Prediction model based on machine learning for short- and long-term adverse events in left atrial appendage closure.

Background: At present, the prediction of adverse events (AE) had practical significance in clinic and the accuracy of AE prediction model after left atrial appendage closure (LAAC) needed to be improved. To identify a good prediction model based on machine learning for short- and long-term AE after LAAC. Methods: In this study, 869 patients were included from the Department of Cardiovascular Medicine of Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital during 2017 and 2021. Univariate and multivariate analyses were conducted for short-term AE after LAAC to determine possible risk factors related with AE. We compared 8 machine learning algorithms for prediction short-term AE, and XGBoost was found to have the best performance. In addition, Cox-regression was used for long-term AE to find out the risk factors and establish a prediction model. Results: In univariate and multivariate analysis, body mass index (BMI) [odds ratio (OR) =0.91], congestive heart failure, hypertension, age ≥75 years, diabetes, stroke2 attack (CHADS2) score (OR =0.49) and bleeding history or predisposition, labile international normalized ratio (INR), elderly, drug/alcohol usage (BLED) score (OR =1.71) were shown to be significant risk factors for short-term AE. The XGbosst algorithm was used to predict short-term AE based on 15 possible risk factors. For long-term AE, Cox regression was used for the prediction. The CHADS2 score [hazard ratio (HR) =1.43], hypertension (HR =2.18), age more than 75 (HR =0.49), diabetes (HR =0.57), BLED score (HR=0.28), stroke (HR =19.8), hepatopathy (HR =3.97), nephropathy (HR =2.93), INR instability (HR =4.18), drinking (HR =2.67), and drugs (HR =2.36) were significant risk factors for long-term AE. The XGBoost had a good receiver operating characteristic (ROC) curve and area under the curve (AUC) was 0.85. The accuracy of the XGBoost model stayed at nearly 0.95. Conclusions: In short- and long-term AE, CHADS2 score and BLED score were the most obvious risk factors. Several other risk factors also played roles in AE of LAAC. The incidence of long-term AE is under 15% and LAAC is effective and safe. The XGBoost model had good prediction accuracy and ROC curve.

Left atrial appendage occlusion in a mirror-image dextrocardia: A case report and review of literature.

BACKGROUND: In mirror-image dextrocardia, the anterior-posterior position of the cardiac chambers and great vessels is maintained, but the left-right orientation of the abdominal organs is reversed. The abnormal anatomy of the heart poses surgical challenges and problems in dealing with surgical risk and monitoring complications. There are few reports on closure of the left atrial appendage (LAA) in dextrocardia and no reports on the application of enhanced recovery after surgery (ERAS) following LAA occlusion (LAAO) procedures. CASE SUMMARY: The objective for this case was to ensure perioperative safety and accelerate postoperative recovery from LAAO in a patient with mirror-image dextrocardia. ERAS was guided by the theory and practice of nursing care. Atrial fibrillation was diagnosed in a 77-year-old male patient, in whom LAAO was performed. The 2019 guidelines for perioperative care after cardiac surgery recommend that the clinical nursing procedures for patients with LAAO should be optimized to reduce the incidence of perioperative complications and ensure patient safety. Music therapy can be used throughout perioperative treatment and nursing to improve the anxiety symptoms of patients. CONCLUSION: The procedure was uneventful and proceeded without complications. Anxiety symptoms were improved.

Single-cell RNA sequencing of mouse left ventricle reveals cellular diversity and intercommunication.

Previous studies have revealed the diversity of the whole cardiac cellulome but not refined the left ventricle, which was essential for finding therapeutic targets. Here, we characterized single-cell transcriptional profiles of the mouse left ventricular cellular landscape using single-cell RNA sequencing (10× Genomics). Detailed t-distributed stochastic neighbor embedding (tSNE) analysis revealed the cell types of left ventricle with gene markers. Left ventricular cellulome contained cardiomyocytes highly expressed Trdn, endothelial cells highly expressed Pcdh17, fibroblast highly expressed Lama2, and macrophages highly expressed Hpgds, also proved by in situ hybridization. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis (ListHits > 2, P < 0.05) were employed with the DAVID database to investigate subtypes of each cell type with the underlying functions of differentially expressed genes (DEGs). Endothelial cells included 5 subtypes, fibroblasts comprising 7 subtypes, and macrophages contained 11 subtypes. The key representative DEGs (P < 0.001) were Gja4 and Gja5 in cluster 3 of endothelial cells, Aqp2 and Thbs4 in cluster 2 of fibroblasts, and Clec4e and Trem-1 in cluster 3 of macrophages perhaps involved in the occurrence of atherosclerosis, heart failure, and acute myocardial infarction proved by literature review. We also revealed extensive networks of intercellular communication in left ventricle. We suggested possible therapeutic targets for cardiovascular disease and autocrine and paracrine signaling underpins left ventricular homeostasis. This study provided new insights into the structure and function of the mammalian left ventricular cellulome and offers an important resource that will stimulate studies in cardiovascular research.

Inhibition of Notch1-mediated inflammation by intermedin protects against abdominal aortic aneurysm via PI3K/Akt signaling pathway.

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. In this study, we found Notch intracellular domain (NICD) and hes1 expression were higher in AAA patients' aortas than in healthy controls. In angiotensin II (AngII)-induced AAA mouse model, IMD treatment significantly reduced AAA incidence and maximal aortic diameter. IMD inhibited AngII-enlarged aortas and -degraded elastic lamina, reduced NICD, hes1 and inflammatory factors expression, decreased infiltration of CD68 positive macrophages and the NOD-like receptor family pyrin domain containing 3 protein level. IMD inhibited lipopolysaccharide-induced macrophage migration in vitro and regulated macrophage polarization. Moreover, IMD overexpression significantly reduced CaCl2-induced AAA incidence and down-regulated NICD and hes1 expression. However, IMD deficiency showed opposite results. Mechanically, IMD treatment significantly decreased cleavage enzyme-a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) level. Pre-incubation with IMD17-47 (IMD receptors blocking peptide) and the phosphatidylinositol 3-kinase/protein kinase b (PI3K/Akt) inhibitor LY294002 reversed ADAM10 level. In conclusion, exogenous and endogenous IMD could inhibit the development of AAA by inhibiting Notch1 signaling-mediated inflammation via reducing ADAM10 through IMD receptor and PI3K/Akt pathway.

Intermedin alleviates pathological cardiac remodeling by upregulating klotho.

Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, dysfunction, and eventually leading to heart failure. Intermedin (IMD), as a paracrine/autocrine peptide, has a protective effect in cardiovascular diseases. In this study, we elucidated the role and the underlying mechanism of IMD in pathological remodeling. Pathological remodeling mouse models were induced by abdominal aorta constriction for 4 weeks or angiotensin II (Ang II) infusion for 2 weeks in wildtype, IMD-overexpression, IMD-knockout and klotho-knockdown mice. Western blot, real-time PCR, histological staining, echocardiography and hemodynamics were used to detect the role of IMD in cardiac remodeling. Cardiac hypertrophy, fibrosis and dysfunction were significantly aggravated in IMD-knockout mice versus wildtype mice, and the expression of klotho was downregulated. Conversely, cardiac remodeling was alleviated in IMD-overexpression mice, and the expression of klotho was upregulated. Hypertension induced by Ang II infusion rather than abdominal aorta constriction was mitigated by IMD. However, the cardioprotective effect of IMD was blocked in klotho-knockdown mice. Similar results were found in cultured neonatal rat cardiomyocytes, which was pretreated with IMD before Ang II stimulation. Mechanistically, IMD inhibited the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the activity of calcineurin to protect against cardiac hypertrophy through upregulating klotho in vivo and in vitro. Furthermore, peroxisome proliferator-activated receptor γ (PPARγ) might mediate IMD upregulating klotho. In conclusion, pathological remodeling may be alleviated by endogenous IMD, which inhibits the expression of calcineurin and p-CaMKII by upregulating klotho via the PPARγ pathway. It suggested that IMD might be a therapeutic target for heart disease.

Intermedin1-53 attenuates aging-associated vascular calcification in rats by upregulating sirtuin 1.

Vascular calcification is a common phenomenon in older adults. Intermedin (IMD) is a cardiovascular bioactive peptide inhibiting vascular calcification. In this study, we aimed to investigate whether IMD1-53 attenuates aging-associated vascular calcification. Vascular calcification was induced by vitamin D3 plus nicotine (VDN) in young and old rats. The calcification in aortas was more severe in old rats treated with VDN than young control rats, and IMD expression was lower. Exogenous administration of IMD1-53 significantly inhibited the calcium deposition in aortas and the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) in VDN-treated old rats. Moreover, levels of aging-related p16, p21 and ß-galactosidase were all greatly decreased by IMD1-53. These results were further confirmed in rat and human VSMCs in vitro. In addition, IMD-deficient mouse VSMCs showed senescence features coinciding with osteogenic transition as compared with wild-type mouse VSMCs. Mechanistically, IMD1-53 significantly increased the expression of the anti-aging factor sirtuin 1 (sirt1); the inhibitory effects of IMD1-53 on calcification and senescence were blocked by sirt1 knockdown. Furthermore, preincubation with inhibitors of PI3K, AMPK or PKA efficiently blunted the upregulatory effect of IMD1-53 on sirt1. Consequently, IMD1-53 could attenuate aging-associated vascular calcification by upregulating sirt1 via activating PI3K/Akt, AMPK and cAMP/PKA signaling.

Intermedin1-53 Ameliorates Homocysteine-Promoted Atherosclerotic Calcification by Inhibiting Endoplasmic Reticulum Stress.

AIM: Vascular calcification (VC) is thought to be an independent predictor of cardiovascular morbidity and mortality. Intermedin1-53 (IMD) is a cardiovascular protective peptide and can inhibit vascular medial calcification in rats. In this study, we investigated the effect of IMD on atherosclerotic calcification induced by a high-fat diet plus homocysteine (Hcy) and the potential mechanisms. METHODS: ApoE-/- mice were fed a high-fat diet with Hcy in drinking water to induce atherosclerotic calcification. RESULTS: As compared to the high-fat diet alone, Hcy treatment significantly increased atherosclerotic lesion areas and the number of calcified nodules in aortic roots and was reduced by IMD infusion or 4-phenylbutyric acid (PBA) treatment. In vitro, as compared to calcifying medium alone, Hcy treatment further increased alkaline phosphatase activity, calcium content, and calcium nodule number in human aorta vascular smooth muscle cells (HA-VSMCs), all blocked by IMD or PBA pretreatment. Mechanistically, IMD or PBA significantly alleviated endoplasmic reticulum stress (ERS) activation compared with Hcy treatment. In parallel, IMD or PBA attenuated the messenger RNA levels of osteogenic markers and inflammatory cytokines in aortas and their protein levels in lesions of aortic roots. In vitro, Hcy treatment significantly increased the protein levels of osteoblast-like cell markers in primary rat VSMCs and inflammation markers in mouse peritoneal macrophages, all decreased with IMD or PBA pretreatment. Intermedin1-53 pretreatment also markedly reduced the protein levels of ERS markers in rat VSMCs and mouse peritoneal macrophages. CONCLUSIONS: Intermedin1-53 protects against Hcy-promoted atherosclerotic calcification in ApoE-/- mice by inhibiting ERS.