顽固性心绞痛是指存在客观的心肌缺血的依据，心绞痛症状严重，最大限度内科治疗无效，不适合介入或手术治疗，或多次治疗无效的心绞痛。由于人类寿命的延长，这部分患者越来越多，这对心绞痛的治疗提出了新的要求。目前对顽固性心绞痛的治疗包括非常规药物治疗、治疗性血管再生、经皮激光血运重建术、脊髓刺激、增强型体外反搏，心脏冲击波疗法及经皮心肌冷冻疗法等，新的治疗方法也在不断探索中。

Refractory angina pectoris is an angina, with an objective evidence of myocardial ischemia and persistence of symptoms despite optimal medical therapy, life style modification treatments, and revascularization therapies. With the increase in life expectancy, more and more patients with angina pectoris refractory requires a new antianginal therapeutics. Currently, there were the non-conventional therapies to treat the refractory angina pectoris,which include pharmacotherapy, therapeutic angiogenesis, percutaneous myocardial laser revascularisation, spinal cord stimulation, enhanced external counterpulsation. Recently,some novel strategies such as cardiac shock wave therapy and percutaneous myocardial cryotherapy are also trying to treat the refractory angina pectoris.

［1］American Stroke Association American Heart Association: Heart disease and stroke statistics—2005 Update［EB/OL］［2008-10-08］. http://www.americanheart.org/downloadable/heart/1105390918119HD SStats2005Update.pdf.
［2］Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)［J］. Circulation, 2007,116(7):803-877.
［3］马涛, 曹国扬, 欧阳泽伟. 小剂量尿激酶加合心爽治疗顽固性心绞痛疗效分析［J］. 医学临床研究 2007, 24(11): 1973-1974.
MA Tao, CAO Guoyang, OUYANG Zewei. Therapeutic effect of refractory angina using low-dose urokinase with diltiazem［DB/OL］. Journal of Clinical Research, 2007,24(11):1973-1974.
［4］Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina［DB/OL］. Cochrane Database Syst Rev, 2005, 19(4):CD003614.
［5］Grabczewska Z, Biaoszyński T, Szymański P, et al. The effect of trimetazidine added to maximal anti-ischemic therapy in patients with advanced coronary artery disease［J］. Cardiol J, 2008,15(4):344-350.
［6］Chaitman B. Late breaking trial results: the CARISA trial. Presented at the American Heart Association Scientific Sessions［C］. Anaheim:［s.n.］, 2001.
［7］Venkataraman R, Belardinelli L, Blackburn B, et al. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images［J］. JACC Cardiovasc Imaging, 2009, 2(11):1301-1309. 
［8］Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial［J］. Lancet, 2008, 372(9641):807-816.
［9］Kster R, Kaehler J, Meinertz T.Treatment of stable angina pectoris by ivabradine in every day practice: the REDUCTION study［J］. Am Heart J, 2009,158(4):e51-57.
［10］Ripa C, Germano G, Caparra A. Ivabradine use in refractory unstable angina: a case report［J］. Int J Immunopathol Pharmacol, 2009, 22(3): 849-52.
［11］The IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact of Nicorandil in Angina (IONA) randomized trial［J］. Lancet, 2002,359(9314):1269-1275.
［12］Lee KH, Kim SH, Lim HE, et al. Effectiveness of intravenous administration of nicorandil in a patient with variant angina refractory to continuous intravenous nitroglycerin［J］. Int J Cardilol, 2007,120(1):e9-12.
［13］Hendel RC, Henry TD, Rocha-Singh K, et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose-dependent effect［J］. Circulation, 2000,101(2):118-121.
［14］Clletti FL, Waugh JM, Amabile PG, et al. Vascular endothelial growth factor enhances atherosclerotic plaque progression［J］. Nat Med, 2001, 7(4):425-429.
［15］Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis［J］. Circulation, 2003, 107(10):1359-65.
［16］Simons M, Annex B H, Laham R J, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial［J］. Circulation, 2002,105(7):788-793.
［17］Henry TD, Grines CL,Watkins MW, et al. Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials［J］. J Am Coll Cardiol, 2007, 50(11):1038-1046.
［18］Beeres SL, Bax JJ, Dibbets P, et al. Effect of intramyocardial injection of autologous bone marrow-derived mononuclear cells on perfusion, function, and viability in patients with drug-refractory chronic ischemia［J］. J Nucl Med, 2006, 47(4):574-580.
［19］Beeres SL, Bax JJ, Dibbets-Schneider P, et al. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia: twelve-month follow-up results［J］. Am Heart J, 2006, 152(4):684.e11-6.
［20］Beeres SL, Lamb HJ, Roes SD, et al. Effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia［J］. J Magn Reson Imaging, 2008, 27(5):992-997.
［21］Losordo DW, Schatz RA, White CJ, et al. Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial［J］. Circulation, 2007, 115(25):3165-3172.
［22］Kovacic JC, Macdonald P, Feneley MP, et al. Safety and efficacy of consecutive cycles of granulocyte-colony stimulating factor, and an intracoronary CD133+ cell infusion in patients with chronic refractory ischemic heart disease: the G-CSF in angina patients with IHD to stimulate neovascularization (GAIN I) trial［J］. Am Heart J, 2008, 156(5):954-963.
［23］Wehberg KE, Answini G, Wood D, et al. Intramyocardial injection of autologous platelet-rich plasma combined with transmyocardial revascularization［J］. Cell Transplant, 2009,18(3):353-359.
［24］Oesterle SN, Sanborn TA, Ali N, et al. Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomized trial. Potential Class Improvement From Intramyocardial Channels［J］. Lancet, 2000, 356(9243): 1705-1710.
［25］Akay MH, Cheong BY, Frazier OH. Use of magnetic resonance imaging to assess myocardial perfusion after transmyocardial laser revascularization［J］. Heart Surg Forum, 2009, 12(4):e199-201.
［26］Briones E, Lacalle JR, Marin I. Transmyocardial laser revascularization versus medical therapy for refractory angina［DB/OL］. Cochrane Database Syst Rev, 2009, (1):CD003712.(Review)
［27］Yoshida K, Inoue T, Hirakawa N, et al. Endoscopic thoracic sympathectomy as a novel strategy for vasospastic angina refractory to medical treatments［J］. J Cardiol, 2008,52(1):49-52.
［28］Fricke E, Eckert S, Dongas A. Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina［J］. Nuklearmedizin,2009,48(3):104-109.
［29］Anselmino M, Ravera L, De Luca A, et al, Spinal cord stimulation and 30-minute heart rate variability in refractory angina patients［J］. Pacing Clin Electrophysiol, 2009,32(1):37-42.
［30］Taylor RS, De Vries J, Buchser E, et al. Spinal cord stimulation in the treatment of refractory angina: systematic review and meta-analysis of randomised controlled trials［J］. BMC Cardiovasc Disorders, 2009,9:13.
［31］McNab D, Khan SN, Sharples LD, et al. An open label, single-centre, randomized trial of spinal cord stimulation vs percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial［J］. Eur Heart J, 2006, 27(9):1048-1053.
［32］Dyer MT, Goldsmith K, Khan S, et al. Clinical and cost-effectiveness analysis of an open label, single-centre, randomised trial of spinal cord stimulation (SCS) versus percutaneous myocardial laser revascularisation (PMR) in patients with refractory angina pectoris: The SPiRiT trial［J］. Trials, 2008, 30(9):40.
［33］Luo JY, Wu GF, Xiong Y, et al. Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia［J］. Chin Med J (Engl), 2009,122(10):1188-1194.
［34］Arora RR, Chou TM, Jain D et al. The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes［J］. J Am Coll Cardiol, 1999, 33(7):1833-1840.
［35］Arora RR, Chou TM, Jain D, et al. Effects of enhanced external counterpulsation on health-related quality of life continue 12 months after treatment: a substudy of the multicenter study of enhanced external counterpulsation［J］. J Investig Med, 2002, 50(1):25-32.
［36］Hashemi M, Hoseinbalam M, Khazaei M. Long-term effect of enhanced external counterpulsation on endothelial function in the patients with intractable angina［J］. Heart Lung Circ, 2008,17(5):383-387.
［37］Kumar A, Aronow WS, Vadnerkar A, et al. Effect of enhanced external counterpulsation on clinical symptoms, quality of life, 6-minute walking distance, and echocardiographic measurements of left ventricular systolic and diastolic function after 35 days of treatment and at 1-year follow up in 47 patients with chronic refractory angina pectoris［J］. Am J Ther, 2009,16(2):116-118.
［38］Campbell AR, Satran D, Zenovich AG, et al. Enhanced external counterpulsation improves systolic blood pressure in patients with refractory angina［J］. Am Heart J, 2008,156(6):1217-1222.
［39］Bondesson S, Pettersson T, Erdling A, et al. Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris［J］. Coron Artery Dis, 2008,19(8):627-634.
［40］Khattab AA, Brodersen B, Schuermann-Kuchenbrandt D, et al. Extracorporeal cardiac shock wave therapy: first experience in the everyday practice for treatment of chronic refractory angina pectoris［J］. Int J Cardiol, 2007, 121(1):84-85.
［41］Prinz C, Lindner O, Bitter T, et al. Extracorporeal cardiac shock wave therapy ameliorates clinical symptoms and improves regional myocardial blood flow in a patient with severe coronary artery disease and refractory angina［J］. Case Report Med, 2009,2009:639594.
［42］Gallo R, Fefer P, Freeman M, et al. A first-in-man study of percutaneous myocardial cryotreatment in nonrevascularizable patients with refractory angina［J］. Catheter Cardiovasc Interv, 2009,74(3):387-394