Augusto C. Lopes

Intravascular Ultrasound Guidance to Minimize the Use of Iodine Contrast in Percutaneous Coronary Intervention: The MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) Randomized Controlled Trial

Objective To evaluate the impact of IVUS guidance on the final volume of contrast agent utilized in patients undergoing PCI.

First-in-man randomised comparison of a novel sirolimus- eluting stent with abluminal biodegradable polymer and thin- strut cobalt-chromium alloy: INSPIRON-I trial

AIMS The INSPIRON-I trial is a first-in-man evaluation of the safety and efficacy of the Inspiron drug-eluting stent, a sirolimus-eluting stent with abluminal biodegradable polymer coating and thin cobalt-chromium alloy. METHODS AND RESULTS This is a randomised, multicentre comparison between Inspiron and a stent with the same metallic structure but without polymer coating or drug elution (Cronus). The primary objective was to evaluate the in-segment late loss (LLL) at six months. Secondary endpoints included percent in-stent obstruction as measured by intravascular ultrasound (IVUS) at six months and major adverse cardiac events (MACE). Fifty-eight patients were enrolled (60 lesions), 39 for Inspiron and 19 for Cronus. Baseline clinical and angiographic characteristics of both groups were similar. At six months, the in-segment LLL was reduced in the Inspiron group compared to the control group (0.19±0.16 mm vs. 0.58±0.4 mm, respectively; p<0.001), as well as the percent neointimal obstruction (7.8±7.1% vs. 26.5±11.4%; p<0.001). At two-year follow-up, incidence of MACE was similar between groups (7.9 vs. 21.1%, respectively; p=0.20), with lower target lesion revascularisation for Inspiron (0 vs. 21.1%, respectively; p=0.01) and no stent thrombosis. CONCLUSIONS Sirolimus eluted from an abluminal biodegradable polymer on a cobalt-chromium alloy proved effective in reducing restenosis at six months.

Constraining OCT with Knowledge of Device Design Enables High Accuracy Hemodynamic Assessment of Endovascular Implants

Background Stacking cross-sectional intravascular images permits three-dimensional rendering of endovascular implants, yet introduces between-frame uncertainties that limit characterization of device placement and the hemodynamic microenvironment. In a porcine coronary stent model, we demonstrate enhanced OCT reconstruction with preservation of between-frame features through fusion with angiography and a priori knowledge of stent design. Methods and Results Strut positions were extracted from sequential OCT frames. Reconstruction with standard interpolation generated discontinuous stent structures. By computationally constraining interpolation to known stent skeletons fitted to 3D ‘clouds’ of OCT-Angio-derived struts, implant anatomy was resolved, accurately rendering features from implant diameter and curvature (n = 1 vessels, r2 = 0.91, 0.90, respectively) to individual strut-wall configurations (average displacement error ~15 μm). This framework facilitated hemodynamic simulation (n = 1 vessel), showing the critical importance of accurate anatomic rendering in characterizing both quantitative and basic qualitative flow patterns. Discontinuities with standard approaches systematically introduced noise and bias, poorly capturing regional flow effects. In contrast, the enhanced method preserved multi-scale (local strut to regional stent) flow interactions, demonstrating the impact of regional contexts in defining the hemodynamic consequence of local deployment errors. Conclusion Fusion of planar angiography and knowledge of device design permits enhanced OCT image analysis of in situ tissue-device interactions. Given emerging interests in simulation-derived hemodynamic assessment as surrogate measures of biological risk, such fused modalities offer a new window into patient-specific implant environments.

Optimized computer-aided segmentation and 3D reconstruction using intracoronary optical coherence tomography

We present a novel and time-efficient method for intracoronary lumen detection, which produces three-dimensional (3-D) coronary arteries using optical coherence tomographic (OCT) images. OCT images are acquired for multiple patients and longitudinal cross-section (LOCS) images are reconstructed using different acquisition angles. The lumen contours for each LOCS image are extracted and translated to 2-D cross-sectional images. Using two angiographic projections, the centerline of the coronary vessel is reconstructed in 3-D, and the detected 2-D contours are transformed to 3-D and placed perpendicular to the centerline. To validate the proposed method, 613 manual annotations from medical experts were used as gold standard. The 2-D detected contours were compared with the annotated contours, and the 3-D reconstructed models produced using the detected contours were compared to the models produced by the annotated contours. Wall shear stress (WSS), as dominant hemodynamics factor, was calculated using computational fluid dynamics and 844 consecutive 2-mm segments of the 3-D models were extracted and compared with each other. High Pearsons correlation coefficients were obtained for the lumen area (r = 0.98) and local WSS (r = 0.97) measurements, while no significant bias with good limits of agreement was shown in the Bland–Altman analysis. The overlapping and nonoverlapping areas ratio between experts’ annotations and presented method was 0.92 and 0.14, respectively. The proposed computer-aided lumen extraction and 3-D vessel reconstruction method is fast, accurate, and likely to assist in a number of research and clinical applications.

Four-year clinical follow-up of the first-in-man randomized comparison of a novel sirolimus eluting stent with abluminal biodegradable polymer and ultra-thin strut cobalt-chromium alloy: the INSPIRON-I trial

BACKGROUND The Inspiron™ sirolimus-eluting stent (SES) is a low-dose, ultra-thin-strut cobalt-chromium stent abluminally coated with biodegradable polymers (BP). Previous results from the INSPIRON-I trial, a first-in-man study, have proven the efficacy of the novel stent in reducing neointimal proliferation. The present report aims at evaluating the long-term clinical outcomes of patients enrolled into the INSPIRON-I trial (Clinical Trials Gov. identifier: NCT01093391). METHODS A total of 57 patients (60 lesions) were randomly allocated in a 2:1 ratio to treatment with the Inspiron™ SES vs. its equivalent Cronus™ bare metal stent (BMS, both by Scitech Medical™, Aparecida de Goiânia, Goiás, Brazil), in four tertiary centers. The primary endpoint of the present analysis was the occurrence of major adverse cardiac events (MACE) [death, myocardial infarction (MI), target vessel revascularization (TVR) and/or target lesion revascularization (TLR)] at 4 years. RESULTS Baseline clinical and angiographic characteristics of both groups were similar. After 4 years, the primary endpoint occurred in 7.9% vs. 23.5% of patients in Inspiron and control groups respectively (P=0.11). The rate of death/MI was similar between the groups, but there was a significant decrease in the risk of repeat revascularization in the Inspiron group compared to the control arm TLR (0.0% vs. 23.5% respectively, P=0.02). There were no stent thromboses in the study population. CONCLUSIONS The novel Inspiron™ SES showed a sustained safe and effective clinical profile after 4-year of follow-up, with very low adverse events and null stent thrombosis (ST) occurrence.

A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

Background Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions. Objective to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions. Methods Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI. Results According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH. Conclusion Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

Intravascular Ultrasound Guidance to Minimize the Use of Iodine Contrast in Percutaneous Coronary Intervention

Objective To evaluate the impact of IVUS guidance on the final volume of contrast agent utilized in patients undergoing PCI.

Quantification of thrombus formation in malapposed coronary stents deployed in vitro through imaging analysis

Stent thrombosis is a major complication of coronary stent and scaffold intervention. While often unanticipated and lethal, its incidence is low making mechanistic examination difficult through clinical investigation alone. Thus, throughout the technological advancement of these devices, experimental models have been indispensable in furthering our understanding of device safety and efficacy. As we refine model systems to gain deeper insight into adverse events, it is equally important that we continue to refine our measurement methods. We used digital signal processing in an established flow loop model to investigate local flow effects due to geometric stent features and ultimately its relationship to thrombus formation. A new metric of clot distribution on each microCT slice termed normalized clot ratio was defined to quantify this distribution. Three under expanded coronary bare-metal stents were run in a flow loop model to induce clotting. Samples were then scanned in a MicroCT machine and digital signal processing methods applied to analyze geometric stent conformation and spatial clot formation. Results indicated that geometric stent features play a significant role in clotting patterns, specifically at a frequency of 0.6225 Hz corresponding to a geometric distance of 1.606 mm. The magnitude-squared coherence between geometric features and clot distribution was greater than 0.4 in all samples. In stents with poor wall apposition, ranging from 0.27 mm to 0.64 mm maximum malapposition (model of real-world heterogeneity), clots were found to have formed in between stent struts rather than directly adjacent to struts. This early work shows how the combination of tools in the areas of image processing and signal analysis can advance the resolution at which we are able to define thrombotic mechanisms in in vitro models, and ultimately, gain further insight into clinical performance.

Fully automated lumen segmentation of intracoronary optical coherence tomography images

Optical coherence tomography (OCT) provides high-resolution cross-sectional images of arterial luminal morphology. Traditionally lumen segmentation of OCT images is performed manually by expert observers; a laborious, time consuming effort, sensitive to inter-observer variability process. Although several automated methods have been developed, the majority cannot be applied in real time because of processing demands. To address these limitations we propose a new method for rapid image segmentation of arterial lumen borders using OCT images that involves the following steps: 1) OCT image acquisition using the raw OCT data, 2) reconstruction of longitudinal cross-section (LOCS) images from four different acquisition angles, 3) segmentation of the LOCS images and 4) lumen contour construction in each 2D cross-sectional image. The efficiency of the developed method was evaluated using 613 annotated images from 10 OCT pullbacks acquired from 10 patients at the time of coronary arterial interventions. High Pearson’s correlation coefficient was obtained when lumen areas detected by the method were compared to areas annotated by experts (r=0.98, R2=0.96); Bland-Altman analysis showed no significant bias with good limits of agreement. The proposed methodology permits reliable border detection especially in lumen areas having artifacts and is faster than traditional techniques making it capable of being used in real time applications. The method is likely to assist in a number of research and clinical applications - further testing in an expanded clinical arena will more fully define the limits and potential of this approach.

In vivo deformation of stented coronary vessel centerline with cardiac motion: Implications for angiography-OCT fusion

This study aims to quantify in vivo deformation of stented coronary vessel centerlines due to cardiac motion to understand the potential errors in fusing optical coherence tomography (OCT) with angiography. We first evaluated the static error and test the reproducibility of a vessel centerline reconstruction method derived from the stereoscopic theory in vitro and in vivo. Two phantom models mimicking coronary artery bifurcations were used for in vitro static conditions, and four coronary arteries (2.75 mm ± 0.14 mm) of two Yorkshire swine implanted with 3.0 mm × 17 mm bare metal stents were used for in vivo dynamic conditions. Our method depicted a strong linear correlation (R2 = 0.91) between the reconstructed geometry and the actual geometry with the error of 2.3 mm ± 1.8 mm across various angles between paired images (50°-130°) in vitro. This method also showed higher accuracy in the stented segments length and curvature compared to currently available methods (the root mean square error = 0.76 pixel vs. 1.3 pixel), and good reproducibility across various angles (50°-130°) and in two different cardiac cycles in vivo. The reconstructed vessel centerlines did not deform significantly over a cardiac cycle in vivo (error of length = 0.17 mm ± 0.16 mm, maximum curvature = 0.13 ± 0.09 with error = 0.07 ± 0.06 in the stented segment; four different cardiac phases, 6 ± 2 time-points). Despite small sample size, the results may support using the vessel centerline as a fusion path for non-ECG-gated intravascular images, such as OCT images, because cardiac motions introduce only a small error in the vessel centerline reconstruction.