Abstract: Background. A certain minimal luminal cross-sectional area has been traditionally used in clinical practice as a cut-off value to determine severity of left main coronary artery (LMCA) stenosis. The severity of stenosis, however, depends on the baseline luminal area (ie, area prior to stenosis), which may vary among individuals. The present study was undertaken to define normal LMCA luminal area using current technology in vivo. Methods. LMCA luminal area was determined using multislice computed tomography coronary angiography. Eighty-six subjects with normal coronary arteries and calcium score of zero were included in this study. Left ventricular (LV) mass and LV volumes (systolic, diastolic) were also measured. Results. A wide distribution was found in LMCA luminal area, with median value 17.3 mm2 and range 8.1-33.9 mm2. A relationship was found between log(LMCA luminal area) and log(LV mass) (r=.515; P<.001) and with body surface area (r=.273; P=.01). Significant relationships were also found between LMCA luminal area and LV volumes (systolic, diastolic). In multiple regression analysis, however, the LV mass was the only independent predictor of LMCA luminal area. Conclusion. LMCA luminal area varies substantially among individuals with normal coronary arteries and is related to many other factors. The data suggest that the current practice of using a minimal luminal area cut-off when assessing LMCA stenosis may be misleading, and thus available information should be individualized.
J INVASIVE CARDIOL 2017;29(7):246-249. Epub 2017 February 15.
Key words: left main, luminal area, left ventricular mass
Significant left main coronary artery (LMCA) stenosis is treated with revascularization either by coronary artery bypass graft surgery or percutaneous coronary intervention.1-3 Coronary arteriography, intravascular ultrasound (IVUS), and computed tomography (CT) coronary angiogram can be used to define the severity of disease.4-6 Traditionally, a certain minimal luminal cross-sectional area used by IVUS has been used in clinical practice as a cut-off value to determine whether LMCA stenosis is significant and requires revascularization;7-9 however, the severity of stenosis of any artery, including the LMCA, should be related to the baseline luminal area of the artery prior to the development of atherosclerosis. This may be related to several factors such as left ventricular (LV) mass, body surface area (BSA), and others.10-14 The present study was undertaken to define LMCA luminal area in individuals with normal coronary arteries and to determine factors related to LMCA luminal area using current in vivo technology.
Study population. This observational, cross-sectional study included 86 individuals who were studied at The Ohio State University Medical Center. All subjects had normal coronary arteries by CT coronary angiography and a calcium score of zero. The clinical indications for performing CT coronary angiography were atypical chest pain, exertional dyspnea, abnormal cardiovascular functional study, abnormal electrocardiogram, and/or history of syncope or cardiac arrhythmias. The cross-sectional luminal area of the LMCA was determined in all subjects using standard CT coronary angiogram techniques.14 Due to the fact that the pre-test probability for coronary artery disease in these individuals was low, non-invasive CT coronary angiography was performed instead of coronary arteriography, which requires an invasive cardiac catheterization procedure.
Age, gender, and the presence of diabetes mellitus, arterial hypertension, hyperlipidemia, and tobacco smoking were determined. The protocol of the study was approved by The Ohio State University Institutional Review Board (IRB).
CT coronary angiography. A 64-slice scanner (Somatom 64; Siemens) was used to determine the cross-sectional luminal area of the LMCA. The detector collimation was 32 x 0.6 mm, which resulted in 64 slices/rotation with an overlap of 0.3 mm; the reconstructed slice resolution was approximately 0.4 mm. The tube voltage was 120 kV and the gantry rotation speed was 330 ms/rotation. Electrocardiogram dose modulation was applied to reduce radiation exposure. If the heart rate was greater than 70 beats/minute prior to imaging, a beta-blocking agent was administered. A timing bolus scan was performed to determine the appropriate delay to peak signal intensity in the aortic root. For coronary angiogram imaging, an inspiratory breath-hold was performed and 80 mL iodinated non-ionic, monomeric contrast agent (Iohexol) injection was administered at 5 mL/second followed by a saline flush. Electrocardiographically gated thin section data sets were reconstructed and image analysis (Aquarius, TeraRecon) was performed. Multiplanar reformatting was used to generate cross-sectional images using semi-automated software (Vessel Analysis 3.6, TeraRecon); this technique yields a vessel centerline using the full-width-half maximum standard method to delineate the contrast-filled vessel. The luminal area of the LMCA was measured in all studied subjects, as described previously in our laboratory.14 Measurements of LV end-systolic volume, LV end-diastolic volume, and LV ejection fraction were also determined. LV mass was determined in end-diastole from contiguous short-axis multiphase images covering the heart using standardized postprocessing software (Argus; Siemens). Image analyses were performed blinded.
Statistical analysis. Descriptive data are shown as either mean ± standard deviation or as a median with a low and high range. Associations between LMCA luminal area with nominal variables and continuous variables were assessed using two-sample t-tests and Pearson correlation r, respectively; simple linear regression analysis was used where LMCA luminal area and other variables were expressed on a logarithmic scale to conform to a normal distribution. A stepwise multiple regression procedure was used to determine all the independent predictors of LMCA luminal area. A P-value <.05 was considered statistically significant.
Baseline characteristics of the study population are shown in Table 1. The distribution of LMCA luminal area for each individual is shown in Figure 1A; there is a great variation among these individuals with normal coronary arteries. The LMCA mean and median luminal area were 17.9 ± 6.2 mm2 (Figure 1B) and 17.3 mm2 (range, 8.1-33.9 mm2; Figure 1C), respectively. Mean and median BSA were 1.9 ± 0.2 m2 and 1.9 m2 (range, 1.3-2.7 m2), respectively.
Simple linear regression analysis demonstrated a weak, but statistically significant linear relationship between log(LMCA luminal area) and BSA (r=.273; P=.01) (Figure 2). Simple linear regression analysis also demonstrated a statistically significant linear relationship between log(LMCA luminal area) and log(LV mass) (r=.515; P<.001) (Figure 3). Correlations were also found between log(LMCA luminal area) and log(LV end-systolic volume) (r=.457; P<.001), and between log(LMCA luminal area) and log(LV end-diastolic volume) (r=.541; P<.001). There was no correlation between LMCA luminal area and LV ejection fraction. When all these parameters were analyzed together in a multiple regression analysis, LV mass was the only independent predictor of LMCA luminal area.
Two-sample t-test demonstrated a significant association between log(LMCA luminal area) and diabetes mellitus (P=.01); those with diabetes mellitus had a 30% increase in LMCA luminal area. Two-sample t-test showed that there was no association between diabetes mellitus and BSA (P=.81), but the average LV mass among patients with diabetes mellitus was 32% higher compared to patients without diabetes mellitus (P=.01); however, the number of patients with diabetes mellitus was relatively small (n = 10).
Two-sample t-test demonstrated a significantly greater LMCA luminal area in left or co-dominant coronary arteries (21.9 ± 7.9 mm2) when compared with right dominant coronary arteries (17.2 ± 5.6 mm2; P=.01).
Two-sample t-tests showed no association between log(LMCA luminal area) and gender (P=.07), arterial hypertension (P=.95), hyperlipidemia (P=.47), or tobacco smoking (P=.61). Simple linear regression analysis showed no association between log(LMCA luminal area) and age (P=.82).
The present study demonstrated that in individuals with normal coronary arteries, LMCA luminal area depends on anthropometric parameters and LV structure. In multiple regression analysis, however, only LV mass was independently related to LMCA luminal area. In clinical practice, IVUS is a valuable imaging tool to determine LMCA luminal area and to risk-stratify patients who may need coronary revascularization. An LMCA minimal luminal area of less than 4.8 mm2, 6.0 mm2, or 7.5 mm2, as determined by IVUS, has been used as a hard cut-off value to determine whether LMCA stenosis is significant and requires revascularization;5,7-9 however, the severity of stenosis of any artery depends on the baseline luminal area of the artery (ie, area prior to the development of atherosclerosis). This study demonstrated that LMCA luminal area differs significantly among normal individuals (Figure 1A), with a wide range from 8.1-33.9 mm2 (median luminal area, 17.3 mm2) (Figure 1C). Furthermore, LMCA luminal area, as shown in this study and suggested previously, depends on several other factors including BSA and LV mass.10-14 LMCA luminal area was also found to be related to LV end-systolic and end-diastolic volumes; however, LV volume depends on the body size of the individual. In a multiple regression analysis, however, LV mass was the only independent predictor of LMCA luminal area. The data from this study, therefore, challenge the notion of using a single cut-off minimal luminal area value in order to determine significant LMCA disease.
A significant correlation was also found between LMCA luminal area and diabetes mellitus; this association most likely was secondary to greater LV mass that was seen in patients with diabetes mellitus. The number of patients with diabetes mellitus, however, was too small to allow for further analysis. In addition, LMCA luminal area was significantly greater in left or co-dominant coronary arteries compared with right dominant coronary arteries. LV mass was not greater in the subgroup of patients with arterial hypertension. The individuals studied were relatively younger, with an average age of 44 years; thus, the duration of hypertension was relatively short. The short duration of arterial hypertension most likely did not have any measurable effect on LV mass.
Previous studies have demonstrated an excellent agreement between LMCA luminal area as determined by CT coronary angiogram and IVUS,15-18 and IVUS has been shown to have a good agreement with pathology specimens.19,20 Due to the low probability of coronary artery disease in these individuals and due to the fact that CT coronary angiography is non-invasive, CT coronary angiography was used in this study rather than invasive coronary arteriography with IVUS.
This study consisted of individuals without coronary artery disease. Early stages of coronary atherosclerosis, however, cannot totally be excluded. The fact that no atherosclerotic plaque or calcium was detected in the entire coronary arterial tree by CT imaging strongly suggested that these individuals were free of any coronary atherosclerosis.21-23 It is a possibility that the contrast agent used during CT imaging may have potentially exerted a vasodilator effect on the coronary arteries; this effect is expected to be mostly in the smaller arteries rather than in the LMCA. Furthermore, a non-ionic, monomeric contrast agent was used to minimize this effect.24
This study was conducted in individuals without valvular heart disease such as aortic stenosis, aortic regurgitation, or mitral regurgitation, or patients with severe longstanding arterial hypertension, which may increase LV mass. Thus, we cannot comment on how LV mass will alter LMCA luminal area in these patients. Nonetheless, the data indicate that LMCA luminal area varies greatly in normal individuals and is related to several factors including BSA, LV volumes, and LV mass when analyzed separately by single regression analysis. In multiple regression analysis, however, LV mass was the only independent predictor of LMCA luminal area. Hence, the severity of LMCA stenosis for an individual patient cannot be based only on a single value. The data indicate that “one size does not fit all,” and thus available information should be applied to the individual patient by a caring physician who uses common sense and clinical wisdom.25
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From the 1Department of Medicine, Division of Cardiovascular Medicine; 2Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted October 24, 2016, final version accepted November 3, 2016.
Address for correspondence: Konstantinos Dean Boudoulas, MD, Associate Professor of Medicine, The Ohio State University, Department of Medicine/Cardiovascular Medicine, Columbus, Ohio 43210. Email: firstname.lastname@example.org