心力衰竭与心室重构

Editorial Comment （述评）
-by Tang WHW, Huang Y
• Yet even at present, the promising results reported by Li and colleagues may have already opened the opportunity to explore with the latest technologies how synergistic interactions among active TCM ingredients can benefit the syndrome of heart failure. This is a challenge that we should all warmly embrace.
• 可以想象的是，如果芪苈强心胶囊在未来高质量的临床研究中提供更多 关于其对受试者发病率、死亡率益处的证据，那么它将从根本上挑战现
有的关于药物效应动力学研究的科学观念。
Tang WH, Huang Y. Cardiotonic Modulation in Heart Failure: Insights from Traditional Chinese Medicine. J Am Coll Cardiol. 2013;62(12):1073-1074.
生物标志物及应用 情 况 推荐类 别 证据水 平
利钠肽
HF的诊断或排除
HF的预后
达到GDMT目标
非卧床，急性
非卧床，急性
非卧床
I
I
IIa
A
A
B
指导急性失代偿性HF治疗
心肌损伤标志物 附加危险分层 心肌纤维化标志物 附加危险分层
急性
急性，非卧床 非卧床 急性
IIb
I IIb IIb
C
A B A
GDMT, Guideline-Directed Medical Therapy; 指南导向药物治疗 2013 ACCF/AHA Guideline for the Management of Heart Failure. E-Published on June 5, 2013, available at: [http://content.onlinejacc.org/article.aspx?doi=10.1016/j.jacc.2013.05.019 a
利水消肿
葶苈子、泽泻、香加皮
络息成积
心室重构、心脏扩大
强心、利尿、扩血管 缓解心慌气短、 不能平卧、尿少水肿症状
标
兼治
本
抑制RASS与交感神经 减少心室重构
与RASS、交感神经系统激活导致心室重构为慢性心衰病机新概念相吻合
[Cellular Immunology 2009, 260:52-55] Results
Tang WH, Huang Y. Cardiotonic Modulation in Heart Failure: Insights from Traditional Chinese Medicine. J Am Coll Cardiol. 2013;62(12):1073-1074.
Editorial Comment （述评）
•
• • • • • •
临床研究证据级别：由高到低
1. 随机对照研究
2. 前瞻性非随机对照研究
3. 回顾性对照研究 4. 非对照研究或历史对照研究 5. 荟萃分析 6. 病例报道
7. 评论，教授或其他专家意见
Professor Joseph S. Alpert Editor-in-Chief, American Journal of Medicine 2013.7.19 Nanjing
中国心力衰竭诊断和治疗指南 2014
（中华心血管病杂志 2014(42):2） 对芪苈强心临床试验结果进行了描述（参考文献58）
Our work:（我们的研究）
Project1: Working model : AMI remodelingQiliqiangxin attenuates Traditional Chinese Medication cardiac remodeling after acute myocardial infarction in mice
芪苈强心抑制心室重构抗心力衰竭 基础与临床研究证据
南京医科大学第一附属医院心内科
李新立教授
CAD Hyp CM Valv
Arrhythmias LVD Remodeling Low EF Death
Pump Failure
Non Cardiac Factors
Symptoms
CHF
Ventricular Remodeling after Infarction and in Diastolic and Systolic Heart Failure
临床研究简介
Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R. A Multicenter, Randomized, Double-Hale Waihona Puke Baidulind, Parallel-Group, Placebo-Controlled Study of the Effects of Qili Qiangxin Capsules in Patients With Chronic Heart Failure. J Am Coll Cardiol. 2013;62(12):1065-1072.
BNP/NT-proBNP可用于指导 心衰的治疗
• 心衰患者治疗后BNP/NT-proBNP与基线相比下降 达到或超过30%，表明治疗奏效 • 如未下降或下降未达标甚至继续走高，则表明治 疗效果不佳，应继续增强治疗的力度。
中国心力衰竭诊断和治疗指南2014
中华心血管病杂志 2014(42):2
2013 ACCF/AHA HF Guideline 生物 标志物测定建议
-by Tang WHW, Huang Y
• It is conceivable that in the future if qili qiangxin proves to provide morbidity and mortality benefits in rigorous clinical trials, it will fundamentally challenge the existing foundation of scientific inquiry based upon the precise understanding of pharmacodynamics of drug therapies.
Conclusion: Qiliqiangxin improves cardiac function of rats with MI through regulation the balance between TNF-a and IL-10.
[J Cardiovasc Pharmacol, 2012, 59(3): 268-280]
2.The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors.
[American journal of hypertension, 2012, 25, 250-260] QL:0.6mg/kg/day for 4 weeks for mice
Conclusion: 1.QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload.
day MI 0 7 14 Sacrifice 21
QL
21 d
Unpublished data
Results
Saline + sham Saline + MI QL + MI QL + Sham
Unpublished data
Border
Saline + MI Infarct
Remote Remote
The effect of Qiliqiangxin on the echocardiographic and hemodynamic parameters in the infarcted hearts.
4 g/kg/day for 4 weeks for Rats
The ratio of TNF-a/IL-10 in infarcted myocardial tissue was reversed by Qiliqiangxin.
Jessup M, Brozena S. N Engl J Med. 2003;348:2007-18.
脉络学说指导 慢性心衰病机、有效组方及作用研究
“气分”（神经体液调节异常）
气阳虚乏
益气温阳
“血分” 脉络瘀阻
活血通络
丹参、红花
黄芪、附子、人参、桂枝
尿少水肿
“水分”
（钠水滁留）
（血流动力学异常）
Conclusion:
1. QLQX improves both systolic and diastolic cardiac function in SHRs. 2. QLQX downregulate the cardiac chymase signaling pathway and chymase-mediated ang II production.
Study Design
NT-proBNP的水平变化及下降超过 30%的比例
两组NYHA心功能分级描述和比较
LVEF、LVED、6MWD基线与第12 周随访变化趋势
明尼苏达生活质量量表评分变化趋势
心血管复合事件
药物不良事件
EDITORIAL COMMENT
— CARDIOTONIC MODULATION IN HEART FAILURE: INSIGHTS FROM TRADITIONAL CHINESE MEDICINE — 让衰竭的心脏更加强劲-中国传统医学给我们的启示
• 现如今，这项富有前景的研究表明李及他的研究同事们已经打开了一扇 如何利用最新科技研究传统中药活性成分在心力衰竭治疗中协同作用的
大门。这是一个挑战，对此我们应该热烈拥抱。
Tang WH, Huang Y. Cardiotonic Modulation in Heart Failure: Insights from Traditional Chinese Medicine. J Am Coll Cardiol. 2013;62(12):1073-1074.
Jessup et al. N Engl J Med 2003;348:2007-2018
Neurohormonal model of HF
McMurray J, Pfeffer MA.Circulation. 2002;105:2099-106.
Primary targets of treatment in HF
临床试验注册
Li X, Zhang J, Huang J, Ma A, Yang J, Li W, Wu Z, Yao C, Zhang Y, Yao W, Zhang B, Gao R. A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of the Effects of Qili Qiangxin Capsules in Patients With Chronic Heart Failure. J Am Coll Cardiol. 2013;62(12):1065-1072.
Border
Border
QL+ MI Infarct