Deciphering the role of CX3CL1-CX3CR1 in aortic aneurysm pathogenesis: insights from Mendelian randomization and transcriptomic analyses.

Background: The crucial role of inflammation in aortic aneurysm (AA) is gaining prominence, while there is still a lack of key cytokines or targets for effective clinical translation. Methods: Mendelian randomization (MR) analysis was performed to identify the causal relationship between 91 circulating inflammatory proteins and AA and between 731 immune traits and AA. Bulk RNA sequencing data was utilized to demonstrate the expression profile of the paired ligand-receptor. Gene enrichment analysis, Immune infiltration, and correlation analysis were employed to deduce the potential role of CX3CR1. We used single-cell RNA sequencing data to pinpoint the localization of CX3CL1 and CX3CR1, which was further validated by multiplex immunofluorescence staining. Cellchat analysis was utilized to infer the CX3C signaling pathway. Trajectory analysis and the Cytosig database were exploited to determine the downstream effect of CX3CL1-CX3CR1. Results: We identified 4 candidates (FGF5, CX3CL1, IL20RA, and SCF) in multiple two-sample MR analyses. Subsequent analysis of the expression profile of the paired receptor revealed the significant upregulation of CX3CR1 in AA and its positive correlation with pro-inflammatory macrophages. Two sample MR between immune cell traits and AA demonstrated the potential causality between intermediate monocytes and AA. We finally deciphered in single-cell sequencing data that CX3CL1 sent by endothelial cells (ECs) acted on CX3CR1 of intermediated monocytes, leading to its recruitment and pro-inflammatory responses. Conclusion: Our study presented a genetic insight into the pathogenetic role of CX3CL1-CX3CR1 in AA, and further deciphered the CX3C signaling pathway between ECs and intermediate monocytes.

Functional Oxidized Hyaluronic Acid Cross-Linked Decellularized Heart Valves for Improved Immunomodulation, Anti-Calcification, and Recellularization.

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV is cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA. Notably, DHV cross-linked with middle- and high-molecular-weight OHA could drive the macrophage polarization toward the M2 phenotype in vitro. Moreover, DHV cross-linked with middle-molecular-weight OHA scaffolds are further modified with RGD-PHSRN peptide (RPF-OHA/DHV) to block the residual aldehyde groups of the unreacted OHA. The results show that RPF-OHA/DHV not only exhibits anti-calcification properties, but also facilitates endothelial cell adhesion and proliferation in vitro. Furthermore, RPF-OHA/DHV shows excellent performance under an in vivo hemodynamic environment with favorable recellularization and immune regulation without calcification. The optimistic results demonstrate that OHA with different molecular weights has different cross-linking effects on DHV and that RPF-OHA/DHV scaffold with enhanced immune regulation, anti-calcification, and recellularization properties for clinical transformation.

Development and validation of mortality prediction models for heart transplantation using nutrition-related indicators: a single-center study from China.

Objective: We sought to develop and validate a mortality prediction model for heart transplantation (HT) using nutrition-related indicators, which clinicians could use to identify patients at high risk of death after HT. Method: The model was developed for and validated in adult participants in China who received HT between 1 January 2015 and 31 December 2020. 428 subjects were enrolled in the study and randomly divided into derivation and validation cohorts at a ratio of 7:3. The likelihood-ratio test based on Akaike information was used to select indicators and develop the prediction model. The performance of models was assessed and validated by area under the curve (AUC), C-index, calibration curves, net reclassification index, and integrated discrimination improvement. Result: The mean (SD) age was 48.67 (12.33) years and mean (SD) nutritional risk index (NRI) was 100.47 (11.89) in the derivation cohort. Mortality after HT developed in 66 of 299 patients in the derivation cohort and 28 of 129 in the validation cohort. Age, NRI, serum creatine, and triglyceride were included in the full model. The AUC of this model was 0.76 and the C statistics was 0.72 (95% CI, 0.67-0.78) in the derivation cohort and 0.71 (95% CI, 0.62-0.81) in the validation cohort. The multivariable model improved integrated discrimination compared with the reduced model that included age and NRI (6.9%; 95% CI, 1.8%-15.1%) and the model which only included variable NRI (14.7%; 95% CI, 7.4%-26.2%) in the derivation cohort. Compared with the model that only included variable NRI, the full model improved categorical net reclassification index both in the derivation cohort (41.8%; 95% CI, 9.9%-58.8%) and validation cohort (60.7%; 95% CI, 9.0%-100.5%). Conclusion: The proposed model was able to predict mortality after HT and estimate individualized risk of postoperative death. Clinicians could use this model to identify patients at high risk of postoperative death before HT surgery, which would help with targeted preventative therapy to reduce the mortality risk.

Shear stress activates the Piezo1 channel to facilitate valvular endothelium-oriented differentiation and maturation of human induced pluripotent stem cells.

Valvular endothelial cells (VECs) derived from human induced pluripotent stem cells (hiPSCs) provide an unlimited cell source for tissue engineering heart valves (TEHVs); however, they are limited by their low differentiation efficiency and immature function. In our study, we applied unidirectional shear stress to promote hiPSCs differentiation into valvular endothelial-like cells (VELs). Compared to the static group, shear stress efficiently promoted the differentiation and functional maturation of hiPSC-VELs, as demonstrated by the efficiency of endothelial differentiation reaching 98.3% in the high shear stress group (45 dyn/cm2). Furthermore, we found that Piezo1 served as a crucial mechanosensor for the differentiation and maturation of VELs. Mechanistically, the activation of Piezo1 by shear stress resulted in the influx of calcium ions, which in turn initiated the Akt signaling pathway and promoted the differentiation of hiPSCs into mature VELs. Moreover, VELs cultured on decellularized heart valves (DHVs) exhibited a notable propensity for proliferation, robust adhesion properties, and antithrombotic characteristics, which were dependent on the activation of the Piezo1 channel. Overall, our study demonstrated that proper shear stress activated the Piezo1 channel to facilitate the differentiation and maturation of hiPSC-VELs via the Akt pathway, providing a potential cell source for regenerative medicine, drug screening, pathogenesis, and disease modeling. STATEMENT OF SIGNIFICANCE: This is the first research that systematically analyzes the effect of shear stress on valvular endothelial-like cells (VELs) derived from human induced pluripotent stem cells (hiPSCs). Mechanistically, unidirectional shear stress activates Piezo1, resulting in an elevation of calcium levels, which triggers the Akt signaling pathway and then facilitates the differentiation of functional maturation VELs. After exposure to shear stress, the VELs exhibited enhanced proliferation, robust adhesion capabilities, and antithrombotic characteristics while being cultured on decellularized heart valves. Thus, it is of interest to develop hiPSCs-VELs using shear stress and the Piezo1 channel provides insights into the functional maturation of valvular endothelial cells, thereby serving as a catalyst for potential applications in the development of therapeutic and tissue-engineered heart valves in the future.

Morusin Alleviates Aortic Valve Calcification by Inhibiting Valve Interstitial Cell Senescence Through Ccnd1/Trim25/Nrf2 Axis.

The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE-/- mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.

Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells.

BACKGROUND: A main obstacle in current valvular heart disease research is the lack of high-quality homogeneous functional heart valve cells. Human induced pluripotent stem cells (hiPSCs)-derived heart valve cells may help with this dilemma. However, there are no well-established protocols to induce hiPSCs to differentiate into functional heart valve cells, and the networks that mediate the differentiation have not been fully elucidated. METHODS: To generate heart valve cells from hiPSCs, we sequentially activated the Wnt, BMP4, VEGF (vascular endothelial growth factor), and NFATc1 signaling pathways using CHIR-99021, BMP4, VEGF-165, and forskolin, respectively. The transcriptional and functional similarity of hiPSC-derived heart valve cells compared with primary heart valve cells were characterized. Longitudinal single-cell RNA sequencing was used to uncover the trajectory, switch genes, pathways, and transcription factors of the differentiation. RESULTS: An efficient protocol was developed to induce hiPSCs to differentiate into functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells. After 6-day differentiation and CD144 magnetic bead sorting, ≈70% CD144+ cells and 30% CD144- cells were obtained. On the basis of single-cell RNA sequencing data, the CD144+ cells and CD144- cells were found to be highly similar to primary heart valve endothelial cells and primary heart valve interstitial cells in gene expression profile. Furthermore, CD144+ cells had the typical function of primary heart valve endothelial cells, including tube formation, uptake of low-density lipoprotein, generation of endothelial nitric oxide synthase, and response to shear stress. Meanwhile, CD144- cells could secret collagen and matrix metalloproteinases, and differentiate into osteogenic or adipogenic lineages like primary heart valve interstitial cells. Therefore, we identified CD144+ cells and CD144- cells as hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells, respectively. Using single-cell RNA sequencing analysis, we demonstrated that the trajectory of heart valve cell differentiation was consistent with embryonic valve development. We identified the main switch genes (NOTCH1, HEY1, and MEF2C), signaling pathways (TGF-ß, Wnt, and NOTCH), and transcription factors (MSX1, SP5, and MECOM) that mediated the differentiation. Finally, we found that hiPSC-derived valve interstitial-like cells might derive from hiPSC-derived valve endothelial-like cells undergoing endocardial-mesenchymal transition. CONCLUSIONS: In summary, this is the first study to report an efficient strategy to generate functional hiPSC-derived valve endothelial-like cells and hiPSC-derived valve interstitial-like cells from hiPSCs, as well as to elucidate the differentiation trajectory and transcriptional dynamics of hiPSCs differentiated into heart valve cells.

Off-pump versus on-pump coronary artery bypass grafting in elderly patients at 30 days: a propensity score matching study.

BACKGROUND: Elderly patients are at increased risk of perioperative morbidity and mortality after conventional on-pump coronary artery bypass grafting (ONCABG). This study was to determine whether such high-risk population would benefit from off-pump coronary artery bypass grafting (OPCABG). METHODS: A retrospective analysis was performed on patients aged 65 years or older who underwent isolated coronary artery bypass grafting for the first time in Wuhan Union Hospital from January 2015 to January 2021. We used propensity score matching to adjust for differences in baseline characteristics between the ONCABG and OPCABG groups. Morbidity and mortality within 30 days after surgery were compared between the two groups. All operations were performed by experienced cardiac surgeons. RESULTS: A total of 511 patients (ONCABG 202, OPCABG 309) were included. After 1:1 matching, the baseline characteristics of the two groups were comparable (ONCABG 173, OPCABG 173). The OPCABG group had higher rate of incomplete revascularization (13.9% vs. 6.9%; P = .035) than the ONCABG group. However, OPCABG reduced the risk of postoperative renal insufficiency (15.0% vs. 30.1%; P = .001) and reoperation for bleeding (0.0% vs. 3.5%; P = .030). There were no significant differences in early postoperative mortality, myocardial infarction, stroke, and other outcomes between the two groups. CONCLUSIONS: OPCABG is an alternative revascularization method for elderly patients. It reduces the risk of early postoperative renal insufficiency and reoperation for bleeding.

Long-term survival of ischemic cardiomyopathy patients with severe left ventricular dysfunction after CABG vs heart transplantation: A single center retrospective analysis.

BACKGROUND: There are no guidelines on the surgical management for ischemic cardiomyopathy (ICM) patients with severe left ventricular dysfunction. The present study aims to assess the long-term survival of these patients treated with two different surgical techniques, coronary artery bypass grafting (CABG) and heart transplantation (HTx). METHODS: This retrospective study included 218 ICM patients with left ventricular ejection fraction (LVEF) ≤35% who underwent CABG (n = 106) and HTx (n = 112) from 2011 to 2021 in a single center. After propensity adjustment analysis each group consisted of 51 patients. Clinical characteristics were evaluated for all-cause follow-up mortality by the Cox proportional hazards regression model. A risk prediction model was generated from multivariable-adjusted Cox regression analysis and applied to stratify patients with different clinical risks. The long-term survival was estimated by Kaplan-Meier analysis for different surgery groups. RESULTS: Long-term survival was comparable between CABG and HTx groups. After being stratified into different risk subgroups according to risk predictors, the HTx group exhibited superior survival outcomes compared to the CABG group among the high-risk patients (67.8% vs 44.4%, 64.1% vs 38.9%, and 64.1% vs 33.3%, p = 0.047) at 12, 36, and 60 months respectively, while the survival was comparable between HTx and CABG groups among low-risk patients (87.0% vs 97.0%, 82.4% vs 97.0%, and 70.2% vs 91.6%, p = 0.11) at 12, 36, and 60 months respectively in the PSM cohort. CONCLUSION: Long-term survival in ICM patients with severe left ventricular dysfunction who received CABG or HTx was comparable in general. Nonetheless, a favorable outcome of HTx surgery compared to CABG was observed among high-risk patients.

Mitral valve leaflet blood cyst treated with minimally invasive approach: a case report and review of literature.

INTRODUCTION: Cardiac blood cyst is a very rare benign tumor of the heart in adults. Though it is very common in the first half year of life, it regresses with time and its occurrence is very rare in children older than six months and in adults. Until now less than 100 valvular blood cyst cases have been reported in adults. CASE PRESENTATION: We present a case of a 66-year-old male who presented to us with exertional chest tightness, shortness of breath, and right leg weakness for two weeks. He was diagnosed with a cardiac mass two months ago in another hospital. The physical examination was unremarkable. Abdominal ultrasound showed a cyst in the liver and left kidney. Echocardiography showed a mass-occupying lesion of a cystic nature in the mitral valve with moderate mitral regurgitation. Based on echocardiography findings and computed tomography report, the preliminary diagnosis of mitral valve cystic tumor was made. The patient underwent minimally invasive resection of the cyst. The posterior mitral cusp was repaired and a mitral annuloplasty ring was placed. The postoperative recovery was uneventful. The histopathology report confirmed the diagnosis of a cardiac blood cyst. The patient was followed up for six months without any complications. This case is presented to enrich the medical literature on the cardiac blood cyst. CONCLUSION: Although a cardiac blood cyst is a rare entity in adults, it still should be considered in the differential diagnosis of cardiac tumors. Because the natural history and hemodynamic effects are very diverse, large symptomatic cardiac blood cysts, especially in the left heart should be resected to avoid complications.

Developments and Challenges in Durable Ventricular Assist Device Technology: A Comprehensive Review with a Focus on Advancements in China.

Heart transplantation is currently the most effective treatment for end-stage heart failure; however, the shortage in donor hearts constrains the undertaking of transplantation. Mechanical circulatory support (MCS) technology has made rapid progress in recent years, providing diverse therapeutic options and alleviating the dilemma of donor heart shortage. The ventricular assist device (VAD), as an important category of MCS, demonstrates promising applications in bridging heart transplantation, destination therapy, and bridge-to-decision. VADs can be categorized as durable VADs (dVADs) and temporary VADs (tVADs), according to the duration of assistance. With the technological advancement and clinical application experience accumulated, VADs have been developed in biocompatible, lightweight, bionic, and intelligent ways. In this review, we summarize the development history of VADs, focusing on the mechanism and application status of dVADs in detail, and further discuss the research progress and use of VADs in China.

MFG-E8 facilitates heart repair through M1/M2 polarization after myocardial infarction by inhibiting CaMKII.

BACKGROUND: M1/M2 macrophage polarization affects patient outcomes after myocardial infarction (MI). The relationship between milk fat globule-epidermal growth factor 8 (MFG-E8) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on macrophage polarization after MI is unknown. To investigate the functional role of MFG-E8 in modulating cardiac M1/M2 macrophage polarization after MI, especially its influence on CaMKII signaling. METHODS: Human ventricular tissue and blood were obtained from patients with MI and controls. MFG-E8-KO mice were constructed (C57BL/6). The mice were randomized to WT-sham, sham-MFG-E8-KO, WT-PBS, rmMFG-E8 (WT injected with rmMFG-E8 10 min after MI), and MFG-E8-KO. The mouse macrophage cell line RAW264.7 was obtained. CaMKII, p-CaMKII, Akt, and NF-κB p65 were determined by qRT-PCR, western blot, and immunofluorescence. RESULTS: The MFG-E8 levels were significantly enhanced after MI in the hearts and plasma of patients with MI compared with controls. The MFG-E8 levels were significantly increased in the hearts and plasma of mice after MI. MFG-E8 was derived from cardiac fibroblasts. The administration of rmMFG-E8 improved ventricular remodeling and cardiac function after MI. rmMFG-E8 did not suppress infiltrating monocyte/macrophages into the peri-infarct area. rmMFG-E8 suppressed the polarization of macrophages to the M1 phenotype and promoted the polarization of macrophages to the M2 phenotype. rmMFG-E8 suppressed CaMKII-dependent signaling in macrophages. CONCLUSIONS: MFG-E8 and CaMKII appear to collaboratively regulate myocardial remodeling and M1/M2 macrophage polarization after MI. These observations suggest new roles for MFG-E8 in inhibiting M1 but promoting M2 macrophage polarization.

Early left ventricular systolic function is a more sensitive predictor of adverse events after heart transplant.

BACKGROUND: First-phase ejection fraction (EF1) is a novel measure of early changes in left ventricular systolic function. This study was to investigate the prognostic value of EF1 in heart transplant recipients. METHODS: Heart transplant recipients were prospectively recruited at the Union Hospital, Wuhan, China between January 2015 and December 2019. All patients underwent clinical examination, biochemistry measures [brain natriuretic peptide (BNP) and creatinine] and transthoracic echocardiography. The primary endpoint was a combined event of all-cause mortality and graft rejection. RESULTS: In 277 patients (aged 48.6 ± 12.5 years) followed for a median of 38.7 [26.8-45.0] months, there were 35 (12.6%) patients had adverse events including 20 deaths and 15 rejections. EF1 was negatively associated with BNP (ß = -0.220, p < 0.001) and was significantly lower in patients with events compared to those without. EF1 had the largest area under the curve in ROC analysis compared to other measures. An optimal cut-off value of 25.8% for EF1 had a sensitivity of 96.3% and a specificity of 97.1% for prediction of events. EF1 was the most powerful predictor of events with hazard ratio per 1% change in EF1: 0.628 (95%CI: 0.555-0.710, p < 0.001) after adjustment for left ventricular ejection fraction and global longitudinal strain. CONCLUSIONS: Early left ventricular systolic function as measured by EF1 is a powerful predictor of adverse outcomes after heart transplant. EF1 may be useful in risk stratification and management of heart transplant recipients.

Protein Phosphatase 2A Activation Promotes Heart Transplant Acceptance in Mice.

BACKGROUND: Although heart transplantation is the definitive treatment for heart failure in eligible patients, both acute and chronic transplant rejection frequently occur. Protein phosphatase 2A (PP2A) activity is critical in maintaining tissue and organ homeostasis. In this study, we evaluated the effect of a novel class of small molecule activators of PP2A (SMAPs) on allograft rejection in a mouse heterotopic heart transplantation model. METHODS: Recipient mice were administered with DT-061 (a pharmaceutically optimized SMAP) or vehicle by oral gavage beginning 1 d after transplantation. Histological and immunofluorescence analyses were performed to examine allograft rejection. Regulatory T cells (Treg) from recipient spleens were subjected to flow cytometry and RNA sequencing analysis. Finally, the effect of DT-061 on smooth muscle cells (SMCs) migration and proliferation was assessed. RESULTS: DT-061 treatment prolonged cardiac allograft survival. SMAPs effectively suppressed the inflammatory immune response while increasing Treg population in the allografts, findings corroborated by functional analysis of RNA sequencing data derived from Treg of treated splenic tissues. Importantly, SMAPs extended immunosuppressive agent cytotoxic T lymphocyte-associated antigen-4-Ig-induced cardiac transplantation tolerance and allograft survival. SMAPs also strongly mitigated cardiac allograft vasculopathy as evidenced by a marked reduction of neointimal hyperplasia and SMC proliferation. Finally, our in vitro studies implicate suppression of MEK/ERK pathways as a unifying mechanism for the effect of PP2A modulation in Treg and SMCs. CONCLUSIONS: PP2A activation prevents cardiac rejection and prolongs allograft survival in a murine model. Our findings highlight the potential of PP2A activation in improving alloengraftment in heart transplantation.

Pro-osteogenic role of interleukin-22 in calcific aortic valve disease.

BACKGROUND AND AIMS: Although calcific aortic valve disease (CAVD) is a common valvular disease among elderly populations and its incidence has markedly increased in recent decades, the pathogenesis of CAVD remains unclear. In this study, we explored the potential role of interleukin (IL)-22 and the underlying molecular mechanism in CAVD. METHODS AND RESULTS: Our results showed that IL-22 was upregulated in calcific aortic valves from CAVD patients, and its main sources were CD3+ T cells and CD68+ macrophages. Human aortic valve interstitial cells (VICs) expressed the IL-22-specific receptor IL-22R1, and IL-22R1 expression also was elevated in calcified valves. Treatment of cultured human VICs with recombinant human IL-22 resulted in markedly increased expression of osteogenic proteins Runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), as well as increased matrix calcium deposition. Moreover, siRNA silencing of IL-22R1 blocked the pro-osteogenic effect of IL-22 in VICs. In IL-22-treated VICs, we also observed increased phosphorylation of JAK3 and STAT3 and nuclear translocation of STAT3. Pretreatment with a specific JAK3 inhibitor, WHIP-154, or siRNA knockout of STAT3 effectively mitigated the IL-22-induced osteoblastic trans-differentiation of human VICs. CONCLUSIONS: Together, these data indicate that IL-22 promotes osteogenic differentiation of VICs by activating JAK3/STAT3 signaling. Based on our results demonstrating a pro-osteogenic role of IL-22 in human aortic valves, pharmacological inhibition of IL-22 signaling may represent a potential strategy for alleviating CAVD.

Extracorporeal Left Ventricular Assist Device as a Bridge to Surgery for Ventricular Septal Rupture After Acute Myocardial Infarction.

Ventricular septal rupture (VSR) after acute myocardial infarction (AMI) is a rare but often fatal complication. Surgery is considered the preferred treatment, although the optimal timing is discussed. The immediate preoperative hemodynamic status significantly impacts postoperative outcomes, making mechanical circulatory support (MCS) devices crucial for perioperative hemodynamic stability. We present the case of a 61-year-old woman with no remarkable cardiological history admitted to our hospital with a diagnosis of AMI and VSR. Due to hemodynamic instability and cardiogenic shock, we utilized an intra-aortic balloon pump (IABP) and an extracorporeal left ventricular assist device (extra-VAD) as a bridge to surgery. After 17 days of IABP support, the patient experienced hemodynamic instability, elevated lactate levels, pulmonary edema, and eventually bedside endotracheal infiltration inventor-assisted breathing. Subsequently, the IABP was removed, and the patient underwent 6 days of extra-VAD therapy, resulting in hemodynamic stability, a decline in lactate levels, and a reduction in pulmonary edema on X-ray. Surgical coronary artery bypass grafting and VSR repair were successfully performed without periprocedural complications, and the patient was subsequently discharged. Extra-VAD is useful for serious cardiogenic shock in patients with VSR after AMI and may be considered a reasonable approach as a bridge to surgery.

Short-term study of atrial shunt and improvement of functional mitral regurgitation.

BACKGROUND: This study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions. METHODS: Twenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded. RESULTS: The LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05). CONCLUSION: Following treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients.

Donor/recipient ascending aortic diameter ratio as a novel potential metric for donor selection and improved clinical outcomes in heart transplantation: a propensity score-matched study.

Background: Donor/recipient size matching is paramount in heart transplantation. Body weight, height, body mass index, body surface area, and predicted heart mass (PHM) ratios are generally used in size matching. Precise size matching is important to achieve better clinical outcomes. This study aims to determine the donor/recipient ascending aortic diameter (AAoD) ratio as a metric for donor selection and its effect on postoperative clinical outcomes in heart transplant patients. Methods: We retrospectively reviewed all consecutive patients who underwent heart transplantation from January 2015 to December 2018. A cutoff value of 0.8032 for the donor/recipient AAoD ratio (independent variable for the primary endpoint during unmatched cohort analysis) was determined for predicting in-hospital mortality. The patients were divided into two groups based on the cutoff value. Group A, AAoD < 0.8032 (n = 96), and Group B, AAoD > 0.8032 (n = 265). A propensity score-matched (PSM) study was performed to equalize the two groups comprising 77 patients each in terms of risk. A Cox regression model was developed to identify the independent preoperative variables affecting the primary end-point. The primary endpoint was all-cause in-hospital mortality. Results: A total of 361 patients underwent heart transplantation during the given period. On the multivariate analysis, donor/recipient PHM ratio [HR 16.907, 95% confidence interval (CI) 1.535-186.246, P = 0.021], donor/recipient AAoD ratio < 0.8032 (HR 5.398, 95% CI 1.181-24.681, P = 0.030), and diabetes (HR 3.138, 95% CI 1.017-9.689, P = 0.047) were found to be independent predictors of in-hospital mortality. Group A had higher 3-year mortality than Group B (P = 0.022). The surgery time was longer and postoperative RBC, plasma, and platelets transfusion were higher in Group A (P < 0.05). Although not statistically significant the use of continuous renal replacement therapy (P = 0.054), and extracorporeal membrane oxygenation (P = 0.086), was realatively higher, and ventilation time (P = 0.079) was relatively longer in Group A. Conclusions: The donor/recipient AAoD ratio is a potential metric for patient matching and postoperative outcomes in heart transplantation. A donor/recipient AAoD ratio > 0.8032 could improve post-heart transplantation outcomes and donor heart utilization.