Sarah Geva

Novel fully bioabsorbable salicylate-based sirolimus- eluting stent

AIMS The concept of fully biodegradable stents has emerged as an attractive alternative to current permanent metallic stents, mainly as a potential solution to avoid late stent thrombotic events. We sought to evaluate a novel, fully bioabsorbable sirolimus-eluting stent (SES) synthesised entirely from a unique salicylic-acid polymer, in a clinically relevant animal model. METHODS AND RESULTS Fully biodegradable balloon-expandable stents (n=45) were implanted in a porcine coronary arteries using quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) to optimise stent apposition. Dose density of sirolimus was 8.3 µg/mm of stent length with in vitro studies demonstrating elution over 30 days and complete stent degradation over 12 months. Animals were terminated at 7, 14, 30, 90, and 180 days for complete histological analysis. Optical coherence tomography (OCT) was also performed for the 90- and 180-days samples. All stents were deployed successfully without notable mechanical difficulties. Angiographic diameter stenosis (DS) was 20±16%, 24±4%, and 23±17%, at one, three, and six months, respectively. In parallel, IVUS showed good stent apposition with DS of 21±9%, 25±7%, and 18±3%; and area stenosis (AS) of 35±13%, 33±7%, and 32±4% at one, three, and six months,respectively. OCT further demonstrated good stent apposition with DS of 28±7% and 20±6%, and AS of 37±10% and 33±13% at three and six months, respectively. OCT showed reduction of stent thickness by 23% from three to six months. Histologic analysis confirmed these in vivo findings and revealed a favourable healing process of absorbable stent incorporation into the arterial wall, without excessive thrombotic or inflammatory reactions. CONCLUSIONS This study shows favourable vascular compatibility and efficacy for a novel fully bioabsorbable salicylate-based SES. This device has good mechanical performance during deployment and stays well-apposed to the vessel wall at long-term follow-up. These initial results are highly encouraging and support progress into more extensive preclinical studies as well as early clinical testing.

A third generation ultra-thin strut cobalt chromium stent: histopathological evaluation in porcine coronary arteries

AIMS The present study was designed to evaluate a novel third generation bare-metal stent (BMS) comprised of an ultra-thin-strut, cobalt-chromium platform with fixed geometry, uniform cell size, and superior surface finish in a porcine coronary artery model. METHODS AND RESULTS A total of 47 BMS of two types were implanted in pig coronary arteries using QCA to optimise stent apposition: a commercially available cobalt alloy thin-strut stent (91 microm) as control (Driver; n=17), and an ultra-thin-strut (65 microm) cobalt-chromium stent (Protea; n=18). Animals underwent angiographic restudy and termination one week and one month post-implant for coronary artery histology. In addition, 12 overlapping Protea stents were analysed at one month. At one week, comparable thin neointima and mild inflammation were observed in both groups. At one month, Protea demonstrated significantly lower angiographic % stenosis (2+/-1% vs. 17+/-5%, p=0.006), intimal thickness (0.11+/-0.01 mm vs. 0.23+/-0.03 mm, p=0.003), and histologic % area stenosis (19+/-2% vs. 32+/-3%, p=0.003). Mean stent strut injury scores were low and similar between groups. Angiographic % stenosis, intimal thickness, and histologic % area stenosis of overlapping Protea stents were 3+/-1%, 0.13+/-0.01 mm, and 22+/-2%, respectively, and similar to the single Protea group. Stable fibrocellular neointimal incorporation, with complete endothelialisation and minimal inflammation, were observed at one month in all stents, including overlapped Protea segments. CONCLUSIONS When compared to a commercially available cobalt alloy BMS, the new third generation Protea stent demonstrated favourable coronary arterial response with significant reduction of neointimal formation in the porcine model. Our results showed how seemingly trivial improvements to the BMS technology can result in substantial biological responses. Future, long-term investigations are needed to ascertain the clinical applicability and implications of these findings.

High Incidence of Intramural Thrombus After Overlapping Paclitaxel-Eluting Stent Implantation Angioscopic and Histopathologic Analysis in Porcine Coronary Arteries

Background—Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results—Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P=0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P=0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P=0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P=0.34). Conclusions—In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity.Background— Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results— Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P =0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS ( P <0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P =0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P =0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P =0.34). Conclusions— In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity. Received January 30, 2008; accepted April 24, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

High Incidence of Intramural Thrombus After Overlapping Paclitaxel-Eluting Stent ImplantationCLINICAL PERSPECTIVE

Background—Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results—Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P=0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P=0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P=0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P=0.34). Conclusions—In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity.Background— Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results— Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P =0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS ( P <0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P =0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P =0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P =0.34). Conclusions— In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity. Received January 30, 2008; accepted April 24, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

STENT DEGRADATION OF NOVEL FULLY BIOABSORBABLE SALICYLATE-BASED SIROLIMUS-ELUTING STENT EVALUATED BY OCT IN PIG CORONARY ARTERY

Results: Average strut thickness and area at 1M was similar to post implantation (implant: 0.25mm, 0.14mm2, 1M: 0.26mm, 0.12mm2). Strut Thickness and area gradually decreased over time (3M: 0.23mm and 0.09mm2; 6M: 0.186mm and 0.07mm2, 9M: 0.179mm and 0.066mm2, 12M: 0.158mm and 0.055mm2, respectively, P<0.0001) On the other hands, once OCT signal intensity gradually become lower from 1M to 3M (1M: 6.06W, 3M; 5.92W, P<0.001), then gradually become higher from 3M to 6 M and again (6M: 6.16W, P<0.001). But there are no significantly difference between 6M, 9M and 12M (P=0.51, P=0.31)

COMPARISON OF VASCULAR INFLAMMATION AND ENDOTHELIAL FUNCTION IN RESPONSE TO A NEW NOBORI AND CYPHER DRUG ELUTING STENTS IN PIG CORONARY ARTERIES

Background: Nobori is a 3rd generation Drug Eluting Stent (DES), designed to include drug eluting biodegradable polymer coated only abluminal side of the stent. The new features may differently impact inflammation and endothelium functions as compared to the currently marketed DES. At the present time, preclinical data on direct comparison of these DESs are not available. In this study, we examined vascular inflammation and endothelial function of the segments adjacent to the stent and histology of stented areas of Nobori and Cypher DES.

High Incidence of Intramural Thrombus After Overlapping Paclitaxel-Eluting Stent ImplantationCLINICAL PERSPECTIVE: Angioscopic and Histopathologic Analysis in Porcine Coronary Arteries

Background—Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results—Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P=0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P=0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P=0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P=0.34). Conclusions—In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity.Background— Systematic analysis of in vivo angioscopy and postmortem histopathology for paclitaxel-eluting stents (PES) has not been previously reported. We assessed 1-month angioscopic and histopathologic sequelae of overlapping PES in pig coronary arteries. Methods and Results— Overlapping PES and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS (0.46±0.63 mm versus 1.30±0.50 mm; P =0.01). Angioscopically, PES stent struts were clearly visible and accompanied by substantial red material indicating mural thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS ( P <0.001 versus PES). Macroscopically, mural thrombi were abundant but distributed irregularly throughout the PES, with greater concentration in overlapping segments. Only occasional mural thrombi were noted for BMS. Microscopically, neointima of BMS was fibrocellular and mature, whereas only a thin layer of immature neointima was seen in PES. Neointimal thickness was less in PES than BMS (0.11±0.07 mm versus 0.33±0.12 mm; P =0.018). Additionally, extensive para-strut and intramural thrombi, red blood cell debris, and minute luminal thrombi were observed in PES. Despite normal angioscopic appearance of both proximal and distal nonstented reference segments, endothelium-dependent relaxation to substance P was notably diminished (PES, 0±7% versus BMS, 10±6%; P =0.007), whereas nitroglycerin response was preserved (PES, 9±5% versus BMS, 12±7%; P =0.34). Conclusions— In the porcine coronary model, overlapping PES is associated with marked intramural thrombi, which was accurately detected on angioscopy at 1 month. Moreover, despite normal luminal angioscopic appearance, adjacent nonstented reference segments demonstrated impaired endothelium-dependent vasoreactivity. Received January 30, 2008; accepted April 24, 2008. # CLINICAL PERSPECTIVE {#article-title-2}