RENASCENT III: First in Human Evaluation of the Novel Thin Strut MAGNITUDE Sirolimus-Eluting Ultra-High Molecular Weight MAGNITUDE Bioresorbable Scaffold: 9-Month Imaging and 2-Year Clinical Results
2021; Lippincott Williams & Wilkins; Volume: 14; Issue: 5 Linguagem: Inglês
10.1161/circinterventions.120.010013
ISSN1941-7632
AutoresMarco Ferrone, Alaide Chieffo, Saud Khawaja, Miguel Moncada, Antonio Colombo, Azeem Latib, Giovanni Esposito, Eugenio Stabile, Marisa Avvedimento, Francesco Bedogni, Luca Testa, Juan A. Delgado, Camilo Arana, Boris Vesga, Bernardo Cortese, Akiko Mahera, Juan F. Granada,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoHomeCirculation: Cardiovascular InterventionsVol. 14, No. 5RENASCENT III: First in Human Evaluation of the Novel Thin Strut MAGNITUDE Sirolimus-Eluting Ultra-High Molecular Weight MAGNITUDE Bioresorbable Scaffold: 9-Month Imaging and 2-Year Clinical Results Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBRENASCENT III: First in Human Evaluation of the Novel Thin Strut MAGNITUDE Sirolimus-Eluting Ultra-High Molecular Weight MAGNITUDE Bioresorbable Scaffold: 9-Month Imaging and 2-Year Clinical Results Marco Ferrone, MD Alaide Chieffo, MD Saud A. Khawaja, MD Miguel Moncada, MD Antonio Colombo, MD Azeem Latib, MD Giovanni Esposito, MD, PhD Eugenio Stabile, MD, PhD Marisa Avvedimento, MD Francesco Bedogni, MD Luca Testa, MD Juan Andres Delgado, MD Camilo Arana, MD Boris Vesga, MD Bernardo Cortese, MD Akiko Mahera, MD Juan F. GranadaMD Marco FerroneMarco Ferrone Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY (M.F., J.F.G.). Division of Cardiology, Dept of Advanced Biomedical Sciences, University of Naples "Federico II" (M.F., G.E., E.S., M.A.). Department of Interventional Cardiology, Montevergine Clinic, Mercogliano (M.F.). , Alaide ChieffoAlaide Chieffo https://orcid.org/0000-0002-3505-9112 Interventional Cardiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy (A.C., S.A.K., A.C., A.L.). , Saud A. KhawajaSaud A. Khawaja Interventional Cardiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy (A.C., S.A.K., A.C., A.L.). , Miguel MoncadaMiguel Moncada MMSA Clinica Especializada Medellin Columbia (M.M.). , Antonio ColomboAntonio Colombo https://orcid.org/0000-0002-2940-2455 Interventional Cardiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy (A.C., S.A.K., A.C., A.L.). , Azeem LatibAzeem Latib https://orcid.org/0000-0001-9035-343X Interventional Cardiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy (A.C., S.A.K., A.C., A.L.). , Giovanni EspositoGiovanni Esposito https://orcid.org/0000-0003-0565-7127 Division of Cardiology, Dept of Advanced Biomedical Sciences, University of Naples "Federico II" (M.F., G.E., E.S., M.A.). , Eugenio StabileEugenio Stabile Division of Cardiology, Dept of Advanced Biomedical Sciences, University of Naples "Federico II" (M.F., G.E., E.S., M.A.). , Marisa AvvedimentoMarisa Avvedimento Division of Cardiology, Dept of Advanced Biomedical Sciences, University of Naples "Federico II" (M.F., G.E., E.S., M.A.). , Francesco BedogniFrancesco Bedogni IRCCS Policlinico San Donato, Milan, Italy (F.B., L.T.). , Luca TestaLuca Testa https://orcid.org/0000-0003-4687-3686 IRCCS Policlinico San Donato, Milan, Italy (F.B., L.T.). , Juan Andres DelgadoJuan Andres Delgado Clinical del Norte, Medellin, Colombia (J.A.D.). , Camilo AranaCamilo Arana Angiografia de Occidente S.A., Cali, Colombia (C.A.). , Boris VesgaBoris Vesga https://orcid.org/0000-0001-6258-1195 Instituto del Corazon de Bucaramanga, Universidad Industrial de Santander, Colombia (B.V.). , Bernardo CorteseBernardo Cortese https://orcid.org/0000-0002-5808-7810 Cardiovascular Research Team, San Carlo Clinic, Milano (B.C.). , Akiko MaheraAkiko Mahera https://orcid.org/0000-0002-1910-8447 Cardiovascular Research Foundation, New York (A.M.). , Juan F. GranadaJuan F. Granada Correspondence to: Juan F. Granada, MD, CRF-Skirball Center for Innovation, Columbia University Medical Center, New York. Email E-mail Address: [email protected] https://orcid.org/0000-0003-2399-8320 Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, NY (M.F., J.F.G.). Originally published18 May 2021https://doi.org/10.1161/CIRCINTERVENTIONS.120.010013Circulation: Cardiovascular Interventions. 2021;14:e010013RENASCENT III is a prospective, nonrandomized, single-arm study (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02900937) of the MAGNITUDE a Bioresorbable Drug-Eluting Coronary Scaffold (98 μm) made of polylactic acid with a continuous closed cell zigzag helical design eluting rapamycin (90% of the drug is released by 90 days). The specific manufacturing process of the polymer and the design of the scaffold provide uniform strength in all directions without increasing the scaffold surface area, not causing delay of the scaffold endothelialization.1 The high strength also makes the scaffold less likely to fracture or crack in high stress areas giving the scaffold a more metallic drug eluting stent-like behavior. The degradation process of this particular design peaks at 2 years and is dependent on strut thickness. Seventy patients from 4 centers in Colombia and 4 in Italy were enrolled in the study.Inclusion criteria: patients >18 and <85 years presenting with either stable or unstable angina pectoris, silent ischemia, low or intermediate risk non–ST-segment–elevation myocardial infarction, evidence of myocardial ischemia in a coronary territory previously affected by ST-segment–elevation myocardial infarctionas long as the intervention performed ≥3 months following the ST-segment–elevation myocardial infarction and up to 2 de novo lesions in a native coronary artery with a diameter between 2.5 and 3.7 mm by intravascular ultrasound, lesion length of <14 mm by quantitative coronary (QCA) a percentage visually estimated diameter stenosis ≥50% and <100% and a TIMI flow grade ≥1.A maximum of 2 de-novo native coronary artery lesions for each patient were allowed to be treated per protocol. Successful predilatation of the target lesion was mandatory (1:1). Baseline intravascular ultrasound assessment was performed during the index procedure to evaluate vessel size, degree of calcification, and to determine the appropriate scaffold size. Post-dilatation was not mandatory. Postprocedural intravascular imaging with optical coherence tomography (OCT) was required in all cases. At 9 months, angiographic follow-up with OCT was performed. Follow-up was continued up to 24 months through phone call or ambulatory visits. All the data were collected in dedicated electronic Case Report Forms. The ethics committee at each participating institution approved the protocol, and each patient gave written informed consent before inclusion. As required by national regulations, the approval of the relevant national regulatory agency was obtained. The data are available from the corresponding author upon reasonable request. Additionally, the trial was registered at https://clinicaltrials.gov/ct2/show/NCT02900937.Primary performance end point was in-scaffold late lumen loss measured by QCA at 9 months. Primary safety end point was the incidence of target vessel failure, defined as cardiac death, target vessel myocardial infarction (using the Expert Consensus Document From the Society for Cardiovascular Angiography and Interventions), or clinically indicated target lesion revascularization (using the ARC definition) at 9 months. An independent core lab (Cardiovascular Research Foundation, New York) performed angiographic (QCA) and OCT analysis.Mean age was 64.3±9.7; 65.7 were males; diabetics were 14.3%; mean left ventricular ejection fraction 53.5±8.2%; acute coronary syndrome was the clinical presentation in 42.9%; reference diameter was 2.8±0.3; diameter stenosis was 59.8±8.7%; mean length was 17.4±6.8 mm; moderate/severe calcification was present in 22.9% (Table). Two patients experienced a target vessel myocardial infarctions within the first 30 days. Both events were periprocedural and resulted from an asymptomatic enzymatic rise without EKG changes, including one case of periprocedural OCT-related air embolization. The resulting clinical procedure success rate was 97.1% (n=68). At 9 months, 66 lesions were analyzed at the mandatory angiographic follow-up. At 9 months, TVF rate was 7.4% (n=5) due to 2 periprocedural MI and 3 re-interventions (1 TVR non-Q-wave myocardial infarction not related to the scaffold, 2 ischemia-driven target lesion revascularization). At 24 months, 7 patients were missing at follow-up, and no scaffold thrombosis occurred. In-scaffold late lumen loss was 0.28±0.36 mm at 9 months mainly constituted of neointimal thickness rather than of the reduction of the mean outer scaffold area as demonstrated by the OCT. Other significant QCA measurements were MLD 1.1±0.3 at baseline, 2.5±0.3 mm post-bioresorbable scaffold (BRS) implantation, and 2.3±0.4 mm at 9 months. There was an acute gain of 1.6±0.3 mm post BRS deployment.Table. Procedural CharacteristicsTarget lesion angiographic characteristics (n=74)Mean±SD or % (n)Target arteryLAD43.2% (32)LCx25.7% (19)RCA29.7% (22)Ramus1.4% (1)Proximal-mid lesion location81.1% (60/74)RVD, mm2.8±0.3RVD<2.5 mm by QCA14.7% (10/68)QCA diameter stenosis59.8%±8.7%QCA length, mm17.4±6.8ACC/AHA lesion class type b1-c81.4% (57)Any bifurcation/side branch41.1% (29)Moderate-severe calcification22.9% (16)Preprocedure TIMI 3 flow98.5% (67/68)Preprocedure diameter stenosis59.8%±8.7% (70)Predilatation before implant98.6% (73)Post-dilatation using NC balloon23.3% (17)Max scaffold deployment inflation pressure13.5%±2.4 (72)Final in-segment diameter stenosis14.1±7.3 (70)Failure to cross due to severe calcification tortuosity2.7% (2)Distal dissection treated with DES0Clinical device success*97.3% (72/74)Clinical procedure success†97.1% (68/70)ACC indicates American College of Cardiology; AHA, American Heart Association; DES, drug eluting stent; LAD, left anterior descending artery; LCx, left circumflex artery; NC, noncompliant; QCA, quantitative coronary angiography; RCA, right coronary artery; RVD, reference vessel diameter; and TIMI, Thrombolysis in Myocardial Infarction.* Defined as successful delivery and deployment of the scaffold at the intended target lesion with final residual stenosis <50% of the target lesion by QCA after the index procedure.† Defined as clinical device success with any adjunctive device without the occurrence of major adverse clinical events related to ischemia up to day of discharge.OCT pullbacks were analyzed in 62 lesions during the index procedure (post-scaffold implantation) and 59 lesions at 9 months angiographic FU. The percentage of intrascaffold neointimal hyperplasia volume at 9 months was low (12.7±7%). At 9 months, the total percentage of covered struts was 96.7% (96.6±3.9% were apposed to the vessel wall); the total percentage of uncovered struts was 2.8%±3.4% and the architecture of the implant remained intact compared with baseline values (mean outer scaffold area 7.58±1.32 versus 7.82±1.634 [mm3/mm]).Delayed endotehelalization, low radial force, and higher fracture rate are the main limitations of BRS compared with drug eluting stent. The specific polylactic acid manufacturing process used in the current generation of MAGNITUDE BRS has maintained similar metallic-stent-like mechanical properties compared with previous generations of the same polymeric technology (FORTITUDE 150-μm and APTITUDE 110-μm)2 despite the reduction of the strut thickness (below 100 μm).The Sirolimus-Eluting Ultra-High Molecular Weight MAGNITUDE BRS demonstrated to be safe and effective in our first in man experience up to 2 years.Sources of FundingThis study was funded by Amaranth Medical Inc.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 555.Correspondence to: Juan F. Granada, MD, CRF-Skirball Center for Innovation, Columbia University Medical Center, New York. Email [email protected]orgReference1. Foin N, Lee RD, Torii R, Guitierrez-Chico JL, Mattesini A, Nijjer S, Sen S, Petraco R, Davies JE, Di Mario C, et al.. Impact of stent strut design in metallic stents and biodegradable scaffolds.Int J Cardiol. 2014; 177:800–808. doi: 10.1016/j.ijcard.2014.09.143CrossrefMedlineGoogle Scholar2. Chieffo A, Khawaja SA, Latib A, Vesga B, Moncada M, Delgado JA, Fonseca J, Testa L, Esposito G, Ferrone M, et al.; Collaborators. First-in-human evaluation of a novel sirolimus-eluting ultra-high molecular weight APTITUDE bioresorbable scaffold: 9- and 24-month imaging and clinical results of the RENASCENT II trial.EuroIntervention. 2020; 16:e133–e140. doi: 10.4244/EIJ-D-19-00600CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails May 2021Vol 14, Issue 5Article InformationMetrics Download: 45 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCINTERVENTIONS.120.010013PMID: 34003665 Originally publishedMay 18, 2021 Keywordscoronary artery diseaseangina, unstablepolymermyocardial ischemiastentPDF download SubjectsStentRevascularizationCoronary Artery DiseasePercutaneous Coronary Intervention
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