Significant stenosis of the left main coronary artery (LMCA), generally defined as >50 % reduction in vessel diameter, is found in approximately 4 % of patients undergoing diagnostic coronary angiography.1 A significant narrowing of the LMCA puts a patient at high risk, as the stenosis jeopardises a large amount of the myocardial mass. According to current guidelines, any stenosis of the LMCA >50 % should be treated surgically, regardless of the presence of symptoms or objective signs of ischaemia.2–4 However, this recommendation is based on studies conducted several decades ago5–7 and does not take into account recent changes in medical practice and angiographic quality. The question of how percutaneous coronary intervention (PCI) of the LMCA compares with surgical revascularisation for LMCA disease is currently being evaluated in large randomised trials. But the question of how to define a ‘truly’ significant LMCA lesion is a major concern that has not received the same attention.
Limitations in the Methods Used to Diagnose Left Main Coronary Artery Disease
Myocardial Perfusion Imaging
Non-invasive coronary testing has not been performed in the vast majority of patients undergoing PCI.8,9 Non-invasive coronary testing, particularly myocardial perfusion imaging (MPI), has proved to be highly sensitive and specific in detecting and localising ischaemia in patients with single-vessel disease and normal left ventricular function.10 However, it should be noted that the use of MPI in diagnosing LMCA stenosis is less well established due to the balanced reduction in perfusion during stress that is responsible for false-negative findings.11,12 In addition, since LMCA stenoses are rarely isolated, MPI is of little help in guiding revascularisation due to its limited spatial accuracy.13
Revascularisation decisions in everyday clinical practice are often made on the basis of angiographic estimation using the gold standard of a >50 % reduction in vessel diameter. While it is commonplace to state that angiography is a poor predictor of the actual severity of a stenosis, this is particularly true in the case of LMCA stenosis. In the Collaborative Study in Coronary Artery Surgery (CASS), still considered a landmark study outlining the preferred treatment strategy for patients with LMCA disease, there was large intra- and inter-observer variability in the evaluation of LMCA stenoses severity.14,15 In a recently published study, two independent observers assessed LMCA disease in 213 patients with angiographically equivocal stenoses using both visual and quantitative coronary angiography (QCA).16 Fractional flow reserve (FFR) was measured in all patients to assess the actual severity of the LMCA lesion(s). Angiographic assessment of the lesions, either by QCA or by visual estimation, failed to correctly identify the significance of the stenosis in 29 % of patients. Lesion severity was underestimated in most of these patients (23 %). It is concerning that even in recent studies (SYNTAX, PRCOMBAT), patient management decisions were based only on angiography. As a result, it is likely that many patients who would have benefited from revascularisation were denied treatment on the basis of a stenosis that was considered angiographically non-significant or, conversely, other patients received surgical treatment on the basis of a stenosis that was falsely considered significant.
There are several reasons for the discrepancy between angiographic and haemodynamic assessment of LMCA lesions. These include:
- Catheter overlap with the LMCA, resulting in contrast medium spillover and incomplete mixing of blood and contrast medium in the proximal part of the LMCA.
- Short LMCA with diffuse distribution of atherosclerosis so that a normal comparator segment is lacking.
- The myocardial mass dependent on the LMCA is large and, thus, the amount of blood that flows through it is great.
Intravascular ultrasound (IVUS), an invasive diagnostic modality that provides more anatomically detailed images than angiography, is often advocated as a tool to evaluate LMCA stenoses. Since the physiological severity of a stenosis depends not only on the percent stenosis but also on the mass of myocardium perfused by that given segment and on the collateral circulation, an IVUS theoretically shares the same limitations as angiography in the evaluation of a LMCA stenosis. For this reason, a given cross-sectional area (CSA) will have a completely different physiological meaning in the LMCA than in a small diagonal branch. Consequently, the IVUS cut-off values for indicating significant LMCA stenosis vary from 4.8 to 8 mm2(CSA), and can often be confusing.17–20 Nevertheless, IVUS provides a more accurate and detailed anatomical estimation of lesion severity than angiography, and can be a helpful tool in evaluating LMCA stenosis in cases when PCI is under consideration.
Advantages of Fractional Flow Reserve in Left Main Coronary Artery Lesion Assessment
FFR is a validated, lesion-specific index that accurately reflects the functional significance of a coronary stenosis. FFR provides a precise estimation of the coronary blood supply for a specific myocardial territory, independent of haemodynamic parameters, such as heart rate, blood pressure or changes in myocardial contractility.21 Recent, large, randomised studies have consistently shown that FFR-guided revascularisation strategy using a cut-off value of 0.80 is associated with reduced cost and excellent clinical outcomes.22,23 These advantages are all applicable to the functional assessment of LMCA disease.16 A recent study has demonstrated that an FFR-guided revascularisation strategy can be safely applied to patients with LMCA stenosis. The patients had an equivocal LMCA stenosis on angiography, and coronary artery bypass grafting (CABG) was performed only on patients with an FFR <0.80 across the LMCA stenosis.16 Mortality was surprisingly low for patients who were deferred CABG, based on FFR measurements.
Fractional Flow Reserve Tips, Tricks and Limitations
Although measuring FFR of the LMCA is not technically demanding, the physician should keep some tips and tricks in mind to help ensure accurate measurements:
- A pullback curve should always be obtained in the case of lesions in left anterior descending (LAD) or left circumflex artery (LCx) in order to allow complete functional mapping of the epicardial coronary vasculature.
- The guiding catheter should be disengaged from the ostium when performing measurements.
The main caveat when measuring FFR in the LMCA is that lesions are rarely isolated, making evaluation more complicated. Coexisting stenoses in the LAD or in the LCx will tend to increase the FFR measured across an LMCA stenosis. The influence of downstream lesions on the FFR measurement in the LMCA depends on the severity of those lesions and on the size of the vascular territory supplied by the vessels. A recent experimental study showed that less-severe downstream lesions have only a minor impact on the FFR of the LMCA.24 In general, this problem can be partially solved by using the pullback curve as previously mentioned.
FFR helps ensure ‘correct’ decisions are made in equivocal LMCA lesions where anatomical information provides insufficient guidance, and there are limitations in the value of invasive tests. Ambiguous LMCA lesions can effectively be evaluated using FFR, providing valuable insight into optimal therapeutic decisions. Proper identification of patients who are most likely to benefit from revascularisation is indispensable since unnecessary interventions, or conversely revascularisations that are denied when actually needed, often lead to unfavourable clinical outcomes.
- Angiography is a poor predictor of the actual severity of stenosis and usually underestimates the severity of LMCA lesions.
- LMCA lesions are rarely isolated, making evaluationmore challenging.
- Coexisting stenoses in the LAD or in the LCx tend to increase the FFR measured across an LMCA stenosis.
- FFR can play a significant role in evaluating ambiguous LMCA lesions and impact physician decision-making in this challenging patient population.
- Noto TJ Jr, Johnson LW, Krone R, et al., Cardiac catheterization 1990: A report of the Registry of the Society for Cardiac Angiography and Interventions (SCA&I), Cathet Cardiovasc Diagn, 1991;24:75–83.
- Kushner FG, Hand M, Smith SC Jr, et al., 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, J Am Coll Cardiol, 2009;54(23):2205–41.
- Silber S, Albertsson P, Aviles FF, et al., Guidelines for percutaneous coronary interventions, Eur Heart J, 2005;26(8):804–47.
- Eagle KA, Guyton RA, Davidoff R, et al., ACC/AHA 2004 guideline update for coronary artery bypass graft surgery summary article: A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines, Circulation, 2004;110:1168–76.
- Chaitman BR, Fisher LD, Bourassa MG, et al., Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease. Report of the Collaborative Study in Coronary Artery Surgery (CASS), Am J Cardiol, 1981;48:765–77.
- Prospective randomised study of coronary artery bypass surgery in stable angina pectoris. European Coronary Surgery Study Group, Lancet, 1980;316(8193):491–95.
- Kroncke GM, Kosolcharoen P, Clayman JA, et al., Five-year changes in coronary arteries of medical and surgical patients of the Veterans Administration Randomized Study of Bypass Surgery, Circulation, 1988;78:I144–50.
- Topol EJ, Ellis SG, Cosgrove DM, et al., Analysis of coronary angioplasty practice in the United States with an insurance-claims data base, Circulation, 1993;87:1489–97.
- Lin GA, Dudley RA, Lucas FL, et al., Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention, JAMA, 2008;300:1765–73.
- Go V, Bhatt MR, Hendel RC, The diagnostic and prognostic value of ECG-gated SPECT myocardial perfusion imaging, J Nucl Med, 2004;45:912–21.
- Aarnoudse WH, Botman KJ, Pijls NHJ, False-negative myocardial scintigraphy in balanced three-vessel disease, revealed by coronary pressure measurement, Acute Cardiac Care, 2003;5(2):67–71.
- Berman DS, Kang X, Slomka PJ, et al., Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease, J Nucl Cardiol, 2007;14:521–8.
- Shiba C, Chikamori T, Hida S, et al., Important parameters in the detection of left main trunk disease using stress myocardial perfusion imaging, J Cardiol, 2009;53:43–52.
- Fisher LD, Judkins MP, Lesperance J, Reproducibility of coronary arteriographic reading in the coronary artery surgery study (CASS), Cathet Cardiovasc Diagn, 1982;8:565–75.
- Taylor HA, Deumite NJ, Chaitman BR, et al., Asymptomatic left main coronary artery disease in the Coronary Artery Surgery Study (CASS) registry, Circulation, 1989;79:1171–9.
- Hamilos M, Muller O, Cuisset T, et al., Long-term clinical outcome after fractional flow reserve-guided treatment in patients with angiographically equivocal left main coronary artery stenosis, Circulation, 2009;120:1505–12.
- Abizaid AS, Mintz GS, Abizaid A, et al., One-year follow-up after intravascular ultrasound assessment of moderate left main coronary artery disease in patients with ambiguous angiograms, J Am Coll Cardiol, 1999;34:707–15.
- Jasti V, Ivan E, Yalamanchili V, et al., Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis, Circulation, 2004;110(18):2831–6.
- 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;45:204–11.
- Ricciardi MJ, Meyers S, Choi K, et al., Angiographically silent left main disease detected by intravascular ultrasound: A marker for future adverse cardiac events, Am Heart J, 2003;146:507–12.
- Pijls NH, 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;334:1703–8.
- Tonino P, De Bruyne B, Pijls N, 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 artery disease, N Engl J Med, 2012;367:991–1001.
- Daniels DV, van’t Veer M, Pijls NH, et al., The impact of downstream coronary stenoses on fractional flow reserve assessment of intermediate left main disease, JACC Cardiovasc Interv, 2012;5:1021–5.