Intravascular Ultrasound-Guided Management of Angiographically Intermediate Non-Culprit Coronary Artery Lesions in Acute Coronary Syndrome

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1 Med. J. Cairo Univ., Vol. 85, No. 4, June: , Intravascular Ultrasound-Guided Management of Angiographically Intermediate Non-Culprit Coronary Artery Lesions in Acute Coronary Syndrome FAROUK M. FARES, M.D.; AKRAM M. ABD ELBARY, M.D.; AHMED H. MOWAF, M.D.; MOHAMED A. SHAWKY, M.D. and HELMY H. ELGHAWABY, M.D. The Department of Critical Care Medicine, Faculty of Medicine, Cairo University Abstract Background: The assessment of intermediate coronary lesions using coronary angiography is often challenging. The purpose of this study was to use an intravascular ultrasoundguided strategy to determine the anatomical significance of angiographically intermediate non-culprit coronary lesions to help in their management in the setting of ACS. Methods: We conducted an intravascular ultrasound studies on sixty one angiographically intermediate non-culprit coronary lesions in twenty eight patients with Non ST elevation ACS. Revascularization was recommended when percent area stenosis 70% Results: Minimal and maximal lumen diameters were significantly lower (p<0.001), MLA was significantly lower (p<0.001) and percent area stenosis was significantly higher in revascularization group (p<0.001). MLA & plaque burden are the main predictors for lesion anatomical significance with (p<0.001, OR=0.25, 95% CI= ) and ( p=0.011, OR=2.0, 95% CI= ) respectively. Conclusions: MLA & plaque burden are the main predictors for lesion anatomical significance. Key Words: Intermediate lesions IVUS: Intravascular ultrasound MLA: Minimal lumen area ACS: Acute coronary syndrome. Introduction ACUTE coronary syndromes may frequently arise from lesions with only mild to moderate stenosis since these lesions may be more common than severe obstructive lesions [1-5]. 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 Correspondence to: Dr. Farouk M. Fares, The Department of Critical Care Medicine, Faculty of Medicine, Cairo University percentage of stenosis and the lesion s physiologic importance and considerable inter-observer variability in classifying the lesion s severity [6-8]. IVUS has been used extensively for assessment of intermediate coronary lesions to demonstrate functional significance (the induction of ischemia) together with FFR and other non-invasive measures [9]. An IVUS-measured minimal luminal area (MLA) of <4.0mm 2 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 singlephoton emission computed tomography (SPECT) [10], doppler wire studies [11], and pressure wire measurement [12]. The clinical importance of this criterion has been confirmed by a study showing that deferral of revascularization is safe for patients with an MLA of >4.0mm 2 [13]. Also, IVUS can guide therapeutic strategy in lesions requiring percutaneous coronary intervention (PCI), and assess stent deployment [14]. Aim of work: The use an intravascular ultrasound-guided strategy to determine the anatomical significance of angiographically intermediate non-culprit coronary lesions to help in their management in the setting of ACS. Patients and Methods An observational cross-sectional study was conducted at Critical Care Department, Cairo University between January 2013 and December Inclusion criteria: Twenty eight patients with the diagnosis of unstable angina and non-st- 1335

2 1336 Intravascular Ultrasound-Guided Management of Angiographically Intermediate elevation myocardial infarction had sixty one angiographically-intermediate non-culprit coronary lesions either in culprit or non-culprit vessels. According to the American College of Cardiology and the American Heart Association, intermediate stenosis was defined as having a diameter of 40% and <70%, as measured by quantitative coronary angiography (QCA) [15]. IVUS had been used to further define the severity of these lesions then management either conservatively or by percutaneous coronary intervention (PCI). All patients had clinical evidence of myocardial ischemia in the territory of the culprit vessel including ECG changes, perfusion defects on technetium 99m sestamibi (MIBI) single photon emission computed tomography (SPECT) and regional wall motion abnormalities on echocardiograms. Exclusion criteria: Patients were excluded if they had an ST-elevation acute myocardial infarction, any contraindication to anticoagulation, renal impairment or previous coronary artery bypass grafting (CABG). Diagnostic methods: The diagnostic angiograms were obtained using Digital Imaging and Communications in Medicine (DICOM)-compatible digital systems (Siemens AG model No , Germany & Philips CV20, Netherland). Prior to beginning the IVUS studies, patients were given 10,000 U of unfractionated heparin for systemic anticoagulation. IVUS was performed using conventional 6Fr guiding catheters and a 0.014mm guidewire was positioned distally. IVUS catheters of 40MHz (Atlantis; Boston Scientific Corp., Natick, Massachusetts) were pulled back automatically at a constant speed of 0.5mm/second. The measurements were performed according to the guidelines of the American College of Cardiology for the acquisition, measurement and reporting of IVUS studies [16]. The following parameters were included in the IVUS analyses: Minimal lumen area (MLA), external elastic membrane (EEM) cross sectional area, plaque area, percent area stenosis, remodeling index, minimal and maximal lumen diameters, proximal and distal reference diameter. Plaque burden is calculated as plaque area divided by the EEM cross sectional area. If EEM area increases during atheroma development, the process is termed positive remodeling. If the EEM decreases, the process is termed negative or constrictive remodeling. An index that describes the magnitude and direction of remodeling is expressed as: Lesion EEM CSA/reference EEM CSA. If the lesion EEM area is greater than the reference EEM area, positive remodeling has occurred, and the index will be >1.0. If the lesion EEM area is smaller than the reference EEM area, negative remodeling has occurred, and the index will be <1.0 [17]. Statistical analysis: Pre-coded data was entered on the computer using "Microsoft Office Excel Software" program (2010) for windows. Data was then transferred to the Statistical Package of Social Science Software program, version 21 (SPSS) to be statistically analyzed. Data was summarized using mean, standard deviation, median and inter quartile range for quantitative variables and frequency and percentage for qualitative ones. Comparison between groups was performed using independent sample t-test or one way ANOVA with Tukey s post hoc test for quantitative variables and Chi square or Fisher s exact test for qualitative ones. Pearson correlation coefficients were calculated to get the association between different quantitative variables. Logistic regression analysis was performed to explore the significant predictors of revascularization. p-values less than 0.05 were considered statistically significant, and less than 0.01 were considered highly significant. Results Twenty eight patients presented by NSTEMI ACS with the following demographic & clinical data as in Table (1). Table (1): Demographic and clinical data of study patients. Range Mean ± SD Age (years) ±9.1 Body mass index ±2.9 TIMI risk score ± 1.4 Laboratory results: Hemoglobin (gm%) ± 1.7 Creatinine (mg/dl) ±0.2 Cholesterol (mg/dl) ±30.4 Frequency Percentage (n=28) (%) Gender: Male Female Risk factors: Smoking Diabetes Mellitus Hypertension Dyslipidemia ve Family history History of CAD: Previous MI Previous PCI Clinical diagnosis: Unstable angina NSTEMI

3 Farouk M. Fares, et al Angiographic data: Shown in Table (2) & Fig. (1): Table (2): Number of vessels diseased. Number of patients Percentage Single vessel disease Two vessel disease Multi-vessel disease lesions Visual assessment Significant Intermediate Non-significant lesions=31 lesions=61 lesions=11 7.1% IVUS 60.8% 32.1% Medical treatment Group I=34 Revascularization Group II=27 Fig. (3): Distribution and fate of all lesions. Single vessel disease 55.7% Multi-vessel disease Two vessel disease Fig. (1): Number of vessels diseased. Coronary angiography showed 103 total lesions divided by visual assessment into: Thirty one significant lesions (30.1%) showed more than 70% stenosis. Sixty one intermediate lesions (59.2%) with 40-70% stenosis. Eleven non-significant lesions (10.7%) with less than 40% stenosis. Fifty three (86.8%) of the 61 intermediate lesions were located at the proximal and midportions of the artery. According to the adopted IVUS criteria (percent area stenosis >70%), the lesions were divided into two groups; group I including 34 lesions (55.7%) for deferral of revascularization and group II including 27 lesions (44.3%) for revascularization. 44.3% Group II lesions were more severe, as indicated by a higher percentage of luminal area stenosis (p<0.001) and lower minimal lumen area (p<0.001) detected by IVUS. Also, maximal and minimal lumen diameters were significantly lower in revascularization group than medical treatment group (p<0.001). Mean lesion MLA Mean percent stenosis p< ± ± ± 1.56 p<0.001 Medical treatment Revascularization Fig. (4): Lesion MLA in both groups ± Revascularization Medical treatment Fig. (2): Grouping according to IVUS measures Medical treatment Revascularization Fig. (5): Percent area stenosis in both groups.

4 1338 Intravascular Ultrasound-Guided Management of Angiographically Intermediate Most of the lesions were eccentric and showed negative remodeling [34 lesions (55.7%)] Percentage 44.3 Negative remodelling Positive remodelling Fig. (6): Remodeling of intermediate lesions. Further analysis of IVUS data by Backward stepwise regression model showed that MLA & plaque burden are the main predictors for lesion anatomical significance with (p<0.001, OR=0.25, 95% CI= ) and (p=0.011, OR=2.0, 95% CI= ) respectively. Discussion Assessment of a coronary lesion with intermediate severity continues to be a challenge. It might be tempting to treat all suspect lesions with implantation of a stent. However, there are still procedural complications associated with angioplasty, the inherent risk of restenosis, and late stent thrombosis [18,19]. Although it is preferable to have objective evidence of myocardial ischemia before proceeding with percutaneous coronary revascularization, this is not always feasible or completely reliable. All measures of noninvasive assessment of myocardial ischemia are compared with the presence of a focal stenosis >50% diameter. This cutoff is based on animal studies and human clinical correlations that demonstrate functional significance (the induction of ischemia) with the anatomic presence of a 50% diameter stenosis [9]. An important finding in our study was that most of lesions (49.2%) were located in the proximal segments of the examined arteries. Numerous pathological, angiographic, and imaging studies have shown a proximal predisposition of thin capped fibro-atheroma, acute occlusions, or plaque ruptures [20-25]. This tendency of advanced plaques to develop preferentially in these locations has been explained by the low shear stress conditions generated in areas with tortuosity or many branches. Low shear stress may induce the migration of lipid and monocytes into the vessel wall leading to the progression of the lesion towards a plaque with high risk of rupture [26]. 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 [27,28]. Moreover, previous IVUS studies have demonstrated the correlation between a MLA <4.0mm 2 and decreased fractional flow reserve [29], while a MLA 4.0mm 2 was correlated with a preserved fractional flow reserve and favorable outcomes with deferral of invasive intervention [13]. In the present study, 10% of the lesions diagnosed as moderate by conventional angiography had, in fact, severe stenosis by the adopted IVUS criterion (percent area stenosis >70%). The most obvious finding revealed from the analysis of our data is that minimal lumen area (MLA) & plaque burden were the main predictors for lesion significance for revascularization. These results are in agreement with those obtained by Koo et al. [20] which showed that minimal lumen area was the main determinant of functionally significant stenosis. Furthermore, Kang et al. [30] compared quantitative coronary angiography and intravascular ultrasound (IVUS) with stress myocardial singlephoton emission computed tomography (SPECT). Independent determinants for a positive SPECT were in-segment angiographic diameter stenosis & in-segment IVUS-MLA. Conclusion: Our study shows that intravascular ultrasound is a helpful tool in accurately assessing the degree of stenosis in the coronary lesions that appear angiographically intermediate in patients with ACS. Additionally, MLA & plaque burden are the main predictors for lesion anatomical significance. References 1- AMBROSE J.A., TANNENBAUM M.A., ALEXOPOU- LOS D., et al.: Angiographic progression of coronary artery disease and the development of myocardial infarction. J. Am. Coll. Cardiol., 12: 56-62, 1988.

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