Left Ventricle Segmentation in Echocardiography with Transformer.

Left ventricular ejection fraction (LVEF) plays as an essential role in the assessment of cardiac function, providing quantitative data support for the medical diagnosis of heart disease. Robust evaluation of the ejection fraction relies on accurate left ventricular (LV) segmentation of echocardiograms. Because human bias and expensive labor cost exist in manual echocardiographic analysis, computer algorithms of deep-learning have been developed to help human experts in segmentation tasks. Most of the previous work is based on the convolutional neural networks (CNN) structure and has achieved good results. However, the region occupied by the left ventricle is large for echocardiography. Therefore, the limited receptive field of CNN leaves much room for improvement in the effectiveness of LV segmentation. In recent years, Vision Transformer models have demonstrated their effectiveness and universality in traditional semantic segmentation tasks. Inspired by this, we propose two models that use two different pure Transformers as the basic framework for LV segmentation in echocardiography: one combines Swin Transformer and K-Net, and the other uses Segformer. We evaluate these two models on the EchoNet-Dynamic dataset of LV segmentation and compare the quantitative metrics with other models for LV segmentation. The experimental results show that the mean Dice similarity of the two models scores are 92.92% and 92.79%, respectively, which outperform most of the previous mainstream CNN models. In addition, we found that for some samples that were not easily segmented, whereas both our models successfully recognized the valve region and separated left ventricle and left atrium, the CNN model segmented them together as a single part. Therefore, it becomes possible for us to obtain accurate segmentation results through simple post-processing, by filtering out the parts with the largest circumference or pixel square. These promising results prove the effectiveness of the two models and reveal the potential of Transformer structure in echocardiographic segmentation.

Connexin 37 Regulates the Kv1.3 Pathway and Promotes the Development of Atherosclerosis.

Objective: To investigate the mechanism of Connexin 37 (Cx37) and Kv1.3 pathways in atherosclerosis (AS). Methods: ApoE-/- mice were given a high-fat diet to establish atherosclerosis (AS) model, and macrophages in mice were isolated and extracted to transfect Cx37 vectors with silencing or overexpressing, and Kv1.3 pathway blockers were used to inhibit the pathway activity. The indexes of body weight, blood glucose, and blood lipid of mice were collected. The protein and mRNA expression levels of Cx37 and Kv1.3 were detected by reverse transcription-PCR (RT-PCR), Western blot, and immunofluorescence technique. Oil red O staining was used to observe plaque area. Masson staining was used to detect collagen content. The concentrations of chemokine CCL7 were quantified using the ELISA kits. CCK8 was used to detect cell proliferation. Results: Cx37 and Kv1.3 were highly expressed in macrophages of AS mice, and the expression of Kv1.3 and CCL7 decreased after Cx37 was silenced, and the proliferation of macrophages was also decreased. Wild-type mice and AS model mice were treated with Cx37 overexpression vectors and Kv1.3 pathway blocking, and it was found that Cx37 overexpression could improve the blood lipid and blood glucose levels and increase the area of AS in AS mice. However, blocking the activity of Kv1.3 pathway can reduce the levels of blood lipid and blood glucose, increase the body weight of mice, and reduce the area of AS mice. Blocking the activity of Kv1.3 pathway can slow down the plaque development of AS mice and make its indexes close to wild-type mice. And the use of Kv1.3 pathway blockers on the basis of overexpression of Cx37 indicated that inhibition of Kv1.3 pathway activity did not affect the expression of Cx37, but could inhibit the collagen content in the plaque area of AS mice, inhibit the expression of chemokine CCL7, and reverse the effect of Cx37 overexpression. Conclusion: Cx37 can improve the activity of macrophages by regulating the expression of chemokines and the activity of Kv1.3 pathway in AS mice, and enrich macrophages in inflammatory tissues and expand the area of plaque formation.

MicroRNA-384-5p protects against cardiac hypertrophy via the ALPK3 signaling pathway.

Heart failure is a condition caused by a variety of pathophysiological factors. One important pathological change of chronic heart failure is myocardial hypertrophy. In recent years, several studies have found that dysregulated microRNAs are involved in regulating the pathological process of heart failure. In this study, cardiac hypertrophy models were constructed using isoproterenol (ISO)-/angiotensin-II (Ang-II) to explore the role of miR-384-5p in cardiac hypertrophy and its molecular mechanism in vivo and in vitro. Echocardiography, invasive pressure-volume analysis and hematoxylin-eosin staining were used to explore cardiac structure and function. ALPK3 mRNA and protein expression were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis and miR-384-5p expression were assessed via RT-qPCR. Our findings determined that miR-384-5p was notably decreased in cardiac hypertrophic tissues and cells, and overexpression of miR-384-5p could ameliorate pressure overload. Furthermore, ALPK3 was determined to downregulate the ALPK3 expression to aggravate cardiomyocyte hypertrophy. Our findings provided a potential therapeutic target for the treatment of cardiac hypertrophy.

Decreased Mortality with Beta-Blocker Therapy in HFpEF Patients Associated with Atrial Fibrillation.

BACKGROUND: There are no proven effective treatments that can reduce the mortality in heart failure with preserved ejection fraction (HFpEF), probably due to its heterogeneous nature which will weaken the effect of therapy in clinical studies. We evaluated the effect of beta-blocker treatment in HFpEF patients associated with atrial fibrillation (AF), which is a homogeneous syndrome and has seldom been discussed. METHODS: This retrospective cohort study screened 955 patients diagnosed with AF and HFpEF. Patients with a range of underlying heart diseases or severe comorbidities were excluded; 191 patients were included and classified as with or without beta-blocker treatment at baseline. The primary outcome was all-cause mortality and rehospitalization due to heart failure. Kaplan-Meier curves and multivariable Cox proportional-hazards models were used to evaluate the differences in outcomes. RESULTS: The mean follow-up was 49 months. After adjustment for multiple clinical risk factors and biomarkers for prognosis in heart failure, patients with beta-blocker treatment were associated with significantly lower all-cause mortality (hazard ratio (HR) = 0.405, 95% confidence interval (CI) = 0.233-0.701, p=0.001) compared with those without beta-blocker treatment. However, the risk of rehospitalization due to heart failure was increased in the beta-blocker treatment group (HR = 1.740, 95% CI = 1.085-2.789, p=0.022). There was no significant difference in all-cause rehospitalization between the two groups (HR = 1.137, 95% CI = 0.803-1.610, p=0.470). CONCLUSIONS: In HFpEF patients associated with AF, beta-blocker treatment is associated with significantly lower all-cause mortality, but it increased the risk of rehospitalization due to heart failure.

Therapeutic delivery of cyclin-A2 via recombinant adeno-associated virus serotype 9 restarts the myocardial cell cycle: an in vitro study.

Cyclin­A2, which is downregulated following birth, has previously been established as a key regulator of the cell cycle. The present study aimed to detect the effects of cyclin­A2 on myocardial cells by using recombinant adeno­associated virus 9 (rAAV9). Sixty mice were selected and randomly divided into two groups (n=30). The control group were injected with saline and the experimental group were transfected with the rAAV9­cyclinA2­CMV vector by intravenous injection into the tail vein. Tissues were harvested at two and four weeks following injection. Cyclin­A2 expression levels and localization were evaluated using western blot and immunohistochemical analyses. DNA synthesis and mitosis in the myocardium were confirmed by analyzing proliferating cell nuclear antigen (PCNA) and phospho­histone H3 (H3P) expression levels. Expression of Cyclin­A2 in the myocardium commenced two weeks following tail vein injection in the cyclin­A2­treated group, while no expression was observed in the control group. Four weeks following injection, expression levels of cyclin­A2 were higher than those observed at two weeks following injection into the myocardium (two weeks: 0.146±0.013 vs. 27.1±3.33%, P<0.001; four weeks: 0.142±0.107 vs. 74.4±3.36%, P<0.001). PCNA displayed increased expression levels in the cyclin­A2­treated group (two weeks: 13.1±0.54 vs. 65.8±3.44%, P<0.001; four weeks: 13.2±0.55 vs. 71.2±1.58%, P<0.001); however, no change was observed in those of the control group. By contrast, no significant difference was observed in mitosis marker H3P expression levels between the two groups. Immunohistochemical analysis of cyclin­A2 indicated cytoplasmic, but not nuclear, localization. cyclin­A2 and PCNA expression levels in the liver, lung and kidney showed no significant difference between the two groups (P>0.05). It was therefore concluded that the delivery of cyclin­A2 via rAAV9 to the mouse myocardium restarted the myocardial cell cycle, thereby establishing steady and specific expression in the myocardium. Furthermore, the effect of Cyclin­A2 on the myocardium may provide a novel method for achieving cardiac regeneration following cardiac injury.