钙增敏剂
左西孟旦，是一种新钙增敏剂，可增加心肌收缩力，且不会引起心肌耗氧量增加。其在急性、失代偿性心力衰竭中的作用比慢性心力衰竭更为明显，可能会降低死亡率与住院时间。[168]Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med. 2012;40:634-646.http://www.ncbi.nlm.nih.gov/pubmed/21963578?tool=bestpractice.comLIDO研究（严重低输出量心力衰竭静脉输注左西孟旦与多巴酚丁胺比较）显示，对于严重低输出量心力衰竭患者，左西孟旦在改善生存率和血液动力学方面比多巴酚丁胺更为有效。[169]Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet. 2002;360:196-202.http://www.ncbi.nlm.nih.gov/pubmed/12133653?tool=bestpractice.com左西孟旦与多巴酚丁胺比较在改善中心血液动力学指标和改善左心室功能方面具有优势，可能部分与其抗炎和抗凋亡作用有关。[170]Adamopoulos S, Parissis JT, Iliodromitis EK, et al. Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am J Cardiol. 2006;98:102-106.http://www.ncbi.nlm.nih.gov/pubmed/16784930?tool=bestpractice.com
奈比洛尔
在SENIORS研究（奈必洛尔干预对老年心力衰竭患者的结果和再入院的疗效研究）中发现，奈必洛尔，作为一种心脏选择性的β受体阻滞剂，并具有一氧化氮介导的血管舒张作用，对70岁或以上心力衰竭患者有效且耐受性很好。[171]Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005;26:215-225.http://www.ncbi.nlm.nih.gov/pubmed/15642700?tool=bestpractice.com目前数据显示，开始使用中等剂量的奈必洛尔不会产生像其他β受体阻滞剂使用在心力衰竭患者身上时经常出现的血液动力方面的不良反应；因此，很长的剂量滴定周期对奈比洛尔来说也许是没有必要的。[172]Triposkiadis F, Giamouzis G, Kelepeshis G, et al. Acute hemodynamic effects of moderate doses of nebivolol versus metoprolol in patients with systolic heart failure. Int J Clin Pharmacol Ther. 2007;45:71-77.http://www.ncbi.nlm.nih.gov/pubmed/17323786?tool=bestpractice.com
n-3多不饱和脂肪酸（n3-PUFA）
GISSI-HF研究显示，他汀类药物治疗基础上添加n-3多不饱和脂肪酸小幅度降低心力衰竭患者死亡率和入院治疗率。[173]Tavazzi L, Maggioni AP, Marchioli R, et al; Gissi-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1223-1230.http://www.ncbi.nlm.nih.gov/pubmed/18757090?tool=bestpractice.com 然而，一项2012年的 meta 分析显示，对有心血管疾病史的患者，ω-3脂肪酸补充剂对所有心血管事件的二级预防证据不充分。[174]Kwak SM, Myung SK, Lee YJ, et al. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172:686-694.http://www.ncbi.nlm.nih.gov/pubmed/22493407?tool=bestpractice.com除非有禁忌，否则 ω-3 多不饱和脂肪酸 (PUFA) 补充剂作为 NYHA II-IV 级心力衰竭患者的辅助治疗以降低死亡率和减少心血管疾病住院治疗是合理的。
他汀类药物
仅用于治疗心力衰竭且无其他适应证时，他汀类药物作为辅助治疗并不获益。[84]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147-e239.http://content.onlinejacc.org/article.aspx?articleID=1695825http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com他汀类药物广泛用于不良心血管事件的预防中，包括新发心力衰竭。该药物最初用于降低心血管疾病患者的胆固醇水平，目前在炎症、氧化应激和血管机能方面的有益效果也为人所熟知。迄今为止，还没有足够的临床证据支持他汀类药物作为改善心力衰竭临床结果的主要药物。[84]Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147-e239.http://content.onlinejacc.org/article.aspx?articleID=1695825http://www.ncbi.nlm.nih.gov/pubmed/23747642?tool=bestpractice.com
非特异性免疫调节疗法
炎症介质被认为在心力衰竭的发展过程中发挥作用。在ACCLAIM试验中，非特异性免疫调节疗法降低了住院治疗或死亡的风险，提示该疗法可能对心力衰竭患者有益。[175]Torre-Amione G, Anker SD, Bourge RC, et al. Results of a non-specific immunomodulation therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial. Lancet. 2008;371:228-236.http://www.ncbi.nlm.nih.gov/pubmed/18207018?tool=bestpractice.com
重组人类生长激素
初步研究显示重组人类生长激素可能对左心室功能不全患者产生获益，不过它也可能会增加心律失常的风险[176]Tritos NA, Danias PG. Growth hormone therapy in congestive heart failure due
to left ventricular systolic dysfunction: a meta-analysis. Endocr Pract. 2008;14:40-49.http://www.ncbi.nlm.nih.gov/pubmed/18238740?tool=bestpractice.com[177]Le Corvoisier P, Hittinger L, Chanson P, et al. Cardiac effects of growth hormone treatment in chronic heart failure: A meta-analysis. J Clin Endocrinol Metab. 2007;9:180-185.http://www.ncbi.nlm.nih.gov/pubmed/17062772?tool=bestpractice.com需要进一步研究以决定该疗法的安全性和疗效。
曲美他嗪
在 meta 分析中，曲美他嗪，能将能量产生从脂肪酸氧化转化为葡萄糖氧化，分析显示其对死亡率没有影响，但会提高左室射血分数(LVEF)和心功能分级。[178]Zhang L, Lu Y, Jiang H, et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J Am Coll Cardiol. 2012;59:913-922.http://www.ncbi.nlm.nih.gov/pubmed/22381427?tool=bestpractice.com
干细胞疗法
在心肌缺血性和非心肌缺血性心力衰竭中进行的干细胞疗法试验显示出一些潜在获益。[179]Sánchez LA, Guerrero-Beltrán CE, Cordero-Reyes AM, et al. Use of stem cells in heart failure treatment: where we stand and where we are going. Methodist Debakey Cardiovasc J. 2013;9:195-200.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846072/http://www.ncbi.nlm.nih.gov/pubmed/24298309?tool=bestpractice.com系统性评价干细胞疗法在慢性缺血性心脏病和充血性心力衰竭中的使用，显示在长期的随访中（＞12个月）使用自体骨髓肝细胞治疗降低了心力衰竭所致的死亡率和再入院率，尽管证据的可信度较低。[180]Fisher SA, Brunskill SJ, Doree C, et al. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst Rev. 2014;(4):CD007888.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007888.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24777540?tool=bestpractice.com从短期来看（＜12个月），该疗法在对死亡率方面无明显影响。[180]Fisher SA, Brunskill SJ, Doree C, et al. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure. Cochrane Database Syst Rev. 2014;(4):CD007888.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007888.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24777540?tool=bestpractice.com
基因治疗
一个颇具吸引力的心力衰竭治疗策略是基因治疗。[181]Tilemann L, Ishikawa K, Weber T, et al. Gene therapy for heart failure. Circ Res. 2012;110:777-793.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594844/http://www.ncbi.nlm.nih.gov/pubmed/22383712?tool=bestpractice.com在一项针对 LVEF＜40% 的心力衰竭患者 (n=56) 的小型随机研究中，冠状动脉内给予编码腺苷酸环化酶 6 的 5 型腺病毒 (Ad5.hAC6)，在治疗 4 周时提高了 LVEF，未增加锻炼时间。[182]Hammond HK, Penny WF, Traverse JH, et al. Intracoronary gene transfer of adenylyl cyclase 6 in patients with heart failure: a randomized clinical trial. JAMA Cardiol. 2016;1:163-171.http://jamanetwork.com/journals/jamacardiology/fullarticle/2506673http://www.ncbi.nlm.nih.gov/pubmed/27437887?tool=bestpractice.com在一项规模更大的双盲安慰剂对照研究 (n=250) 中，冠状动脉内输注十万亿（1 乘 10 的 13 次方）个腺病毒伴随病毒 1 (AAV1)/肌浆内质网 Ca2-ATPase (SERCA2a) 的耐脱氧核糖核酸酶颗粒并未改善射血分数降低 (EF≤35%) 的心力衰竭患者的临床病程。[183]Greenberg B, Butler J, Felker GM, et al. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016;387:1178-1186.http://www.ncbi.nlm.nih.gov/pubmed/26803443?tool=bestpractice.com
支持性机械辅助装置
在终末期心力衰竭中使用机械辅助装置是一个研究的热点领域。经报道，在严重心力衰竭患者中，通过使用心室辅助装置延长心肌舒张对各个阶段的少数心力衰竭患者产生了心肌恢复。对于预期可从重大心脏损害中恢复过来的患者（例如心肌缺血，心脏开胸术后休克，或暴发性心肌炎），体外装置可用于支持患者的短期循环。左心室辅助装置提供同样程度的血液动力学支持；其中许多是可植入设备，因此允许用于长期循环支持，患者可走动和出院。[184]Goldstein DJ, Oz MC, Rose EA. Implantable left ventricular assist devices. N Engl J Med. 1998;339:1522-1533.http://www.ncbi.nlm.nih.gov/pubmed/9819452?tool=bestpractice.com这些设备的大部分临床经验源自其在“搭桥移植术”中的使用。[184]Goldstein DJ, Oz MC, Rose EA. Implantable left ventricular assist devices. N Engl J Med. 1998;339:1522-1533.http://www.ncbi.nlm.nih.gov/pubmed/9819452?tool=bestpractice.com[185]DeRose JJ, Argenziano M, Sun BC, et al. Implantable left ventricular assist devices: an evolving long-term cardiac replacement therapy. Ann Surg. 1997;226:461-470.http://www.ncbi.nlm.nih.gov/pubmed/9351714?tool=bestpractice.com[186]DeRose JJ, Jr., Umana JP, Argenziano M, et al. Implantable left ventricular assist devices provide an excellent outpatient bridge to transplantation and recovery. J Am Coll Cardiol. 1997;30:1773-1777.http://www.ncbi.nlm.nih.gov/pubmed/9385906?tool=bestpractice.com[187]Oz MC, Argenziano M, Catanese KA, et al. Bridge experience with long-term implantable left ventricular assist devices. Are they an alternative to transplantation? Circulation. 1997;95:1844-1852.http://www.ncbi.nlm.nih.gov/pubmed/9107172?tool=bestpractice.com[188]Mann DL, Willerson JT. Left ventricular assist devices and the failing heart: a bridge to recovery, a permanent assist device, or a bridge too far? Circulation. 1998;98:2367-2369.http://www.ncbi.nlm.nih.gov/pubmed/9832479?tool=bestpractice.com[189]Helman DN, Addonizio LJ, Morales DL, et al. Implantable left ventricular assist devices can successfully bridge adolescent patients to transplant. J Heart Lung Transplant. 2000;19:121-126.http://www.ncbi.nlm.nih.gov/pubmed/10703686?tool=bestpractice.com[190]Yacoub MH. A novel strategy to maximize the efficacy of left ventricular assist devices as a bridge to recovery. Eur Heart J. 2001;22:534-540.http://www.ncbi.nlm.nih.gov/pubmed/11259141?tool=bestpractice.com[191]Stevenson LW, Rose EA. Left ventricular assist devices: bridges to transplantation, recovery, and destination for whom? Circulation. 2003;108:3059-3063.http://www.ncbi.nlm.nih.gov/pubmed/14691019?tool=bestpractice.com[192]Vitali E, Lanfranconi M, Bruschi G, et al. Left ventricular assist devices as bridge to heart transplantation: the Niguarda Experience. J Card Surg. 2003;18:107-113.http://www.ncbi.nlm.nih.gov/pubmed/12757336?tool=bestpractice.com[193]Topkara VK, Dang NC, Martens TP, et al. Bridging to transplantation with left ventricular assist devices: outcomes in patients aged 60 years and older. J Thorac Cardiovasc Surg. 2005;130:881-882.http://www.ncbi.nlm.nih.gov/pubmed/16153945?tool=bestpractice.com[194]Zimpfer D, Zrunek P, Roethy W, et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc. Surg. 2007;133:689-695.http://www.ncbi.nlm.nih.gov/pubmed/17320566?tool=bestpractice.comREMATCH 试验确定了器械治疗的疗效，将该治疗作为特定不符合移植条件患者的永久性或“终点”治疗。[195]Rose EA, Moskowitz AJ, Packer M, et al. The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg. 1999;67:723-730.http://www.ncbi.nlm.nih.gov/pubmed/10215217?tool=bestpractice.com然而，与机械辅助治疗相关的不良反应也有很多，包括出血、感染、血栓栓塞反应和设备故障。[196]Goldstein DJ, Beauford RB. Left ventricular assist devices and bleeding: adding insult to injury. Ann Thorac Surg. 2003;75:S42-S47.http://www.ncbi.nlm.nih.gov/pubmed/12820734?tool=bestpractice.com[197]Gordon SM, Schmitt SK, Jacobs M, et al. Nosocomial bloodstream infections in patients with implantable left ventricular assist devices. Ann Thorac Surg. 2001;72:725-730.http://www.ncbi.nlm.nih.gov/pubmed/11565648?tool=bestpractice.com[198]Rothenburger M, Schmid C, Huelksen G, et al. Thrombolytic therapy due to thrombus formation associated with left ventricular assist devices. J Heart Lung Transplant. 2005;24:2305.http://www.ncbi.nlm.nih.gov/pubmed/16364888?tool=bestpractice.com在美国，美国食品药品监督管理局已就左心室辅助设备相关的严重不良事件发出警告。这些不良事件包括泵血栓发生率（泵中的血块）升高和较高的卒中发生率。新一代设备的改良将有望进一步延长生存期。目前，机械辅助疗法可能对预期1年生存时间少于50%的患者获益，例如不符合心脏移植，需持续静脉注射正性肌力药。一些报道显示，对衰竭心脏的长时间机械减压，可能偶尔会获得心肌功能的充分恢复，从而使得设备移出。[199]Helman DN, Maybaum SW, Morales DL, et al. Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable? Ann Thorac Surg. 2000;70:1255-1258.http://www.ncbi.nlm.nih.gov/pubmed/11081881?tool=bestpractice.com[200]Birks EJ, Tansley PD, Hardy J, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006;355:1873-1884.http://www.ncbi.nlm.nih.gov/pubmed/17079761?tool=bestpractice.com持续性血液动力监控指导治疗已有研究观察，但要进一步评估。[201]Bourge RC, Abraham WT, Adamson PB, et al. Randomized controlled trial of an
implantable continuous hemodynamic monitor in patients with advanced heart
failure: the COMPASS-HF study. J Am Coll Cardiol. 2008;51:1073-1079.http://www.ncbi.nlm.nih.gov/pubmed/18342224?tool=bestpractice.com[202]Adamson PB, Gold MR, Bennett T, et al. Continuous hemodynamic monitoring in patients with mild to moderate heart failure: results of The Reducing Decompensation Events Utilizing Intracardiac Pressures in Patients With Chronic Heart Failure (REDUCEhf) trial. Congest Heart Fail. 2011;17:248-254.http://onlinelibrary.wiley.com/doi/10.1111/j.1751-7133.2011.00247.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21906250?tool=bestpractice.com
手术策略
已经有许多关于替代性外科手术方法治疗终末期心力衰竭的报告。[203]Klein P, Bax JJ, Shaw LJ, et al. Early and late outcome of left ventricular reconstruction surgery in ischemic heart disease. Eur J Cardiothorac Surg. 2008;34:1149-1157.http://www.ncbi.nlm.nih.gov/pubmed/18760619?tool=bestpractice.com二尖瓣修复术或置换术已经显示可改善继发于左心室扩张的重度二尖瓣反流患者的临床状态。[204]Bolling SF, Pagani FD, Deeb GM, et al. Intermediate-term outcome of mitral reconstruction in cardiomyopathy. J Thorac Cardiovasc Surg. 1998;115:381-388.http://www.ncbi.nlm.nih.gov/pubmed/9475533?tool=bestpractice.com然而，无对照研究来评估该手术对心室功能、再住院治疗和生存率上的效果。一项单中心研究设计评估二尖瓣瓣膜成形术对二尖瓣反流和左心室收缩功能障碍患者死亡率的影响，未显示明确的生存获益。[205]Wu AH, Aaronson KD, Bolling SF, et al. Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol. 2005;45:381-387.http://www.ncbi.nlm.nih.gov/pubmed/15680716?tool=bestpractice.com动脉瘤切除术的一个变体目前发展用于缺血性心脏病患者的治疗，但其在心力衰竭治疗上的作用仍需确定。[206]Athanasuleas CL, Stanley AW, Jr., Buckberg GD, et al. Surgical anterior ventricular endocardial restoration (SAVER) in the dilated remodeled ventricle after anterior myocardial infarction. RESTORE group. Reconstructive Endoventricular Surgery, returning Torsion Original Radius Elliptical Shape to the LV. J Am Coll Cardiol. 2001;37:1199-1209.http://www.ncbi.nlm.nih.gov/pubmed/11807740?tool=bestpractice.com对严重的血液动力学代偿的患者目前没有相应的手术重建技术提供“补救治疗”。
