Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling.

BACKGROUND: Cardiac remodeling in heart failure involves macrophage-mediated immune responses. Recent studies have shown that a PRR (pattern recognition receptor) called dectin-1, expressed on macrophages, mediates proinflammatory responses. Whether dectin-1 plays a role in pathological cardiac remodeling is unknown. Here, we identified a potential role of dectin-1 in this disease. METHODS: To model aberrant cardiac remodeling, we utilized mouse models of chronic Ang II (angiotensin II) infusion. In this model, we assessed the potential role of dectin-1 through using D1KO (dectin-1 knockout) mice and bone marrow transplantation chimeric mice. We then used cellular and molecular assays to discover the underlying mechanisms of dectin-1 function. RESULTS: We found that macrophage dectin-1 is elevated in mouse heart tissues following chronic Ang II administration. D1KO mice were significantly protected against Ang II-induced cardiac dysfunction, hypertrophy, fibrosis, inflammatory responses, and macrophage infiltration. Further bone marrow transplantation studies showed that dectin-1 deficiency in bone marrow-derived cells prevented Ang II-induced cardiac inflammation and dysfunction. Through detailed molecular studies, we show that Ang II binds directly to dectin-1, causing dectin-1 homodimerization and activating the downstream Syk (spleen tyrosine kinase)/NF-κB (nuclear factor kappa B) signaling pathway to induce expression of inflammatory and chemoattractant factors. Mutagenesis studies identified R184 in the C-type lectin domain to interact with Ang II. Blocking dectin-1 in macrophages suppresses Ang II-induced inflammatory mediators and subsequent intercellular cross talk with cardiomyocytes and fibroblasts. CONCLUSIONS: Our study has discovered dectin-1 as a new nonclassical receptor of Ang II and a key player in cardiac remolding and dysfunction. These studies suggest that dectin-1 may be a new target for treating hypertension-related heart failure.

Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis.

Cuproptosis is a recently discovered programmed cell death pattern that affects the tricarboxylic acid (TCA) cycle by disrupting the lipoylation of pyruvate dehydrogenase (PDH) complex components. However, the role of cuproptosis in the progression of ischemic heart failure (IHF) has not been investigated. In this study, we investigated the expression of 10 cuproptosis-related genes in samples from both healthy individuals and those with IHF. Utilizing these differential gene expressions, we developed a risk prediction model that effectively distinguished healthy and IHF samples. Furthermore, we conducted a comprehensive evaluation of the association between cuproptosis and the immune microenvironment in IHF, encompassing infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes. Moreover, we identified two different cuproptosis-mediated expression patterns in IHF and explored the immune characteristics associated with each pattern. In conclusion, this study elucidates the significant influence of cuproptosis on the immune microenvironment in ischemic heart failure (IHF), providing valuable insights for future mechanistic research exploring the association between cuproptosis and IHF.

Targeting Nanoplatform for Atherosclerosis Inhibition and Degradation via a Dual-Track Reverse Cholesterol Transport Strategy.

As a main cause of serious cardiovascular diseases, atherosclerosis is characterized by deposited lipid and cholesterol crystals (CCs), which is considered as a great challenge to the current treatments. In this study, a dual-track reverse cholesterol transport strategy is used to overcome the cumulative CCs in the atherosclerotic lesions via a targeting nanoplatform named as LPLCH. Endowed with the active targeting ability to the plaques, the nanoparticles can be efficiently internalized and achieve a pH-triggered charge conversion for the escape from lysosomes. During this procedure, the liver X receptor (LXR) agonists loaded in nanoparticles are replaced by the deposited lysosomal CCs, leading to a LXR mediated up-regulation of ATP-binding cassette transporte ABCA1/G1 with the local CCs carrying at the same time. Thus, the cumulative CCs are removed in a dual-track way of ABCA1/G1 mediated efflux and nanoparticle-based carrying. The in vivo investigations indicate that LPLCH exhibits a favorable inhibition on the plaque progression and a further reversal of formed lesions when under a healthy diet. And the RNA-sequencing suggests that the cholesterol transport also synergistically activates the anti-inflammation effect. The dual-track reverse cholesterol transport strategy performed by LPLCH delivers an exciting candidate for the effective inhibition and degradation of atherosclerosis.

Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.

Intracardiac echocardiography guided electrified J-wire trans-septal puncture: A prospective randomized controlled trial.

BACKGROUND: Application of electrocautery to a J-wire is used to perform transseptal puncture (TSP), but with limited evidence supporting safety and efficacy. We conducted a prospective randomized controlled trial to evaluate the safety and efficacy of this technique. METHODS: Two hundred consecutive patients were randomized in a 1:1 fashion to either the ICE-guided electrified J-wire TSP group or a conventional Brockenbrough (BRK) needle TSP group. The TSP was performed with a 0.032″ guidewire under 20 W, "coag" mode and was compared to TSP using the BRK needle. The primary safety endpoints were complications related to TSP. The primary efficacy endpoints included the TSP success rate, the total TSP time, and the total procedure time. RESULTS: All patients complete the procedure safely. The electrified J-wire TSP group had a significantly shorter TSP time than BRK needle TSP group. The total procedure time, number of TSP attempts required to achieve successful LA access, width of the intra-atrial shunt at the end of ablation were similar between the two groups. The incidence of new cerebral infarction detected by MRI were similar between the two groups (3/32 patients in the J-wire TSP group and 2/26 patients in conventional BRK TSP group, p = .82). And no difference in the incidence of residual intra-atrial shunt (4.3% vs. 6%, p = .654) during the 3-month's follow up. CONCLUSION: Using an electrified J-wire for TSP under the guidance of ICE appears to be as safe as and more efficient than conventional BRK needle TSP, which may be especially useful in the era of non-fluoroscopy AF ablation.

Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

Macrophage Dectin-1 mediates Ang II renal injury through neutrophil migration and TGF-ß1 secretion.

Macrophage activation has been shown to play an essential role in renal fibrosis and dysfunction in hypertensive chronic kidney disease. Dectin-1 is a pattern recognition receptor that is also involved in chronic noninfectious diseases through immune activation. However, the role of Dectin-1 in Ang II-induced renal failure is still unknown. In this study, we found that Dectin-1 expression on CD68 + macrophages was significantly elevated in the kidney after Ang II infusion. We assessed the effect of Dectin-1 on hypertensive renal injury using Dectin-1-deficient mice infused by Angiotensin II (Ang II) at 1000 ng/kg/min for 4 weeks. Ang II-induced renal dysfunction, interstitial fibrosis, and immune activation were significantly attenuated in Dectin-1-deficient mice. A Dectin-1 neutralizing antibody and Syk inhibitor (R406) were used to examine the effect and mechanism of Dectin-1/Syk signaling axle on cytokine secretion and renal fibrosis in culturing cells. Blocking Dectin-1 or inhibiting Syk significantly reduced the expression and secretion of chemokines in RAW264.7 macrophages. The in vitro data showed that the increase in TGF-ß1 in macrophages enhanced the binding of P65 and its target promotor via the Ang II-induced Dectin-1/Syk pathway. Secreted TGF-ß1 caused renal fibrosis in kidney cells through Smad3 activation. Thus, macrophage Dectin-1 may be involved in the activation of neutrophil migration and TGF-ß1 secretion, thereby promoting kidney fibrosis and dysfunction.

Diagnostic performance of a novel automated CT-derived FFR technology in detecting hemodynamically significant coronary artery stenoses: A multicenter trial in China.

BACKGROUND AND AIMS: Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. METHODS: 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." RESULTS: The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. CONCLUSIONS: The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD.

Three-year clinical outcomes of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: A prospective patient-level pooled analysis of NeoVas trials.

OBJECTIVES: We aimed to evaluate the long-term outcomes of the novel NeoVas sirolimus-eluting bioresorbable scaffold (BRS) for the treatment of de novo coronary artery disease. BACKGROUND: The long-term safety and efficacy of the novel NeoVas BRS are still needed to be elucidated. METHODS: A total of 1103 patients with de novo native coronary lesions for coronary stenting were enrolled. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or ischemia-driven-target lesion revascularization (ID-TLR). RESULTS: A three-year clinical follow-up period was available for 1,091 (98.9%) patients. The cumulative TLF rate was 7.2% with 0.8% for CD, 2.6% for TV-MI, and 5.1% for ID-TLR. Additionally, 128 (11.8%) patient-oriented composite endpoint and 11 definite/probable stent thromboses (1.0%) were recorded. CONCLUSIONS: The extended outcomes of the NeoVas objective performance criterion trial demonstrated a promising 3-year efficacy and safety of the NeoVas BRS in low-risk patients with low complexity in terms of lesions and comorbidities.

Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

The effectiveness and feasibility of using multi-lead ECG monitoring combined with a programmed intracavitary ECG to complete left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBaP) as an alternative method for delivering physiological pacing, is difficult for many primary hospitals that lack the electrophysiological multichannel recorder to carry out. We hope to find a simple and feasible method that combines the multi-lead surface electrocardiogram (ECG) monitoring and the intracavity ECG of the pacing programmer to achieve LBBaP. METHODS: A total of 50 patients with bradycardia indications who attempted permanent pacemaker implantation were included in this study. We referred to multi-lead surface ECG monitoring and pacing system analyzer (PSA), combined with the nine-zone pacing method of the LBBaP, to complete LBBaP. We assessed multiple parameters to verify whether the LBBaP was successfully achieved and used univariable analysis of variance for repeated measures to judge the feasibility and effectiveness of LBBaP without the electrophysiological multichannel recorder. RESULTS: LBBaP was successfully archived without the electrophysiological multichannel recorder in 44 of 50 patients (88%). In the study, paced QRS duration and the stimulus to peak left ventricular activation time (Sti-LVAT) were 117.04 ± 10.34 ms and 71.10 ± 7.91 ms and had no significant changes in the 3-month follow-up. The unipolar pacing threshold and R-wave amplitudes were 0.85 ± 0.32 V and 10.36 ± 5.24 mV at baseline respectively, which also showed stability during the 1-month and 3-month follow-up. During the 3-month follow-up, no lead-related complication was recorded. CONCLUSION: It is effective and feasible to achieve LBBaP combining the multi-lead ECG monitoring and the intracavitary ECG of PSA without the electrophysiological multichannel recorder, which could be an alternative to perform LBBaP.

The specific value of upgrading to left bundle branch area pacing in patients with pacing-induced cardiomyopathy or non-pacing-induced cardiomyopathy related upgrade status: A retrospective study.

AIMS: Left bundle branch area pacing (LBBaP) upgrade can improve cardiac function and clinical outcomes in patients with pacing-induced cardiomyopathy (PICM), but the specific value of LBBaP upgrade, especially compared with the cardiac function level before right ventricular pacing (RVP) in patients with PICM and non-pacing-induced cardiomyopathy-related upgrade status (Non-PICMUS) is still unknown. METHODS: This study retrospectively enrolled 70 patients with LBBaP upgrade (38 patients with PICM and 32 patients with Non-PICMUS). All upgrade patients experienced three stages: before RVP (Pre-RVP), before LBBaP upgrade (Pre-LBBaP), and after LBBaP upgrade (Post-LBBaP). QRS duration (QRSd), lead parameters, echocardiographic indicators, and clinical outcomes evaluation were recorded at multiple time points. RESULTS: At the follow-up of 12 months, for PICM patients, left ventricular ejection fraction (LVEF) significantly increased from 36.6% ± 7.2% to 51.3% ± 8.7% Post-LBBaP (p < .001), and left ventricular end-diastolic diameter (LVEDD) significantly decreased from 61.5 ± 6.4 mm to 55.2 ± 6.5 mm Post-LBBaP (p < .001), but they both failed to restore the level Pre-RVP (both p < .001). For PICM patients, New York Heart Association (NYHA) classification, the number of moderate-to-severe heart failure (NYHA III-IV), and diuretics using rate after the LBBaP upgrade also could not restore to the level Pre-RVP (all p < .001). At the follow-up of 12 months, Non-PICMUS patients after the LBBaP upgrade had no significant improvement in LVEF, LVEDD, and NYHA classification (all p > .05). CONCLUSION: LBBaP upgrade effectively improved the cardiac function and clinical outcomes in PICM patients, but its effectiveness seemed to be limited as the deteriorated cardiac function cannot be completely reversed. For Non-PICMUS patients, the cardiac function and clinical outcomes Post-LBBaP had no significant improvement.

Cardiovascular imaging in conduction system pacing: What does the clinician need?

Permanent pacemakers are used for symptomatic bradycardia and biventricular pacing (BVP)-cardiac resynchronization therapy (BVP-CRT) is established for heart failure (HF) patients traditionally. According to guidelines, patients' selection for CRT is based on QRS duration (QRSd) and morphology by surface electrocardiogram (ECG). Cardiovascular imaging techniques evaluate cardiac structure and function as well as identify pathophysiological substrate changes including the presence of scar. Cardiovascular imaging helps by improving the selection of candidates, guiding left ventricular (LV) lead placement, and optimization devices during the follow-up. Conduction system pacing (CSP) includes His bundle pacing (HBP) and left bundle branch pacing (LBBP) which is screwed into the interventricular septum. CSP maintains and restores ventricular synchrony in patients with native narrow QRSd and left bundle branch block (LBBB), respectively. LBBP is more feasible than HBP due to a wider target area. This review highlights the role of multimodality cardiovascular imaging including fluoroscopy, echocardiography, cardiac magnetic resonance (CMR), myocardial scintigraphy, and computed tomography (CT) in the pre-procedure assessment for CSP, better selection for CSP candidates, the guidance of CSP lead implantation, and the optimization of devices programming after the procedure. We also compare the different characteristics of multimodality imaging and discuss their potential roles in future CSP implantation.

Intracardiac echocardiography is a safe and effective alternative to transesophageal echocardiography for left atrial appendage thrombus evaluation at the time of atrial fibrillation ablation: The ICE-TEE study.

BACKGROUND: Intracardiac echocardiography (ICE) technology has been increasingly accepted as an integral part of atrial fibrillation (AF) ablation procedures. It is still unknown whether ICE can routinely replace transesophageal echocardiography (TEE) for routine thrombus screening in non-selective AF patients. OBJECTIVE: To assess whether ICE can routinely replace TEE in screening for left atrial (LA)/left atrial appendage (LAA) thrombus in general patients undergoing catheter ablation for AF. METHODS: A total of 2003 consecutive patients undergoing AF ablation were included. 1155 patients (ICE group) received intra-procedural ICE examination for LA/LAA thrombus screening, while 848 patients (TEE group) received pre-procedure TEE examination. The incidence of thrombus, peri-procedure complications, and hospital efficiency were assessed. RESULTS: The LA and LAA were adequately visualized in all patients. Five patients in the ICE group and 15 patients in the TEE group were found to have LAA thrombus. The incidence of major periprocedural thrombo-embolic events was comparable between two groups (0.2% vs. 0.1%, p = .76), none were due to undetected LA/LAA thrombus. Other major periprocedural complications occurred at similar rates in both groups, while post-procedure fever was less common in the ICE group (12.7% vs. 17.4%, p < .001). Procedure times and hospital length of stay were both shorter in the ICE group (142 min [87-197 min] vs. 150 min [95-205 min], and 3[2-4] day vs. 4[3-5] day, respectively, both p < .001). CONCLUSIONS: ICE can replace TEE for atrial thrombus screening in AF patients undergoing ablation without increased complications. An "ICE replacing TEE" workflow can also reduce the incidence of postoperative fever and improve hospital efficiency.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Efficacy of Mobile-Based Cognitive Behavioral Therapy on Lowering Low-density Lipoprotein Cholesterol Levels in Patients With Atherosclerotic Cardiovascular Disease: Multicenter, Prospective Randomized Controlled Trial.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. OBJECTIVE: This trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. METHODS: This multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: "CBT ASCVD." The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (<1.8 mmol/L) at the first, third, and sixth months. RESULTS: Finally, 296 participants completed the 6-month follow-up (CBT group: n=148; control group: n=148). At baseline, the mean LDL-C level was 2.48 (SD 0.90) mmol/L, and the LDL-C up-to-standard rate (<1.8 mmol/L) was 21.3%. Mobile-based CBT intervention significantly increased the reduction of LDL-C change (%) at the 6-month follow-up (ß=-10.026, 95% CI -18.111 to -1.940). In addition, this benefit remained when baseline LDL-C <1.8 mmol/L (ß=-24.103, 95% CI -43.110 to -5.095). Logistic regression analysis showed that mobile-based CBT intervention moderately increased the LDL-C up-to-standard rates (<1.8 mmol/L) in the sixth month (odds ratio 1.579, 95% CI 0.994-2.508). For GSE and QL-index, mobile-based CBT intervention significantly increased the change of scores (%) at the 1-, 3-, and 6-month follow-up (all P values <.05). CONCLUSIONS: In patients with ASCVD, mobile-based CBT is effective in reducing LDL-C levels (even for those who already had a standard LDL-C) and can improve self-efficacy and quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046775; https://www.chictr.org.cn/showproj.aspx?proj=127140.

Liver enzymes mediate the association between aldehydes co-exposure and hypertriglyceridemia.

Aldehydes are recognized environmental toxicants that may affect lipid metabolism. For instance, acrolein has been found to increase serum triglyceride (TG) levels exclusively. However, it remains unclear whether other aldehydes are also associated with hypertriglyceridemia (HTG), and what mechanisms may be involved. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2013-2014) to identify associations between serum aldehydes, liver enzymes, and HTG. Serum aldehydes included crotonaldehyde (CRAL), propanaldehyde (3AL), butyraldehyde (4AL), pentanaldehyde (5AL), isopentanaldehyde (I5AL), and heptanaldehyde (7AL). Liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). HTG was defined as fasting TG levels ≥ 1.7 mmol/L. Aldehyde co-exposure was quantified using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), while mediation analysis was performed to investigate the role of liver enzymes. Among 1474 participants (mean age 38.6 years, male 50.0%), 426 were diagnosed with HTG. 4AL, 5AL, I5AL, and 7AL were shown to be positively associated with HTG (all P values <0.05). Aldehydes co-exposure was also positively associated with HTG (OR 1.706, 95%CI 1.299-2.240), with 5AL contributing the highest weight (35.3%). Furthermore, aldehydes co-exposure showed positive associations with ALT, AST, and GGT (all P values <0.05), and all four liver enzymes were positively associated with HTG (all P values <0.05). Mediation analysis revealed that liver enzymes (ALT, AST, and GGT) may mediate the associations of 5AL and 7AL with HTG (all P values <0.05). This study identified a positive association between aldehyde co-exposure and HTG, which may be partially mediated by liver enzymes.

Transcriptome analysis uncovers the autophagy-mediated regulatory patterns of the immune microenvironment in dilated cardiomyopathy.

The relationship between autophagy and immunity has been well studied. However, little is known about the role of autophagy in the immune microenvironment during the progression of dilated cardiomyopathy (DCM). Therefore, this study aims to uncover the effect of autophagy on the immune microenvironment in the context of DCM. By investigating the autophagy gene expression differences between healthy donors and DCM samples, 23 dysregulated autophagy genes were identified. Using a series of bioinformatics methods, 13 DCM-related autophagy genes were screened and used to construct a risk prediction model, which can well distinguish DCM and healthy samples. Then, the connections between autophagy and immune responses including infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes were systematically evaluated. In addition, two autophagy-mediated expression patterns in DCM were determined via the unsupervised consensus clustering analysis, and the immune characteristics of different patterns were revealed. In conclusion, our study revealed the strong effect of autophagy on the DCM immune microenvironment and provided new insights to understand the pathogenesis and treatment of DCM.

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

BACKGROUND: Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload. METHODS: Cardiac-specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac-specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction. Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and nuclear magnetic resonance spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload. RESULTS: We found that PKM1 expression is reduced in failing human and mouse hearts. It is important to note that cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against transverse aortic constriction-induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels. CONCLUSIONS: These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.