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Refractory Angina

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Coronary Heart Disease

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Abstract

A growing number of patients have refractory angina – but limited therapeutic options. Revascularization, medical therapy, and risk factor modification have improved notably, but these patients are left with severe limitations in their quality of life. As described in this chapter, an increasing number of pharmacologic and nonpharmacologic approaches for “no-option patients” are making quality-of-life inroads for this challenging patient population.

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References

  1. Jolicoeur EM, Granger CB, Henry TD, et al. Clinical and research issues regarding chronic advanced coronary artery disease: part I: contemporary and emerging therapies. Am Heart J. 2008;155(3):418–34.

    Article  PubMed  Google Scholar 

  2. Jolicoeur EM, Ohman EM, Temple R, et al. Clinical and research issues regarding chronic advanced coronary artery disease part II: trial design, outcomes, and regulatory issues. Am Heart J. 2008;155(3):435–44.

    Article  PubMed  Google Scholar 

  3. Mannheimer C, Camici P, Chester MR, et al. The problem of chronic refractory angina; report from the ESC joint study group on the treatment of refractory angina. Eur Heart J. 2002;23(5):355–70.

    Article  PubMed  CAS  Google Scholar 

  4. Gibbons RJ, Abrams J, Chatterjee K, et al. American College of Cardiology. American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). ACC/AHA 2002 guideline update for the management of patients with chronic stable angina – summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 2003;41(1):159–68.

    Article  PubMed  Google Scholar 

  5. Mukherjee D, Bhatt DL, Roe MT, Patel V, Ellis SG. Direct myocardial revascularization and angiogenesis – how many patients might be eligible? Am J Cardiol. 1999;84(5):598–600.

    Article  PubMed  CAS  Google Scholar 

  6. Williams B, Menon M, Satran D, et al. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv. 2010;75(6):886–91.

    PubMed  Google Scholar 

  7. Mukherjee D, Comella K, Bhatt DL, Roe MT, Patel V, Ellis SG. Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization. Am Heart J. 2001;142(1):72–4.

    Article  PubMed  CAS  Google Scholar 

  8. Kandzari DE, Lam LC, Eisenstein EL, et al. Advanced coronary artery disease: appropriate end points for trials of novel therapies. Am Heart J. 2001;142(5):843–51.

    Article  PubMed  CAS  Google Scholar 

  9. Allen KB, Dowling RD, Fudge TL, et al. Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina. N Engl J Med. 1999;341(14):1029–36.

    Article  PubMed  CAS  Google Scholar 

  10. Burkhoff D, Schmidt S, Schulman SP, et al. Transmyocardial laser revascularization compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomized trial. ATLANTIC investigators. Angina treatments – lasers and normal therapies in comparison. Lancet. 1999;354(9182):885–90.

    Article  PubMed  CAS  Google Scholar 

  11. Frazier OH, March RJ, Horvath KA. Transmyocardial revascularization with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med. 1999;341(14):1021–8.

    Article  PubMed  CAS  Google Scholar 

  12. Oesterle SN, Sanborn TA, Ali N, et al. Percutaneous transmyocardial laser revascularization for severe angina: the PACIFIC randomised trial. Potential class improvement from intramyocardial channels. Lancet. 2000;356(9243):1705–10.

    Article  PubMed  CAS  Google Scholar 

  13. Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation. 2003;107(10):1359–65.

    Article  PubMed  CAS  Google Scholar 

  14. Kastrup J, Jorgensen E, Ruck A, et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris. A randomized double-blind placebo-controlled study: the Euroinject One Trial. J Am Coll Cardiol. 2005;45(7):982–8.

    Article  PubMed  CAS  Google Scholar 

  15. Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: double-blind, randomized, controlled clinical trial. Circulation. 2002;105(7):788–93.

    Article  PubMed  CAS  Google Scholar 

  16. Stewart DJ, Hilton JD, Arnold JM, et al. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006;13(21):1503–11.

    Article  PubMed  CAS  Google Scholar 

  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 Am Coll Cardiol. 2007;50(11):1038–46.

    Article  PubMed  CAS  Google Scholar 

  18. Henry TD, Satran D, Campbell AR, et al. Long-term mortality in patients with refractory angina. J Am Coll Cardiol. 2008;51:A227.

    Google Scholar 

  19. Bache RJ, Dymek DJ. Local and regional regulation of coronary vascular tone. Prog Cardiovasc Dis. 1981;24(3):191–212.

    Article  PubMed  CAS  Google Scholar 

  20. Lanza GA, Crea F. Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation. 2010;121(21):2317–25.

    Article  PubMed  Google Scholar 

  21. Michaels AD, McCullough PA, Soran OZ, et al. Primer: practical approach to the selection of patients for and application of EECP. Nat Clin Pract Cardiovasc Med. 2006;3(11):623–32.

    Article  PubMed  Google Scholar 

  22. Baim DS, Grossman W. Grossman’s cardiac catheterization, angiography, and intervention. 7th ed. Philadelphia: Lippincott, Williams & Wilkins; 2006.

    Google Scholar 

  23. Khan SN, Dutka DP. A systematic approach to refractory angina. Curr Opin Support Palliat Care. 2008;2(4):247–51.

    Article  PubMed  Google Scholar 

  24. Cesar LA, Gowdak LH, Mansur AP. The metabolic treatment of patients with coronary artery disease: effects on quality of life and effort angina. Curr Pharm Des. 2009;15(8):841–9.

    Article  PubMed  CAS  Google Scholar 

  25. Chazov EI, Lepakchin VK, Zharova EA, et al. Trimetazidine in angina combination therapy – the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study. Am J Ther. 2005;12(1):35–42.

    Article  PubMed  CAS  Google Scholar 

  26. Ashrafian H, Horowitz JD, Frenneaux MP. Perhexiline. Cardiovasc Drug Rev. 2007;25(1):76–97.

    Article  PubMed  CAS  Google Scholar 

  27. Killalea SM, Krum H. Systematic review of the efficacy and safety of perhexiline in the treatment of ischemic heart disease. Am J Cardiovasc Drugs. 2001;1(3):193–204.

    Article  PubMed  CAS  Google Scholar 

  28. Yang EH, Barsness GW. Evolving treatment strategies for chronic refractory angina. Expert Opin Pharmacother. 2006;7(3):259–66.

    Article  PubMed  CAS  Google Scholar 

  29. Ashcroft FM. ATP-sensitive potassium channelopathies: focus on insulin secretion. J Clin Invest. 2005;115(8):2047–58.

    Article  PubMed  CAS  Google Scholar 

  30. IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the impact of nicorandil in angina (IONA) randomised trial. Lancet. 2002;359(9314):1269–75.

    Article  Google Scholar 

  31. Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44(6):954–67.

    Article  PubMed  CAS  Google Scholar 

  32. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006;41(6):1031–8.

    Article  PubMed  CAS  Google Scholar 

  33. Takeo S, Tanonaka K, Shimizu K, Hirai K, Miyake K, Minematsu R. Beneficial effects of lidocaine and disopyramide on oxygen-deficiency-induced contractile failure and metabolic disturbance in isolated rabbit hearts. J Pharmacol Exp Ther. 1989;248(1):306–14.

    PubMed  CAS  Google Scholar 

  34. Noble D, Noble PJ. Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload. Heart. 2006;92 Suppl 4:1–5.

    Google Scholar 

  35. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375–82.

    Article  PubMed  CAS  Google Scholar 

  36. Chaitman BR, Pepine CJ, Parker JO, et al. Combination Assessment of Ranolazine In Stable Angina (CARISA) Investigators. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004;291(3):309–16.

    Article  PubMed  CAS  Google Scholar 

  37. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L. Erica I Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (efficacy of ranolazine in chronic angina) trial. J Am Coll Cardiol. 2006;48(3):566–75.

    Article  PubMed  CAS  Google Scholar 

  38. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297(16):1775–83.

    Article  PubMed  CAS  Google Scholar 

  39. Bennett NM, Arndt TL, Iyer V, et al. Ranolazine refractory angina registry trial: 1-year results [abstract]. J Am Coll Cardiol. 2011;57:E1050.

    Google Scholar 

  40. Egashira K, Hirooka Y, Kuga T, Mohri M, Takeshita A. Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary arteriograms. Circulation. 1996;94(2):130–4.

    Article  PubMed  CAS  Google Scholar 

  41. Lerman A, Burnett Jr JC, Higano ST, McKinley LJ, Holmes Jr DR. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation. 1998;97(21):2123–8.

    Article  PubMed  CAS  Google Scholar 

  42. Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol. 1997;80(3):331–3.

    Article  PubMed  CAS  Google Scholar 

  43. Sinvhal RM, Gowda RM, Khan IA. Enhanced external counterpulsation for refractory angina pectoris. Heart. 2003;89(8):830–3.

    Article  PubMed  CAS  Google Scholar 

  44. 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 Am Coll Cardiol. 1999;33(7):1833–40.

    Article  PubMed  CAS  Google Scholar 

  45. Feldman AM, Silver MA, Francis GS, et al. Enhanced external counterpulsation improves exercise tolerance in patients with chronic heart failure. J Am Coll Cardiol. 2006;48(6):1198–205.

    Article  PubMed  Google Scholar 

  46. Kersten JR, Pagel PS, Chilian WM, Warltier DC. Multifactorial basis for coronary collateralization: a complex adaptive response to ischemia. Cardiovasc Res. 1999;43(1):44–57.

    Article  PubMed  CAS  Google Scholar 

  47. Braith RW, Conti CR, Nichols WW, et al. Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study. Circulation. 2010;122(16):1612–20.

    Article  PubMed  Google Scholar 

  48. Bonetti PO, Barsness GW, Keelan PC, et al. Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll Cardiol. 2003;41(10):1761–8.

    Article  PubMed  Google Scholar 

  49. Michaels AD, Raisinghani A, Soran O, et al. The effects of enhanced external counterpulsation on myocardial perfusion in patients with stable angina: a multicenter radionuclide study. Am Heart J. 2005;150(5):1066–73.

    Article  PubMed  Google Scholar 

  50. Akhtar M, Wu GF, Du ZM, Zheng ZS, Michaels AD. Effect of external counterpulsation on plasma nitric oxide and endothelin-1 levels. Am J Cardiol. 2006;98(1):28–30.

    Article  PubMed  CAS  Google Scholar 

  51. Kiernan TJ, Boilson BA, Tesmer L, Harbuzariu A, Simari RD, Barsness GW. Effect of enhanced external counterpulsation on circulating CD34+ progenitor cell subsets. Int J Cardiol. 2010 Sep 13.

    Google Scholar 

  52. Campbell AR, Satran D, Zenovich AG, et al. Enhanced external counterpulsation improves systolic blood pressure in patients with refractory angina. Am Heart J. 2008;156(6):1217–22.

    Article  PubMed  Google Scholar 

  53. Norrsell H, Eliasson T, Mannheimer C, et al. Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover. Eur Heart J. 1997;18(12):1890–6.

    Article  PubMed  CAS  Google Scholar 

  54. Eliasson T, Mannheimer C, Waagstein F, et al. Myocardial turnover of endogenous opioids and calcitonin-gene-related peptide in the human heart and the effects of spinal cord simulation on pacing-induced angina pectoris. Cardiology. 1998;89(3):170–7.

    Article  PubMed  CAS  Google Scholar 

  55. Hautvast RW, DeJongste MJ, Horst GJ, Blanksma PK, Lie KI. Angina pectoris refractory for conventional therapy – is neurostimulation a possible alternative treatment? Clin Cardiol. 1996;19(7):531–5.

    Article  PubMed  CAS  Google Scholar 

  56. Hautvast RW, Blanksma PK, DeJongste MJ, et al. Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris. Am J Cardiol. 1996;77(7):462–7.

    Article  PubMed  CAS  Google Scholar 

  57. Mannheimer C, Eliasson T, Augustinsson LE, et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: The ESBY study. Circulation. 1998;97(12):1157–63.

    Article  PubMed  CAS  Google Scholar 

  58. Ekre O, Eliasson T, Norrsell H, Wahrborg P, Mannheimer C. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris. Long-term effects of spinal cord stimulation and coronary artery bypass grafting on quality of life and survival in the ESBY study. Eur Heart J. 2002;23(24):1938–45.

    Article  PubMed  CAS  Google Scholar 

  59. Zipes DP, Svorkdal N, Breman D, et al. Spinal cord simulation therapy for patients with refractory angina who are not candidates for revascularization. Eur Heart J. 2002;23:355–70.

    Article  Google Scholar 

  60. Heusch G, Baumgart D, Camici P, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101(6):689–94.

    Article  PubMed  CAS  Google Scholar 

  61. Tune JD, Richmond KN, Gorman MW, Feigl EO. Control of coronary blood flow during exercise. Exp Biol Med (Maywood). 2002;227(4):238–50.

    CAS  Google Scholar 

  62. Chaturvedi A, Dash HH. Locked-in syndrome during stellate ganglion block. Indian J Anaesth. 2010;54(4):324–6.

    Article  PubMed  CAS  Google Scholar 

  63. Henry TD. Review of preclinical and clinical results with vascular endothelial growth factors for therapeutic angiogenesis. Curr Interv Cardiol Rep. 2000;2(3):228–41.

    PubMed  Google Scholar 

  64. Giordano FJ, Ping P, McKirnan MD, et al. Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart. Nat Med. 1996;2(5):534–9.

    Article  PubMed  CAS  Google Scholar 

  65. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7(4):430–6.

    Article  PubMed  CAS  Google Scholar 

  66. Grines CL, Watkins MW, Helmer G, et al. Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris. Circulation. 2002;105:1291–7.

    Article  PubMed  CAS  Google Scholar 

  67. Grines CL, Watkins MW, Mahmarian JJ, et al. Angiogene GENe Therapy (AGENT-2) Study Group. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol. 2003;42(8):1339–47.

    Article  PubMed  CAS  Google Scholar 

  68. Stewart DJ, Kutryk MJ, Fitchett D, et al. NORTHERN Trial I. Mol Ther. 2009;17(6):1109–15.

    Article  PubMed  CAS  Google Scholar 

  69. Ruel M, Beanlands RS, Lortie M, et al. Concomitant treatment with oral L-arginine improves the efficacy of surgical angiogenesis in patients with severe diffuse coronary artery disease: the endothelial modulation in angiogenic therapy randomized controlled trial. J Thorac Cardiovasc Surg. 2008;135(4):762.

    Article  PubMed  CAS  Google Scholar 

  70. Erbs S, Linke A, Schachinger V, et al. Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the doppler substudy of the reinfusion of enriched progenitor cells and infarct remodeling in acute myocardial infarction (REPAIR-AMI) trial. Circulation. 2007;116(4):366–74.

    Article  PubMed  Google Scholar 

  71. 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. Circulation. 2007;115(25):3165–72.

    Article  PubMed  Google Scholar 

  72. Losordo DW, Henry TD, Davidson C, et al. for the ACT34-CMI Investigators. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011;109(4):428-36.

    Google Scholar 

  73. Horvath KA, Cohn LH, Cooley DA, et al. Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease. J Thorac Cardiovasc Surg. 1997;113(4):645–53.

    Article  PubMed  CAS  Google Scholar 

  74. Leon MB, Kornowski R, Downey WE, et al. A blinded, randomized, placebo-controlled trial of percutaneous laser myocardial revascularization to improve angina symptoms in patients with severe coronary disease. J Am Coll Cardiol. 2005;46(10):1812–9.

    Article  PubMed  Google Scholar 

  75. Yang EH, Barsness GW, Gersh BJ, Lerman A. Current and future treatment strategies for refractory angina. Mayo Clin Proc. 2004;79(10):1284–92.

    Article  PubMed  Google Scholar 

  76. Vale PR, Losordo DW, Milliken CE, et al. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation. 2001;103:2138–43.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cardiovascular Division, University of Minnesota Hospital, Minneapolis, MN, USA

    Mohammad Sarraf MD

  2. Mercy Hospital, Coon Rapids, MN, USA

    Daniel J. Hellrung MD

  3. Minneapolis Heart Institute Foundation, Minneapolis, MN, USA

    Timothy D. Henry MD

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  1. Mohammad Sarraf MD
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  2. Daniel J. Hellrung MD
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  3. Timothy D. Henry MD
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Correspondence to Timothy D. Henry MD .

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Editors and Affiliations

  1. Edgcumbe Place 6, St. Paul, 55116, Minnesota, USA

    Zeev Vlodaver

  2. University of Minnesota, Delaware Street S.E. 420, Minneapolis, 55455, Minnesota, USA

    Robert F. Wilson

  3. 4-112 Nils Hasselmo Hall, University of Minnesota, Church Street S.E. 312, Minneapolis, 55455, Minnesota, USA

    Daniel J. Garry

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Sarraf, M., Hellrung, D.J., Henry, T.D. (2012). Refractory Angina. In: Vlodaver, Z., Wilson, R., Garry, D. (eds) Coronary Heart Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1475-9_24

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