American Journal of Cardiovascular Drugs

, Volume 10, Supplement 2, pp 27–32 | Cite as

Persistent Angina

The Araba Phoenix of Cardiology
  • Mario MarzilliEmail author
  • Alda Huqi
  • Doralisa Morrone
Review Article


Percutaneous coronary intervention (PCI) has not been shown to reduce mortality in patients with stable coronary artery disease (CAD). The long-term clinical success of PCI is defined as the persistent relief of signs and symptoms of myocardial ischemia for more than 6 months after the index procedure. Data from large trials investigating the use of PCI in patients with stable CAD show that angina is still experienced in a large number of patients one year after the procedure and that this proportion increases over time. These data are, however, largely from post-hoc analyses of studies powered to measure other end points. We conducted the first prospective study investigating the incidence of persistent angina and inducible ischemia in patients with stable CAD undergoing PCI rated as ‘successful’ by the interventional cardiologist, and present an interim analysis of data from 220 patients. The mean age of our patients was 65 years; they were mostly male, mildly obese, hypertensive and dyslipidemic. Most patients had single-vessel disease affecting the left anterior descending artery and received a drug-eluting stent, and all patients had a positive stress test before PCI. At the follow-up visit, which was performed within 4 weeks of the index procedure, 52% of patients still had a positive stress test. Before PCI, 66% of patients reported experiencing angina on exertion. At the follow-up visit, one-third of those patients were still experiencing angina. Patients experiencing persistent angina (21% of the study population) graded their symptoms as improved (66%), unchanged (33%) or worsened (1%) after the procedure. We hypothesize that coronary microvascular dysfunction is a possible cause of persistent angina in this highly select group of patients. Risk factors for microvascular dysfunction include dyslipidemia, smoking and diabetes. It is currently difficult to dissect the relative contributions of coronary artery stenosis and microvascular dysfunction in precipitating myocardial ischemia. A better understanding of these mechanisms could reduce the number of unnecessary PCI procedures. Moreover, treatment options in patients who continue to experience angina despite ‘optimal’ medical therapy and ‘successful’ PCI are urgently required.


Percutaneous Coronary Intervention Stable Coronary Artery Disease Total Chronic Occlusion Microvascular Dysfunction Coronary Flow Velocity Reserve 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge Eugenia Capati and Rossella Urselli for their contributions to this study, and Neil Reynolds of inScience Communications, a Wolters Kluwer business, who provided medical writing support funded by Pfizer. The authors have no conflicts of interest relevant to the content of this review.


  1. 1.
    Bucher HC, Hengstler P, Schindler C, et al. Percutaneous transluminal coronary angioplasty versus medical treatment for non-acute coronary heart disease: metaanalysis of randomised controlled trials. BMJ 2000 Jul 8; 321(7253): 73–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Brophy JM, Belisle P, Joseph L. Evidence for use of coronary stents. A hierarchical Bayesian meta-analysis. Ann Intern Med 2003 May 20; 138(10): 777–86.PubMedGoogle Scholar
  3. 3.
    Hueb W, Soares PR, Gersh BJ, et al. The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results. J Am Coll Cardiol 2004 May 19; 43(10): 1743–51.PubMedCrossRefGoogle Scholar
  4. 4.
    Smith Jr SC, Feldman TE, Hirshfeld Jr JW, et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006 Feb 21; 113(7): e166–286.PubMedCrossRefGoogle Scholar
  5. 5.
    Hemingway H, Crook AM, Feder G, et al. Underuse of coronary revascula-rization procedures in patients considered appropriate candidates for re-vascularization. N Engl J Med 2001 Mar 1; 344(9): 645–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Henderson RA, Pocock SJ, Clayton TC, et al. Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. J Am Coll Cardiol 2003 Oct 1; 42(7): 1161–70.PubMedCrossRefGoogle Scholar
  7. 7.
    CABRI Trial Participants. First-year results of CABRI (Coronary Angioplasty versus Bypass Revascularisation Investigation). CABRI Trial Participants. Lancet 1995 Nov 4; 346(8984): 1179–84.CrossRefGoogle Scholar
  8. 8.
    Hlatky MA, Rogers WJ, Johnstone I, et al. Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med 1997 Jan 9; 336(2): 92–9.PubMedCrossRefGoogle Scholar
  9. 9.
    King 3rd SB, Lembo NJ, Weintraub WS, et al. A randomized trial comparing coronary angioplasty with coronary bypass surgery. Emory Angioplasty versus Surgery Trial (EAST). N Engl J Med 1994 Oct 20; 331(16): 1044–50.PubMedCrossRefGoogle Scholar
  10. 10.
    RITA Trial Participants. Coronary angioplasty versus coronary artery bypass surgery: the Randomized Intervention Treatment of Angina (RITA) trial. Lancet 1993 Mar 6; 341(8845): 573–80.CrossRefGoogle Scholar
  11. 11.
    Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007 Apr 12; 356(15): 1503–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Spertus JA, Winder JA, Dewhurst TA, et al. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol 1995 Feb; 25(2): 333–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Venkitachalam L, Kip KE, Mulukutla SR, et al. Temporal trends in patient-reported angina at 1 year after percutaneous coronary revascularization in the stent era: a report from the National Heart, Lung, and Blood Institute-Sponsored 1997–2006 Dynamic Registry Cir Cardiovasc Qual Outcomes. 2009 Nov; 2(6): 607–15. Epub 2009 Oct 13.CrossRefGoogle Scholar
  14. 14.
    Lim HE, Shim WJ, Rhee H, et al. Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison among adenosine, standard-dose dipyridamole, and high-dose dipyridamole. J Am Soc Echocardiogr 2000 Apr; 13(4): 264–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Kaufmann PA, Camici PG. Myocardial blood flow measurement by PET: technical aspects and clinical applications. J Nucl Med 2005 Jan; 46(1): 75–88.PubMedGoogle Scholar
  16. 16.
    Uren NG, Marraccini P, Gistri R, et al. Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. J Am Coll Cardiol 1993 Sep; 22(3): 650–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Pupita G, Maseri A, Kaski JC, et al. Myocardial ischemia caused by distal coronary-artery constriction in stable angina pectoris. N Engl J Med 1990 Aug 23; 323(8): 514–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007 Feb 22; 356(8): 830–40.PubMedCrossRefGoogle Scholar
  19. 19.
    Feigl EO. The paradox of adrenergic coronary vasoconstriction. Circulation 1987 Oct; 76(4): 737–45.PubMedCrossRefGoogle Scholar
  20. 20.
    Sambuceti G, Marzullo P, Giorgetti A, et al. Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease. Circulation 1994 Oct; 90(4): 1696–705.PubMedCrossRefGoogle Scholar
  21. 21.
    Sambuceti G, Marzilli M, Mari A, et al. Coronary microcirculatory vasoconstriction is heterogeneously distributed in acutely ischemic myocardium. Am J Physiol Heart Circ Physiol 2005 May; 288(5): H2298–305.PubMedCrossRefGoogle Scholar
  22. 22.
    van Liebergen RA, Piek JJ, Koch KT, et al. Immediate and long-term effect of balloon angioplasty or stent implantation on the absolute and relative coronary blood flow velocity reserve. Circulation 1998 Nov 17; 98(20): 2133–40.PubMedCrossRefGoogle Scholar
  23. 23.
    Deligonul U, Vandormael MG, Shah Y, et al. Prognostic value of early exercise stress testing after successful coronary angioplasty: importance of the degree of revascularization. Am Heart J 1989 Mar; 117(3): 509–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Nishida T, Di Mario C, Kern MJ, et al. Impact of final coronary flow velocity reserve on late outcome following stent implantation. Eur Heart J 2002 Feb; 23(4): 331–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Piek JJ, Boersma E, Voskuil M, et al. The immediate and long-term effect of optimal balloon angioplasty on the absolute coronary blood flow velocity reserve. A subanalysis of the DEBATE study. Doppler Endpoints Balloon Angioplasty Trial Europe. Eur Heart J 2001 Sep; 22(18): 1725–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Kern MJ, Puri S, Bach RG, et al. Abnormal coronary flow velocity reserve after coronary artery stenting in patients: role of relative coronary reserve to assess potential mechanisms. Circulation 1999 Dec 21–28; 100(25): 2491–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Herrmann J, Haude M, Lerman A, et al. Abnormal coronary flow velocity reserve after coronary intervention is associated with cardiac marker elevation. Circulation 2001 May 15; 103(19): 2339–45.PubMedCrossRefGoogle Scholar
  28. 28.
    Czernin J, Barnard RJ, Sun KT, et al. Effect of short-term cardiovascular conditioning and low-fat diet on myocardial blood flow and flow reserve. Circulation 1995 Jul 15; 92(2): 197–204.PubMedCrossRefGoogle Scholar
  29. 29.
    Dayanikli F, Grambow D, Muzik O, et al. Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography. Circulation 1994 Aug; 90(2): 808–17.PubMedCrossRefGoogle Scholar
  30. 30.
    Gould KL, Martucci JP, Goldberg DI, et al. Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium. Circulation 1994 Apr; 89(4): 1530–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Kaufmann PA, Gnecchi-Ruscone T, Schafers KP, et al. Low density lipo-protein cholesterol and coronary microvascular dysfunction in hyper-cholesterolemia. J Am Coll Cardiol 2000 Jul; 36(1): 103–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endo-thelium-dependent dilation in healthy young adults. Circulation 1993 Nov; 88 (5 Pt 1): 2149–55.PubMedCrossRefGoogle Scholar
  33. 33.
    Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, et al. Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation 2000 Sep 12; 102(11): 1233–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 1995 Sep 1; 92(5): 1094–100.PubMedCrossRefGoogle Scholar
  35. 35.
    Di Carli MF, Janisse J, Grunberger G, et al. Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes. J Am Coll Cardiol 2003 Apr 16; 41(8): 1387–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Nitenberg A, Valensi P, Sachs R, et al. Impairment of coronary vascular reserve and ACh-induced coronary vasodilation in diabetic patients with angio-graphically normal coronary arteries and normal left ventricular systolic function. Diabetes 1993 Jul; 42(7): 1017–25.PubMedCrossRefGoogle Scholar
  37. 37.
    Pitkanen OP, Nuutila P, Raitakari OT, et al. Coronary flow reserve is reduced in young men with IDDM. Diabetes 1998 Feb; 47(2): 248–54.PubMedCrossRefGoogle Scholar
  38. 38.
    Yokoyama I, Momomura S, Ohtake T, et al. Reduced myocardial flow reserve in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1997 Nov 15; 30(6): 1472–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Agati L, Tonti G, Galiuto L, et al. Quantification methods in contrast echocardiography. Eur J Echocardiogr 2005 Dec; 6 Suppl. 2: S14–20.PubMedCrossRefGoogle Scholar
  40. 40.
    Gibson CM, Cannon CP, Murphy SA, et al. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation 2002 Apr 23; 105(16): 1909–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Gibson CM, Cannon CP, Murphy SA, et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000 Jan 18; 101(2): 125–30.PubMedCrossRefGoogle Scholar
  42. 42.
    Jerosch-Herold M, Wilke N, Stillman AE. Magnetic resonance quantification of the myocardial perfusion reserve with a Fermi function model for constrained deconvolution. Med Phys 1998 Jan; 25(1): 73–84.PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  1. 1.Division of Cardiovascular Medicine, Cardiothoracic DepartmentUniversity of PisaPisaItaly

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