Title Page Section: Rebuttal Title: When Would the Assessment of Fractional Flow Reserve be Non-Reproducible? Brief Title: Fractional Flow Reserve Reproducibility Word Count: 801 Key Words: Coronary Collaterals, Coronary Artery Disease, Atherosclerosis Authors, academic degrees, and affiliations: Wassef Karrowni, MD Interventional and Endovascular Cardiology UnityPoint Clinic-St Luke's Hospital Cedar Rapids, IA 52403 Kanu Chatterjee, MD Kanu and Docey Edwards Chatterjee Chair in Cardiovascular Medicine, University of Iowa, Iowa City, IA 52242 Emeritus Professor of Medicine University of California, San Francisco Corresponding Author: Wassef Karrowni, MD UnityPoint Clinic-St Luke's Hospital 202 10th Street SE, Suite 225 Cedar Rapids, IA 52403 E-mail: [email protected] Office: 319-364-7101 Fax: 319-861-3014
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ccd.25385
Catheterization and Cardiovascular Interventions
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2 The presence and extent of myocardial ischemia are the major determinants of the potential benefit of coronary revascularization (1-5). Assessment of fractional flow reserve (FFR) has become an important tool in the interventional catheterization laboratory to help with decision making with respect to revascularization. FFR is a lesion specific index of functional significance that is independent of hemodynamics, thus making it a highly accurate and reproducible indicator of whether a particular stenosis could be held responsible for ischemia (6,7). Revascularization of an FFR positive stenosis is associated with improved outcome and deferring stenting in an FFR negative stenosis is safe and associated with excellent long-term outcome (2,6,8,9). There are several clinical scenarios in which there would be dynamic changes in the FFR values obtained necessitating caution with the interpretation of the results: 1) Acute coronary syndrome (ACS): FFR measured in ACS patients could be high in the acute setting because of the stunned myocardium. However, repeat FFR measurement several days later after the myocardium recovers and receives more flow could be significantly lower (3,4,10). 2) Serial coronary lesions: In the presence of serial stenoses, FFR measurement is influenced and typically the distal lesion makes the FFR value of the proximal one higher than what it actually is (11). Thus, it is important in these cases to start with a pull-back recording and fix the lesion with largest gradient first; after that FFR reassessment of the second lesion is performed and decision whether a second stent should be placed is made (9). 3) Recanalization of a chronic total occlusion (CTO): This was nicely demonstrated in the case presented in the Letter to the Editor where the FFR in the collateral donor vessel (left anterior descending artery in this case), increased to non-ischemic level after the collateral recipient vessel (right coronary artery in this case) was recanalized (12). After CTO recanalization, the collateral resistance increases immediately and thus the flow in the donor vessel decreases (13). Consequently, the pressure gradient across the stenosis in the donor vessel would decrease increasing the FFR value. Based on the above discussion and the case presented by Gangadharan et al. in the Letter to the Editor (12), there are several clinical scenarios where FFR needs to be reassessed after the initial conditions change in order to make the right decision whether not to leave an obstructive lesion untreated or to avoid an unnecessary stent.
Catheterization and Cardiovascular Interventions
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Catheterization and Cardiovascular Interventions
3 References: 1.
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Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900-7. 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;49:2105-11. Shaw LJ, Berman DS, Maron DJ 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. Circulation 2008;117:128391. Tonino PA, De Bruyne B, Pijls NH et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24. De Bruyne B, Pijls NH, Kalesan B et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001. Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 1993;87:1354-67. De Bruyne B, Baudhuin T, Melin JA et al. Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation 1994;89:1013-22. Davies RF, Goldberg AD, Forman S et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization. Circulation 1997;95:2037-43. Pijls NH, Sels JW. Functional measurement of coronary stenosis. J Am Coll Cardiol 2012;59:1045-57. Samady H, Lepper W, Powers ER et al. Fractional flow reserve of infarctrelated arteries identifies reversible defects on noninvasive myocardial perfusion imaging early after myocardial infarction. J Am Coll Cardiol 2006;47:2187-93. Pijls NH, De Bruyne B, Bech GJ et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans. Circulation 2000;102:2371-7. Gangadharan V, Sumption K, Prinz A. Collateral Circulation in Chronic Total Occlusion: Implications in Percutaneous Intervention and Clinical Management. Cathet. Cardiovasc. Intervent. 2013.
Catheterization and Cardiovascular Interventions
Catheterization and Cardiovascular Interventions
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4 13.
Werner GS, Richartz BM, Gastmann O, Ferrari M, Figulla HR. Immediate changes of collateral function after successful recanalization of chronic total coronary occlusions. Circulation 2000;102:2959-65.
Catheterization and Cardiovascular Interventions
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ccd.25385
Catheterization and Cardiovascular Interventions
Page 2 of 4
2 The presence and extent of myocardial ischemia are the major determinants of the potential benefit of coronary revascularization (1-5). Assessment of fractional flow reserve (FFR) has become an important tool in the interventional catheterization laboratory to help with decision making with respect to revascularization. FFR is a lesion specific index of functional significance that is independent of hemodynamics, thus making it a highly accurate and reproducible indicator of whether a particular stenosis could be held responsible for ischemia (6,7). Revascularization of an FFR positive stenosis is associated with improved outcome and deferring stenting in an FFR negative stenosis is safe and associated with excellent long-term outcome (2,6,8,9). There are several clinical scenarios in which there would be dynamic changes in the FFR values obtained necessitating caution with the interpretation of the results: 1) Acute coronary syndrome (ACS): FFR measured in ACS patients could be high in the acute setting because of the stunned myocardium. However, repeat FFR measurement several days later after the myocardium recovers and receives more flow could be significantly lower (3,4,10). 2) Serial coronary lesions: In the presence of serial stenoses, FFR measurement is influenced and typically the distal lesion makes the FFR value of the proximal one higher than what it actually is (11). Thus, it is important in these cases to start with a pull-back recording and fix the lesion with largest gradient first; after that FFR reassessment of the second lesion is performed and decision whether a second stent should be placed is made (9). 3) Recanalization of a chronic total occlusion (CTO): This was nicely demonstrated in the case presented in the Letter to the Editor where the FFR in the collateral donor vessel (left anterior descending artery in this case), increased to non-ischemic level after the collateral recipient vessel (right coronary artery in this case) was recanalized (12). After CTO recanalization, the collateral resistance increases immediately and thus the flow in the donor vessel decreases (13). Consequently, the pressure gradient across the stenosis in the donor vessel would decrease increasing the FFR value. Based on the above discussion and the case presented by Gangadharan et al. in the Letter to the Editor (12), there are several clinical scenarios where FFR needs to be reassessed after the initial conditions change in order to make the right decision whether not to leave an obstructive lesion untreated or to avoid an unnecessary stent.
Catheterization and Cardiovascular Interventions
Page 3 of 4
Catheterization and Cardiovascular Interventions
3 References: 1.
2.
3.
4.
5.
6.
7.
8.
9. 10.
11.
12.
Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900-7. 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;49:2105-11. Shaw LJ, Berman DS, Maron DJ 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. Circulation 2008;117:128391. Tonino PA, De Bruyne B, Pijls NH et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24. De Bruyne B, Pijls NH, Kalesan B et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001. Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation 1993;87:1354-67. De Bruyne B, Baudhuin T, Melin JA et al. Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation 1994;89:1013-22. Davies RF, Goldberg AD, Forman S et al. Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization. Circulation 1997;95:2037-43. Pijls NH, Sels JW. Functional measurement of coronary stenosis. J Am Coll Cardiol 2012;59:1045-57. Samady H, Lepper W, Powers ER et al. Fractional flow reserve of infarctrelated arteries identifies reversible defects on noninvasive myocardial perfusion imaging early after myocardial infarction. J Am Coll Cardiol 2006;47:2187-93. Pijls NH, De Bruyne B, Bech GJ et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery: validation in humans. Circulation 2000;102:2371-7. Gangadharan V, Sumption K, Prinz A. Collateral Circulation in Chronic Total Occlusion: Implications in Percutaneous Intervention and Clinical Management. Cathet. Cardiovasc. Intervent. 2013.
Catheterization and Cardiovascular Interventions
Catheterization and Cardiovascular Interventions
Page 4 of 4
4 13.
Werner GS, Richartz BM, Gastmann O, Ferrari M, Figulla HR. Immediate changes of collateral function after successful recanalization of chronic total coronary occlusions. Circulation 2000;102:2959-65.
Catheterization and Cardiovascular Interventions
