Sebastiaan de Winter

Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-l-Lactic Acid Coronary Stents Igaki-Tamai Stents

Background— The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. Methods and Results— Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. Conclusion— Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

Retrospective image-based gating of intracoronary ultrasound images for improved quantitative analysis: The intelligate method

Quantitative analysis of intracoronary ultrasound (ICUS) studies is performed on a series of tomographic cross‐sectional ICUS images acquired during a motorized 0.5 mm/sec catheter pullback. Catheter displacement in the vascular lumen during the cardiac cycle causes an anatomically shuffled ICUS study, which results in a sawtooth‐shaped appearance of the coronary segment in longitudinal reconstructed views in quantitative coronary ultrasound software packages. This hampers contour detection and leads to a laborious time‐consuming semiquantitative analysis process that may produce inaccurate results. To solve these problems, in the past, online ECG‐gated acquisition hardware has been applied. This article describes a novel image‐based gating method called Intelligate, which features automatic retrospective selection of end‐diastolic frames from videotaped or digitally stored ICUS studies. Our evaluation shows that there are no quantitative differences between analysis results of hardware ECG‐gated and Intelligated ICUS studies. Catheter Cardiovasc Interv 2004;61:84–94.

A novel approach for quantitative analysis of intracoronary optical coherence tomography: High inter-observer agreement with computer-assisted contour detection

Objective: This study aims to examine observer‐related variability of quantitative optical coherence tomography (OCT) derived measurements from both in vitro and in vivo pullback data. Background: Intravascular OCT is a new imaging modality using infrared light and offering 10 times higher image resolution (15 μm) compared to intravascular ultrasound. The quantitative analysis of in vivo intracoronary OCT imaging is complicated by the presence of blood, motion artifacts and the large quantity of information that has to be processed. Methods: We developed a standardized, automated quantification process for intracoronary OCT pullback data with inter‐observer variability assessed both in vitro by using postmortem human coronary arteries and in vivo by studying simple and complex coronary pathology and outcomes following stent implantation. The consensus between measurements by two observers was analyzed using the intraclass and interclass correlation coefficient and the reliability coefficients. Bland–Altman plots were generated to assess the relationship between variability and absolute measurements. Results: In vitro OCT assessment was performed in nine postmortem coronary arteries. The time needed for semiautomated contour detection of a 15‐mm long coronary segment was ∼40 min. The absolute and relative difference between lumen area measurements derived from two observers was low [0.02 ± 0.10 mm2; (0.3 ± 0.5)% respectively] with excellent correlation confirmed by linear regression analysis (R2 = 0.99; P < 0.001). Similarly, in vivo measurements demonstrated a high correlation with the main source of inter‐observer variation occurring as a result of coronary dissection and motion artifact. The absolute and relative difference between measurements were 0.11 ± 0.33 mm2 (1.57 ± 0.05)% for lumen area (R2 = 0.98; P < 0.001), 0.17 ± 0.68 mm2 (1.44 ± 0.08)% for stent area (R2 = 0.94; P < 0.001), and 0.26 ± 0.72 mm2 (14.08 ± 0.37)% for neointimal area (R2 = 0.78; P < 0.001). Conclusions: Highly accurate computer‐assisted quantitative analysis ofintracoronary OCT pullbacks is feasible with low inter‐observer variability. The presented approach allows for observer independent analysis of detailed vessel structures, and may be a valuable tool for future longitudinal studies incorporating OCT.

Reproducibility of coronary Fourier domain optical coherence tomography: quantitative analysis of in vivo stented coronary arteries using three different software packages.

AIMS Fourier domain optical coherence tomography (FD OCT) enables imaging of long coronary artery segments within few seconds, employing high data acquisitions, speed and fast automated catheter pullback. However, the reproducibility of these high-speed pullbacks in the clinical situation is unknown. We tested the reproducibility of in vivo, intracoronary FD OCT and assessed the influence of different computer-assisted algorithms on quantitative analysis. METHODS AND RESULTS In patients undergoing elective coronary stenting, two repeated FD OCT pullbacks (20 mm/sec), were acquired. Lumen area (LA) and stent area (SA) were measured at 1 mm longitudinal intervals (n=18 pullbacks, n=326 frames). Inter-study variability in terms of absolute difference of mean LA, mean SA and minimum LA was very low (-0.06±0.28 mm2, -0.05±0.29 mm2 and -0.11±0.33 mm2 in software 1) Sources of variability were incomplete visualisation of the vessel circumference, ambiguous luminal borders and drift of internal catheter calibration (Z-offset). Inter-software variability for LA and SA was low (R2=0.98 ~ 1.00, p<0.01, respectively). CONCLUSIONS FD OCT shows excellent reproducibility for consecutive pullbacks and represents a reliable tool for the in vivo assessment of stented coronaries. Computer-assisted quantitative analysis of FD OCT may be a valuable tool for future studies.

Fully Automatic Three-Dimensional Quantitative Analysis of Intracoronary Optical Coherence Tomography: Method and Validation

Objectives and background: Quantitative analysis of intracoronary optical coherence tomography (OCT) image data (QOCT) is currently performed by a time‐consuming manual contour tracing process in individual OCT images acquired during a pullback procedure (frame‐based method). To get an efficient quantitative analysis process, we developed a fully automatic three‐dimensional (3D) lumen contour detection method and evaluated the results against those derived by expert human observers. Methods: The method was developed using Matlab (The Mathworks, Natick, MA). It incorporates a graphical user interface for contour display and, in the selected cases where this might be necessary, editing. OCT image data of 20 randomly selected patients, acquired with a commercially available system (Lightlab imaging, Westford, MA), were pulled from our OCT database for validation. Results: A total of 4,137 OCT images were analyzed. There was no statistically significant difference in mean lumen areas between the two methods (5.03 ± 2.16 vs. 5.02 ± 2.21 mm2; P = 0.6, human vs. automated). Regression analysis showed a good correlation with an r value of 0.99. The method requires an average 2–5 sec calculation time per OCT image. In 3% of the detected contours an observer correction was necessary. Conclusion: Fully automatic lumen contour detection in OCT images is feasible with only a select few contours showing an artifact (3%) that can be easily corrected. This QOCT method may be a valuable tool for future coronary imaging studies incorporating OCT.

Quantitative multi-modality imaging analysis of a bioabsorbable poly-L-lactic acid stent design in the acute phase: a comparison between 2- and 3D-QCA, QCU and QMSCT-CA

AIMS To investigate if three-dimensional (3D) based quantitative techniques are comparable to each other and to explore possible differences with respect to the reference method of 2D-QCA in the acute phase and to study whether non-invasive MSCT could potentially be applied to quantify luminal dimensions of a stented coronary segment with a novel bioabsorable drug-eluting stent made of poly-l-lactic-acid (PLLA). METHODS AND RESULTS Quantitative imaging data derived from 16 patients enrolled at our institution in a first-in-man trial (ABSORB) receiving a biodegradable stent and who were imaged with standard coronary angiography and intravascular ultrasound were compared. Shortly, after stenting the patients also underwent a MSCT procedure. Standard 2D-QCA showed significant smaller stent lengths (p < 0.01). Although, the absolute measured stent diameters and areas by 2D-QCA tend to be smaller, the differences failed to be statistically different when compared to the 3D based quantitative modalities. Measurements made by non-invasive QMSCT-CA of implanted PLLA stents appeared to be comparable to the other 3D modalities without significant differences. CONCLUSIONS Three-dimensional based quantitative analyses showed similar results quantifying luminal dimensions as compared to 2D-QCA during an evaluation of a new bioabsorbable coronary stent design in the acute phase. Furthermore, in biodegradable stents made of PLLA, non-invasive QMSCT-CA can be used to quantify luminal dimensions.

Monitoring in vivo absorption of a drug-eluting bioabsorbable stent with intravascular ultrasound-derived parameters a feasibility study.

OBJECTIVES The aim of this study was to investigate the feasibility of using quantitative differential echogenicity to monitor the in vivo absorption process of a drug-eluting poly-l-lactic-acid (PLLA) bioabsorbable stent (BVS, Abbott Vascular, Santa Clara, California). BACKGROUND A new bioabsorbable, balloon-expanded coronary stent was recently evaluated in a first-in-man study. Little is known about the absorption process in vivo in diseased human coronary arteries. METHODS In the ABSORB (Clinical Evaluation of the BVS everolimus eluting stent system) study, 30 patients underwent treatment with the BVS coronary stent system and were examined with intracoronary ultrasound (ICUS) after implantation, at 6 months and at 2-year follow-up. Quantitative ICUS was used to measure dimensional changes, and automated ICUS-based tissue composition software (differential echogenicity) was used to quantify plaque compositional changes over time in the treated regions. RESULTS The BVS struts appeared as bright hyperechogenic structures and showed a continuous decrease of their echogenicity over time, most likely due to the polymer degradation process. In 12 patients in whom pre-implantation ICUS was available, at 2 years the percentage-hyperechogenic tissue was close to pre-implantation values, indicating that the absorption process was either completed or the remaining material was no longer differentially echogenic from surrounding tissues. CONCLUSIONS Quantitative differential echogenicity is a useful plaque compositional measurement tool. Furthermore, it seems to be valuable for monitoring the absorption process of bioabsorbable coronary stents made of semi-crystalline polymers.

Serial in vivo intravascular ultrasound-based echogenicity changes of everolimus-eluting bioresorbable vascular scaffold during the first 12 months after implantation insights from the ABSORB B trial.

OBJECTIVES This study sought to investigate quantitative and homogeneity differential echogenicity changes of the ABSORB scaffold (1.1) during the first year after implantation. BACKGROUND The imaging of the ABSORB bioresorbable vascular scaffold degradation by intravascular ultrasound (IVUS) has previously demonstrated diminishing gray-level intensity of the struts over time that can be evaluated by IVUS-based differential echogenicity. The first generation of ABSORB (1.0) showed a 50% reduction in hyperechogenicity at 6 months and restoration of the pre-ABSORB implantation values at 2 years. The second generation of ABSORB (1.1), investigated in the ABSORB B trial, was modified to prolong the duration of luminal scaffolding. METHODS A total of 63 patients were examined by IVUS immediately post-implantation and at 6-month (Cohort B1, n = 28) or 12-month (Cohort B2, n = 35) follow-up. IVUS-based tissue composition analysis software was used to quantify changes in hyperechogenicity over time in the scaffolded regions. Relative changes in hyperechogenicity were calculated as: 100 × (% hyperechogenicity at follow-up - % hyperechogenicity at baseline)/% hyperechogenicity at baseline. RESULTS At 6- and 12-month follow-up, there was a 15% (from 22.58 ± 9.77% to 17.42 ± 6.69%, p = 0.001) and 20% (from 23.51 ± 8.57% to 18.25 ± 7.19%, p < 0.001) reduction in hyperechogenicity, respectively, compared with post-implantation values. No difference in hyperechogenicity changes were observed between the proximal, medial, or distal part of the scaffolded segment. CONCLUSIONS Quantitative differential echogenicity changes of the ABSORB scaffold (1.1) during the first 12 months after implantation are lower compared with those previously observed with its first generation (1.0), confirming the value of the manufacturing changes and suggesting a slower degradation rate of the scaffold.

Long-Term (>10 Years) Clinical Outcomes of First-In-Man Biodegradable Poly-l-lactic Acid Coronary Stents: Igaki-Tamai Stents

Background— The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. Methods and Results— Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. Conclusion— Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

Coronary calcium significantly affects quantitative analysis of coronary ultrasound: importance for atherosclerosis progression/regression studies.

BackgroundCoronary atherosclerosis is a dynamic process, which progresses differently in coronary segments containing noncalcified or calcified plaques. This may have implications for the study of the effects of therapy on progression/regression. ObjectiveTo test this hypothesis, we performed a post-hoc analysis on data of a randomized trial in which perindopril treatment was compared with placebo on progression/regression of atherosclerosis with regard to the degree of calcification. Methods and ResultsThe intracoronary ultrasound data of 118 patients, who were enrolled in the multicentre, double-blinded randomized trial (PERSPECTIVE), were analysed. Vessel, lumen and plaque areas were measured in 711 5-mm-long matched coronary segments (perindopril 360, placebo 351). Each individual intracoronary ultrasound cross-section was binary labelled for the presence of calcium (yes/no), and the degree of calcium was assessed as a percentage of length. The segments were classified into three groups: 0–25, 25–50 and 50–100% (percentage of length) calcification. Coronary plaques with no or little calcium (0–25%) regressed on perindopril and did not change on placebo (−0.33±1.74 vs. −0.03±1.66, respectively; P = 0.04). Plaques containing moderate calcium (group 25–50%) did not change and plaques with severe amounts of calcification (group 50–100%) equally progressed. ConclusionNoncalcified plaques may be amenable to regression with ACE inhibitor treatment. The method, which considers the amount of calcium content in a plaque, may lead to new insights for quantitative analysis of the effects of therapy in progression/regression studies of atherosclerosis.