Recycle or die: the role of autophagy in cardioprotection

Autophagy is a highly conserved cellular process responsible for the degradation of long-lived proteins and organelles. Autophagy occurs at low levels under normal conditions, but is upregulated in response to stress such as nutrient deprivation, hypoxia, mitochondrial dysfunction, and infection. Upregulation of autophagy may be beneficial to the cell by recycling of proteins to generate free amino acids and fatty acids needed to maintain energy production, by removing damaged organelles, and by preventing accumulation of protein aggregates. In contrast, there is evidence that enhanced autophagy can contribute to cell death, possibly through excessive self-digestion. In the heart, autophagy has an essential role for maintaining cellular homeostasis under normal conditions and increased autophagy can be seen in conditions of starvation, ischemia/reperfusion, and heart failure. However, the functional significance of autophagy in heart disease is unclear and controversial. Here, we review the literature and discuss the evidence that autophagy can have both beneficial and detrimental roles in the myocardium depending on the level of autophagy, and discuss potential mechanisms by which autophagy provides protection in cells.     

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.     

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology’s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC’s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.     

慢性充血性心力衰竭心脏再同步化治疗研究进展

心电学异常往往合并心衰共存于心肌病患者中 ,异常的心电顺序使心脏收缩和舒张不协调 ,从而损害心功能。近来短期和长期研究发现应用心脏起搏可使心脏活动再同步、改善心功能、提高生活质量和生存率 ,认为心脏再同步化疗法是严重心衰合并心电学异常患者的一种理想的非药物辅助治疗选择。其潜在的机制包括 :心脏整体活动的再同步化 ,拮抗神经内分泌活性、逆转心脏重塑 ,抗心律失常等。该方法有严格的适应证 ,可根据患者情况选择不同的方法。文章综述了心脏失同步化的病理生理及心脏再同步化治疗相关临床试验、显效机制、技术关键及存在的问题     

Association of the angiotensin-converting enzyme gene polymorphism with chronic heart failure in Chinese Han patients

BACKGROUND: An insertion/deletion (I/D) polymorphism is present in the 16th intron of the angiotensin-converting enzyme (ACE) gene and is associated with serum and tissue ACE level. Some studies have shown that the DD genotype is associated with some cardiovascular diseases; while ACE polymorphism's effect on chronic heart failure (CHF) remains uncertain. AIM: To investigate the association of the ACE gene I/D polymorphism with CHF in the Chinese Han population. METHODS: The genotype was determined by polymerase chain reaction in 102 normal controls and in 79 patients with CHF. Plasma angiotensin (Ang) levels were assessed by radio-immunity assay. Left ventricular end-diastolic diameters (LVDD) and left ventricular ejection fractions were assessed by echocardiography. RESULTS: The ACE gene polymorphism distribution was similar in patients and control subjects. However, ACE gene DD polymorphism was associated with a more severe condition, greater LVDD [mm: DD: 71+/-7, ID: 62+/-5, II: 60+/-5, P<0.001 DD vs. ID, P<0.001 DD vs. II] and higher plasma Ang II level [pg/ml DD: 92+/-19, ID: 79+/-21, II: 65+/-17 P<0.05 DD vs. ID, P<0.001 DD vs. II]. CONCLUSION: In Chinese Han patients with CHF, ACE gene DD polymorphism might be a marker of a more severe condition, and a higher level of activation of the renin-angiotensin system.     

急性心力衰竭患儿血浆脑钠素变化及意义

为探讨急性心力衰竭患儿血浆脑钠素(BNP)的变化及其与心功能的关系,随机选取不同病因的充血性心力衰竭(CHF)患儿46例作为观察组,另选择肺炎患儿40例、先天性心脏病患儿31例、健康儿40例作对照组;所有病例均采用酶联免疫吸附法分别检测血浆BNP,心力衰竭患儿在心衰期和恢复期用多普勒超声测量心脏指数(CI)及左室射血分数(LVEF)。结果显示,CHF患儿心衰早期BNP即开始升高,心衰期达高峰,恢复期渐下降,但仍高于对照组(P<0.001);心衰时心脏CI、LVEF值均明显下降(P<0.01);CHF患儿心衰时升高的BNP水平与CI、LVEF呈负相关(P<0.05)。表明CHF患儿血BNP水平明显升高,且与心衰程度关系密切。     

Value and limitations of human myocardial biopsy.

Twenty-three myocardial biopsies from 22 patients with various cardiological diseases were examined by light and electron microscopy. The amount of fibrosis, endocardial thickening, “whorling of myofibers”, “irregular running of myofibers”, fat infiltration and lipofuscein granules were compared to cardiological parameters such as the function group of the patients, cardiac index, stroke index and the pulmonary capillary wedge pressure. The histological grading showed a weak correlation to the function group of the patients and the pulmonary capillary wedge pressure, but not to the cardiac index or stroke index. While patients with an almost normal heart function had a normal histology, both normal and abnormal histology were seen in patiens with severe heart disease. It was not possible to relate any morphological changes in the myocardium, neither at the light microscopical nor at the ultrastructural level to specific heart diseases as for example primary or alcoholic cardiomyopathy. However, severe contraction artefacts disturbed both the light microscopical and especially the ultrastructural evaluation of the specimens.This problem is discussed and in order to diminish the risk of misinterpretation of myocardial biopsy specimens, recommendations are given with regard to fixation, mincing and embedding of the specimens as well as to the evaluation of both the light microscopic slides and the ultrathin sections.     

Lipoprotein(a): An independent,genetic, and causal factor for cardiovascular disease and acute myocardial infarction

Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy.     

充血性心力衰竭伴消化道症状患者的胃液体排空功能

观察了２７例充血性心力衰竭伴消化道症状患者的胃液体排空功能。结果发现，与正常人比较，心力衰竭患者胃排空时间延迟（２８．１２±６．３３ｍｉｎ比３５．３０±１０．２８ｍｉｎ，Ｐ＜０．０１），胃体收缩频率降低（Ｐ＜０．００１），血浆胃泌素水平较低。消化道症状及心力衰竭严重程度与胃排空障碍有关。说明胃动力学障碍是充血性心力衰竭患者产生消化道症状的机制之一。