心力衰竭.docx

1、心力衰竭心力衰竭：过去、现在、将来 心力衰竭（Heart Failure，HF）是一种复杂的临床综合征，主要指心脏排血功能障碍，不能适应机体组织代谢需要，所引起的一种严重的病理生理状态，故亦称为心功能不全。心力衰竭可由多种心血管病和非心血管病所引起，包括动脉硬化、瓣膜病、心肌病、高血压、心律失常、严重感染、急慢性肺疾患、内分泌和电解质紊乱-等等。它是各种心血管疾病的终末阶段，预后差、死亡率高，当前还是一个不治之症。它是心血管系统最复杂、最普遍、历史最久远、危害人类生命健康最严重的疾病。 过去 心力衰竭是人类最早认识的疾病之一。早在公元前五世纪，约距今2500年前，希腊Hippocrates医生

2、就曾描述过呼吸衰竭和全身水肿的心衰症状。由于当时缺乏对心脏和循环系统的了解，所以长期以来，心力衰竭仅仅作为一种临床症状（Heart Failure as a Clinical Syndrome）。直到16世纪由于解剖学的发展，William Harvey 最先建立了血液循环的理论，心力衰竭才被认为是一种循环疾病（Heart Failure as a Circulatory Disorder）。18世纪由于发现了心室扩张和肥厚，才逐渐认识到心力衰竭是由于心脏结构的改变所引起的（Altered Architecture of Heart）。直到1918年Ernest H Staling “心定律”

3、的发现，建立了循环生理学，心力衰竭才被认为是血液动力学的障碍（Abnormal Hemodynamics），是由于心输出量不足所引起的，并且提出了收缩性和舒张性心功能不全两种类型。进入20世纪，由于对肾脏生理的认识和利尿药应用，心力衰竭又进一步被认为是一种体液平衡失调性疾病（Disordered Fluid Balance），从而完成了心力衰竭血液动力学的病理基础。在这一时期其诊断主要依赖体征、物理检查和X-Ray，治疗主要应用利尿药和强心剂（洋地黄）。 现在 进入20世纪中叶，由于生物化学、细胞生物学和电生理学的发展，特别是肌肉收缩/舒张和兴奋收缩偶联机制的研究，使心力衰竭进入现代医学生物学

4、的新时代。心力衰竭被认为是一种生化功能异常（Biochmical Abnormalities），主要表现在心脏能量（ATP）生成和供应不足（Energy Starvation）、神经内分泌反应异常（Neurohumoral Response）和心肌收缩力衰弱、心输出量的极端降低（Depressed Contractility）。特别是进入80年代，由于心血管活性多肽、神经介质、细胞因子和生长因子的研究和发展，炎症、免疫、应激、代谢、再塑、代偿、细胞和基质的改变极大地丰富和深化了心力衰竭的内涵和发病机理，成为现代心力衰竭的核心和基础。因此，心力衰竭现在被认为是一种神经内分泌调节障碍（Neurom

5、oral Regulatory Disorders）所引起的循环动力学结构和功能失代偿性的严重疾病。其诊断主要依靠影像诊断和Biomarkers。药物治疗的认识亦发生了深刻的变化：40-60年代强调洋地黄和利尿剂，到70-80年代正性肌力药和血管扩张剂，到目前的-阻断剂，ACE酶抑制剂的广泛使用。并且出现了一系列防治心力衰竭的新药物如肾素、醛固酮抑制剂、心钠素及其受体激动剂、内皮素和AVP拮抗剂，炎性细胞因子的拮抗剂、心肌代谢和PPAR受体调节剂、免疫调节剂和促血管和细胞生成因子等等。 未来 进入21世纪，人类基因组计划的完成，生物医学进入了“组”（Genome）医学和系统生物学的新时代。心血

6、管GWAS分析和干细胞的研究，将心力衰竭的研究推向细胞分子医学的新阶段。整合和修复将成为心力衰竭未来研究的主要方向（Intergration and Regeneration Medicine）。作为一种复杂性疾病，从分子到细胞，从基因到蛋白，从结构到功能，从生理到病理，从损伤到修复，从局部到整体，从发病到防治，从分析到综合，多层次多因素的各种“Omics”的系统整合和网路调控（System and Networks Medicine）将成为心力衰竭未来研究的主要内容。生物标记、分子影像、基因诊断、网络模拟、将成为临床诊断、疾病分型、药物选择、预后评估的主要诊断依据。靶向治疗、分子治疗、细胞治

7、疗、再生治疗、生物治疗、基因治疗、移植治疗、机械辅助治疗、个体化治疗、组合治疗将成为未来心力衰竭主要防治方法。在通向未来的道路上，现在已经启航！虽然，路途依然遥远，或许还需30-50年或更长的征程，但充满了憧憬和期望心力衰竭将一定可以成为可治之症！ 期望 心力衰竭作为最严重的心血管病症一直是心血管基础和临床研究的重点、热点和焦点。从1753至今的360年间，世界上总计发表了10万篇研究报告，其中前200年（1753-1955）有1000篇，1955-2000年近50年间约有35000篇，而最近10年发表的文献已超过60000余篇，为前50年发表的文献总和的2倍。反应了当前心力衰竭研究高速发展的

8、势态和广泛关注。新机理、新通路、新基因、新Biomarkers、新药物、新技术、新概念日新月异！ 我国有近500万成年人患心力衰竭，约占全世界的四分之一。而且，由于老龄化和高血压等心血管发病率的增加，心力衰竭的发病人数正在迅速攀升。虽然，我国最近发布了首部“心力衰竭诊断和治疗指南”，可以规范现在的治疗，但不能从根本上防治。心力衰竭仍然是一个“不治之症”和“顽难之症”。我们只有依靠科学的发展，依靠新技术、新方法和新药物，早防、早治、治标、治本才能彻底防治心力衰竭。衷心呼吁我国的基础和临床科学工作者抓住机遇，迎头赶上。增强使命感和责任感，在未来心力衰竭基础和临床研究工作中做出应有的贡献！我们应该有

9、所作为！亦大有作为！ CMBI搜集了近5000篇心力衰竭的综述和进展报告，组织过多次“心力衰竭”（ 205、 290、 320）和“基因组医学”（ 475、 127）、“心血管干细胞和再生医学”（ 347、 113、 10）、系统生物学（ 399、 272）、转化医学（ 443、 420）、生物标记物（ 481、 450）、MicroRNA（ 464、 372）、表观遗传学（ 438、 201）、基因治疗（ 439）、新药研发（ 477）等未来医学的专题报告。这里我们又集中搜集了近两年来一些重要的“心力衰竭”的综述和论文，供大家参考。 William Harvey (10.1161/CIRCH

10、EARTFAILURE.108.772756) The Galens view and The view after Harvey of circulation (10.1161/CIRCHEARTFAILURE.108.772756) Failing heart operating on the descending limb of the Starling curve (10.1161/CIRCHEARTFAILURE.108.772756) Subcellular remodelling and corresponding changes in their major functions

11、 during the development of heart failure (10.1093/cvr/cvn281) Excitation-contraction signaling in cardiomyocytes (10.1016/j.acvd.2010.04.004) Cardiovascular continuum (10.1177/175*91777) Cellular and Immunologic Events That Lead to CHF (10.1016/j.jacc.2008.11.046) Progression of LV dysfunction to ad

12、vanced heart failure (10.1016/j.paed.2008.10.005) Proliferative signaling pathways that mediate cardiac hypertrophy (10.1161/CIRCHEARTFAILURE.108.772756) American Heart Association 2005 classification of heart failure (HF) (10.4065/?84.8.718) Changing management of heart failure over the past 40 yea

13、rs (10.1161/CIRCHEARTFAILURE.108.772756) Current genomic approaches in the study of complex diseases (10.1016/j.trsl.2007.10.005) Clinico-genomic biosignatures to predict health, disease, and environmental/drug response (10.1016/j.jacc.2005.06.075) miRNAs in LV remodeling (10.1161/CIRCRESAHA.108.183

14、087 ) Environmental causes of epigenetic modifications (10.2215/CJN.03670807) A system biology approach to understanding cardiovascular disease (10.1007/s10741-009-9138-x) Modelling and network analysis (from www.mycib.ac.uk/ & Inferring GRNs from gene expression profiling data (10.1093/bib/bbp028)

15、Human disease network (10.1371/journal.pone.0006536) Bone Marrow-cardiac axis for cell-based myocardial repair (10.1016/j.ejcts.2010.04.022) Application of human stem cell-derived cardiomyocytes (10.1016/j.pharmthera.2010.01.010) Workflow for precision diagnostics in personalized medicine (10.3410/B

16、1-73) Abnormalities of calcium metabolism and myocardial contractility depression in the failing heart Agents with inotropic properties for the management of acute heart failure syndromes Aging and heart failure Antioxidant treatment for heart failure Apoptosis-a potentially reversible, meta-stable

17、state of the heart Assessing and grading congestion in acute heart failure AVP receptor antagonists in patients with CHF Biology of TNF and IL-10, and their imbalance in heart failure Biomarker guided therapy for heart failure Biomarker-guided therapy in chronic heart failure Biomarkers in heart fai

18、lure-a clinical review biomarkers in heart failure Biomarkers of inflammation in heart failure Blocking aldosterone in heart failure cardiac myosin activators Cardiac-targeted delivery of regulatory RNA molecules and genes for the treatment of heart failure Cardiorenal syndrome in decompensated hear

19、t failure cell death in heart failure Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy Clinical applications of N-terminal pro B-type natriuretic peptide in heart failure and other cardiovascular diseases Control of autocrine and paracrine myocardial signals Current

20、 Concepts in Diastolic Heart Failure Current Perspectives on Cardiac Function in Patients With Diastolic Heart Failure Do Calcium Channel Blockers Increase the Diagnosis of Heart Failure in Patients With Hypertension Drug Therapy of Heart Failure-An Immunologic View. Energy metabolism in heart failu

21、re and remodelling Exercise training, inflammation and heart failure Extracellular matrix fibrotic markers in heart failure Extracellular matrix remodeling during the progression of volume overload-induced heart failure Functions for the cardiomyokine, MANF, in cardioprotection, hypertrophy and hear

22、t failure Galectin-3-a novel mediator of heart failure development and progression Gene therapy for heart failur Gene Therapy in Heart Failure Genetic variation in the natriuretic peptide system and heart failure Genomics and Proteomics in Heart Failure Research Genomics, heart failure and sudden ca

23、rdiac death Glucose and insulin abnormalities in patients with heart failure Granulocyte colony-stimulating factor for ischemic heart failure GRK2 as a novel gene therapy target in heart failure Heart failure and personalized medicine. Heart failure therapy-beyond the guidelines. Hyponatremia in hea

24、rt failure Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery Impaired Glucose Tolerance and Insulin Resistance in Heart Failure Inflammation as a therapeutic target in heart failure Intervention for apoptosis in cardiomyopathy Intracellular d

25、evastation in heart failure Investigation and management of congestive heart failure Ion Channels, Transporters, and Pumps as Targets for Heart Failure Therapy. Istaroxime, a first in class new chemical entity exhibiting SERCA-2 activation and NaK-ATPase inhibition-a new promising treatment for acut

26、e heart failure syndromes Levosimendan-from basic science to clinical practice Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure. Mechanisms of Pharmacogenomic Effects of Genetic Variation within the Cardiac Adrenergic Network in Heart Failure MiR423-5p A

27、s a Circulating Biomarker for Heart Failure. Mitochondria in heart failure Mitochondrial centrality in heart failure Molecular forms of natriuretic peptides in heart failure- Monocytes in heart failure Multi-marker strategies in heart failure Multimarker Approach for the Prediction of Heart Failure

28、Incidence in the Community. Oxidative stress and hypertension Parasympathetic Nervous System and Heart Failure Perspective on the clinical application of troponin in heart failure and states of cardiac injury Pharmacological treatment of chronic systolic heart failure Pharmacology of vasopressin ant

29、agonists Phosphodiesterase inhibition in heart failure Potential of endothelin-1 and vasopressin antagonists for the treatment of congestive heart failure PPAR transcriptional activator complex polymorphisms and the promise of individualized therapy for heart failure Primary prevention of heart fail

30、ure-an update. Programmed cell death in cardiac myocytes Proinflammatory cytokines in heart failure Protein kinase C in heart failure Protein kinase C as a heart failure therapeutic target Recent Advances in Cardiovascular Risk Reduction Regulation of central angiotensin type 1 receptors and sympath

31、etic outflow in heart failure Relaxin, a pleiotropic vasodilator for the treatment of heart failure Relaxin-A New Approach for the Treatment of Acute Congestive Heart Failure. Reninangiotensinaldosterone system (RAAS) pharmacogenomics-implications in heart failure management Reversible heart failure-the role of inflammatory activation Role of autophagy in heart failure associated with aging role of endothelial progenitor cells in heart failure Role of guany