Invasive FFR — Current Applications and New Developments

Open access


Myocardial ischemia caused by coronary atherosclerosis is the main cause of cardiovascular mortality, which is the first cause of death in developed countries. Inducible myocardial ischemia is a negative prognostic factor for coronary artery disease patients, and it represents a major risk stratification marker for predicting mortality. The evolution of these patients depends largely on the extension of the ischemic myocardial mass and the severity of the inducible ischemia. Most patients do not show angiographically significant coronary stenosis. Therefore, such patients do not undergo coronary revascularization therapies, even though they present functional stenoses that trigger myocardial ischemia under stress conditions, which subsequently lead to a high risk for major adverse cardiovascular events. We performed a review that aims to pinpoint invasive techniques used for evaluating the functional impact of a coronary lesion that is considered non-significant upon angiographic examination, but which triggers episodes of myocardial ischemia under stress conditions, and to describe the functional markers that show the highest specificity for predicting ischemic risk, in order to recommend invasive coronary revascularization.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Shaw LJ Berman DS Marin DJ et al. Optimal medical therapy with or without percutaneous coronaru interventions to reduce ischaemic burden: results from the Clinical Outcomes Utilizing Revascularization and aggressive drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008;117:1283-1291.

  • 2. Erne P Schoenenberger AW Burckhardt D et al. Effects of percutaneous coronary interventions in silent ischaemia after myocardial infarction: The SWISS II randomized controlled trial. JAMA. 2007;297:1985-1991.

  • 3. Pijls NH van Schaardenburgh P Manoharan G et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow up of the DEFER Study. J Am Coll Cardiol. 2007;49:2105-2111.

  • 4. Lin GA Dudley RA Lucas FL Malenka DJ Vittinghoff E Redberg RF. Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention. JAMA. 2008;300:1765-1773.

  • 5. Melikian N De Bondt P Tonino P et al. Comparison between visual assessment and quantitative angiography versus fractional flow reserve for native coronary narrowing of moderate severity. Am J Cardiol. 2002;90:210-215.

  • 6. Christou MA Siontis GC Katristris DG Ioannidis JP. Meta-analysis of fractional flow reserve versus quantitative coronary angiography and noninvasive imaging for evaluation of myocardial ischemia. Am J Cardiol. 2007;99:450-456.

  • 7. Tonino PA de Bruyne B Pijls NH et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360:213-224.

  • 8. Bourdarias JP. Coronary reserve: concept and physiological variations. Eur Heart J. 1995;16(supplI):2-6.

  • 9. Jeremias A Whitbourn RJ Filardo SD et al. Adequacy of intracoronary versus intravenous adenosine-induced maximal coronary hyperemia for fractional flow reserve measurements. Am Heart J. 2000;140:651-657.

  • 10. Pijls NH Tonino PA Fearon WF. Fractional flow reserve for guiding PCI. N Engl J Med. 2009;360:2026-2027.

  • 11. Vranckx P Cutlip DE Mc Fadden EP Kern MJ Mahran R Muller O. Coronary pressure derived fractional flow reserve measurements: recommendations for standardization recording and reporting as a core laboratory technique. Proposal for integration in clinical trials. Circ Cardiovasc Interv. 2012;5:312-317.

  • 12. Tonino PA Fearon WF De Bruyne B et al. Angiographic versus functional severity of coronary artery stenosis in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol. 2010;55:2816-2821.

  • 13. Lilly LS Harvard Medical School. Pathophysiology of heart disease: a collaborative project of medical students and faculty. 5th ed. Baltimore/MD: Wolters Kluwer Lippincott Williams & Wilkins; 2011.

  • 14. Leonardi RA Townsend JC Patel CA et al. Left ventricular end-diastolic pressure affects measurement of fractional flow reserve. Cardiovasc Revasc Med. 2013;14:218-222.

  • 15. De Bruyne B Piljs NH Kalesan B et al. Fractional flow reserve – guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2009;360:213-224.

  • 16. De Bruyne B Piljs NH Barbato E et al. Intracoronary and intravenous adenosine 5-triphosphate adenosine papaverine and contrast medium to assess fractional flow reserve in humans. Circulation. 2003;107:1877-1883.

  • 17. Yong AS Daniels D De Bruyne B et al. Fractional flow reserve assessment of left main stenosis in the presence of downstream coronary stenoses. Circ Cardiovasc Interv. 2013;6:161-165.

  • 18. Bech GJ de Bruyne B Piljs NH et al. Fractional flow reserve to determine the appropiatenes of angioplasty in moderate coronary stenosis; a randomized trial. Circulation. 2001;103:2928-2934.

  • 19. De Bruyne B Piljs NH Bartunek J et al. Fraxctional flow reserve in patients with prior myocardial infarction. Circulation. 2001;104:157-162.

  • 20. Pijls NH. Fractional flow reserve to guide coronary revascularization. Circ J. 2013;77:561-569.

  • 21. Van Belle E Rioufol G Pouillot C et al. Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry. Circulation. 2014;129:173-185.

  • 22. Melikian N Cuisset T Hamilos M De Bruyne B. Fractional flow reserve – the influence of the collateral circulation. Int J Cardiol. 2009;132:e109-e110.

  • 23. Wijns W Kohl P Danchin N et al. Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-thoracic Surgery (EACTS). Eur Heart J. 2010;31:2501-2555.

  • 24. Koo BK Park KW Kang HJ et al. Physiological evaluation of the provisional side branch intervention strategy for bifurcation lesion using fractional flow reserve. Eur Heart J. 2008;29:726-732.

  • 25. Koo BK. Physiologic evaluation of bifurcation lesions using fractional flow reserve. J Interv Cardiol. 2009;22:110-113.

  • 26. Fearon WF Shilane D Piljs NH et al. Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve. Circulation. 2013;128:1335-1340.

  • 27. Ntalianis A Sles JW Davidavicius G et al. Fractional flow reserve for the assessment of nonculprit coronary artery stenoses in patients with acute myocardial infarction. JACC Cardiovasc Interv. 2010;3:1274-1281.

  • 28. Levine GN Bates ER Blankenship et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines ant the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574-651.

  • 29. Fearon WF. Percutaneous Coronary Intervention Should Be Guided by Fractional Flow reserve Measurement. Circulation. 2014;129:1860-1870.

  • 30. Burzotta F Leone AM De Maria GL et al. Fractional flow reserve or optical coherence tomography guidance to revascularize intermediate coronary stenosis using angioplasty (FORZA) trial: study protocol for a randomized controlled trial. Trials. 2014;15:140.

  • 31. Meuwissen M Chamuleau SA Siebes M et al. Role of variability in microvascular resistence on fractional flow reserve and coronary blood velocity reserve in intermediate coronary lesions. Circulation. 2001;103:184-187.

  • 32. Sen S Escaned J Malik IS et al. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study. J Am Coll Cardiol. 2012;59:1392-1402.

  • 33. Berry C van t Veer M Witt N et al. VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): a multicenter study in consecutive patients. J Am Coll Cardiol. 2013;61:1421-1427.

  • 34. Escaned J Echavarria-Pinto M Garcia-Garcia HM et al. Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADIVSE II International Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II). JACC Cardiovasc Interv. 2015;8:824-833.

  • 35. Nijjer SS Sen S Petraco R et al. Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease. JACC Cardiovasc Interv. 2014;7:1386-1396.

  • 36. Van Belle E. DEFINE REAL: a prospective observational non-randomised European multicentre registry collecting real-life information for the utilisation of iFR in assessing coronary stenosis relevance in the multivessel disease patient population. Presented at: EuroPCR 2016.

  • 37. Stone GW Maehara A Lansky AJ et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226-235.

  • 38. Johnson NP Gould KL Di Carli MF Taqueti VR. Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future? J Am Coll Cardiol. 2016;67:2772-2788.

  • 39. Nijjer SS Sen S Petraco R et al. Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio. Heart. 2013;99:1740-1748

  • 40. Fearon WF Aarnoudse W Pijls NH et al. Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation. Circulation. 2004;109:2269-2272.

  • 41. De Bruyne B Barbato E. Quantitative assessment of the coronary microvasculature: new tools for the black box. Circulation. 2013;127:2378-2379.

  • 42. Fearon WF Low AF Yong AS et al. Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation. 2013;127:2436-2441.

Journal information
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 210 111 11
PDF Downloads 116 76 9