of electrogram dispersion-guided driver mapping and ablation in atrial fibrillation (AF) at different stages of progression. METHODS: A total of 256 consecutive patients with AF who had undergone pulmonary vein isolation (PVI) plus driver ablation or conventional ablation were divided into three groups: paroxysmal atrial fibrillation (PAF; group A, n = 51); persistent atrial fibrillation (PsAF; group B, n = 38); and long standing-persistent atrial fibrillation (LS-PsAF; group C, n = 39). PVI was performed with the guidance of the ablation index. The electrogram dispersion was analyzed for driver mapping. RESULTS: The most prominent driver regions were at roof (28.0%), posterior wall (17.6%), and bottom (21.3%). From patients with PAF to those with PsAF and LS-PsAF: the complexity of extra-pulmonary vein (PV) drivers including distribution, mean number, and area of dispersion region increased (P < .001). Patients who underwent driver ablation vs conventional ablation had higher procedural AF termination rate (76.6% vs 28.1%; P < .001). With AF progression, the termination rate gradually decreased from group A to group C, and the role of PVI in AF termination was also gradually weakened from group A to group C (39.6%, 7.4%, and 4.3%; P < .001) in patients with driver ablation. At the end of the follow-up, the rate of sinus rhythm maintenance was higher in patients with driver ablation than those with conventional ablation (89.1% vs 70.3%; P < .001). CONCLUSION: The formation of extra-PV drivers provides an important mechanism for AF maintenance with their complexity increasing with AF progression. Electrogram dispersion-guided driver ablation appears to be an efficient adjunctive approach to PVI for AF treatment.

Long non-coding RNA LEF1-AS1 is involved in the progression of retinoblastoma through regulating the Wnt/ß-catenin pathway.

The lymphoid enhancer binding factor 1 antisense RNA 1 (LEF1-AS1) has been suggested to function as a tumour-associated lncRNA in several types of human cancers, but there is no study to date about the role of LEF1-AS1 in retinoblastoma. In our study, LEF1-AS1 expression was increased in retinoblastoma tissues and cell lines compared with paired adjacent normal tissues and the retinal pigment epithelial cell line, respectively. Meanwhile, we found that patients with retinoblastoma with IIRC D-E or undifferentiated type had notably higher levels of LEF1-AS1 expression than those with IIRC A-C or differentiated type. High LEF1-AS1 expression predicted poor disease-free survival in patients with retinoblastoma. The in vitro assays suggested that silencing of LEF1-AS1 suppressed retinoblastoma cell proliferation, migration, and invasion through regulating the Wnt/ß-catenin pathway. In conclusion, LEF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.

Extra pulmonary vein driver mapping and ablation in paroxysmal atrial fibrillation by electrogram dispersion analysis.

BACKGROUND: The adjunctive approach is still unknown for atrial fibrillation (AF), which cannot be terminated after pulmonary vein isolation (PVI). We hypothesized that the driver ablation plus PVI was superior to PVI alone. METHODS AND RESULTS: A total of 98 patients with paroxysmal AF were enrolled in this study and were divided into two groups, with one group undergoing PVI (n = 49) and the other group undergoing PVI + driver ablation (n = 49). The driver regions were defined as clusters of bipolar electrograms that displayed spatial dispersion spread over mean AF cycle length at a minimum of three adjacent bipolars of a PentaRay catheter. During the procedure, the most prominent driver regions before PVI were the roof (n = 27; 55.1%), PV antrum (n = 23; 46.9%), and the inferoposterior wall (n = 11; 22.4%). PVI can eliminate all drivers at PV antrum, but only terminate 30.4% of AF in the driver group. The AF termination rate in the driver ablation group was significantly higher than that in conventional ablation (93.9% vs 40.6%; P < 0.001). The rate of freedom from atrial tachyarrhythmia episodes by a single procedure at 6 months was significantly higher in the driver group than in the conventional group (91.6% vs 72.4%; P = 0.02). CONCLUSION: The present method is effective for AF driver identification. It guided ablation adjunctive to PVI increasing the rate of AF termination and improving the outcomes in patients with paroxysmal AF.

T-Cell Mineralocorticoid Receptor Controls Blood Pressure by Regulating Interferon-Gamma.

RATIONALE: Hypertension remains to be a global public health burden and demands novel intervention strategies such as targeting T cells and T-cell-derived cytokines. Mineralocorticoid receptor (MR) antagonists have been clinically used to treat hypertension. However, the function of T-cell MR in blood pressure (BP) regulation has not been elucidated. OBJECTIVE: We aim to determine the role of T-cell MR in BP regulation and to explore the mechanism. METHODS AND RESULTS: Using T-cell MR knockout mouse in combination with angiotensin II-induced hypertensive mouse model, we demonstrated that MR deficiency in T cells strikingly decreased both systolic and diastolic BP and attenuated renal and vascular damage. Flow cytometric analysis showed that T-cell MR knockout mitigated angiotensin II-induced accumulation of interferon-gamma (IFN-γ)-producing T cells, particularly CD8+ population, in both kidneys and aortas. Similarly, eplerenone attenuated angiotensin II-induced elevation of BP and accumulation of IFN-γ-producing T cells in wild-type mice. In cultured CD8+ T cells, T-cell MR knockout suppressed IFN-γ expression whereas T-cell MR overexpression and aldosterone both enhanced IFN-γ expression. At the molecular level, MR interacted with NFAT1 (nuclear factor of activated T-cells 1) and activator protein-1 in T cells. Finally, T-cell MR overexpressing mice manifested more elevated BP compared with control mice after angiotensin II infusion and such difference was abolished by IFN-γ-neutralizing antibodies. CONCLUSIONS: MR may interact with NFAT1 and activator protein-1 to control IFN-γ in T cells and to regulate target organ damage and ultimately BP. Targeting MR in T cells specifically may be an effective novel approach for hypertension treatment.

Long-Term Effect of Different Optimizing Methods for Cardiac Resynchronization Therapy in Patients with Heart Failure: A Randomized and Controlled Pilot Study.

AIM: During cardiac resynchronization therapy (CRT), optimized programming of the atrioventricular (AV) delay and ventricular-to-ventricular (VV) interval can lead to improved hemodynamics, symptomatic response, and left ventricular systolic function. Currently, however, there is no recommendation for the best optimization method. This study aimed to compare the long-term clinical outcomes of 4 different CRT optimization methods. METHODS: One hundred and twenty-four consecutive CRT patients with severe heart failure and left bundle-branch block configuration were randomly assigned into four groups to undergo AV/VV delay optimization through echocardiogram (ECHO; n = 30), electrocardiogram (ECG; n = 32), QuickOpt algorithm (n = 28), and nominal AV/VV (n = 36) groups. Patients were followed up and underwent examinations, including New York Heart Association (NYHA) cardiac functional classification, 6-min walking distance (6MWD), and echocardiography, at 6, 12, 24, 36, and 48 months, respectively. The patients' survival and clinical outcomes were compared among the four groups. RESULTS: Kaplan-Meier survival analyses showed that the median survival was the same in the 4 groups: ECHO, 43 months; ECG, 44 months; QuickOpt, 44 months, and nominal, 41 months. At the 6-month follow-up, the reduction in left ventricular end diastolic diameter (LVEDD) was significantly less in the nominal group (-1.91 ± 2.58 mm) than that in the other three groups (ECHO: -3.70 ± 2.78 mm, p = 0.012; ECG: -3.53 ± 3.14 mm, p = 0.020; QuickOpt: -3.46 ± 2.65 mm, p = 0.032); 6MWD was significantly shorter in the nominal group (87.88 ± 34.76 m) than that in the other three groups (ECHO: 120.63 ± 56.93 m, p = 0.006; ECG: 114.97 ± 54.95 m, p = 0.020; QuickOpt: 114.57 ± 35.41 m, p = 0.027). Left ventricular ejection fraction (LVEF) significantly increased in ECHO (7.23 ± 2.76%, p = 0.010), ECG (8.50 ± 3.17%, p < 0.001), and QuickOpt (8.39 ± 2.90%, p < 0.001) compared with the nominal group (5.35 ± 2.59%). There were no significant differences among the groups in the aforementioned parameters at 24, 36, and 48 months, respectively. CONCLUSION: While LVEDD, LVEF, 6MWD, and NYHA were significantly improved in ECHO, ECG, and QuickOpt at 6 months, there were no significant improvements in any of the groups at 12, 24, and 48 months. These findings suggested that the long-term effect of the four CRT methods for heart failure was not significantly different.

Optimal endpoint for catheter ablation of longstanding persistent atrial fibrillation: A randomized clinical trial.

BACKGROUND: In longstanding persistent atrial fibrillation (LPeAF), the ideal endpoint of ablation remains to be determined. This study was to explore the value of pursuing AF termination or no with the same strategy during ablation on the long-term outcomes in patients with LPeAF. METHODS: Utilized "CCL" strategy is a fixed ablation approach consisting of circumferential pulmonary vein antrum isolation, ablation of complex fractionated atrial electrogram, and linear ablation between two anatomical structures (the mitral isthmus, left atrial roof). Note that 400 patients were randomized to group A (technical endpoint) and group B (pursuing AF termination). RESULTS: A group with technical endpoint had lower rate of acute AF termination (AF→sinus rhythm, 3.5% vs 18.1%; AF→atrial tachycardia, 23.7% vs 44.7%; P < 0.01) and shorter duration of ablation (164.9 ± 20.8 vs 223.4 ± 24.9, P < 0.01), radiofrequency delivery time (69.8 ± 18.1 vs 102.2 ± 26.3, P < 0.01), and x-ray exposure time (18.2 ± 8.8 vs 27.9 ± 12.4, P < 0.01) than those in B group (pursuing AF termination). During follow-up, freedom from atrial arrhythmias did not differ between the two groups after a single ablation procedure (46.5% vs 54.3%, P=0.12) and the final ablation procedure (60.1% vs 65.8%, P  =  0.24). CONCLUSION: In patients of LPeAF, pursuing AF termination during ablation was associated with similar long-term clinical outcome compared to that with technical endpoint. Ablation to termination is not the best strategy during ablation.

Eplerenone Prevents Atrial Fibrosis via the TGF-ß Signaling Pathway.

OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies. TGF-ß1-stimulated atrial fibroblasts were treated with EPL or vehicle for the in vitro studies including Western blotting and qRT-PCR studies. In addition, Smad7 siRNA was used to knock down Smad7. RESULTS: EPL inhibited atrial fibrosis in the Tx mice. In addition, EPL suppressed the expression of fibrosis-related molecules induced by TGF-ß1 in vivo and in vitro. This occurred in concert with a downregulation of Smad7 protein expression and an upregulation of p-Smad2/3 protein expression. In addition, knockdown of Smad7 by siRNA abolished the protective roles of EPL. CONCLUSIONS: EPL inhibited atrial fibrosis in Tx mice. The underlying mechanism may involve increased protein expression of Smad7, which enhances the inhibitory feedback regulation of TGF-ß1/Smad signaling.

Polarization-controlled images based on double-exposure polarization holography in an azobenzene liquid-crystalline polymer.

Polarization-controlled optical image operations were demonstrated based on the double-exposure polarization holographic method. Two images were stored in the same volume of an azobenzene liquid-crystalline polymer by recording superimposed holograms, a pair of polarization gratings with one spatial frequency, using two orthogonal circularly polarized 532 nm beams and were reconstructed with a 650 nm laser. The recorded polarization holographic gratings were investigated to show distinctive polarization selectivity, high diffraction efficiency, and good stability. The brightness and the polarization of the diffracted images were found to be dependent on the polarization of the readout beam, and two images could be reconstructed individually or simultaneously.

Chronic N-methyl-D-aspartate receptor activation induces cardiac electrical remodeling and increases susceptibility to ventricular arrhythmias.

BACKGROUND: N-Methyl-d-aspartate receptors, also known as NMDA Receptors or NMDAR, are glutamate receptors that control calcium ion channels and regulate synaptic plasticity. Acute NMDAR activation can induce ventricular arrhythmias (VAs). However, the influence of chronic NMDAR activation on cardiac electrophysiology remains unknown. METHODS AND RESULTS: Wistar rats were randomly administered 0.9% saline (CTL group), NMDA (N group), or NMDA plus MK801 (N+M group) for 14 days. Compared with the CTL group, the N group displayed elevated heart rate and prolonged QT, QTc, and TpTe intervals in the electrocardiogram (P < 0.05 for all). Then, the S1 S2 , S1 S1 , and Burst pacing were performed to assess the characteristics of repolarization; threshold of action potential duration (APD) alternans; beat-to-beat variability of repolarization (BVR); and VAs susceptibility in the left ventricular. The prolonged APD at 90% repolarization (APD90 ); decreased ERP/APD90 ; increased dispersion of APD90 , ERP, and ERP/APD90 ; decreased threshold of APD alternans; increased BVR; and incidence of VAs were showed in the N group compared with those of the CTL group (P < 0.01 for all). Moreover, chronic NMDA administration reduced the expression of Kv4.2, Kv4.3, KChIP2, and Kv11.1 proteins, and induced mild myocardial interstitial fibrosis (P < 0.01 for all). Importantly, these alterations induced by NMDA were normalized by co-treatment with MK801. CONCLUSION: Chronic NMDAR activation prolonged repolarization, induced electrical instability, and facilitated VAs, which may be associated with reduced Ito and IKr and myocardial fibrosis.

Value of the monocyte-to-high-density lipoprotein cholesterol ratio in refining the detection of prevalent heart failure: Insights from the NHANES 1999-2018.

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999-2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non-HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings.

Short-term dietary teprenone improved thermal tolerance and mitigated liver damage caused by heat stress in juvenile largemouth bass (Micropterus salmoides).

Heat stress seriously threatens fish survival and health, demanding immediate attention. Teprenone is a gastric mucosal protective agent that can induce heat shock protein expression. This research investigated the effects of teprenone on largemouth bass (Micropterus salmoides) subjected to heat stress. Juvenile fish were assigned to different groups: group C (control group, 0 mg teprenone/kg diet), T0, T200, T400, and T800 (0, 200, 400, and 800 mg teprenone/kg diet, respectively), which were fed for 3 days, followed by a day without the diet. All groups except group C were subjected to acute heat stress (from 24 °C to 35 °C at 1 °C per hour and then maintained at 35 °C for 3 h). The results were as follows: The critical thermal maxima were significantly higher in the T200, T400, and T800 groups compared with the T0 group (P < 0.05). Heat stress caused severe damage to the tissue morphology of the liver, while teprenone significantly reduced this injury (P < 0.05). Serum cortisol concentration decreased gradually as teprenone concentration increased, and the lowest concentration was observed in the T800 group (P < 0.05). Compared with the T0 group, the serum activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase were significantly lower in the T200, T400, and T800 groups (P < 0.05). The liver activities of catalase, total superoxide dismutase, and peroxidase were significantly higher in the T200 group than in the T0 group (P < 0.05). Transcript levels of the heat shock proteins (hsp90, hsp70, hspa5, and hsf1) and caspase family (caspase3 and caspase9) in the liver of the T200 group were significantly higher than those of the T0 group (P < 0.05). Western blot results showed that HSP70 and HSPA5 in the liver were significantly upregulated in the T200 group compared with the T0 group (P < 0.05). In summary, dietary teprenone improved thermal tolerance, alleviated heat stress damage in the liver, enhanced antioxidant capacity, and upregulated heat shock proteins in juvenile largemouth bass. This study offers theoretical support for applying teprenone in aquaculture to reduce financial losses caused by abiotic factors.

Investigating the combinatorial effects of radiofrequency ablation and anticoagulants in patients with atrial fibrillation and left atrial appendage thrombosis after successful thrombolysis.

The present study investigated the synergistic effects of radiofrequency ablation and various anticoagulants on adverse outcomes in patients with atrial fibrillation (AF) and left atrial appendage thrombosis following successful thrombolysis. Patients diagnosed with AF and left atrial appendage thrombosis post-successful thrombolysis (n=92) were retrospectively analysed. They were divided into two groups: Group A received radiofrequency ablation combined with an anticoagulant, while Group B received an anticoagulant alone and in combination with antiarrhythmic drugs. Subgroup analyses were conducted based on left atrial diameter (>45 mm), duration of AF (>1 year) and types of anticoagulants. Univariate and multivariate logistic regression analyses were performed to assess stroke and mortality risks in patients with AF with left atrial appendage thrombosis after dissolution. Multivariate logistic regression analysis identified AF duration (>1 year), left atrial diameter (>45 mm) and BNP level as significant risk factors for stroke (P<0.05). Compared with NOACs, the traditional anticoagulants (warfarin) demonstrated higher survival rates and lower stroke incidence in Group B (P<0.05); however, no significant difference was observed within Group A (P>0.05). Radiofrequency ablation combined with anticoagulants appeared to be more effective in treating AF with left atrial appendage thrombosis post-dissolution compared with anticoagulants alone. Attention to AF duration and left atrial diameter is crucial during early patient management. However, the choice between warfarin or NOACs for patients with AF and left atrial appendage thrombosis warrants further investigation.