男性内源性性激素水平与冠心病范围及左心室射血分数的相关性

摘要 目的：探究男性内源性性激素水平与冠心病范围及左心室射血分数（LVEF）的相关性。方法：将2018年6月至2020年6月于我院接受治疗的96例经冠状动脉造影术（CAG）确诊为冠心病的96例患者纳入研究,按照临床分型将其区分为稳定型心绞痛（SAP,30例）、不稳定型心绞痛（UAP,30例）、急性心肌梗死（AMI,36例）,另选同期CAG检测结果提示冠状动脉管腔直径狭窄率<50 %的50例个体为对照组,检测入组对象的睾酮（Ts）、雌二醇（E₂）水平,评估计算入组对象的Gensini积分以及LVEF,对比不同组别之间Ts、E₂、Gensini积分以及LVEF差异,Spearman相关分析探究Ts、E₂与Gensini积分、LVEF的相关性,最后将患者按照Genisini评分区分为狭窄轻型组与严重组,Logistic回归分析影响冠脉狭窄的危险因素。结果：（1）比较显示,冠心病各组间Ts、E₂、Gensini积分以及LVEF差异明显,以AMI组患者Ts、E₂和LVEF水平最低,Gensini积分最高（P<0.05）;（2）Spearman相关性分析显示,Ts、E₂均与Gensini积分呈负相关,与LVEF呈正相关（P<0.05）;（3）多因素Logistic回归分析显示Ts、E₂水平是影响冠脉狭窄程度的独立危险因素（P<0.05）。结论：男性内源性性激素水平同其冠心病范围和LVEF呈现密切相关性,是影响冠脉狭窄程度的独立危险因素,可以考虑将其应用于临床冠脉狭窄的诊断与鉴别中。     

组织多普勒成像对射血分数正常的心衰患者左心功能评价

目的:探讨组织多普勒成像(TDI)技术评价射血分数正常的心衰患者左室长轴功能特点。方法:选取30名健康人(Ⅰ组)、EF>50%的心衰患者30名(Ⅱ组)和EF<50%的心衰患者30名(Ⅲ组)作为研究对象,采用TDI在二尖瓣环室间隔(ivs)、侧壁(l)、前壁(a)、后壁(p)、下壁(d)测量其Sm、DSm、IVCTm、TSm、Em、Am、IVRTm、TEm等指标。结果:Ⅰ组、Ⅱ组、Ⅲ组DSm、Sm逐渐减低,(P<0.05);而IVCTm、TSm逐渐升高(P<0.05);IVRTm、TEm在Ⅰ组、Ⅲ组、Ⅱ组逐渐升高(P<0.05);DSm及TEm在诊断EF>50%心衰患者心功能的指标中ROC曲线下面积最大,同样DSp及TEp在五个位点中ROC曲线下面积最大。结论:射血分数正常的心衰患者存在收缩减低;DSm及TEm是诊断EF>50%心衰患者心功能比较有效的指标;后壁是诊断的最佳位点。     

通心络对急性心肌梗死保守治疗患者疗效观察

目的:观察通心络胶囊对急性心肌梗死(AMI)未接受经皮冠状动脉介入治疗(PCI)或溶栓治疗后患者的疗效。方法:对我院收治的ST段抬高未实施PCI或溶栓治疗的AMI患者,随机分为常规药物治疗作为对照组(20例)和同时加服用通心络胶囊的治疗组(20例)。于发病后一月内观察再发心绞痛、急性心血管事件、左室射血分数(LVEF)改变。结果:通心络组心功能改善较对照组明显,通心络组再发心绞痛及急性心血管事件较对照组明显减少。结论:通心络对急性心肌梗死保守治疗患者不仅减少心绞痛发作及急性心血管事件的发生而且可改善心功能。     

Ventriculographie isotopique : comparaison de l’acquisition sur gamma caméra CZT cardio dédiée à l’acquisition planaire

IntroductionGated equilibrium radionuclide venticulography is often used to determine left ventricule ejection fraction (LVEF), especially in case of follow up when cardio-toxic drugs are administred. During the last decade, the use of cardiac specific (CZT) gamma cameras has spread. They directly acquire 3D data. We wanted to determine the agreement between three nuclear medicine LVEF measurement techniques. We also wanted to determine the repeatability of these techniques.MethodsBetween April 16, 2016 and February 4, 2017 we consecutively included 77 patients who were adressed to the nuclear medicine department of CHU Martinique for LVEF measurement. Patients were injected with 99*Technetium labelled albumin. Usual planar scintigraphy was performed to serve as reference and 3D data was acquired with a CZT cardiac gamma camera. 3D data was analyzed directly with BPGS software, and also reprojected to planar data which was analyzed like the conventional planar acquisition.ResultsSeventy patients had acquisitions with both gamma cameras. The LVEF values from the CZT camera data were significantly higher than the reference planar LVEF measurements (+6.2 for 3D analysis, P < 0.01, concordance interval [?8.0; 20.3] and +1.7 for planar reprojection, P = 0.01, concordance interval [?8.9; 12.2]. For all three methods, the intra-method concordance intervals were within [?5; 5].ConclusionOur results indicate the same measurement method must be used in case of LVEF follow up. The variation between theses methods could lead to the false conclusion of impairment of LVEF (which is suspected in case of a 10% LVEF drop). Our secondary outcome show a good repeatability for all three techniques. Further studies should be initiated to determine which method is the most accurate and to determine the reproductibility of the CZT data acquisition process.     

Genetic predisposition to left ventricular dysfunction: a multigenic and multi-analytical approach

Background

Left ventricular dysfunction (LVD) is a complex, multifactorial condition, caused by mechanical, neurohormonal, and genetic factors. We have previously observed association of renin–angiotensin–aldosterone system (RAAS), matrix metalloproteinases (MMPs) and inflammatory pathway genes with LVD. Therefore the present study was undertaken to identify the combination of genetic variants and their possible interactions contributing towards genetic susceptibility to LVD in the background of coronary artery disease (CAD).

Methods and results

The study included 230 healthy controls and 510 consecutive patients with angiographically confirmed CAD. Among them, 162 with reduced left ventricle ejection fraction (LVEF ≤ 45%) were categorized as having LVD. We analyzed 11 polymorphisms of RAAS, MMPs and inflammatory pathways. Single locus analysis showed that AT1 A1166C (p value < 0.001; OR = 3.67), MMP9 R668Q (p value = 0.007; OR = 3.48) and NFKB1-94 ATTG ins/del (p value = 0.013; OR = 2.01) polymorphisms were independently associated with LVD when compared with both non-LVD patients and healthy controls. High-order gene–gene interaction analysis, using classification and regression tree (CART) and multifactor dimensionality reduction (MDR) revealed that AT1 A1166C and NFKB1-94 ATTG ins/del polymorphisms jointly increased the risk of LVD to great extent (p-value = 0.001; OR = 8.55) and best four-factor interaction model consisted of AT1 A1166C, MMP7 A-181G, MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms with testing accuracy of 0.566 and cross validation consistency (CVC) = 9/10 (permutation p < 0.001) showed increased risk for LVD respectively.

Conclusion

AT1 A1166C independently and in combination with MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms plays important role in conferring genetic susceptibility to LVD in CAD patients.     

Late gadolinium enhancement MRI quantification to predict left ventricular remodeling after acute myocardial infarction

ObjectivesInfarct size is a major surrogate marker for prognosis in the context of myocardial infarction. There is a growing interest in validating a quantitative assessment approach in order to: (1) standardize these analyses; (2) to precise the individual prognosis of our patients. Several methods are available and were tested across their capacity to predict left ventricular (LV) remodeling at three months.Patients and methodsLate gadolinium enhancement-MRI was performed on day 5 and after a period of three months in 92 patients with STEMI. LV volumes and scar parameters were assessed visually (by using a four scale score) and quantitatively on day 5 and at three months. Dichotomous thresholds were defined first visually (VISUAL), then by 2, 5 and 6 standard deviations above remote myocardium, and by the full-width at half-maximum (FWHM) method.ResultsAll infarct sizing methods showed great relation to LV remodeling at three months (ROC analysis). Univariate predictors of an LV end-systolic volume index (LVESVi) superior to 70 mL/m² were: heart failure, creatin kinase peak and infarct size at day 5. FWHM was shown to be the best of all quantitative methods. An infarct size superior to 44 grams predicted a LVESVi > 70 mL/m² with a sensitivity of 90% and a specificity of 92.5%. FWHM reproducibility was good (r = 0.895, P < 0.0001, Bland Altman bias of 0.8 g).ConclusionIn the context of STEMI, FWHM is a tough and reproducible algorithm to quantitatively assess late gadolinium hyperenhancement, greatly related to functional prognosis at three months follow-up.     

Myeloperoxidase,a possible biomarker for the early diagnosis of cardiac diastolic dysfunction with preserved ejection fraction

The current study was conducted on a sample of 91 patients diagnosed with diastolic dysfunction (DD) with preserved systolic function caused by a painful chronic ischaemic cardiopathy – angina pectoris stable at the effort. The diagnosis was established following anamnesis, electrocardiogram, and echocardiography. Myeloperoxidase (MPO) serum levels were assessed in all patients and then these values were correlated with some of the echocardiography parameters that proved the mentioned diagnosis.

In conclusion, the execution of this investigation triad (electrocardiogram, echocardiography, and MPO) allows:

• Stratifying the patients depending on the disease risk by early detecting of any possible DD with preserved systolic function.

• The use of the MPO increased circulating levels as a biomarker for diagnosis and risk due to the statistically significant correlation between those and the results of the other two aforementioned paraclinical investigation.

     

The desumoylating enzyme sentrin-specific protease 3 contributes to myocardial ischemia reperfusion injury

Sentrin-specific protease 3 (SENP3), a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia reperfusion (MIR) injury is unclear. Here, we observed that SENP3 was expressed and upregulated in the mouse heart depending on reactive oxygen species (ROS) production in response to MIR injury. By utilizing siRNA-mediated cardiac specific gene silencing, SENP3 knockdown was demonstrated to significantly reduce MIR-induced infarct size and improve cardiac function. Mechanistic studies indicated that SENP3 silencing ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum (ER) stress and mitochondrial-mediated apoptosis pathways. By contrast, adenovirus-mediated cardiac SENP3 overexpression significantly exaggerated MIR injury. Further molecular analysis revealed that SENP3 promoted mitochondrial translocation of dynamin-related protein 1 (Drp1) in reperfused myocardium. In addition, mitochondrial division inhibitor-1 (Mdivi-1), a pharmacological inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken together, we provide the first direct evidence that SENP3 upregulation pivotally contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3 suppression may hold therapeutic promise for constraining MIR injury.     

Simultaneous dual-isotope 123I/99mTc acquisition using CZT-based cameras: Toward a one-stop-shop SPECT in heart failure patients

The CZT-cameras (DNM 530c and DSPECT) have only recently been introduced, and the impact of the increased energy resolution remains unknown. This paper summarizes the evidence on the assessment of: (i) the left ventricular function, (ii) the ¹²³I/^99mTc mismatch, and (iii) the heart-to-mediastinum ratio (HMR) of ¹²³I-metaiodobenzylguanidine (MIBG) uptake under dual-isotope conditions (^99mTc and ¹²³I) using cadmium-zinc-telluride (CZT) technology. The diagnostic accuracy of CZT cameras for myocardial sympathetic innervation imaging, left ventricular function and perfusion assessment using perfusion-gated SPECT have only been established in a few studies, under single-isotope conditions. Limited evidence is available regarding simultaneous dual-isotope acquisition using CZT-cameras. However, recently reported data have shown that CZT cameras allow, in dual-isotope (¹²³I and ^99mTc) acquisitions and under routine conditions: (i) a simultaneous and accurate segmental study of myocardial innervation and perfusion (match and mismatch), (ii) the ventricular function assessment (EDV, ESV and LVEF), and (iii) the determination of the late HMR of cardiac ¹²³I-MIBG uptake in patients with heart failure. However, this latter should be performed using transaxial reconstructed images and a linear correction based on phantom data acquisitions.

Exosomal Mst1 transfer from cardiac microvascular endothelial cells to cardiomyocytes deteriorates diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM) is characterized by cardiac microvascular endothelial cells (CMECs) injury and cardiomyocyte (CM) dysfunction. Exosomes mediated cellular communication between CMECs and CM has emerging roles in the pathogenesis of DCM, but the underlining mechanisms are unclear. Mammalian sterile 20-like kinase 1 (Mst1), a key component in Hippo pathway which participates in regulating organ size, apoptosis and autophagy, is involved in the development of DCM. We generated the endothelial-specific Mst1 transgenic mice (Tg-Mst1^EC) and constructed diabetic model with streptozotocin (STZ). Interestingly, Tg-Mst1^EC mice suffered from worse cardiac function and aggravated insulin resistance compared with non-transgenic (NTg) diabetic mice. The content of Mst1 protein was increased, while Mst1 mRNA had no significant change in CM isolated from diabetic Tg-Mst1^EC mice. In vitro, CMECs-derived exosomes were taken up by CM and increased Mst1 protein content which inhibited autophagy, as well as enhanced apoptosis in high glucose (HG) cultured CM as evidenced by immunofluorescence and western blot analysis. In addition, Mst1 inhibited glucose uptake under diabetic condition by disrupting the glucose transporter type 4 (GLUT4) membrane translocation through decreasing the interaction between Daxx and GLUT4, as well as enhancing the association of Mst1 and Daxx. Our study exemplifies pleiotropic effects of Mst1-enriched exosomes released from CMECs on inhibiting autophagy, promoting apoptosis and suppressing the glucose metabolism in CM.