Clinical Feasibility of Novel Paclitaxel-Coated Balloon with Shellac plus Vitamin E Excipient in Patients with De Novo Coronary Artery Lesion

Clinical Feasibility of Novel Paclitaxel-Coated Balloon with Shellac plus Vitamin E Excipient in Patients with De Novo Coronary Artery Lesion | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Feasibility of Novel Paclitaxel-Coated Balloon with Shellac plus Vitamin E Excipient in Patients with De Novo Coronary Artery Lesion Jeen Hwa Lee, Jung Rae Cho, Jung-Sun Kim, Dae Young Cheon, Jaehyuk Choi, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7696486/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Drug-coated balloons (DCBs) are increasingly used for de novo coronary lesions (DNCLs), particularly in small vessels. The GENOSS DCB is a novel paclitaxel-coated balloon using a shellac plus vitamin E excipient, previously effective in in-stent restenosis, but its feasibility in DNCLs remains unclear. This study evaluated the clinical feasibility of GENOSS DCBs in DNCLs. Methods This was a prospective, multicenter, single-arm pilot study of patients with DNCLs (2.0–4.0 mm in diameter). The primary endpoint was in-segment late lumen loss (LLL) at 6 months. Secondary endpoints included device/procedure success rate, restenosis rate, cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization (TLR) at 6-month follow-up. Results A total of 20 patients (mean age 66.0 ± 10.3 years; 70% male) were enrolled from two academic centers. Device and procedure success was achieved in all patients. The 6-month in-segment LLL was –0.17 ± 0.3 mm, and no restenosis was observed. Diameter stenosis improved from 48.5 ± 13.8% post-DCB to 23.69 ± 9.3% at 6 months. One non-TLR was reported, with no cardiac death, myocardial infarction, stent thrombosis, or TLR. Conclusions GENOSS DCBs showed favorable angiographic and clinical outcomes at 6 months, supporting their feasibility as a treatment for DNCLs. drug-coated balloon percutaneous coronary intervention paclitaxel de novo lesions coronary artery disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Drug-coated balloons (DCBs) have emerged as a key therapeutic option for in-stent restenosis (ISR), with recent guidelines acknowledging their efficacy and safety in clinical practice. DCBs deliver antiproliferative drugs directly to the vessel wall, inhibiting neointimal hyperplasia without the need for permanent implantation, which has facilitated their widespread adoption in ISR management(1-5). Recently, DCBs have also been recognized as a potential therapeutic option for treating de novo coronary lesions (DNCLs)(6-9). Several studies have demonstrated that DCBs achieve clinical outcomes comparable to those of drug-eluting stents in small coronary arteries, where stent implantation may be associated with a higher risk of complications(10-19). Various antiproliferative agents have been used in DCBs, but paclitaxel remains the preferred choice due to its high lipophilicity, rapid vessel wall penetration, and ability to irreversibly stabilize microtubules, effectively inhibiting neointimal hyperplasia(3, 20-23). As a result, paclitaxel-based DCBs continue to be the primary tools for clinical application. The GENOSS DCB (Genoss, Korea) incorporates a novel excipient formulation of shellac and vitamin E, designed to improve paclitaxel delivery and retention at the target lesion, potentially reducing restenosis rates compared to other DCBs. The theoretical difference in the paclitaxel formulation between GENOSS DCB (crystalline) and other DCBs (amorphous) might result in better performance, despite the paclitaxel concentration being the same at 3 µg/mm 2 (Figures 1, 2). While preliminary studies have suggested potential benefits of this novel DCB in in-stent stenosis lesions(24), its efficacy and safety in treating DNCLs have not been comprehensively evaluated. This prospective, multicenter, single-arm study aims to evaluate the efficacy and safety of GENOSS DCBs in patients with DNCLs, focusing on angiographic outcomes. This exploratory clinical trial was conducted as part of a government project, a collaborative project between the Korea Health Industry Development Institute and Industry. Methods Study Design and Population This study included 20 participants from two academic centers in Korea: Hallym University Kangnam Sacred Heart Hospital and Severance Hospital. Eligible participants were adults aged 19 years or older with DNCLs measuring 2.0 mm to 4.0 mm in diameter, who required percutaneous coronary intervention (PCI). Patients with stable angina, unstable angina, or silent ischemia who had not undergone prior interventional treatment for the target lesion were included. The clinical exclusion criteria were as follows: ST-segment elevation myocardial infarction (STEMI) within the previous 48 hours, cardiogenic shock, left ventricular ejection fraction < 30%, severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min), contraindications or suspected intolerance to paclitaxel, aspirin, P2Y12 inhibitors, a life expectancy of less than 1 year, and pregnancy or lactation. Angiographic exclusion criteria included restenosis lesions, bypass graft lesions, chronic total occlusions, left main coronary lesions, and angiographic findings requiring stent implantation (e.g., persistent flow limitation due to dissection, residual stenosis > 30%, or thrombolysis in myocardial infarction [TIMI] flow < 3). The study protocol was approved by the institutional review boards of Hallym University Kangnam Sacred Heart Hospital Institution Review Board (IRB number: 2022-12-001) and Yonsei University Health system, Severance Hospital Institutional Review Board (IRB number: 2024-0049), and written informed consent was obtained from all participants. Intervention After informed consent was obtained, participants underwent preprocedural evaluation and received standard medications, including antiplatelet therapy. Antiplatelet therapy consisted of a loading dose of 300 mg aspirin and 600 mg clopidogrel administered prior to coronary angiography, followed by maintenance doses of 100 mg aspirin and 75 mg clopidogrel once daily for up to 6 months post-PCI. Other medications, such as statins and antianginal agents, were administered at the physician’s discretion. On the day of the procedure, coronary angiography was performed to confirm eligibility criteria, and pre-dilation was conducted with a standard balloon catheter, using a balloon-to-artery ratio of 1:1. If predilation was successful, the GENOSS DCB was applied to the target lesion. The time from vascular access to balloon inflation at nominal pressure was kept within 3 minutes to minimize balloon exposure to blood prior to inflation. The drug-coated balloon catheter was inflated for 60 seconds to ensure adequate drug delivery to the vessel wall. If patients experienced discomfort, inflation was performed in two 30-second intervals. Patients in whom predilation was unsuccessful or who developed significant complications, such as severe vascular dissection, were excluded from the study and received alternative treatments according to institutional protocols. After the procedure, patients were monitored during hospitalization and followed up at 1 and 6 months for efficacy and safety assessments. Angiographic assessments were conducted before, immediately after the procedure, and at the 6-month follow-up via analysis of identical projections. Quantitative coronary angiographic analysis was performed by an experienced technician (K.G.S from Kangnam Sacred Heart Hospital), who was blinded to study conditions. The measurements included the number of lesions, lesion location, minimum lumen diameter (MLD), reference vessel diameter (RVD), stenosis rate (%), lesion length, balloon diameter, balloon length, and balloon inflation pressure. Additionally, blood vessel dissection after predilation and the National Heart, Lung, and Blood Institute (NHLBI) classification of the dissection were recorded. Study Device The investigational device, the GENOSS DCB Paclitaxel-Coated PTCA Balloon Catheter, is a balloon-expandable catheter coated with paclitaxel and an excipient combination of shellac and vitamin E. The catheter is designed for rapid and effective drug delivery to the vessel wall during PCI. The hydrophilic coating and radiopaque markers ensure smooth delivery and accurate placement within the lesion. The catheter diameter ranged from 2.0 mm to 4.0 mm, and the balloon length varied from 10 mm to 40 mm. The device is approved for the treatment of in-stent restenosis but was evaluated in this study for de novo coronary artery lesions. Study Endpoints The primary efficacy endpoint was in-lesion late lumen loss (LLL) at 6 months post-procedure, as measured by coronary angiography. LLL was defined as the change in vessel diameter (MLD, mm) after 6 months, subtracted from the dilated vessel diameter (MLD, mm) immediately after intervention. The vessel diameter was measured at the narrowest section within the lesion. Other endpoints included the device success rate, defined as the successful delivery and inflation of the balloon at the target lesion with < 30% residual stenosis. The procedural success rate was defined as the device success rate without clinical events during hospitalization. Restenosis was defined as diameter stenosis (DS, %) of at least 50% compared to the reference vessel at 6-month follow-up coronary angiography. Target vessel failure was defined as the composite outcome of cardiac death, target-vessel myocardial infarction, or ischemia-driven target vessel revascularization. Major adverse cardiac events (MACEs) included cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization (TLR), or target vessel revascularization (TVR) at 6 months post-procedure. Cardiac death was defined as any death not clearly of extracardiac origin or myocardial infarction, according to guidelines(25). Myocardial infarction was defined according to the universal definition proposed by the Society for Cardiovascular Angiography and Interventions (SCAI)(26). TLR was defined as any repeat revascularization within the DCB-treated segment, and TVR was defined as any repeat revascularization of the target vessel. Non-TLR referred to a TLR event in coronary arteries other than those treated with DCBs at the index PCI. Probable or definite stent thrombosis was defined according to the Bleeding Academic Research Consortium(BARC) criteria(27). Statistical Analysis Statistical analyses were performed on the intention-to-treat (ITT) population, including all patients who received the investigational device. Descriptive statistics summarized patient demographics, baseline characteristics, and procedural data. Continuous variables were presented as means ± standard deviations or medians with interquartile ranges, as appropriate. Categorical variables were summarized as counts and percentages. The primary efficacy endpoint, in-lesion late lumen loss, was analyzed using paired t-tests or Wilcoxon signed-rank tests, depending on the normality of data distribution. Secondary endpoints, such as device success rates and procedural success rates, were expressed as frequencies and percentages. A two-tailed p-value of <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 22 (IBM; Armonk, NY, USA). Results Twenty patients from two centers were treated with the GENOSS DCB for DNCLs. The mean age was 66.0 ± 10.3 years, and 70% were male. Baseline characteristics showed a high prevalence of cardiovascular risk factors: hyperlipidemia (80%), diabetes mellitus (35%), and prior PCI (40%). Prior to the index procedure, 20% had a history of myocardial infarction and 25% had cerebrovascular disease. Despite these comorbidities, none had undergone coronary artery bypass grafting, and only 5% had congestive heart failure. Most patients had stable angina (80%); 10% presented with unstable angina and 10% with non–ST-elevation myocardial infarction (NSTEMI) (Table 1). The most frequently treated vessel was the left anterior descending artery (40%), followed by the left circumflex artery (35%), right coronary artery (20%), and ramus intermedius (5%). Most patients had single-vessel disease (65%). The mean balloon diameter was 2.1 ± 0.4 mm, and the average length was 15.8 ± 2.9 mm. The maximum inflation pressure was 11.1 ± 4.5 atm (Table 2). Coronary dissection occurred in three patients and was classified as NHLBI class A. All patients underwent coronary angiography at 6 months. Quantitative coronary angiography showed that, before the procedure, the RVD and MLD were 2.40 ± 0.5 mm and 0.53 ± 0.2 mm, respectively, corresponding to a preprocedural DS of 77.7 ± 8.5%. Immediately after the procedure, the in-segment RVD was 2.20 ± 0.4 mm, and the MLD increased to 1.12 ± 0.4 mm, reducing the DS to 48.5 ± 13.8%. At the 6-month follow-up, the MLD further increased to 1.78 ± 0.3 mm and the DS decreased to 23.7 ± 9.3%. The primary endpoint, in-segment LLL at 6 months, was −0.17 ± 0.3 mm, indicating a slight increase in lumen diameter compared with the postprocedural measurement. No restenosis was observed on follow-up angiography (Table 3). Cumulative distribution curves for MLD at baseline, postprocedure, and follow-up are shown in Figure 3. For secondary endpoints, both device success and procedural success were achieved in all patients, with no procedural complications. During the 6-month follow-up, there were no cases of cardiac death, myocardial infarction, stent thrombosis, TLR, or TVR. Only one non-TLR event was observed (Table 4). A representative case involved a 73-year-old female patient with stable angina, a history of ischemic stroke, and stage III chronic kidney disease (serum creatinine, 1.52 mg/dL; eGFR, 34 mL/min) (Figure 4). Baseline coronary angiography showed significant distal left circumflex artery stenosis, with an RVD of 1.68 mm and an MLD of 0.35 mm, corresponding to a DS of 78%. Following angioplasty with a 2.5 × 35 mm GENOSS DCB, the RVD and MLD increased to 2.09 mm and 1.63 mm, respectively, reducing the DS to 22%. At the 6-month follow-up on guideline-directed medical therapy, including dual antiplatelet therapy (aspirin and clopidogrel) and statins, follow-up angiography showed further luminal enlargement, with an RVD of 2.60 mm, an MLD of 2.34 mm, and a DS of 10%. This case exemplifies “late lumen enlargement,” with a calculated LLL of −0.71 mm. Discussion This prospective pilot study evaluated the clinical feasibility of the GENOSS DCB, a novel paclitaxel-coated balloon with a shellac and vitamin E excipient, in patients with DNCLs. The GENOSS DCB demonstrated an increase in the MLD at the 6-month follow-up compared with the postprocedure state (in-segment LLL: –0.17 ± 0.3 mm), consistent with the late lumen enlargement. No cases of restenosis were observed, and DS improved from 48.5 ± 13.8% post-procedure to 23.7 ± 9.3% at follow-up. Procedural outcomes were favorable, with 100% device and procedural success rates and no MACE, including cardiac death, myocardial infarction, stent thrombosis, or TLR, reported during the follow-up period. Previous randomized trials assessing paclitaxel-coated DCBs in de novo small vessel disease have consistently reported that in-segment LLL at follow-up angiography is lower than that of drug-eluting stents(11, 13, 16). The BELLO (Balloon Elution and Later Loss Optimization) trial reported an in-segment LLL of 0.05 ± 0.37 mm at the 6-month follow-up angiography after paclitaxel-coated DCB treatment(11), and the RESTORE SVD (Assess the Efficacy and Safety of RESTORE Paclitaxel Eluting Balloon Versus RESOLUTE Zotarolimus Eluting Stent for the Treatment of Small Coronary Vessel Disease) study demonstrated an in-segment LLL of 0.25 ± 0.42 mm at the 9-month follow-up(13). The PICCOLETO II (Drug Eluting Balloon Efficacy for Small Vessel Disease Treatment) trial reported an even lower in-segment LLL of 0.01 ± 0.25 mm at 6 months(16). A single-center study evaluated the effects on the side-branch ostium after treatment of DNCLs of the main vessels with paclitaxel-coated balloons assessed with optical coherence tomography (OCT). The Sequent Please DCB (B. Braun, Melsungen, Germany) was used in this trial, and the in-segment LLL of the main vessels was –0.01 ± 0.18 mm at 9 months, along with an increase in the side-branch ostial lumen area(28). In comparison, our study reported an in-segment LLL of –0.17 ± 0.3 mm at 6 months following treatment with the GENOSS DCB, suggesting a favorable angiographic response relative to previous reports. While cross-trial comparisons should be interpreted with cautious, these findings suggest that the GENOSS DCB may yield competitive luminal outcomes among current paclitaxel-coated balloons technologies. A potential explanation for late lumen enlargement is that paclitaxel has been shown to induce positive vascular remodeling over time, which may have contributed to the lower LLL(20, 21, 29). This mechanism is supported by histopathological findings from preclinical studies comparing sirolimus- and paclitaxel-coated balloons, where paclitaxel demonstrated greater neointimal modulation(30). However, considering that prior randomized studies using paclitaxel-coated DCBs have reported varying degrees of LLL(11, 13, 16), additional factors may also have influenced our results. A distinguishing feature of our study was the use of a standardized, mandatory lesion preparation protocol, in which all patients underwent sufficient predilation before DCB application. This ensures optimal vessel compliance and drug uptake and is consistent with the recommendations of the International DCB Consensus Group(10). In contrast, earlier studies allowed lesion preparation at the discretion of the operator, which may have introduced variability in balloon expansion and drug delivery. Optimal lesion preparation has been associated with reduced adverse event rates following DCB treatment(31, 32), and the Consensus Group recommends the use of a semi- or noncompliant balloon with a balloon-to-artery ratio of 1:1(10). Recent studies that adopted this standardized predilation protocol also reported luminal enlargement after paclitaxel-coated DCB use. Such luminal enlargement can also be assessed by either OCT(28, 33) or intravascular ultrasound (IVUS) immediately after DCB intervention and at follow-up, revealing an increased MLD and lumen area(34). These procedural refinements may have contributed to the improved acute luminal gain and sustained vessel patency observed in our cohort. In addition, our study demonstrated favorable clinical results, with no major adverse cardiac events observed at the 6-month follow-up, except for a single case of nontarget vessel revascularization. In contrast, other studies evaluating DCBs in de novo coronary lesions have reported higher clinical event rates at 12 months. For example, the BELLO trial reported a 10.0% MACE rate(11), whereas the PICCOLETO II and RESTORE SVD studies reported MACE rates of 5.6% and 4.4%, respectively, at one year(13, 16). In the BASKET-SMALL 2 (Basel Stent Kosten-Effektivitäts Trial-Drug-Coated Balloons versus Drug-eluting Stents in Small Vessel Interventions) trial, the DCB group experienced a 7.5% of MACE, including 3.1% cardiac death, 1.6% myocardial infarction, 3.4% TVR, and 0.79% of stent thrombosis(14). Although the shorter follow-up period in our study limits direct comparison, the comparable angiographic parameters (LLL and DS) suggest that the favorable clinical outcomes may be sustained over time. This projection is supported by previous studies demonstrating a strong correlation between late lumen loss and diameter stenosis at 6−9 months and the risk of TLR at one year(35). Recently, the REC-CAGE FREE I trial compared paclitaxel-coated DCBs with sirolimus-eluting stents in patients with de novo noncomplex coronary artery disease. The study enrolled 2,272 patients from 41 centers in China who achieved successful target vessel predilation and randomized them 1:1 to either DCB or sirolimus-eluting stent treatment. The primary endpoint—a composite of cardiac death, target vessel myocardial infarction, and TLR at 2 years—was significantly greater in the DCB group than in the sirolimus-eluting stent group (6.4% vs. 3.4%, p = 0.0008 for non-inferiority). This difference was primarily driven by higher rates of TLR (repeat procedures) in the DCB group (3.1% vs. 1.2%)(36). Several factors may account for these findings. Subgroup analyses revealed that outcomes in patients with small vessel disease (< 3 mm diameter) were comparable between the two groups, supporting the continued use of DCBs in this subset. Furthermore, when these results are interpreted, it is important to consider several factors, including vessel diameter heterogeneity with more small vessel disease included in the DCB group, suboptimal predilation in the DCB group that could not be adequately compensated by subsequent stent implantation, better-than-expected performance of sirolimus-eluting stents, or lower performance of DCBs. These factors may have contributed to the unfavorable results observed in the overall population. A recent randomized trial compared the GENOSS DCB with the iopromide-based SeQuent Please Neo DCB in patients with de novo coronary artery disease, demonstrating non-inferiority of the GENOSS DCB in terms of 6-month in-lesion late lumen loss (0.06 ± 0.38 mm vs. 0.09 ± 0.36 mm, p for non-inferiority = 0.001) and similar clinical outcomes at 12 months(37). While that study provided valuable head-to-head comparative data between two paclitaxel-coated balloons, the present study adds complementary insights by focusing on the feasibility and detailed vascular response of GENOSS DCBs in a real world, all-comer population. In particular, our study reports a lower in-segment LLL (−0.17 ± 0.3 mm) and visual evidence of late lumen enlargement, possibly attributable to standardized lesion preparation and optimal balloon sizing, which were rigorously implemented in our protocol. Limitations This study has several limitations. First, the small sample size of 20 patients limits the generalizability of the findings. Although this pilot study provides preliminary insights into the efficacy and safety of GENOSS DCBs, larger studies are needed to confirm these results and better define device performance in broader populations. Second, the single-arm design without a control group prevents direct comparisons with other treatment modalities, such as drug-eluting stents or other drug-coated balloons. This design limitation makes it difficult to determine whether the observed outcomes are specific to GENOSS DCBs or could have been similarly achieved with alternative interventions. Third, there is potential for selection bias, as patient enrollment was based on predefined inclusion and exclusion criteria. Although the study aimed to include an all-comers population, the final cohort predominantly consisted of patients with small-vessel disease, potentially excluding those with more complex or high-risk lesions. Finally, vascular response was assessed only by quantitative coronary analysis. The use of intravascular imaging techniques such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) could have provided more detailed insights into vessel wall changes and drug delivery efficacy. Nevertheless, all angiographic analyses were performed by an experienced, study-blinded technician, ensuring consistency and minimizing interpretive bias. Despite these limitations, the present findings suggest that this novel paclitaxel-coated balloon with shellac and vitamin E excipients may be a promising treatment option for de novo coronary lesions, with minimal late lumen loss and evidence of late lumen enlargement. Conclusions This study provides preliminary evidence supporting the clinical feasibility of GENOSS DCBs in the management of de novo coronary lesions. While the results are encouraging, they should be interpreted with caution given the study’s limitations. Further large-scale, controlled trials are warranted to validate these findings and determine whether GENOSS DCBs can be established as a standard therapeutic option for de novo coronary artery disease. Abbreviations DCB = drug-coated balloon DNCL = de novo coronary lesions ISR = in-stent restenosis MLD = minimum lumen diameter RVD = reference vessel diameter DS = diameter stenosis LLL = late lumen loss TLR = target lesion revascularization TVR = target vessel revascularization Declarations Ethics approval and consent to participate All studies adhered to the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The study protocol was approved by the institutional review boards of Hallym University Kangnam Sacred Heart Hospital Institution Review Board (IRB number: 2022-12-001) and Yonsei University Health system, Severance Hospital Institutional Review Board (IRB number: 2024-0049), and written informed consent was obtained from all participants. Consent for publication Written informed consent for publication of this case details and accompanying images was obtained from the patient prior to inclusion in the manuscript. Availability of data and materials Additional data to that included in the manuscript can be provided under request. Author’s contributions Jeen Hwa Lee, Jung Rae Cho wrote the main manuscript text. All authors reviewed the manuscript. Acknowledgments: None Sources of Funding: No funds, grants, or other support was received. Disclosures The authors declare no competing interests. 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Vascular Response, Downstream Effect, and Pharmacokinetics After Sirolimus- and Paclitaxel-Coated Balloons in Porcine Coronary Arteries. Catheter Cardiovasc Interv. 2025. Tanaka A, Latib A, Jabbour RJ, Kawamoto H, Giannini F, Ancona M, et al. Impact of Angiographic Result After Predilatation on Outcome After Drug-Coated Balloon Treatment of In-Stent Coronary Restenosis. Am J Cardiol. 2016;118(10):1460-5. Kufner S, Joner M, Schneider S, Tölg R, Zrenner B, Repp J, et al. Neointimal Modification With Scoring Balloon and Efficacy of Drug-Coated Balloon Therapy in Patients With Restenosis in Drug-Eluting Coronary Stents: A Randomized Controlled Trial. JACC Cardiovasc Interv. 2017;10(13):1332-40. Ann SH, Her AY, Singh GB, Okamura T, Koo BK, Shin ES. Serial Morphological and Functional Assessment of the Paclitaxel-coated Balloon for de Novo Lesions. Rev Esp Cardiol (Engl Ed). 2016;69(11):1026-32. Ann SH, Balbir Singh G, Lim KH, Koo BK, Shin ES. Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study. PLoS One. 2016;11(1):e0147057. Pocock SJ, Lansky AJ, Mehran R, Popma JJ, Fahy MP, Na Y, et al. Angiographic surrogate end points in drug-eluting stent trials: a systematic evaluation based on individual patient data from 11 randomized, controlled trials. J Am Coll Cardiol. 2008;51(1):23-32. Gao C, He X, Ouyang F, Zhang Z, Shen G, Wu M, et al. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024;404(10457):1040-50. Shin ES, Park Y, Lee JY, Her AY, Chon MK, Kim S, et al. A Prospective Randomized Trial Comparing 2 Different Paclitaxel-Coated Balloons in De Novo Coronary Artery Disease. JACC Asia. 2025;5(1):15-24. Tables Table 1. Clinical baseline characteristics Baseline characteristics G ENOSS DCB (N=20) Age, y 66.0 ± 10.3 Male, n 14 (70.0) Body mass index, kg/m2* 26.2 ± 3.1 Hypertension, n 2 (10.0) Diabetes mellitus, n 7 (35.0) Insulin treatment, n 1 (5.0) Hyperlipidemia, n 16 (80.0) Chronic kidney disease, n 2 (10.0) Renal failure, n 2 (10.0) Prior myocardial infarction, n 4 (20.0) Prior percutaneous coronary intervention, n 8 (40.0) Prior coronary artery bypass graft, n 0 (0) Prior congestive heart failure, n 1 (5.0) Prior cerebrovascular disease, n 5 (25.0) Cancer, n 1 (5.0) Current smoker, n 3 (15.0) Clinical diagnosis Stable angina, n 16 (80.0) Unstable angina, n 2 (10.0) NSTEMI, n 2 (10.0) STEMI, n 0 (0) The values are the means ± SDs, n(%), or n. *Body mass index is the weight in kilograms divided by the square of the height in meters. DCB = drug-coated balloon; NSTEMI = non-ST-elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction Table 2. Angiographic and procedural baseline characteristics Baseline characteristics Genoss DCB (N=20) Target vessel location Left anterior descending artery, n 8 (40.0) Left circumflex artery, n 7 (35.0) Right coronary artery, n 4 (20.0) Ramus intermedius artery, n 1 (5.0) Extent of coronary artery disease One vessel disease, n 13 (65) Two vessel disease, n 4 (20) Three vessel disease, n 3 (15) Study balloon diameter, mm 15.8 ± 2.9 Study balloon length, mm 2.1 ± 0.4 Maximum study balloon pressure, atm 11.1 ± 4.5 The values are the means ± SDs, n(%), or n. DCB = drug-coated balloon Table 3. Serial quantitative coronary angiographic results Angiographic results Genoss DCB (N=20) Pre-procedure N=20 RVD, mm 2.40 ± 0.5 MLD, mm 0.53 ± 0.2 DS, % 77.7 ± 8.5 Post-DCB N=20 RVD in-segment, mm 2.20 ± 0.4 MLD in-segment, mm 1.12 ± 0.4 DS in-segment, % 48.5 ± 13.8 6-month follow-up N=20 RVD in-segment, mm 1.87 ± 1.0 MLD in-segment, mm 1.78 ± 0.3 DS in-segment, % 23.7 ± 9.3 LLL in-segment, mm -0.17 ± 0.3 The values are the means ± SDs, n(%), or n. DCB = drug-coated balloon; RVD = reference vessel diameter; MLD = minimal lumen diameter; DS = diameter stenosis; LLL = late lumen loss Table 4. Clinical outcomes at 6 months Clinical outcomes N=20 follow-up duration (days) 180 days DOCO cardiac death, n 0 myocardial infarction, n 0 TLR/TVR, n 0 POCO any death, n 0 any myocardial infarction, n 0 any revascularization, n 1 (5.0) definite and probable stent thrombosis definite stent thrombosis, n 0 probable stent thrombosis, n 0 The values are the means ± SDs, n(%), or n. DOCO = device-oriented composite outcomes; POCO = patient-oriented composite outcome; TLR = target lesion revascularization; TVR = target vessel revascularization Additional Declarations No competing interests reported. Supplementary Files 5.png Central illustration. Angiographic and morphological improvements with GENOSS DCB in de novo lesions DCB = drug-coated balloon; CAG = coronary angiography; DNCL = de novo coronary lesions; RVD = reference vessel diameter; MLD = minimal lumen diameter; DS = diameter stenosis; LLL = late lumen loss Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7696486","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":531849033,"identity":"dcc8230c-76be-4281-a05e-9fec3a1aa814","order_by":0,"name":"Jeen Hwa Lee","email":"","orcid":"","institution":"Hallym University Dongtan Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jeen","middleName":"Hwa","lastName":"Lee","suffix":""},{"id":531849034,"identity":"282751ae-b600-4148-ac20-908df9eb7c37","order_by":1,"name":"Jung Rae Cho","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApklEQVRIiWNgGAWjYBACxgaGBAaGCtK1nCHdqjZSVDPPPvDwwcd5d+QNjvc+YPhRsY0IC/oSkg1nbntmuOHMcQPGnjO3idDSw5AmzbvtMOPMGWkMzIxtxGr5O+ew/cz5z0jRwthwOLFfgo14LcmGPccOJ/fzpDEcJMovhj08iQ9+1By2bWM/xvjgRwUxWhp4EuCcA4TVA4E8AztxCkfBKBgFo2AEAwB/fzshn7JVRAAAAABJRU5ErkJggg==","orcid":"","institution":"Kangnam Sacred Heart Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jung","middleName":"Rae","lastName":"Cho","suffix":""},{"id":531849035,"identity":"2cad0646-26f2-455b-95e5-9810662a64d1","order_by":2,"name":"Jung-Sun Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jung-Sun","middleName":"","lastName":"Kim","suffix":""},{"id":531849036,"identity":"a146b875-9af1-4d13-b333-71dfc2291841","order_by":3,"name":"Dae Young Cheon","email":"","orcid":"","institution":"Hallym University Dongtan Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dae","middleName":"Young","lastName":"Cheon","suffix":""},{"id":531849037,"identity":"81720067-6431-4320-9344-c918f61665f2","order_by":4,"name":"Jaehyuk Choi","email":"","orcid":"","institution":"Hallym University Dongtan Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jaehyuk","middleName":"","lastName":"Choi","suffix":""},{"id":531849038,"identity":"999d3343-cd13-4297-96c1-6cb1b5917413","order_by":5,"name":"Yong-Joon Lee","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yong-Joon","middleName":"","lastName":"Lee","suffix":""},{"id":531849039,"identity":"79bc3d50-221e-4a21-8d96-f8281337c3f7","order_by":6,"name":"Sang-Hyup Lee","email":"","orcid":"","institution":"Yonsei University College of 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"Geum","lastName":"Shin","suffix":""},{"id":531849046,"identity":"3fdba3c0-74e0-41a9-a29e-6bdb21e3a192","order_by":13,"name":"Min-Kyung Kang","email":"","orcid":"","institution":"Kangnam Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Min-Kyung","middleName":"","lastName":"Kang","suffix":""},{"id":531849047,"identity":"21b63e26-66d5-4124-8630-fa3dc859b3cc","order_by":14,"name":"Seonghoon Choi","email":"","orcid":"","institution":"Kangnam Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Seonghoon","middleName":"","lastName":"Choi","suffix":""},{"id":531849048,"identity":"adffd62e-012f-4f08-b506-b9ab0b8b0c46","order_by":15,"name":"Namho Lee","email":"","orcid":"","institution":"Kangnam Sacred Heart Hospital","correspondingAuthor":false,"prefix":"","firstName":"Namho","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-09-23 16:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7696486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7696486/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94050601,"identity":"83f87790-e159-4894-86e0-f4378b32beeb","added_by":"auto","created_at":"2025-10-21 23:47:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":70280,"visible":true,"origin":"","legend":"\u003cp\u003eComponents of the GENOSS DCB\u003c/p\u003e\n\u003cp\u003eThe GENOSS drug-coated balloon illustration shows its key components: the balloon surface is coated with paclitaxel 3 µg/mm\u003csup\u003e2\u003c/sup\u003e and the shellac plus vitamin E excipient enhances drug retention and delivery. Radiopaque markers and a hydrophilic coating aid in precise positioning and deliverability.\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; LDL = low-density lipoprotein; TPGS = tocopherol polyethylene glycol succinate\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/83047900ec515fa485fc8e17.png"},{"id":94051049,"identity":"c5fe5988-c5d2-4f9f-9509-b5e05896dd3d","added_by":"auto","created_at":"2025-10-21 23:55:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":92786,"visible":true,"origin":"","legend":"\u003cp\u003eStructural advantages of the GENOSS DCB\u003c/p\u003e\n\u003cp\u003eSchematic comparison showing the crystalline formulation of paclitaxel used in the GENOSS DCB \u003cem\u003eversus\u003c/em\u003ethe amorphous formulations used in conventional DCBs. The shellac and vitamin E matrix in GENOSS DCB allows for optimized drug transfer and sustained tissue concentration.\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; TPGS = tocopherol polyethylene glycol succinate; PTX = paclitaxel\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/ded6e71dcda80fae181eb9cb.png"},{"id":94050600,"identity":"458b5640-f8f8-47fd-b730-551d11f97ac0","added_by":"auto","created_at":"2025-10-21 23:47:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":141344,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative frequency distribution of minimal lumen diameter\u003c/p\u003e\n\u003cp\u003eCumulative distribution curves of in-segment MLD at baseline, immediately post-DCB, and at the 6-month follow-up. The rightward shift in the follow-up curve demonstrated a consistent increase in lumen diameter over time, reflecting late lumen enlargement.\u003c/p\u003e\n\u003cp\u003eMLD = minimal lumen diameter\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/1c1fd8fb538795343d5fb6ac.png"},{"id":94050602,"identity":"c6b12d03-6042-405b-821e-5e37003b7f88","added_by":"auto","created_at":"2025-10-21 23:47:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":168410,"visible":true,"origin":"","legend":"\u003cp\u003eRepresentative angiographic and schematic outcomes after GENOSS DCB treatment in a patient with stable angina\u003c/p\u003e\n\u003cp\u003eBaseline and follow-up coronary angiography of a 73-year-old female with distal LCx stenosis treated with a 2.5x35 mm GENOSS DCB. The MLD improved from 0.35 mm to 2.34 mm at 6 months, with a calculated late lumen loss of -0.71 mm. The corresponding schematic illustrates the observed luminal gain and restoration of vessel patency.\u003c/p\u003e\n\u003cp\u003eLCx = left circumflex artery\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; RVD = reference vessel diameter; MLD = minimal lumen diameter; DS = diameter stenosis; LLL = late lumen loss\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/f70ad9f8d202822f375f24a1.png"},{"id":94051050,"identity":"c41f276a-6ac2-465a-b705-6aab07b102a0","added_by":"auto","created_at":"2025-10-21 23:56:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1254681,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/193e9fa3-de70-4fdd-9a13-97b0b6624c7c.pdf"},{"id":94050603,"identity":"02658c2e-6827-4ef4-80a6-ee669e28cf2c","added_by":"auto","created_at":"2025-10-21 23:47:55","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":274575,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentral illustration. Angiographic and morphological improvements with GENOSS DCB in de novo lesions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; CAG = coronary angiography; DNCL = de novo coronary lesions; RVD = reference vessel diameter; MLD = minimal lumen diameter; DS = diameter stenosis; LLL = late lumen loss\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7696486/v1/1639c7e98f268397ca60fa85.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Feasibility of Novel Paclitaxel-Coated Balloon with Shellac plus Vitamin E Excipient in Patients with De Novo Coronary Artery Lesion","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDrug-coated balloons (DCBs) have emerged as a key therapeutic option for in-stent restenosis (ISR), with recent guidelines acknowledging their efficacy and safety in clinical practice. DCBs deliver antiproliferative drugs directly to the vessel wall, inhibiting neointimal hyperplasia without the need for permanent implantation, which has facilitated their widespread adoption in ISR management(1-5). Recently, DCBs have also been recognized as a potential therapeutic option for treating de novo coronary lesions (DNCLs)(6-9). Several studies have demonstrated that DCBs achieve clinical outcomes comparable to those of drug-eluting stents in small coronary arteries, where stent implantation may be associated with a higher risk of complications(10-19).\u003c/p\u003e\n\u003cp\u003eVarious antiproliferative agents have been used in DCBs, but paclitaxel remains the preferred choice due to its high lipophilicity, rapid vessel wall penetration, and ability to irreversibly stabilize microtubules, effectively inhibiting neointimal hyperplasia(3, 20-23). As a result, paclitaxel-based DCBs continue to be the primary tools for clinical application. The GENOSS DCB (Genoss, Korea) incorporates a novel excipient formulation of shellac and vitamin E, designed to improve paclitaxel delivery and retention at the target lesion, potentially reducing restenosis rates compared to other DCBs. The theoretical difference in the paclitaxel formulation between GENOSS DCB (crystalline) and other DCBs (amorphous) might result in better performance, despite the paclitaxel concentration being the same at 3 µg/mm\u003csup\u003e2\u003c/sup\u003e (Figures 1, 2).\u003c/p\u003e\n\u003cp\u003eWhile preliminary studies have suggested potential benefits of this novel DCB in in-stent stenosis lesions(24), its efficacy and safety in treating DNCLs have not been comprehensively evaluated. This prospective, multicenter, single-arm study aims to evaluate the efficacy and safety of GENOSS DCBs in patients with DNCLs, focusing on angiographic outcomes. This exploratory clinical trial was conducted as part of a government project, a collaborative project between the Korea Health Industry Development Institute and Industry.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study included 20 participants from two academic centers in Korea: Hallym University Kangnam Sacred Heart Hospital and Severance Hospital. Eligible participants were adults aged 19 years or older with DNCLs measuring 2.0 mm to 4.0 mm in diameter, who required percutaneous coronary intervention (PCI). Patients with stable angina, unstable angina, or silent ischemia who had not undergone prior interventional treatment for the target lesion were included. The clinical exclusion criteria were as follows: ST-segment elevation myocardial infarction (STEMI) within the previous 48 hours, cardiogenic shock, left ventricular ejection fraction \u0026lt; 30%, severe renal impairment (estimated glomerular filtration rate [eGFR] \u0026lt; 30 mL/min), contraindications or suspected intolerance to paclitaxel, aspirin, P2Y12 inhibitors, a life expectancy of less than 1 year, and pregnancy or lactation. Angiographic exclusion criteria included restenosis lesions, bypass graft lesions, chronic total occlusions, left main coronary lesions, and angiographic findings requiring stent implantation (e.g., persistent flow limitation due to dissection, residual stenosis \u0026gt; 30%, or thrombolysis in myocardial infarction [TIMI] flow \u0026lt; 3). The study protocol was approved by the institutional review boards of Hallym University Kangnam Sacred Heart Hospital Institution Review Board (IRB number: 2022-12-001) and Yonsei University Health system, Severance Hospital Institutional Review Board (IRB number: 2024-0049), and written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter informed consent was obtained, participants underwent preprocedural evaluation and received standard medications, including antiplatelet therapy. Antiplatelet therapy consisted of a loading dose of 300 mg aspirin and 600 mg clopidogrel administered prior to coronary angiography, followed by maintenance doses of 100 mg aspirin and 75 mg clopidogrel once daily for up to 6 months post-PCI. Other medications, such as statins and antianginal agents, were administered at the physician’s discretion.\u003c/p\u003e\n\u003cp\u003eOn the day of the procedure, coronary angiography was performed to confirm eligibility criteria, and pre-dilation was conducted with a standard balloon catheter, using a balloon-to-artery ratio of 1:1. If predilation was successful, the GENOSS DCB was applied to the target lesion. The time from vascular access to balloon inflation at nominal pressure was kept within 3 minutes to minimize balloon exposure to blood prior to inflation. The drug-coated balloon catheter was inflated for 60 seconds to ensure adequate drug delivery to the vessel wall. If patients experienced discomfort, inflation was performed in two 30-second intervals. Patients in whom predilation was unsuccessful or who developed significant complications, such as severe vascular dissection, were excluded from the study and received alternative treatments according to institutional protocols. After the procedure, patients were monitored during hospitalization and followed up at 1 and 6 months for efficacy and safety assessments.\u003c/p\u003e\n\u003cp\u003eAngiographic assessments were conducted before, immediately after the procedure, and at the 6-month follow-up via analysis of identical projections. Quantitative coronary angiographic analysis was performed by an experienced technician (K.G.S from Kangnam Sacred Heart Hospital), who was blinded to study conditions. The measurements included the number of lesions, lesion location, minimum lumen diameter (MLD), reference vessel diameter (RVD), stenosis rate (%), lesion length, balloon diameter, balloon length, and balloon inflation pressure. Additionally, blood vessel dissection after predilation and the National Heart, Lung, and Blood Institute (NHLBI) classification of the dissection were recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Device\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe investigational device, the GENOSS DCB Paclitaxel-Coated PTCA Balloon Catheter, is a balloon-expandable catheter coated with paclitaxel and an excipient combination of shellac and vitamin E. The catheter is designed for rapid and effective drug delivery to the vessel wall during PCI. The hydrophilic coating and radiopaque markers ensure smooth delivery and accurate placement within the lesion. The catheter diameter ranged from 2.0 mm to 4.0 mm, and the balloon length varied from 10 mm to 40 mm. The device is approved for the treatment of in-stent restenosis but was evaluated in this study for de novo coronary artery lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Endpoints\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary efficacy endpoint was in-lesion late lumen loss (LLL) at 6 months post-procedure, as measured by coronary angiography. LLL was defined as the change in vessel diameter (MLD, mm) after 6 months, subtracted from the dilated vessel diameter (MLD, mm) immediately after intervention. The vessel diameter was measured at the narrowest section within the lesion. Other endpoints included the device success rate, defined as the successful delivery and inflation of the balloon at the target lesion with \u0026lt; 30% residual stenosis. The procedural success rate was defined as the device success rate without clinical events during hospitalization. Restenosis was defined as diameter stenosis (DS, %) of at least 50% compared to the reference vessel at 6-month follow-up coronary angiography. Target vessel failure was defined as the composite outcome of cardiac death, target-vessel myocardial infarction, or ischemia-driven target vessel revascularization. Major adverse cardiac events (MACEs) included cardiac death, myocardial infarction, stent thrombosis, target lesion revascularization (TLR), or target vessel revascularization (TVR) at 6 months post-procedure. Cardiac death was defined as any death not clearly of extracardiac origin or myocardial infarction, according to guidelines(25). Myocardial infarction was defined according to the universal definition proposed by the Society for Cardiovascular Angiography and Interventions (SCAI)(26). TLR was defined as any repeat revascularization within the DCB-treated segment, and TVR was defined as any repeat revascularization of the target vessel. Non-TLR referred to a TLR event in coronary arteries other than those treated with DCBs at the index PCI. Probable or definite stent thrombosis was defined according to the Bleeding Academic Research Consortium(BARC) criteria(27).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed on the intention-to-treat (ITT) population, including all patients who received the investigational device. Descriptive statistics summarized patient demographics, baseline characteristics, and procedural data. Continuous variables were presented as means ± standard deviations or medians with interquartile ranges, as appropriate. Categorical variables were summarized as counts and percentages. The primary efficacy endpoint, in-lesion late lumen loss, was analyzed using paired t-tests or Wilcoxon signed-rank tests, depending on the normality of data distribution. Secondary endpoints, such as device success rates and procedural success rates, were expressed as frequencies and percentages. A two-tailed p-value of \u0026lt;0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 22 (IBM; Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTwenty patients from two centers were treated with the GENOSS DCB for DNCLs. The mean age was 66.0 ± 10.3 years, and 70% were male. Baseline characteristics showed a high prevalence of cardiovascular risk factors: hyperlipidemia (80%), diabetes mellitus (35%), and prior PCI (40%). Prior to the index procedure, 20% had a history of myocardial infarction and 25% had cerebrovascular disease. Despite these comorbidities, none had undergone coronary artery bypass grafting, and only 5% had congestive heart failure. Most patients had stable angina (80%); 10% presented with unstable angina and 10% with non–ST-elevation myocardial infarction (NSTEMI) (Table 1).\u003c/p\u003e\n\u003cp\u003eThe most frequently treated vessel was the left anterior descending artery (40%), followed by the left circumflex artery (35%), right coronary artery (20%), and ramus intermedius (5%). Most patients had single-vessel disease (65%). The mean balloon diameter was 2.1 ± 0.4 mm, and the average length was 15.8 ± 2.9 mm. The maximum inflation pressure was 11.1 ± 4.5 atm (Table 2). Coronary dissection occurred in three patients and was classified as NHLBI class A.\u003c/p\u003e\n\u003cp\u003eAll patients underwent coronary angiography at 6 months. Quantitative coronary angiography showed that, before the procedure, the RVD and MLD were 2.40 ± 0.5 mm and 0.53 ± 0.2 mm, respectively, corresponding to a preprocedural DS of 77.7 ± 8.5%. Immediately after the procedure, the in-segment RVD was 2.20 ± 0.4 mm, and the MLD increased to 1.12 ± 0.4 mm, reducing the DS to 48.5 ± 13.8%. At the 6-month follow-up, the MLD further increased to 1.78 ± 0.3 mm and the DS decreased to 23.7 ± 9.3%. The primary endpoint, in-segment LLL at 6 months, was −0.17 ± 0.3 mm, indicating a slight increase in lumen diameter compared with the postprocedural measurement. No restenosis was observed on follow-up angiography (Table 3). Cumulative distribution curves for MLD at baseline, postprocedure, and follow-up are shown in Figure 3.\u003c/p\u003e\n\u003cp\u003eFor secondary endpoints, both device success and procedural success were achieved in all patients, with no procedural complications. During the 6-month follow-up, there were no cases of cardiac death, myocardial infarction, stent thrombosis, TLR, or TVR. Only one non-TLR event was observed (Table 4).\u003c/p\u003e\n\u003cp\u003eA representative case involved a 73-year-old female patient with stable angina, a history of ischemic stroke, and stage III chronic kidney disease (serum creatinine, 1.52 mg/dL; eGFR, 34 mL/min) (Figure 4). Baseline coronary angiography showed significant distal left circumflex artery stenosis, with an RVD of 1.68 mm and an MLD of 0.35 mm, corresponding to a DS of 78%. Following angioplasty with a 2.5 × 35 mm GENOSS DCB, the RVD and MLD increased to 2.09 mm and 1.63 mm, respectively, reducing the DS to 22%. At the 6-month follow-up on guideline-directed medical therapy, including dual antiplatelet therapy (aspirin and clopidogrel) and statins, follow-up angiography showed further luminal enlargement, with an RVD of 2.60 mm, an MLD of 2.34 mm, and a DS of 10%. This case exemplifies “late lumen enlargement,” with a calculated LLL of −0.71 mm.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective pilot study evaluated the clinical feasibility of the GENOSS DCB, a novel paclitaxel-coated balloon with a shellac and vitamin E excipient, in patients with DNCLs. The GENOSS DCB demonstrated an increase in the MLD at the 6-month follow-up compared with the postprocedure state (in-segment LLL: –0.17 ± 0.3 mm), consistent with the late lumen enlargement. No cases of restenosis were observed, and DS improved from 48.5 ± 13.8% post-procedure to 23.7 ± 9.3% at follow-up. Procedural outcomes were favorable, with 100% device and procedural success rates and no MACE, including cardiac death, myocardial infarction, stent thrombosis, or TLR, reported during the follow-up period.\u003c/p\u003e\n\u003cp\u003ePrevious randomized trials assessing paclitaxel-coated DCBs in de novo small vessel disease have consistently reported that in-segment LLL at follow-up angiography is lower than that of drug-eluting stents(11, 13, 16). The BELLO (Balloon Elution and Later Loss Optimization) trial reported an in-segment LLL of 0.05 ± 0.37 mm at the 6-month follow-up angiography after paclitaxel-coated DCB treatment(11), and the RESTORE SVD (Assess the Efficacy and Safety of RESTORE Paclitaxel Eluting Balloon Versus RESOLUTE Zotarolimus Eluting Stent for the Treatment of Small Coronary Vessel Disease) study demonstrated an in-segment LLL of 0.25 ± 0.42 mm at the 9-month follow-up(13). The PICCOLETO II (Drug Eluting Balloon Efficacy for Small Vessel Disease Treatment) trial reported an even lower in-segment LLL of 0.01 ± 0.25 mm at 6 months(16). A single-center study evaluated the effects on the side-branch ostium after treatment of DNCLs of the main vessels with paclitaxel-coated balloons assessed with optical coherence tomography (OCT). The Sequent Please DCB (B. Braun, Melsungen, Germany) was used in this trial, and the in-segment LLL of the main vessels was –0.01 ± 0.18 mm at 9 months, along with an increase in the side-branch ostial lumen area(28). In comparison, our study reported an in-segment LLL of –0.17 ± 0.3 mm at 6 months following treatment with the GENOSS DCB, suggesting a favorable angiographic response relative to previous reports. While cross-trial comparisons should be interpreted with cautious, these findings suggest that the GENOSS DCB may yield competitive luminal outcomes among current paclitaxel-coated balloons technologies.\u003c/p\u003e\n\u003cp\u003eA potential explanation for late lumen enlargement is that paclitaxel has been shown to induce positive vascular remodeling over time, which may have contributed to the lower LLL(20, 21, 29). This mechanism is supported by histopathological findings from preclinical studies comparing sirolimus- and paclitaxel-coated balloons, where paclitaxel demonstrated greater neointimal modulation(30). However, considering that prior randomized studies using paclitaxel-coated DCBs have reported varying degrees of LLL(11, 13, 16), additional factors may also have influenced our results. A distinguishing feature of our study was the use of a standardized, mandatory lesion preparation protocol, in which all patients underwent sufficient predilation before DCB application. This ensures optimal vessel compliance and drug uptake and is consistent with the recommendations of the International DCB Consensus Group(10). In contrast, earlier studies allowed lesion preparation at the discretion of the operator, which may have introduced variability in balloon expansion and drug delivery. Optimal lesion preparation has been associated with reduced adverse event rates following DCB treatment(31, 32), and the Consensus Group recommends the use of a semi- or noncompliant balloon with a balloon-to-artery ratio of 1:1(10). Recent studies that adopted this standardized predilation protocol also reported luminal enlargement after paclitaxel-coated DCB use. Such luminal enlargement can also be assessed by either OCT(28, 33) or intravascular ultrasound (IVUS) immediately after DCB intervention and at follow-up, revealing an increased MLD and lumen area(34). These procedural refinements may have contributed to the improved acute luminal gain and sustained vessel patency observed in our cohort.\u003c/p\u003e\n\u003cp\u003eIn addition, our study demonstrated favorable clinical results, with no major adverse cardiac events observed at the 6-month follow-up, except for a single case of nontarget vessel revascularization. In contrast, other studies evaluating DCBs in de novo coronary lesions have reported higher clinical event rates at 12 months. For example, the BELLO trial reported a 10.0% MACE rate(11), whereas the PICCOLETO II and RESTORE SVD studies reported MACE rates of 5.6% and 4.4%, respectively, at one year(13, 16). In the BASKET-SMALL 2 (Basel Stent Kosten-Effektivitäts Trial-Drug-Coated Balloons versus Drug-eluting Stents in Small Vessel Interventions) trial, the DCB group experienced a 7.5% of MACE, including 3.1% cardiac death, 1.6% myocardial infarction, 3.4% TVR, and 0.79% of stent thrombosis(14). Although the shorter follow-up period in our study limits direct comparison, the comparable angiographic parameters (LLL and DS) suggest that the favorable clinical outcomes may be sustained over time. This projection is supported by previous studies demonstrating a strong correlation between late lumen loss and diameter stenosis at 6−9 months and the risk of TLR at one year(35).\u003c/p\u003e\n\u003cp\u003eRecently, the REC-CAGE FREE I trial compared paclitaxel-coated DCBs with sirolimus-eluting stents in patients with de novo noncomplex coronary artery disease. The study enrolled 2,272 patients from 41 centers in China who achieved successful target vessel predilation and randomized them 1:1 to either DCB or sirolimus-eluting stent treatment. The primary endpoint—a composite of cardiac death, target vessel myocardial infarction, and TLR at 2 years—was significantly greater in the DCB group than in the sirolimus-eluting stent group (6.4% vs. 3.4%, \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.0008 for non-inferiority). This difference was primarily driven by higher rates of TLR (repeat procedures) in the DCB group (3.1% vs. 1.2%)(36). Several factors may account for these findings. Subgroup analyses revealed that outcomes in patients with small vessel disease (\u0026lt; 3 mm diameter) were comparable between the two groups, supporting the continued use of DCBs in this subset. Furthermore, when these results are interpreted, it is important to consider several factors, including vessel diameter heterogeneity with more small vessel disease included in the DCB group, suboptimal predilation in the DCB group that could not be adequately compensated by subsequent stent implantation, better-than-expected performance of sirolimus-eluting stents, or lower performance of DCBs. These factors may have contributed to the unfavorable results observed in the overall population.\u003c/p\u003e\n\u003cp\u003eA recent randomized trial compared the GENOSS DCB with the iopromide-based SeQuent Please Neo DCB in patients with de novo coronary artery disease, demonstrating non-inferiority of the GENOSS DCB in terms of 6-month in-lesion late lumen loss (0.06 ± 0.38 mm vs. 0.09 ± 0.36 mm, \u003cem\u003ep\u003c/em\u003e for non-inferiority = 0.001) and similar clinical outcomes at 12 months(37). While that study provided valuable head-to-head comparative data between two paclitaxel-coated balloons, the present study adds complementary insights by focusing on the feasibility and detailed vascular response of GENOSS DCBs in a real world, all-comer population. In particular, our study reports a lower in-segment LLL (−0.17 ± 0.3 mm) and visual evidence of late lumen enlargement, possibly attributable to standardized lesion preparation and optimal balloon sizing, which were rigorously implemented in our protocol.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study has several limitations. First, the small sample size of 20 patients limits the generalizability of the findings. Although this pilot study provides preliminary insights into the efficacy and safety of GENOSS DCBs, larger studies are needed to confirm these results and better define device performance in broader populations. Second, the single-arm design without a control group prevents direct comparisons with other treatment modalities, such as drug-eluting stents or other drug-coated balloons. This design limitation makes it difficult to determine whether the observed outcomes are specific to GENOSS DCBs or could have been similarly achieved with alternative interventions. Third, there is potential for selection bias, as patient enrollment was based on predefined inclusion and exclusion criteria. Although the study aimed to include an all-comers population, the final cohort predominantly consisted of patients with small-vessel disease, potentially excluding those with more complex or high-risk lesions. Finally, vascular response was assessed only by quantitative coronary analysis. The use of intravascular imaging techniques such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) could have provided more detailed insights into vessel wall changes and drug delivery efficacy. Nevertheless, all angiographic analyses were performed by an experienced, study-blinded technician, ensuring consistency and minimizing interpretive bias. Despite these limitations, the present findings suggest that this novel paclitaxel-coated balloon with shellac and vitamin E excipients may be a promising treatment option for de novo coronary lesions, with minimal late lumen loss and evidence of late lumen enlargement.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study provides preliminary evidence supporting the clinical feasibility of GENOSS DCBs in the management of de novo coronary lesions. While the results are encouraging, they should be interpreted with caution given the study’s limitations. Further large-scale, controlled trials are warranted to validate these findings and determine whether GENOSS DCBs can be established as a standard therapeutic option for de novo coronary artery disease.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eDCB = drug-coated balloon\u003c/p\u003e\n\u003cp\u003eDNCL = de novo coronary lesions\u003c/p\u003e\n\u003cp\u003eISR = in-stent restenosis\u003c/p\u003e\n\u003cp\u003eMLD = minimum lumen diameter\u003c/p\u003e\n\u003cp\u003eRVD = reference vessel diameter\u003c/p\u003e\n\u003cp\u003eDS = diameter stenosis\u003c/p\u003e\n\u003cp\u003eLLL = late lumen loss\u003c/p\u003e\n\u003cp\u003eTLR = target lesion revascularization\u003c/p\u003e\n\u003cp\u003eTVR = target vessel revascularization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll studies adhered to the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.\u0026nbsp;The study protocol was approved by the institutional review boards of Hallym University Kangnam Sacred Heart Hospital Institution Review Board (IRB number: 2022-12-001) and Yonsei University Health system, Severance Hospital Institutional Review Board (IRB number: 2024-0049), and written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of this case details and accompanying images was obtained from the patient prior to inclusion in the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdditional data to that included in the manuscript can be provided under request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor’s contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJeen Hwa Lee, Jung Rae Cho wrote the main manuscript text. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of Funding:\u0026nbsp;\u003c/strong\u003eNo funds, grants, or other support was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNeumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40(2):87-165.\u003c/li\u003e\n\u003cli\u003eByrne RA, Neumann FJ, Mehilli J, Pinieck S, Wolff B, Tiroch K, et al. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. 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JACC Asia. 2022;2(2):170-9.\u003c/li\u003e\n\u003cli\u003eThygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. Circulation. 2012;126(16):2020-35.\u003c/li\u003e\n\u003cli\u003eMoussa ID, Klein LW, Shah B, Mehran R, Mack MJ, Brilakis ES, et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI). J Am Coll Cardiol. 2013;62(17):1563-70.\u003c/li\u003e\n\u003cli\u003eCutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115(17):2344-51.\u003c/li\u003e\n\u003cli\u003eHer AY, Ann SH, Singh GB, Kim YH, Okamura T, Garg S, et al. 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Am J Cardiol. 2016;118(10):1460-5.\u003c/li\u003e\n\u003cli\u003eKufner S, Joner M, Schneider S, T\u0026ouml;lg R, Zrenner B, Repp J, et al. Neointimal Modification With Scoring Balloon and Efficacy of Drug-Coated Balloon Therapy in Patients With Restenosis in Drug-Eluting Coronary Stents: A Randomized Controlled Trial. JACC Cardiovasc Interv. 2017;10(13):1332-40.\u003c/li\u003e\n\u003cli\u003eAnn SH, Her AY, Singh GB, Okamura T, Koo BK, Shin ES. Serial Morphological and Functional Assessment of the Paclitaxel-coated Balloon for de Novo Lesions. Rev Esp Cardiol (Engl Ed). 2016;69(11):1026-32.\u003c/li\u003e\n\u003cli\u003eAnn SH, Balbir Singh G, Lim KH, Koo BK, Shin ES. Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study. PLoS One. 2016;11(1):e0147057.\u003c/li\u003e\n\u003cli\u003ePocock SJ, Lansky AJ, Mehran R, Popma JJ, Fahy MP, Na Y, et al. Angiographic surrogate end points in drug-eluting stent trials: a systematic evaluation based on individual patient data from 11 randomized, controlled trials. J Am Coll Cardiol. 2008;51(1):23-32.\u003c/li\u003e\n\u003cli\u003eGao C, He X, Ouyang F, Zhang Z, Shen G, Wu M, et al. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024;404(10457):1040-50.\u003c/li\u003e\n\u003cli\u003eShin ES, Park Y, Lee JY, Her AY, Chon MK, Kim S, et al. A Prospective Randomized Trial Comparing 2 Different Paclitaxel-Coated Balloons in De Novo Coronary Artery Disease. JACC Asia. 2025;5(1):15-24.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Clinical baseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eG\u003c/strong\u003e\u003cstrong\u003eENOSS\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;DCB (N=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge, y\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66.0\u0026nbsp;\u0026plusmn;\u0026nbsp;10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBody mass index, kg/m2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26.2\u0026nbsp;\u0026plusmn;\u0026nbsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHypertension, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDiabetes mellitus, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (35.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Insulin treatment, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHyperlipidemia, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChronic kidney disease, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRenal failure, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior myocardial infarction, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior percutaneous coronary intervention, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior coronary artery bypass graft, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior congestive heart failure, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePrior cerebrovascular disease, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCancer, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCurrent smoker, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eClinical diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Stable angina, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Unstable angina, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;NSTEMI, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;STEMI, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe values are the means\u0026nbsp;\u0026plusmn;\u0026nbsp;SDs, n(%), or n.\u003c/p\u003e\n\u003cp\u003e*Body mass index is the weight in kilograms divided by the square of the height in meters.\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; NSTEMI = non-ST-elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Angiographic and procedural baseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGenoss DCB (N=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTarget vessel location\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft anterior descending artery, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLeft circumflex artery, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7 (35.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRight coronary artery, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRamus intermedius artery, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eExtent of coronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOne vessel disease, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTwo vessel disease, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThree vessel disease, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStudy balloon diameter, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15.8\u0026nbsp;\u0026plusmn;\u0026nbsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStudy balloon length, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.1\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMaximum study balloon pressure, atm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11.1\u0026nbsp;\u0026plusmn;\u0026nbsp;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe values are the means\u0026nbsp;\u0026plusmn;\u0026nbsp;SDs, n(%), or n.\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Serial quantitative coronary angiographic results\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAngiographic results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenoss DCB (N=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePre-procedure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eN=20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRVD, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.40\u0026nbsp;\u0026plusmn;\u0026nbsp;0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMLD, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.53\u0026nbsp;\u0026plusmn;\u0026nbsp;0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDS, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e77.7\u0026nbsp;\u0026plusmn;\u0026nbsp;8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePost-DCB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eN=20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRVD in-segment, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.20\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMLD in-segment, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.12\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDS in-segment, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e48.5\u0026nbsp;\u0026plusmn;\u0026nbsp;13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6-month follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eN=20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRVD in-segment, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.87\u0026nbsp;\u0026plusmn;\u0026nbsp;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMLD in-segment, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.78\u0026nbsp;\u0026plusmn;\u0026nbsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDS in-segment, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23.7\u0026nbsp;\u0026plusmn;\u0026nbsp;9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLLL in-segment, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-0.17\u0026nbsp;\u0026plusmn;\u0026nbsp;0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe values are the means\u0026nbsp;\u0026plusmn;\u0026nbsp;SDs, n(%), or n.\u003c/p\u003e\n\u003cp\u003eDCB = drug-coated balloon; RVD = reference vessel diameter; MLD = minimal lumen diameter; DS = diameter stenosis; LLL = late lumen loss\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Clinical outcomes at 6 months\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003efollow-up duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e180 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDOCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ecardiac death, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003emyocardial infarction, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTLR/TVR, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePOCO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eany death, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eany myocardial infarction, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eany revascularization, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003edefinite and probable stent thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003edefinite stent thrombosis, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eprobable stent thrombosis, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe values are the means\u0026nbsp;\u0026plusmn;\u0026nbsp;SDs, n(%), or n.\u003c/p\u003e\n\u003cp\u003eDOCO = device-oriented composite outcomes; POCO = patient-oriented composite outcome; TLR = target lesion revascularization; TVR = target vessel revascularization\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"drug-coated balloon, percutaneous coronary intervention, paclitaxel, de novo lesions, coronary artery disease","lastPublishedDoi":"10.21203/rs.3.rs-7696486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7696486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDrug-coated balloons (DCBs) are increasingly used for de novo coronary lesions (DNCLs), particularly in small vessels. The GENOSS DCB is a novel paclitaxel-coated balloon using a shellac plus vitamin E excipient, previously effective in in-stent restenosis, but its feasibility in DNCLs remains unclear. This study evaluated the clinical feasibility of GENOSS DCBs in DNCLs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a prospective, multicenter, single-arm pilot study of patients with DNCLs (2.0–4.0 mm in diameter). The primary endpoint was in-segment late lumen loss (LLL) at 6 months. Secondary endpoints included device/procedure success rate, restenosis rate, cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization (TLR) at 6-month follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 20 patients (mean age 66.0 ± 10.3 years; 70% male) were enrolled from two academic centers. Device and procedure success was achieved in all patients. The 6-month in-segment LLL was –0.17 ± 0.3 mm, and no restenosis was observed. Diameter stenosis improved from 48.5 ± 13.8% post-DCB to 23.69 ± 9.3% at 6 months. One non-TLR was reported, with no cardiac death, myocardial infarction, stent thrombosis, or TLR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGENOSS DCBs showed favorable angiographic and clinical outcomes at 6 months, supporting their feasibility as a treatment for DNCLs.\u003c/p\u003e","manuscriptTitle":"Clinical Feasibility of Novel Paclitaxel-Coated Balloon with Shellac plus Vitamin E Excipient in Patients with De Novo Coronary Artery Lesion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-21 23:47:50","doi":"10.21203/rs.3.rs-7696486/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"56bf50e5-f086-4dc7-8508-27e77890b807","owner":[],"postedDate":"October 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-21T23:47:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-21 23:47:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7696486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7696486","identity":"rs-7696486","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}