Hospital-Level Disparities in the Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction.

There are limited contemporary data evaluating the relation between hospital characteristics and outcomes of patients with cardiac arrest complicating acute myocardial infarction (AMI-CA). As such, we used the National Inpatient Sample database (2000 to 2017), to identify adult admissions with primary diagnosis of AMI and concomitant CA. Interhospital transfers were excluded, and hospitals were classified based on location and teaching status (rural, urban nonteaching, and urban teaching) and bed size (small, medium, and large). Among 494,083 AMI-CA admissions, 9.3% received care at rural hospitals, 43.4% at urban nonteaching hospitals, and 47.3% at urban teaching hospitals. Compared with urban nonteaching and teaching hospitals, AMI-CA admissions at rural hospitals received lower rates of cardiac and noncardiac procedures. Admissions to urban teaching hospitals had higher rates of acute organ failure, concomitant cardiogenic shock, and cardiac and noncardiac procedures. When hospitals were stratified by bed size, 9.8% of AMI-CA admissions were admitted to small capacity hospitals, 26.0% to medium capacity, and 64.2% to large capacity hospitals. The use of cardiac and noncardiac procedures was lower in small hospitals with higher rates of use in medium and large hospitals. In-hospital mortality was higher in urban nonteaching (adjusted odds ratio [OR] 1.17; 95% confidence interval [CI]1.14 to 1.20; p <0.001) and urban teaching hospitals (adjusted OR 1.36; 95% CI 1.32 to 1.39; p <0.001) compared with rural hospitals. Compared with small hospitals, medium (adjusted OR 1.11; 95% CI 1.08 to 1.14; p <0.001) and large hospitals (adjusted OR 1.22; 95% CI 1.19 to 1.25; p <0.001) were associated with higher in-hospital mortality. In conclusion, AMI-CA admissions to large and urban hospitals had higher in-hospital mortality compared with small and rural hospitals potentially owing to greater acuity.

Meta-Analysis of Duration of Dual Antiplatelet Therapy in Acute Coronary Syndrome Treated With Coronary Stenting.

We aimed to evaluate if a shorter course of DAPT followed by P2Y12 inhibitor monotherapy is as effective as a 12-month course with fewer bleeding events. PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials of ACS patients comparing dual antiplatelet therapy (DAPT) for 1 to 3 months followed by a P2Y12 inhibitor to 12-month DAPT. Quality assessment was performed with the Cochrane Collaboration risk of bias assessment tool. Five randomized clinical trials were included, with a total of 18,046 participants. Antiplatelet strategies were aspirin and P2Y12 inhibitor for 12 months compared with aspirin and P2Y12 inhibitor for 1 to 3 months followed by P212 inhibitor alone. Patients randomized to 1 to 3 months of DAPT followed by P2Y12 inhibitor monotherapy had lower rates of major bleeding (1.42% vs 2.53%; OR 0.53; 95% CI 0.42-0.67; p < 0.001; I2 = 0%) and all-cause mortality (1.00% vs 1.42%; OR 0.71; 95% CI 0.53-0.95; p = 0.02; I2=0%) with similar major adverse cardiac events (MACE) (2.66% vs 3.11%; OR 0.86; 95% CI 0.71 - 1.03; p = 0.10; I2 = 0 %) compared to 12 months of DAPT. In conclusion, shorter course of DAPT for 1 to 3 months followed by P2Y12 inhibitor monotherapy reduces major bleeding and all course mortality without increasing major adverse cardiac events compared with traditional DAPT for 12 months.

Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease.

OBJECTIVES: This study investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx). BACKGROUND: Local hemodynamic forces such as WSS play an important role in atherogenesis through their effect on endothelial cells. The study hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD). METHODS: Forty-four patients with CAD underwent coronary angiography, fractional flow reserve, and endothelial function testing. Segments with >10% vasoconstriction after acetylcholine (Ach) infusion were defined as having severe EDFx. WSS, calculated using 3-dimensional angiography, velocity measurements, and computational fluid dynamics, was defined as low (<1 Pa), intermediate (1 to 2.5 Pa), or high (>2.5 Pa). RESULTS: Median age was 52 years, 73% were women. Mean fractional flow reserve was 0.94 ± 0.06. In 4,510 coronary segments, median WSS was 3.67 Pa. A total of 24% had severe EDFx. A higher proportion of segments with low WSS had severe EDFx (71%) compared with intermediate WSS (22%) or high WSS (23%) (p < 0.001). Segments with low WSS demonstrated greater vasoconstriction in response to Ach than did intermediate or high WSS segments (-10.7% vs. -2.5% vs. +1.3%, respectively; p < 0.001). In a multivariable logistic regression analysis, female sex (odds ratio [OR]: 2.44; p = 0.04), diabetes (OR: 5.01; p = 0.007), and low WSS (OR: 9.14; p < 0.001) were independent predictors of severe EDFx. CONCLUSIONS: In patients with nonobstructive CAD, segments with low WSS demonstrated more vasoconstriction in response to Ach than did intermediate or high WSS segments. Low WSS was independently associated with severe EDFx.

Catheter-Based Embolectomy for Acute Pulmonary Embolism: Devices, Technical Considerations, Risks, and Benefits.

A significant number of patients with high-risk pulmonary embolism have contraindications to thrombolytic therapy. Catheter-based therapy may be helpful and consists of a multitude of catheters and techniques, some old and some new. Although there are few data supporting the use of any of these techniques, there has been a recent rise in interest and use of catheter-based pulmonary embolectomy. This text describes the contemporary devices used in pulmonary embolism treatment, discusses their challenges, and proposes some future directions.

Safety of catheter-directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE). BACKGROUND: The use of CDT for the treatment of acute submassive and massive PE is increasing in frequency. However, its safety and efficacy have not been well elucidated. METHODS: This study is made of two parts: one is a two-center registry of acute PE patients treated with CDT. The safety outcome evaluated was any major complication including fatal, intracranial (ICH), intraocular, or retroperitoneal hemorrhage or any overt bleeding requiring transfusion or surgical repair. The efficacy outcome was acute change in invasive pulmonary artery systolic pressure (PASP). The second part is a meta-analysis of all contemporary studies that used CDT for PE. Reported outcomes are the same as in the registry, with the addition of right ventricular to left ventricular (RV/LV) ratio change. RESULTS: In the registry, 137 patients were included (age 59 ± 15, 50% male, 88% submassive PE). ICH occurred in two patients and major complications in 13 (9.4%). PASP decreased post procedure by 19 ± 15 mm Hg (95% CI 16-23). In the meta-analysis, 16 studies were included with 860 patients. Rate of ICH was 0.35% and the major complication rate was 4.65%, most requiring transfusion only. In-hospital mortality was 12.9% in the massive and 0.74% in the submassive group. All studies showed improvement in PASP and/or RV/LV ratio post CDT. CONCLUSIONS: CDT is associated with a low major complication rate. Randomized studies are needed to evaluate its efficacy relative to anticoagulation alone. © 2017 Wiley Periodicals, Inc.

Oscillatory wall shear stress is a dominant flow characteristic affecting lesion progression patterns and plaque vulnerability in patients with coronary artery disease.

Although experimental studies suggest that low and oscillatory wall shear stress (WSS) promotes plaque transformation to a more vulnerable phenotype, this relationship has not been examined in human atherosclerosis progression. Thus, the aim of this investigation was to examine the association between oscillatory WSS, in combination with WSS magnitude, and coronary atherosclerosis progression. We hypothesized that regions of low and oscillatory WSS will demonstrate progression towards more vulnerable lesions, while regions exposed to low and non-oscillatory WSS will exhibit progression towards more stable lesions. Patients (n = 20) with non-flow-limiting coronary artery disease (CAD) underwent baseline and six-month follow-up angiography, Doppler velocity and radiofrequency intravascular ultrasound (VH-IVUS) acquisition. Computational fluid dynamics models were constructed to compute time-averaged WSS magnitude and oscillatory WSS. Changes in VH-IVUS-defined total plaque and constituent areas were quantified in focal regions (i.e. sectors; n = 14 235) and compared across haemodynamic categories. Compared with sectors exposed to low WSS magnitude, high WSS sectors demonstrated regression of total plaque area (p < 0.001) and fibrous tissue (p < 0.001), and similar progression of necrotic core. Sectors subjected to low and oscillatory WSS exhibited total plaque area regression, while low and non-oscillatory WSS sectors demonstrated total plaque progression (p < 0.001). Furthermore, compared with low and non-oscillatory WSS areas, sectors exposed to low and oscillatory WSS demonstrated regression of fibrous (p < 0.001) and fibrofatty (p < 0.001) tissue and similar progression of necrotic core (p = 0.82) and dense calcium (p = 0.40). Herein, we demonstrate that, in patients with non-obstructive CAD, sectors subjected to low and oscillatory WSS demonstrated regression of total plaque, fibrous and fibrofatty tissue, and progression of necrotic core and dense calcium, which suggest a transformation to a more vulnerable phenotype.

Quantification of the focal progression of coronary atherosclerosis through automated co-registration of virtual histology-intravascular ultrasound imaging data.

The goal of this study was to evaluate the accuracy of a novel algorithm that circumferentially co-registers serial virtual histology-intravascular ultrasound (VH-IVUS) data for the focal assessment of coronary atherosclerosis progression. Thirty-three patients with an abnormal non-invasive cardiac stress test or stable angina underwent baseline and follow-up (6 or 12 months) invasive evaluation that included acquisition of VH-IVUS image data. Baseline and follow-up image pairs (n = 4194) were automatically co-registered in the circumferential direction via a multi-variate cross-correlation algorithm. Algorithm stability and accuracy were assessed by comparing results from multiple iterations of the algorithm (iteration 1 vs. iteration 2) and against values determined manually by two expert VH-IVUS readers (algorithm vs. two expert readers). Furthermore, focal plaque progression values were compared between the algorithm and expert readers following co-registration by the independently determined angles. Strong agreement in circumferential co-registration angles were observed across multiple iterations of the algorithm (stability) and between the algorithm and expert readers (accuracy; all concordance correlation coefficients >0.98). Furthermore, circumferential co-registration angles determined by the algorithm were not statistically when compared to values determined by two expert readers (p = 0. 99). Bland-Altman analysis indicated minimal bias when comparing focal VH-IVUS defined plaque progression in corresponding sectors following circumferential co-registration between the algorithm and expert readers. Finally, average differences in changes in total plaque and constituent areas between the algorithm and readers were within the average range of difference between readers (interobserver variability). We present a stable and validated algorithm to automatically circumferentially co-register serial VH-IVUS imaging data for the focal quantification of coronary atherosclerosis progression.

Comparison of angiographic and IVUS derived coronary geometric reconstructions for evaluation of the association of hemodynamics with coronary artery disease progression.

Wall shear stress (WSS) has been investigated as a prognostic marker for the prospective identification of rapidly progressing coronary artery disease (CAD) and atherosclerotic lesions likely to gain high-risk (vulnerable) characteristics. The goal of this study was to compare biplane angiographic vs. intravascular ultrasound (IVUS) derived reconstructed coronary geometries to evaluate agreement in geometry, computed WSS, and association of WSS and CAD progression. Baseline and 6-month follow-up angiographic and IVUS imaging data were collected in patients with non-obstructive CAD (n = 5). Three-dimensional (3D) reconstructions of the coronary arteries were generated with each technique, and patient-specific computational fluid dynamics models were constructed to compute baseline WSS values. Geometric comparisons were evaluated in arterial segments (n = 9), and hemodynamic data were evaluated in circumferential sections (n = 468). CAD progression was quantified from serial IVUS imaging data (n = 277), and included virtual-histology IVUS (VH-IVUS) derived changes in plaque composition. There was no significant difference in reconstructed coronary segment lengths and cross-sectional areas (CSA), however, IVUS derived geometries exhibited a significantly larger left main CSA than the angiographic reconstructions. Computed absolute time-averaged WSS (TAWSSABS) values were significantly greater in the IVUS derived geometries, however, evaluations of relative TAWSS (TAWSSREL) values revealed improved agreement and differences within defined zones of equivalence. Associations between VH-IVUS defined CAD progression and angiographic or IVUS derived WSS exhibited poor agreement when examining TAWSSABS data, but improved when evaluating the association with TAWSSREL data. We present data from a small cohort of patients highlighting strong agreement between angiographic and IVUS derived coronary geometries, however, limited agreement is observed between computed WSS values and associations of WSS with CAD progression.

Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double-Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease.

BACKGROUND: We hypothesized that nebivolol, a ß-blocker with nitric oxide-mediated activity, compared with atenolol, a ß-blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. METHODS AND RESULTS: In this pilot double-blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow-up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low-WSS segments in the nebivolol cohort (P=0.06). Low-WSS regions were associated with greater plaque progression (P<0.0001) and constrictive remodeling (P=0.04); conversely, high-WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling (P=0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin-capped fibroatheromas per vessel. Importantly, after adjusting for ß-blocker, low-WSS segments remained significantly associated with lumen loss and plaque progression. CONCLUSION: Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low-WSS segments in the nebivolol arm. Both ß-blockers had similar effects on oxidative stress, microvascular function, and endothelial function. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/. Unique identifier: NCT01230892.

Immediate post-traumatic pulmonary embolism is not associated with right ventricular dysfunction.

BACKGROUND: Post-traumatic pulmonary embolic events are associated with significant morbidity. Computed tomographic (CT) measurements can be predictive of right ventricular (RV) dysfunction after pulmonary embolus. However, it remains unclear whether these physiologic effects or clinical outcomes differ between early (<48 hours) vs late (≥48 hours) post-traumatic pulmonary embolism (PE). METHODS: All patients with traumatic injury and CT evidence of PE between 2008 and 2013 were identified. The study population was divided into 2 groups based on the time of diagnosis of the PE. The primary outcome was PE-related mortality. RESULTS: Fifty patients were identified (14 early PE and 36 late PE). Patients sustaining a late PE had a higher PE-related mortality rate (16.7% vs 0%), larger RV diameters, RV/left ventricular diameter ratios, RV volumes, and RV/left ventricular volume ratios (all P < .05). CONCLUSIONS: Early post-traumatic PE appears to be associated with fewer RV physiologic changes than late post-traumatic PE and may be representative of primary pulmonary thrombosis. It remains to be seen whether early CT findings of PE should be managed according to previously established guidelines for embolic disease.

Public Reporting in ST Segment Elevation Myocardial Infarction.

Public reporting provides transparency and improved quality of care. However, methods in estimating risk adjusted mortality in ST-segment myocardial infarction, particularly in cardiogenic shock and cardiac arrest are contentious. There are concerns that this has resulted in risk-averse behavior in publicly reporting states, resulting in suboptimal care in these patients.

Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker released from leukocytes and endothelial cells that has been associated with atherosclerotic cardiovascular disease. We hypothesized that plasma suPAR level is an independent predictor of coronary microvascular function. METHODS: Coronary blood flow velocity and plasma suPAR levels were evaluated in patients with non-obstructive coronary artery disease. Coronary flow reserve (CFR) was calculated as the ratio of hyperemic to basal average peak blood flow velocity and coronary microvascular dysfunction was defined as CFR ≤ 2.0 in the setting of a fractional flow reserve value of ≥0.75. Plasma suPAR levels were measured using ELISA technique. The association between suPAR and CFR was investigated using univariate and multivariate regression analyses. RESULTS: In 66 patients, 47% were men, 26% had diabetes, 68% had hypertension and 76% had dyslipidemia. Mean age was 55 ± 12 years and median suPAR level 2.82 (2.08-3.40) ng/mL. Plasma suPAR levels correlated with age (r = 0.31, p = 0.01), body mass index (r = 0.25, p = 0.04) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.33, p = 0.009). While median suPAR level was not significantly different in patients with different cardiovascular risk factors, patients on statin therapy had significantly higher suPAR level (p = 0.03). SuPAR correlated negatively with CFR and, after multivariate adjustment for established cardiovascular risk factors, medications profiles and hs-CRP, suPAR remained an independent predictor of CFR (B = -0.30, p = 0.04), indicating an independent association between suPAR level and coronary microvascular function. CONCLUSIONS: In this cross-sectional study, plasma suPAR level was an independent predictor of coronary microvascular function. Larger prospective clinical trials are warranted to investigate the prognostic value of this novel biomarker and the role of immune dysregulation in coronary microvascular disease.

Focal association between wall shear stress and clinical coronary artery disease progression.

Wall shear stress (WSS) has been investigated as a potential prospective marker to identify rapidly progressing coronary artery disease (CAD) and potential for lesions to acquire vulnerable characteristics. Previous investigations, however, are limited by a lack of understanding of the focal association between WSS and CAD progression (i.e., data are notably spatially averaged). Thus, the aim of this investigation was to examine the focal association between WSS and coronary atherosclerosis progression, and compare these results to those determined by spatial averaging. Five patients with CAD underwent baseline and 6-month follow-up angiographic and virtual histology-intravascular ultrasound imaging to quantify CAD progression. Patient-specific computational fluid dynamics models were constructed to compute baseline WSS values, which were either averaged around the entire artery circumference or examined in focal regions (sectors). Analysis of data within each sector (n = 3871) indicated that circumferentially averaged and sector WSS values were statistically different (p < 0.05) and exhibited poor agreement (concordance correlation coefficient = 0.69). Furthermore, differences were observed between the analysis techniques when examining the association of WSS and CAD progression. This investigation highlights the importance of examining spatially heterogeneous variables at a focal level to reduce the affect of data reduction and warrants implementation in a larger clinical study to determine the predictive power in prospectively identifying rapidly progressing and/or vulnerable coronary plaques.

Combination of plaque burden, wall shear stress, and plaque phenotype has incremental value for prediction of coronary atherosclerotic plaque progression and vulnerability.

AIMS: Large plaque burden, certain phenotypes, and low wall shear stress (WSS) are associated with adverse outcomes and high WSS with development of plaque vulnerability. We aimed to investigate the incremental value of the combination of plaque burden, WSS and plaque phenotype for prediction of coronary atherosclerotic plaque progression and vulnerability. METHODS: Twenty patients with CAD underwent baseline and 6-month follow-up coronary virtual histology-intravascular ultrasound (VH-IVUS) and computational fluid dynamics modeling for calculation of WSS. Low WSS was defined as <10 dynes/cm(2) and high WSS as ≥25 dynes/cm(2). Baseline plaque characteristics and WSS were related to plaque progression and vulnerability. RESULTS: In 2249 VH-IVUS frames analyzed, coronary segments with both plaque burden >40% and low WSS had significantly greater change in plaque area at follow-up (+0.68 ± 1.05 mm(2)), compared to segments with plaque burden >40% without low WSS (-0.28 ± 1.32 mm(2)) or segments with low WSS and plaque burden ≤40% (+0.05 ± 0.71 mm(2)) (p = 0.047). Among plaque phenotypes, pathologic intimal thickening (PIT) had the greatest increase in necrotic core (NC) area (p = 0.06) and greatest decrease in fibro-fatty (FF) area (p < 0.0001). At follow-up, compared to segments with either plaque burden >60%, PIT, or high WSS, those with a combination of plaque burden >60%, PIT, and high WSS developed greater increase in NC area (p = 0.002), greater decrease in FF (p = 0.004) and fibrous areas (p < 0.0001), and higher frequency of expansive remodeling (p = 0.019). CONCLUSION: Combination of plaque burden, WSS, and plaque phenotype has incremental value for prediction of coronary plaque progression and increased plaque vulnerability in patients with non-obstructive CAD.

Computational Fluid Dynamics Simulations of Hemodynamics in Plaque Erosion.

PURPOSE: We investigated whether local hemodynamics were associated with sites of plaque erosion and hypothesized that patients with plaque erosion have locally elevated WSS magnitude in regions where erosion has occurred. METHODS: We generated 3D, patient-specific models of coronary arteries from biplane angiographic images in 3 human patients with plaque erosion diagnosed by optical coherence tomography (OCT). Using computational fluid dynamics, we simulated pulsatile blood flow and calculated both wall shear stress (WSS) and oscillatory shear index (OSI). We also investigated anatomic features of plaque erosion sites by examining branching and local curvature in x-ray angiograms of barium-perfused autopsy hearts. RESULTS: Neither high nor low magnitudes of mean WSS were associated with sites of plaque erosion. OSI and local curvature were also not associated with erosion. Anatomically, 8 of 13 hearts had a nearby bifurcation upstream of the site of plaque erosion. CONCLUSIONS: This study provides preliminary evidence that neither hemodynamics nor anatomy are predictors of plaque erosion, based upon a very unique dataset. Our sample sizes are small, but this dataset suggests that high magnitudes of wall shear stress, one potential mechanism for inducing plaque erosion, are not necessary for erosion to occur.

Framework to co-register longitudinal virtual histology-intravascular ultrasound data in the circumferential direction.

Considerable efforts have been directed at identifying prognostic markers for rapidly progressing coronary atherosclerotic lesions that may advance into a high-risk (vulnerable) state. Intravascular ultrasound (IVUS) has become a valuable clinical tool to study the natural history of coronary artery disease (CAD). While prospectively IVUS studies have provided tremendous insight on CAD progression, and its association with independent markers (e.g., wall shear stress), they are limited by the inability to examine the focal association between spatially heterogeneous variables (in both circumferential and axial directions). Herein, we present a framework to automatically co-register longitudinal (in-time) virtual histology-intravascular ultrasound (VH-IVUS) imaging data in the circumferential direction (i.e., rotate follow-up image so circumferential basis coincides with corresponding baseline image). Multivariate normalized cross correlation was performed on paired images (n = 636) from five patients using three independent VH-IVUS defined parameters: artery thickness, VH-IVUS defined plaque constituents, and VH-IVUS perivascular imaging data. Results exhibited high correlation between co-registration rotation angles determined automatically versus manually by an expert reader ( r(2) = 0.90). Furthermore, no significant difference between automatic and manual co-registration angles was observed ( 91.31 ±1.04(°) and 91.07 ±1.04(°), respectively; p = 0.48) and Bland-Altman analysis yielded excellent agreement ( bias = 0.24(°), 95% CI +/- 16.33(°)). In conclusion, we have developed, verified, and validated an algorithm that automatically co-registers VH-IVUS imaging data that will allow for the focal examination of CAD progression.

Association of coronary wall shear stress with atherosclerotic plaque burden, composition, and distribution in patients with coronary artery disease.

BACKGROUND: Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition. METHODS AND RESULTS: Twenty-seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm(2) increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS). CONCLUSIONS: IN PATIENTS WITH CORONARY ARTERY DISEASE: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.).