Anatomy is Destiny, But Physiology is Here Today

J INVASIVE CARDIOL 2010;22:417–418

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In the current busy catheterization laboratory, the operator is under constant pressure to get cases accomplished with dispatch, yet under obligation to ask, as Barry Rutherford has often reminded us, not what we can do, but what we should do. Coronary angiography, long considered the “gold standard” for decision-making regarding treatment of coronary stenoses in both acute and chronic coronary artery disease (CAD), has known limitations. The dye-filled artery projects a shadow which is a two-dimensional representation of a three-dimensional structure. The diameter of the most severe stenosis can be relatively easily chosen and measured, but the choice of a non-diseased reference diameter may be hampered by the fact that on post-mortem studies it is clear that coronary plaque is ubiquitous, and thus it is somewhat arbitrary where one defines the reference segment.¹ To better understand the three-dimensional nature of coronary plaque and its physiologic significance, non-angiographic assessments including anatomic intravascular ultrasound (IVUS)² and physiologic flow measurements, fractional flow reserve (FFR)3 have been increasingly utilized. For IVUS, accepted definitions have evolved to discriminate between “significant” and “non-significant” lesions in the proximal portions of the major coronary arteries⁴ and in the left main stem.⁵ Specifically, lesions with minimal luminal cross-sectional areas ≥ 4.0 mm² in a proximal coronary artery or ≥ 7.5 mm² in the left main stem may be left for medical therapy rather than treated by intervention. IVUS can also give information about the nature and potential vulnerability of the obstructing plaque^6,7 and its overall amount8 which may be useful both for research purposes and for the prognosis and treatment decisions regarding the patient. Similarly, for FFR, the finding of a distal coronary/aortic pressure ratio of ≥ 0.75 at peak distal vasodilatation with adenosine predicts a benign course for the lesion treated non-interventionally.^3,9 A number of different studies have been done looking at outcomes with FFR-guided intervention, and the most recent guidelines of the ACC-AHA regarding this suggest that there may be a “gray zone” such that lesions with FFR 10 In this issue of the Journal, Dr. Lockie and colleagues¹¹ report a series of real world consecutive cath lab cases in which patients with moderate (50–75% angiographic diameter stenosis) coronary lesions were investigated with intravenous adenosine-stimulated maximal hyperemic flow and decisions regarding intervention were made with a discriminant cutoff for FFR of 0.75. Of the 5,609 interventional patients seen during the time period studied, 300 patients underwent pressure wire measurements with the important finding that 75% of the patients studied avoided a revascularization procedure on one of the arteries studied as a result of the FFR measurement. This is another brick solidly cemented into the structure of evidence surrounding the safety of deferring intervention in patients whose stenoses are not physiologically flow-impairing. That edifice, with a foundation dating back to the original Doppler coronary flow reserve measurements, has been further strengthened recently with the results of the DEFER study,¹² which used a randomization schema to show that performance of intervention on patients with a FFR ≥ 0.75 showed no benefit over medical therapy and that both the medically treated and interventional patients with initial FFR ≥ 0.75 did better than the interventional patients whose FFR had initially been 13 randomizing to FFR-guided intervention (with a trigger for intervention of FFR ≤ 0.8) versus angiographically-driven intervention resulted in the placement of fewer stents (1.9 versus 2.7) per patient in the FFR group and a lower incidence of the adverse primary endpoint of death, myocardial infarction and repeat revascularization (13.2% versus 18.3%). Finally there was also a cost savings ($5,332 in the FFR group versus $6,007 in the angiography group) and a length of stay advantage (3.4 versus 3.7 days), and both were statistically significant. Having established that angiography is not the be-all and end-all of the decision-making process in how to treat stable coronary disease, do we chose IVUS or FFR as the supplementary modality in evaluating the intermediate lesion, and why? If we want to intervene, we better do IVUS. This is suggested by Nam and colleagues in their recent study¹⁴ of 167 consecutive patients with intermediate lesions (40–70% diameter stenosis), in which either FFR 15 Perhaps it would be wise to turn back to where we were at the beginning and ask again not what we can do, but what we should do. At this point the complementarity of FFR and IVUS should be clear, but are we still missing the point? It is easy with a well-understood basis to treat a patient who has disabling angina, and easier still to stop a heart attack in progress with an elegant intervention, but further research and thought remains needed to find those intermediate lesions which may become unstable and cause heart damage and death. It seems obvious from the data that for the majority of intermediate lesions, physiologic assessment rules the day and benign outcomes are expected, but better assessment techniques such as optical coherence tomography, as well as fast, low radiation dose CTA, and possibly newer probes that may be used with PET imaging to view the areas of inflammation in the vessel wall are required to enhance our understanding of how this disease evolves clinically from its stable state into a dangerous taker of lives and sapper of strength. Meanwhile let’s perform FFR on those intermediate lesions and not be tempted to use IVUS to increase our clinical volume!

References

1. Topol, EJ, Nissen SE. Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in ischemic heart disease. Circulation 1995;92:2333–2342. 2. Yock PG, Fitzgerald P, White N, et al. Intravascular ultrasound as a guiding modality for mechanical atherectomy and laser ablation. Echocardiography. 1990;7:425–431. 3. Bech GJ, De Bruyne B, Pijls NH, et al. Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: A randomized trial. Circulation 2001;103: 2928–2934. 4. Abizaid AS, Mintz GS, Mehran R, et al. Long-term follow-up after percutaneous transluminal coronary angioplasty was not performed based on intravascular ultrasound findings: Importance of lumen dimensions. Circulation 1999;100:256–261. 5. Fassa AA, Wagatsuma K, Higano ST, et al. Intravascular ultrasound-guided treatment for angiographically indeterminate left main coronary artery disease: A long-term follow-up study. J Am Coll Cardiol 2005;45:204–211. 6. Ge J, Baumgart D, Haude M, et al. Role of intravascular ultrasound imaging in identifying vulnerable plaques. Herz 1999;24:32–41. 7. Schaar JA, de Korte CL, Mastik F, et al. Characterizing vulnerable plaque features with intravascular elastography. Circulation 2003;108:2636–2641. 8. Böse D, von Birgelen C, Erbel R. Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis. J Am Coll Cardiol 2007;49:925–932. 9. Kern MJ, Samady H. Current concepts of integrated coronary physiology in the catheterization laboratory. J Am Coll Cardiol 2010;55:173–185. 10. Kern MJ, Lerman A, Bech JW, et al. Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: A scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation 2006;114:1321–1341. 11. Lockie T, Perera D, De Silva K, et al. The impact of measuring fractional flow reserve on decision making in the cath lab in a cohort of patients being considered for coronary revascularization. J Invasive Cardiol 2010;22:413–416. 12. Pijls NH, van Schaardenburgh P, Manoharan G, et al. Percutaneous coronary intervention of functionally non-significant stenoses: 5-year follow-up of the DEFER study J Am Coll Cardiol 2007;49:2105–2111. 13. Tonino PA, De Bruyne B, Pijls NH, et al; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–224. 14. Nam C-W, Yoon H-J, Cho Y-K, et al. Outcomes of percutaneous coronary intervention in intermediate coronary artery disease: Fractional flow reserve-guided versus intravascular ultrasound-guided. JACC Intervent 2010;3:812–817. 15. Hodgson JM. If You Want to Stent ... Do Intravascular Ultrasound! JACC Intervent 2010;3:818–820.

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From the Lenox Hill Heart and Vascular Institute, New York New York. The author reports no conflicts of interest regarding the content herein. Address for correspondence: J.R. Wilentz, MD, FACC, Lenox Hill Heart and Vascular Institute, 130 East 77th St, New York NY 10075. E-mail: wilentz@gmail.com