A setup to characterize the tensile mechanical properties of poly(L-lactic acid) materials applied in bioresorbable polymer stents

A method for testing mechanical properties of miniature poly(L-lactic acid)(PLLA) specimens is instrumented and set up in this research. This method is specially designed to measure mechanical properties, including elasticity modulus, yield strength and breaking elongation, of miniature PLLA specimens in three different shapes at various tensile speeds and temperatures. Moreover, the measurement results are significantly dependent on the tensile speeds and temperatures. This phenomenon further verifies the obvious existence of the viscoelasticity of PLLA. Finally, it can be concluded that, with this method, mechanical properties of PLLA can be better investigated and understood, especially for PLLA used for biodegradable polymer stents.

Coronary Endothelium‐Dependent Vasomotor Function After Drug‐Eluting Stent and Bioresorbable Scaffold Implantation

Background Early generation drug‐eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium‐dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device‐related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable‐polymer everolimus‐eluting Xience (n=44), bioresorbable‐polymer sirolimus‐eluting Orsiro (n=35), polymer‐free biolimus‐eluting Biofreedom (n=24), bioactive endothelial‐progenitor cell‐capturing sirolimus‐eluting Combo DES (n=25), polymer‐based everolimus‐eluting Absorb (n=44), and Mg‐based sirolimus‐eluting Magmaris BRS (n=34) underwent endothelium‐dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow‐up. Crude vasomotor responses of distal segments to low‐dose acetylcholine (10 −6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (−8.4%±12.6%) and durable‐polymer DES had the most physiologic (−0.4%±11.8%; P =0.014). High‐dose acetylcholine (10 −4 mol/L) showed similar responses between groups (ranging from −10.8%±11.6% to −18.1%±15.4%; P =0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable‐polymer DES) to 2.5%±4.5% (bioactive DES; P =0.056). In multivariate models, endothelium‐dependent vasomotor response was associated with age, bioresorbable‐polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low‐dose and 68.9% with high‐dose acetylcholine, without differences between groups. Conclusions At follow‐up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Early and chronic phased local coagulative responses following bioresorbable-polymer drug-eluting stent implantation

Background Neointimal maturation after bioresorbable-polymer (BP) drug-eluting stent (DES) implantation will not be complete in the absorption phase of the polymer. We have previously reported local persistent hypercoagulation after sirolimus-eluting stent (SES) implantation by measuring local plasma prothrombin fragment 1+2 (F1+2) levels. The aim of this study is to examine time-dependent local coagulative response after BP-DES implantation. Methods Sixty-four patients who were treated about ten months earlier with coronary angioplasty, with no evidence of restenosis, were studied [durable-polymer (DP)-DES {SES; Cypher®: 26pts and everolimus-eluting stent (EES); Xience®: 16pts} and BP-DES (BP-EES; Synergy®: 10pts and BP-SES; Ultimaster®: 12pts)]. We measured plasma levels of F1+2 sampled in coronary sinus (CS) and sinus of Valsalva (V) at the early (2±1 months) and chronic (10±2 months) phases. The transcardiac gradient (Δ) was defined as CS level minus V level. Results No significant differences were observed in the percent diameter stenosis between the DP- and BP- DES groups (11.5±15.5 vs 14.1±11.9%). The ΔF1+2 was significantly lower in the BP-DES group than in the DP-DES group at the chronic phase (7.5±16.1 vs 16.4±17.1pmol/l, p<0.05). In the BP-DES group, the ΔF1+2 did not differ significantly between the early and chronic phases (7.0±14.1 vs 7.5±16.1pmol/l, NS). Conclusion Lower local coagulative response was observed at the chronic phase after BP-DES implantation compared to DP-DES implantation, and local hypercoagulation after BP-DES implantation was not observed at the early phase compared to the chronic phase. These findings might lead to the possibility of shorter dual antiplatelet therapy after BP-DES implantation. FUNDunding Acknowledgement Type of funding sources: None.

In-stent restenosis due to delayed healing of abluminal bioresorbable polymer everolimus-eluting stent: insight from histopathological evaluation with directional coronary atherectomy

Histopathological evaluation of the in-stent restenosis (ISR) sample in this case suggested that the ISR was potentially caused by a polymer residue of the bioresorbable polymer everolimus-eluting stent.

Safety and Effectiveness of the SVELTE Fixed-Wire and Rapid Exchange Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Systems for the Treatment of Atherosclerotic Lesions: Results of the OPTIMIZE Randomized Study

Background: The SVELTE fixed-wire and rapid exchange bioresorbable-polymer sirolimus-eluting coronary stent systems (SVELTE sirolimus-eluting stent [SES]) are novel, low-profile devices designed to facilitate direct stenting, transradial access, and enhance procedural efficiencies. Methods: Eligible subjects (N=1639) scheduled to undergo percutaneous coronary intervention for non–ST-segment–elevation myocardial infarction or stable coronary artery disease were randomly assigned (1:1) to treatment with either SVELTE SES or a control durable polymer everolimus-eluting coronary stent. The primary end point was 12-month target lesion failure and a noninferiority margin was specified as 3.58% with an expected event rate of 6.5%. Results: Target lesion failure was observed in 10.3% of SVELTE SES and 9.5% of control everolimus-eluting stent subjects under intention to treat analysis (difference=0.8%; P NI =0.034). Clinically indicated target lesion revascularization and stent thrombosis were observed in 1.5% versus 1.9% ( P =0.57) and 0.38% versus 0.51% ( P =0.72) of SVELTE SES versus control everolimus-eluting stent–treated subjects, respectively. Protocol-defined target vessel myocardial infarction (9.4% versus 8.2%) was higher than anticipated and more frequent at sites that utilized troponin versus creatine kinase myocardial band assays. Conclusion: The SVELTE SES did not meet the prespecified threshold for noninferiority. Unexpectedly, high rates of target vessel myocardial infarction in both treatment groups contributed to higher than expected rates of target lesion failure, effectively underpowering the study. No differences between the SVELTE SES and control everolimus-eluting stent were observed for primary clinical or angiographic end point events. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03190473.

Impact of Coronary Calcification on Clinical Outcomes After Implantation of Newer‐Generation Drug‐Eluting Stents

Background Percutaneous coronary intervention of calcified lesions was associated with worse outcomes in the era of bare‐metal and first‐generation drug‐eluting stents. Data on percutaneous coronary intervention of calcified lesions with newer‐generation drug‐eluting stents are scarce. Therefore, we investigated the impact of lesion calcification on clinical outcomes in patients undergoing percutaneous coronary intervention with a bioresorbable‐polymer sirolimus‐eluting stent or a durable‐polymer everolimus‐eluting stent. Methods and Results Patients (n=2361) from BIOFLOW II, IV, and V trials were categorized into moderate/severe versus none/mild lesion calcification by a core laboratory. End points were target‐lesion failure (TLF) (cardiac death, target‐vessel myocardial infarction, or target‐lesion revascularization) and probable/definite stent thrombosis at 2 years. The agreement in calcification assessment between the operator and the core laboratory was weak (weighted κ, 0.23). Patients with moderate/severe calcification (n=303; 16%) had higher TLF (13.5% versus 8.4%; P =0.003) and stent thrombosis rates (2.1% versus 0.2%; P <0.0001), whereas target‐lesion revascularization was not different between the groups (5.0% versus 3.9%; P =0.302). After adjustment, calcification did not emerge as an independent predictor of TLF (adjusted hazard ratio [aHR], 1.37; 95% CI, 0.89–2.08; P =0.148) but did for target‐vessel myocardial infarction (aHR, 1.66; 95% CI, 1.03–2.68; P =0.037). TLF rates were similar between bioresorbable‐polymer sirolimus‐eluting stent and durable‐polymer everolimus‐eluting stent (12.6% versus 15.4%, P =0.482) in moderate/severe calcification. In none/mild calcification, the bioresorbable‐polymer sirolimus‐eluting stent showed lower TLF (7.5% versus 10.3%, P =0.045). Conclusions With newer‐generation drug‐eluting stents, moderate/severe lesion calcification was not associated with more TLF after adjustment for the higher risk of patients with coronary calcification, whereas the rate of target‐vessel myocardial infarction was higher. The bioresorbable‐polymer sirolimus‐eluting stent and durable‐polymer everolimus‐eluting stent were equally effective and safe in calcified lesions. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT01356888, NCT01939249, NCT02389946.

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.