Plaque that Makes a Patient Vulnerable

It has long been recognized that evaluation of the severity of stenoses in the left main is more difficult than at most other sites in the coronary tree, although much of supporting data dates from the time when patients underwent angiography in rotating cradles. Nonetheless, vessel overlap and eccentric stenoses still plague angiographic assessment of lesions at this prognostically important site. But the severity of stenosis is a poor harbinger of events. Granted, randomized trials performed in the distant past suggested bypass surgery is superior to medical therapy alone for patients with > 50% lesions at this site. Their relevance, in an era of aggressive statin therapy, soon to be available agents that dramatically increase HDL and when bypass surgery is not the only means technically available for revascularization is questionable, and only of modest assistance to the patient and treating physician. Now and today, however, which patient with a left main narrowing needs revascularization? To answer this question one needs to know the natural history with contemporary medical therapy. Perhaps surprisingly, little is known. Perhaps it’s not so surprising, however, as measures beyond angiography (IVUS, OCT, virtual histology, thermography, palpagraphy to name some) to assess local plaque stability are only now undergoing a thorough evaluation. Prior to the report in this month’s Journal by Jimenez-Navarro (see pages 398–400),1 probably the most relevant contemporary report assessing the natural history of disease at this site was that by Abizaid,2 describing one year clinical outcomes after IVUS in 122 patients with “ambiguous” angiograms. Patients (average age 63 years, 67% male, 26% diabetics) had angiographic reference diameter of 3.9 mm and diameter stenosis of 42 ± 16%. Importantly, the former, but not the latter, correlated well with IVUS measurements (r = 0.49 and r = 0.11 respectively). During follow-up there were four cardiac deaths (two after bypass surgery), no myocardial infarctions, and 17 coronary revascularizations (overall MACE = 14%). MACE were correlated with diabetes, additional disease, and MLD by IVUS. In univariate testing, plaque volume was also related MACE, but was apparently co-linear with MLD, and not an independent correlate in their analysis. Other than measurement of calcium arc, morphologic parameters such as hard or soft plaque were not reported. Nor were lipid management or anti-platelet therapy. Another important study about which to be aware is that of Iyisoy and Tuzcu3 describing non-atherosclerotic narrowing of the left main in up to 10% of the 182 recent transplant recipients they examined. What does the report by Jimenez-Navarro et al. add or not add? Multiple modest sized longitudinal studies, principally evaluating sites other than the left main, have generally confirmed the prognostic value of FFR first described by Pijls.4,5 In the current report twenty patients with 30–50% stenoses and normal FFR (> 0.75) were followed for an average of about two years. No patient died suddenly or had a myocardial infarction. Two underwent subsequent coronary revascularization. The authors acknowledge the limitations of a small patient cohort and are careful to state that FFR is a “potentially” useful indicator of clinical events in this setting. Is it safe to defer revascularization for a less than angiographically “significant” lesion in the left main if the FFR is > 0.75? Possibly. Possibly not. The problem is that an error here may well be fatal. From a statistical standpoint the upper limits of the 95% confidence range for a twenty patient study with no MACE is 15%. Is that an adequate safety margin? I think not. Further, a recent report by Chan and colleagues6 suggests that FFR may not be nearly as reliable a predictor of future adverse events in diabetics than non-diabetics. Conversely, under some circumstances a left main narrowing due to “reverse remodeling” without evidence plaque by IVUS may be quite safe to follow conservatively (albeit frequently). Several of us at the Cleveland Clinic are doing just that, providing there is little or no evidence of atherosclerosis elsewhere. Having said that, FFR as well as other imaging modalities mentioned above deserve further study in this arena. Certainly the principal message in dealing with patients with left main blockages has remained the same over the years. This is not a place to make a mistake. Until we know much more about the natural history of various types of coronary plaque, under normal circumstances if there is a question whether to revascularize or not, it’s better to err on the side of revascularization. The best means to do that remains another incompletely answered question.

1. Jimenez-Navarro M, Hernandez-Garcia J, Alonso-Briales J, et al. Should we treat patients with moderately severe stenosis of the left main coronary artery and negative FFR results? J Invas Cardiol 2004:16:398–400. 2. Abizaid AS, Mintz G, 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 1999:34:3:707–715. 3. Iyisoy A, Ziada K, Schoenhagen P, et al. Intravascular ultrasound evidence of ostial narrowing in nonatherosclerotic left main coronary arteries. Am J Cardiol 2002:90:773–775. 4. Pijls N, De Bruyne B, Willem Bech J, et al. Coronary pressure measurement to assess the hemodynamic significance of serial stenoses within one coronary artery. Validation in humans. Circulation 2000;102:2371–2377. 5. Bech G, De Bruyne B, Pijls N, et al. Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis: A randomized trial. Circulation 2001:103:2928–2934 6. Chan C, Kinlay S, Popma J, et al. Effect of diabetes mellitus on the predictive value of myocardial fractional flow reserve. J Am Coll Cardiol 2003:41:6(abstract).