Objective To explore the efficacy and safety of dapagliflozin in patients with paroxysmal atrial fibrillation (PAF) combined with heart failure with preserved ejection fraction (HFpEF). Methods A total of 120 patients with PAF combined with HFpEF treated at Jinshan Hospital of Fudan University from July 2022 to July 2023 were selected and randomly divided into the dapagliflozin group (n＝60, standard treatment combined with dapagliflozin) and the control group (n＝60, standard treatment combined with placebo). After 12 months of follow-up, the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS), PAF duration, recurrence rate and frequency of PAF, left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction, P-wave dispersion, blood pressure, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), and glycated hemoglobin A_1C (HbA_1C) were compared between the two groups. Cardiovascular outcomes and adverse events were observed. Results A total of 10 patients lost to follow-up, and 110 patients were included in the analysis (55 in each group). After 12 months of treatment, the KCCQ-TSS in the dapagliflozin group was significantly higher than that in the control group ([61.68±2.65] points vs [44.98±4.76] points, P＜0.001). The PAF duration in the dapagliflozin group was significantly shorter than that in the control group ([144±18] min vs [270±24] min, P＝0.045). After treatment, frequency of PAF, NT-proBNP levels, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left atrial diameter, P-wave dispersion, and HbA_1C levels showed statistical differences between the two groups (P＜0.05). The heart failure readmission rate and PAF recurrence rate in the dapagliflozin group were significantly lower than those in the control group (P＜0.05). There was no significant difference in the incidence of adverse events between the two groups during treatment. Conclusions Dapagliflozin improves patients’ quality of life, reduces PAF duration and recurrence rate, decreases heart failure readmission rate, lowers NT-proBNP levels, reverses cardiac remodeling, and demonstrates favorable safety in patients with PAF combined with HFpEF.

Objective To explore the protective effect of exercise-induced metabolite-3 (EIM-3) on myocardial ischemia-reperfusion (I/R) injury and explore its underlying molecular mechanisms. Methods The physicochemical properties and half-life of EIM-3 were analyzed using the Human Metabolome Database (HMDB, https://hmdb.ca/). A primary rat cardiomyocyte hypoxia/reoxygenation (H/R) injury model was established. Cell apoptosis and viability were assessed using TUNEL assay and cell counting kit-8, respectively. Lactate dehydrogenase (LDH) levels in the cell culture supernatant were measured. Intracellular reactive oxygen species (ROS) levels were detected. Transcriptomic analysis was performed to identify potential signaling pathways and targets of EIM-3. Results Plasma levels of EIM-3 were elevated post-exercise. EIM-3 was characterized as a phospholipid small-molecule compound with a partition coefficient (logP) of 5.58 and a solubility (logS) of −7.6, indicating favorable lipophilicity and cell membrane permeability. In cardiomyocytes H/R injury modles, EIM-3 significantly inhibited apoptosis, increased cell viability, reduced intracellular ROS levels, and decreased LDH release (P＜0.01). Transcriptomic analysis suggested that EIM-3 exerts its protective function potentially by regulating glucose metabolim. Quantitative real-time polymerase chain reaction results confirmed that EIM-3 significantly upregulated the transcriptional level of pyruvate kinase M2 (PKM2) in a dose-dependent manner (P＜0.001). Conclusions EIM-3 protects cardiomyocytes against I/R injury by modulating glucose metabolim. This study provides foundational insights into the mechanisms underlying exercise-induced cardioprotection.

Objective To establish a stable mouse model of chronic myocardial ischemia in coronary artery disease and preliminarily elucidate the electrophysiological mechanisms of T-wave flattening under ischemic conditions.Methods APOE-/-mice were randomly divided into a model group and a lipid-lowering drug(LLD)group and subjected to a high-fat diet for 3 months.C57BL/6J mice fed a normal diet were used as the control group.Electrocardiograms were used to assess the mice before and after modeling,and cardiac perfusion was evaluated via nuclear PET/CT scans.Hematoxylin-eosin and oil red O staining were employed to assess pathological atherosclerosis(AS)plaque formation.Mouse myocardial cells were isolated,and action potentials were recorded.Results After modeling,mice in the model group exhibited a significant increase in cholesterol(CHO)and low-density lipoprotein C(LDL-C),along with the appearance of lipid plaques in the aorta.Lesions in the LLD group were noticeably reduced,and no plaques formed in the control group.Myocardial nuclear scans revealed impaired blood perfusion in the hearts of the model group mice that was significantly lower than that in the LLD and control groups.The electrocardiograms indicated a significant reduction in T/QRS in both the model and LLD groups,with no significant changes observed in the control group.Myocardial cell action potential recordings revealed an accelerated repolarization rate in the inner-layer myocardial cells under ischemia,and a reduction in the inner-to-outer potential difference was identified as the primary electrophysiological mechanism underlying T-wave flattening.Conclusions APOE-/-mice can be used to establish a model of chronic myocardial ischemia.The increased repolarization rate of inner-layer myocardial cells is likely to be the main cause of T-wave flattening in electrocardiograms under ischemic conditions.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

OBJECTIVE: To evaluate a modified subtraction coronary computed tomography angiography (CCTA) technique with a two-breathhold approach in terms of image quality and stenosis grading of calcified coronary segments and in the detection of significant coronary stenosis in segments with severe calcification. MATERIALS AND METHODS: The institutional board approved this study, and all subjects provided written consent. A total of 128 patients were recruited into this trial, of which 32 underwent subtraction CCTA scans and invasive coronary angiography (ICA). The average Agatston score was 356 ± 145. In severely calcified coronary segments, the presence of significant (> 50%) stenosis was assessed on both conventional CCTA and subtraction CCTA images, and the results were finally compared with ICA findings as the gold standard. RESULTS: For severely calcified segments, the image quality in conventional CCTA significantly improved from 2.51 ± 0.98 to 3.12 ± 0.94 in subtraction CCTA (p < 0.001). In target segments, specificity (70% vs. 87%; p = 0.005) and positive predictive value (61% vs. 79%, p < 0.01) were improved using subtraction CCTA in comparison with conventional CCTA, with no loss in the negative predictive value. The segment-based diagnostic accuracy for detecting significant stenosis was significantly better in subtraction CCTA than in conventional CCTA (area under the receiver operating characteristic curve, 0.94 vs. 0.85; p = 0.03). CONCLUSION: This modified subtraction CCTA method showed lower misregistration and better image quality in patients with limited breathhold capability. In comparison with conventional CCTA, modified subtraction CCTA would allow stenosis regrading and improve the diagnostic accuracy in coronary segments with severe calcification.
Angiography ; Constriction, Pathologic ; Coronary Angiography ; Coronary Stenosis ; Humans ; Methods ; ROC Curve ; Sensitivity and Specificity

Objective Myocardial bridging is a congenital anomaly.However,little data is available for patients with myocardial bridging (MB) associated with acute myocardial infarction (AMI).The goals of this study are to evaluate characteristics of MB in patients with AMI.Methods From March 1999 to February 2006,137 patients with both MB and AMI,were identified by coronary angiography,including 117 men and 20 women with an average age of 60.77±12.01 years (range 30-83 years) were enrolled in the present study.Results There were 119 patients with MB at the middle segment of left anterior descending artery (LAD),15 patients at distal segment of LAD,2 patients at middle segment of left circumflex (LCX),and 1 at the proximal segment of the obtuse marginal branch (OM) of LCX.There are 36 patients with non-ST elevation acute myocardial infarction (NSTEAMI),38 patients with anterior ST elevation AMI (STEAMI),40 patients with inferior STEAMI and 23 patients with inferior-posterior STEAMI.Risk factors such as hypertension,diabetes,hyperlipidemia and smoking were not different among four groups.Patients with anterior AMI included 8 patients who showed no stenosis at the segment of MB.Conclusion Patients with MB and ST elevation AMI were mainly inferior AMI.MB might be one of the causes of AMI.

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

Objective To observe the efficacy of antithrombotic treatment of acute ST-segment elevation myocardial infarction patients with failure primary percutaneous coronary intervention because of high thrombus burden,and its effect on elective percutaneous coronary intervention.Methods Eight acute ST-segment elevation myocardial infarction patients were enrolled,who suffered from failure of primary percutaneous coronary intervention because of high thrombus burden.Summarize the antithrombotic strategies in perioperative and postoperative period,the operative strategies and the follow-up coronary intervention were recorded and reviewed.Results All the patients were male and most of them had acute inferior myocardial infarction with right coronary occluded because of high thrombus burden.Four patients received thrombus aspiration and balloon dilation.One patient received thrombus aspiration and the other three patients did not receive coronary intervention.Tirofiban were given in perioperative period to all the patients.Low molecular weight heparin was given to 6 patients.Dual antiplatelet therapy was given to 6 patients (aspirin 100 mg/day plus clopidogrel 75 mg/day) and 1 patient required up-titration of aspirin to 200 mg/day.Coronary angiography were repeated (29.00 ± 23.25) days later,and the thrombus in the culprit vessels disappeared in two patients,and coronary stent implantation was performed in three patients.Conclusions The routine antithrombotic strategies play limited roles in thrombus clearance in acute ST segment elevation myocardial infarction patients with failure primary percutaneous coronary intervention because of high thrombus burden.The time for the thrombus to be totally organized and the timing of elective percutaneous coronary intervention are still uncertain and need to be further studied.

Objective To investigate the feasibility of subtraction coronary computed tomography angiography (Sub-CCTA) for the diagnosis of coronary heart disease in the segment with severe calcification.Methods A retrospective analysis was performed on 27 patients who underwent clinically indicated digital subtraction angiography (DSA) and CCTA using a 320-detector row CT.Compared with the results of DSA,sensitivity,specificity,positive predictive value,negative predictive value and accuracy of Con-CCTA and Sub-CCTA were calculated.The clinical diagnostic accuracy of the two imaging methods was evaluated using the receiver operating characteristic (ROC) curve.The stenosis of coronary segments was divided into four grades (Ⅰ,Ⅱ,Ⅲ,Ⅳ).Kappa coefficient was used to measure agreement between two imaging methods.Image quality of 4-scale grade scoring method was used and t test was conducted.Results A total of 52 segments with severe calcification were evaluated.The scores of image quality in Con-CCTA and Sub-CCTA were 2.8 ± 0.5 and 3.4 ± 0.7,respectively.There was significant difference between them (t =5.9,P ＜ 0.05).Compared with the result of DSA as the golden standard,the Kappa coefficients were 0.55 and 0.81 respectively in Con-CCTA and Sub-CCTA for the quantitative evaluation of the severe calcified segments.The sensitivity,specificity,positive predictive value and negative predictive value and accuracy of Con-CCTA were 81.0％,63.1％,63.1％,81.1％ and 70.8 ％;and for Sub-CCTA they were 90.5 ％,85.2％,82.1 ％,92.0％ and 87.5 ％ respectively.Compared with Con-CCTA,the area under the ROC curve of Con-CCTA and Sub-CCTA were 0.84 (95％CI:0.70-0.93) and 0.96 (95％ CI:0.86-1.00),respectively,and the difference was statistically significant (P =0.03).Conclusions Sub-CCTA can improve the diagnostic accuracy of coronary artery stenosis in severe calcified segment.Application of subtraction technique in CCTA can reduce or even eliminate the artifacts caused by severe calcified plaque,and has a good clinical application prospect.