Systematic analysis of myocardial immune progression in septic cardiomyopathy: Immune-related mechanisms in septic cardiomyopathy.

Background: The immune infiltration and molecular mechanisms underlying septic cardiomyopathy (SC) have not been completely elucidated. This study aimed to identify key genes related to SC and elucidate the potential molecular mechanisms. Methods: The weighted correlation network analysis (WGCNA), linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, CIBERSORT, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and gene set enrichment analysis (GSEA) were applied to assess the key pathway and hub genes involved in SC. Results: We identified 10 hub genes, namely, LRG1, LCN2, PTX3, E LANE, TCN1, CLEC4D, FPR2, MCEMP1, CEACAM8, and CD177. Furthermore, we used GSEA for all genes and online tools to explore the function of the hub genes. Finally, we took the intersection between differential expression genes (DEGs) and hub genes to identify LCN2 and PTX3 as key genes. We found that immune-related pathways played vital roles in SC. LCN2 and PTX3 were key genes in SC progression, which mainly showed an anti-inflammatory effect. The significant immune cells in cardiomyocytes of SC were neutrophils and M2 macrophages. Conclusion: These cells may have the potential to be prognostic and therapeutic targets in the clinical management of SC. Excessive anti-inflammatory function and neutrophil infiltration are probably the primary causes of SC.

Successful treatment of complex coronary chronic total occlusions improves midterm outcomes.

BACKGROUND: Data regarding outcomes of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) is still limited. Our aim was to evaluate clinical outcomes in patients after successful CTO PCI when compared to patients with failed PCI. METHODS: The cohort study enrolled 145 eligible patients with attempted PCI of CTO. Detailed baseline clinical and procedural data, and in-hospital complications were analyzed. The primary end point was occurrence of major adverse cardiac events (MACE). RESULTS: Median follow-up was 11.49±2.01 months. Successful revascularization was associated with a significantly lower 1-year MACE compared to failed revascularization [hazard ratio (HR): 0.026; 95% confidence interval (CI): 0.004-0.176; P=0.0002]. A J-CTO score of ≥3 was associated with a significantly higher 1-year MACE compared with a J-CTO score of <3 in patients undergoing PCI (HR: 4.819; 95% CI: 1.463-15.870; P=0.0097). Moreover, in patients with a J-CTO score ≥3, success of CTO PCI was associated with significantly lower risk of 1-year MACE than failure of CTO revascularization (HR: 0.114; 95% CI: 0.023-0.569; P=0.0081). Multivariate analysis identified the J-CTO score (HR: 2.10; 95% CI: 1.09-4.04; P=0.026) as a positive predictor, and the success of CTO PCI (HR: 0.17; 95% CI: 0.05-0.59; P=0.005) as a negative significant independent predictor of MACEs. CONCLUSIONS: Among patients with CTOs, high J-CTO score was independently associated with worse clinical outcomes. Furthermore, successful PCI was associated with a lower risk of midterm MACE compared with failed revascularization of CTOs.

Whole Genome Sequence Identified a Rare Homozygous Pathogenic Mutation of the DSG2 Gene in a Familial Arrhythmogenic Cardiomyopathy Involving Both Ventricles.

BACKGROUND: This study was designed to identify the pathogenic mutation in a Chinese family with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) using whole genome sequencing (WGS). METHODS AND RESULTS: Probands II:1 and II:2 underwent routine examinations for diagnosis. Genomic DNA was extracted from the peripheral blood of family members and analyzed using WGS. A total of 60,285 single-nucleotide polymorphisms (SNP) and 13,918 insertions/deletions (InDel) occurring in the exonic regions of genes and predisposing to cardiomyopathies and arrhythmias were identified. When filtered using the 1000 Genomes Project (2014 version), NHLBI ESP6500, and ExAC databases, 12 missense SNP and 2 InDel in exonic regions remained, the allele frequencies of which were <0.01 or unknown. The potentially pathogenic mutations that occurred in the genes DSG2, PKP4, PRKAG2, FOXD4, CTTN, and DMD, which were identified by SIFT or PolyPhen-2 software as "damaging," were validated using Sanger sequencing. Probands II:1 and II:2 shared an extremely rare homozygous mutation in the DSG2 (p.F531C) gene, which was also demonstrated using intersection analysis of WGS data from probands II:1 and II:2. Electron microscopy and histological staining of myocardial biopsies showed widened and destroyed intercalated discs, and interrupted, atrophic, and disarranged myocardial fibers, and hyperplastic interstitial fibers, collagen fibers, and adipocytes were infiltrated and invaded. CONCLUSIONS: A homozygous mutation of DSG2 p.F531C was identified as the pathogenic mutation in patients with ARVC/D involving both ventricles, as a result of widened and impaired intercalated discs, interrupted myocardial fibers, and abnormally hyperplastic interstitial fibers, collagen fibers, and adipocytes.

Clinical Prediction Score for Successful Retrograde Procedure in Chronic Total Occlusion Percutaneous Coronary Intervention.

OBJECTIVE: To develop and validate a prediction score for a successful retrograde procedure in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: A total of 228 CTO lesions in 223 patients who underwent PCI by retrograde approach were analyzed. All subjects were randomly grouped to a derivation set and a validation set at a ratio of 2:1. A successful retrograde procedure was set as the end point. Each of the identified predictors for the end point by logistic regression was assigned 1 point and summed. RESULTS: Independent predictors of a successful retrograde procedure were Werner's score [odds ratio (OR) 4.841, 95% confidence interval (CI) 1.952-12.005, p = 0.001], diameter of distal CTO segment (OR 5.263, 95% CI 2.067-13.398, p < 0.001) and tortuous collateral (type b; OR 0.119, 95% CI 0.032-0.444, p = 0.002). The predictive model developed in the derivation set stratified the difficulty of achieving a successful retrograde procedure into 4 grades - very difficult (10.5%), difficult (23.7%), intermediate (50.7%) and easy (15.1%) - and was demonstrated significantly in the validation set: very difficult (15.8%), difficult (18.4%), intermediate (47.4%) and easy (18.4%). The area under the receiver-operating characteristic curve was 0.832 ± 0.042 for the derivation set and 0.912 ± 0.041 for the validation set with an almost equal performance. CONCLUSIONS: According to the experience of our center, this model performed excellently in predicting the difficulty in achieving a successful retrograde procedure.

[Clinical analysis of coronary artery disease in elderly patients with sleep disordered breathing].

OBJECTIVE: To understand the prevalence of sleep disordered breathing (SDB) in elderly patients with coronary artery disease (CAD) and explore the relations between SDB and CAD. METHODS: Sixty-two elderly patients with and 18 without CAD identified by coronary angiography underwent examinations by polysomnography (PSG). Left ventricular ejection fraction (LVEF) was measured by 99Tc equilibrium radionuclide angiography. RESULTS: In the 62 elderly patients with CAD, 53.2% had SDB, a rate significantly higher that (22.2%) in the 18 non-CAD patients. The CAD patients with SDB had higher respiratory disturbance index (RDI) and body mass index (BMI) and lower arterial saturation of oxygen (SaO2) during sleep, with longer duration of low SPO2 (less that 90%). The incidence of hypertension was higher in CAD patients with SDB than in those without SDB. No significant correlation was found between the severity of coronary artery disease and RDI (r=-0.16, P>0.05). CONCLUSION: The elderly patients with CAD have higher incidence of SDB, and appropriate interventions should be administered in those with severe SDB.

[Relationship between chronic congestive heart failure and sleep-disordered breathing in elderly patients].

OBJECTIVE: To determine the prevalence of sleep disordered breathing (SDB) in elderly patients with chronic congestive heart failure (CHF) and explore the relations between SDB and left ventricular function. METHODS: By means of polysomnography, 56 elderly patients with CHF were divided into non-SDB, mild SDB, moderate SDB, and severe SDB groups, and the left ventricular ejection fraction (LVEF) was measure by (99)Tc equilibrium radionuclide angiography. RESULTS: In the 56 elderly patients with CHF, 38 (67.9%) had SDB, including 12 (21.4%) mild SDB, 14 (25.0%) moderate SDB, and 12 (21.4%) severe SDB patients. Thirty (53.6%) of the 56 patients with CHF had obstructive sleep apnea (OSA), 4 (7.1%) had central sleep apnea and 22 (39.2%) had mixed sleep apnea. The moderate and severe SDB groups had lower minimum arterial oxyhemoglobin saturation during sleep than the non-SDB groups, and the apnea-hyponea index was closely related to LVEF (r=-0.74, P<0.01). CONCLUSION: The prevalence of SDB, predominantly OSA, is high in elderly patients with CHF. Moderate and severe SDB might affect the left ventricular function in these patients, who require polysomnography monitoring.