1 Arashijora

Ivus Mla Bibliography

Conventional angiography is the gold standard in clinical practice for diagnosing atherosclerotic compromise of the coronary artery tree. However, coronary angiography has several known limitations, including a lack of correlation between the percentage of stenosis and the lesion’s physiologic importance1 and considerable interobserver variability in classifying the lesion’s severity.2,3

Intravascular ultrasound (IVUS) has been shown to detect atherosclerotic compromise that cannot be detected by conventional angiography.4 Using tomographic slices to analyze the coronary artery, IVUS provides absolute luminal measurements. An IVUS-measured minimum luminal cross-sectional area (MLA) of ≤ 4.0 mm2 has been used as a marker of severe coronary artery stenosis, which correlates well with the findings of other methods for diagnosing myocardial ischemia, including single-photon emission computed tomography,5 Doppler wire studies6 and pressure wire measurement.7 The clinical importance of this criterion has been confirmed by a study8 showing that deferral of revascularization is safe for patients with an MLA of > 4.0 mm2.8

In this study, we investigated the rate of severe coronary artery stenosis (MLA ≤ 4.0 mm2) detected by IVUS in patients whose angiograms showed intermediate stenosis and who had evidence of myocardial ischemia. Because IVUS is more invasive, expensive and laborious than angiography, we also sought to identify angiographic factors that would predict an IVUS-measured MLA of ≤ 4.0 mm2. This could potentially minimize undue interventions and reduce cost, time and further coronary manipulation related to fractional or coronary flow reserve assessment.

Methods

Patients. This prospective, observational study was conducted at Rede D’or Hospitais (Rio de Janeiro, Brazil) and was approved by the institutional review board. Fifty-six patients, with 63 angiographically-intermediate coronary artery stenoses, underwent IVUS to further define the severity of their lesions. According to the American College of Cardiology and the American Heart Association, intermediate stenosis was defined as having a diameter of ≥ 30% and < 70%, as measured by quantitative coronary angiography (QCA) using CASSII software (Cardiovascular Angiographic Analysis System; Pie Medical, Maastricht, The Netherlands).9 All patients had clinical evidence of myocardial ischemia or functional test results indicative of ischemia in the territory of the culprit vessel. The clinical setting included stable angina, unstable angina and non-ST-elevation myocardial infarction.

The inclusion criteria were clinical history or functional test results indicating myocardial ischemia on stress testing, stress echocardiography or single-photon emission tomography, at least one intermediate lesion, as described above, and a de novo lesion in a native coronary artery. Patients were excluded if they had an ST-elevation acute myocardial infarction, anycontraindication to anticoagulation, or in-stent restenosis saphenous vein graft lesions.

Diagnostic methods. All analyses were performed offline. The diagnostic angiograms were obtained using Digital Imaging and Communications in Medicine (DICOM)-compatible digital systems (H-5000, Phillips Medical Systems, Eindhoven, Holland; and Siemens Medical Systems Coroskop Top digitalacquisition DICOM matrix 512 x 521).

For calibration of the QCA software, we used the final portion of the empty guiding catheter in the angiographic projection that showed the lesion best, with no foreshortening and with the most severe degree of stenosis. The software automat ically provided thr ee parameters: (1) percentage of stenosis; (2) minimum luminal diameter (MLD); and (3) lesion length. We also used the reference segment diameters for comparative analyses with the IVUS results. The reference segment was defined as the segment least affected by atherosclerosis within a 10 mm span proximal and distal to the target lesion. This definition was carefully followed for both angiography and IVUS to ensure that the measurements were done at exactly the same site for both diagnostic methods. We used the classification system from the National Heart, Lung, and Blood Institute’s Coronary Artery Surgery Study for lesion localization and definition of the proximal, medial and distal portions of the arteries.10

Prior to beginning the IVUS studies, patients were given 10,000 U of unfractionated heparin for systemic anticoagulation. IVUS was performed using conventional 6 or 7 Fr guiding catheters and a 0.014 mm guidewire was positioned distally. IVUS catheters of 30 or 40 MHz (UltraCross®, Discovery or Atlantis®; Boston Scientific Corp., Natick, Massachusetts) were pulled back automatically at a constant speed of 0.5 mm/second. The following parameters were included in the IVUS analyses: MLA, reference segment plaque burden, luminal area of stenosis, remodeling index, atheroma eccentricity (eccentricity index), reference segment luminal diameter and MLD. The measurements were performed according to the guidelines of the American College of Cardiology for the acquisition, measurement and reporting of IVUS studies.11 We defined positive remodeling as having a remodeling index above 1.05, and negative as having an index below 0.95.12

Statistical analyses. We used the NCSS statistical software package (Kaysville, Utah) for data analysis. The data were described for the whole population and further stratified into two groups based on their MLA. Group 1 included lesions with a MLA ≤ 4.0 mm2, and Group 2 included lesions with a MLA > 4.0 mm2.

Continuous data with normal distribution were described as means ± standard deviation (SD), and categorical data were described as frequency among the two groups. For inferential analyses, comparisons of numerical variables between both groups were performed using the two-tailed unpaired t-test or the Mann-Whitney U-test for parametric and nonparametric variables, respectively. Comparisons of categorical data between groups were performed using the chi-squared or Fisher’s exact tests. Multiple logistic regression was performed using QCA-derived parameters to assess for angiographic predictors of severe luminal stenosis (MLA ≤ 4 mm2).

Results

Four patients with 1 lesion each were excluded from the study, as 3 of the lesions had poor-quality IVUS data and 1 had a poor-quality angiogram. The final group was composed of 52 patients with 59 intermediate lesions. The average age of the patients was 61 ± 13 years, and 28 (54%) were men. Twenty-five patients (48%) had dyslipidemia, 14 (27%) were smokers, 32 (62%) had high blood pressure, 9 (17%) had diabetes and 22 (42%) had a family history of coronary artery disease. Thirty patients (58%) had acute coronary syndrome (TIMI RISK > 3 for unstable angina or non-ST-elevation MI) and underwent coronary angiography as part of an early invasive strategy. The remaining 22 patients had chronic stable angina (n = 14) or chest pain of recent onset (n = 8) and were submitted to coronary angiography due to the presence of myocardial ischemia during stress testing. Two of these patients showed ECG changes during treadmill testing; 12 had perfusion defects in the territory of the culprit lesion on technetium Tc 99m sestamibi (MIBI) SPECT, and 8 showed akinesia on stress dobutamine echocardiograms.

The IVUS data and lesion characteristics are summarized in Table 1. There was a high frequency of severe stenosis (MLA ≤ 4.0 mm2), as assessed by IVUS. Thirty-seven patients (71%) had at least 1 severe stenosis, and these stenoses accounted for 40 (68%) of the lesions in the overall group. Most of the lesions were eccentric and showed negative remodeling. The Group 1 lesions were more severe, as indicated by a higher percentage of luminal area stenosis and higher plaque burden. An important reference segment compromise was evident in the overall group, as shown by the average plaque burden of 33.67 ± 15.01% at these sites.

Table 2 describes the angiographic analyses. Fifty-three (90%) of the 59 lesions were located at the proximal or midportions of the artery (35 of 40 in Group 1 and 18 of 19 in Group 2). The Group 1 lesions were longer and had lower MLD than did the Group 2 lesions. Although the severity of stenosis was higher among Group 1 lesions, none of the lesions showed more than 70% stenosis.

A comparison of the IVUS and angiography results revealed a significant underestimation of the reference segment luminal diameter by angiography, even though the MLD measurements by the two methods were similar (Table 3). Linear regression analysis showed a weak correlation between the two methods for the assessment of reference segment luminal diameter (r = 0.4; p < 0.001).

Multiple logistic regression was performed to identify predictors of a MLA ≤ 4 mm2. The analysis included the QCA derived parameters of proximal reference diameter, interpolated reference diameter, distal reference diameter, MLD and percentage of stenosis. The only predictor of small MLA was the diameter of the distal reference segment. Figure 1 shows theresults of a receiver operating characteristic curve using the QCA-derived distal reference diameter to predict a MLA ≤ 4.0 mm2. A diameter < 2.42 mm was predictive of a small MLA on IVUS, with a sensitivity of 90% and a specificity of 55%. Conversely, a diameter of 3.25 mm excluded a small MLA with high specificity (90%), although the sensitivity was low (26%).

Discussion

In this group of patients, 68% of the lesions (in 71% of the patients) diagnosed as moderate by conventional angiography had, in fact, severe stenosis by the adopted IVUS criterion (MLA ≤ 4.0 mm2).

Atherosclerotic involvement of the arterial wall in apparently normal coronary segments seems to be a ubiquitous phenomenon.4 The clinical importance of coronary narrowing has been questioned, since the majority of acute myocardial infarctions originate from previously nonobstructive lesions.13–20 This concept of lesion vulnerability has changed the clinical approach to diagnosing and treating coronary artery disease, since the odds of an adverse event are not directly related to the severity of coronary artery stenosis.21,22 For example, revascularization of stenotic lesions in clinically stable patients might not affect long-term survival.23–27 Despite its sectional design, the present study confirms the above concept, as the frequency of lesions with MLA ≤ 4.0 mm2 was greater than that of lesions with MLA > 4.0 mm2 in patients with stable angina (35% versus 6.7%; p = 0.04), but not in those with unstable angina (56.8% versus 60%). Furthermore, in the clinical setting of stable angina, 13 of 14 patients (93%) had a MLA ≤ 4.0 mm2.

When we compared the two patient groups with regard to QCA-derived percent stenosis parameters, we found a higher degree of stenosis in Group 1 (MLA ≤ 4.0 mm2). The frequency of reference segment compromise was high, as 67.2% of the Group 1 lesions showed a plaque burden of > 30% at these sites. The linear regression results comparing angiography and IVUS showed a poor correlation with respect to the evaluation of stenosis-percentage parameters, luminal diameter at the lesion site, luminal diameter at reference segments and lesion length. The average MLD did not differ when measured by either method, but the reference segment diameter was underestimated by angiography (Table 3).

The decision to intervene on a lesion is frequently made in the catheterization laboratory based on the visual estimation of the lesion’s severity. Lesions with more than 70% stenosis on visual quantification are usually considered hemodynamically significant and submitted to intervention. However, data from pressure wire evaluation of lesions with less than 70% compromise of luminal diameter have shown that they are also frequently associated with impaired flow reserve and myocardial ischemia.28,29 Moreover, previous IVUS studies have demonstrated the correlation between a MLA < 4.0 mm2 and decreased fractional flow reserve,30 while a MLA ≥ 4.0 mm2 was correlated with a preserved fractional flow reserve and favorable outcomes with deferral of invasive intervention.8 In the present study, we found a high frequency of MLA < 4.0 mm2 in patients with known myocardial ischemia whose angiograms could not demonstrate a high degree of coronary stenosis.

Diffusely compromised arteries may present as small-caliber vessels with non-severe stenosis because the angiogram is limited to the lumen and the stenosis percentage is relative to the reference segment luminal diameter. In this study, angiography probably underestimated the severity of luminal stenosis because it could not detect atherosclerotic compromise in the reference segments. This was supported by the smaller luminal diameter of these segments (although the MLD was similar for both methods) and the high plaque burden detected by IVUS in these segments.

The finding that a distal luminal reference diameter < 2.42 mm is predictive of a small MLA can be used to further stratify patients with intermediate coronary lesions and is evidence of myocardial ischemia in a population with a higher risk of severe coronary stenosis and a small luminal area. Conversely, a QCA-measured distal reference diameter ≥ 3.25 mm could indicate that no further testing is needed, as such a diameter excluded a small MLA on IVUS with a specificity of 90%. These findings could be applied clinically to identify patients who should undergo IVUS to confirm the presence of severe coronary stenosis and patients for whom IVUS would cause unnecessary risk and expense.

Conclusions

In this population of patients with clinical evidence of myocardial ischemia and angiographically-intermediate lesions, the frequency of severe lesions detected by IVUS was high. This underestimation of stenosis by angiography may stem from its inability to detect atherosclerotic compromise of reference segments, thereby providing less precise measurements of luminal diameter at these sites compared to IVUS.

Distal reference segment diameter was the only predictor of a small MLA and could be used to stratify these lesions into groups with higher and lower risk of severe stenosis.

Acknowledgment. The authors thank Pierrette Lo for editorial assistance.

Abstract

Objectives This study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional flow reserve (FFR) as the standard.

Background The evaluation of significant LMCA stenosis remains challenging.

Methods We identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement.

Results The FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio [OR]: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm2 (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm2 in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA.

Conclusions In patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm2 is a useful index of an FFR of ≤0.80.

Because of the limitations on the assessment of the severity of left main coronary artery (LMCA) stenosis, the intravascular ultrasound (IVUS)-derived minimal lumen area (MLA) has frequently been used as a surrogate marker of significant LMCA stenosis. An IVUS MLA of 6 mm2 has conventionally been considered an indication for revascularization, and this criterion was supported by a recent prospective registry study (1,2). However, this cutoff value may overestimate the actual functional significance of stenosis and thereby increase the rate of unnecessary percutaneous coronary intervention.

Recently, we reported that a more stringent IVUS MLA cutoff value of 4.8 mm2 better corresponded to a fractional flow reserve (FFR) of ≤0.80 in patients with isolated LMCA stenosis (3). However, that study was limited by its small sample population. Therefore, we expanded the study population and re-evaluated the optimal IVUS-derived parameters for the functional significance of isolated LMCA stenosis. In addition, we performed various subgroup analyses and adjustments of the IVUS MLA for several anthropometric measurements to determine how patient characteristics affected the optimal cutoff value.

Methods

Study population

Between January 1, 2010 and December 31, 2012, 112 patients with isolated ostial and shaft LMCA stenosis that had been evaluated by FFR and IVUS before intervention were identified from an IVUS and FFR database. Patients with abnormal regional wall motion, significant distal lesions (angiographic diameter stenosis of >50% within the left anterior descending artery or left circumflex artery), myocardial infarction, angiographic evidence of thrombi-containing lesions, and those in whom the IVUS-imaging catheter failed to cross the lesion due to severe stenosis or tortuosity were excluded. The treatment strategy was left to the operator’s discretion. This study was approved by the institutional review board, and all patients provided written informed consent.

Angiographic analysis

Quantitative coronary angiographic (QCA) measurements, including the percentage of diameter stenosis, reference vessel diameter, and minimal luminal diameter, were acquired using standard techniques with automated edge-detection algorithms (CAAS-5, Pie-Medical, Maastricht, the Netherlands) in the angiographic analysis center of the CardioVascular Research Foundation (Seoul, Korea). Angiographic image acquisition was performed at target sites using ≥2 angiographic projections of the coronary narrowing. The reference diameter was determined by interpolation outside the obstructions boundaries but within LMCA (4).

FFR measurement

Equalization was performed with the guidewire sensor positioned at the tip of the guiding catheter. Then, a 0.014-inch pressure guidewire (Radi, St. Jude Medical, Uppsala, Sweden) was advanced into the coronary artery and positioned ≥3 cm distal to the LM lesion in either the left anterior descending or left circumflex artery, depending on which was least diseased distally. The FFR was measured under maximal hyperemia induced by an intravenous adenosine infusion administered through a central vein at 140 to 280 μg/kg/min. Hyperemic pressure pull-back recordings were performed as previously described (3). In patients with an ostial LM stenosis, care was taken to withdraw the guiding catheter from the LM during FFR assessment.

IVUS imaging and analysis

After FFR assessment, IVUS imaging was performed after intracoronary administration of 0.2 mg nitroglycerin using motorized transducer pullback (0.5 mm/s) and a commercial scanner (Boston Scientific/SCIMED, Minneapolis, Minnesota) consisting of a rotating 40-MHz transducer within a 3.2-F imaging sheath. Off-line quantitative IVUS analysis was performed in a core laboratory at the Asan Medical Center using computerized planimetry (EchoPlaque 3.0, Indec Systems, Mountain View, California) as previously described (5). The MLA and external elastic membrane area were measured at the site within the LM coronary segment above the carina at which the lumen was smallest. The plaque burden at the MLA site was calculated as (external elastic membrane area – lumen area) / external elastic membrane area × 100 (%). To determine the reproducibility of the measurements, MLA in 20 randomly selected patients were analyzed at different times by 2 independent blinded observers and by the same observer. Inter- and intraobserver variability were assessed using the 2-way random single measure intraclass correlation coefficient and the 1-way random 2-measure intraclass correlation coefficient, respectively. The inter- and intraobserver agreements regarding MLA measured by IVUS was excellent, with intraclass correlation coefficient values of 0.986 (95% Confidence Interval [CI]: 0.953 to 0.995; p < 0.001) and 0.978 (95% CI: 0.945 to 0.991; p < 0.001), respectively.

Statistical analysis

Continuous variables are presented as the mean ± SD, and they were compared using the Student t test. Categorical variables are presented as counts or percentages, and they were compared using the chi-square or Fisher exact tests. Receiver-operating curve analysis was performed to assess the discriminative powers of the IVUS and QCA parameters for an FFR of ≤0.80 using MedCalc (MedCalc Software, Mariakerke, Belgium) to define the sensitivity, specificity, positive predictive value, and negative predictive value with 95% confidence intervals (CI). The optimal cutoff values of the IVUS and QCA parameters for an FFR of ≤0.80 were identified as the values for which the sum of the sensitivity and specificity was greatest.

Multivariate logistic regression analysis was performed to identify the independent factors of an FFR of ≤0.80. We constructed 2 models. Model 1 included the clinical, IVUS, and QCA variables, and model 2 included the variables in model 1 plus additional echocardiographic variables. Variables were chosen by backward stepwise multivariate logistic regression analysis using a threshold of 0.05 for variable elimination. Variables that significantly associated with an FFR of ≤0.80 in univariate analyses were entered into final model. The variables entered in final models were rupture, body mass index, age, and MLA in model 1 and rupture, body mass index, age, MLA, and left ventricular (LV) mass in model 2. We computed the shrinkage factor to measure the overfitting using the likelihood ratio of the fitted model. Shrinkage factor was 0.93 and 0.94 for model 1 and model 2, respectively. The shrinkage factor quantifies the overfitting of a model where values >0.85 might not be of concern (6).

All statistical analyses were performed using SPSS (version 12.0, SPSS, Inc., Chicago, Illinois). A p value of < 0.05 was considered indicative of statistical significance.

Results

Baseline characteristics

The clinical characteristics of the 112 patients with isolated LMCA stenosis are summarized in Table 1. Their mean age was 60 years of age, 74% were men, 29% had a history of diabetes, 5% had a history of previous myocardial infarction, and 36% presented with acute coronary syndrome. Table 2 shows their coronary angiography, IVUS, and echocardiographic results. The mean FFR was 0.78 ± 0.09, the mean diameter stenosis 46.9 ± 11.4%, and the mean minimal lumen area 4.8 ± 2.2 mm2. Overall, 66 lesions (59%) had an FFR of ≤0.80 at maximum hyperemia. The LMCA lesions with an FFR of ≤0.80 exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter stenosis, longer lesion length, smaller minimal lumen area, larger plaque burden, and more frequent plaque rupture.

Table 1

Baseline Characteristics

Table 2

Coronary Angiographic, IVUS, and Echocardiographic Characteristics

Parameters of the functional significance of LMCA

Multivariable linear and logistic regression analysis including clinical, angiographic, and IVUS variables identified plaque rupture (odds ratio [OR]: 4.47; 95% CI: 1.356 to 14.8; p = 0.014), body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001) as independent factors of an FFR of ≤0.80. In addition, when the echocardiographic variable of LV mass was included in the preceding model, LV mass (OR: 1.01; 95% CI: 1.00 to 1.03; p = 0.03), age (OR: 0.94; 95% CI: 0.90 to 0.99; p = 0.021), and IVUS MLA (OR: 0.34; 95% CI: 0.21 to 0.54; p < 0.001) were independent factors of an FFR of ≤0.80 (Table 3).

Table 3

Independent Factors of Functionally Significant LMCA Stenosis

Cutoff values of parameter

The best cutoff value of IVUS MLA within the LM (minimizing the distance between the curve and the upper corner of the graph) for an FFR of ≤0.80 was 4.5 mm2 (77% sensitivity, 82% specificity, area under the curve = 0.83; 95% CI: 0.759 to 0.960; p < 0.001) (Fig. 1). The FFR was >0.80 in only 10 (17.2%) of 58 lesions with an MLA of ≤4.5 mm2 (“mismatch”). Among the 54 lesions with an MLA of >4.5 mm2, only 13 (24.1%) had an FFR of ≤0.80 (“reverse mismatch”) (Fig. 2). Table 4 shows the optimal cutoff values of the IVUS MLA for various subgroups; these ranged between 4.1 mm2 and 4.5 mm2. In addition, we adjusted the MLA for the body mass index, body surface area, and LV mass assessed by echocardiography. However, these adjustments did not improve the diagnostic accuracy over that of the unadjusted IVUS MLA (Fig. 3).

Figure 1

Cutoff Values and Corresponding Diagnostic Accuracies of IVUS-Derived Parameters of an FFR of ≤0.80

(A) Minimal lumen area; (B) plaque burden; (C) diameter stenosis, and (D) minimal lumen diameter. AUC = area under the curve; FFR = fractional flow reserve; IVUS = intravascular ultrasound; NPV = negative predictive value; PPV = positive predictive value.

Figure 2

Scatter Plot of IVUS MLA Versus FFR

MLA = minimal lumen area; other abbreviations as in Figure 1.

Figure 3

The Cutoff Values and Corresponding Diagnostic Accuracies of the IVUS-Derived MLA Adjusted for Various Anthropometric Measurements

AUC = area under the curve; BMI = body mass index; BSA = body surface area; CI = confidence interval; LV = left ventricle; other abbreviations as in Figures 1 and 2.

The optimal cutoff values for plaque burden, diameter stenosis, and minimal lumen diameter were 77%, 51%, and 1.9 mm, respectively (Fig. 1).

Table 4

Optimal Cutoff Values of the MLA for the Detection of Functionally Significant LMCA Stenosis for Various Subgroups

Discussion

In this study, we found several clinical and anatomical factors that could be associated with the functional significance of LMCA stenosis. The presence of plaque rupture was a strong factor of functionally significant stenosis in diseased LMCA (3). The body mass index and LV mass assessed by echocardiography were also identified, possibly because these factors may be associated with the extent of the myocardium supplied by the LMCA.

An IVUS MLA of ≤4.5 mm2 was an independent factor of an FFR of ≤0.80. In subgroup analyses, the cutoff values of IVUS MLA associated with an FFR of ≤0.80 ranged between 4.1 and 4.5 mm2. In addition, adjustment for the body mass index, body surface area, or LV mass assessed by echocardiography did not improve the accuracy of the IVUS MLA for an FFR of ≤0.80. Traditionally, an MLA of 6.0 mm2 was considered to represent functionally significant LMCA stenosis. This value was derived primarily from Murray law, with an MLA of 4.0 mm2, considered to represent the ischemic threshold of the left anterior descending artery or left circumflex artery, and was supported by a clinical study comparing the IVUS MLA and FFR values (1,2). However, the IVUS MLA value corresponding to ischemia-producing lesions of non-LM epicardial coronary arteries was recently reported to be <3 mm2 (between 2.1 mm2 and 3.07 mm2) (7–10). The application of Murray law to these values suggests that the IVUS MLA of a stenotic LM coronary artery that corresponds to an FFR of ≤0.80 should be <5 mm2, which is similar to our finding of an IVUS MLA cutoff value of 4.5 mm2 (Fig. 4). In addition, the previous study enrolled a smaller number of patients (55 patients) with less-significant LMCA stenosis (mean FFR: 0.86) than our study population did (mean FFR: 0.78, N = 112), which may explain the larger cutoff value identified in the earlier study (1).

Figure 4

Geometric Abstractions

Geometric abstractions from Murray law, Finet law, and H-K law. H-K = Huo and Kassab; LAD = left anterior descending; LCX = left circumflex; LM = left main.

The accuracy of the IVUS MLA for functional significance is higher for LMCA stenosis than for non-LMCA stenosis (3,7). This was previously attributed to the simplicity of the morphologic characteristics of isolated ostial and shaft LMCA stenosis, including the uniformly large vessel size, short lesion length, and lack of side branches and other anatomical factors that could potentially affect FFR (3). Considering the prognostic importance of detection of significant LMCA stenosis, this greater accuracy may not justify the decision to treat or not to treat on the basis of an IVUS MLA alone because the cutoff value identified in the current study still yielded a 16% rate of mismatch and a 25% rate of reverse mismatch. In addition, relative to non-LMCA epicardial coronary artery stenosis, LMCA stenosis produced a higher frequency of “reverse mismatch” (11). This finding could be attributed to the greater amount of myocardium supplied and high frequency of plaque rupture in LMCA disease. Therefore, especially in cases of intermediate ostial and shaft LMCA stenosis, direct FFR measurement remains crucial to reduce the risk of overtreatment or undertreatment. However, in cases of complex LMCA stenosis in which FFR or noninvasive functional evaluation would be inaccurate, an IVUS MLA of 4.5 mm2 could be a useful criterion for revascularization.

We found that plaque rupture was identified as an independent factor of functionally significant LMCA stenosis, which was consistent with the findings of previous studies (3,11). Theoretically, a complex or irregular lumen made by plaque rupture could produce greater flow resistance and energy loss of fluid, thus resulting in a greater pressure drop and reduction of FFR. In addition, thrombotic material superimposed on a ruptured site may increase the roughness of the vessel surface, resulting in the further increase of the flow resistance. Therefore, among lesions with the same degree of angiographic stenosis, the various shapes of a ruptured plaque could reduce the FFR value (11).

Study limitations

First, the current study included only Asian subjects, who may have relatively small hearts. In an attempt to overcome this limitation, we tried to adjust the IVUS MLA with respect to various anthropometric measurements, including the body surface area, body mass index, and LV mass. However, none of these adjustments improved the diagnostic accuracy, which suggested that these factors might not significantly affect the optimal cutoff value of the IVUS MLA for identifying functionally significant stenosis. Further larger studies or inter-racial studies will be necessary to evaluate the impact of ethnicity and/or body size. Second, we excluded patients with significant left anterior descending artery disease or left circumflex artery stenosis. However, isolated LMCA stenoses are very rare, with most stenoses associated with disease in the left anterior descending artery and/or left circumflex artery, both of which tend to increase FFR measured across the LMCA stenosis. Therefore, in this case, the reassessment for the functional significance of intermediate LMCA stenosis was recommended after the correction of distal coronary artery stenosis (12).

Conclusions

In patients with isolated ostial and shaft LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm2 is a useful index of an FFR of ≤0.80.

Footnotes

  • The study is supported by the Korea Healthcare Technology Research and Development Project, Ministry of Health and Welfarehttp://dx.doi.org/10.13039/501100003625 (#A120711), and CardioVascular Research Foundation, Seoul, Republic of Korea. Dr. Koo has received lecture fees and a research grant from St. Jude Medicalhttp://dx.doi.org/10.13039/100006279. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. S.-J. Park and Dr. Ahn contributed equally to this paper.

Abbreviations and Acronyms
CI
confidence interval
FFR
fractional flow reserve
IVUS
intravascular ultrasound
LMCA
left main coronary artery
LV
left ventricular
MLA
minimal lumen area
OR
odds ratio
QCA
quantitative coronary angiogram
  • Received June 25, 2013.
  • Revision received February 7, 2014.
  • Accepted February 13, 2014.
  • American College of Cardiology Foundation

References

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