Clinical Outcomes of Deferred Lesions With Angiographically Insignificant Stenosis But Low Fractional Flow Reserve

Background Data are limited regarding outcomes of deferred lesions in patients with angiographically insignificant stenosis but low fractional flow reserve (FFR). We investigated the natural history of angiographically insignificant stenosis with low FFR among patients who underwent routine 3‐vessel FFR measurement. Methods and Results From December 2011 to March 2014, 1136 patients with 3298 vessels underwent routine 3‐vessel FFR measurement (3V FFR‐FRIENDS study, ClinicalTrials.gov identifier NCT01621438), and this study analyzed the 2‐year clinical outcomes of 1024 patients with 2124 lesions with angiographically insignificant stenosis (percentage of diameter stenosis <50%), in which revascularization was deferred. All lesions were classified according to FFR values, using a cutoff of 0.80 (high FFR >0.80 versus low FFR ≤0.80). The primary end point was outcome of major adverse cardiovascular events (a composite of cardiac death, myocardial infarction, and ischemia‐driven revascularization) at 2 years. Mean angiographic percentage of diameter stenosis and FFR of total lesions were 32.5±10.3% and 0.91±0.08%, respectively. Among the total lesions with angiographically insignificant stenosis, 8.7% showed low FFR (185 lesions). The incidence of lesions with low FFR was 2.5%, 3.8%, 9.0%, and 15.1% in categories of percentage of diameter stenosis <20%, 20% to 30%, 30% to 40%, and 40% to 50%, respectively. At 2‐year follow‐up, the low‐FFR group showed a significantly higher risk of major adverse cardiovascular events compared with the high FFR group (3.3% versus 1.2%, hazard ratio: 3.371; 95% CI, 1.346–8.442; P=0.009). In multivariable analysis, low FFR was the most powerful independent predictor of future MACE in deferred lesions with angiographically insignificant stenosis (adjusted hazard ratio: 2.617; 95% CI, 1.026–6.679; P=0.044). Conclusions In deferred angiographically insignificant stenosis, lesions with low FFR showed significantly higher event rates than those with high FFR. FFR was an independent predictor of future major adverse cardiovascular events in lesions with angiographically insignificant stenosis. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01621438.

[1]  P. Stella,et al.  Deferral vs. performance of percutaneous coronary intervention of functionally non-significant coronary stenosis: 15-year follow-up of the DEFER trial. , 2015, European heart journal.

[2]  Volker Klauss,et al.  Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial , 2015, The Lancet.

[3]  Charles A. Taylor,et al.  Coronary Artery Axial Plaque Stress and its Relationship With Lesion Geometry: Application of Computational Fluid Dynamics to Coronary CT Angiography. , 2015, JACC. Cardiovascular imaging.

[4]  Chi‐Hang Lee,et al.  Usefulness of combined intravascular ultrasound parameters to predict functional significance of coronary artery stenosis and determinants of mismatch. , 2015, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[5]  K. Dimopoulos,et al.  Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease , 2015, Heart.

[6]  R. Virmani,et al.  Biomechanical factors in atherosclerosis: mechanisms and clinical implications. , 2014, European heart journal.

[7]  B. Koo,et al.  Characteristics of Function-Anatomy Mismatch in Patients with Coronary Artery Disease , 2014, Korean Circulation Journal.

[8]  William Wijns,et al.  Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses. , 2014, European heart journal.

[9]  S. Tansuphaswadikul,et al.  Visual-functional mismatch and results of fractional flow reserve guided percutaneous coronary revascularization. , 2014, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[10]  Helmut Baumgartner,et al.  2014 ESC/EACTS 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). Developed with the special contribution of the European Association of Percutaneous , 2014, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[11]  Nikola Jagic,et al.  Fractional flow reserve-guided PCI for stable coronary artery disease. , 2014, The New England journal of medicine.

[12]  M. Kern.  Seeing and not believing: Understanding the visual‐functional mismatch between angiography and FFR , 2014, Catheterization and cardiovascular interventions.

[13]  R. Rajendran,et al.  Optical coherence tomographic image of an angiographically borderline lesion with a significant fractional flow reserve. , 2014, Journal of the American College of Cardiology.

[14]  B. Dimitrov,et al.  Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?: The RIPCORD Study , 2014, Circulation. Cardiovascular interventions.

[15]  T. Akasaka,et al.  Prevalence of visual–functional mismatch regarding coronary artery stenosis in the CVIT-DEFER registry , 2014, Cardiovascular Intervention and Therapeutics.

[16]  Seung‐Jung Park,et al.  Trends in the outcomes of percutaneous coronary intervention with the routine incorporation of fractional flow reserve in real practice. , 2013, European heart journal.

[17]  K. Gould,et al.  Coronary Anatomy to Predict Physiology: Fundamental Limits , 2013, Circulation. Cardiovascular imaging.

[18]  Seung‐Jung Park,et al.  Sex differences in the visual-functional mismatch between coronary angiography or intravascular ultrasound versus fractional flow reserve. , 2013, JACC. Cardiovascular interventions.

[19]  Jing Li,et al.  Long-term outcomes of fractional flow reserve-guided vs. angiography-guided percutaneous coronary intervention in contemporary practice. , 2013, European heart journal.

[20]  R. Torguson,et al.  FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study. , 2013, Journal of the American College of Cardiology.

[21]  Eun Bo Shim,et al.  Visual-functional mismatch between coronary angiography and fractional flow reserve. , 2012, JACC. Cardiovascular interventions.

[22]  Jeffrey L. Anderson,et al.  2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: Executive Summary , 2012, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[23]  U. Siebert,et al.  Clinical ResearchInterventional CardiologyFractional Flow Reserve Versus Angiography for Guiding Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease: 2-Year Follow-Up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) Study , 2010 .

[24]  P. Serruys,et al.  Myocardial infarction adjudication in contemporary all-comer stent trials: balancing sensitivity and specificity. Addendum to the historical MI definitions used in stent studies. , 2010, EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology.

[25]  Habib Samady,et al.  Current concepts of integrated coronary physiology in the catheterization laboratory. , 2010, Journal of the American College of Cardiology.

[26]  J. Gillard,et al.  Plaque rupture: plaque stress, shear stress, and pressure drop. , 2008, Journal of the American College of Cardiology.

[27]  Guido Germano,et al.  Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden: Results From the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial Nuclear Substudy , 2008, Circulation.

[28]  William Wijns,et al.  Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. , 2007, Journal of the American College of Cardiology.

[29]  P. Serruys,et al.  Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions , 2007, Circulation.

[30]  D. Berman,et al.  Optimal medical therapy with or without PCI for stable coronary disease. , 2007, The New England journal of medicine.

[31]  K. Berhane,et al.  Inference in Spline‐Based Models for Multiple Time‐to‐Event Data, with Applications to a Breast Cancer Prevention Trial , 2003, Biometrics.

[32]  P. Doriot.  Estimation of the supplementary axial wall stress generated at peak flow by an arterial stenosis. , 2003, Physics in medicine and biology.

[33]  R. Mates,et al.  Fluid Dynamics of Coronary Artery Stenosis , 1978, Circulation research.

[34]  M. Hellmich,et al.  Correlation between optical coherence tomography-derived intraluminal parameters and fractional flow reserve measurements in intermediate grade coronary lesions: a comparison between diabetic and non-diabetic patients , 2014, Clinical Research in Cardiology.

[35]  Helmut Baumgartner,et al.  ESC / EACTS Guidelines on myocardial revascularization , 2014 .

[36]  B. Gersh,et al.  Angiographic Versus Functional Severity of Coronary Artery Stenoses in the FAME Study: Fractional Flow Reserve Versus Angiography in Multivessel Evaluation , 2011 .

[37]  G. Levine,et al.  ACCF/AHA/SCAI Practice Guideline 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 and the Society for Cardiovascular Angiography and Interventions , 2011 .