Prospective Deep Learning-based Quantitative Assessment of Coronary Plaque by CT Angiography Compared with Intravascular Ultrasound.

AIMS: Coronary computed tomography angiography provides noninvasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicenter international study compared an automated deep-learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). METHODS AND RESULTS: The study included clinically stable patients with known coronary artery disease from 15 centers in the U.S. and Japan. An artificial intelligence (AI)-enabled plaque analysis service was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm. Mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. CONCLUSIONS: Artificial intelligence enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.[ClinicalTrails.gov identifier: NCT05138289].

Optical Coherence Tomography-Based Functional Stenosis Assessment: FUSION-A Prospective Multicenter Trial.

BACKGROUND: Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)-based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses. METHODS: FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%-90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals. RESULTS: After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%; P=0.01) and specificity (76.6% versus 75%; P=0.01). The area under the curve was 0.88 (95% CI, 0.84-0.92; P<0.0001). CONCLUSIONS: OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04356027.

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.

1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial.

OBJECTIVES: The aim of this study was to identify the post-percutaneous coronary intervention (PCI) target value of instantaneous wave-free ratio (iFR) that would best discriminate clinical events at 1 year in the DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study. BACKGROUND: The impact of residual ischemia detected by iFR post-PCI on clinical and symptom-related outcomes is unknown. METHODS: Blinded iFR pull back was performed after successful stent implantation in 500 patients. The primary endpoint was the rate of residual ischemia, defined as iFR ≤0.89, after operator-assessed angiographically successful PCI. Secondary endpoints included clinical events at 1 year and change in Seattle Angina Questionnaire angina frequency (SAQ-AF) score during follow-up. RESULTS: As reported, 24.0% of patients had residual ischemia (iFR ≤0.89) after successful PCI, with 81.6% of cases attributable to angiographically inapparent focal lesions. Post-PCI iFR ≥0.95 (present in 182 cases [39%]) was associated with a significant reduction in the composite of cardiac death, spontaneous myocardial infarction, or clinically driven target vessel revascularization compared with post-PCI iFR <0.95 (1.8% vs 5.7%; P = 0.04). Baseline SAQ-AF score was 73.3 ± 22.8. For highly symptomatic patients (baseline SAQ-AF score ≤60), SAQ-AF score increased by ≥10 points more frequently in patients with versus without post-PCI iFR ≥0.95 (100.0% vs 88.5%; P = 0.01). CONCLUSIONS: In DEFINE PCI, despite angiographically successful PCI, highly symptomatic patients at baseline without residual ischemia by post-PCI iFR had greater reductions in anginal symptoms at 1 year compared with patients with residual ischemia. Achieving post-PCI iFR ≥0.95 was also associated with improved 1-year event-free survival. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

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.

Blinded Physiological Assessment of Residual Ischemia After Successful Angiographic Percutaneous Coronary Intervention: The DEFINE PCI Study.

OBJECTIVES: This study sought to evaluate the incidence and causes of an abnormal instantaneous wave-free ratio (iFR) after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Impaired coronary physiology as assessed by fractional flow reserve is present in some patients after PCI and is prognostically relevant. METHODS: DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) was a multicenter, prospective, observational study in which a blinded iFR pull back was performed after angiographically successful PCI in 562 vessels in 500 patients. Inclusion criteria were angina with either multivessel or multilesion coronary artery disease with an abnormal baseline iFR. The primary endpoint of the study was the rate of residual ischemia after operator-assessed angiographically successful PCI, defined as an iFR <0.90. The causes of impaired iFR were categorized as stent related, untreated proximal or distal focal stenosis, or diffuse atherosclerosis. RESULTS: An average of 1.1 vessels per patient had abnormal baseline iFRs, with a mean value of 0.69 ± 0.22, which improved to 0.93 ± 0.07 post-PCI. Residual ischemia after angiographically successful PCI was present in 112 patients (24.0%), with a mean iFR in that population of 0.84 ± 0.06 (range 0.60 to 0.89). Among patients with impaired post-PCI iFRs, 81.6% had untreated focal stenoses that were angiographically inapparent, and 18.4% had diffuse disease. Among the focal lesions, 38.4% were located within the stent segment, while 31.5% were proximal and 30.1% were distal to the stent. Post-PCI vessel angiographic diameter stenosis was not a predictor of impaired post-procedural iFR. CONCLUSIONS: Blinded post-PCI physiological assessment detected residual ischemia in nearly 1 in 4 patients after coronary stenting despite an operator-determined angiographically successful result. Most cases of residual ischemia were due to inapparent focal lesions potentially amenable to treatment with additional PCI. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

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.

Japan-United States of America Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (Japan-USA HARMONEE) study: primary results of the pivotal registration study of combined endothelial progenitor cell capture and drug-eluting stent in patients with ischaemic coronary disease and non-ST-elevation acute coronary syndrome.

Aims: Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (HARMONEE) (NCT02073565) was a randomized pivotal registration trial of the Combo stent, which combined sirolimus and an abluminal bioabsorbable polymer with a novel endoluminal anti-CD34+ antibody coating designed to capture endothelial progenitor cells (EPC) and promote percutaneous coronary intervention (PCI) site healing. Methods and results: Clinically stabilized PCI subjects were randomized 1:1 to receive Combo or everolimus-eluting stents (EES). Between February 2014 and June 2016, 572 subjects with 675 coronary lesions underwent 1-year angiography and fractional flow reserve, with optical coherence tomography (OCT) in the first 140 patients. The primary clinical endpoint was non-inferior 1-year target vessel failure (TVF). The primary mechanistic endpoint of EPC capture activity was superior strut coverage by OCT. Target vessel failure occurred in 7.0% Combo (20/287) vs. 4.2% EES (12/285), a 2.8% [95% confidence interval (95% CI) -1.0%, 6.5%] difference, meeting the non-inferiority hypothesis (P = 0.02). There were no cardiac deaths, with one stent thrombosis observed in the EES group. Quantitative coronary angiography late loss with Combo was equivalent to EES. Optical coherence tomography strut coverage at 1 year was superior with Combo vs. EES [91.3% (95% CI 88.7%, 93.8%) vs. 74.8% (95% CI 70.0%, 79.6%), P < 0.001], with homogeneous tissue in 81.2% vs. 68.8%, respectively. Conclusion: Combo stent demonstrated non-inferior 1-year TVF and late loss in a randomized comparison to EES, with superior strut-based tissue coverage by OCT as a surrogate of EPC capture technology activity.

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.

Sex differences in the effect of diabetes mellitus on platelet reactivity and coronary thrombosis: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study.

BACKGROUND: Whether the consequences of diabetes mellitus (DM) are worse for women than for men treated with drug-eluting stents (DES) and antiplatelet therapy remain unclear. METHODS: Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were stratified according to sex and DM status. We investigated the sex-specific effect of DM on high on-clopidogrel platelet reactivity (HPR), defined as a P2Y12 reaction units ≥208, and the adjusted association of DM on the 2-year risk for coronary thrombotic events (CTE), defined as spontaneous myocardial infarction or definite or probable stent thrombosis. RESULTS: Out of 8582 patients included in the study, 829 were women with DM (9.6%) and 1954 were men with DM (16.2%). The prevalence of insulin-treated DM (ITDM) was greater in women (p<0.0001). By multivariable logistic regression, DM was associated with a greater likelihood of HPR that was uniform between sexes (pint=0.88). Following adjustment for baseline variables and HPR, in women a stepwise increase in risk for CTEs was observed in the transition from no DM to non-ITDM (NITDM) (adjusted hazard ratio [adjHR]: 1.31; 95% CI: 0.78-2.18) to ITDM (adjHR: 2.69; 95% CI: 1.23-3.45). This increase in risk associated with subtypes of DM was of smaller magnitude in men (for NITDM, adjHR: 1.04; 95% CI: 0.77-1.39; for ITDM, adjHR: 1.46; 95% CI: 1.05-2.03; pint=0.016). CONCLUSIONS: In a population treated with DES and antiplatelet therapy, the risk for CTE associated with DM seems to be greater in women and was independent of HPR.

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.

Sex Differences in the Clinical Impact of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents: Results From the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

BACKGROUND: Sex differences in the outcomes after percutaneous coronary intervention with drug-eluting stents and in the response to clopidogrel therapy have been reported; however, the differential risk of high platelet reactivity (HPR) on clopidogrel in women versus men is unknown. METHODS AND RESULTS: We compared 8448 patients enrolled in the ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) according to sex and the presence/absence of HPR on clopidogrel (defined as P2Y12 reactivity units >208). Study end points were definite and probable stent thrombosis (ST), clinically relevant bleeding, all-cause mortality, myocardial infarction, and major adverse cardiac events (comprising mortality, myocardial infarction, and target lesion revascularization). HPR was more common among women (1118/2163, 51.7%) than men (2491/6285, 39.6%). HPR was associated with a roughly double risk of 1-year ST in both women and men (women with versus without HPR: 1.4% versus 0.7%; hazard ratio [HR], 2.02; 95% confidence interval [CI], 0.82-4.95; P=0.12; and men: 1.2% versus 0.5%; HR, 2.42; 95% CI, 1.36-4.30; P=0.002; Pinteraction=0.73). HPR was associated with almost half the rate of clinically relevant bleeding in women (women: HPR versus no HPR, 5.3% versus 9.8%; HR, 0.54; 95% CI, 0.40-0.74; P<0.001), whereas men had similar rates of bleeding regardless of HPR status (men: HPR versus no HPR, 5.7% versus 5.9%; HR, 0.96; 95% CI, 0.78-1.18; P=0.70; Pinteraction=0.003). In propensity-adjusted models, HPR was an independent predictor of ST and myocardial infarction in men; although both associations were nonsignificant among women, no interaction was observed in the associations between HPR and either ST or myocardial infarction. Conversely, HPR was an independent predictor of reduced bleeding only in women (women: adjusted HR, 0.58; 95% CI, 0.41-0.82; P=0.002; and men: adjusted HR, 0.83; 95% CI, 0.65-1.04; P=0.11; Pinteraction=0.01). CONCLUSIONS: In the current analysis, the associated risk of HPR for ST was similar in both sexes. However, HPR was associated with significantly reduced bleeding only among women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

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.

Predictors and Long-Term Clinical Impact of Acute Stent Malapposition: An Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Intravascular Ultrasound Substudy.

BACKGROUND: The impact of acute stent malapposition (ASM) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention is still controversial. We sought to evaluate predictors and long-term clinical outcomes of ASM. METHODS AND RESULTS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective multicenter study of 8663 patients undergoing percutaneous coronary intervention using drug-eluting stents. In a prespecified intravascular ultrasound-guided substudy, 2072 patients with 2446 culprit lesions had post-percutaneous coronary intervention intravascular ultrasound and were classified according to the presence or absence of ASM. After intravascular ultrasound-guided percutaneous coronary intervention, the overall prevalence of ASM after successful drug-eluting stents implantation was 14.4% per patient and 12.6% per lesion. Compared to lesions without ASM, lesions with ASM had larger in-stent lumen areas, larger stent areas, and larger in-stent vessel areas. A larger mean plaque area along with more attenuated plaque was observed in lesions with ASM versus lesions without ASM. Lesions with ASM had greater proximal and distal reference lumen areas and more distal, but not proximal, reference calcium compared to lesions without ASM. At 2-year follow-up, there was no significant difference in the incidence of cardiac death; myocardial infarction; early, late, or very late stent thrombosis; or clinically driven target lesion revascularization in patients with ASM versus those without ASM. Furthermore, ASM was not an independent predictor of 2-year major adverse cardiac events or target lesion revascularization even when forced into the multivariate model. CONCLUSIONS: In patients treated with intravascular ultrasound-guided drug-eluting stents implantation, ASM was not associated with adverse clinical events during long-term follow-up including, but not limited to, stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.