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Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI
Cardiovascular Revascularization Medicine xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI☆ Nigussie Bogale a,b,⁎, Mathieu Lempereur b, Imran Sheikh b, David Wood b, Jacqueline Saw b, Anthony Fung b a b
Stavanger University Hospital, Stavanger, Norway Vancouver General Hospital, Vancouver, BC, Canada
a r t i c l e
i n f o
Article history: Received 12 September 2015 Received in revised form 13 December 2015 Accepted 22 December 2015 Available online xxxx Keywords: OCT Intermediate coronary lessions NSTEMI
a b s t r a c t Introduction: Coronary angiography is commonly performed following non-ST segment elevation myocardial infarction (NSTEMI) to assess the need for revascularization. Some of these patients have myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA). Patients without severe obstructive lesions are usually treated conservatively. However, coronary angiography has known limitations in the assessment of lesion severity. We report our experience of using coronary Optical Coherence Tomography (OCT) in a series of patients without severe obstructive coronary lesions. Methods: 165 patients underwent coronary OCT at Vancouver General Hospital. NSTEMI was the clinical presentation in 70 patients and 26 had angiographically intermediate lesions with 40%–69% diameter stenosis. Prior to OCT image acquisition, intracoronary nitroglycerin 100–200 μg was administered. Blood in the vessel was displaced using contrast media by manual injections. Results: OCT of the angiographically intermediate lesions showed larger minimal luminal area (MLA) than the angiographically severe lesions (MLA 3.3 mm2 ± 1.8 mm2 vs. 1.6 mm2 ± 0.6 mm2, p b 0.001) and less severe % lumen area stenosis (54.2% ± 11.4% vs. 70.9% ± 6.8%, p = 0.001). Plaque rupture or intracoronary thrombus was detected in 8/26 (31%) patients. PCI with stent deployment was performed in 16 patients (62%). Conclusion: In stabilized patients with NSTEMI and angiographically intermediate disease, OCT examination confirmed the lack of severe anatomical stenosis in most patients. However, OCT also identified coronary lesions with unstable features. Further research is needed to help guide management of this subgroup of patients. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Pathological examination of patients with acute coronary syndrome (ACS) typically showed intracoronary thrombus with plaque rupture, erosion or calcium nodules [1]. Optical coherence tomography (OCT) has high spatial resolution, and previous studies have documented its ability in characterizing such complicated plaque features. Consensus documents on image acquisition, measurement and reporting as well as detailed image description have been published [2,3]. Patients with recent non-ST elevation myocardial elevation (NSTEMI) have elevated cardiac biomarkers, and in general, have higher short-term cardiac risk [4,5]. Most of these patients have severe angiographic lesions (≥ 70% diameter stenosis), and they are typically treated with revascularization [6]. A minority of patients present with less severe angiographic lesions, and are more likely treated with medical
☆ Disclosures: The authors report no financial relationships or conflicts of interest regarding the content of this manuscript. ⁎ Corresponding author at: Stavanger University Hospital, Department of Cardiology, Stavanger, Norway and Vancouver General Hospital, Vancouver, Canada. Tel.: + 47 41309313. E-mail address: [email protected] (N. Bogale).
therapy alone. A recent clinical review by Nicoli et al. used the term “myocardial infarctions (MI) with no obstructive coronary atherosclerosis (MINOCA)” to describe this smaller, but important subgroup of patients. The authors also proposed treatment algorithm including the use of intracoronary imaging [7]. Coronary angiography has known limitations in the assessment of lesion severity [8]. OCT maybe particularly useful in this setting to better evaluate lesion severity and characteristics. We report our experience with OCT in patients with intermediate lesions who are clinically stable. 2. Methods We retrospectively evaluated all consecutive OCTs that were performed in 165 patients at Vancouver General Hospital from November 2010 to March 2013. Seventy (42%) were performed in patients presenting with NSTEMI. We excluded OCTs that were performed in lesions with prior stenting in the same vessel (n = 22), bypass vein grafts (n = 2), inadequate imaging (n = 4) and imaging for other indications (spasm, spontaneous coronary artery dissection and intramural hematoma) (n = 6). The current report focuses on the remaining 36 cases. Based on the angiographic visual estimates, 26 cases were classified as intermediate (40% to 69% diameter stenosis) and 10 cases were
http://dx.doi.org/10.1016/j.carrev.2015.12.007 1553-8389/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
2
N. Bogale et al. / Cardiovascular Revascularization Medicine xxx (2016) xxx–xxx
Fig. 1. Flowchart of OCT cases. * SCAD = Spontaneous Coronary Artery Dissection and ** IMH = Intramural Hematoma.
classified as severe (≥70% diameter stenosis) (Fig. 1). We did not perform OCT examination in any patient with b 40% diameter stenosis. All imaging was acquired using the second generation Fourier domain (FD) OCT (C7-XR/ILUMIEN™ system from St. Jude Medical/LightLab Imaging, Westford MA, USA). Prior to image acquisition, 100–200 μg of nitroglycerin was administered. Scanning of the region of interest was performed by automated pullback at a speed of 20 mm/s. We typically inject 9–14 ml of contrast media manually via the guiding catheter to clear
blood from the imaging field. Images were acquired digitally and stored locally for evaluation and analysis on a dedicated work-station. Longitudinal image runs were scanned to examine the areas of interests. Minimal luminal area (MLA) was measured after proper Z-offset calibration. Proximal and distal reference areas were measured and the average was registered as average reference vessel luminal area. 3. Statistical analysis Continuous variables are presented as means ± standard deviations. Categorical variables are presented as numbers and percentages.
Table 1 Baseline characteristics. Severity of Angiographic Stenosis
Intermediate (n = 26)
Severe (n = 10)
p-value
Age (mean ± SD) Male (n, %) Days: admission to procedure (median, range) ECG (n, %) New ST elevation New ST depression New T wave inversion Non-specific ST changes Normal LV function (n, %) Regional wall motion abnormality LV EF b 50% Location of culprit lesion (n, %) LM LAD LCx RCA Peak Troponin-I level (median and range)
64 ± 14 16 (62%) 2 [1–7]
57 ± 10 7 (70%) 2(1–3)
0.16 0.64 0.35 0.17
0 1 (4%) 8 (31%) 6 (23%) 11 (42%)
0 0 6 (60%) 2 (20%) 2 (20%) 0.47
8 (31%) 8 (30%)
2 (20%) 0
1 (4%) 19 (73%) 0 6 (23%) 1.7 (0.07–22)
0 8 (80%) 1 (10%) 1 (10%) 0.7 (0.06–8.5)
0.97
0.35
Table 2 OCT characteristics of studied subjects. Severity of Angiographic Stenosis
Intermediate (n = 26)
Severe (n = 10)
p-value
OCT MLA (mm2, mean ± SD) OCT average reference lumen area (mm2, mean ± SD) OCT % area stenosis (mean ± SD) OCT morphology (n, %) Thrombus Plaque rupture Calcific nodule Thrombus and rupture Thrombus, rupture and calcific nodule Lipid plaque TCFAa Neovascularization Patients with MLA ≤ 1.9 mm2 (n, %)
3.3 ± 1.8 7.4 ± 3.1
1.6 ± 0.6 5.5 ± 1.9
b0.001 0.033
54.2 ± 11.4
70.9 ± 6.8
7 (27%) 6 (23%) 1 (4%) 5 (19%) 1 (4%) 18 (69) 10 (38) 4 (15) 3 (12)
3 (30%) 1 (10%) 0 0 0 7 (70) 2 (20) 0 8 (80)
a
0.001 0.41
b0.001
TCFA = thin cap fibroatheroma.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
N. Bogale et al. / Cardiovascular Revascularization Medicine xxx (2016) xxx–xxx
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Fig. 2. Angiographically intermediate lesion with plaque rupture in mid RCA (*). Although this plaque rupture is deep with dissection into the media, with a cavity that spans N¼ of the circumference of the vessel (**), it is relatively short in length (***) (b3 mm in length).
Statistical analyses were performed by SPSS statistical software 19.0 (SPSS Inc., Chicago, IL, USA). 4. Results Angiography was performed at a median of 2 days (range 1–7 days) following admission with NSTEMI. Twenty-six cases were classified as intermediate (40%–69% diameter stenosis) and 10 cases as angiographically severe (≥ 70% diameter stenosis) (Fig. 1). Distributions of ECG findings, LV function and studied coronary vessel were similar in both groups (Table 1). Culprit lesion was identified based on ECG, wall motion abnormality on ventriculogram and angiographic findings. Based on OCT measurements, both the minimal luminal area (MLA) and % area stenosis were significantly less severe in the angiographically intermediate group (p b 0.001, Table 2 and Figs. 2 and 3). Using the criteria established by Gonzalo et al. [9], OCT showed small MLA ≤ 1.9 mm2 in 3 patients (12%) in the angiographically intermediate group. Qualitatively, lipid arc was observed in 18 patients (69%), thin cap fibroatheroma in 10 patients (38%) and neovascularization in 4 patients (15%). Plaque rupture was seen in 7 patients (27%) and intraluminal thrombus in 6 (23%) patients. Both plaque rupture and thrombus were observed in 5 patients, while 3 patients had either of
the two features. A total of 8 patients (31%) had both or either of the two features. FFR was performed in 6 patients (23%) and PCI with stent deployment was done in 16 patients (62%) with angiographically intermediate lesions. All patients except one received drug eluting stent. The decision to perform PCI was done at the discretion of the treating physicians mostly based on the small size of the MLA (ranging from 1.9 to 2.2 mm2), or the desire to “seal” a ruptured plaque. (See Tables 3 and 4.) 5. Discussion Current guidelines support the use of coronary angiography to assess the need for revascularization in NSTEMI [10,11]. If a culprit lesion is clearly identified and severe (defined as ≥ 70% diameter stenosis based on visual estimate), then revascularization is usually prescribed. Alternatively, if a culprit lesion is not clearly identified, or not angiographically severe, then conservative medical therapy is usually advocated. Thus angiography plays an important role to assess the need for revascularization. However, angiography has well known limitations, and can underestimate lesion severity especially in the presence of diffuse disease [8]. In addition, patients presenting with non-obstructive lesions and ACS have risk of long-term recurrent ischemic events [12].
Fig. 3. Erosion without rupture. Small amount of platelet rich thrombus with minimal dorsal shadowing at 3–6 o'clock (*).
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
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Table 3 Baseline characteristics and findings in patients with non-obstructive lesions. Case #
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Age
64 67 44 70 51 48 82 65 76 85 67 75 73 75 43 67 67 73 50 51 77 45 55 68 37 77
Gender
M F M M M F F F F F M M M M M F F F M M M F M M M M
ECG
T inver. normal normal normal normal ST depr. normal T inver. normal normal normal T inver. non spec. normal non spec. T inver. non spes T inver. non spec. non spec. non spec. T inver. normal normal T inver. T inver.
Troponin
0.08 0.16 6.90 0.07 1.80 3.40 0.20 0.40 0.70 3.98 0.34 1.50 22 2.30 3.80 5.85 4.0 2.8 0.4 0.12 2.7 0.95 1.25 –c 19.4 4.6
LV fun.
normal normal normal normal normal WMA normal WMA normal normal normal WMA WMA normal normal WMA normal WMA WMA normal WMA normal WMA normal normal WMA
Angiography
OCT
vessel
% steno.
MLA
Ave ref.
% area ste.
thrombus
rupture
Calc.nod.
LAD LAD RCA LAD LAD LAD LAD LAD LAD RCA LAD LAD LAD LM LAD LAD LAD LAD RCA LAD LAD LAD LAD RCA RCA RCA
50 50 60 60 60 50 50 60 30 50 50 40 50 50 60 60 50 50 50 30 50 60 60 50 60 60
2.9 2.3 2.7 2.1 2.7 2.4 4.8 2.1 1.6 2.1 4.2 2.1 1.9 5.0 7.2 2.1 2.7 2.7 2.2 9.7 4.5 2.6 1.8 3.6 4.0 3.1
7.62 7.08 6.26 6.65 6.80 5.56 9.96 6.00 3.32 3.32 6.71 7.75 5.59 12.8 15.1 5.80 4.35 5.19 3.54 14.0 11.5 5.99 4.95 9.50 9.5 7.5
62 60 57 68 77 58 51 65 48 55 38 68 65 53 48 64 39 48 61 31 57 57 64 38 42 41
none none yes none Yes none none none none none none none none yes yes none none none yes none yes none none none yes none
none none yes none yes none none none none none none none none none yes none none none yes no yes none none yes none none
none none none none none none none none none none none none none none yes none none none none none none none none none none none
FFR
Days after admission
PCI done
not sig not sig no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR not sig not sig no FFR no FFR no FFR no FFR signifi. not sig no FFR no FFR
1 2 3 2 1 1 2 1 7 4 1 3 4 5 2 1 3 3 2 1 1 3 1 7 2 7
no no yes (D) yes (D) yes (D) no no yes (D) noa yes (D) no yes (D) yes (D) yes (D) yes (D) yes (D) no no nob no yes (D) yes (D) yes (D) yes (D) yes (D) yes (B)
(D) = drug eluting stent and (B) = bare metal stent. a Too distal for stenting b Had also LM stenosis and referred to CABG c Only high sensitive troponin T available.
The literature on the use of fractional flow reserve (FFR) to guide treatment in ACS is not robust, but newer reports describe similar benefits of using FFR in ACS compared to stable angina using the same threshold value of 0.8 [13–16]. Conceptually, unstable coronary plaques can precipitate ACS, which may not be severely stenotic and hemodynamically obstructive. With this background, the use of OCT in the setting of NSTEMI but without severe angiographic lesions may be particularly attractive. Among all the imaging modalities, OCT provides the most accurate and reproducible quantitative measurements of the coronary lumen [17]. In addition, OCT allows examination of the culprit lesion morphology [3] with unparalleled details (Figs. 4 and 5). However, it is important to emphasize that OCT does not provide information on the functional severity of coronary stenosis. The correlation of OCT derived MLA with FFR was modest, although a cut-off MLA of b1.9 mm2 has been reported by Gonzalo et al. investigators to be the best threshold to predict ischemia related lesions [18].
In our study, the group with intermediate angiographic stenoses had larger MLA (3.3 mm2 ± 1.8 mm2 vs. 1.6 mm2 ± 0.6 mm2, p b 0.001) and less severe % area stenosis (54.2% ± 11.4% vs. 70.9% ± 6.8%, p = 0.001) than angiographically severe lesions. None of the patients with intermediate angiographic stenosis had severe area stenosis using the traditional cut-off value of 75%. In our study, only 3 out of 26 patients (12%) had MLA value of ≤1.9 mm 2 (Gonzalo Criteria (9)) involving lesions in mid LAD, but because the reference vessel lumen area was also small, these lesions were not severe based on % lumen area stenosis criteria [18]. Qualitatively, a significant minority (8 out of 26, 31%) of our patients with intermediate disease had unstable plaque morphology including plaque rupture and intracoronary thrombus. The majority (18 patients, 69%) did not have features suggestive of intracoronary thrombus, plaque rupture or calcium nodules. Of note, even among those with positive findings, the amount of thrombus seen was small, and the magnitude of plaque rupture was modest (Figs. 2, 3 and 5), as all these features of interest were b10 mm in length. Previous OCT studies in acute
Table 4 Baseline characteristics and findings in patients with obstructive lesions. Case #
1 2 3 4 5 6 7 8 9 10
Age
46 64 64 42 65 72 64 44 53 54
Gender
M F M M M M M F F M
ECG
T inver. non spec. T inver. normal T inver. normal T inver. T inver. T inver. non spec.
Troponin
2.59 0.06 0.50 1.53 0.91 0.10 2.46 0.22 0.30 8.50
LV fun.
normal normal normal normal normal normal normal normal WMA WMA
angiography
OCT
vessel
% steno.
MLA
Ave ref.
% area ste.
thrombus
rupture
Calc.nod.
LAD LCx LAD RCA LAD LAD LAD LAD LAD LAD
80 70 70 70 70 60 70 90 70 70
1.51 0.77 2.09 1.49 1.80 1.49 1.94 0.82 1.43 2.67
5.01 4.07 5.80 5.30 4.79 3.90 5.97 3.80 6.17 10.68
70 81 64 72 62 62 68 78 77 75
yes none none none none none none none none none
yes none none none none none none none none none
none none none none none none none none none yes
FFR
Days after admission
PCI done
no FFR no FFR signifi. no FFR signifi. not sig. no FFR no FFR no FFR signifi.
2 2 1 2 3 2 2 3 2 2
yes (D) yes (B) yes (B) yes (D) yes (B) noa noa yes (D) yes (D) yes (D)
(D) = drug eluting stent and (B) = bare metal stent. a Both patients referred to CABG.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
N. Bogale et al. / Cardiovascular Revascularization Medicine xxx (2016) xxx–xxx
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Fig. 4. Calcium nodule abutting lumen.
coronary syndrome showed a high frequency of unstable features [19], but those OCT studies were done early or soon after clinical presentation, and it is possible that some of these features may have phased out due to pharmacological intervention. Recent reports using near infrared spectroscopy (NIRS) documented its efficacy in detecting large lipid cores at the culprit site in patients with ACS but without severe obstructive lesions [20]. The concept of “plaque sealing” will be further explored in future clinical trials. However, prior trials have not shown significant reduction in major cardiovascular adverse events [21]. Based on these observations and lack of definitive trials, most clinicians advocate treatment of such patients with optimal medical therapy including dual antiplatelet therapy (DAPT) [22] as ruptured plaques with small thrombus are believed to heal spontaneously.
There are several limitations in this study, which need to be acknowledged. It is a single center study and angiographic assessments were visual. Decisions on final treatment strategy vary, and follow-up data are not available as we were not allowed to contact patients for a retrospective study. In summary, in stabilized NSTEMI patients without ongoing pain and adequate medical therapy, angiography can identify a small subgroup of patients with intermediate coronary lesions (b 70% diameter stenosis). On OCT examination, severe obstructive disease is rarely seen. While plaques with unstable features are seen in up to one third of the cases, it is uncommon to find large clot burden or severe plaque disruption. It is unknown whether “sealing” of such unstable plaques can prevent future recurrent clinical events. Long-term studies assisted by
Fig. 5. Intermediate proximal RCA lesion (*) with intraluminal thrombus with dorsal shadowing (**).
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
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intracoronary imaging are needed to further characterize the outcome of this group of patients. Funding sources No outside funding supported this study. Acknowledgments None. References [1] Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83(3): 361–6. [2] Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation. J Am Coll Cardiol 2012;59(12):1058–72. [3] Bezerra HG, Costa MA. Will intravascular OCT shed light on vascular biology? JACC Cardiovasc Imaging 2010;3(1):85–7. [4] Terkelsen CJ, Lassen JF, Norgaard BL, Gerdes JC, Jensen T, Gotzsche LB, et al. Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort. Eur Heart J 2005;26(1):18–26. [5] Braunwald E, Morrow DA. Unstable angina: is it time for a requiem? Circulation 2013;127(24):2452–7. [6] Niccoli G, Stefanini GG, Capodanno D, Crea F, Ambrose JA, Berg R. Are the culprit lesions severely stenotic? JACC Cardiovasc Imaging 2013;6(10):1108–14. [7] Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J 2015;36(8):475–81. [8] Johnson NP, Kirkeeide RL, Gould KL. Coronary anatomy to predict physiology: fundamental limits. Circ Cardiovasc Imaging 2013;6(5):817–32. [9] Gonzalo N, Escaned J, Alfonso F, Jimenez-Quevedo P, Zakhem B, Banuelos C, et al. Is refined OCT guidance of stent implantation needed? EuroIntervention 2010(6 Suppl. G):G145–53. [10] Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey Jr DE, et al. 2012 ACCF/ AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012;60(7):645–81.
[11] Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35(37):2541–619. [12] Rossini R, Capodanno D, Lettieri C, Musumeci G, Limbruno U, Molfese M, et al. Longterm outcomes of patients with acute coronary syndrome and nonobstructive coronary artery disease. Am J Cardiol 2013;112(2):150–5. [13] Sels JW, Tonino PA, Siebert U, Fearon WF, Van't Veer M, De Bruyne B, et al. Fractional flow reserve in unstable angina and non-ST-segment elevation myocardial infarction experience from the FAME (fractional flow reserve versus angiography for multivessel evaluation) study. JACC Cardiovasc Interv 2011;4(11):1183–9. [14] Carrick D, Behan M, Foo F, Christie J, Hillis WS, Norrie J, et al. Usefulness of fractional flow reserve to improve diagnostic efficiency in patients with non-ST elevation myocardial infarction. Am J Cardiol 2013;111(1):45–50. [15] Hennigan B, Layland J, Fearon WF, Oldroyd KG. Fractional flow reserve and the index of microvascular resistance in patients with acute coronary syndromes. EuroIntervention 2014(10 Suppl. T):T55–63. [16] Layland J, Oldroyd KG, Curzen N, Sood A, Balachandran K, Das R, et al. Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-STsegment elevation myocardial infarction: the British Heart Foundation FAMOUSNSTEMI randomized trial. Eur Heart J 2015;36(2):100–11. [17] Kubo T, Akasaka T, Shite J, Suzuki T, Uemura S, Yu B, et al. OCT compared with IVUS in a coronary lesion assessment: the OPUS-CLASS study. JACC Cardiovasc Imaging 2013;6(10):1095–104. [18] Gonzalo N, Escaned J, Alfonso F, Nolte C, Rodriguez V, Jimenez-Quevedo P, et al. Morphometric assessment of coronary stenosis relevance with optical coherence tomography: a comparison with fractional flow reserve and intravascular ultrasound. J Am Coll Cardiol 2012;59(12):1080–9. [19] Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, et al. Assessment of culprit lesion morphology in acute myocardial infarction: ability of optical coherence tomography compared with intravascular ultrasound and coronary angioscopy. J Am Coll Cardiol 2007;50(10):933–9. [20] Madder RD, Husaini M, Davis AT, Van Oosterhout S, Harnek J, Gotberg M, et al. Detection by near-infrared spectroscopy of large lipid cores at culprit sites in patients with non-st-segment elevation myocardial infarction and unstable angina. Catheter Cardiovasc Interv 2015;86(6):1014–21. [21] Rodes-Cabau J, Bertrand OF, Larose E, Dery JP, Rinfret S, Urena M, et al. Five-year follow-up of the plaque sealing with paclitaxel-eluting stents vs medical therapy for the treatment of intermediate nonobstructive saphenous vein graft lesions (VELETI) trial. Can J Cardiol 2014;30(1):138–45. [22] Ramanath VS, Armstrong DF, Grzybowski M, Rahnama-Mohagdam S, Tamhane UU, Gordon K, et al. Receipt of cardiac medications upon discharge among men and women with acute coronary syndrome and nonobstructive coronary artery disease. Clin Cardiol 2010;33(1):36–41.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI☆ Nigussie Bogale a,b,⁎, Mathieu Lempereur b, Imran Sheikh b, David Wood b, Jacqueline Saw b, Anthony Fung b a b
Stavanger University Hospital, Stavanger, Norway Vancouver General Hospital, Vancouver, BC, Canada
a r t i c l e
i n f o
Article history: Received 12 September 2015 Received in revised form 13 December 2015 Accepted 22 December 2015 Available online xxxx Keywords: OCT Intermediate coronary lessions NSTEMI
a b s t r a c t Introduction: Coronary angiography is commonly performed following non-ST segment elevation myocardial infarction (NSTEMI) to assess the need for revascularization. Some of these patients have myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA). Patients without severe obstructive lesions are usually treated conservatively. However, coronary angiography has known limitations in the assessment of lesion severity. We report our experience of using coronary Optical Coherence Tomography (OCT) in a series of patients without severe obstructive coronary lesions. Methods: 165 patients underwent coronary OCT at Vancouver General Hospital. NSTEMI was the clinical presentation in 70 patients and 26 had angiographically intermediate lesions with 40%–69% diameter stenosis. Prior to OCT image acquisition, intracoronary nitroglycerin 100–200 μg was administered. Blood in the vessel was displaced using contrast media by manual injections. Results: OCT of the angiographically intermediate lesions showed larger minimal luminal area (MLA) than the angiographically severe lesions (MLA 3.3 mm2 ± 1.8 mm2 vs. 1.6 mm2 ± 0.6 mm2, p b 0.001) and less severe % lumen area stenosis (54.2% ± 11.4% vs. 70.9% ± 6.8%, p = 0.001). Plaque rupture or intracoronary thrombus was detected in 8/26 (31%) patients. PCI with stent deployment was performed in 16 patients (62%). Conclusion: In stabilized patients with NSTEMI and angiographically intermediate disease, OCT examination confirmed the lack of severe anatomical stenosis in most patients. However, OCT also identified coronary lesions with unstable features. Further research is needed to help guide management of this subgroup of patients. © 2016 Elsevier Inc. All rights reserved.
1. Introduction Pathological examination of patients with acute coronary syndrome (ACS) typically showed intracoronary thrombus with plaque rupture, erosion or calcium nodules [1]. Optical coherence tomography (OCT) has high spatial resolution, and previous studies have documented its ability in characterizing such complicated plaque features. Consensus documents on image acquisition, measurement and reporting as well as detailed image description have been published [2,3]. Patients with recent non-ST elevation myocardial elevation (NSTEMI) have elevated cardiac biomarkers, and in general, have higher short-term cardiac risk [4,5]. Most of these patients have severe angiographic lesions (≥ 70% diameter stenosis), and they are typically treated with revascularization [6]. A minority of patients present with less severe angiographic lesions, and are more likely treated with medical
☆ Disclosures: The authors report no financial relationships or conflicts of interest regarding the content of this manuscript. ⁎ Corresponding author at: Stavanger University Hospital, Department of Cardiology, Stavanger, Norway and Vancouver General Hospital, Vancouver, Canada. Tel.: + 47 41309313. E-mail address: [email protected] (N. Bogale).
therapy alone. A recent clinical review by Nicoli et al. used the term “myocardial infarctions (MI) with no obstructive coronary atherosclerosis (MINOCA)” to describe this smaller, but important subgroup of patients. The authors also proposed treatment algorithm including the use of intracoronary imaging [7]. Coronary angiography has known limitations in the assessment of lesion severity [8]. OCT maybe particularly useful in this setting to better evaluate lesion severity and characteristics. We report our experience with OCT in patients with intermediate lesions who are clinically stable. 2. Methods We retrospectively evaluated all consecutive OCTs that were performed in 165 patients at Vancouver General Hospital from November 2010 to March 2013. Seventy (42%) were performed in patients presenting with NSTEMI. We excluded OCTs that were performed in lesions with prior stenting in the same vessel (n = 22), bypass vein grafts (n = 2), inadequate imaging (n = 4) and imaging for other indications (spasm, spontaneous coronary artery dissection and intramural hematoma) (n = 6). The current report focuses on the remaining 36 cases. Based on the angiographic visual estimates, 26 cases were classified as intermediate (40% to 69% diameter stenosis) and 10 cases were
http://dx.doi.org/10.1016/j.carrev.2015.12.007 1553-8389/© 2016 Elsevier Inc. All rights reserved.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
2
N. Bogale et al. / Cardiovascular Revascularization Medicine xxx (2016) xxx–xxx
Fig. 1. Flowchart of OCT cases. * SCAD = Spontaneous Coronary Artery Dissection and ** IMH = Intramural Hematoma.
classified as severe (≥70% diameter stenosis) (Fig. 1). We did not perform OCT examination in any patient with b 40% diameter stenosis. All imaging was acquired using the second generation Fourier domain (FD) OCT (C7-XR/ILUMIEN™ system from St. Jude Medical/LightLab Imaging, Westford MA, USA). Prior to image acquisition, 100–200 μg of nitroglycerin was administered. Scanning of the region of interest was performed by automated pullback at a speed of 20 mm/s. We typically inject 9–14 ml of contrast media manually via the guiding catheter to clear
blood from the imaging field. Images were acquired digitally and stored locally for evaluation and analysis on a dedicated work-station. Longitudinal image runs were scanned to examine the areas of interests. Minimal luminal area (MLA) was measured after proper Z-offset calibration. Proximal and distal reference areas were measured and the average was registered as average reference vessel luminal area. 3. Statistical analysis Continuous variables are presented as means ± standard deviations. Categorical variables are presented as numbers and percentages.
Table 1 Baseline characteristics. Severity of Angiographic Stenosis
Intermediate (n = 26)
Severe (n = 10)
p-value
Age (mean ± SD) Male (n, %) Days: admission to procedure (median, range) ECG (n, %) New ST elevation New ST depression New T wave inversion Non-specific ST changes Normal LV function (n, %) Regional wall motion abnormality LV EF b 50% Location of culprit lesion (n, %) LM LAD LCx RCA Peak Troponin-I level (median and range)
64 ± 14 16 (62%) 2 [1–7]
57 ± 10 7 (70%) 2(1–3)
0.16 0.64 0.35 0.17
0 1 (4%) 8 (31%) 6 (23%) 11 (42%)
0 0 6 (60%) 2 (20%) 2 (20%) 0.47
8 (31%) 8 (30%)
2 (20%) 0
1 (4%) 19 (73%) 0 6 (23%) 1.7 (0.07–22)
0 8 (80%) 1 (10%) 1 (10%) 0.7 (0.06–8.5)
0.97
0.35
Table 2 OCT characteristics of studied subjects. Severity of Angiographic Stenosis
Intermediate (n = 26)
Severe (n = 10)
p-value
OCT MLA (mm2, mean ± SD) OCT average reference lumen area (mm2, mean ± SD) OCT % area stenosis (mean ± SD) OCT morphology (n, %) Thrombus Plaque rupture Calcific nodule Thrombus and rupture Thrombus, rupture and calcific nodule Lipid plaque TCFAa Neovascularization Patients with MLA ≤ 1.9 mm2 (n, %)
3.3 ± 1.8 7.4 ± 3.1
1.6 ± 0.6 5.5 ± 1.9
b0.001 0.033
54.2 ± 11.4
70.9 ± 6.8
7 (27%) 6 (23%) 1 (4%) 5 (19%) 1 (4%) 18 (69) 10 (38) 4 (15) 3 (12)
3 (30%) 1 (10%) 0 0 0 7 (70) 2 (20) 0 8 (80)
a
0.001 0.41
b0.001
TCFA = thin cap fibroatheroma.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
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Fig. 2. Angiographically intermediate lesion with plaque rupture in mid RCA (*). Although this plaque rupture is deep with dissection into the media, with a cavity that spans N¼ of the circumference of the vessel (**), it is relatively short in length (***) (b3 mm in length).
Statistical analyses were performed by SPSS statistical software 19.0 (SPSS Inc., Chicago, IL, USA). 4. Results Angiography was performed at a median of 2 days (range 1–7 days) following admission with NSTEMI. Twenty-six cases were classified as intermediate (40%–69% diameter stenosis) and 10 cases as angiographically severe (≥ 70% diameter stenosis) (Fig. 1). Distributions of ECG findings, LV function and studied coronary vessel were similar in both groups (Table 1). Culprit lesion was identified based on ECG, wall motion abnormality on ventriculogram and angiographic findings. Based on OCT measurements, both the minimal luminal area (MLA) and % area stenosis were significantly less severe in the angiographically intermediate group (p b 0.001, Table 2 and Figs. 2 and 3). Using the criteria established by Gonzalo et al. [9], OCT showed small MLA ≤ 1.9 mm2 in 3 patients (12%) in the angiographically intermediate group. Qualitatively, lipid arc was observed in 18 patients (69%), thin cap fibroatheroma in 10 patients (38%) and neovascularization in 4 patients (15%). Plaque rupture was seen in 7 patients (27%) and intraluminal thrombus in 6 (23%) patients. Both plaque rupture and thrombus were observed in 5 patients, while 3 patients had either of
the two features. A total of 8 patients (31%) had both or either of the two features. FFR was performed in 6 patients (23%) and PCI with stent deployment was done in 16 patients (62%) with angiographically intermediate lesions. All patients except one received drug eluting stent. The decision to perform PCI was done at the discretion of the treating physicians mostly based on the small size of the MLA (ranging from 1.9 to 2.2 mm2), or the desire to “seal” a ruptured plaque. (See Tables 3 and 4.) 5. Discussion Current guidelines support the use of coronary angiography to assess the need for revascularization in NSTEMI [10,11]. If a culprit lesion is clearly identified and severe (defined as ≥ 70% diameter stenosis based on visual estimate), then revascularization is usually prescribed. Alternatively, if a culprit lesion is not clearly identified, or not angiographically severe, then conservative medical therapy is usually advocated. Thus angiography plays an important role to assess the need for revascularization. However, angiography has well known limitations, and can underestimate lesion severity especially in the presence of diffuse disease [8]. In addition, patients presenting with non-obstructive lesions and ACS have risk of long-term recurrent ischemic events [12].
Fig. 3. Erosion without rupture. Small amount of platelet rich thrombus with minimal dorsal shadowing at 3–6 o'clock (*).
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Table 3 Baseline characteristics and findings in patients with non-obstructive lesions. Case #
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26
Age
64 67 44 70 51 48 82 65 76 85 67 75 73 75 43 67 67 73 50 51 77 45 55 68 37 77
Gender
M F M M M F F F F F M M M M M F F F M M M F M M M M
ECG
T inver. normal normal normal normal ST depr. normal T inver. normal normal normal T inver. non spec. normal non spec. T inver. non spes T inver. non spec. non spec. non spec. T inver. normal normal T inver. T inver.
Troponin
0.08 0.16 6.90 0.07 1.80 3.40 0.20 0.40 0.70 3.98 0.34 1.50 22 2.30 3.80 5.85 4.0 2.8 0.4 0.12 2.7 0.95 1.25 –c 19.4 4.6
LV fun.
normal normal normal normal normal WMA normal WMA normal normal normal WMA WMA normal normal WMA normal WMA WMA normal WMA normal WMA normal normal WMA
Angiography
OCT
vessel
% steno.
MLA
Ave ref.
% area ste.
thrombus
rupture
Calc.nod.
LAD LAD RCA LAD LAD LAD LAD LAD LAD RCA LAD LAD LAD LM LAD LAD LAD LAD RCA LAD LAD LAD LAD RCA RCA RCA
50 50 60 60 60 50 50 60 30 50 50 40 50 50 60 60 50 50 50 30 50 60 60 50 60 60
2.9 2.3 2.7 2.1 2.7 2.4 4.8 2.1 1.6 2.1 4.2 2.1 1.9 5.0 7.2 2.1 2.7 2.7 2.2 9.7 4.5 2.6 1.8 3.6 4.0 3.1
7.62 7.08 6.26 6.65 6.80 5.56 9.96 6.00 3.32 3.32 6.71 7.75 5.59 12.8 15.1 5.80 4.35 5.19 3.54 14.0 11.5 5.99 4.95 9.50 9.5 7.5
62 60 57 68 77 58 51 65 48 55 38 68 65 53 48 64 39 48 61 31 57 57 64 38 42 41
none none yes none Yes none none none none none none none none yes yes none none none yes none yes none none none yes none
none none yes none yes none none none none none none none none none yes none none none yes no yes none none yes none none
none none none none none none none none none none none none none none yes none none none none none none none none none none none
FFR
Days after admission
PCI done
not sig not sig no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR no FFR not sig not sig no FFR no FFR no FFR no FFR signifi. not sig no FFR no FFR
1 2 3 2 1 1 2 1 7 4 1 3 4 5 2 1 3 3 2 1 1 3 1 7 2 7
no no yes (D) yes (D) yes (D) no no yes (D) noa yes (D) no yes (D) yes (D) yes (D) yes (D) yes (D) no no nob no yes (D) yes (D) yes (D) yes (D) yes (D) yes (B)
(D) = drug eluting stent and (B) = bare metal stent. a Too distal for stenting b Had also LM stenosis and referred to CABG c Only high sensitive troponin T available.
The literature on the use of fractional flow reserve (FFR) to guide treatment in ACS is not robust, but newer reports describe similar benefits of using FFR in ACS compared to stable angina using the same threshold value of 0.8 [13–16]. Conceptually, unstable coronary plaques can precipitate ACS, which may not be severely stenotic and hemodynamically obstructive. With this background, the use of OCT in the setting of NSTEMI but without severe angiographic lesions may be particularly attractive. Among all the imaging modalities, OCT provides the most accurate and reproducible quantitative measurements of the coronary lumen [17]. In addition, OCT allows examination of the culprit lesion morphology [3] with unparalleled details (Figs. 4 and 5). However, it is important to emphasize that OCT does not provide information on the functional severity of coronary stenosis. The correlation of OCT derived MLA with FFR was modest, although a cut-off MLA of b1.9 mm2 has been reported by Gonzalo et al. investigators to be the best threshold to predict ischemia related lesions [18].
In our study, the group with intermediate angiographic stenoses had larger MLA (3.3 mm2 ± 1.8 mm2 vs. 1.6 mm2 ± 0.6 mm2, p b 0.001) and less severe % area stenosis (54.2% ± 11.4% vs. 70.9% ± 6.8%, p = 0.001) than angiographically severe lesions. None of the patients with intermediate angiographic stenosis had severe area stenosis using the traditional cut-off value of 75%. In our study, only 3 out of 26 patients (12%) had MLA value of ≤1.9 mm 2 (Gonzalo Criteria (9)) involving lesions in mid LAD, but because the reference vessel lumen area was also small, these lesions were not severe based on % lumen area stenosis criteria [18]. Qualitatively, a significant minority (8 out of 26, 31%) of our patients with intermediate disease had unstable plaque morphology including plaque rupture and intracoronary thrombus. The majority (18 patients, 69%) did not have features suggestive of intracoronary thrombus, plaque rupture or calcium nodules. Of note, even among those with positive findings, the amount of thrombus seen was small, and the magnitude of plaque rupture was modest (Figs. 2, 3 and 5), as all these features of interest were b10 mm in length. Previous OCT studies in acute
Table 4 Baseline characteristics and findings in patients with obstructive lesions. Case #
1 2 3 4 5 6 7 8 9 10
Age
46 64 64 42 65 72 64 44 53 54
Gender
M F M M M M M F F M
ECG
T inver. non spec. T inver. normal T inver. normal T inver. T inver. T inver. non spec.
Troponin
2.59 0.06 0.50 1.53 0.91 0.10 2.46 0.22 0.30 8.50
LV fun.
normal normal normal normal normal normal normal normal WMA WMA
angiography
OCT
vessel
% steno.
MLA
Ave ref.
% area ste.
thrombus
rupture
Calc.nod.
LAD LCx LAD RCA LAD LAD LAD LAD LAD LAD
80 70 70 70 70 60 70 90 70 70
1.51 0.77 2.09 1.49 1.80 1.49 1.94 0.82 1.43 2.67
5.01 4.07 5.80 5.30 4.79 3.90 5.97 3.80 6.17 10.68
70 81 64 72 62 62 68 78 77 75
yes none none none none none none none none none
yes none none none none none none none none none
none none none none none none none none none yes
FFR
Days after admission
PCI done
no FFR no FFR signifi. no FFR signifi. not sig. no FFR no FFR no FFR signifi.
2 2 1 2 3 2 2 3 2 2
yes (D) yes (B) yes (B) yes (D) yes (B) noa noa yes (D) yes (D) yes (D)
(D) = drug eluting stent and (B) = bare metal stent. a Both patients referred to CABG.
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
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Fig. 4. Calcium nodule abutting lumen.
coronary syndrome showed a high frequency of unstable features [19], but those OCT studies were done early or soon after clinical presentation, and it is possible that some of these features may have phased out due to pharmacological intervention. Recent reports using near infrared spectroscopy (NIRS) documented its efficacy in detecting large lipid cores at the culprit site in patients with ACS but without severe obstructive lesions [20]. The concept of “plaque sealing” will be further explored in future clinical trials. However, prior trials have not shown significant reduction in major cardiovascular adverse events [21]. Based on these observations and lack of definitive trials, most clinicians advocate treatment of such patients with optimal medical therapy including dual antiplatelet therapy (DAPT) [22] as ruptured plaques with small thrombus are believed to heal spontaneously.
There are several limitations in this study, which need to be acknowledged. It is a single center study and angiographic assessments were visual. Decisions on final treatment strategy vary, and follow-up data are not available as we were not allowed to contact patients for a retrospective study. In summary, in stabilized NSTEMI patients without ongoing pain and adequate medical therapy, angiography can identify a small subgroup of patients with intermediate coronary lesions (b 70% diameter stenosis). On OCT examination, severe obstructive disease is rarely seen. While plaques with unstable features are seen in up to one third of the cases, it is uncommon to find large clot burden or severe plaque disruption. It is unknown whether “sealing” of such unstable plaques can prevent future recurrent clinical events. Long-term studies assisted by
Fig. 5. Intermediate proximal RCA lesion (*) with intraluminal thrombus with dorsal shadowing (**).
Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007
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intracoronary imaging are needed to further characterize the outcome of this group of patients. Funding sources No outside funding supported this study. Acknowledgments None. References [1] Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83(3): 361–6. [2] Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation. J Am Coll Cardiol 2012;59(12):1058–72. [3] Bezerra HG, Costa MA. Will intravascular OCT shed light on vascular biology? JACC Cardiovasc Imaging 2010;3(1):85–7. [4] Terkelsen CJ, Lassen JF, Norgaard BL, Gerdes JC, Jensen T, Gotzsche LB, et al. Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort. Eur Heart J 2005;26(1):18–26. [5] Braunwald E, Morrow DA. Unstable angina: is it time for a requiem? Circulation 2013;127(24):2452–7. [6] Niccoli G, Stefanini GG, Capodanno D, Crea F, Ambrose JA, Berg R. Are the culprit lesions severely stenotic? JACC Cardiovasc Imaging 2013;6(10):1108–14. [7] Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management. Eur Heart J 2015;36(8):475–81. [8] Johnson NP, Kirkeeide RL, Gould KL. Coronary anatomy to predict physiology: fundamental limits. Circ Cardiovasc Imaging 2013;6(5):817–32. [9] Gonzalo N, Escaned J, Alfonso F, Jimenez-Quevedo P, Zakhem B, Banuelos C, et al. Is refined OCT guidance of stent implantation needed? EuroIntervention 2010(6 Suppl. G):G145–53. [10] Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey Jr DE, et al. 2012 ACCF/ AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012;60(7):645–81.
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Please cite this article as: Bogale N, et al, Optical coherence tomography (OCT) evaluation of intermediate coronary lesions in patients with NSTEMI, Cardiovasc Revasc Med (2016), http://dx.doi.org/10.1016/j.carrev.2015.12.007