Accuracy of IVUS-Based Machine Learning Segmentation Assessment of Coronary Artery Dimensions and Balloon Sizing.

Background: Accurate intravascular ultrasound (IVUS) measurements are important in IVUS-guided percutaneous coronary intervention optimization by choosing the appropriate device size and confirming stent expansion. Objectives: The purpose of this study was to assess the accuracy of machine learning (ML) automatic segmentation of coronary artery vessel and lumen dimensions and balloon sizing. Methods: Using expert analysis as the gold standard, ML segmentation of 60 MHz IVUS images was developed using 8,076 IVUS cross-sectional images from 234 patients, which were randomly split into training (83%) and validation (17%) data sets. The performance of ML segmentation was then evaluated using an independent test data set (437 images from 92 patients). The endpoints were the agreement rate between ML vs experts' measurements for appropriate balloon size selection, and lumen and acute stent areas. Appropriate balloon size was determined by rounding down from the mean vessel diameter or rounding up from the mean lumen diameter to the next balloon size. The difference of lumen area ≥0.5 mm2 was considered as clinically significant. Results: ML model segmentation correlated well with experts' segmentation for training data set with a correlation coefficient of 0.992 and 0.993 for lumen and vessel areas, respectively. The agreement rate in lumen and acute stent areas was 85.5% and 97.0%, respectively. The agreement rate for appropriate balloon size selection was 70.6% by vessel diameter only and 92.4% by adding lumen diameter. Conclusions: ML model IVUS segmentation measurements were well-correlated with those of experts and selected an appropriate balloon size in more than 90% of images.

Optical coherence tomography in coronary atherosclerosis assessment and intervention.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.

OBJECTIVES: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. METHODS: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. RESULTS: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. CONCLUSION: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

The IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact (IMPROVE) trial: Study design and rationale.

Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) has been shown in clinical trials, registries, and meta-analyses to reduce recurrent major adverse cardiovascular events after PCI. However, IVUS utilization remains low. An increasing number of high-risk or complex coronary artery lesions are treated with PCI, and we hypothesize that the impact of IVUS in guiding treatment of these complex lesions will be of increased importance in reducing major adverse cardiovascular events while remaining cost-effective. The "IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact" trial (registered on clinicaltrials.gov: NCT04221815) is a multicenter, international, clinical trial randomizing subjects to IVUS-guided versus angiography-guided PCI in a 1:1 ratio. Patients undergoing PCI involving a complex lesion are eligible for enrollment. Complex lesion is defined as involving at least 1 of the following characteristics: chronic total occlusion, in-stent restenosis, severe coronary artery calcification, long lesion (≥28 mm), or bifurcation lesion. The clinical investigation will be conducted at approximately 120 centers in North America and Europe, enrolling approximately 2,500 to 3,100 randomized subjects with an adaptive design. The primary clinical end point is the rate of target vessel failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. The co-primary imaging end point is the final post-PCI minimum stent area assessed by IVUS. The primary objective of this study is to assess the impact of IVUS guidance on the PCI treatment of complex lesions.

Additive Value of High-Density Lipoprotein Cholesterol and C-Reactive Protein Level Assessment for Prediction of 2-year Mortality After Transcatheter Aortic Valve Implantation.

Available prediction models are inaccurate in elderly who underwent transcatheter aortic valve implantation (TAVI). The aim of present study was to analyze the separate and combined prognostic values of baseline HDL-C and C-reactive protein (CRP) levels in patients treated successfully with TAVI who had complete 2-year follow-up. We analyzed 334 patients treated with TAVI from 01/2010 to 07/2017 who had measurements of HDL-C and CRP on admission or during qualification for the procedure. Baseline HDL-C ≤46 mg/dl (areas under the curve [AUC] = 0.657) and CRP ≥0.20 mg/dl (AUC = 0.634) were predictive of 2-year mortality. After stratification with both cutoffs, patients with low HDL-C and concomitant high CRP most often had LVEF ≤50% and were high risk as per EuroSCORE II. Those with isolated CRP elevation had the lowest frequency of LVEF ≤50%, but more sarcopenia (based on psoas muscle area). After adjustment in the multivariate analysis for other identified predictors including EuroSCORE II and statin therapy, isolated HDL-C ≤46 mg/dl (identified in 40 patients) and isolated CRP ≥0.20 mg/dl (n = 109) were both independent predictors of 2-year mortality (hazard ratio [HR] = 2.92 and HR = 2.42, respectively) compared with patients with both markers within established cutoffs (n = 105) who had the lowest 2-year mortality (9.5%). Patients with both markers exceeding cutoffs (n = 80) had the highest risk (HR = 4.53) with 2-year mortality of 42.5%. High CRP was associated with increased mortality within the first year of follow-up, whereas low HDL-C increased mortality in the second year. The combination of both markers with EuroSCORE II enhanced mortality prediction (AUC = 0.697). In conclusion, low baseline HDL-C and high CRP jointly contribute to the prediction of increased all-cause mortality after TAVI.

Optical coherence tomography and intravascular ultrasound assessment of the anatomic size and wall thickness of a muscle bridge segment.

OBJECTIVE: To use optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in assessing myocardial bridging (MB) vessel size and wall thickness. BACKGROUND: During stent implantation, MB is associated with complications, especially perforation. METHODS: OCT and IVUS were performed in 56 patients with typical angiographic "milking" from November 2016 to May 2017. The vessel area and thickness in the MB segments and adjacent proximal and distal reference segments were measured and compared with eight normal left anterior descending (LAD) segment (no atherosclerosis in a segment that was at least 20 mm long and that began ~40 mm distal to the LAD ostium). RESULTS: Compared with the reference vessel size distal to the MB segment (6.3 ± 1.8 mm2 ), the IVUS-measured size of the tunneled vessel during diastole was significantly smaller (6.0 ± 1.9 mm2 , p < 0.05) (remodeling index = 0.79 ± 0.18). The minimum intramyocardial arterial wall thickness was 0.16 ± 0.02 mm, significantly thinner than that of the mean reference (0.22 ± 0.03 mm, p < 0.001). The location of the thinnest arterial wall was in the distal and middle MB segments in 45 (80.4%) and 11 (19.6%) patients, respectively, and was not related to the degree of systolic compression or remodeling index. The walls of the middle and distal MB subsegments, but not of the proximal MB subsegment, were thinner than that of the comparison group of normal LADs. CONCLUSION: The coronary vessel involved in an MB is both smaller and thinner than that of the adjacent non-MB segment. This may explain the increased frequency and severity of coronary perforation during stent implantation.

Intravascular Ultrasound Assessment of In-Stent Restenosis in Saphenous Vein Grafts.

Outcomes after percutaneous coronary interventions (PCI) in saphenous vein grafts (SVG) are inferior compared with native coronary arteries, but the mechanisms of SVG in-stent restenosis (ISR) have not been well-described. Thus, we aimed to evaluate the patterns of SVG ISR using intravascular ultrasound (IVUS) in 54 SVG ISR lesions. Stent underexpansion was defined as minimum stent area (MSA) <5 mm2. The time from stent implantation to presentation with ISR (9 BMS, 18 first-generation DES, and 27 second-generation DES) was 3.7 ± 3.0 years. IVUS-defined ISR patterns were categorized as mechanical (33%) or biological (67%). Mechanical patterns comprised 10 cases of stent underexpansion (MSA = 4.2 ± 0.9 mm2), 6 stent fractures or deformations, and 2 uncovered aorto-anastomotic lesions. Biological patterns comprised 19 cases of neoatherosclerosis, 13 excessive neointimal hyperplasia (NIH, 65 ± 11%), and 4 thrombi. Compared with biological patterns of ISR, mechanical patterns were more frequently located at the SVG anastomosis (72% vs 39%, p = 0.04) and at the SVG hinge motion site (55% vs 21%, p = 0.02). Although patients with mechanical patterns of ISR presented earlier than those with biological patterns (2.3 vs 4.4 years, p = 0.009), 61% of them were diagnosed >1 year after stent implantation. In conclusion, SVG ISR is dominated by biological patterns including neoatherosclerosis. Mechanical patterns of SVG ISR are associated with earlier presentation and location at graft anastomosis or hinge motion site.

Optical Coherence Tomography Assessment of Morphological Characteristics in Suspected Coronary Artery Disease, but Angiographically Nonobstructive Lesions.

BACKGROUND/PURPOSE: We sought to evaluate the morphological characteristics of nonobstructive coronary lesions in patients with ischemic symptoms and/or signs. MATERIALS/METHODS: We used optical coherence tomography (OCT) to assess the presumed culprit lesion in 142 patients with suspected coronary artery disease in whom coronary angiography showed no lesion with a diameter stenosis ≥50%. Patients with a clinical diagnosis of acute coronary syndrome (ACS, n = 31, including 2 ST-elevation myocardial infarction, 9 non-ST-elevation myocardial infarction, and 20 unstable angina pectoris) were compared to those with stable coronary artery disease (CAD) (n = 111) including 79 patients with stable angina and 32 patients with silent ischemia (positive non-invasive stress test only). RESULTS: The overall prevalence of thrombus, plaque rupture, intimal laceration, or calcified nodule in the combined groups was 23.2% (33/142) including 15 thrombus, 12 plaque rupture, 9 calcified nodule, and 8 intimal laceration (not mutually exclusive) without differences between ACS and stable CAD patients. Also the prevalence of thin-cap fibroatheroma was not significantly different between ACS and stable patients (12.9% vs 6.3%, p = 0.22). Minimum lumen area (3.1 mm2 [2.3, 4.1] versus 3.2 mm2 [2.4, 4.7], p = 0.7) and area stenosis (49.9% [37.1, 56.4] versus 48.1% [37.8, 55.8], p = 0.9) were similar between ACS and stable CAD patients. CONCLUSION: In patients presenting with ischemic symptoms and/or signs, but angiographically nonobstructive culprit lesions, approximately 25% had abnormal findings by OCT-whether patients presented with acute/unstable or stable CAD.

Intravascular ultrasound assessment of the effects of rotational atherectomy in calcified coronary artery lesions.

We sought to clarify intravascular ultrasound (IVUS) features of rotational atherectomy (RA) of calcified lesions. IVUS was performed post-RA and post-stent in 38 lesions and analyzed every 1 mm. Pre-intervention IVUS was performed when the IVUS catheter crossed the lesion (n = 11). Calcium Index was average calcium angle multiplied by calcium length. We compared lowest (n = 13), middle (n = 13), and highest (n = 12) Calcium Index tertiles. Reverberations (multiple reflections from calcium) with a concave-shaped lumen in the post-RA IVUS were considered to represent RA-related calcium modification. Newly visible perivascular tissue through a previously solid arc of calcium in the post-stent IVUS was also evaluated. Comparing the pre and post-RA IVUS, maximum reverberation angle, and length increased significantly after RA (angle, from 45° [31, 67] to 96° [50, 148], p = 0.003; length, from 4.0 mm [2.0, 6.0] to 8.0 mm [4.0, 14.0], p = 0.005). In the post-RA IVUS, reverberations had a larger angle in the middle and highest Calcium Index tertiles (lowest, 91° [64, 133]; middle, 135° [107, 201]; highest, 150° [93, 208], p = 0.03). Post-stent newly visible perivascular tissue was more frequent in the middle and highest Calcium Index tertiles (lowest, 30.8%; middle, 69.2%; highest, 75.0%, p = 0.049). Minimum stent area was similar after calcium modification by RA irrespective of the severity of the Calcium Index (lowest, 6.7 mm2 [5.7, 8.9]; middle, 5.6 mm2 [4.9, 6.8]; highest, 6.7 mm2 [5.9, 8.2], p = 0.2). Greater calcium modification by RA occurs in severely calcified lesions with smaller lumen diameters to mitigate against stent underexpansion.

Impact of bleeding assessment and adjudication methodology on event rates and clinical trial outcomes: insights from the HORIZONS-AMI trial.

AIMS: Bleeding is a major safety outcome in cardiovascular trials. The present study assessed the impact of the adjudication process of bleeding events on three-year outcomes in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. METHODS AND RESULTS: HORIZONS-AMI enrolled 3,602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. An independent CEC reviewed 445 potential bleeding events identified from three sources: 339 site-reported (SR), 35 CEC-identified, and 71 database (DB)-triggered events based on programmatic identification of a decline in haemoglobin of ≥3 g/dL or in haematocrit by ≥9%; of those, 383/445 (86.1%) met the protocol definition of major bleeding. By multivariable analysis, CEC-confirmed bleeding was an independent predictor of cardiovascular death (hazard ratio [HR] 2.84, 95% confidence interval [CI]: 1.81-4.45, p<0.0001) and all-cause death (HR 2.70, 95% CI: 1.92-3.79, p<0.0001) at three years. Non-CEC-confirmed bleeding was also a predictor of cardiovascular death (HR 3.45, 95% CI: 1.47-8.11, p=0.005) and all-cause death (HR 2.41, 95% CI: 1.11-5.23, p=0.03) at three years. CONCLUSIONS: In the HORIZONS-AMI trial, adjudication of bleeding via a centralised CEC process resulted in identification of a larger number of events than were SR. All CEC-confirmed bleeding events were independently predictive of three-year cardiovascular and all-cause mortality. The association of non-CEC-confirmed bleeding with mortality merits further investigation.

Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study).

Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

Iterative Image Reconstruction Improves the Accuracy of Automated Plaque Burden Assessment in Coronary CT Angiography: A Comparison With Intravascular Ultrasound.

OBJECTIVE: The purpose of this study was to determine whether use of iterative image reconstruction algorithms improves the accuracy of coronary CT angiography (CCTA) compared with intravascular ultrasound (IVUS) in semiautomated plaque burden assessment. MATERIALS AND METHODS: CCTA and IVUS images of seven coronary arteries were acquired ex vivo. CT images were reconstructed with filtered back projection (FBP) and adaptive statistical (ASIR) and model-based (MBIR) iterative reconstruction algorithms. Cross-sectional images of the arteries were coregistered between CCTA and IVUS in 1-mm increments. In CCTA, fully automated (without manual corrections) and semiautomated (allowing manual corrections of vessel wall boundaries) plaque burden assessments were performed for each of the reconstruction algorithms with commercially available software. In IVUS, plaque burden was measured manually. Agreement between CCTA and IVUS was determined with Pearson correlation. RESULTS: A total of 173 corresponding cross sections were included. The mean plaque burden measured with IVUS was 63.39% ± 10.63%. With CCTA and the fully automated technique, it was 54.90% ± 11.70% with FBP, 53.34% ± 13.11% with ASIR, and 55.35% ± 12.22% with MBIR. With CCTA and the semiautomated technique mean plaque burden was 54.90% ± 11.76%, 53.40% ± 12.85%, 57.09% ± 11.05%. Manual correction of the semiautomated assessments was performed in 39% of all cross sections and improved plaque burden correlation with the IVUS assessment independently of reconstruction algorithm (p < 0.0001). Furthermore, MBIR was superior to FBP and ASIR independently of assessment method (semiautomated, r = 0.59 for FBP, r = 0.52 for ASIR, r = 0.78 for MBIR, all p < 0.001; fully automated, r = 0.40 for FBP, r = 0.37 for ASIR, r = 0.53 for MBIR, all p < 0.001). CONCLUSION: For the quantification of plaque burden with CCTA, MBIR led to better correlation with IVUS than did traditional reconstruction algorithms such as FBP, independently of the use of a fully automated or semiautomated assessment approach. The highest accuracy for quantifying plaque burden with CCTA can be achieved by using MBIR data with semiautomated assessment.

Relation Between Renal Function and Coronary Plaque Morphology (from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Virtual Histology-Intravascular Ultrasound Substudy).

We sought to examine the relation between various degrees of renal function and coronary plaque morphology by grayscale and virtual histology intravascular ultrasound (IVUS). ADAPT-DES was a prospective, multicenter registry of 8,582 consecutive patients treated using coronary drug-eluting stents with a prespecified grayscale and virtual histology-IVUS substudy. A lesion-level analysis of study participants was performed by comparing IVUS parameters of culprit and nonculprit lesions across tertiles of estimated creatinine clearance (CrCl). Preintervention IVUS imaging of 762 patients identified 898 culprit and 752 nonculprit native coronary artery lesions. Patients in the lowest CrCl tertile were older, more often women, and more often presented with stable angina. Compared with the middle and upper tertiles, the lowest tertile was significantly associated with culprit lesion smaller mean external elastic membrane cross-sectional area (12.9 vs 14.2 mm3/mm vs 14.9 mm3/mm, p <0.0001), smaller mean lumen cross-sectional area (5.5 mm3/mm vs 5.8 mm3/mm vs 6.1 mm3/mm, p = 0.002), and more dense calcium volume (11.5% vs 10.2% vs 9.7%, p = 0.02). Similar trends were found in the nonculprit lesions. Plaque rupture was least common in patients in the lowest tertile. On multivariable analysis, independent predictors of greater dense calcium volume were lower CrCl, hyperlipidemia, female gender, and presentation without ST-segment elevation myocardial infarction. In conclusion, in the present large-scale IVUS study diminishing renal function was associated with increased coronary calcification and decreased coronary vessel and lumen sizes, with a graded response according to the reduction in CrCl. In addition, these patients were more likely to present with stable angina versus patients with normal renal function who were more likely to present with an acute coronary syndrome.

Morphological assessment of chronic total occlusions by combined coronary computed tomographic angiography and intravascular ultrasound imaging.

AIMS: The relationship between CTO morphology and vessel remodelling is unclear. We described chronic total occlusion (CTO) morphology using coronary computed tomographic angiography (CCTA) combined with intravascular ultrasound (IVUS). METHODS AND RESULTS: Pre-intervention CCTA and IVUS of 130 CTO lesions (128 patients) were evaluated. Based on CCTA, positive CTO lesion remodelling [PR, maximum CTO segment vessel diameter > proximal reference vessel diameter (RVD)] was seen in 44 (33.8%) lesions. In the other 86 lesions without PR, 74 (56.9%) had a minimum CTO segment vessel diameter >50% of the proximal RVD and were classified as non-PR; 12 (9.2%) lesions had a minimum CTO segment vessel diameter ≤50% of the proximal RVD and were classified as collapse. Comparing the three groups, CTO with PR had the greatest maximum atheroma cross-sectional area (CSA) while the collapse group had the least atheroma CSA (16.0 mm2 [12.0, 19.4] vs. 9.1 mm2 [6.0, 15.9], P < 0.001). The maximum arc of attenuated plaque was greatest in the PR group (51° [0, 167]); and the maximum arc of calcium was greatest in the non-PR group (91° [51, 174]). In the collapse group distal to the occluded segment, there was a normal-appearing vessel by IVUS that corresponded to the collapsed segment by CCTA; its minimum plaque burden was 33.2% [19.9, 38.1] with a smooth concave-shaped lumen surface, implying that the CCTA collapse segment was not occluded. CONCLUSION: Not all CTOs are the same with regard to lesion remodelling and underlying morphology. The combination of IVUS and CCTA can help to categorize CTO morphology.