BACKGROUND:For patients undergoing surgical valve procedures with concomitant coronary artery disease, current guidelines recommend that coronary artery bypass grafting (CABG) should be anatomically guided on the basis of stenosis severity, as assessed by coronary angiography. We aimed to test whether a physiologically guided strategy using angiography-derived fractional flow reserve (FFR) could improve clinical outcomes in this population. METHODS:FAVOR IV-QVAS is an investigator-initiated, multicentre, randomised, triple-blind trial done at 12 tertiary hospitals in China. Eligible patients were aged 18 years or older and were scheduled for valve surgery, with at least one clinically significant stenosis in a major coronary artery. Patients were randomly assigned (1:1) to undergo physiologically guided CABG (for lesions with an angiography-derived FFR value ≤0·80) or anatomically guided CABG (for lesions with a stenosis diameter ≥50% on coronary angiography). Randomisation was done using a web-based program and stratified by site with fixed blocks of four. Patients, surgeons, follow-up physicians, and outcome assessors were masked to treatment allocation. The primary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and new renal failure requiring dialysis within 30 days after surgery. The key secondary outcome was a composite of death, myocardial infarction, stroke, unplanned coronary revascularisation, and hospitalisation for unstable angina or heart failure at a minimum follow-up of 1 year. The primary analysis of the primary and key secondary outcomes was done in a modified intention-to-treat population that included all randomly assigned patients who underwent surgery and had available data for the primary outcome. Missing data for the primary outcome were planned to be analysed using complete-case analysis or multiple imputation, with a proportion of missing data of 2% as the threshold. This trial is registered at ClinicalTrials.gov (NCT03977129); extended follow-up is ongoing. FINDINGS:Between Aug 4, 2019, and Aug 13, 2024, 793 patients were enrolled. 396 were randomly assigned to the angiography-derived FFR group and 397 to the coronary angiography group; one patient in the coronary angiography group declined surgery and was excluded from the modified intention-to-treat population. The median age was 65 years (IQR 59-70), 221 (28%) patients were female, and 571 (72%) were male. Concomitant CABG was done in 223 (56%) patients in the angiography-derived FFR group and in 388 (98%) patients in the coronary angiography group. The primary outcome occurred in 31 (7·8%) patients in the angiography-derived FFR group and 53 (13·4%) in the coronary angiography group (absolute difference -5·6 percentage points [95% CI -9·9 to -1·3]; risk ratio 0·58 [95% CI 0·38 to 0·89]; p=0·011). Death within 30 days occurred in 11 (2·8%) patients in the angiography-derived FFR group and 17 (4·3%) patients in the coronary angiography group. At a median follow-up of 27 months (28 months [IQR 18-44] in the angiography-derived FFR group and 27 months [18-42] in the coronary angiography group), the key secondary outcome occurred in 82 (20·7%) patients in the angiography-derived FFR group and in 106 (26·8%) patients in the coronary angiography group (hazard ratio 0·74 [95% CI 0·55-0·98]; p=0·036). INTERPRETATION:Among patients undergoing valve surgery with concomitant coronary artery disease, physiologically guided CABG using angiography-derived FFR reduced the incidence of the composite perioperative outcome compared with anatomically guided CABG. These findings support a selective approach to surgical coronary revascularisation guided by physiological assessment in patients undergoing valve procedures. FUNDING:Shanghai Hospital Development Center, Shanghai Municipal Science and Technology Commission, and Ministry of Science and Technology of the People's Republic of China.
OBJECTIVES:We evaluated the safety and efficacy of transcatheter aortic valve replacement (TAVR) up to 1-year follow-up for patients with severe pure aortic valve regurgitation (AR) or mixed severe aortic valve regurgitation and aortic valve stenosis (AR+AS) using a novel self-expandable bioprosthesis. METHODS:From 2021 to 2022, transapical TAVR using Ken-Valve (Jenscare Biotechnology Ltd, Ningbo, China) was performed in 142 symptomatic patients (mean age 70.3 ± 5.5 years) with pure AR (n = 109) or AR+AS (n = 33) across 15 hospitals in China. All patients were considered high-risk or inoperable after heart team evaluation, with a mean Society of Thoracic Surgeons score of 5.9 ± 3.0%, and 99.3% in NYHA class III/IV. Procedural characteristics, echocardiography data, and clinical outcomes up to 1-year were analysed. RESULTS:Technical success was achieved in 97.2% of cases. Two (1.4%) patients were converted to open surgery due to unsuitable anatomy or valve migration during the procedure. New permanent pacemakers were implanted in 20 (14.1%) patients. Three (2.1%) patients had stroke, and 3 (2.1%) patients had major bleeding. Thirty-day mortality was 2.1%, and all-cause mortality at 1-year was 5.6% (8/142). Mean aortic valve gradient and effective orifice area (EOA) at 1-year postoperatively were 9.4 ± 5.4 mmHg and 1.9 ± 0.6 cm2, respectively. Significant improvement in clinical symptoms, positive left ventricular remodelling, and quality of life were observed up to 1-year. There was no significant difference in mortality, complications, and haemodynamic performance between patients with pure AR and AR+AS at 1-year. CONCLUSIONS:TAVR using the Ken-Valve was safe and effective in patients with pure AR or mixed AR+AS in mid-term. CLINICAL REGISTRATION NUMBER:NCT03788590.
We aimed to establish a rat TR model to further investigate the mechanisms of right heart remodeling and organ damage induced by TR. Intervention group rats (n = 6) underwent coronary stent system implantation via transjugular approach. The control group (n = 6) underwent the same procedure, except for coronary stent implantation. All rats survived at 8 weeks follow-up postoperatively. TR occurred immediately after the implantation of coronary stent in the intervention group. The right ventricular fractional area change (FAC) decreased by 33.9
Objective:Heart transplantation (HT) is the ultimate treatment option for patients with end-stage heart failure, and its prognostic evaluation has consistently been a focal point in clinical research. This article primarily explores the impact of the pre-operative Model for End-Stage Liver Disease (MELD) and its derivative scoring systems on the prognosis of HT patients. Methods:A retrospective analysis was conducted on the data of patients who underwent HT at Shanghai Changhai Hospital from January 2018 to January 2024. All included patients were scored using the MELD and its upgraded versions (MELD-XI, MELD-albumin). Initially, the preoperative baseline of survival group and non-survival group were compared. Subsequently, the association between various MELD scores and patient prognosis was analyzed using the Receiver Operating Characteristic (ROC) curve. Based on the higher Area Under the Curve (AUC), MELD-albumin was selected as the research indicator. Patients were then divided into high-score group and low-score group according to its optimal cutoff value, and the perioperative data of the two groups were compared. Results:A total of 170 patients were included in this study, with 159 patients (93.5%) in survival group and 11 patients (6.5%) in non-survival group. Comparison of preoperative and intraoperative baseline data between the two groups revealed that the non-survival group had a lower preoperative platelet count, higher preoperative creatinine levels and BNP levels, a lower left ventricular ejection fraction (LVEF), and higher scores in MELD, MELD-XI, and MELD-albumin compared to the survival group. ROC analysis demonstrated that the AUC values for preoperative MELD scores in predicting in-hospital mortality were 0.806, 0.842 for MELD-XI, and 0.843 for MELD-albumin. MELD-albumin was selected as the primary indicator. Based on the optimal cutoff value of 8.4, patients were divided into low-score group (MELD-albumin ≤8.4, 128 cases) and high-score group (MELD-albumin >8.4, 42 cases) to explore its relationship with perioperative prognosis in HT. The results showed statistical differences between the two groups in preoperative white blood cell count, platelet count, monocyte count, bilirubin, creatinine, BNP, international normalized ratio (INR), and procalcitonin levels, while no statistical differences were observed in intraoperative data. Regarding prognosis, the high-score group had a higher mortality rate (19% vs. 2.3%, P = 0.0004) and a higher proportion of patients suffering postoperative acute kidney injury (AKI) (38% vs. 18.7%, P = 0.023) and receiving continuous renal replacement therapy (CRRT) (14.3% vs. 4.7%, P = 0.039). Conclusion:This study confirms that the preoperative MELD-albumin score is an independent predictor of in-hospital mortality in HT patients, and its optimal cutoff value of 8.4 can effectively distinguish between high-risk and low-risk populations.
BACKGROUND:Transcatheter tricuspid valve replacement (TTVR) is emerging as a promising surgical alternative for high-risk patients with tricuspid regurgitation (TR). Nonetheless, the feasibility of more dedicated devices and the need for additional clinical evidence warrant further exploration. OBJECTIVES:The purpose of this study was to report the 1-year outcomes of the TRAVEL (Transcatheter Right Atrial-Ventricular Valve Replacement With LuX-Valve) study with the LuX-Valve system for patients with severe TR. METHODS:A total of 126 patients with symptomatic severe TR were prospectively enrolled in the single-arm, multicenter TRAVEL study from June 2020 to August 2021. All patients underwent TTVR via the transatrial approach using the LuX-Valve system. The primary endpoint was all-cause mortality and hospitalization for heart failure at 1-year follow-up. Clinical and echocardiographic outcomes were reported. RESULTS:At baseline, all enrolled patients (mean age 65.8 ± 7.5 years, 79.4% women) were at high surgical risk (mean Society of Thoracic Surgeons score 9.2% ± 4.4%), with severe or greater TR and NYHA functional class ≥ III. In 1-year follow-up, all-cause mortality was 10.3%, and 4.0% of patients were hospitalized for heart failure. TR was reduced to mild or less in 95.2% (P < 0.001), with decreases in right atrial systolic volume (-38.3 ± 21.7 mL; P < 0.001) and mid right ventricular end-systolic diameter (-6.4 ± 2.3 mm; P < 0.001). NYHA functional class I or II was achieved in 79.8% (P < 0.001), and 6-minute walking distance increased by 71.3 ± 42.8 m (P < 0.001). CONCLUSIONS:The 1-year outcomes of the TRAVEL study showed a sustained reduction in TR among patients who underwent LuX-Valve TTVR, accompanied by significant right heart reverse remodeling and improved functional status. Favorable procedural success and survival benefits were also demonstrated. (the TRAVEL Trial: Transcatheter Right Atrial-Ventricular Valve Replacement With LuX-Valve; NCT04436653).
Aortic valve calcification is a significant contributor to the development of aortic valve stenosis, a condition for which effective pharmacological treatments are currently limited. Sodium-glucose cotransporter 2 inhibitors, such as canagliflozin (CANA), have demonstrated promising cardioprotective effects, irrespective of diabetes status. This study aims to investigate the therapeutic effects and underlying mechanisms of CANA on aortic valve calcification. In an aortic valve wire injury mouse model, treatment with CANA significantly reduced aortic valve peak velocity, inhibited leaflet thickening, and decreased calcium deposition. Furthermore, CANA enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase (HO-1) and reduced the levels of the oxidative stress marker 8-OHdG. In an in vitro osteogenic model of valvular interstitial cells (VICs), CANA treatment effectively reduced the expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 and decreased the formation of calcium nodules. Additionally, CANA activated the Nrf2/HO-1 antioxidant signaling pathway in VICs under calcification induction conditions, while significantly reducing the accumulation of reactive oxygen species and mitochondrial superoxide. In an ex vivo model of human aortic valve calcification, CANA treatment led to a reduction in calcified nodule formation and ALP expression, along with the activation of the Nrf2/HO-1 signaling pathway and a decrease in 8-OHdG levels. The protective effects of CANA on aortic valve calcification were partially reversed by the Nrf2 inhibitor ML385 or small interfering RNA-mediated NRF2 knockdown, confirming the involvement of the Nrf2/HO-1 pathway. Importantly, CANA-induced Nrf2/HO-1 activation in VICs was mediated by the AMPK pathway. In summary, CANA effectively delayed aortic valve calcification by enhancing the AMPK/Nrf2/HO-1 antioxidant signaling pathway, suggesting that CANA may hold therapeutic potential for preventing or slowing the progression of aortic valve stenosis.
Aim Acute aortic dissection (AAD) represents a cardiovascular ailment characterised by a notable mortality rate. Chronobiological patterns can offer a predictive framework for anticipating the onset of AAD. Method Data were gathered from 1,151 patients diagnosed with AAD at Changhai Hospital in Shanghai, China, spanning 2000-2023. The chi(2) test was used to assess whether specific periods exhibited significantly different seasonal/weekly distributions compared with others. Fourier models were utilised for the analysis of rhythmicity in monthly/circadian distribution. Publicly available genome-wide association studies datasets were used to establish the causal relationship between chronotype and AAD. Two sets of genetics instruments were used for analysis, derived from publicly available genetic summary data: 75 single-nucleotide polymorphisms (SNPs) significantly associated with chronotype; and SNPs associated with AAD in the FinnGen consortium. Results The mean age was 51.5 +/- 13.8 years, with 665 patients (57.8%) aged <55 years. Among the 1,151 patients, 80.9% were male. The distribution of DeBakey types was 73.2% (843) for DeBakey I, 21% (242) for DeBakey II, and 5.7% (66) for DeBakey III. Comorbidities included hypertension in 58.5% (673 cases) and diabetes in 7.8% (90 cases). A peak occurred during colder periods (winter/December), and a trough was noted in warmer periods (summer/June). Weekly distribution exhibited no significant variation. Fourier analysis revealed a statistically significant circadian variation (p<0.0001) with a trough between 23:00 and 00:00, a prominent peak from 07:00 to 08:00, and a minor peak between 20:00 and 21:00. Subgroup analyses identified circadian rhythmicity in all subgroups, except for the DeBakey III group and the female group. Using the 75 chronotype-related SNPs, evidence was found of a potential causal effect of chronotype on the risk of AAD, as the inverse-variance weighting analysis showed that self-report chronotype of morningness was associated with a decreased risk of AAD. Conclusions The findings substantiate that the initiation of AAD displays noteworthy seasonal, monthly, and circadian patterns. The Mendelian randomisation analysis also indicated that the onset of acute aortic dissection is related to circadian rhythm. These findings offer a fresh perspective, facilitating the identification of triggering factors for AAD and bolstering preventive measures for this catastrophic event.
OBJECTIVES:To evaluate the effects of 75% ethanol on the disinfection efficacy, biocompatibility, extracellular matrix (ECM) integrity, and mechanical properties of swim bladders from Hypophthalmichthys nobilis, a promising biomaterial for cardiovascular applications. METHODS:Swim bladders were immersed in 75% ethanol for 30, 60, or 120 minutes, followed by phosphate-buffered saline (PBS) rinsing. Disinfection efficacy was assessed using bacterial cultures; cytotoxicity and blood compatibility were evaluated using CCK-8 assays and hemolysis tests. The decellularization efficiency, ECM integrity, and mechanical properties were analyzed through histological staining, DNA quantification, and uniaxial tensile test. RESULTS:75% ethanol effectively disinfected the swim bladder with minimal cytotoxicity and good hemocompatibility. Histological staining demonstrated preservation of collagen fibers, elastin, and glycosaminoglycans (GAGs), indicating minimal impact on the ECM structure. The uniaxial tensile test revealed that ethanol immersion caused tissue dehydration and increased stiffness, but these effects were reversible after PBS rinsing, with mechanical properties returning to baseline. DNA content and tissue thickness normalized following PBS washing, suggesting that ethanol did not impair decellularization. CONCLUSIONS:75% ethanol is an effective disinfectant for swim bladder biomaterials, preserving biocompatibility, ECM structure, and mechanical properties after rinsing. These findings support the use of swim bladder-derived scaffolds in cardiovascular tissue engineering applications.
Background: Calcific aortic valve disease (CAVD) is a prevalent valvular heart disease characterized by the fibrocalcific remodeling of the aortic valves, leading to significant health issues among the elderly population worldwide. The aberrant expression of long noncoding RNAs (lncRNAs) is closely associated with the pathogenesis of various diseases. Methods and Results: A total of 241 differentially expressed lncRNAs were identified in calcified aortic valve tissues (fold change of ≥ 2 and p value < 0.05), including 65 upregulated and 176 downregulated lncRNAs. The expression of the Top 5 upregulated lncRNAs was monitored during the calcification of valvular interstitial cell (VIC). Notably, the expression of lnc-PRDM8-3 and lnc-COL6A1-6 in VICs increased significantly after calcification induction and was sustained at high levels. Inhibition of lnc-COL6A1-6, but not lnc-PRDM8-3, obviously alleviated the calcification of VICs, as evidenced by a marked reduction in calcium deposition, decreased alkaline phosphatase activity, and downregulated expression of Runx2 and OPN. Bioinformatic analysis predicted that lnc-COL6A1-6 might serve as a competing endogenous RNA for 11 miRNAs, potentially regulating the expression of 784 target genes. Among these, the Top 50 target genes were found to be significantly enriched in autophagy-related biological processes. Consistently, elevated levels of the autophagic markers Beclin 1 and LC3β were detected in calcified aortic valve tissues. Inhibition of lnc-COL6A1-6 significantly reduced autophagic flux in VICs under calcification-inducing conditions. Importantly, pharmacological inhibition of autophagy using chloroquine abolished the anticalcific effects of lnc-COL6A1-6 knockdown. Conclusions: The present study identified a lnc-COL6A1-6-mediated miRNA-mRNA regulatory network in aortic valve calcification. Knockdown of lnc-COL6A1-6 could mitigate VIC calcification by attenuating autophagic activity, highlighting its potential as a therapeutic target for CAVD.
The impact of QRS duration on postoperative LBBB and its implications for the prognosis of patients undergoing transcatheter aortic valve replacement (TAVR) remained uncertain. This study enrolled consecutive patients who underwent TAVR with self-expanding prostheses in our department from September 2017 to January 2021. Based on the pro-discharge electrocardiogram, patients were categorized into 3 groups: Group-NCD (no conduction disorder), Group-sLBBB (LBBB, QRS ≥ 150 ms), and Group-mLBBB (LBBB, QRS < 150 ms). Basic characteristics were compared among these groups. Furthermore, differences in left ventricular ejection fraction (LVEF), survival rates, and clinical events were assessed at baseline, discharge, and during a one-year follow-up period. A total of 56 patients were included in the study. With 17 (30.36%) experiencing new-onset LBBB, of which eleven had a QRS duration ≥ 150 ms. Group-sLBBB exhibited a longer left ventricular end-diastolic diameter at baseline. At a one-year follow-up, the LVEF improved in Group-NCD, but not in the LBBB groups. At discharge, the LVEF of Group-sLBBB was lower than that of Group-NCD (52.82 ± 11.48 vs 61.48 ± 10.10, P = .036) and remained lower at follow-up (57.10 ± 9.49 vs 65.85 ± 7.58, P = .011). Additionally, the LVEF of Group-sLBBB was lower than that of Group-mLBBB at discharge (52.82 ± 11.48 vs 63.17 ± 4.31, P = .018). However, there were no significant differences in survival and event-free survival among the groups. The study revealed a notable occurrence of new-onset LBBB following TAVR, with a majority of cases exhibiting a significantly prolonged QRS duration (≥150 ms). While the presence of LBBB did not impact one-year survival or clinical events, it did exert adverse effects on LVEF. Notably, when QRS duration was markedly prolonged, these adverse effects manifested earlier and were more pronounced.
BACKGROUND:Accumulative evidence has shown that systemic lupus erythematosus (SLE) increases the risk of various cardiovascular diseases including atrial fibrillation (AF). The study aimed to screen potential key genes underlying co-pathogenesis between SLE and AF, and to discover therapeutic targets for AF. METHODS:Differentially expressed genes (DEGs) were identified, and co-expressed gene modules were obtained through weighted gene co-expression network analysis (WGCNA) based on the AF and SLE expression profiles from the GEO database. Subsequently, machine learning algorithms including LASSO regression and support vector machine (SVM) method were employed to identify the candidate therapeutic target for SLE-related AF. Furthermore, the therapeutic role of TMEM45A was validated both in vivo and vitro. RESULTS:Totally, 26 DEGs were identified in SLE and AF. The PPI network combined with WGCNA identified 51 key genes in SLE and AF. Ultimately, Machine learning-based methods screened three hub genes in SLE combined with AF, including TMEM45A, ITGB2 and NFKBIA. The cMAP analysis exposed KI-8751 and YM-155 as potential drugs for AF treatment. Regarding TMEM45A, the aberrant expression was validated in blood of SLE patients. Additionally, TMEM45A expression was up-regulated in the atrial tissue of patients with AF. Furthermore, TMEM45A knockdown alleviated AF occurrence and atrial fibrosis in vivo and Ang II-induced NRCFs fibrosis in vitro. CONCLUSION:The crosstalk genes underlying co-pathogenesis between SLE and AF were unraveled. Furthermore, the pro-fibrotic role of TMEM45A was validated in vivo and vitro, highlighting its potential as a therapeutic target for AF.
Decellularized extracellular matrix (dECM), a promising tissue engineering scaffold for cardiovascular applications, might exhibit enhanced durability when endowed with anticalcification and antithrombotic properties. Herein, we present a biomimetic bilayer hydrogel coating applied to acellular swim bladders (ASBs). First, we designed an endothelium-mimicking (HCT) hydrogel coating, comprising alternately assembled endothelial glycocalyx macromolecule hyaluronic acid, copper ions, and tannic acid. Subsequently, a hydrophilic methacrylated silk fibroin (SilMA) hydrogel was incorporated as the outer coating layer. Notably, the HCT hydrogel penetrated and anchored into the ASB matrix, forming an interpenetrating network that enhanced the biostability and mechanical properties of the ASB matrix. Additionally, the SilMA hydrogel enhanced the hydrophilicity and antifouling properties of the HCT coating. In vitro experiments and subcutaneous implantation further revealed that the bilayer hydrogel (H/S) coating exhibited excellent biocompatibility, hemocompatibility, antibacterial activity, and anticalcification properties. Furthermore, a blood circulation model and rabbit shunt assay confirmed the great anticoagulation properties of the H/S coating. Moreover, in an in vivo rat carotid aorta replacement model, the H/S coating effectively promoted endothelialization, enhanced vascular remodeling, prevented calcification and thrombosis, and ultimately improved ASB durability. Based on these findings, our endothelium-mimicking hydrophilic bilayer hydrogel coating holds great promise as a surface modification strategy for tissue engineering scaffolds.
Transcatheter tricuspid valve replacement (TTVR) is emerging as a promising surgical alternative for high-risk patients with tricuspid regurgitation (TR). Nonetheless, the feasibility of more dedicated devices and the need for additional clinical evidence warrant further exploration. The purpose of this study was to report the 1-year outcomes of the TRAVEL (Transcatheter Right Atrial-Ventricular Valve Replacement With LuX-Valve) study with the LuX-Valve system for patients with severe TR. A total of 126 patients with symptomatic severe TR were prospectively enrolled in the single-arm, multicenter TRAVEL study from June 2020 to August 2021. All patients underwent TTVR via the transatrial approach using the LuX-Valve system. The primary endpoint was all-cause mortality and hospitalization for heart failure at 1-year follow-up. Clinical and echocardiographic outcomes were reported. At baseline, all enrolled patients (mean age 65.8 ± 7.5 years, 79.4% women) were at high surgical risk (mean Society of Thoracic Surgeons score 9.2% ± 4.4%), with severe or greater TR and NYHA functional class ≥ III. In 1-year follow-up, all-cause mortality was 10.3%, and 4.0% of patients were hospitalized for heart failure. TR was reduced to mild or less in 95.2% (P < 0.001), with decreases in right atrial systolic volume (-38.3 ± 21.7 mL; P < 0.001) and mid right ventricular end-systolic diameter (-6.4 ± 2.3 mm; P < 0.001). NYHA functional class I or II was achieved in 79.8% (P < 0.001), and 6-minute walking distance increased by 71.3 ± 42.8 m (P < 0.001). The 1-year outcomes of the TRAVEL study showed a sustained reduction in TR among patients who underwent LuX-Valve TTVR, accompanied by significant right heart reverse remodeling and improved functional status. Favorable procedural success and survival benefits were also demonstrated. (the TRAVEL Trial: Transcatheter Right Atrial-Ventricular Valve Replacement With LuX-Valve; NCT04436653).
This study investigated the causal relationships between cytokines, chemokines, neutrophil-related factors, sleep traits, and CMR-derived cardiovascular phenotypes using two-sample Mendelian randomization (MR) analysis. The primary method employed was inverse variance weighted (IVW) analysis, supplemented with MR-Egger and weighted median analyses. We identified 24 significant associations, excluding the SNP rs2001329 related to sleep duration. Notably, CXCL9 showed a strong association with right ventricular peak atrial filling rate (OR = 587.45), while IL-5 was associated with right ventricular stroke volume (OR = 2.45). IL-7 and IL-18 significantly impacted four CMR-derived phenotypes each. Left ventricular ejection fraction was frequently affected by IL-1β, IL-18, CCL2, CXCL9, and NETs. Sensitivity analyses indicated minimal pleiotropy or heterogeneity except for sleep duration. This research highlights crucial cytokines and chemokines that modulate cardiac function through their relationships with cardiovascular phenotypes.
The tricuspid valve is known as “the forgotten valve”. Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease. TR is often late in the course of the disease when it becomes symptomatic, often being a marker of late-stage chronic heart failure with a poor prognosis and high mortality rate at long-term follow-up. Despite the clear correlation between TR and mortality, most TR patients are under-treated. Neither pharmacologic nor surgical treatment demonstrates a significant survival benefit. Isolated tricuspid valve surgery has the highest mortality rate of all valve surgeries. Therefore, there is an urgent clinical need for minimally invasive therapies to meet the needs of patients with TR. In recent years, a variety of transcatheter tricuspid valve interventions representing less invasive alternatives to surgery have shown promising results, which bring hope to patients with severe TR. The purpose of this review is to provide a complete and updated overview on current transcatheter tricuspid valve interventions and clinical evidence.
Abstract Dilated cardiomyopathy (DCM), a major cause of heart failure in young adults, is characterized by ventricular dilation and progressive heart muscle dysfunction. Cellular mechanisms driving DCM have not been elucidated despite advances in genomic medicine. This study performed comprehensive multimodal single-cell analysis integrating RNA sequencing, assay for transposase-accessible chromatin with sequencing, and spatial transcriptomics data of cardiac tissues from patients with DCM and control subjects. The complex cellular heterogeneity and a novel neuro-cardiac interface were identified in DCM. The neuronal signaling pathways, including GABA receptor signaling and WT1 transcription factor activity, were profoundly dysregulated in the cardiomyocytes of patients with DCM. Cell-cell signaling analysis revealed that the communication patterns were altered, especially the upregulation of IGF and NRG signaling, suggesting a redefined role of adipocytes and lymphatic cells in DCM pathogenesis. The results of neuronal marker immunostaining analysis were consistent with those of bioinformatics analysis and indicated a potential cross-talk between cardiomyocytes and neurons. The findings of this study provided novel insights into the molecular mechanisms of DCM and identified potential therapeutic targets for DCM, which will enable the development of precision therapeutic approaches for cardiomyopathies.
Background Sex-related dissimilarities' influence on outcomes following thoracic aortic surgery is poorly understood. Our aim is to examine sex-related disparities in patients undergoing thoracic aortic aneurysm (TAA). Methods A total of 455 cases undergoing thoracic aortic aneurysm (TAA) surgery were consecutively enrolled between December 2009 and December 2015 in a Chinese hospital. Primary outcomes, including overall mortality and related risk factors, were evaluated. Cox regression is utilized to recognize the independent risk factor of these consequences. Results Females, compared to males, had greater indexed aortic diameters and higher aortic transvalvular pressure differences. For the location of aortic aneurysms, females had a higher rate of aortic arch involvement, while males had a higher rate of root involvement. Females underwent less frequent complex proximal aortic operations compared with males (29.5% versus 46.9%; p < 0.001). Women and men both had a lower rate of aortic transvalvular pressure difference and LV volume index 7 days after thoracic aortic surgery. The overall mortality for the women's groups (11%) was suggestively greater compared to 4.9% for the men's groups (p = 0.026). Renal failure and aortic arch involvement were the main risk factors associated with males' survival, while maximum indexed aortic diameter and cross-clamp time were the risk factors associated with females' survival. Conclusions The outcome after TAA surgery was less favorable in women with significantly increased overall mortality. It highlights the need to focus on implementing personalized surgery strategies and gender-specific guidelines in treating female patients following TAA surgery.
Background: The treatment strategy of early nutritional support after cardiac surgery has gradually been adopted. However, there are no scientific guidelines for the timing and specific programs of early nutritional support. Methods: A retrospective, single-center analysis (2021-2023) was carried out including elderly patients who were admitted for valvular heart disease and received open-heart valve replacement surgery. We designated patients who started the optimized nutritional support after surgery as the optimized enteral nutritional support strategy TN (EN) group and those who received traditional nutritional support as the traditional nutritional support strategy (TN) group. The nutritional and immune indexes, postoperative complications, length of hospital stay, and hospitalization cost of the two groups were compared and analyzed. Results: We identified 378 eligible patients, comprising 193 (51%) patients in the EN group and 185 (49%) patients in the TN group. There was no significant difference in hospital mortality between the two groups, but the proportion of nosocomial pneumonia was significantly lower in the EN group than in the TN group (P < 0.001). In the Poisson regression analysis, EN was not associated with an increase in gastrointestinal complications (P = 0.549). The EN group also seemed to have shorter hospital stays and lower hospitalization expenses (P < 0.001). In the comparison of postoperative gastrointestinal complications, fewer patients experienced diarrhea (P = 0.021) and abdominal distension (P = 0.033) in the EN group compared with the TN group. Conclusion: The optimal nutritional support strategy could effectively improve the clinical outcome of high-risk patients with valvular heart disease.
Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by β-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.
Background: The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. Methods: In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. Results: A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C -reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8 +/- 21.8 vs. 34.9 +/- 13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9 +/- 6.96 vs. 8.9 +/- 2.92 cmH 2 O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade >= III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Conclusions: Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.