Abstract
Purpose of Review
The goal of this review is to offer an updated and comprehensive summary of the available options for performing both invasive and noninvasive functional assessments of coronary artery disease.
Recent Findings
Fractional flow reserve (FFR) is an invasive functional coronary assessment of ischemia associated with clinical outcomes. In recent years, alternative pressure wire measurements that do not require hyperemic agents have been developed. Measurements such as instantaneous wave-free ratio (iFR) are non-inferior to FFR, result in shorter procedure times, and eliminate side effects related to the use of vasodilatory agents. With advances in technology and computational fluid dynamics, non-invasive methods based on invasive and non-invasive coronary angiograms have been developed to allow for hyperemia-free and wire-free assessments.
Summary
Accurate methods to diagnose clinically significant ischemic heart disease are essential, and these novel systems are safer than they have been in the past. This review offers a comprehensive overview and guidance on best practices in conducting these assessments.
Opinion Statement
This review aims to highlight best practices in conducting functional coronary assessments to diagnose clinically significant coronary artery disease. Although coronary angiography is the gold standard for diagnosing coronary artery disease, two-dimensional imaging has limitations. Understanding whether a vessel has an ischemia-causing, physiologically significant obstruction requires additional evaluation beyond a visually-interpreted coronary angiogram. Fractional flow reserve (FFR) has been extensively studied and determined to be an effective tool for clinical decision-making in the approach to revascularization for ischemic heart disease. Instantaneous wave-free ratio (iFR) is another assessment method (not requiring the use of hyperemic agents) that has been directly compared to and proven to be non-inferior to FFR in randomized control trials. Measurements such as the diastolic hyperemia-free ratio (DFR) and the resting full-cycle ratio (RFR) have subsequently been compared to iFR. Analytic software such as FFRangio and Quantitative flow ratio (QFR), which utilize images from invasive coronary angiograms, are growing in popularity as a methodology for evaluating stenoses. There are potential benefits of a reduced procedure time, contrast use, and fluoroscopy time with this strategy. Coronary computed tomography angiography-derived FFR is a non-invasive method of determining the likelihood a stenosis is causing significant ischemia. Discussion with patients of the risks and benefits of all available options is a best practice. Intermediate severity obstructive epicardial stenoses in major epicardial vessels should be further evaluated by physiology in symptomatic or high risk patients. Functional assessments for coronary microvascular disease should be performed in patients with documented ischemia, a history of potentially cardiac symptoms, and lack of obstructive disease. Noninvasive options also diagnose obstructive coronary artery disease with high accuracy.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
Maron DJ, Kostuk WJ, Knudtson M, et al. Optimal medical therapy with or without PCI for stable coronary disease. Published online 2014;1503–1516.
Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med. 2020;382(15):1395–407. https://doi.org/10.1056/nejmoa1915922.
Mehta SR, Wood DA, Storey RF, et al. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med. 2019;381(15):1411–21. https://doi.org/10.1056/nejmoa1907775.
Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(3):E18–114. https://doi.org/10.1161/CIR.0000000000001038/FORMAT/EPUB.
Neumann FJ, Sechtem U, Banning AP, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41(3):407–77. https://doi.org/10.1093/eurheartj/ehz425.
Tonino PAL, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–24.
De Bruyne B, Pijls NHJ, Kalesan B, et al. Fractional flow reserve–guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991–1001. https://doi.org/10.1056/nejmoa1205361.
Götberg M, Christiansen EH, Gudmundsdottir IJ, et al. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N Engl J Med. 2017;376(19):1813–23. https://doi.org/10.1056/NEJMOA1616540/SUPPL_FILE/NEJMOA1616540_DISCLOSURES.PDF.
Davies JE, Sen S, Dehbi HM, et al. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med. 2017;376(19):1824–34. https://doi.org/10.1056/nejmoa1700445.
• Puymirat E, Cayla G, Simon T, et al. Multivessel PCI guided by FFR or angiography for myocardial infarction. New Eng J Med. 2021;385(4):297–308. https://doi.org/10.1056/NEJMOA2104650/SUPPL_FILE/NEJMOA2104650_DATA-SHARING.PDF. In patients with ST-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy for the composite primary outcomes of death, myocardial infarction, or urgent revascularization at 1 year.
Kovarnik T, Hitoshi M, Kral A, et al. Fractional flow reserve versus instantaneous wave-free ratio in assessment of lesion hemodynamic significance and explanation of their discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study. J Am Heart Assoc. 2022;11(9):21490. https://doi.org/10.1161/JAHA.121.021490.
Physiology-guided vs angiography-guided non-culprit lesion complete revascularization for acute MI & multivessel disease (COMPLETE-2) ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT05701358?id=NCT05701358&draw=2&rank=1&load=cart. Accessed 14 Mar 2023.
Koo BK, Hu X, Kang J, et al. Fractional flow reserve or intravascular ultrasonography to guide PCI. N Engl J Med. 2022;387(9):779–89. https://doi.org/10.1056/nejmoa2201546.
Kajiya F, Zamir M, Carlier S. Cardiac hemodynamics, coronary circulation and interventional cardiology. Annal Biomed Eng. 2005;33(12 SPEC. ISS.):1728–1734. https://doi.org/10.1007/s10439-005-8777-x.
Morris PD, Al-Lamee RK, Berry C. Coronary physiological assessment in the catheter laboratory: haemodynamics, clinical assessment and future perspectives. Heart. 2022;108(21):1737–46. https://doi.org/10.1136/heartjnl-2020-318743.
Pijls NHJ, Van Son JAM, 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(4):1354–67. https://doi.org/10.1161/01.CIR.87.4.1354.
Pijls NHJ, De Bruyne B, Van Der Voort P, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1995;334(26):1703–8. https://doi.org/10.1161/01.CIR.92.11.3183.
Pijls NHJ, de Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334(26):1703–8. https://doi.org/10.1056/nejm199606273342604.
Achenbach S, Rudolph T, Rieber J, et al. Performing and interpreting fractional flow reserve measurements in clinical practice: an expert consensus document. Interv Cardiol. 2017;12(2):97–109. https://doi.org/10.15420/icr.2017.
Vranckx P, Cutlip DE, McFadden EP, Kern MJ, Mehran R, Muller O. Coronary pressure-derived fractional flow reserve measurements: recommendations for standardization, recording, and reporting as a core laboratory technique. Proposals for integration in clinical trials. Circulation. 2012;5(2):312–317. https://doi.org/10.1161/CIRCINTERVENTIONS.112.968511.
Petraco R, Al-Lamee R, Gotberg M, et al. Real-time use of instantaneous wave–free ratio: results of the ADVISE in-practice: an international, multicenter evaluation of instantaneous wave–free ratio in clinical practice. Am Heart J. 2014;168(5):739–48. https://doi.org/10.1016/J.AHJ.2014.06.022.
Petraco R, Park JJ, Sen S, et al. Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation. EuroIntervention. 2013;8(10):1157–65. https://doi.org/10.4244/EIJV8I10A179.
Shuttleworth K, Smith K, Watt J, Smith JAL, Leslie SJ. Hybrid instantaneous wave-free ratio–fractional flow reserve versus fractional flow reserve in the real world. Front Cardiovasc Med. 2017;4. https://doi.org/10.3389/FCVM.2017.00035.
Abe M, Tomiyama H, Yoshida H, Doba N. Diastolic fractional flow reserve to assess the functional severity of moderate coronary artery stenoses: comparison with fractional flow reserve and coronary flow velocity reserve. Circulation. 2000;102(19 SUPPL.):2365–70. https://doi.org/10.1161/01.CIR.102.19.2365.
Ligthart J, Masdjedi K, Witberg K, et al. Validation of resting diastolic pressure ratio calculated by a novel algorithm and its correlation with distal coronary artery pressure to aortic pressure, instantaneous wave-free ratio, and fractional flow reserve: The DPR study. Circulation. 2018;11(12):1–10. https://doi.org/10.1161/CIRCINTERVENTIONS.118.006911.
Kumar G, Desai R, Gore A, et al. Real world validation of the nonhyperemic index of coronary artery stenosis severity—resting full-cycle ratio—RE-VALIDATE. Catheter Cardiovasc Interv. 2020;96(1):E53–8. https://doi.org/10.1002/ccd.28523.
Svanerud J, Ahn JM, Jeremias A, et al. Validation of a novel non-hyperaemic index of coronary artery stenosis severity: the resting full-cycle ratio (VALIDATE RFR) study. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2018;14(7):806–14. https://doi.org/10.4244/EIJ-D-18-00342.
Fearon WF, Achenbach S, Engstrom T, et al. Accuracy of fractional flow reserve derived from coronary angiography. Circulation. 2019;139(4):477–84. https://doi.org/10.1161/CIRCULATIONAHA.118.037350.
• Witberg G, De Bruyne B, Fearon WF, et al. Diagnostic performance of angiogram-derived fractional flow reserve: a pooled analysis of 5 prospective cohort studies. JACC Cardiovasc Intervent. 2020;13(4):488–497. https://doi.org/10.1016/J.JCIN.2019.10.045. In the largest study to date of the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was consistent across subgroups.
Scoccia A, Tomaniak M, Neleman T, Groenland FTW, Plantes ACZ des, Daemen J. Angiography-based fractional flow reserve: state of the art. Curr Cardiol Reports. 2022;24(6):667–678. https://doi.org/10.1007/s11886-022-01687-4.
• Xu B, Tu S, Song L, et al. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021;398(10317):2149–2159. https://doi.org/10.1016/S0140-6736(21)02248-0. In FAVOR III China, among patients undergoing PCI, a non-invasive QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard of care angiography guidance.
Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris I. A variant form of angina pectoris. Preliminary report. Am J Med. 1959;27(3):375–388. https://doi.org/10.1016/0002-9343(59)90003-8.
Matta A, Bouisset F, Lhermusier T, et al. Coronary artery spasm: new insights. J Interv Cardio. 2020;2020. https://doi.org/10.1155/2020/5894586.
Sueda S, Kohno H, Fukuda H, et al. Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine. Angiology. 2004;55(4):403–11. https://doi.org/10.1177/000331970405500407.
Pristipino C, Beltrame JF, Finocchiaro ML, et al. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation. 2000;101(10):1102–8. https://doi.org/10.1161/01.CIR.101.10.1102.
Nobuyoshi M, Abe M, Nosaka H, et al. Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. Am Heart J. 1992;124(1):32–8. https://doi.org/10.1016/0002-8703(92)90917-K.
McCord J, Jneid H, Hollander JE, et al. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association acute cardiac care committee of the council on clinical cardiology. Circulation. 2008;117(14):1897–907. https://doi.org/10.1161/CIRCULATIONAHA.107.188950/FORMAT/EPUB.
Zafar A, Drobni ZD, Mosarla R, et al. The incidence, risk factors, and outcomes with 5-fluorouracil–associated coronary vasospasm. JACC: CardioOncol. 2021;3(1):101–109. https://doi.org/10.1016/J.JACCAO.2020.12.005.
Horio Y, Yasue H, Rokutanda M, et al. Effects of intracoronary injection of acetylcholine on coronary arterial diameter. Am J Cardiol. 1986;57(11):984–9. https://doi.org/10.1016/0002-9149(86)90743-5.
Zaya M, Mehta PK, Bairey Merz CN. Provocative testing for coronary reactivity and spasm. J Am Coll Cardiol. 2014;63(2):103–9. https://doi.org/10.1016/j.jacc.2013.10.038.
Intervention C. Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J. 2014;78(11):2779–801. https://doi.org/10.1253/circj.CJ-66-0098.
Takahashi T, Samuels BA, Li W, et al. Safety of provocative testing with intracoronary acetylcholine and implications for standard protocols. J Am Coll Cardiol. 2022;79(24):2367–78. https://doi.org/10.1016/j.jacc.2022.03.385.
Okumura K, Yasue H, Matsuyama K, et al. Effect of acetylcholine on the highly stenotic coronary artery: difference between the constrictor response of the infarct-related coronary artery and that of the noninfarct-related artery. J Am Coll Cardiol. 1992;19(4):752–8. https://doi.org/10.1016/0735-1097(92)90513-M.
Shin D IL, Baek SH, Her SH, et al. The 24-month prognosis of patients with positive or intermediate results in the intracoronary ergonovine provocation test. JACC Cardiovasc Interv. 2015;8(7):914–923. https://doi.org/10.1016/j.jcin.2014.12.249.
Nørgaard BL, Leipsic J, Gaur S, et al. Diagnostic performance of noninvasive fractional flow reserve derived from coronary computed tomography angiography in suspected coronary artery disease: the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014;63(12):1145–55. https://doi.org/10.1016/J.JACC.2013.11.043.
Douglas PS, Pontone G, Hlatky MA, et al. Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFR(CT): outcome and resource impacts study. Eur Heart J. 2015;36(47):3359–3367. https://doi.org/10.1093/eurheartj/ehv444.
Douglas PS, De Bruyne B, Pontone G, et al. 1-year outcomes of FFRCT-guided care in patients with suspected coronary disease: the PLATFORM study. J Am Coll Cardiol. 2016;68(5):435–45. https://doi.org/10.1016/j.jacc.2016.05.057.
Nanna MG, Vemulapalli S, Fordyce CB, et al. The prospective randomized trial of the optimal evaluation of cardiac symptoms and revascularization: rationale and design of the PRECISE trial. Am Heart J. 2022;245(1):136–48. https://doi.org/10.1016/j.ahj.2021.12.004.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the evaluation and diagnosis of chest pain: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. 2021;144. https://doi.org/10.1161/cir.0000000000001030.
Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;144(22):e368–454. https://doi.org/10.1161/CIR.0000000000001029.
Feher A, Sinusas AJ. Quantitative assessment of coronary microvascular function. Circulation. 2017;10(8). https://doi.org/10.1161/CIRCIMAGING.117.006427.
Herzog BA, Husmann L, Valenta I, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography. Added Value of Coronary Flow Reserve. J Am College Cardio. 2009;54(2):150–156. https://doi.org/10.1016/j.jacc.2009.02.069.
Indorkar R, Kwong RY, Romano S, et al. Global coronary flow reserve measured during stress cardiac magnetic resonance imaging is an independent predictor of adverse cardiovascular events. JACC Cardiovasc Imaging. 2019;12(8P2):1686–1695. https://doi.org/10.1016/j.jcmg.2018.08.018.
Pathan F, Marwick TH. Myocardial perfusion imaging using contrast echocardiography. Prog Cardiovasc Dis. 2015;57(6):632–43. https://doi.org/10.1016/j.pcad.2015.03.005.
Funding
This work was supported by the Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
T. A. M. has served as a consultant for HeartFlow, Inc. N. R. S. has received honoraria or served as a consultant for Abbott, Philips, Shockwave, and Zoll. N. R. S. also has stock options in Stallion Catheter (personal). The other authors have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Kerkar, A.P., Juratli, J.H., Kumar, A.A. et al. Best Practices for Physiologic Assessment of Coronary Stenosis. Curr Treat Options Cardio Med 25, 159–174 (2023). https://doi.org/10.1007/s11936-023-00984-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11936-023-00984-7