陈旧性前壁心肌梗死患者自体骨髓单个核细胞移植后左室心肌灌注及收缩功能的变化

目的　评价经冠状动脉内自体骨髓单个核细胞移植对陈旧性心肌梗死患者心功能和心肌灌注的影响及其安全性。方法与结果　入选 10例陈旧性前壁心肌梗死患者 ,在冠状动脉造影和介入治疗后 ,经冠状动脉内灌注导管将自体骨髓单个核细胞缓慢注入前降支。随访 3个月后 ,左室射血分数由术前 4 5 3%± 9 8%升高至 5 4 5 %± 6 5 % (P =0 0 0 3) ;2 0 1 Tl心肌灌注显像 (SPECT)显示左心室心肌灌注明显改善 ,即刻和延迟心肌灌注评分分别由术前的 2 9 5± 5 8和 2 8 6± 6 3降低至 2 3 9±5 7和 2 3 0± 6 1(P均 <0 0 1) ,没有手术有关的并发症和恶性心律失常发生。结论　陈旧性前壁心肌梗死患者经冠状动脉内自体骨髓单个核细胞移植 ,可显著改善左室收缩功能和心肌灌注 ,并且具有良好的临床操作安全性。     

在体骨髓原位造血细胞间纳米通道的扫描电子显微镜(SEM)证据

 目的  探讨在体骨髓细胞之间是否存在细胞间纳米通道(intercellular nanotubes)。方法  利用扫描电子显微镜(scanning electron microscope,SEM)在体原位观察C57BL/6小鼠骨髓中细胞间纳米通道的分布、形态以及可能的形成机制。结果  骨髓造血细胞之间存在纳米通道结构。SEM显示该结构在骨髓组织中散在分布,位于骨髓内血窦内、外侧。骨髓造血细胞间纳米通道的管径粗细不均,平均长度为5.85 μm (1.58~18.54 μm),平均直径为364 nm (202~541 nm),还可见一些小颗粒状物质黏附在纳米通道表面。此外,小鼠骨髓造血细胞可能通过伸出突起的形式形成细胞间纳米通道。结论  本研究首次为小鼠骨髓造血细胞之间存在细胞间纳米通道提供了形态学证据。     

In-stent fractional flow reserve variations and related optical coherence tomography findings: the FFR–OCT co-registration study

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR?<?0.94 was defined as suboptimal. At a median of 63 days after PCI (interquartile range: 59–64 days), 18 out of 26 patients (72%) had suboptimal FFR. The in-stent drop in FFR was significantly higher in patients with suboptimal FFR vs. patients with optimal FFR (0.08?±?0.07 vs. 0.01?±?0.02, p?<?0.001). Receiver operating characteristic curve analysis showed that an in-stent FFR variation of >?0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06?±?0.80 vs. 0.51?±?0.23 mm²; p?=?0.018) and higher neointimal thickness of covered struts (respectively 0.11?±?0.07 vs. 0.06?±?0.01 mm; p?=?0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.     

Impact of Omega-3 supplementation on homocysteine levels in humans: A systematic review and meta-regression analysis of randomized controlled trials

AimsAlthough some evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) supplementation influences enzymes involved in forming homocysteine (Hcy) and improving hyperhomocysteinemia, these findings are still contradictory in humans. The aim of this systematic and meta-analysis study was to investigate the effects of omega-3 supplementation on Hcy using existing randomized controlled trials (RCTs).Data synthesisAvailable databases, including PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, and Embase, were searched to find relevant RCTs up to June 2021. The effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI).ConclusionA total of 20 RCT studies with 2676 participants were included in this article. Our analyses have shown that omega-3 supplementation significantly reduced plasma Hcy levels (WMD: 1.34 μmol/L; 95% CI: 1.97 to ?0.72; P < 0.001) compared to the control group. The results of subgroup analysis showed that omega-3 supplementation during the intervention <12 weeks and with a dose ≥3 gr per day causes a more significant decrease in Hcy levels than the intervention ≥12 weeks and at a dose <3 gr. In addition, omega-3 supplements appear to have more beneficial effects in individuals with high levels of normal Hcy. This meta-analysis showed that omega-3 supplementation significantly improved Hcy. However, further studies are needed to confirm the findings.     

Metabolic syndrome screening in adolescents: New scores AI_METS based on artificial intelligence techniques

Background and aimsMetabolic syndrome (MetS) definitions in adolescents based on the percentiles of its components are rather complicated to use in clinical practice. The aim of this study was to test the validity of artificial intelligence (AI)-based scores (AI_METS) that do not use these percentiles for MetS screening for adolescents.Methods and resultsThis study included 1086 adolescents aged 12 to 18. The cohort underwent anthropometric measurements and blood tests. Mean blood pressure (MBP), and triglyceride glucose index (TyG) were calculated. Explainable AI methods are used to extract the learned function. Gini importance techniques were tested and used to build new scores for the screening of MetS. IDF, Cook, De Ferranti, Viner, and Weiss definitions of MetS were used to test the validity of these scores.MetS prevalence was 0.4%–4.7% according to these definitions. AI_METS used age, waist circumference, MBP, and TyG index. They offer area under the curves (AUCs) 0.91, 0.93, 0.89, 0.93, and 0.98; specificity 81%, 75%, 72%, 80%, and 97%; and sensitivity 90%, 100%, 90%, 100%, and 100%, respectively, for the detection of MetS according to these definitions. Considering only MBP offers a better specificity and sensitivity to detect MetS than considering only TyG index. MBP offers slightly lower performance than AI_METS.ConclusionAI techniques have proven their ability to extract knowledge from data. They allowed us to generate new scores for MetS detection in adolescents without using specific percentiles for each component. Although these scores are less intuitive than the percentile-based definition, their accuracy is rather effective for the detection of MetS.     

Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions.Methods and resultsA total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m² and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14–20.93), while no association was found when either NAFLD or HT was considered alone.ConclusionOvert atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.     

Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM.Methods and resultsThree hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E′, and higher E/E’ (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05).ConclusionsMiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.     

High leptin status indicates an increased risk of mortality and heart failure in stable coronary artery disease

Background and aimsLeptin is an adipocyte-derived peptide involved in energy homeostasis and body weight regulation. The position of leptin in cardiovascular pathophysiology remains controversial. Some studies suggest a detrimental effect of hyperleptinemia on the cardiovascular (CV) system, while others assume the role of leptin as a neutral or even protective factor. We have explored whether high leptin affects the mortality and morbidity risk in patients with stable coronary heart disease.Methods and resultsWe followed 975 patients ≥6 months after myocardial infarction or coronary revascularization in a prospective study. All-cause or cardiovascular death, non-fatal cardiovascular events (recurrent myocardial infarction, stroke, or any revascularization), and hospitalizations for heart failure (HF) we used as outcomes.High serum leptin concentrations (≥18.9 ng/mL, i.e., 4th quartile) were associated with worse survival, as well as with a higher incidence of fatal vascular events or hospitalizations for HF. Even after full adjustment for potential covariates, high leptin remained to be associated with a significantly increased 5-years risk of all-cause death [Hazard risk ratio (HRR) 2.10 (95%CIs:1.29–3.42), p < 0.003], CV death [HRR 2.65 (95%CIs:1.48–4.74), p < 0.001], and HF hospitalization [HRR 1.95 (95% CIs:1.11–3.44), p < 0.020]. In contrast, the incidence risk of non-fatal CV events was only marginally and non-significantly influenced [HRR 1.27 (95%CIs:0.76–2.13), p = 0.359].ConclusionsHigh leptin concentration entails an increased risk of mortality, apparently driven by fatal CV events and future worsening of HF, on top of conventional CV risk factors and the baseline status of left ventricular function.     

The GLP-1 Receptor Agonist Liraglutide Increases Myocardial Glucose Oxidation Rates via Indirect Mechanisms and Mitigates Experimental Diabetic Cardiomyopathy

BackgroundType 2 diabetes (T2D) increases risk for cardiovascular disease. Of interest, liraglutide, a therapy for T2D that activates the glucagon-like peptide-1 receptor to augment insulin secretion, reduces cardiovascular-related death in people with T2D, though it remains unknown how liraglutide produces these actions. Notably, the glucagon-like peptide-1 receptor is not expressed in ventricular cardiac myocytes, making it likely that ventricular myocardium-independent actions are involved. We hypothesized that augmented insulin secretion may explain how liraglutide indirectly mediates cardioprotection, which thereby increases myocardial glucose oxidation.MethodsC57BL/6J male mice were fed either a low-fat diet (lean) or were subjected to experimental T2D and treated with either saline or liraglutide 3× over a 24-hour period. Mice were subsequently euthanized and had their hearts perfused in the working mode to assess energy metabolism. A separate cohort of mice with T2D were treated with either vehicle control or liraglutide for 2 weeks for the assessment of cardiac function via ultrasound echocardiography.ResultsTreatment of lean mice with liraglutide increased myocardial glucose oxidation without affecting glycolysis. Conversely, direct treatment of the isolated working heart with liraglutide had no effect on glucose oxidation. These findings were recapitulated in mice with T2D and associated with increased circulating insulin levels. Furthermore, liraglutide treatment alleviated diastolic dysfunction in mice with T2D, which was associated with enhanced pyruvate dehydrogenase activity, the rate-limiting enzyme of glucose oxidation.ConclusionsOur data demonstrate that liraglutide augments myocardial glucose oxidation via indirect mechanisms, which may contribute to how liraglutide improves cardiovascular outcomes in people with T2D.