Tissue-level evidence of fibroblast activation protein inhibitor imaging in hypertrophic obstructive cardiomyopathy: a case series.

Background: Myocardial fibrosis is a key pathological factor for the occurrence of ventricular arrhythmias in hypertrophic obstructive cardiomyopathy (HOCM). Case summary: This case series reports on two patients diagnosed with HOCM who underwent 18F-fibroblast activation protein inhibitor (FAPI) positron-emission tomography/computed tomography imaging and Morrow myotomy procedure. The collected myocardial tissue was examined histopathologically. Both patients exhibited intense and heterogeneous 18F-FAPI uptake in the septum, with significant number of activated fibroblasts. Discussion: Enhanced 18F-FAPI uptake was observed before irreversible fibrosis, and the degree of 18F-FAPI uptake was higher in tissue with greater fibrosis. 18F-FAPI imaging may provide a promising tool for guiding surgical strategy in HOCM, and further research is needed to fully explore its potential in clinical practice.

Differential expression profiles and bioinformatics analysis of tRNA-derived small RNAs in epicardial fat of patients with atrial fibrillation.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

The predictive and prognostic value of risk factors in patients receiving hybrid coronary revascularization with postoperative pulmonary complications.

Background: The mortality rate of coronary artery disease ranks first in developed countries, and coronary revascularization therapy is an important cornerstone of its treatment. The postoperative pulmonary complications (PPCs) in patients receiving one-stop hybrid coronary revascularization (HCR) aggravate the dysfunction of multiple organs such as the heart and lungs, therefore increasing mortality. However, the risk factors are still unclear. The objective of this study was to explore the risk factors of PPCs after HCR surgery. Methods: In this study, the perioperative data of 311 patients undergoing HCR surgery were reviewed. All patients were divided into two groups according to whether the PPCs occurred. The baseline information and surgery-related indicators in preoperative laboratory examination, intraoperative fluid management, and anesthesia management were compared between the two groups. Results: Advanced age [odds ratio (OR): 1.065, 95% confidence interval (CI): 1.030-1.101, P<0.001], high body mass index (BMI; OR: 1.113, 95% CI: 1.011-1.225, P=0.02), history of percutaneous coronary intervention (PCI) surgery (OR: 2.831, 95% CI: 1.388-5.775, P=0.004), one-lung volume ventilation (OR: 3.804, 95% CI: 1.923-7.526, P<0.001), inhalation of high concentration oxygen (OR: 3.666, 95% CI: 1.719-7.815, P=0.001), the application of positive end-expiratory pressure (PEEP; OR: 2.567, 95% CI: 1.338-4.926, P=0.005), and long one-lung ventilation time (OR: 1.015, 95% CI: 1.006-1.023, P=0.001) may be risk factors for postoperative PPCs in patients undergoing one-stop coronary revascularization surgery. Using the above seven factors to jointly predict the risk of PPCs in patients undergoing one-stop coronary revascularization surgery, the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) =0.873, 95% CI: 0.835-0.911, sensitivity: 84.81%, and specificity: 75.82%; the predictive model was shown to be effective. Conclusions: Patients undergoing HCR surgery with advanced age, high BMI, a history of PCI surgery, one-lung volume ventilation, inhalation of high concentration oxygen, use of PEEP, and prolonged single lung ventilation are more prone to PPCs.

Alterations in the gut mycobiome with coronary artery disease severity.

BACKGROUND: Coronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. METHODS: In this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FINDINGS: Based on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. INTERPRETATION: In conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FUNDING: This work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202417, Ggyfz202308), the Beijing Natural Science Foundation (No. 7222068); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

Long noncoding RNA and messenger RNA profiling in epicardial adipose tissue of patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) constitutes a significant complication following coronary artery bypass graft surgery (CABG), potentially linked to epicardial adipose tissue (EAT). This investigation seeks to elucidate the association between POAF and EAT at the genetic level. METHODS: EAT and clinical data from patients undergoing CABG were systematically acquired, adhering to established inclusion and exclusion criteria. Patients were categorized into POAF and Non-POAF groups based on the presence or absence of POAF. High-throughput sequencing data of EAT were subjected to differential expression analysis and gene function assessment. A random selection of long noncoding RNAs (lncRNAs) underwent quantitative real-time polymerase chain reaction (qRT-PCR) for validation of the high-throughput sequencing findings. Coexpression analysis was employed to elucidate the interactions between lncRNAs and messenger RNAs (mRNAs). RESULTS: RNA sequencing yielded a total of 69,685 transcripts (37,740 coding and 31,945 noncoding sequences), representing 16,920 genes. Within this dataset, 38 mRNAs and 12 lncRNAs exhibited differential expression between the POAF and Non-POAF groups (P < 0.05, fold change > 1.5). The qRT-PCR results for lncRNAs corroborated the sequencing findings (P < 0.01). Functional enrichment analysis of genes and the coexpression network indicated that these differentially expressed RNAs were primarily implicated in processes such as cell growth, differentiation, signal transduction, as well as influencing tissue fibrosis and ion transmembrane transport. CONCLUSIONS: This study unveils a potential association between myocardial fibrosis and ion channels co-regulated by mRNAs and lncRNAs, closely linked to the emergence of new-onset POAF, after accounting for clinical risk factors. This discovery holds promise for further advances in clinical and fundamental research.

Drug-coated balloons: A better revascularization strategy in patients with multivessel coronary artery disease undergoing one-stop hybrid coronary revascularization surgery.

BACKGROUND: The optimal revascularization strategy for non-left anterior descending coronary artery (LAD) lesions during one-stop hybrid coronary revascularization (HCR) surgery lacks current evidence. AIMS: This study aimed to compare the outcomes of the drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in patients with non-small non-LAD lesions undergoing one-stop HCR. METHODS: A total of 141 consecutive patients with multivessel coronary artery disease (MVCAD) undergoing one-stop HCR between June 1, 2018 and March 1, 2022 were retrospectively included in this study. In-hospital outcomes and mid-term major adverse cardiovascular and cerebrovascular events (MACCE) were observed. Kaplan-Meier curve analysis was used to evaluate the MACCE-free survival rate. The Cox proportional hazard model was used to identify risk factors of mid-term MACCE. RESULTS: Thirty-eight and 103 patients received only DCB or DES therapy, respectively, in this study. There were no significant differences in demographic characteristics and laboratory parameters between the two groups. The in-hospital MACCE rate in the DES group was numerically higher than that in the DCB group (9.7% vs. 5.3%, respectively), but the difference was not statistically significant (P = 0.4). The incidence of MACCE after patients' discharge was significantly higher in the DES group (22% vs. 5.3%, respectively, P = 0.02) during a median follow-up of 20 months. After multivariable Cox proportional hazard analysis, DCB therapy was independently associated with reduced risk of mid-term MACCE (hazard ratio, 0.21; 95% confidence interval, 0.06-0.91; P = 0.04). CONCLUSION: For patients with MVCAD undergoing one-stop HCR, DCB therapy may be the optimal revascularization strategy for non-small non-LAD coronary artery lesions with a significantly lower rate of mid-term MACCE.

Expression profiles and functional analysis of tRNA-derived small RNAs in epicardial adipose tissue of patients with heart failure.

BACKGROUND: Heart failure is considered an epidemic disease in the modern world. Since it presents as a multifactorial, systemic disease, a comprehensive understanding of the underlying mechanism is essential. Epicardial adipose tissue (EAT) is increasingly recognized to be metabolically active and is able to secrete myriad bioactive molecules, including exosomes carrying tRNA-derived small RNAs (tsRNAs). Mounting evidence has suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but no studies have focused on the influence of tsRNA in EAT on cardiac dysfunction. METHODS: To investigate the regulatory mechanism of tsRNAs of EAT associated with HF, we collected EAT from HF (n = 5) patients and controls (n = 5) and used a combination of RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and bioinformatics to screen the expression profiles of tsRNAs in HF. RESULTS: We ultimately identified an expression profile of 343 tsRNAs in EAT. Of those, a total of 24 tsRNAs were significantly differentially expressed between HF and controls: 17 were upregulated and 7 were downregulated (fold change >1.5, p < 0.05). Four tsRNAs (tiRNA-Pro-TGG-001, tRF-Met-CAT-002, tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011) were randomly selected and validated by qRT-PCR. Bioinformatics analyses revealed a dense interaction of target genes between tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011. Based on functional analysis, these two tRFs might play a protective role by regulating sphingolipid and adrenergic signaling pathways by targeting genes mainly contributing to calcium ion transport. CONCLUSIONS: Our study profiled tsRNA expression in EAT with HF and identified a comprehensive dimension of potential target genes and tsRNA-mRNA interactions.

The development of heart failure involves a complex mechanistic network, which until now, has not been clarified.Excess epicardial adipose tissue may promote heart failure via unknown mechanisms.Our current study profiled transfer RNAs expression in epicardial adipose tissue with heart failure and identified a comprehensive dimension of potential target genes and transfer RNAs -mRNA interactions for the pathogenesis of deterioration in cardiac function.

Fibroblast activation protein imaging in atrial fibrillation: a proof-of-concept study.

BACKGROUND: To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity. METHODS: We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted 18F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent 18F-FAPI PET/CT imaging. RESULTS: RA of AF beagles showed increased 18F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial 18F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, 18F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial 18F-FAPI activity (OR = 3.01, P = .046). CONCLUSION: This proof-of-concept study suggests that 18F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.

99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart.

BACKGROUND: This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart. METHODS: In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography. RESULTS: In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities. CONCLUSION: In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.

Comparisons of different new-generation transcatheter aortic valve implantation devices for patients with severe aortic stenosis: a systematic review and network meta-analysis.

BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.

An examination of causal associations and shared risk factors for diabetes and cardiovascular diseases in the East Asian population: A Mendelian randomization study.

Background: One of the major contributors to disability and mortality among diabetics is cardiovascular disease (CVD), with coronary artery disease (CAD) as the most prevalent type. However, previous studies have provided controversial evidence linking diabetes to other types of CVDs, such as atrial fibrillation (AF). In addition, the risk factors that predispose people to the risk of diabetes and its complications differ across ethnicities, but the disease risk profiles in the East Asian population have been less investigated. Methods: The causal association between type 2 diabetes (T2D) and two types of CVDs (i.e., AF and CAD) in the East Asian population was first studied using Mendelian randomization (MR) analyses. Next, we examined the causal effect of 49 traits on T2D and CAD to identify their separate and shared risk factors in East Asians. A causal mediation analysis was performed to examine the role of T2D in mediating the relationship between the identified shared risk factors and CAD. Results: T2D was causally associated with CAD, but not AF, in East Asians. A screening of the risk factors indicated that six and 11 traits were causally associated with T2D and CAD, respectively, with suggestive levels of evidence. Alkaline phosphatase (ALP) was the only trait associated with both T2D and CAD, as revealed by the univariable MR analyses. Moreover, the causal association between ALP and CAD no longer existed after adjusting T2D as a covariable in the causal mediation study. Conclusion: Our study highlights the risk profiles in the East Asian population, which is important in formulating targeted therapies for T2D and CVDs in East Asians.

SGLT2i alleviates epicardial adipose tissue inflammation by modulating ketone body-glyceraldehyde-3-phosphate dehydrogenase malonylation pathway.

AIMS: Inflammation in the epicardial adipose tissue (EAT) is a contributor to atrial fibrillation. Studies have reported that sodium glucose co-transporter 2 inhibitor (SGLT2i) can alleviate EAT inflammation. However, the mechanism remains elusive. This study aims to investigate the molecular mechanism of SGLT2i in reducing EAT inflammation and to explore the effects of SGLT2i on atrial fibrosis in atrial fibrillation. METHODS: Sprague-Dawley rats were injected with angiotensin II to induce atrial fibrillation and randomly assigned to receive SGLT2i ( n  = 6) or vehicle ( n  = 6). Macrophages (RAW264.7) were treated with ketone bodies; ACC1 knockdown/overexpression and malonyl-CoA overexpression were performed in vitro . The levels of inflammatory cytokines, ACC1, and malonyl-CoA were examined by ELISA. GAPDH malonylation was measured by co-immunoprecipitation. RESULTS: In atrial fibrillation rats, SGLT2i increased the ketone body levels and decreased the expression of ACC1 and alleviated EAT inflammation and atrial fibrosis. In RAW264.7 cells, ketone bodies decreased the levels of ACC1, malonyl-CoA, and GAPDH malonylation, accompanied by reduced inflammatory cytokines. ACC1 knockdown decreased the expression of malonyl-CoA and GAPDH malonylation and alleviated lipopolysaccharide (LPS)-induced macrophage inflammation; these effects were inhibited by malonyl-CoA overexpression. Furthermore, the protective effects of ketone bodies on macrophage inflammation were abrogated by ACC1 overexpression. CONCLUSION: SGLT2i alleviates EAT inflammation by reducing GAPDH malonylation via downregulating the expression of ACC1 through increasing ketone bodies, thus attenuating atrial fibrosis.

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction.

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography-tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

Declined plasma microfibrillar-associated protein 4 levels in acute coronary syndrome.

BACKGROUND: Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. METHODS: We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan-Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. RESULTS: Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174-0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = - 0.311 and - 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan-Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009). CONCLUSIONS: MFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted.

A Novel Reperfusion Strategy for Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Prospective Case Series.

BACKGROUND: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it "volume-controlled reperfusion (VCR)". The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. METHODS: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. RESULTS: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. CONCLUSION: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.

Thrombospondin-1 plasma levels associated with in-hospital major adverse cardiovascular events in patients with acute coronary syndrome.

BACKGROUND: Thrombospondin-1, a large matricellular glycoprotein, exerts multifaced biological effects on the cardiovascular system and is correlated with cardiovascular diseases. Its plasma levels and correlation with in-hospital prognosis are yet unclear in the acute coronary syndrome population. The present study aimed to evaluate the correlation between thrombospondin-1 plasma levels and in-hospital adverse events in patients with acute coronary syndrome. METHODS: This is a cross-sectional study. A total of 341 inpatients with acute coronary syndrome were recruited in Beijing Chaoyang Hosipital from May 2021 to November 2021. The thrombospondin-1 plasma levels were measured, and the in-hospital major adverse cardiovascular events, including all-cause death, recurrent ischemia, arrhythmias, and heart failure, were recorded. This correlation was assessed by logistic regression analysis. RESULTS: The thrombospondin-1 plasma levels were higher in patients with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction compared to those in unstable angina (P < 0.001), while the differences between the two different types of myocardial infarction were not statistically different. Thrombospondin-1 plasma levels were correlated with GRACE score, leukocytes, neutrophils, platelets, troponin I, creatine kinase-MB, D-dimer, C-reactive protein, erythrocyte sedimentation rate, and log10 brain natriuretic peptide. Furthermore, thrombospondin-1 plasma levels were associated with the in-hospital major adverse cardiovascular events in patients with acute coronary syndrome (P = 0.001). CONCLUSIONS: Thrombospondin-1 plasma levels were higher in patients with myocardial infarction than those in unstable angina. The high thrombospondin-1 plasma levels were associated with in-hospital major adverse cardiovascular events.

Comparisons of Drug-Eluting Balloon versus Drug-Eluting Stent in the Treatment of Young Patients with Acute Myocardial Infarction.

BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.

99mTc-sestamibi and 18F-fluorodeoxyglucose imaging in patients with cardiogenic shock: A pilot study.

Background: Whether perfusion/metabolism imaging differs between matched ST-segment elevation myocardial infarction (STEMI) patients with and without cardiogenic shock (CS) remains unknown. Methods: Seventeen STEMI patients with CS (13 men, 60 ± 12 years) and 16 matched STEMI patients without CS (15 men, 54 ± 15 years) were prospectively recruited. All patients underwent baseline 99mTc-sestamibi/18F-fluorodeoxyglucose (FDG) imaging and echocardiography 6 ± 2 days post-infarction. Nine patients with CS and seven without CS had repeated imaging 98 ± 7 days post-infarction. The total perfusion deficit (TPD) and total FDG uptake deficit (TFD) were calculated to assess the percentages of impaired perfusion and metabolism over the left ventricle. Patients were followed up for 337 days (213-505 days) and the major adverse cardiac events (MACE) were recorded. Results: TPD was greater in patient with CS and was independently related to the presence of CS (OR: 4.36, p = 0.013). Both acute- and convalescent TFD were inversely related to the improvement ratio of LVEF (r-values: -0.62, -0.73; both p < 0.05). MACE occurred in 16 patients (10 CS and 6 non-CS), and acute TFD was predictive of MACE in those with CS (HR: 2.06, p = 0.038). Conclusion: In this pilot study, we demonstrated that STEMI patients with CS had a significantly increased TPD, which was relevant to the presence of CS. Acute TFD was associated with improvement in LVEF, and was predictive of MACE in patients with CS.

The integrative network of circRNA, miRNA and mRNA of epicardial adipose tissue in patients with atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia that affects approximately 1-2% of the general population. The mechanism of AF pathogenesis remains unclear. Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been shown to be closely related to AF. EAT has a biological impact on neighboring myocardium by producing a myriad of bioactive molecules, including exosomes carrying circular RNAs (circRNAs). As a new category of noncoding RNAs, circRNAs can work as efficient sponges for specific microRNAs and efficiently regulate gene expression. MATERIAL AND METHODS: To investigate the regulatory mechanism of circRNAs of EAT in patients with AF, we collected EAT from AF (n=6) patients and non-AF (n=6) controls and profiled their circRNA expression with the RNA-sequencing method. RESULTS: RNA sequencing detected a total of 2159 circRNAs in EAT, among which 528 were upregulated and 579 were downregulated. The top highly expressed EAT circRNAs corresponded to genes involved in inflammation and cell proliferation, including SUPT5H, CCDC62, DPY19L1P1, RASGRP1, AP3S1, CGNL1, KAT2B, BNIP2, and SACS. The top three circRNAs with higher FCs (fold changes) were hsa_circ_0099634, hsa_circ_0000932 and hsa_circ_0097669 (FC=25.6), while lower FCs were identified in hsa_circ_0135289, hsa_circ_0098155 and hsa_circ_0079672. A network involving these noncoding RNAs and mRNAs was also constructed to predict their potential biological functions in the pathology of AF. CONCLUSIONS: Our study provided novel insight into EAT's roles in AF and proposed interactions, including possible mediators.

The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey.

BACKGROUND: Leukocyte telomere length (LTL) is a robust marker of biological aging, which is associated with obesity. Recently, the visceral adiposity index (VAI) has been proposed as an indicator of adipose distribution and function. OBJECTIVE: To evaluated the association between VAI and LTL in adult Americans. METHODS: There were 3193 participants in U.S. National Health and Nutrition Examination Surveys (1999-2002) included in this analysis. LTL was measured using quantitative PCR (qPCR) and expressed as telomere to single-gene copy ratio (T/S ratio). We performed multiple logistic regression models to explore the association between VAI and LTL by adjusting for potential confounders. RESULTS: Among all participants, VAI was associated with the shorter LTL (ß: - 14.81, 95% CI - 22.28 to - 7.34, p < 0.001). There were significant differences of LTL in VAI tertiles (p < 0.001). Participants in the higher VAI tertile had the shorter LTL (1.26 ≤ VAI < 2.46: ß = - 130.16, 95% CI [ - 183.44, - 76.87]; VAI ≥ 2.46: ß = - 216.12, 95% CI [ - 216.12, - 81.42], p for trend: < 0.001) comparing with the lower VAI tertile. We also found a non-linear relationship between VAI and LTL. VAI was negatively correlated with LTL when VAI was less than 2.84. CONCLUSIONS: The present study demonstrates that VAI is independently associated with telomere length. A higher VAI is associated with shorter LTL. The results suggest that VAI may provide prediction for LTL and account for accelerating the biological aging.