Archivi del mese: ottobre 2020

A new paradigm shift

“There are more things in heaven and earth, Horatio, Than are dreamt of in your philosophy” ( Shakespeare, Hamlet  I.5:159–167)

From the obstructive paradigm to a more complex one.

The slow twilight of coronary “luminology” and revascularization interventions, in chronic coronary sindromes.

The new conundrum of INOCA*, in the evidences of two 2020 trials: ISCHEMIA and CIAO. Somethings are slowly changing, in the knowledge of coronary artery disease.

*Ischemia with non-obstructive coronary arteries 

The traditional coronary obstructive paradigm conditioned, for some decades, the treatment of chronic coronary syndromes (CCS, formerly known as stable coronary artery disease).

The DuckRabbit optical illusion.
This image was first used by Wittgenstein and later, by Kuhn, in 1970, to illustrate his famous concept of paradigm shift. Different perception looking at the same image, on the left or right side. photo Wikimedia Commons.

The obstructive paradigm in CCS, involves the search for inducible myocardial ischemia at non-invasive tests, and the finding of some obstructions in the lumen of the main epicardial coronary branches, with invasive coronary angiography. Assuming that the found ischemia is due to significant stenosis in the main coronary branches.

In acute coronary syndromes (ACS), on the other hand, the obstructive paradigm has already changed for at least twenty years, from the first athero-obstructive model to the current athero-thrombotic one, that is, a sudden thrombotic complication of an atherosclerotic plaque, even not significant.

Between the 80s and the first decade of the 2000s, coronary elective interventions, wether surgical, with coronary artery bypass graft (CABG) or percutaneous, with coronary angioplasty (PCI), reached a considerable numbers of procedures, following the athero-obstructive paradigm. The Jones DS’s book, “Broken Hearts”, critically disclosed these data to the general public in 2013, and caused a sensation. (1)

In elective coronary interventions, the benefits on survival have been proved only for some small subgroups, with critical obstructions on the left main or on the proximal LAD. (2, 3) This type of obstructions can currently be ruled out, non-invasively and with high sensitivity, by CT coronary angiography. However, in most of elective interventions, at follow-up there was no reduction in heart attacks or a reduction in mortality, compared to the optimal medical treatment indicated by the guidelines. (4, 5, 6, 7)

In a famous article, as early as 1995, Topol and Nissen were the first to express their concern about the so-called luminology and the dissociation between clinical and angiographic findings. (8)

Their concerns were subsequently confirmed by a growing number of well-known opinion makers, among interventional cardiologists:

Editorial JAMA, October 15, 2008.

The impact of what is between the lumen and the adventitia of the vessel (the plaque not visible with angiography) is becoming more and more relevant to lesion functional significance and future outcomes.” (9)

“it is possible to have no ischemia in the presence of significant stenosis (NIPSS) … or the presence of ischemia with no significant stenosis (PINSS)” (10)

“A large proportion of patients (up to 70%) undergoing coronary angiography because of angina and evidence of myocardial ischaemia do not have obstructive coronary arteries.” (11)

Elective coronary procedures in the United States, from 2003 to 2016, dropped by about half, both in CABG and PCI. (12)

In March of this year, the long-awaited ISCHEMIA study was finally published (13). Its ancillary study CIAO, in patients with symptoms and ischemia without obstructive coronary (INOCA), was presented at 2020 ACC-WCC meeting (14), with relevant topics about the role of microvascular disfunction and its greater prevalence in women.

Mechanisms of myocardial ischaemia in INOCA and obstructive coronary artery disease. CAD, coronary artery disease; FFR, fractional flow reserve.
European Heart Journal (2020) 0, 1-21.

These studies have sparked interesting discussions, which are still ongoing, but is likely to have implications for clinical practice. (15)

“ The results of ISCHEMIA should be used to educate and modify our clinical practice, even if they are unexpected and do not validate our preconceived beliefs.” (Rasha Al-Lamee, Alice K. Jacobs, Circulation. 2020;142(5):517-519. © 2020 American Heart Association, Inc.) (16)

Something is changing in the knowledge of coronary artery disease and in the management of CCS.

See references 11 to 16 with links, for this year’s news on the subject:


  1. Jones DS : Broken hearts: The Tangled History of Cardiac Care. 2013 Johns Hopkins University Press.
  2. Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Survival data.[No authors listed] Circulation. 1983 Nov;68(5):939-50. doi: 10.1161/01.cir.68.5.939.
  3. Takaro T, Hultgren HN, Lipton MJ, Detre KM. The VA cooperative randomized study of surgery for coronary arterial occlusive disease II. Subgroup with significant left main lesions. Circulation. 1976;54(6 Suppl:III):107–17. – PubMed
  4. Boden WE, O’Rourke RA, Teo KK, et al. COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-1516. doi:10.1056/NEJMoa070829 
  5. Frye RL, August P, Brooks MM, et al. BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-2515. doi: 10.1056/NEJMoa0805796 
  6. De Bruyne B, Fearon WF, Pijls NH, Barbato E, et al. FAME 2 Trial Investigators. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014;371:1208–1217. doi: 10.1056/NEJMoa1408758
  7. Al-Lamee R, Thompson D, Dehbi HM et al. ORBITA investigators.Lancet 2018 Jan 6;391(10115):31-40.
  8. Topol EJ, Nissen SE: Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995 Oct 15;92(8):2333-42. doi: 10.1161/01.cir.92.8.2333.
  9. Colombo A, Panoulas VF.  Diagnostic Coronary Angiography Is Getting Old!  JACC: Cardiovascular Imaging, 2015, Vol.8 (1), p.11-13.
  10. Ahmadi A, Kini A, Narula J. Discordance Between Ischemia and Stenosis, or PINSS and NIPSS. JACC: Cardiovascular Imaging, Vol. 8, (1), p. 111-4, 2015. 
  11. Kunadian V, Chieffo A, Camici PG et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries… European Heart Journal, July 2020 ehaa503,  INOCA
  12. Alkhouli M, Alqahtani F, Kalra A, et al. Trends in characteristics and outcomes of patients undergoing coronary revascularization in the United States, 2003-2016.  JAMA Netw Open. 2020;3(2):e1921326. doi:10.1001/ jamanetworkopen.2019.21326 
  13. Ischemia trial : Initial Invasive or Conservative Strategy for Stable Coronary Disease. Maron DJ, et al. N Engl J Med. 2020. PMID: 32227755 Clinical Trial.
  14. American College of Cardiology 2020 Scientific Session (ACC.20)/World Congress of Cardiology (WCC): Abstract 411-16. Presented March 30, 2020. CIAO Finds Symptoms, Ischemia Don’t Match in Puzzle That Is INOCA – Medscape – Apr 07, 2020. 
  15. What Do ISCHEMIA and CIAO Tell Us About CVD? – Medscape – Aug 28, 2020
  16. Rasha Al-Lamee, MBBS, MA, PhD; Alice K. Jacobs, MD. ISCHEMIA Trial: Was It Worth the Wait? Circulation. August 11 2020;142(5):517-519.