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Introduction: Risk-stratification of individual coronary plaques is an important goal to detect high-risk plaques likely to progress/destabilize, which could inform preemptive intervention to prevent adverse cardiac events. IVUS imaging, the current gold standard to assess plaque risk, has shown that biomechanical variables, particularly local ESS, contributes critical synergistic prognostic insight when combined with anatomic high-risk plaque features. Non-invasive risk assessment of coronary plaques with CCTA would be invaluable to enable broad population risk screening, but it is unknown whether CCTA, which has less spatial resolution than IVUS, can adequately measure the critical local biomechanical and anatomic variables. Aim: To compare the accuracy of ESS computation of local ESS metrics by non-invasive CCTA vs invasive IVUS imaging. Methods: We analyzed 30 arteries (22 LAD, 4 LCx,4 RCA) from 30 patients selected from a registry of patients who underwent both IVUS and CCTA of the same artery for suspected CAD. CCTA images were acquired using a CCTA with either 64 or 256 detector rows. We segmented lumen, vessel, and plaque areas with both IVUS (manual segmentation) and CCTA (AI based software; Cleerly Inc, NY). Co-registration of IVUS and CCTA Images was performed using fiduciary anatomic landmarks. Images from IVUS and CCTA were used to generate a 3-D arterial reconstruction, and local ESS distribution was assessed by computational fluid dynamics and reported in consecutive 3-mm segments. Results: Table Conclusion: Compared to IVUS values, 256-slice is more accurate than 64-slice CCTA to measure lumen and vessel areas, but computation of detailed local ESS (average, low and high) is similar by both CCTA methods. Local ESS evaluation using non-invasive CCTA is feasible and comparable to invasive gold standard IVUS and is suitable to characterize the local flow patterns that play an important role in plaque development, progression, and destabilization

Introduction: The role of endothelial shear stress (ESS) in the development of coronary plaque erosion is unknown. High ESS gradient (ESSG) has been hypothesized to promote plaque erosion, but no studies have included matched control stable plaques with the same minimal and reference lumen area (MLA, RLA, respectively). No studies examined the location of plaque erosion (proximal vs distal to MLA of the culprit plaque) related to the max magnitude of upslope vs downslope of the lumen obstruction. Aims: (1) to compare ESSG between plaques with erosion and similar control plaques that remained stable; (2) among erosion plaques, to study the effect of max slope steepness (Δ lumen area/frame) up- and down-stream from the culprit plaque MLA on thrombus location. Methods: We studied 46 patients from TOTAL and COMPLETE trials who underwent angiography and OCT imaging: 46 arteries: 27 LAD, 6 LCX, 13 RCA. Plaques were divided into Plaque Erosion (n=24) with OCT features of erosion before PCI (17 definite, 7 probable erosion) and matched coronary plaques from separate control patients (n=22) without plaque disruption. Orthogonal angiographic views were used to generate a 3-D arterial reconstruction, and angio centerline was combined with OCT centerline. Local ESS distribution was assessed by computational fluid dynamics and reported in consecutive 3-mm segments. Among the plaque erosions, we calculated the up- and down-slope (Δ lumen area/frame) of lumen obstruction for each culprit plaque. Results: See Table Conclusion: In plaques with similarly severe obstruction, plaque erosion is associated with higher max ESS and max ESSG vs plaques that remain stable. Proximal plaque erosion/thrombus is associated with steeper plaque upslope vs downslope, and distal plaque erosion/thrombus is associated with steeper plaque downslope vs upslope. Absolute ESSG is higher in downslope vs upslope erosions. These features may help prognosticate individual plaques at risk for future erosion.

Introduction: Low ESS, a pro-inflammatory stimulus, is an important predictor of coronary plaque development/progression. Whether low ESS adds incremental predictive value for future major adverse cardiac events (MACE) in untreated coronary lesions in high-risk patients with an acute coronary syndrome (ACS) is unknown. Methods: In the PROSPECT study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of non-culprit (nc) lesion MACE from untreated coronary lesions in 3 year followup (f/u) were large plaque burden (PB), small minimum lumen area (MLA), and thin cap fibroatheroma (TCFA) morphology. In the present analysis, all nc-lesions leading to a new MACE in f/u (nc-MACE lesions, n=50) and ~4-fold randomly selected control nc-lesions without f/u MACE (nc-non-MACE lesions) were analyzed. Baseline ESS for each lesion was calculated using computational fluid dynamics. A propensity score for low ESS was determined accounting for PB, MLA, TCFA, artery and location in the artery. Local ESS (lowest ESS in 90 o arc around the artery) was then examined for incremental association with MACE. Results: Imaging was sufficient for analysis in 32 nc-MACE lesions. Two nc-MACE lesions were excluded due to unreliable lesion morphology. Non-fibroatheromas were too few for analysis and excluded. Final dataset included 145 lesions: 13 nc-MACE TCFA, 10 nc-MACE thick cap fibroatheroma (ThCFA), and 122 non-nc-MACE lesions (63 TCFA, 59 ThCFA). Cumulative frequency distribution shows lesions responsible for future nc-MACE frequently exhibited low ESS (Figure). In a propensity-adjusted multivariable model, low ESS was strongly associated with nc-MACE in f/u (odds ratio 0.16 [95% CI 0.06-0.40], p Conclusions: After accounting for large PB, small MLA, TCFA, and lesion location, low local ESS adds significant and substantial incremental predictive value to identify high-risk untreated lesions likely to cause MACE during 3 year followup.

Background: The natural history and the role of the atherosclerotic plaque located behind the stent (PBS) are still poorly understood. We evaluated the serial changes in PBS following bare-metal (BMS) compared with first-generation drug-eluting stent (DES) implantation and the impact of these changes on in-stent neointimal hyperplasia (NIH). Methods: 3D coronary reconstruction by angiography and intravascular ultrasound were serially performed after intervention and at 6- to 10-month follow-up in 157 Japanese patients treated with BMS (n=90) and DES (n=98; 68 sirolimus-eluting and 30 paclitaxel-eluting stents) included in the PREDICTION Study. Each reconstructed stented coronary artery was divided into consecutive 1.5-mm segments. External elastic lamina, lumen, stent, and PBS area were measured for each segment at both baseline and follow-up. At follow-up NIH area was assessed. Due to the very low rate of events in our population we used significant NIH (defined as NIH area >50% of stent area) as a binary anatomic outcome. Results: Patient, lesion, and stent characteristics were comparable between BMS and DES. There was a significant decrease in PBS area after BMS (median relative change: -7.2%, IQR -19.3 to 5.2%, p Conclusions: The PBS significantly decreased 6 to 10 months after BMS implantation, whereas after DES it increased. The decrease in PBS area was significantly associated with the development of NIH at follow-up in both stent types. These findings raise the possibility of a communication between the lesion within the stent and the underlying native atherosclerotic plaque, and may have important implications regarding the pathobiology of in-stent restenosis.

Background : ECG parameters such as low heart rate variability (HRV) identify patients at high risk post-ACS. We recently developed morphological variability (MV), a novel technique that quantifies differences in the morphology of entire beats using a dynamic time-warping algorithm. MV incorporates strictly more information than HRV, potentially offering a more complete evaluation of the ECG. We assessed the relationship among MV, HRV, and outcomes after NSTEACS. Methods: MV and HRV were calculated in 863 pts from the DISPERSE2 trial using the first 24 hrs of continuous ECG (CECG) after randomization for NSTEACS. Using each measure, pts were split into high and low variability groups (cutpoint for HRV (SDNN)= 75ms and for MV=0.7). Ischemia on CECG was defined as ≥1mm ST dep lasting ≥1min. Results: A total of 144 (16.7%) pts had high MV and 58 (6.7%) had low HRV. Pts with high MV experienced higher rates of death, death/MI/severe recurrent ischemia (SRI), and ischemia detected on CECG compared to low MV. (Table-Figure ) This relationship remained consistent in pts with no ischemia on CECG (hazard ratio for D/MI/SRI =2.5, p=0.016). There was no difference in mortality or ischemia on CECG in pts with low HRV v high HRV, but pts with low HRV did have higher rates of death/MI/SRI. (Table) Conclusions: MV correlates significantly with poor cardiovascular outcomes, including death, after NSTEACS, even after controlling for other high risk features and even among pts without electrocardiographic evidence of ischemia. MV may offer a new non-invasive measure for risk stratification after ACS.

Objectives: We investigated the role of V alone or in combination with S on the histomorphologic characteristics of thin cap fibroatheromas (TCFAs), and tested the hypothesis that V or VS attenuate the proinflammatory effect of low endothelial shear stress (ESS). We used vascular profiling of swine coronary arteries for in vivo assessment of ESS to prospectively identify these low ESS areas that are prone to develop TCFAs. Methods: 12 diabetic hyperlipidemic swine were allocated into 3 treatment groups: placebo (P, n=4), V (n=4) and VS (n=4). Blood pressure, serum cholesterol and glucose were similar between the treatment groups. IVUS-based geometrically correct 3D reconstruction of the coronary arteries was performed at baseline (wk 23) and follow up (wk 30). Baseline ESS was calculated using computational fluid dynamics and plaque-free subsegments of interest were identified (n=109). Coronary arteries (n=31) were harvested at follow up, cryosectioned at the subsegments of interest and stained histologically. Intima/media ratio and inflammation (CD45) were quantified. Lesions were classified into atheromas without evidence of fibrous cap (n=82) and TCFAs (n=60). Results: V alone or in combination with S reduced the amount of plaque inflammation, particularly in TCFAs (Fig A ). V and VS attenuated the proinflammatory effect of local low ESS compared to P (Fig B ). Conclusion: V alone or in combination with S exerts a stabilizing effect of reducing plaque inflammation, even in high-risk regions with low ESS. These results suggest a mechanism of regional atheroprotection associated with V or VS.

Improvements in solid-state digital technology have enhanced transtelephonic transmission of electrocardiography (ECG) data and increased the accuracy of software-based analysis systems. These advances, in addition to better signal quality and greater computer arrhythmia interpretation capabilities, have opened new potential uses for ambulatory electrocardiography (AECG). Traditional uses of AECG for arrhythmia detection have expanded as the result of increased use of multichannel and telemetered signals. The clinical application of arrhythmia monitoring to assess drug and device efficacy has been further defined by new studies. The analysis of transient ST-segment deviation remains controversial, but considerably more data are now available, especially about the prognostic value of detecting asymptomatic ischemia. Heart rate variability (HRV) analysis has shown promise for predicting mortality rates in cardiac patients at high risk. Despite these advances, a true automated analysis system has not been perfected and technician/physician participation is still essential. The widespread availability and low cost of personal computers and workstations has allowed for the development of extremely sophisticated and automated signal processing algorithms. Current AECG equipment provides for the detection and analysis of arrhythmias and ST-segment deviation as well as more sophisticated analyses of R-R intervals, QRS-T morphology including late potentials, Q-T dispersion, and T-wave alternans. There are 2 categories of AECG recorders: continuous recorders, typically used for 24 to 48 hours to investigate symptoms and ECG events that are likely to occur within that time frame, and intermittent recorders, which may be used for long periods of time (weeks to months) to provide briefer, intermittent recordings for investigating events that occur infrequently. ### A. Continuous Recorders Rapidly evolving technologies now allow for direct recording of the ECG signal in a digital format using solid-state recording devices. The direct digital recording avoids all of the biases introduced by the mechanical features of tape recording devices and the problems associated with …