Angina in Patients with Non-obstructive Coronary Angiograms: Six-years Follow-up

Sergio Vancheri, Viviana Milino, Michael Henein, Corrado Tamburino


Background and Aim: About one third of patients undergoing coronary angiography for angina have non-obstructive coronary artery disease (CAD). Until recent years the prognosis has been thought to be favourable and no treatment were recommended. More recently, an increased risk of cardiovascular (CV) events has been documented in these patients compared with a general population. We aimed to evaluate the long term persistence of angina and the occurrence of major CV events in patients with stable angina and non-obstructive CAD.

Methods: We retrospectively evaluated all patients with effort angina referred to the cardiac catheterization  laboratory of the Cardiovascular Unit, University of Catania, Sicily, between 1st July 2008 and 31st December 2009, because of a clinical suspicion of myocardial ischemia, without obstructive CAD, defined as <50% stenosis of left main stem or <70% in any epicardial coronary artery.

Results: Among 2574 patients (2025 men and 549 women) referred for diagnostic coronary angiography, 151 (5.8%) had non-obstructive coronary angiograms. Six-years follow-up was available in 127 patients (63 men and 64 women). Persistence of angina was reported in 20.4%. Four patients (3.1%) had acute myocardial infarction and two (1.6%) had stroke.

Conclusion: During a six-years follow-up, persistence of angina and occurrence of acute major CV events were found in a significant proportion of patients with stable angina and non-obstructive coronary angiograms.


Coronary artery disease, angina, non-obstructive coronary angiograms

Full Text:

441.pdf HTML


Zoll PM, Wessler S, Blumgart HL. Angina pectoris. The American journal of medicine 1951;11:331-57.

Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease. The Task Force on the management of stable coronary artery disease of the European Society of Cardiology 2013;34:2949-3003. doi:10.1093/eurheartj/eht296

Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. New England Journal of Medicine 2010;362:886-95. DOI: 10.1056/NEJMoa0907272

Lee B-K, Lim H-S, Fearon WF, et al. Invasive Evaluation of Patients With Angina in the Absence of Obstructive Coronary Artery Disease. Circulation 2015;131:1054-60. doi: 10.1161/CIRCULATIONAHA.114.012636.

Sano K, Kawasaki M, Okubo M, et al. In Vivo Quantitative Tissue Characterization of Angiographically Normal Coronary Lesions and the Relation With Risk Factors. A Study Using Integrated Backscatter Intravascular Ultrasound. Circulation Journal 2005;69:543-9.

Yilmaz A, Sechtem U. Angina pectoris in patients with normal coronary angiograms: current pathophysiological concepts and therapeutic options. Heart 2012;98:1020-9.

Lanza GA, Crea F. Primary Coronary Microvascular Dysfunction: Clinical Presentation, Pathophysiology, and Management. Circulation 2010;121:2317-25. doi: 10.1161/CIRCULATIONAHA.109.900191.

Ohba K, Sugiyama S, Sumida H, et al. Microvascular Coronary Artery Spasm Presents Distinctive Clinical Features With Endothelial Dysfunction as Nonobstructive Coronary Artery Disease. Journal of the American Heart Association 2012;1:e002485. doi: 10.1161/JAHA.112.002485.

Lichtlen PR, Bargheer K, Wenzlaff P. Long-term prognosis of patients with anginalike chest pain and normal coronary angiographic findings. Journal of the American College of Cardiology 1995;25:1013-8.

Papanicolaou MN, Califf RM, Hlatky MA, et al. Prognostic implications of angiographically normal and insignificantly narrowed coronary arteries. The American Journal of Cardiology 1986;58:1181-7.

Kemp HG, Kronmal RA, Vlietstra RE, Frye RL. Seven year survival of patients with normal or near normal coronary arteriograms: A CASS registry study. Journal of the American College of Cardiology 1986;7:479-83.

Humphries KH, Pu A, Gao M, Carere RG, Pilote L. Angina with “normal” coronary arteries: Sex differences in outcomes. American Heart Journal 2008;155:375-81. doi: 10.1016/j.ahj.2007.10.019

Olson MB, Kelsey SF, Matthews K, et al. Symptoms, myocardial ischaemia and quality of life in women. Results from the NHLBI-sponsored WISE Study 2003;24:1506-14.

Tavella R, Cutri N, Tucker G, Adams R, Spertus J, Beltrame JF. Natural history of patients with insignificant coronary artery disease. European Heart Journal - Quality of Care and Clinical Outcomes 2016;2:117-24. DOI:

Maddox TM, Stanislawski MA, Grunwald GK, et al. Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA 2014;312:1754-63. doi: 10.1001/jama.2014.14681

Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. European Heart Journal 2012;33:734-44. doi: 10.1093/eurheartj/ehr331

Bugiardini R, Bairey Merz C. Angina with “normal” coronary arteries: A changing philosophy. JAMA 2005;293:477-84.

Huang F-YMD, Huang B-TMD, Lv W-YMD, et al. The Prognosis of Patients With Nonobstructive Coronary Artery Disease Versus Normal Arteries Determined by Invasive Coronary Angiography or Computed Tomography Coronary Angiography: A Systematic Review. Medicine 2016;95:e3117. doi: 10.1097/MD.0000000000003117.

Paulin S. Grading and measuring coronary artery stenoses. Catheterization and Cardiovascular Diagnosis 1979;5:213-8.

Douglas PS, Patel MR, Bailey SR, et al. Hospital Variability in the Rate of Finding Obstructive Coronary Artery Disease at Elective, Diagnostic Coronary Angiography. Journal of the American College of Cardiology 2011;58:801-9. doi: 10.1016/j.jacc.2011.05.019.

Sedlak TL, Lee M, Izadnegahdar M, Merz CNB, Gao M, Humphries KH. Sex differences in clinical outcomes in patients with stable angina and no obstructive coronary artery disease. American Heart Journal 2013;166:38-44. doi: 10.1016/j.ahj.2013.03.015.

Isner JM, Salem DN, Banas Jr JS, Levine HJ. Long-term clinical course of patients with normal coronary arteriography: Follow-up study of 121 patients with normal or nearly normal coronary arteriograms. American Heart Journal 1981;102:645-53.

Graf S, Khorsand A, Gwechenberger M, et al. Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease. Journal of Nuclear Medicine 2007;48:175-81.

De Bruyne B, Hersbach F, Pijls NHJ, et al. Abnormal Epicardial Coronary Resistance in Patients With Diffuse Atherosclerosis but “Normal” Coronary Angiography. Circulation 2001;104:2401-6.

Schoenhagen P, Nissen SE, Tuzcu EM. Coronary arterial remodeling: From bench to bedside. Current Atherosclerosis Reports 2003;5:150-4.

El Tahlawi M, Sakrana A, Elmurr A, Gouda M, Tharwat M. The relation between coronary tortuosity and calcium score in patients with chronic stable angina and normal coronaries by CT angiography. Atherosclerosis 2016;246:334-7. doi: 10.1016/j.atherosclerosis.2016.01.029.

Ho KY, Kang JY, Yeo B, Ng WL. Non-cardiac, non-oesophageal chest pain: the relevance of psychological factors. Gut 1998;43:105-10.

Kemp Jr HG, Vokonas PS, Cohn PF, Gorlin R. The anginal syndrome associated with normal coronary arteriograms: Report of a six year experience. The American journal of medicine 1973;54:735-42.

Giampaoli S, Palmieri L, Donfrancesco C, Noce CL, Pilotto L, Vanuzzo D. Cardiovascular health in Italy. Ten-year surveillance of cardiovascular diseases and risk factors: Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 1998–2012. European Journal of Preventive Cardiology 2015;22:9-37. doi: 10.1177/2047487315589011.

Wilson PW, D'Agostino RB, Levy D, Belanger A, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47.

Pitts WR, Lange RA, Cigarroa JE, Hillis LD. Repeat coronary angiography in patients with chest pain and previously normal coronary angiogram. The American Journal of Cardiology 1997;80:1086-7.

Shewan LG, Coats AJS, Henein M. Requirements for ethical publishing in biomedical journals. International Cardiovascular Forum Journal 2015;2:2, DOI: 10.17987/icfj.v2i1.4.


Copyright (c) 2017 The Authors

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.