Ex vivo validation of 45 MHz intravascular ultrasound backscatter tissue characterization.

AIMS: The objectives of the present study are to describe the algorithm for VH(®) IVUS using the 45-MHz rotational IVUS catheter and the associated ex vivo validation in comparison to the gold standard histology. METHODS AND RESULTS: The first phase of the present study was to construct the 45 MHz VH IVUS algorithm by using a total of 55 human coronary artery specimens [111 independent coronary lesions and 510 homogenous regions of interest (ROIs)], obtained at autopsy. Regions were selected from histology and matched with their corresponding IVUS data to build the plaque classification system using spectral analysis and statistical random forests. In the second phase, the ex vivo validation of the VH IVUS algorithm assessed a total of 1060 ROIs (120 lesions from 60 coronary arteries) in comparison with histology. In an independent manner, two interventional cardiologists also classified a randomly selected subset of the ROIs for assessment of inter- and intra-observer reproducibility of VH IVUS image interpretation.When including all ROIs, the predictive accuracies were 90.8% for fibrous tissue, 85.8% for fibro fatty tissue, 88.3% for necrotic core, and 88.0% for dense calcium. The exclusion of ROIs in the acoustically attenuated areas improved the predictive accuracies, ranging from 91.9 to 96.8%. The independent analysis of randomly selected 253 ROIs showed substantial agreement for inter-observer (k = 0.66) and intra-observer (k = 0.88) reproducibility. CONCLUSION: Tissue classification by 45 MHz VH IVUS technology, when not influenced by calcium-induced acoustic attenuation, provided combined tissue accuracy >88% to identify tissue types compared with the gold standard histologic assessment, with high inter- and intra-observer reproducibility.

Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial.

OBJECTIVES: The authors sought to report the temporal stability of an untreated, nonculprit lesion phenotype in patients presenting with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The temporal stability of the untreated, nonculprit lesion phenotype has been studied using intravascular ultrasound-virtual histology (IVUS) in patients with stable ischemic heart disease, but not in STEMI patients. METHODS: As part of a formal substudy of the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, baseline and 13-month follow-up IVUS was performed in 99 untreated nonculprit lesions in 63 STEMI patients. Lesions were classified as pathological intimal thickening (PIT), IVUS-derived thin-cap fibroatheroma (TCFA), thick-cap fibroatheroma (ThCFA), fibrotic plaque, or fibrocalcific plaque. RESULTS: The frequency of TCFA increased from 41% at baseline to 54% at follow-up, whereas ThCFAs decreased from 41% to 34% and PIT decreased from 16% to 8%. Among the 41 lesions classified at baseline as TCFA, at follow-up, 32 (78%) were still classified as TCFA, whereas 9 (22%) were classified as ThCFAs or fibrotic plaques. An additional 21 lesions at follow-up were newly classified as TCFA, developing from either PIT or ThCFA. TCFA at baseline that evolved into non-TCFAs trended toward a more distal location than TCFA that did not change (p = 0.12). In lesions classified as TCFA, the minimum lumen area (MLA) decreased from 8.1 (interquartile range [IQR]: 7.4 to 8.8) mm(2) at baseline to 7.8 (IQR: 7.2 to 8.4) mm(2) at follow-up, p < 0.05; this was associated with an increase in percent necrotic core at the MLA site (14% [IQR: 12 to 16] to 19% [IQR: 17 to 22], p < 0.0001) and over the entire length of the lesion (14% [IQR: 12 to 16] to 18% [IQR: 17 to 20], p < 0.0001). CONCLUSIONS: Untreated nonculprit lesions in STEMI patients frequently have TCFA morphology that does not change during 13-month follow-up and is accompanied by a decrease in MLA and an increase in necrotic core. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Relation between angiographic lesion severity, vulnerable plaque morphology and future adverse cardiac events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study).

Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)-intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤ 4 mm(2), IVUS plaque burden ≥ 70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥ 70%, minimum luminal area ≤ 4 mm(2), and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.

The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization.

OBJECTIVES: We used virtual histology intravascular ultrasound (VH-IVUS) to investigate the natural history of coronary artery lesion morphology. BACKGROUND: Plaque stability is related to its histological composition. METHODS: We performed serial (baseline and 12-month follow-up) VH-IVUS studies and examined 216 nonculprit lesions (plaque burden >or=40%) in 99 patients. Lesions were classified into pathological intimal thickening (PIT), VH-IVUS-derived thin-capped fibroatheroma (VH-TCFA), thick-capped fibroatheroma (ThCFA), fibrotic plaque, and fibrocalcific plaque. RESULTS: At baseline, 20 lesions were VH-TCFAs; during follow-up, 15 (75%) VH-TCFAs "healed," 13 became ThCFAs, 2 became fibrotic plaque, and 5 (25%) VH-TCFAs remained unchanged. Compared with VH-TCFAs that healed, VH-TCFAs that remained VH-TCFAs located more proximally (values are median [interquartile range]) (16 mm [15 to 18 mm] vs. 31 mm [22 to 47 mm], p = 0.013) and had larger lumen (9.1 mm(2) [8.2 to 10.7 mm(2)] vs. 6.9 mm(2) [6.0 to 8.2 mm(2)], p = 0.021), vessel (18.7 mm(2) [17.3 to 28.6 mm(2)] vs. 15.5 mm(2) [13.3 to 16.6 mm(2)]; p = 0.010), and plaque (9.7 mm(2) [9.6 to 15.7 mm(2)] vs. 8.4 mm(2) [7 to 9.7 mm(2)], p = 0.027) areas; however, baseline VH-IVUS plaque composition did not differ between VH-TCFAs that healed and VH-TCFAs that remained VH-TCFAs. Conversely, 12 new VH-TCFAs developed; 6 late-developing VH-TCFAs were PITs, and 6 were ThCFAs at baseline. In addition, plaque area at minimum lumen sites increased significantly in PITs (7.8 mm(2) [6.2 to 10.0 mm(2)] to 9.0 mm(2) [6.5 to 12.0 mm(2)], p < 0.001), VH-TCFAs (8.6 mm(2) [7.3 to 9.9 mm(2)] to 9.5 mm(2) [7.8 to 10.8 mm(2)], p = 0.024), and ThCFAs (8.6 mm(2) [6.8 to 10.2 mm(2)] to 8.8 mm(2) [7.1 to 11.4 mm(2)], p < 0.001) with a corresponding decrease lumen areas, but not in fibrous or fibrocalcific plaque. CONCLUSIONS: Most VH-TCFAs healed during 12-month follow-up, whereas new VH-TCFAs also developed. PITs, VH-TCFAs, and ThCFAs showed significant plaque progression compared with fibrous and fibrocalcific plaque.

Analysis of the long-term effects of drug-eluting stents on coronary arterial wall morphology as assessed by virtual histology intravascular ultrasound.

BACKGROUND: Animal models show impairment of arterial healing after drug-eluting stents (DES) compared with bare-metal stents (BMS). Virtual histology intravascular ultrasound (VH-IVUS) offers an opportunity to assess lesion morphology in vivo. METHODS: We used VH-IVUS in 80 patients to assess long-term (median = 10 months) native artery vascular responses after 76 implantations of DES compared with 32 BMS. The presence of "necrotic core abutting the lumen" was evaluated at baseline and follow-up. RESULTS: At baseline, necrotic core abutting the lumen through the stent struts was observed in 76% of DES and 75% of BMS. Although the percentage of necrotic core within the plaque behind the stents did not change during follow-up in DES (23% [18%, 28%] to 22% [17%, 27%], P = .57) or BMS (22% [19%, 27%] to 20% [12%, 26%], P = .29), necrotic core abutting the lumen through the stent struts decreased more in BMS (75% to 19%, P < .001) than DES (76% to 61%, P = .036) because of the lack of an overlying, protective neointima in DES-treated lesions. Furthermore, within the adjacent reference segments, the incidence of necrotic core abutting the lumen decreased in BMS-treated lesions (proximal 23% to 0%, P = .023; distal 21% to 0%, P = .023), but not in DES (proximal 22% to 17%, P = .48; distal 23% to 21%, P = .82). CONCLUSIONS: Serial VH-IVUS analysis of DES-treated lesions showed a greater frequency of unstable lesion morphometry at follow-up compared with BMS. The apparent mechanism was a suppression of the protective neointimal hyperplasia layer coupled with a lack of vulnerable plaque resolution at reference segments in DES compared with BMS.

Relation between individual plaque components and overall plaque burden in the prospective, multicenter virtual histology intravascular ultrasound registry.

The impact of total plaque burden on absolute and relative amounts of each virtual histologic (VH) intravascular ultrasound (IVUS) plaque component has yet to be studied. We analyzed gray-scale and VH-IVUS findings in the first 990 patients enrolled in the 3,000+ patient global VH-IVUS registry. Whole pullback plaque burden and absolute and relative cross-sectional areas of fibrous tissue, fibrofatty plaque, dense calcium, and necrotic core were analyzed using a linear regression statistical model. Overall, absolute cross-sectional areas of each of the 4 plaque components correlated with total plaque cross-sectional area; however, the correlation between fibrous tissue and total plaque cross-sectional area was stronger than the correlation between fibrofatty plaque, dense calcium, or necrotic core and total plaque cross-sectional area. This was also true overall for each of the subgroups analyzed (gender, age, and presence/absence of acute coronary syndromes). Slope of the regression line relating each plaque component to overall plaque mass showed that 50% of the plaque cross-sectional area increase was because of fibrous tissue with a more gradual increase in fibrofatty plaque, dense calcium, and necrotic core. However, when comparing relative amounts of each plaque component with total plaque cross-sectional area, there was no significant relation between the increase in fibrous tissue, fibrofatty plaque, dense calcium, and necrotic core and the increase in total plaque cross-sectional area. In conclusion, only the absolute area of each plaque component correlated to overall plaque area, not the relative amount of each plaque; therefore, VH-IVUS plaque component increases must be analyzed by controlling for increases in plaque mass.

Impact of gender and age on in vivo virtual histology-intravascular ultrasound imaging plaque characterization (from the global Virtual Histology Intravascular Ultrasound [VH-IVUS] registry).

Virtual histology intravascular ultrasound (VH-IVUS) analyses were performed in the first 990 patients enrolled in the 3,000+ patient global VH-IVUS Registry to assess the impact of gender and age on in vivo VH-IVUS plaque characterization. The 990 patients were divided into 3 age group terciles (<58, 58 to 68, and >68 years) and again divided according to gender. In conclusion, (1) both women and men had an increase in plaque with increasing age; (2) at any age, men had more plaque than women; (3) percentages of dense calcium and necrotic core increased with increasing patient age in both men and women; and (4) gender differences were lowest in the oldest tercile (>68 years).

Technology insight: in vivo coronary plaque classification by intravascular ultrasonography radiofrequency analysis.

Acute coronary syndromes or sudden coronary death are often the first manifestations of coronary artery disease. In the majority of patients, acute coronary syndrome events are caused by plaque rupture in flow-limiting and non-flow-limiting angiographically intermediate stenoses. Histopathologic analyses have shown that plaque composition is related to the occurrence of acute clinical events and, therefore, to the vulnerability of the plaque. The emerging importance of adaptive coronary remodeling processes, such as the compensatory enlargement of the coronary artery in response to initial lesion development, has focused our interest on the nonstenotic lesions of the coronary tree. In vivo intravascular ultrasonography can demonstrate the discrepancies between the actual extent of coronary atherosclerosis and that seen by angiographic imaging. The spectral analysis of intravascular ultrasonography derived radiofrequency data enables more precise analysis of plaque composition and type than grayscale intravascular ultrasonography.

Automated coronary plaque characterisation with intravascular ultrasound backscatter: ex vivo validation.

AIMS: Atherosclerosis is considered both a systemic and focal disease. Current diagnostic tools do not allow adequate in vivo identification and characterisation of lesions. Advanced spectral analysis of IVUS backscatter has displayed the potential for real-time plaque characterisation. The aim of this study is to determine the ex vivo accuracy of automated plaque characterisation by spectral analysis of intravascular ultrasound (IVUS) backscatter. METHODS AND RESULTS: Plaques (n=184) from 51 coronary arteries were imaged by IVUS. The arteries were then pressure fixed and matching histology collected. Regions were selected from histology and corresponding IVUS data were used to build the plaque classification system using spectral analysis and classi-fication trees. Tissue-maps were validated ex vivo by comparison with histology via 899 selected regions (n=94 plaques) that comprised 471 fibrous tissue (FT), 130 fibro-fatty (FF), 132 necrotic-core (NC) and 156 dense-calcium (DC) regions. The overall predictive accuracies were 93.5% for FT, 94.1% for FF, 95.8% for NC, and 96.7% for DC with sensitivities and specificities ranging from 72% to 99%. The Kappa statistic was calculated to be 0.845 indicating very high agreement with histology. CONCLUSIONS: Automated spectral analysis of IVUS backscatter provides accurate ex vivo information on plaque composition, with considerable potential for assessment of plaque vulnerability in real-time.