医汇心血管学术 > 心血管专业进展翻译


发表于 2014-10-09 14:41:07
Abstract 1 of 8Arrhythmia/Electrophysiology Prevention of Ventricular Arrhythmias With Sarcoplasmic Reticulum Ca2+ ATPase Pump Overexpression in a Porcine Model of Ischemia ReperfusionBackground— Ventricular arrhythmias are life-threatening complications of heart failure and myocardial ischemia. Increased diastolic Ca2+ overload occurring in ischemia leads to afterdepolarizations and aftercontractions that are responsible for cellular electric instability. We inquired whether sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) overexpression could reduce ischemic ventricular arrhythmias by modulating Ca2+ overload. Methods and Results— SERCA2a overexpression in pig hearts was achieved by intracoronary gene delivery of adenovirus in the 3 main coronary arteries. Homogeneous distribution of the gene was obtained through the left ventricle. After gene delivery, the left anterior descending coronary artery was occluded for 30 minutes to induce myocardial ischemia followed by reperfusion. We compared this model with a model of permanent coronary artery occlusion. Twenty-four–hour ECG Holter recordings showed that SERCA2a overexpression significantly reduced the number of episodes of ventricular tachycardia after reperfusion, whereas no significant difference was found in the occurrence of sustained or nonsustained ventricular tachycardia and ventricular fibrillation in pigs undergoing permanent occlusion. Conclusions— We show that Ca2+ cycling modulation using SERCA2a overexpression reduces ventricular arrhythmias after ischemia-reperfusion. Strategies that modulate postischemic Ca2+ overload may have clinical promise for the treatment of ventricular arrhythmias.Abstract 2 of 8Epidemiology Tumor Necrosis Factor- and Mortality in Heart FailureA Community Study Background— Tumor necrosis factor- (TNF), an inflammatory cytokine, was reported to be elevated in trials of heart failure (HF) with reduced ejection fraction (EF) and associated with mortality. Whether this is true for HF with preserved EF is unknown, and community data are lacking. We evaluated the distribution of TNF, its association with baseline characteristics and mortality, and its benefit in assessing risk in community HF patients. Methods and Results— Olmsted County residents with active HF from July 2004 to March 2007 (n=486; mean age, 76.7 years; EF 50%, 55%) were prospectively recruited. Clinical characteristics and TNF were measured. Elevated TNF (more than the assay limit of normal of 2.8 pg/mL) was present in 143 (29%). Higher TNF was associated with decreased creatinine clearance, nonsmoking status, anemia, and greater comorbidity (Ptrend<0.05 for all). Mortality increased with increasing TNF (P=0.016), with 1-year mortality estimates of 16%, 18%, 23%, and 32% from the lowest to highest quartile, respectively. After adjustment for age, sex, and EF, the hazard ratios for death were 1.24, 1.37, and 1.90 from the second to the highest TNF quartile, respectively (Ptrend=0.007). TNF contributed to risk assessment as indicated by increases in the area under the receiver operating characteristic curves in all models examined (P<0.05 for all). Results did not differ by EF (P=0.60 interaction term of TNF and EF). Conclusions— TNF was elevated in a large portion of community HF patients, was associated with a large decrease in survival, and provided a significant incremental increase in risk assessment above established indicators. TNF is useful for risk assessment in HF patients with preserved and reduced EF.Abstract 3 of 8Heart Failure Predictors of Outcome in Patients With Suspected MyocarditisBackground— The objective of this study was to identify the prognostic indicators in patients with suspected myocarditis who underwent endomyocardial biopsy. Methods and Results— Between 1994 and 2007, 181 consecutive patients (age, 42±15 years) with clinically suspected viral myocarditis were enrolled and followed up for a mean of 59±42 months. Endomyocardial biopsies were studied for inflammation with histological (Dallas) and immunohistological criteria. Virus genome was detected by polymerase chain reaction. The primary end point was time to cardiac death or heart transplantation. In 38% of the patients (n=69), the Dallas criteria were positive. Immunohistological signs of inflammation were shown in 50% (n=91). Genomes of cardiotropic virus species were detected in 79 patients (44%). During follow-up, 22% of the patients (n=40) reached the primary end point. Three independent predictors were identified for the primary end point, namely New York Heart Association class III or IV at entry (hazard ratio, 3.20; 95% confidence interval, 1.36 to 7.57; P=0.008), immunohistological evidence of inflammatory infiltrates in the myocardium (hazard ratio, 3.46; 95% confidence interval, 1.39 to 8.62; P=0.008), and β-blocker therapy (hazard ratio, 0.43; 95% confidence interval, 0.21 to 0.91; P=0.027). Ejection fraction, left ventricular end-diastolic pressure, and left ventricular end-diastolic dimension index were predictive only in univariate, not in multivariate, analysis. Neither the Dallas criteria nor the detection of viral genome was a predictor of outcome. Conclusions— For patients with suspected myocarditis, advanced New York Heart Association functional class, immunohistological signs of inflammation, and lack of β-blocker therapy, but not histology (positive Dallas criteria) or viral genome detection, are related to poor outcome.Abstract 4 of 8Heart Failure Increased Cardiac Myocyte Progenitors in Failing Human HeartsBackground— Increasing evidence, derived mainly from animal models, supports the existence of endogenous cardiac renewal and repair mechanisms in adult mammalian hearts that could contribute to normal homeostasis and the responses to pathological insults. Methods and Results— Translating these results, we isolated small c-kit+ cells from 36 of 37 human hearts using primary cell isolation techniques and magnetic cell sorting techniques. The abundance of these cardiac progenitor cells was increased nearly 4-fold in patients with heart failure requiring transplantation compared with nonfailing controls. Polychromatic flow cytometry of primary cell isolates (<30 µm) without antecedent c-kit enrichment confirmed the increased abundance of c-kit+ cells in failing hearts and demonstrated frequent coexpression of CD45 in these cells. Immunocytochemical characterization of freshly isolated, c-kit–enriched human cardiac progenitor cells confirmed frequent coexpression of c-kit and CD45. Primary cardiac progenitor cells formed new human cardiac myocytes at a relatively high frequency after coculture with neonatal rat ventricular myocytes. These contracting new cardiac myocytes exhibited an immature phenotype and frequent electric coupling with the rat myocytes that induced their myogenic differentiation. Conclusions— Despite the increased abundance and cardiac myogenic capacity of cardiac progenitor cells in failing human hearts, the need to replace these organs via transplantation implies that adverse features of the local myocardial environment overwhelm endogenous cardiac repair capacity. Developing strategies to improve the success of endogenous cardiac regenerative processes may permit therapeutic myocardial repair without cell delivery per se.Abstract 5 of 8Interventional Cardiology Prevalence and Prognostic Significance of Preprocedural Cardiac Troponin Elevation Among Patients With Stable Coronary Artery Disease Undergoing Percutaneous Coronary InterventionResults From the Evaluation of Drug Eluting Stents and Ischemic Events RegistryBackground— Although cardiac troponin (cTn) elevation is associated with periprocedural complications during percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes, the prevalence and prognostic significance of preprocedural cTn elevation among patients with stable coronary artery disease undergoing PCI are unknown. Methods and Results— Between July 2004 and September 2006, 7592 consecutive patients who underwent attempted stent placement at 47 hospitals throughout the United States were enrolled in a prospective multicenter registry. We analyzed the frequency of an elevated cTn immediately before PCI and its relationship to in-hospital and 1-year outcomes among patients who underwent PCI for either stable angina or a positive stress test. Among the stable coronary artery disease population (n=2382, 31.4%), 142 (6.0%) had a cTn level above the upper limit of normal before the procedure. Compared with patients who had normal baseline cTn, patients with elevated cTn had a higher rate of in-hospital death or myocardial infarction (13.4% versus 5.6%; P<0.001) and a trend toward higher rates of urgent repeat PCI (1.4% versus 0.2%; P=0.06). In multivariable analyses adjusted for demographic, clinical, angiographic, and procedural factors, baseline cTn elevation remained independently associated with the composite of death or myocardial infarction at hospital discharge (odds ratio, 2.1; 95% confidence interval, 1.2 to 3.8; P=0.01) and at the 1-year follow-up (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.3; P=0.005). Conclusions— Baseline elevation of cTn is relatively common among patients with stable coronary artery disease undergoing PCI and is an independent prognostic indicator of ischemic complications. If these data are confirmed in future studies, consideration should be given to routine testing of cTn before performance of PCI in this patient population.Abstract 6 of 8Molecular Cardiology Requirement for p38 Mitogen-Activated Protein Kinase Activity in Neointima Formation After Vascular InjuryBackground— Angioplasty and stent delivery are performed to treat atherosclerotic vascular disease but often cause deleterious neointimal lesion formation. Previously, growth factor receptor-bound protein 2 (Grb2), an intracellular linker protein, was shown to be essential for neointima formation and for p38 mitogen-activated protein kinase (MAPK) activation in vascular smooth muscle cells (SMCs). In this study, the role of vascular SMC p38 MAPK in neointimal development was examined. Methods and Results— Compound transgenic mice were generated with doxycycline-inducible SMC-specific expression of dominant-negative p38 MAPK (DN-p38). Doxycycline treatment resulted in the expression of DN-p38 mRNA and protein in transgenic arteries. Doxycycline-treated compound transgenic mice were resistant to neointima formation 21 days after carotid injury and showed reduced arterial p38 MAPK activation. To explore the mechanism by which p38 MAPK promotes neointima formation, an in vitro SMC culture system was used. Inhibition of p38 MAPK in cultured SMCs by treatment with SB202190 or small interfering RNA blocked platelet-derived growth factor–induced SMC proliferation, DNA replication, phosphorylation of the retinoblastoma protein, and induction of minichromosome maintenance protein 6. Conclusions— SMC p38 MAPK activation is required for neointima formation, perhaps because of its ability to promote retinoblastoma protein phosphorylation and minichromosome maintenance protein 6 expression.Abstract 7 of 8Pericardial Disease Corticosteroids for Recurrent PericarditisHigh Versus Low Doses: A Nonrandomized Observation Background— Corticosteroid use is widespread in recurrent pericarditis, even if rarely indicated, and high doses (eg, prednisone 1.0 to 1.5 mg · kg–1 · d–1) are generally recommended, although only weak evidence supports their use with possible severe side effects. The aim of this work was to compare side effects, recurrences and other complications, and hospitalizations of a low- versus high-dose regimen of prednisone for recurrent pericarditis. Methods and Results— A retrospective review of all cases of recurrent pericarditis treated with corticosteroids according to different regimens from January 1996 to June 2004 was performed in 2 Italian referral centers. One hundred patients with recurrent pericarditis (mean age, 50.1±15.8 years; 57 females) were included in the study; 49 patients (mean age, 47.5±16.0; 25 females) were treated with low doses of prednisone (0.2 to 0.5 mg · kg–1 · d–1), and 51 patients (mean age, 52.6±15.3; 32 females) were treated with prednisone 1.0 mg · kg–1 · d–1. Baseline demographic and clinical characteristics were well balanced across the groups. Each initial dose was maintained for 4 weeks and then slowly tapered. After adjustment for potential confounders (age, female gender, nonidiopathic origin), only high doses of prednisone were associated with severe side effects, recurrences, and hospitalizations (hazard ratio, 3.61; 95% confidence interval, 1.96 to 6.63; P<0.001). Conclusions— Use of higher doses of prednisone (1.0 mg · kg–1 · d–1) for recurrent pericarditis is associated with more side effects, recurrences, and hospitalizations. Lower doses of prednisone should be considered when corticosteroids are needed to treat pericarditis.Abstract 8 of 8Special Report Translating Research Into Practice for Healthcare ProvidersThe American Heart Association’s Strategy for Building Healthier Lives, Free of Cardiovascular Diseases and Stroke The American Heart Association’s (AHA’s) mission is "to build healthier lives, free of cardiovascular diseases and stroke." This first article in a 2-part series will serve to present an overview of the work the AHA has undertaken to translate evidence into practice for healthcare professionals. It describes the extensive work of the AHA to support and further the delivery of evidence-based medicine, which includes the following: (1) supporting scientific discovery and the next generation of healthcare professionals and researchers; (2) disseminating scientific information; (3) developing evidence-based guidelines and statements; (4) creating and advocating for the implementation of performance indicators/measures; (5) developing clinical decision support and quality improvement tools; and developing directed-cause campaigns, all of which can lead to improved patient care. This article also discusses the need for novel approaches and some of the AHA’s evolving strategies to help address gaps in care. The second article, which will be published shortly after this one, will examine the AHA’s efforts to engage and empower healthcare consumers to become more involved with their own health and health care. Key Words: cardiovascular diseases • research • stroke 第一篇 心律失常/电生理学猪缺血再灌注模型中出现肌浆网钙ATP酶过表达时室性心律失常的预防背景——室性心律失常在心衰和心肌缺血疾病中是一种危及生命的并发症。缺血时的舒张期钙超载导致后除极和后收缩是细胞内电不稳定的主要原因。我们探讨是否肌浆网Ca2+ ATP酶泵 (SERCA2a)的过表达可以通过调整钙超载状态降低缺血性室性心律失常的发生方法——通过在3支主要冠脉血管内递送腺病毒制作猪的SERCA2a过表达模型。基因通过左室均匀分布。基因递送后,夹闭左冠状动脉前降支30分钟后开放造成缺血再灌注损伤。我们将此模型与持续性冠状动脉闭塞模型相比较。24小时动态心电图记录holter显示SERCA2a过表达可显著降低再灌注后室性心动过速的发作,然而在永久闭塞冠脉的对照组猪中,持续性和非持续性室性心律失常以及室颤的发生率无显著差异。结论——研究表明通过SERCA2a过表达调整钙离子循环可降低缺血再灌注后室性心律失常的发生,用这种方法调整缺血后钙超载对临床室性心律失常的治疗可能具有巨大的应用前景。 第二篇一个关于在心衰中,肿瘤坏死因子-α和死亡率的社区研究背景----肿瘤坏死因子-α是一种炎症因子,在多个EF下降心衰的临床试验中发现增加,并与死亡率相关,但是EF维持在正常的心衰是否亦如此,社区的研究数据还缺乏。我们评估了肿瘤坏死因子-α水平分布,与基线特征和死亡率之间的联系,已经用在社区心衰病人评估的益处。方法和结果---收集了2004年7月到2007年3月奥姆斯特德县居民中活动性心衰的患者(n=486,平均年龄76.7岁,EF50%-55%)。测量临床的参数和TNF.在143例中发现TNF水平增高(高于正常检测的水平2.8pg/ml)。高水平的TNF伴有肌酐清除率的水平降低,非吸烟状态,贫血和高同患多病率(所有Ptrend均<0.05)。TNF增加,死亡率明显增加(P=0.016),一年预期亡率的四分位数从低到高分别是16%, 18%, 23%和32%。调整年龄、性别和EF的影响,死亡危害率四分位数从第二到最高的比分别为1.24, 1.37和1.90(Ptrend=0.007)。所有模型的接受者抽检特性曲线下面积增加显示TNF有利于危险评估(P均<0.05)。同过EF分析,结果没有差异((P=0.60 ,interaction term of TNF and EF)结论---TNF在大部分社区心衰患者中增加,伴有随存在率减低,在风险评估上述既定的指标上并提供了明显的增量增加,。TNF有利于EF正常和下降的心衰患者危险评估。 第三篇 心力衰竭可疑心肌炎病人的预后因素背景—本次研究的目的是确定接受过心内膜心肌活检的可疑心肌炎病人的预后因素。 方法和结果—我们收集了1994到2007年间临床怀疑病毒性心肌炎的181名连续病例(年龄, 42±15 岁)并进行了随访(平均随访时间59±42 月)。同时我们按照组织学标准(Dallas标准)及免疫组织学标准对这些病人的心内膜心肌活检标本有无炎症进行了分析,并应用聚合酶链反应检测病毒基因组。研究的主要终止点是心源性猝死或心脏移植。38%的病人(n=69)符合Dallas标准,50%的病人(n=91)有免疫组织学炎症表现,74名病人(44%)的活检标本中检测到了亲心性病毒的基因组。在随访期间,22%的病人(n=40)达到了主要终止点。我们确定了三项彼此独立的预测因素,分别是纽约心脏病学会心脏功能分级III或IV级(风险比, 3.20; 95% 可信区间, 1.36 to 7.57; P=0.008),心肌免疫组织学炎症浸润表现(风险比, 3.46; 95% 可信区间l, 1.39 to 8.62; P=0.008), β受体阻滞剂治疗(风险比, 0.43; 95%可信区间, 0.21 to 0.91; P=0.027)。射血分数,左室舒张末压力及左心室舒张末期内径指数只在单变量分析的情况下有预测作用,在多变量分析时无法预测病人的预后,而Dallas标准和活检检测到病毒基因组都不能准确预测病人预后。结论—对于可疑心肌炎病人而言,纽约心脏病学会心脏功能分级高,免疫组织学炎症表现及缺少β受体阻滞剂治疗与预后不良相关,而组织学表现符合Dallas标准或活检检测到病毒基因组与预后不良没有确切关系。 第四篇心衰患者体内增加的心肌祖细胞研究背景:近年来,不断有实验表明,成年哺乳动物体内存在内源性心肌细胞的自我修复及更新的证据,这种自我修复有助于心功能恢复到正常水平及对心脏本身对病理损伤的应激。方法和结果:我们采用原代细胞分离方法及核磁细胞筛选技术从37位心衰患者中的36位患者体内成功分离出小型c-kit阳性细胞。相比未发生心衰的控制组患者,这些需要心脏移植治疗的心衰患者其体内丰富的心肌祖细胞是前者数量的4倍之多。显色流式祖细胞分离(<30 µm)未发现这类人群中c-kit祖细胞的增加,这进一步证实了心衰可导致患者体内c-kit阳性细胞的增加,且证实了这类细胞会频繁的共表达CD45分子。我们采用免疫细胞化学特征性标记这些离体的、c-kit表达丰富的心肌祖细胞后,亦发现c-kit及CD45存在频繁的共表达现象。将新生大鼠心室肌细胞及原位心肌祖细胞共培养后发现,前者形成新的人心肌细胞的频率要相对高于后者。这些收缩的、新的心肌细胞呈相对幼稚形态,采用频繁电耦合该类心肌细胞可诱导它们向成熟肌性细胞分化。结论:尽管心衰患者体内心肌祖细胞的数量众多,亦具有像成熟心肌细胞分化的潜力,但是心衰的治疗手段仍以心脏移植手术为主,局部的心肌环境实际上并不利于心肌祖细胞的自我恢复及衍化。如何有效改善内源性心肌细胞的再生而非本质上的心肌细胞移植将对心肌的自我修复起到进一步的积极作用,这亦将是今后心衰治疗的方向。 第五篇 介入心脏病学稳定冠状动脉疾病行经皮冠脉介入治疗(PCI)患者术前心脏肌钙蛋白抬高的流行性和对预后的重要性。背景—虽然在急性冠脉综合症行PCI的患者中,肌钙蛋白抬高与术后并发症相关,但在稳定冠脉疾病行PCI的患者中术前肌钙蛋白抬高的流行性和对预后的重要性仍不为人知。方法和结果—在2004年7月至2006年9月间,在美国47所医院7592名行支架置入治疗患者被招募在一个前瞻性多中心注册研究。在那些稳定心绞痛或运动试验阳性行PCI的患者间,我们分析在PCI前肌钙蛋白升高的频率和他们与住院期间和随访1年时结果间的关系。在稳定的冠脉病变的人群中(n=2382, 31.4%),142 (6.0%)名患者在PCI前肌钙蛋白水平在正常上限。与肌钙蛋白在正常基线的患者比较,肌钙蛋白升高的患者有更高的住院死亡或心肌梗死率(13.4% 比5.6%; P<0.001)和一个更高的急诊再次PCI的趋势(1.4% 比 0.2%; P=0.06)。在调整了人口、临床、血管造影和手术因素的多变量分析中,基线肌钙蛋白升高持续与出院(优势比, 2.1; 95% 可信区间, 1.2 至 3.8; P=0.01)和1年随访(优势比, 2.0; 95%可信区间, 1.2 至 3.3; P=0.005)时的死亡或心肌梗死独立相关。结论—肌钙蛋白基线升高在行PCI 的稳定冠脉病变患者中是相对普遍的,是缺血并发症的独立预后预测因子。如果这些数据在将来的研究中被证实,在稳定冠脉病变患者中行PCI前常规行肌钙蛋白检查应该被考虑。第六篇血管损伤后新生内膜形成需要p38MAPK活化背景:支架和血管成形术经常用于治疗粥样硬化性血管疾病,但经常发生有害的新生内膜形成,过去,一种膜内连接蛋白,生长因子受体结合蛋白2发现在血管平滑肌中与新生内膜形成和激活p38丝裂蛋白活化蛋白激酶有关,这项研究观察血管平滑肌p38_ MAPK在新生内膜中的作用。方法与结果:多西环素诱导的SMC特异性显性阴性表达p38_ MAPK大鼠,多西环素处理的DN-p38POST 西环素处理的转基因小鼠新生内膜抵抗,动脉p38 MAPK活化降低。应用离体SMC孵育系统探索p38_ MAPK 提高新生内膜形成的机制。应用SB202190或是RNAi阻断血小板源性生长因子诱导SMC增生,DNA复制和视网膜母细胞瘤蛋白质磷酸化和诱导微型染色体维持蛋白6表达。结论:新生内膜形成须有SMC p38_ MAPK活化,其可能机制为提高视网膜母细胞瘤蛋白质磷酸化和微型染色体维持蛋白6表达。第七篇高剂量与低剂量糖皮质激素用于复发性心包炎的比较:一项非随机观察背景——糖皮质激素广泛的用于复发性心包炎,即使很少有指征,而且高剂量(如,泼尼松1.0-1.5mg/Kg.天)常常被推荐,虽然仅有较弱的证据支持这种应用而且可能有严重的副作用。这项研究的目的是比较低剂量和高剂量泼尼松用于复发性心包炎的副作用、复发、其它合并症和住院。方法和结果:本研究回顾性研究了在2个意大利转诊中心1996年1月到2004年6月接受糖皮质激素治疗的任何原因的复发性心肌炎的病例。100例复发性心包炎患者(平均年龄50.1±15.8岁,57例女性)被纳入本研究,49例患者(平均年龄47.5±16.0岁,25例女性)接受低剂量泼尼松(0.2-0.5mg/Kg.天),51例患者(平均年龄52.6±15.3岁,32例女性)接受1.0mg/Kg.天泼尼松治疗。两组患者基线人口统计学和临床特征相似。所有的起始剂量均持续4周,然后逐步减量。在校正了潜在的混杂因素(年龄、女性、非特发性病因)之后,仅有高剂量泼尼松与严重副作用、复发和住院相关(危险比,3.61;95%可信区间1.96-6.63;P<0.001)。结论:应用高剂量泼尼松(1.0mg/Kg.天)治疗复发性心包炎与较多的副作用、复发和住院相关。当需要用糖皮质激素治疗心包炎的时候,应该考虑选择低剂量。 第八篇 专业报道---为健康护理提供者把研究转入实践美国心脏病协会的构建健康生活,摆脱心血管疾病和中风策略美国心脏病协会的使命是“构建健康生活,摆脱心血管疾病和中风。”这个两部分连载书的第一篇文章将负责提供一个综述,关于美国心脏病协会已经实施的为健康护理专家把证据转入实践的工作。它用来描述美国心脏病协会的全面工作以支持和发展循证医学的传播,循证医学包括如下方面:(1),支持健康护理专家和研究者的科学发现和接续发现;(2),散布科学的信息;(3),发展循证方针和综述;(4),构造和倡导测量的实施;(5),发展临床决定证据和质量修改工具,发展直接证据活动,它们可以提高病人健康状况。这个文章也讨论了发展新颖方法和美国心脏病协会的发展策略的必要性,以便帮助抚平医疗的差距。将会在本文发表之后很快出版第二篇文章,将会调查美国心脏病协会的成就来给予健康护理消费者力量,使他们变得更加关注他们的健康和健康护理。关键字:心血管疾病 研究 中风 来源:丁香园

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