In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris — DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial

doi:10.1016/j.ijcard.2017.12.053

International Journal of Cardiology

Volume 255, 15 March 2018, Pages 22-28

https://doi.org/10.1016/j.ijcard.2017.12.053 Get rights and content

Highlights

•
The drug-eluting absorbable metal scaffold DREAMS 2G showed a continuous favourable safety profile and stable performance outcomes up to 12 months.
•
We assessed baseline, 6- and 12-month imaging data of DREAMS 2G in the context of the international, first-in-man BIOSOLVE-II trial.
•
Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound derived radiofrequency data analysis and echogenicity were evaluated.
•
Optical coherence tomography attenuation and backscattering analysis were also performed.
•
Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed up to 12 months; importantly, these changes occurred with preservation of the lumen size.

Abstract

Rationale

Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall.

Objectives

We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G).

Methods and results

The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7 mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed.

There was hardly any difference in curvature between pre-procedure and 12 months (− 0.0019; p = 0.48). The change in angulation from pre- to 12 months was negligible (− 3.58°; 95% CI [− 5.97, − 1.20]), but statistically significant. At 6 months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of − 0.489; p = 0.055) and with fibrous volume a positive relationship (estimate of 0.53, p = 0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6 months (Δ 6 months vs. post-proc. is − 13.5 [95% CI − 14.6, − 12.4]) and at 12 months (Δ 12 months vs. post-proc. is − 14.0 [95% CI − 15.4, − 12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6 months and at 12 months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6 months; thereafter, they remained unchanged.

Conclusion

Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12 months; importantly, these changes occurred with preservation of the lumen size between 6 and 12 months.

NCT01960504

Introduction

Bioresorbable scaffolds (BRS) are newly approved devices in Europe for treating stable patients with obstructive coronary lesions. Since these devices are fully resorbable, they might overcome some of the problems related to the everlasting presence of metallic stents in coronary arteries. While it is expected that BRS may confer clinical benefit in long-term studies, early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall [1].

The BIOSOLVE-II study assessed a newly redesigned second-generation drug-eluting absorbable metal scaffold (Magmaris — DREAMS 2G). The magnesium backbone of DREAMS 2G has been improved and it has a drug-polymer combination composed of sirolimus/poly-l-lactide (Biotronik AG, Buelach, Switzerland) [2], [3]. The clinical reports showed a continuous favorable safety profile and stable performance outcomes up to 12 months [4]; however, the mechanistic explanation of these optimal results is uncertain.

We therefore assessed, the baseline, 6-month and 12-month imaging performance of DREAMS 2G with regard to the serial geometrical changes in angiographic curvature, angulation and vasomotion, as well as to the temporal changes in bioresorption process as assessed by optical coherence tomography (OCT) attenuation and backscattering analyses, and intravascular ultrasound (IVUS) derived-radiofrequency (RF) data analysis and -echogenicity.

Section snippets

Study design and population

BIOSOLVE-II is a prospective, multi-center, first-in-man study which evaluates the safety and performance of DREAMS 2G (drug-eluting absorbable metal scaffold system — Biotronik AG, Buelach, Switzerland) in 123 patients (Fig. 1 supplement online). Key inclusion criteria: patients with stable or unstable angina or documented silent ischemia, a maximum of 2 single de novo lesions (length of ≤ 21 mm) in 2 separate coronary arteries (with a reference vessel diameter between 2.2 and 3.7 mm). Exclusion

Results

Between October 2013 and May 2015, 123 subjects were enrolled. Baseline parameters are listed in Table 1 supplement online. In 2 lesions, DREAMS 2G could not be implanted due to insufficient pre-dilatation; follow-up of these 2 subjects was consequently not included in this analysis. Most patients were male and had stable angina (71.5%) at baseline. At 12-months follow-up, 100 (86.2%) patients were symptom-free. Detailed 12-month clinical follow-up has been previously reported [4].

Discussion

The main findings of our study are: 1) restoration of the vessel geometry was observed between baseline and 6 and 12 months; 2) vasomotion signs were observed at follow-up and there was a relationship with underlying IVUS-derived radiofrequency data plaque composition; 3) many objective signs of bioresorption were documented by means of optical coherence tomography derived attenuation and backscattered measurements and with the use of serial assessments of IVUS-derived radiofrequency data and

Conclusion

Serial imaging of DREAMS 2G was associated with restoration of the anatomy of the treated segment and significant bioresorption of the scaffold by 6 and 12 months after its implantation in diseased human coronary arteries. This enables the vessel to react to vasoactive agents in relation with composition of the underlying vessel wall without the interference of the device since it has been bioreabsorbed. The coronary lumen is being preserved from 6 to 12 months, which speaks to the halting of the

Funding

This work was supported by Biotronik (https://clinicaltrials.gov/ct2/show/NCT01960504) AG, Buelach, Switzerland.

Conflict of interest

H.M.G, K.K., A.H., P.A.L., A.A., J.E. and J.D. declare no conflict of interest.

M.H. reports study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac Dimensions, Medtronic, Volcano, and Lilly.

R.T. reports personal fees from Biotronik and Abbott Vascular.

C.v.B. has been an unpaid consultant to Biotronik and other device-manufacturing companies and reports institutional research grants from Biotronik, Medtronic, Boston Scientific, and AstraZeneca.

W.W. reports grants from Abbott

Acknowledgement

Sameer Desale performed the statistical analysis for this report.

References (11)

H.M. Garcia-Garcia et al.
Assessing bioresorbable coronary devices: methods and parameters
JACC Cardiovasc. imaging
(Nov 2014)
M. Haude et al.
Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial
Lancet
(Mar 9 2013)
T. Yonetsu et al.
Comparison of incidence and time course of neoatherosclerosis between bare metal stents and drug-eluting stents using optical coherence tomography
Am. J. Cardiol.
(Oct 1 2012)
J.J. Wentzel et al.
Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress distribution
J. Biomech.
(Oct 2000)
J. Gomez-Lara et al.
Angiographic geometric changes of the lumen arterial wall after bioresorbable vascular scaffolds and metallic platform stents at 1-year follow-up
JACC Cardiovasc. Interv.
(Jul 1 2011)

There are more references available in the full text version of this article.

Cited by (59)

Optimal lesion preparation before implantation of a Magmaris bioresorbable scaffold in patients with coronary artery stenosis: Rationale, design and methodology of the OPTIMIS study
2024, Contemporary Clinical Trials Communications
Percutaneous coronary intervention with implantation of a bioresorbable scaffold (BRS) provide the vessel support for a limited period allowing the vessel to restore normal vasomotion after degradation of the BRS, opposed to treatment with drug-eluting stents where the metal persist in the vessel wall. Late lumen loss and reduction in lumen area after implantation have been reported. The purpose of this study was to investigate whether intense pre-dilatation before BRS implantation resulted in less reduction of minimal lumen area at 6- and 12-month follow-up after implantation of a Magmaris BRS (MgBRS). Coronary imaging with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) was assessed to track changes in lumen and vessel dimensions.
The prospective Optimal lesion PreparaTion before Implantation of the Magmaris bioresorbable scaffold In patients with coronary artery Stenosis (OPTIMIS) study randomly assigned eighty-two patients with chronic coronary syndrome to two pre-dilatation treatment strategies. Patients were randomized in a 1:1 ratio to pre-dilatation with either a non-compliant scoring balloon or a standard non-compliant balloon prior to implantation of a MgBRS. The treated segment was evaluated with OCT and IVUS at baseline, after 6 and 12 months to assess changes in lumen and vessel dimensions. The hypothesis was that more intense pre-dilatation with a non-compliant scoring balloon before MgBRS implantation can reduce the risk of late lumen reduction compared to standard pre-dilatation. The power calculation used expected MLA after 6 months (6.22 mm² for the scoring balloon and 5.01 mm² for the standard non-compliant balloon), power of 80 %, significance level of 0.05 and expected drop-out rate of 15 %, requiring 82 patients to be enrolled.
Eighty-two patients were included in the study. Enrollment was from December 2020 to September 2023.
The hypothesis was that more intense pre-dilatation with a non-compliant scoring balloon before MgBRS implantation can reduce the risk of late lumen reduction compared to standard pre-dilatation.
In vitro and in vivo studies on bioactive hydroxyapatite-coated magnesium for glaucoma drainage implant
2024, Journal of Magnesium and Alloys
Given the alarmingly increasing rates of glaucoma worldwide and the lack of satisfactory treatments, there is a dire need to explore more feasible treatment options. Magnesium (Mg) is an essential element in maintaining the functional and structural integrity of vital ocular tissues, but Mg and its alloys are rarely mentioned in ophthalmic applications. Our previous research found that hydroxyapatite-coated Mg (Mg@HA) shows the best biocompatibility and bioactivity, and exhibits the effect of inhibiting fibrosis after filtration surgery in the rabbit model, which is expected to be a promising material for glaucoma drainage device. In this study, we further demonstrated the anti-fibrosis effect of Mg@HA from the molecular signal level and the efficacy of implantation in the rabbit filtration surgery model. In vitro experiments showed the surface modification of Mg affects the adhesion behavior and the reorganization of cytoskeleton of Human Western blot analysis and immunofluorescence found that Mg@HA regulates the adhesion and motility of human Tenon's capsule fibroblasts mainly by down-regulating the phosphorylation of Smad2 and Smad3 in the canonical transforming growth factor-beta (TGF - β) signaling pathway. By observing and recording the condition of filtering blebs and intraocular pressure after surgery, the effectiveness of Mg@HA applied in the rabbit filtration surgery model was further evaluated. In conclusion, the application of hydroxyapatite-coated Mg in the eye has good biocompatibility and has the potential to resist postoperative glaucoma filtration fibrosis, which may be mediated by the regulation of the TGFβ/Smad signaling pathway.
Mg alloy cardio-/cerebrovascular scaffolds: Developments and prospects
2023, Journal of Magnesium and Alloys
Vascular scaffolds are one of the important application fields of biodegradable Mg alloys, and related research has been carried out for more than 20 years. In recent years, the application expansion of Mg alloy vascular scaffolds has brought new challenges to the research of related fields. This review focuses on the relevant advances in the field of Mg alloys for both cardio-/cerebrovascular scaffolds. The frequently investigated alloy series for vascular scaffolds were reviewed. The bottleneck of processing of Mg alloy minitubes was elucidated. The idea of functionalized surface modification was also pointed out in this review, and the authors put forward guidelines based on research experience in terms of scaffold structural design and degradation behavior evaluation. Finally, suggestions for further research directions of Mg alloy vascular scaffolds were provided.
Phase-field modeling of pitting and mechanically-assisted corrosion of Mg alloys for biomedical applications
2023, Acta Biomaterialia
A phase-field model is developed to simulate the corrosion of Mg alloys in body fluids. The model incorporates both Mg dissolution and the transport of Mg ions in solution, naturally predicting the transition from activation-controlled to diffusion-controlled bio-corrosion. In addition to uniform corrosion, the presented framework captures pitting corrosion and accounts for the synergistic effect of aggressive environments and mechanical loading in accelerating corrosion kinetics. The model applies to arbitrary 2D and 3D geometries with no special treatment for the evolution of the corrosion front, which is described using a diffuse interface approach. Experiments are conducted to validate the model and a good agreement is attained against in vitro measurements on Mg wires. The potential of the model to capture mechano-chemical effects during corrosion is demonstrated in case studies considering Mg wires in tension and bioabsorbable coronary Mg stents subjected to mechanical loading. The proposed methodology can be used to assess the in vitro and in vivo service life of Mg-based biomedical devices and optimize the design taking into account the effect of mechanical deformation on the corrosion rate. The model has the potential to advocate further development of Mg alloys as a biodegradable implant material for biomedical applications.
A physically-based model is developed to simulate the corrosion of bioabsorbable metals in environments that resemble biological fluids. The model captures pitting corrosion and incorporates the role of mechanical fields in enhancing the corrosion of bioabsorbable metals. Model predictions are validated against dedicated in vitro corrosion experiments on Mg wires. The potential of the model to capture mechano-chemical effects is demonstrated in representative examples. The simulations show that the presence of mechanical fields leads to the formation of cracks accelerating the failure of Mg wires, whereas pitting severely compromises the structural integrity of coronary Mg stents. This work extends phase-field modeling to bioengineering and provides a mechanistic tool for assessing the service life of bioabsorbable metallic biomedical devices.
Improving biocompatibility for next generation of metallic implants
2023, Progress in Materials Science
The increasing need for joint replacement surgeries, musculoskeletal repairs, and orthodontics worldwide prompts emerging technologies to evolve with healthcare's changing landscape. Metallic orthopaedic materials have a shared application history with the aerospace industry, making them only partly efficient in the biomedical domain. However, suitability of metallic materials in bone tissue replacements and regenerative therapies remains unchallenged due to their superior mechanical properties, eventhough they are not perfectly biocompatible. Therefore, exploring ways to improve biocompatibility is the most critical step toward designing the next generation of metallic biomaterials. This review discusses methods of improving biocompatibility of metals used in biomedical devices using surface modification, bulk modification, and incorporation of biologics. Our investigation spans multiple length scales, from bulk metals to the effect of microporosities, surface nanoarchitecture, and biomolecules such as DNA incorporation for enhanced biological response in metallic materials. We examine recent technologies such as 3D printing in alloy design and storing surface charge on nanoarchitecture surfaces, metal-on-metal, and ceramic-on-metal coatings to present a coherent and comprehensive understanding of the subject. Finally, we consider the advantages and challenges of metallic biomaterials and identify future directions.
Recent advances in surface endothelialization of the magnesium alloy stent materials
2023, Journal of Magnesium and Alloys
Magnesium and its alloy have good mechanical properties and biodegradability, and have become the hotspot of the next-generation biodegradable vascular stent materials. However, their rapid degradation in vivo and poor biocompatibility are still the bottlenecks of clinical applications for the cardiovascular stents. In particular, how to induce the repair and regeneration of the vascular endothelial with normal physiological functions on the surface of the magnesium alloy stent materials represents the key to its clinical application in the field of cardiovascular stents. It has been believed that it is an ideal way to completely solve the postoperative complications through constructing the multifunctional anti-corrosive bioactive coating on the magnesium alloy surface to induce the formation of vascular endothelium with normal physiological functions. However, how to construct a corrosion-resistant multifunctional bioactive coating with the good endothelial regeneration abilities on the magnesium alloy surface still faces a great challenge. This paper mainly focused on highlighting and summarizing the recent advances in the surface endothelialization of the magnesium alloy materials for the vascular stent, including the bio-inert coating, in-situ immobilization of bioactive molecules on the surface, polymer coating loaded with bioactive factors, novel multifunctional polymer coating, bioactive micropatterns, bioactive layer with glycocalyx-like structure, NO-releasing coating and bioactive sol-gel coating. The advantages and disadvantages of these strategies were discussed and analyzed. Finally, in the senses of future development and clinical application, this paper analyzed and summarized the development direction and prospect of surface endothelialization of the magnesium alloy vascular stents. It is anticipated that this review can give the new cues to the surface endothelialization of the cardiovascular magnesium alloy stents and promote future advancements in this field.

View all citing articles on Scopus

View full text

In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris — DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial

Highlights

Abstract

Rationale

Objectives

Methods and results

Conclusion

Introduction

Section snippets

Study design and population

Results

Discussion

Conclusion

Funding

Conflict of interest

Acknowledgement

JACC Cardiovasc. imaging

Lancet

Am. J. Cardiol.

J. Biomech.

JACC Cardiovasc. Interv.