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Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs)., Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065., Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3·7 (IQR 3·0-4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0-15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2-10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25-4·13) and non-culprit lesion-specific MACEs (7·83, 4·12-14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0-10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4-17·6)., Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes., Funding: Abbott Vascular, Infraredx, and The Medicines Company., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Intraplaque haemorrhage is considered a major contributor to lesion progression. We assessed coronary lesions with intraplaque haemorrhage using intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS)., Methods and Results: We evaluated coronary arteries from autopsy hearts using 40MHz IVUS and NIRS and compared the imaging findings to histopathology. A total of 2324 2-mm long histological segments from 101 coronary arteries from 56 autopsy hearts were included. Intraplaque haemorrhage was found pathologically in 0.8% (18/2324) of segments. Segments with intraplaque haemorrhage had more fibroatheromas (FAs) with a greater IVUS plaque burden, a greater prevalence of IVUS echolucent zones, and a higher NIRS-lipid core burden index (LCBI) compared to segments without intraplaque haemorrhage (FAs: 72.2% vs. 18.3%, P < 0.0001; plaque burden: 59.7% [95% confidence interval: 55.5, 64.0] vs. 48.6% [45.8, 51.3], P < 0.0001; echolucent zones: 88.9% vs. 2.8%, P < 0.0001; NIRS-LCBI: 176 [88, 264] vs. 72 [53, 91], P = 0.02). The 16 IVUS superficial echolucent zones with intraplaque haemorrhage had more late FAs but shorter echolucent zone lengths (0.9 mm [0.7, 1.1] vs. 1.7 mm [1.5, 1.9], P < 0.0001) compared to 65 IVUS superficial echolucent zones without intraplaque haemorrhage., Conclusions: Intracoronary imaging features consistent with intraplaque haemorrhage included a greater plaque burden, a higher NIRS-LCBI, and a greater prevalence of IVUS echolucent zones compared to lesions without intraplaque haemorrhage., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Background: This study sought to determine the frequency of large lipid-rich plaques (LRP) in the coronary arteries of individuals with high coronary artery calcium scores (CACS) and to determine whether the CACS correlates with coronary lipid burden., Methods and Results: Combined near-infrared spectroscopy and intravascular ultrasound was performed in 57 vessels in 20 asymptomatic individuals (90% on statins) with no prior history of coronary artery disease who had a screening CACS ≥300 Agatston units. Among 268 10-mm coronary segments, near-infrared spectroscopy images were analyzed for LRP, defined as a bright yellow block on the near-infrared spectroscopy block chemogram. Lipid burden was assessed as the lipid core burden index (LCBI), and large LRP were defined as a maximum LCBI in 4 mm ≥400. Vessel plaque volume was measured by quantitative intravascular ultrasound. Vessel-level CACS significantly correlated with plaque volume by intravascular ultrasound ( r =0.69; P <0.0001) but not with LCBI by near-infrared spectroscopy ( r =0.24; P =0.07). Despite a high CACS, no LRP was detected in 8 (40.0%) subjects. Large LRP having a maximum LCBI in 4 mm ≥400 were infrequent, found in only 5 (25.0%) of 20 subjects and in only 5 (1.9%) of 268 10-mm coronary segments analyzed., Conclusions: Among individuals with a CACS ≥300 Agatston units mostly on statins, CACS correlated with total plaque volume but not LCBI. This observation may have implications on coronary risk among individuals with a high CACS considering that it is coronary LRP, rather than calcification, that underlies the majority of acute coronary events., (© 2017 American Heart Association, Inc.)

Objectives: We sought to examine near-infrared spectroscopy (NIRS) imaging findings of aortocoronary saphenous vein grafts (SVGs)., Background: SVGs are prone to develop atherosclerosis similar to native coronary arteries. They have received little study using NIRS., Methods: We examined the clinical characteristics and imaging findings from 43 patients who underwent NIRS imaging of 45 SVGs at our institution between 2009 and 2016., Results: The mean patient age was 67 ± 7 years and 98% were men, with high prevalence of diabetes mellitus (56%), hypertension (95%), and dyslipidemia (95%). Mean SVG age was 7 ± 7 years, mean SVG lipid core burden index (LCBI) was 53 ± 60 and mean maxLCBI 4 mm was 194 ± 234. Twelve SVGs (27%) had lipid core plaques (2 yellow blocks on the block chemogram), with a higher prevalence in SVGs older than 5 years (46% vs. 5%, P = 0.002). Older SVG age was associated with higher LCBI (r = 0.480, P < 0.001) and higher maxLCBI 4 mm (r = 0.567, P < 0.001). On univariate analysis, greater annual total cholesterol exposure was associated with higher SVG LCBI (r = 0.30, P = 0.042) and annual LDL-cholesterol and triglyceride exposure were associated with higher SVG maxLCBI 4 mm (LDL-C: r = 0.41, P = 0.020; triglycerides: r = 0.36, P = 0.043). On multivariate analysis, the only independent predictor of SVG LCBI and maxLCBI 4mm was SVG age. SVG percutaneous coronary intervention was performed in 63% of the patients. An embolic protection device was used in 96% of SVG PCIs. Periprocedural myocardial infarction occurred in one patient., Conclusions: Older SVG age and greater lipid exposure are associated with higher SVG lipid burden. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: In a previous exploratory analysis, intracoronary near-infrared spectroscopy (NIRS) found the majority of culprit lesions in ST-segment-elevation myocardial infarction (STEMI) to contain a maximum lipid core burden index in 4 mm (maxLCBI4mm) of >400. This initial study was limited by a small sample size, enrollment at a single center, and post hoc selection of the maxLCBI4mm ≥400 threshold. This study was designed a priori to substantiate the ability of NIRS to discriminate STEMI culprit from nonculprit segments and to confirm the performance of the maxLCBI4mm ≥400 threshold., Approach and Results: At 2 centers in the United States and Sweden, 75 STEMI patients underwent intracoronary NIRS imaging after establishing thrombolysis in myocardial infarction 3 flow, but before stenting. Blinded core laboratory analysis defined the culprit segment as the 10-mm segment distal to the proximal angiographic culprit margin. The remaining vessel was divided into contiguous 10-mm nonculprit segments. The maxLCBI4mm of culprit segments (median [interquartile range]: 543 [273-756]) was 4.4-fold greater than nonculprit segments (median [interquartile range]: 123 [0-307]; P<0.001). Receiver-operating characteristic analysis demonstrated that maxLCBI4mm differentiated culprit from nonculprit segments with high accuracy (c-statistic=0.83; P<0.001). A threshold maxLCBI4mm ≥400 identified STEMI culprit segments with a sensitivity of 64% and specificity of 85%., Conclusions: This study substantiates the ability of NIRS to accurately differentiate STEMI culprit from nonculprit segments and confirms that a threshold maxLCBI4mm ≥400 is detected by NIRS in the majority of STEMI culprits., (© 2016 American Heart Association, Inc.)

Aims: A recent study demonstrated that intracoronary near-infrared spectroscopy (NIRS) findings in non-target vessels are associated with major adverse cardiovascular and cerebrovascular events (MACCE). It is unknown whether NIRS findings at non-stented sites in target vessels are similarly associated with future MACCE. This study evaluated the association between large lipid-rich plaques (LRP) detected by NIRS at non-stented sites in a target artery and subsequent MACCE., Methods and Results: This study evaluated 121 consecutive registry patients undergoing NIRS imaging in a target artery. After excluding stented segments, target arteries were evaluated for a large LRP, defined as a maximum lipid core burden index in 4 mm (maxLCBI4 mm) ≥400. Excluding events in stented segments, Cox regression analysis was performed to evaluate for an association between a maxLCBI4 mm ≥400 and future MACCE, defined as all-cause mortality, non-fatal acute coronary syndrome, and cerebrovascular events. NIRS detected a maxLCBI4 mm ≥400 in a non-stented segment of the target artery in 17.4% of patients. The only baseline clinical variable marginally associated with MACCE was ejection fraction (HR 0.96, 95% CI 0.93-1.00, P = 0.054). A maxLCBI4 mm ≥400 in a non-stented segment at baseline was significantly associated with MACCE during follow-up (HR 10.2, 95% CI 3.4-30.6, P < 0.001)., Conclusion: Detection of large LRP by NIRS at non-stented sites in a target artery was associated with an increased risk of future MACCE. These findings support ongoing prospective studies to further evaluate the ability of NIRS to identify vulnerable patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objectives: Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries., Approach and Results: Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo., Conclusions: Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma., (© 2015 American Heart Association, Inc.)

Objectives: This study sought to determine whether pre-percutaneous coronary intervention (PCI) plaque characterization using near-infrared spectroscopy identifies lipid-rich plaques at risk of periprocedural myonecrosis and whether these events may be prevented by the use of a distal protection filter during PCI., Background: Lipid-rich plaques may be prone to distal embolization and periprocedural myocardial infarction (MI) in patients undergoing PCI., Methods: Patients undergoing stent implantation of a single native coronary lesion were enrolled in a multicenter, prospective trial. Near-infrared spectroscopy and intravascular ultrasound were performed at baseline, and lesions with a maximal lipid core burden index over any 4-mm length (maxLCBI4mm) ≥600 were randomized to PCI with versus without a distal protection filter. The primary endpoint was periprocedural MI, defined as troponin or a creatine kinase-myocardial band increase to 3 or more times the upper limit of normal., Results: Eighty-five patients were enrolled at 9 U.S. sites. The median (interquartile range) maxLCBI4mm was 448.4 (274.8 to 654.4) pre-PCI and decreased to 156.0 (75.6 to 312.6) post-PCI (p < 0.0001). Periprocedural MI developed in 21 patients (24.7%). The maxLCBI4mm was higher in patients with versus without MI (481.5 [425.6 to 679.6] vs. 371.5 [228.9 to 611.6], p = 0.05). Among 31 randomized lesions with maxLCBI4mm ≥600, there was no difference in the rates of periprocedural MI with versus without the use of a distal protection filter (35.7% vs. 23.5%, respectively; relative risk: 1.52; 95% confidence interval: 0.50 to 4.60, p = 0.69)., Conclusions: Plaque characterization by near-infrared spectroscopy identifies lipid-rich lesions with an increased likelihood of periprocedural MI after stent implantation, presumably due to distal embolization. However, in this pilot randomized trial, the use of a distal protection filter did not prevent myonecrosis after PCI of lipid-rich plaques., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Intracoronary near-infrared spectroscopy (NIRS) in ST-segment elevation myocardial infarction (STEMI) has demonstrated substantial lipid in STEMI culprit plaques. Thrombus aspiration during primary PCI reduces distal embolization and improves reperfusion. This study was performed to examine if aspiration thrombectomy reduces the lipid content of acute coronary syndrome (ACS) culprit plaques., Methods and Results: NIRS-IVUS imaging was performed in patients with an ACS at two hospitals in the US and Sweden. After establishment of TIMI 3 flow with an undersized balloon, NIRS was performed, followed by aspiration thrombectomy, followed by repeated NIRS. The same culprit segment was identified on the post-aspiration chemogram. The culprit lipid content was quantified before and after thrombectomy as the lipid core burden index (LCBI). Aspirates were examined by histological staining for lipids, calcium, and macrophages. In 18 ACS patients (age 65 ± 11, 61% male), culprit lesions were characterized by high lipid content prior to aspiration thrombectomy. Thrombectomy resulted in a 28% reduction in culprit lesion lipid content (pre-aspiration LCBI 466 ± 141 vs. post-aspiration 335 ± 117, P = 0.0001). In addition to thrombus, histological analysis of aspirates demonstrated the presence of lipids, calcium, and macrophages, indicating that fragments of atherosclerotic plaques had been aspirated., Conclusion: Thrombectomy aspirates both thrombus and lipid-rich fragments of the culprit atherosclerotic plaques, thereby reducing material that may embolize during stenting. Reduction of lipid content before stenting might contribute to the beneficial effects of thrombectomy and may be particularly useful if a large lipid core is present at the culprit site., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objectives: This study assessed grayscale intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) detection of a histological fibroatheroma (FA)., Background: NIRS-detected, lipid-rich plaques (LRPs) and IVUS-detected attenuated plaques are considered to be vulnerable., Methods: IVUS-attenuated plaque and NIRS-LRP (yellow or tan block chemogram) were compared with histopathology in 1,943 sections of 103 coronary arteries from 56 autopsied hearts., Results: IVUS-superficial attenuation and NIRS-LRP showed a similar high specificity of approximately 95%, whereas IVUS-superficial attenuation alone had a poor sensitivity (vs. NIRS-LRP) in detecting FAs (36% vs. 47%; p = 0.001). Compared with FA sections with superficial attenuation, FA sections without superficial attenuation had a smaller plaque burden (57.1% vs. 67.7%), a larger arc of calcium (79.7° vs. 16.8°), and a lower prevalence of a ≥20% histological necrotic core (28% vs. 50%) or late FA (14% vs. 37%; all p < 0.05). Compared with FA sections with NIRS-LRP, FA sections without NIRS-LRP showed a smaller plaque burden (58.0% vs. 63.3%) and a lower prevalence of a ≥20% necrotic core (27% vs. 46%). Conversely, non-FAs with NIRS-LRP (vs. non-FAs without LRP) showed a larger plaque burden (55.1% vs. 46.3%), a greater prevalence of a ≥20% histological lipid pool (34% vs. 5%), and mostly pathological intimal thickening (50%) or fibrocalcific plaque (33%). When sections showed either IVUS attenuation or NIRS-LRP, the sensitivity for predicting a FA was significantly higher compared with IVUS attenuation alone (63% vs. 36%; p < 0.001) or NIRS-LRP alone (63% vs. 47%; p < 0.001). When sections showed both IVUS attenuation and NIRS-LRP, the positive predictive value improved compared with IVUS attenuation alone (84% vs. 66%; p < 0.001) or NIRS-LRP alone (84% vs. 65%; p < 0.001)., Conclusions: NIRS-LRP was more accurate than IVUS for predicting plaque containing a necrotic core or a large lipid pool, and the combination was more accurate than either alone., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Three intravascular ultrasound (IVUS) signatures have been associated with coronary artery disease instability: echo attenuation, an intraplaque echolucent zone, and spotty calcification. The aim of this study was to investigate the substrates responsible for these IVUS signatures in a relatively large series of post-mortem human coronary samples., Background: The exact mechanisms and pathological correlates underlying echo attenuation, an intraplaque echolucent zone, and spotty calcification remain poorly understood., Methods: IVUS was compared with near-infrared spectroscopic detection of lipid core plaque and histopathology in 2,294 vessel segments from 151 coronary specimens from 62 patients at necropsy using the modified American Heart Association classification., Results: IVUS detected echo-attenuated plaques in 18.3% of segments, echolucent plaques in 10.5% of segments, and spotty calcification in 14.4% of segments. Histopathologically, 91.4% of echo-attenuated plaques corresponded to either a fibroatheroma (FA) with a necrotic core (NC) or pathological intimal thickening with a lipid pool; almost all segments with superficial echo attenuation indicated the presence of an FA with an advanced NC. Echolucent plaques indicated the presence of a relatively smaller lipid or NC compared with echo-attenuated plaques (thickness: 0.51 mm [interquartile range (IQR): 0.35 to 0.64 mm] vs. 0.70 mm [IQR: 0.54 to 0.92 mm] [p < 0.001]; arc: 74.5° [IQR: 59.0° to 101.0°] vs. 90° [IQR: 70.0° to 112.0°] [p < 0.001]), although 82.8% of superficial echolucent zones indicated an NC-containing FA. IVUS spotty calcification, especially when superficial in location (72.6%), was often associated with an FA with calcium deposits and had smaller arcs of calcium in the setting of FA compared with fibrocalcific plaques (37.5° [IQR: 23.0° to 53.0°] vs. 59.0° [IQR: 46.0° to 69.0°]; p < 0.001). Comparisons between IVUS and near-infrared spectroscopy revealed that echo-attenuated plaques contained the highest probability of near-infrared spectroscopy-derived lipid core plaque, followed by echolucent plaques and spotty calcifications., Conclusions: This study demonstrated that echo-attenuated plaque, especially superficial echo attenuation, was the most reliable IVUS signature for identifying a high-risk plaque (i.e., an FA containing a large NC)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

With an estimated 300,000 cases occurring per year in the United States alone, sudden cardiac death remains a major public health problem and in many cases is the first manifestation of coronary artery disease. Autopsy studies have established that the causative event in many cases of sudden death is rupture of an intracoronary lipid core plaque with subsequent thrombus formation. Until recently, identification of lipid core plaque in vivo has not been possible; however, a combined near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) catheter has become available that can detect lipid core plaque in patients undergoing coronary angiography. In this report, we present findings in 5 patients who experienced a documented sudden cardiac arrest, were successfully resuscitated, and then were studied with intracoronary NIRS-IVUS to assess the extent and location of lipid core plaque. Although the detection of lipid core plaque at the culprit site in victims of sudden death is not novel, the novelty of the present report is that NIRS permitted identification of the large lipid core plaque underlying sudden cardiac arrest in vivo, a finding in striking accord with prior autopsy observations implicating ruptured lipid core plaque in the pathogenesis of sudden cardiac death.

Objectives: This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI)., Background: Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients., Methods: We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI(4mm))., Results: MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445 to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm) >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%)., Conclusions: The present study has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a signature of plaques causing STEMI., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures., Methods and Results: The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI(4 mm) ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI(4 mm) ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI(4 mm) (P=0.0002)., Conclusions: NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention.

Objectives: The aim of this study was to compare the findings of near-infrared spectroscopy (NIRS), intravascular ultrasound (IVUS) virtual histology (VH), and grayscale IVUS obtained in matched coronary vessel segments of patients undergoing coronary angiography., Background: Intravascular ultrasound VH has been developed to add tissue characterization to the grayscale IVUS assessment of coronary plaques. Near-infrared spectroscopy is a new imaging technique able to identify lipid core-containing coronary plaques (LCP)., Methods: We performed NIRS and IVUS-VH pullbacks in a consecutive series of 31 patients with a common region of interest (ROI) between 2 side branches. For each ROI, we analyzed the chemogram blocks by NIRS, plaque area and plaque burden by grayscale IVUS, and tissue types by IVUS-VH. The chemogram block is a summary metric of a 2-mm vertical slice of the chemogram. The value ranges from 0 to 1 according to the presence of lipids and represents the probability of LCP with a color scale from red (low probability) through orange and tan to yellow (high probability)., Results: Plaque area (mm(2)) increases as percentage VH derived-necrotic core (NC) content (4.6 ± 2.7 vs. 7.4 ± 3.5 vs. 8.6 ± 3.4 vs. 7.9 ± 3.3, grouped in percentage NC quartiles, p<0.001) and chemogram block probability color bin thresholds increase (4.9 ± 3.8 red, 7.3 ± 3.6 orange, 8.1 ± 3.4 tan, and 8.7 ± 3.4 yellow, p<0.001). The correlation between the block chemogram detection of lipid core and percentage NC content by VH was weak (r=0.149). Correction for the presence of calcium does not improve this correlation., Conclusions: Larger plaque area by grayscale IVUS was more often associated with either elevated percentage VH-NC or LCP by NIRS; however, the correlation between the detection of LCP by NIRS and necrotic core by VH is weak., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether catheter-based near-infrared spectroscopy (NIRS) signals obtained with a novel catheter-based system from coronaries of patients are similar to those from autopsy specimens and to assess initial safety of NIRS device., Background: An intravascular NIRS system for detection of lipid core-containing plaques (LCP) has been validated in human coronary autopsy specimens. The SPECTACL (SPECTroscopic Assessment of Coronary Lipid) trial was a parallel first-in-human multicenter study designed to demonstrate the applicability of the LCP detection algorithm in living patients., Methods: Intracoronary NIRS was performed in patients undergoing percutaneous coronary intervention. Acquired spectra were blindly compared with autopsy NIRS signals with multivariate statistics. To meet the end point of spectral similarity, at least two-thirds of the scans were required to have >80% of spectra similar to the autopsy spectra., Results: A total of 106 patients were enrolled; there were no serious adverse events attributed to NIRS. Spectroscopic data could not be obtained in 17 (16%) patients due to technical limitations, leaving 89 patients for analysis. Spectra from 30 patients were unblinded to test the calibration of the LCP detection algorithm. Of the remaining 59 blinded cases, after excluding 11 due to inadequate data, spectral similarity was demonstrated in 40 of 48 spectrally adequate scans (83% success rate, 95% confidence interval: 70% to 93%, median spectral similarity/pullback: 96%, interquartile range 10%). The LCP was detected in 58% of 60 spectrally similar scans from both cohorts., Conclusions: This intravascular NIRS system safely obtained spectral data in patients that were similar to those from autopsy specimens. These results demonstrate the feasibility of invasive detection of coronary LCP with this novel system. (SPECTACL: SPECTroscopic Assessment of Coronary Lipid; NCT00330928).

Objectives: This study sought to assess agreement between an intravascular near-infrared spectroscopy (NIRS) system and histology in coronary autopsy specimens., Background: Lipid core plaques cannot be detected by conventional tests, yet are suspected to be the cause of most acute coronary syndromes. Near-infrared spectroscopy is widely used to determine the chemical content of substances. A NIRS system has been developed and used successfully in 99 patients., Methods: Scanning NIRS was performed through blood in 212 coronary segments from 84 autopsy hearts. One histologic section was analyzed for every 2 mm of artery. Lipid core plaque of interest (LCP) was defined as a lipid core >60 degrees in circumferential extent, >200-microm thick, with a mean fibrous cap thickness <450 microm. The first 33 hearts were used to develop the algorithm; the subsequent 51 validation hearts were used in a prospective, double-blind manner to evaluate the accuracy of NIRS in detecting LCP. A NIRS-derived lipid core burden index for an entire artery was also validated by comparison to histologic findings., Results: The LCPs were present in 115 of 2,649 (4.3%) sections from the 51 validation hearts. The algorithm prospectively identified LCP with a receiver-operator characteristic area of 0.80 (95% confidence interval [CI]: 0.76 to 0.85). The lipid core burden index detected the presence or absence of any fibroatheroma with an area under the curve of 0.86 (95% CI: 0.81 to 0.91). A retrospective analysis of lipid core burden index conducted in extreme artery segments with either no or extensive fibroatheroma yielded an area under the curve of 0.96 (95% CI: 0.92 to 1.00), confirming the accuracy of spectroscopy in identifying plaques with markedly different lipid content under ideal circumstances., Conclusions: This novel catheter-based NIRS system accurately identified lipid core plaques through blood in a prospective study in coronary autopsy specimens. It is expected that this novel capability will be of assistance in the management of patients with coronary artery disease.

This review describes efforts to use near-infrared (NIR) spectroscopy to identify chemical components of coronary artery plaques as a means to assess vulnerability. Near-infrared spectroscopy has been well-validated by the physical sciences as a method to characterize chemical composition of various bio-materials and could be ideal to detect vulnerable coronary plaques in patients. Recent studies in aortic and coronary artery autopsy specimens have confirmed the ability of the technique to identify lipid-rich thin-cap fibroatheromas through blood. A catheter-based system has been developed to address the challenges-of access to the coronary artery, blood, motion, and the need to scan-that must be overcome for use in patients. Initial clinical experience in six patients with stable angina demonstrates that high-quality NIR spectra can be safely obtained. Additional studies are planned to validate the ability of the technique to identify lipid-rich coronary artery plaques and ultimately link chemical characterization with subsequent occurrence of an acute coronary syndrome.

Background: A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy., Methods and Results: A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 microm by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively., Conclusions: NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.