Five-Year Outcomes of Moderate or Ambiguous Left Main Coronary Artery Disease

And the Intravascular Ultrasound Predictors of Events

ABSTRACT: The long-term outcome of a moderately diseased left main coronary artery (LMCA) remains unknown. One hundred and fourteen patients who underwent angiographic and intravascular ultrasound (IVUS) evaluation for moderate LMCA disease ( 90° at the MLA site. By multiple logistic regression analysis, plaque burden at the MLA (odds ratio = 1.34, 95% confidence interval 1.04–1.73; p = 0.025) was the only independent predictor of events. In conclusion, moderately diseased LMCAs had a 5-year event rate of 8%. The occurrence of future events in moderate diseased LMCAs is dependent on the amount of disease at the MLA site. J INVASIVE CARDIOL 2008;20:635–639 Significant obstructive disease of the left main coronary artery (LMCA) (≥ 50% diameter stenosis [DS]) is associated with a poor long-term prognosis.1–5 It is widely accepted that patients with a ≥ 50% LMCA DS should be candidates for coronary artery bypass graft surgery (CABG) in order to improve long-term outcomes.2,3,6–10 Conversely, the long-term prognosis of patients with moderate LMCA disease remains unknown, although Abizaid et al11 reported 1-year outcomes after assessment by intravascular ultrasound (IVUS), and Fassa et al5 suggested a threshold of a LMCA minimum luminal area (MLA) (≥ 7.5 mm2 to be able to safely defer revascularization with the mean follow-up period of 3.5 ± 2.1 years. Coronary angiography is still regarded as the gold standard in terms of the quantification of coronary artery disease, but there are limitations, especially when the severity of disease is mild to moderate,12–14 and especially when the LMCA is involved.14,15 The aim of this study was to report 5-year outcomes of patients with angiographically moderate or ambiguous LMCA disease who underwent IVUS analysis without intervention (CABG or percutaneous coronary intervention [PCI]) and to investigate predictors for long-term cardiac events. Methods Patient population. Among patients from June 2001 to August 2003 at the Washington Hospital Center, 146 were suited to the inclusion criteria of this study as follows: angiographically moderate LMCA disease ( 50% DS that was not treated by PCI. IVUS imaging and analysis. We used 1 of 2 commercially available systems: Atlantis SR, Galaxy (Boston Scientific Corp./SCIMED, Natick, Massachusetts) or Eagle Eye (Volcano Therapeutics, Inc., Rancho Cordova, California). IVUS imaging was performed after intravenous administration of 150–200 µg of nitroglycerin. The ultrasound catheter was advanced beyond the LMCA bifurcation into the left anterior descending or circumflex artery and was pulled back to the aorto-ostial junction using a motorized transducer pullback at 0.5 mm/s or 1.0 mm/sec. All IVUS images were recorded onto s-VHS videotapes or CDs for offline analysis. Cross-sectional area measurements of external elastic membrane (EEM) area, luminal area (LA), plaque and media area (P&M = EEM minus LA), and plaque burden (P&M divided by EEM) were performed every 1 mm over the entire length of each LMCA lesion using TapeMeasure 4.2.16C (Indec Systems, Inc, Mountain View, California) in order to allow normalized volumetric as well as planar analysis. Reference segments were the LMCA cross-sections with the largest lumen and least amount of plaque, and the average value of the proximal and distal was used, although, like the angiogram, the distal reference was used for ostial lesions and proximal reference for distal bifurcated lesions. Lesion length was measured using automatic pullback. The remodeling index was defined as the EEM area at minimum luminal area (MLA) site divided by the reference EEM area. Calcium was brighter than the reference adventitia, with shadowing of deeper arterial structure; the arc of calcium was measured with a protractor centered on the lumen. Clinical data and definitions. Baseline demographic and in-hospital complication data were recorded and entered prospectively into our database by a dedicated data coordinating center. The occurrence of cardiac events or the need for coronary revascularization was recorded and adjudicated by source documentation. The data for this study came from our database under the Health Insurance Portability and Accountability Act of 1996 waiver, and the Institutional Review Board approved the study. Clinical follow up was performed by telephone contact. Cardiac events that were tabulated included death, myocardial infarction, PCI of the LMCA and CABG. All deaths were considered cardiac unless otherwise documented. Statistical analysis. Statistical analysis was performed using SPSS, Version 11.0 (SPSS Inc., Chicago, Illinois) or SAS 9.1 (SAS Institute Inc., Cary, North Carolina). Continuous variables were reported as mean ± 1 standard deviation (SD) and compared using the Student’s t-test or, if the data were not normally distributed, the Mann-Whitney test. Categorical variables were reported as frequencies and compared using chi-square statistics. A p-value 0.10 considered to indicate lack of deviation between the model and observed event rates). Event-free survival probability was calculated according to the Kaplan-Meier method. Results Four-year cardiac events and clinical characteristics (Table 1). The original group of 146 patients (91 males) had an average age of 62.9 ± 10.1 years, 39 (27%) had diabetes mellitus, and 29 (20%) had prior myocardial infarction. Seventy-two (48%) had an untreated non-LMCA coronary artery stenosis with a DS > 50%. On IVUS analysis at the MLA site, EEM area was 20.1 ± 5.6 mm2, MLA 10.3 ± 3.7 mm2, and plaque burden 48 ± 13%. An arc of calcium > 90° at the MLA site was seen in 29 cases (20%). The final study group of 100 patients had no significant differences compared with the original 146 patients. Six patients (6%) died (1 of cardiac causes and 5 of unknown causes that, by definition, were presumed to be cardiac) at a mean follow up of 31.5 ± 17.0 months post-IVUS assessment. Two patients (2%) had CABG at a mean follow up of 19.0 ± 7.1 months because of LMCA disease in addition to other vessel disease progression. There were no patients who underwent PCI for LMCA disease or a myocardial infarction during the follow-up period. Accordingly, the event group was composed of 8 patients, and the total event rate was 8%. Patients with events were more frequently older and male and more often had prior myocardial infarction than the no-event group. Coronary angiographic analysis (Figure 1, Table 1). Quantitative coronary angiographic analysis did not show any differences between the event and no-event groups, although there were trends for more patients (63%) with an untreated non-LMCA coronary artery stenosis with a DS > 50% in the event group compared with the no-event group (42%), with more untreated left anterior descending artery disease (81% vs. 56%) and less untreated right coronary artery disease (20% vs. 51%). Figure 1 indicates the distribution of diameter stenosis of the LMCA in the study population. IVUS analysis (Figure 1, Table 2). Figure 1 indicates the distribution of the MLA of the LMCA in the study population. Patients with events had significantly larger P&M and plaque burdens over the entire length of the lesion. In particular, the MLA site, P&M areas (13.1 ± 3.5 vs. 8.5 ± 3.0 mm2; p 90° at the MLA site was also more frequent in the event group (75% vs. 10%; p 90° at the MLA site were entered into the multivariate logistic regression model. The only independent predictor of cardiac events was plaque burden at the MLA site (OR = 1.340, 95% CI, 1.037–1.732; p = 0.025). Figure 2 shows the Kaplan-Meyer survival curve from any cardiac events among study patients. Discussion The present study demonstrates that moderately diseased LMCA had a 5-year event rate of 8%, and that the only independent predictor of cardiac events was plaque burden at the MLA site. This is in contradistinction to 1-year events that appear to be more dependent on LMCA luminal dimensions.11 It is reported that patients with significant LMCA disease (DS > 50%) have a poor prognosis1–5 and surgical therapy can significantly improve the survival rate compared to the medical therapy.2,3,6–10 Conley et al1 reported that the degree of LMCA stenosis influenced its prognosis, such that patients with ≥ 70% LMCA stenosis had significantly lower 3-year survival rates compared to normal LMCA patients. However, Conley et al1 also identified 53 patients with 50–70% LMCA stenosis and 3-vessel coronary artery disease who had a similar 3-year survival rate compared to 479 patients with normal LMCA and 3-vessel coronary artery disease. Abizaid et al11 reported that among 122 patients with a mean 42% angiographic LMCA DS, the 1-year event rate was 14% (3% death and 11% need for any revascularization). In the current study 100 patients with 32 ± 9% angiographic LMCA DS had an 8% event rate (6% death and 2% need of CABG) during the 5-year follow-up period (Table 1). Fassa et al5 reported that the major adverse cardiac event rate at 3 years was approximately 22% (28 out of 126 cases) in patients with moderately diseased LMCA who did not undergo revascularization. Since quantitative coronary angiography is not suited to the determination of mild-to-moderate LMCA disease12–14 or mild-to-moderate LMCA stenosis,14,15 several recent studies utilized IVUS analysis to evaluate angiographically ambiguous moderate LMCA disease.4,11,20–22 Abizaid et al11 reported that the LMCA lesion site minimum luminal diameter (OR = 0.17, 95% CI, 0.05–0.59; p = 0.005) was an independent predictor of 1-year cardiac events, although there were also statistical differences in the LA (6.8 ± 4.4 vs. 10.0 ± 5.3 mm2), P&M area (15.7 ± 5.2 vs. 11.9 ± 5.9 mm2) and plaque burden (70 ± 14 vs. 53 ± 18%) between patients with and without events. Ricciardi et al4 reported that MLA was an independent predictor for future cardiac events during 2-year follow up. Fassa et al5 reported that events in nonrevascularized patients with an LMCA MLA > 7.5 mm2 was not different from patients who were revascularized, while the outcome of patients with an LMCA MLA 50% stenosis in 95.3% of patients with LMCA disease, with 52.1% of patients with LMCA disease having coexistent 3-vessel disease. Abizaid et al11 suggested that untreated lesions in other coronary arteries and diabetes mellitus were independent predictors for 1-year prognosis of patients with moderate LMCA disease. In the current study, the presence of another stenotic vessel did not predict 5-year events. Study limitations. The main limitation of this study is the small number of patients with events and the fact that this is a retrospective, single-center experience. The cause of death in many was also undetermined. Second, there may have been selection bias regarding which patients would undergo IVUS imaging and IVUS-based decisions to revascularize or not to revascularize. Third, although there were no differences in patient characteristics, coronary angiography findings and IVUS parameters between the original 146 patients and the 100 study patients, the number of patients lost to follow up was substantial and might have affected the current results. Finally, since 8 adverse outcomes during the follow-up period were small compared to the number of independent variables in multivariate analysis, this might also have influenced the results. Conclusion In selected patients evaluated by IVUS, moderately diseased LMCAs had a 5-year event rate of 8%; this was dependent of the extent of disease, not of the degree of luminal compromise.

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