Optical Coherence Tomography-Guided PCI for ISHLT Grade 3 Cardiac Allograft Vasculopathy: A 1 -Year Follow-Up Case Report

Optical Coherence Tomography-Guided PCI for ISHLT Grade 3 Cardiac Allograft Vasculopathy: A 1 -Year Follow-Up Case Report | 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 Case Report Optical Coherence Tomography-Guided PCI for ISHLT Grade 3 Cardiac Allograft Vasculopathy: A 1 -Year Follow-Up Case Report Yuan Liang, Yan Wang, Youcheng Shen, Zhijiang Liu, Changyin Shen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6644260/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: International Society for Heart and Lung Transplantation (ISHLT) Grade 3 cardiac allograft vasculopathy (CAV) poses challenges for revascularization due to diffuse fibrotic lesions and neovascularization. While optical coherence tomography (OCT) enables high-resolution imaging, evidence for OCT-guided percutaneous coronary intervention (PCI) in high-risk patients with comorbidities like chronic kidney disease (CKD), chronic hepatitis B (CHB), or metabolic dysfunction remains limited. Case Presentation: A 39-year-old male with ISHLT Grade 3 CAV, CKD stage 3b, (eGFR 42.5 mL/min/1.73 m²), CHB, and severe hyperglycemia (HbA1c 15.7%) underwent OCT-guided PCI. Coronary angiography(CAG) revealed diffuse stenosis in the left anterior descending (LAD) and right coronary artery (RCA). OCT identified fibrotic-neovascular plaques in the LAD and fibrotic-lipidic plaques in the RCA, prompting implantation of sirolimus-eluting stents (SES) to address CAV-specific neointimal hyperplasia. To mitigate CKD-related risks, iso-osmolar contrast, pre-procedural hydration, aspirin and clopidogrel were used for antiplatelet therapy. At 6-month follow-up, CAG/OCT showed patent stents with minimal neointimal hyperplasia and a Type B dissection in the proximal RCA, which was successfully managed with additional SES implantation. At 1-year, coronary computed tomography angiography (CCTA) confirmed sustained stent patency without new stenosis; renal function remained stable (eGFR 47.88 mL/min/1.73 m²), improved glycemic control(HbA1c 8.3%), and no major adverse events occurred. Conclusion: This case shows OCT-guided SES implantation is feasible in high-risk CAV patients with complex conditions, highlighting OCT’ s role in precise lesion assessment and risk-adaptive strategies that led to stable outcomes at 1 year. Despite its single-case nature, it underscores the need for larger studies to confirm long-term benefits. Cardiac allograft vasculopathy Optical coherence tomography Percutaneous coronary intervention Figures Figure 1 Figure 2 Figure 3 Introduction CAV, a leading post-transplant complication, affects 30% adults with significant coronary disease within 5 years [1]. Driven by alloimmune-mediated endothelial injury, CAV features diffuse intimal fibrosis, neovascularization, and smooth muscle proliferation—distinct from atherosclerosis. ISHLT Grade 3 CAV (≥50% stenosis in ≥2 major vessels, often involving branches) causes progressive ischemia, limited revascularization, and high restenosis due to vessel rigidity. Conventional angiography has limited ability to identify intravascular lesions, while intravascular ultrasound (IVUS, 100–150 μm resolution) fails to detect small neovessels (50–100 μm) and fibrotic plaques, hindering stent optimization and increasing risks. OCT optimizes revascularization with high-resolution (10–20 μm) imaging, visualizing small neovessels and fibrous/lipid plaques missed by angiography and IVUS due to lower resolution. A landmark review by Volleberg et al. showed that OCT-guided PCI reduces stent underexpansion by 30% and detects edge dissections, key predictors of late stent failure, particularly in complex fibrotic or neovascular lesions [2]. Although 2023 ISHLT guidelines(Class IIa, Level B) recommend SES for neointimal hyperplasia in CAV [3], evidence for OCT-guided strategies in high-risk subgroups including stage 3b CKD, CHB, and metabolic dysfunction remains limited, These patients face heightened risks of contrast nephropathy, bleeding, and stent failure due to overlapping pathobiological mechanisms (e.g., uremic toxin-induced fibrosis, viral-mediated immune activation, and metabolic endothelial damage). Here, we report a complex case of ISHLT Grade 3 CAV managed with OCT-guided SES implantation, demonstrating 1-year outcomes and actionable insights for high-risk populations. Case Presentation A 39-year-old East Asian male presented with a 3-month history of recurrent presyncope (2 episodes, triggered by standing) and NYHA class III dyspnea (limiting to climbing one flight of stairs, resolving at rest), without chest pain or hemoptysis. In 2018, he underwent orthotopic heart transplantation for dilated cardiomyopathy, with a long-term immunosuppressive regimen including tacrolimus 2 mg daily (target trough 5–10 ng/mL, 7.8 ng/mL in February 2023) and mycophenolate mofetil (MMF) 1000 mg twice daily. Another medical history included pre-transplantation CHB (treated with entecavir 0.5 mg daily, undetectable viral load) and stage 3b CKD, which progressed from normal renal function to stage 3b over 4 years post-transplant due to tacrolimus-induced nephrotoxicity. No hereditary cardiovascular or renal diseases reported in his family history. Physical examination showed heart rate 83 bpm, blood pressure 125/76 mmHg, SpO₂ 97% on low-flow oxygen (2 L/min via nasal cannula), respiratory rate 21/min. Laboratory findings included: Inflammation: Leukocytosis 11.00×10⁹/L, elevated high-sensitivity C-reactive protein 3.92 mg/L, and erythrocyte sedimentation rate 26 mm/h, without evidence of acute infection or autoimmune activation. CKD stage 3b：Serum creatinine 153 μmol/L, urine protein negative (dipstick), eGFR 42.50 mL/min/1.73 m² by the CKD-EPI equation(stable 40–45 mL/min/1.73 m² over 1 year, tacrolimus nephrotoxicity) Cardiac biomarkers: High-sensitivity troponin T 11.58 ng/L and creatine kinase-MB 21 U/L within normal limits, ruling out acute coronary syndrome. Heart failure：Brain natriuretic peptide 781 pg/mL. Metabolism：Random glucose 29.2 mmol/L, HbA1c 15.7%, and urine glucose (++++), urine ketones negative, initiated basal-bolus insulin regimen (8 units insulin aspart pre-meal, 18 units insulin glargine at bedtime). Triglycerides 2.89 mmol/L, low-density lipoprotein cholesterol (LDL-C, 2.03 mmol/L), and high-density lipoprotein cholesterol 0.72 mmol/L. Immunosuppression and hepatitis B status: tacrolimus trough level 6.9 ng/mL; CHB (HBsAg positive, HBV DNA 331 IU/mL, stable on entecavir with undetectable viral load). Electrocardiography showed sinus rhythm (78 bpm) with a QRS duration of 83 ms, QTc of 445 ms, and nonspecific T wave changes. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 54%, mild left atrial enlargement (40 mm; normal <34 mm), and 1+ Doppler mitral regurgitation, E/e' ratio 15 (elevated left ventricle filling pressure), without regional wall motion abnormalities. CCTA demonstrated 60–90% stenosis in the LAD and RCA arteries. Chest CT showed mild bilateral pulmonary fibrosis and small calcified nodules in the left upper lobe (chronic changes no active infection or pulmonary embolism). Preliminary diagnosis: 1) ISHLT Grade 3 CAV; 2) Ischemic cardiomyopathy with heart failure (NYHA Class III). 3) Chronic hepatitis B virus infection 4)Type 2 diabetes mellitus. Per 2023 ISHLT guidelines (Class IIb Level C) [3], re-transplantation is a definitive cure for advanced CAV but carries risks of rejection, complications, and long-term management challenges. The patient declined it due to economic and donor limitations. For coronary revascularization, given the patient's multiple comorbidities, PCI was chosen via shared decision-making to avoid CABG-related acute kidney injury risk and mitigate surgical stress worsening CHB reactivation or hyperglycemia complications. Despite tacrolimus nephrotoxicity, the perioperative dose was maintained at 2 mg daily (trough 6.6–7.8 ng/mL) to avoid acute rejection risk: reducing levels below 5 ng/mL increases acute cellular rejection risk, especially during the proinflammatory PCI period. This decision was supported by stable eGFR (40–48 mL/min/1.73 m² for 1 year) and negative urine protein, indicating controlled nephrotoxicity without active injury. Guided by 2023 ISHLT recommendations (Class IIa, Level B) [3], SES were prioritized over bare-metal stents and paclitaxel-eluting stents (PES) to target CAV-specific neointimal hyperplasia, a process driven by alloimmune-mediated smooth muscle cell proliferation. This selection capitalized on SES’ s mechanistic specificity: mTOR pathway inhibition directly addresses the fibroproliferative phenotype of CAV lesions, whereas PES—by suppressing cell migration rather than proliferation—are less aligned with CAV’ s underlying pathology of intimal fibrosis and neovascularization. To minimize contrast nephropathy, pre-procedural hydration hydration included pre-procedural isotonic saline (1 mL/kg/h, 6h prior) and post-procedural continuation at the same rate for 12h. Dual antiplatelet therapy(DAPT) included 300 mg aspirin and 600 mg clopidogrel (loading doses), preferred over renally excreted agents (e.g., ticagrelor) to balance ischemic and bleeding risks in CKD. SES implantation followed OCT guidance (Dragonfly Duo catheter) and OCT images were analyzed by a blinded core laboratory according to 2012 consensus standards [4], measuring minimum lumen area (MLA) and minimum stent area (MSA) to guide optimal stent apposition and sizing. CAG revealed diffuse long-segment stenosis in proximal/mid LAD (90% stenosis, TIMI 2–3 flow) and proximal/mid RCA (subtotal occlusion, TIMI 2 flow), with a normal left circumflex (TIMI 3 flow). Guided by SYNTAX I score 12, PCI with OCT optimization addressed diffuse fibrotic lesions: after non-compliant balloon pre-dilation (2.0×20 mm, 12 atm, 6 seconds) in LAD, OCT showed fibrotic plaques with neovessels (50–150 μm diameter, 3–5 vessels/mm²; MLA 0.65 mm², proximal/distal reference diameters 1.76/1.12 mm, no severe calcification), prompting sequential 2.5×38 mm and 3.0×26 mm SES implantation (3 mm overlap) with 13–15 atm post-dilation (10 seconds) for MSA 4.21 mm² (80% expansion) and final TIMI 3 flow/complete coverage; in RCA, after Miracle 3 guidewire passage and compliant balloon pre-dilation (2.0×20 mm, 10–12 atm, 6 seconds), OCT identified fibrotic-lipidic plaques (MLA 1.79 mm², proximal/distal reference diameters 1.99/1.90 mm), leading to two 2.75×28 mm SES deployed at 13–15 atm (7 seconds) with high-pressure post-dilation (same pressure, 7 seconds) for MSA 5.61 mm² (85% expansion) and angiographic TIMI 3 flow/full coverage. Unfractionated heparin maintained ACT 250–300 seconds, and iso-osmolar contrast(250ml) minimized nephropathy risk The final diagnosis confirmed ISHLT Grade 3 CAV criteria, necessitating revascularization for ischemia and functional improvement. Postoperatively, NYHA class improved from III to II, with resolved dizziness/dyspnea and only mild exertional fatigue (CCS I). Post-procedural 24-hour serum creatinine was 159 μmol/L, eGFR 48.54 mL/min/1.73 m². DAPT included aspirin 100 mg + clopidogrel 75 mg daily for 12 months, followed by lifelong aspirin (100 mg) to balance risks; atorvastatin 20 mg daily targeted LDL-C <1.8mol/L, and tacrolimus trough levels were maintained at 6–7 ng/mL to minimize nephrotoxicity (no dose changes during PCI). At 6-month follow-up, CAG/OCT revealed a 5-mm Type B dissection in the proximal RCA with medial involvement, 30% residual stenosis, and TIMI 3 flow. Based on OCT-measured depth and stenosis, a 4.0×12 mm SES was implanted to cover the lesion, remain TIMI 3 flow and suppressing neointimal hyperplasia via local sirolimus release to avoid late stent failure from untreated dissections. 12-month outcomes showed stable HbA1c 8.3%, LDL-C 56 mg/dL, CKD stage 3b (eGFR 47.88 mL/min1.73 m²), CCTA-confirmed stent patency (no new stenosis), stable tacrolimus levels (6.6–6.9 ng/mL), and no major complications. Discussion and conclusion CAV, a leading cause of late graft failure, poses challenges in patients with complex comorbidities. This case demonstrates the feasibility of OCT-guided SES implantation in ISHLT Grade 3 CAV with stage 3b CKD, CHB, and severe hyperglycemia, achieving stable 1-year outcomes. The patient’s comorbidities likely accelerated CAV via distinct mechanisms, shaping OCT-visible plaques. CKD drives vascular fibrosis as uremic toxins like asymmetric dimethylarginine activate mTOR, inducing coronary (e.g., LAD) smooth muscle fibrosis and 50–150 μm neovessels (3–5/mm²), worsened by oxidative stress, inflammation, and microRNA/EV signaling. SES target mTOR locally to suppress fibrosis and neovascularization in CKD-related vascular injury[5]. Severe hyperglycemia damages endothelial cells via mitochondrial stress (reactive oxygen species) and accumulation of advanced glycation end-products (AGEs), promoting the formation of RCA fibrous-lipidic plaques. Concurrently, transforming growth factor-β (TGF-β) upregulation drives smooth muscle cell migration, exacerbating intimal hyperplasia. This pathogenic cascade—mediated by mammalian target of mTOR pathway activation—is more effectively mitigated by SES, which locally inhibit mTOR to suppress both fibroproliferation and AGEs-induced oxidative stress, compared to PES, whose anti-migration effects are limited to smooth muscle cell kinetics without addressing the upstream mitochondrial/AGEs-mTOR axis.[6-7]. CHB promotes CAV via residual inflammation and metabolic dysfunction even with long-term entecavir suppression of HBV: persistent liver inflammation releases IL-6/TNF-α to damage endothelial cells, induce adhesion molecules, and facilitate immune cell infiltration[8], while Treg dysfunction and Th1 overactivation exacerbate chronic rejection-related vascular inflammation[9]. Meanwhile, lipid disorders drive smooth muscle cell proliferation through the mTOR pathway, and oxidative stress impairs endothelial repair by reducing nitric oxide (NO) and increasing endothelin-1 (ET-1), collectively accelerating CAV progression. CAG remain standard for CAV assessment(Class Ia, Level C) [3], but its 2D imaging underestimates vessel wall disease (e.g., intimal hyperplasia), leading to poor stent sizing and higher in-stent restenosis(ISR) risk. In small vessels (≤2.5 mm, common in CAV), SES guided by CAG alone has a 39% ISR rate (vs. 17% in larger vessels, P=0.003)[10]. To address these limitations, IVUS and OCT serve as critical adjuncts to CAG. 2023 ISHLT guidelines recommend OCT combined with CAG for CAV assessment as Class IIa, level C, while IVUS combined with CAG is Class IIb, level C, but OCT’ s 10–20 μm resolution allows for better visualization of subtle CAV lesions such as intimal hyperplasia, neovascularization, and thrombus. A 2021 state-of-the-art review emphasized OCT’ s role in visualizing layered fibrotic plaques and neovessels, critical for tailoring stent dimensions in rigid, diffusely diseased vessels[11]. Besides, the ILUMIEN IV trial （NCT03507777） demonstrated that OCT-guided PCI achieved larger MSA(5.72 vs. 5.36 mm², P<0.001) and 64% lower stent thrombosis in complex CAD lesions [12], but direct evidence for CAV is lacking. Furthermore, in CKD patients, OCT’ s extra contrast use poses more contrast nephropathy risk without prophylaxis due to poor renal clearance. Besides, its shallow penetration (1–2 mm) requires IVUS for deep calcifications (≥500 μm), a contrast-free, CKD-safe tool. Combining OCT precision with IVUS safety in guiding coronary revascularization may balance accuracy and safety, critical for high-risk patients with CKD and complex lesions. Future research is warranted to determine their long-term efficacy and safety in this specific population. Calcineurin inhibitors (CNIs) and MMF suppress immune cell activation but do not address CAV’ s key drivers: smooth muscle proliferation and neointimal hyperplasia. Guidelines recommend mTOR inhibitors (e.g., sirolimus) for their dual action: suppressing T-cell-mediated immunity while directly inhibiting vascular smooth muscle cell proliferation and neointimal formation but systemic mTOR inhibition was contraindicated here due to CKD and uncontrolled diabetes. When systemic mTOR inhibition was contraindicated, a SES offered a localized solution: a 2021 analysis showed SES had no binary restenosis at 6 months [0% vs. 4% with everolimus-eluting stents(EES), P＞0.05], aligning with SES’ s ability to inhibit neointimal hyperplasia at the lesion site—critical for CAV’ s diffuse intimal fibrotic and neovascular lesions [13]. This strategy avoids the systemic side `effects of oral mTOR inhibitors while capitalizing on the rapamycin analogue’ s proven efficacy in suppressing smooth muscle proliferation, as supported by comparable late lumen loss (0.14 ± 0.15 mm for SES vs. 0.19 ± 0.15 mm for EES). This leverages SES to deliver sirolimus directly to OCT-identified lesions, inhibiting local smooth muscle proliferation and avoiding systemic toxicity—critical for patients intolerant of oral mTOR inhibitors. By using localized rapamycin analogues, this approach balances guideline-recommended mTOR inhibition with patient comorbidities, offering a pragmatic CAV revascularization strategy. Considering the diffuse and progressive lesion patterns of CAV, both CABG and PCI are considered palliative therapies. CABG as a salvage strategy, especially when ISR cannot be controlled by medical therapy or repeat PCI, is limited by CAV’s diffuse distal small-vessel involvement (<2.0 mm), making anastomosis hard and revascularization incomplete; grafts (especially venous) develop accelerated intimal hyperplasia in the immunoinflammatory environment, with poor long-term patency. Comorbidities like CKD and diabetes further raise surgery risks like acute kidney injury and wound issues. Besides, a meta-analysis of 1,520 patients showed higher overall mortality with CABG vs. PCI (42.3% vs. 21.4%, P=0.049), driven by 30-day mortality 8.5× higher in CABG (36.4% vs. 4.3%, P<0.001) [14], confirming PCI as the safer short-term choice. However, CAV’ s diffuse vascular involvement—affecting coronary arteries and distal branches—and limited suitable intervention segments complicate target lesion selection during PCI. This often causes incomplete revascularization due to lesions extending beyond stent length or mismatched vessel diameter. Additionally, PCI may mechanically injure the vessel wall, activating immune-driven smooth muscle cell growth and increasing in-stent restenosis (ISR) risk, forming a "intervention-injury-restenosis" cycle. Long-term data show CABG improves survival and reduces repeat revascularization in CAV versus PCI. Another meta-analysis reported a 5-year mortality rate of 17.0% with CABG vs. 14%–40.4% with PCI, reflecting its advantage in diffuse disease where PCI has higher restenosis and incomplete revascularization risks [15]. Despite the good short-term outcomes achieved with OCT-guided PCI in managing CAV lesions in this case, long-term follow-up is still needed to determine the value of this treatment modality. The proximal RCA Type B dissection likely results from CAV-specific fibro - lipidic plaques and 13–15 atm high - pressure dilation. When the OCT-detected plaques have uneven fibrous caps and stiff lipid cores, they are prone to medial tears under stress, which is a unique feature of CAV's fibrotic vessels. CAV’s rigid, fibrotic arteries concentrate stress at weak plaque areas or stent edges due to reduced elasticity. The 6-month-detected dissection probably originated from early micro-injuries worsened by tacrolimus, which delays endothelial repair. This complication shows OCT has a dual role. It can assess acute lesions and monitor chronic conditions. It detected the delayed healing and guided the bailout stenting. The patient’s CKD stage 3b combined with tacrolimus therapy likely made vascular repair worse. As a single-case, single-center report, findings may not apply broadly and could reflect individual variation or selection bias. While OCT-guided PCI showed short-term success, long-term risks like stent restenosis, late thrombosis, and progression of untreated CAV lesions need longer follow-up. OCT requires contrast dye, posing kidney injury risks in CKD, and its shallow imaging depth might miss deep vessel changes. Immunosuppressants may have affected healing, though their link to the 6-month dissection was unclear. Comorbidities’ (CHB, severe hyperglycemia) specific impacts on CAV weren’t confirmed with biomarker tests, and antiplatelet choices were based on theory, not personalized data. Larger studies are needed to validate long-term safety and efficacy in complex CAV patients. Abbreviations CAV: Cardiac allograft vasculopathy; CHB: Chronic hepatitis B; CKD: Chronic kidney disease; CCTA: Coronary computed tomography angiography; HbA1c: Hemoglobin A1c; ISHLT: International Society for Heart and Lung Transplantation; IVUS: Intravascular ultrasound; OCT: Optical coherence tomography; PCI: Percutaneous coronary intervention; SES: Sirolimus-eluting stents Declarations Conflict of interest The authors declare that they have no competing interests. Author Contributions declaration : Yuan Liang and Yan Wang were responsible for manuscript writing and revision Changyin Shen and Bei Shi contributed to the study design and implementation ; Youcheng Shen and Zhijiang Liu conducted imaging data analysis . All authors read and approved the final manuscript. Acknowledgements We would like to thank the patient for his consent to share his case. Funding No funding was received. Data availability The anonymized patient data supporting the findings of this study are available from the corresponding author, Changyin Shen ( [email protected] ), upon reasonable request. The data are not publicly available due to ethical restrictions regarding patient privacy and institutional guidelines for handling clinical data. Clinical trial number Not applicable Ethics approval and consent to participate Patient data were fully anonymized in this case report, with all identifiable information (name, hospital number, address, etc.) removed, and no characteristic markers included in imaging materials. In accordance with the guidelines of the Affiliated Hospital of Zunyi Medical University, ethical review and patient consent were not required for this study based on de-identified clinical data. Consent for publication The patient provided written informed consent for the publication of their clinical details, including demographic information, medical history, and imaging studies (CAG, CCTA and OCT images, shown in Figs. 1-3). All identifiable information was anonymized before submission, and the patient was informed that the images would be used in an academic context without revealing their identity. The patient was fully informed of the purpose of publication, the nature of the data to be disclosed, and their right to withdraw consent at any stage. Conflict of interest The authors declare that they have no competing interests. References Hsich E, Singh TP, Cherikh WS, Stehlik J. The International thoracic organtransplant registry of the International Society for Heart and Lung Transplantation: Thirty-ninth adult heart transplantation report-2022; focus on transplant for restrictive heart disease[J]. Journal of Heart and Lung Transplantation, 2022;41(10):1366-1375. 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Optical coherence tomography-guided versus angiography-guided PCI[J]. The New England Journal of Medicine, 2023, 389(16): 1466-1476. DOI: 10.1056/NEJMoa2305861. Hawranek M, Pyka Ł, Szyguła-Jurkiewicz B, et al. Everolimus-eluting stents versus sirolimus-eluting stents in patients with cardiac allograft vasculopathy[J]. Postępy Kardiol Interwencyjnej, 2021, 17(4): 349-355. DOI: 10.5114/aic.2021.111891. Luc JGY, Choi JH, Rizvi SA, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in heart transplant recipients with coronary allograft vasculopathy: a systematic review and meta-analysis of 1,520 patients. Ann Cardiothorac Surg. 2018;7(1):19-30. doi:10.21037/acs.2018.01.10 El-Andari R, Bozso SJ, Fialka NM, et al. Coronary artery revascularization in heart transplant patients: a systematic review and meta-analysis. Cardiology . 2022;147(3):348-363. doi:10.1159/000524781. Additional Declarations No competing interests reported. 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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-6644260","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":473528133,"identity":"c1378d01-59f8-404e-9b2a-b4f790a77bd0","order_by":0,"name":"Yuan Liang","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Liang","suffix":""},{"id":473528134,"identity":"91bba02c-3db7-4d76-be65-551f5169d459","order_by":1,"name":"Yan Wang","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Wang","suffix":""},{"id":473528135,"identity":"f41d958c-1dd9-4751-af4f-286ca32e2bf5","order_by":2,"name":"Youcheng Shen","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Youcheng","middleName":"","lastName":"Shen","suffix":""},{"id":473528136,"identity":"8be2a228-1399-4956-9c82-e8fe805428f2","order_by":3,"name":"Zhijiang Liu","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhijiang","middleName":"","lastName":"Liu","suffix":""},{"id":473528139,"identity":"73a43e49-fbcb-4827-b67d-b40791f65b17","order_by":4,"name":"Changyin Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYDACCSBmbGCAkB8MbORI08I4oyDNmBQtDAzMPB8OJxLUIT+7+diDnzvs8uQjktse2xgwJzCwHz66AZ8WgzvH0g17zyQXG95IbDfOMWDLY+BJS7uBV4tEjpk0Yxtz4sYZiW3SOQY8xQwSPGZ4tcjPyP8G1FIP0WJhIJHYQEgLw40cNqCWw4nzJYBaGAwMCGsxuJFmJtnbdjxxA8/DNskegwRjNkJ+kZ+R/EziZ1t14vz29GcSP/78l+NnP3wMv8Pg1l1IgDDYiFIOtq7/ANFqR8EoGAWjYIQBAFiWSu45uNAJAAAAAElFTkSuQmCC","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Changyin","middleName":"","lastName":"Shen","suffix":""},{"id":473528142,"identity":"b780bf5b-342a-4f20-aa46-c926cf54de56","order_by":5,"name":"Bei Shi","email":"","orcid":"","institution":"Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Bei","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2025-05-12 08:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6644260/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6644260/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85385012,"identity":"4d1527e6-c81b-4766-939d-e33d9016fd35","added_by":"auto","created_at":"2025-06-25 09:41:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62179,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePre- and post-procedural CAG and OCT findings of LAD and RCA lesions in July 2023\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e showed fibrotic plaques with neovessels in LAD middle segment (white arrows pointed); \u003cstrong\u003ec\u003c/strong\u003e showd fibrotic-lipidic plaques in RCA in middle segment ; \u003cstrong\u003eb \u003c/strong\u003eand \u003cstrong\u003ed\u003c/strong\u003e showed Post-procedural CAG and OCT optimal stent apposition with MSA in LAD and RCA\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6644260/v1/f6ab4a138f5a9ea9e38d404d.jpg"},{"id":85385014,"identity":"842bcf06-5ae6-434d-a02d-86b930c21657","added_by":"auto","created_at":"2025-06-25 09:41:10","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69925,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFollow-up CAG and OCT findings of LAD and RCA lesions in January 2024\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea and b \u003c/strong\u003eshowed\u003cstrong\u003e \u003c/strong\u003edemonstrate optimal stent apposition with MSA in middle segment of LAD/RCA; \u003cstrong\u003ec \u003c/strong\u003eshowed\u003cstrong\u003e \u003c/strong\u003ea 5-mm Type B dissection in the proximal segmentof RCA(white arrow point); \u003cstrong\u003ed \u003c/strong\u003eshowed optimal stent apposition in the proximal segment of RCA\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6644260/v1/532289f5409172d9072bc840.jpg"},{"id":85385013,"identity":"e27c0492-be5b-4196-b617-ac2b8ddc866e","added_by":"auto","created_at":"2025-06-25 09:41:10","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":26124,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCCTA findings in June 2023 and June 2024\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea \u003c/strong\u003eshowed\u003cstrong\u003e \u003c/strong\u003e60–90% stenosis in the LAD and RCA arteries (white arrows pointd); \u003cstrong\u003eb\u003c/strong\u003e confirmed stent patency (no new stenosis) in 1-year follow-up\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6644260/v1/c621398f8b6796cfa59cb135.jpg"},{"id":98380788,"identity":"c22af50e-8da3-4819-bc33-0ee456316b33","added_by":"auto","created_at":"2025-12-17 07:41:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":856950,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6644260/v1/b3d98c80-f6f5-406d-bc1d-af7020477b9d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Optical Coherence Tomography-Guided PCI for ISHLT Grade 3 Cardiac Allograft Vasculopathy: A 1 -Year Follow-Up Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCAV, a leading post-transplant complication, affects 30% adults with significant coronary disease within 5 years [1]. Driven by alloimmune-mediated endothelial injury, CAV features diffuse intimal fibrosis, neovascularization, and smooth muscle proliferation—distinct from atherosclerosis. ISHLT Grade 3 CAV (≥50% stenosis in\u0026nbsp;≥2 major vessels, often involving branches) causes progressive ischemia, limited revascularization, and high restenosis due to vessel rigidity. Conventional angiography has limited ability to identify intravascular lesions, while intravascular ultrasound (IVUS, 100–150 μm resolution) fails to detect small neovessels (50–100 μm) and fibrotic plaques, hindering stent optimization and increasing risks. OCT optimizes revascularization with high-resolution (10–20 μm) imaging, visualizing small neovessels and fibrous/lipid plaques missed by angiography and IVUS due to lower resolution. A landmark review by Volleberg et al. showed that OCT-guided PCI reduces stent underexpansion by 30% and detects edge dissections, key predictors of late stent failure, particularly in complex fibrotic or neovascular lesions [2].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough 2023 ISHLT guidelines(Class IIa, Level B) recommend SES for neointimal hyperplasia in CAV [3], evidence for OCT-guided strategies in high-risk subgroups including stage 3b CKD, CHB, and metabolic dysfunction remains limited, These patients face heightened risks of contrast nephropathy, bleeding, and stent failure due to overlapping pathobiological mechanisms (e.g., uremic toxin-induced fibrosis, viral-mediated immune activation, and metabolic endothelial damage). Here, we report a complex case of ISHLT Grade 3 CAV managed with OCT-guided SES implantation, demonstrating 1-year outcomes and actionable insights for high-risk populations.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 39-year-old East Asian male presented with a 3-month history of recurrent presyncope (2 episodes, triggered by standing) and NYHA class III dyspnea (limiting to climbing one flight of stairs, resolving at rest), without chest pain or hemoptysis. In 2018, he underwent orthotopic heart transplantation for dilated cardiomyopathy, with a long-term immunosuppressive regimen including tacrolimus 2 mg daily (target trough 5–10 ng/mL, 7.8 ng/mL in February 2023) and mycophenolate mofetil (MMF) 1000 mg twice daily. Another medical history included pre-transplantation CHB (treated with entecavir 0.5 mg daily, undetectable viral load) and stage 3b CKD, which progressed from normal renal function to stage 3b over 4 years post-transplant due to tacrolimus-induced nephrotoxicity. No hereditary cardiovascular or renal diseases reported in his family history.\u003c/p\u003e\n\u003cp\u003ePhysical examination showed heart rate 83 bpm, blood pressure 125/76 mmHg, SpO₂ 97% on low-flow oxygen (2 L/min via nasal cannula), respiratory rate 21/min. Laboratory findings included:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInflammation: Leukocytosis 11.00×10⁹/L, elevated high-sensitivity C-reactive protein 3.92 mg/L, and erythrocyte sedimentation rate 26 mm/h, without evidence of acute infection or autoimmune activation.\u003c/p\u003e\n\u003cp\u003eCKD stage 3b：Serum creatinine 153 μmol/L, urine protein negative (dipstick), eGFR 42.50 mL/min/1.73 m² by the CKD-EPI equation(stable 40–45 mL/min/1.73 m² over 1 year, tacrolimus nephrotoxicity)\u003c/p\u003e\n\u003cp\u003eCardiac biomarkers: High-sensitivity troponin T 11.58 ng/L and creatine kinase-MB 21 U/L within normal limits, ruling out acute coronary syndrome. Heart failure：Brain natriuretic peptide 781 pg/mL.\u003c/p\u003e\n\u003cp\u003eMetabolism：Random glucose 29.2 mmol/L, HbA1c 15.7%, and urine glucose (++++), urine ketones negative, initiated basal-bolus insulin regimen (8 units insulin aspart pre-meal, 18 units insulin glargine at bedtime). Triglycerides 2.89 mmol/L, low-density lipoprotein cholesterol (LDL-C, 2.03 mmol/L), and high-density lipoprotein cholesterol 0.72 mmol/L.\u003c/p\u003e\n\u003cp\u003eImmunosuppression and hepatitis B status: tacrolimus trough level 6.9 ng/mL; CHB (HBsAg positive, HBV DNA 331 IU/mL, stable on entecavir with undetectable viral load).\u003c/p\u003e\n\u003cp\u003eElectrocardiography showed sinus rhythm (78 bpm) with a QRS duration of 83 ms, QTc of 445 ms, and nonspecific T wave changes. Echocardiography revealed a left ventricular ejection fraction (LVEF) of 54%, mild left atrial enlargement (40 mm; normal \u0026lt;34 mm), and 1+ Doppler mitral regurgitation, E/e' ratio 15 (elevated left ventricle filling pressure), without regional wall motion abnormalities. CCTA demonstrated 60–90% stenosis in the LAD and RCA arteries. Chest CT showed mild bilateral pulmonary fibrosis and small calcified nodules in the left upper lobe (chronic changes no active infection or pulmonary embolism).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePreliminary diagnosis: 1) ISHLT Grade 3 CAV; 2) Ischemic cardiomyopathy with heart failure (NYHA Class III). 3) Chronic hepatitis B virus infection 4)Type 2 diabetes mellitus. Per 2023 ISHLT guidelines (Class IIb Level C) [3], re-transplantation is a definitive cure for advanced CAV but carries risks of rejection, complications, and long-term management challenges. The patient declined it due to economic and donor limitations. For coronary revascularization, given the patient's multiple comorbidities, PCI was chosen via shared decision-making to avoid CABG-related acute kidney injury risk and mitigate surgical stress worsening CHB reactivation or hyperglycemia complications.\u003c/p\u003e\n\u003cp\u003eDespite tacrolimus nephrotoxicity, the perioperative dose was maintained at 2 mg daily (trough 6.6–7.8 ng/mL) to avoid acute rejection risk: reducing levels below 5 ng/mL increases acute cellular rejection risk, especially during the proinflammatory PCI period. This decision was supported by stable eGFR (40–48 mL/min/1.73 m² for 1 year) and negative urine protein, indicating controlled nephrotoxicity without active injury.\u003c/p\u003e\n\u003cp\u003eGuided by 2023 ISHLT recommendations (Class IIa, Level B) [3], SES were prioritized over bare-metal stents and paclitaxel-eluting stents (PES) to target CAV-specific neointimal hyperplasia, a process driven by alloimmune-mediated smooth muscle cell proliferation. This selection capitalized on SES’ s mechanistic specificity: mTOR pathway inhibition directly addresses the fibroproliferative phenotype of CAV lesions, whereas PES—by suppressing cell migration rather than proliferation—are less aligned with CAV’ s underlying pathology of intimal fibrosis and neovascularization.\u003c/p\u003e\n\u003cp\u003eTo minimize contrast nephropathy, pre-procedural hydration hydration included pre-procedural isotonic saline (1 mL/kg/h, 6h prior) and post-procedural continuation at the same rate for 12h. Dual antiplatelet therapy(DAPT) included 300 mg aspirin and 600 mg clopidogrel (loading doses), preferred over renally excreted agents (e.g., ticagrelor) to balance ischemic and bleeding risks in CKD.\u003c/p\u003e\n\u003cp\u003eSES implantation followed OCT guidance (Dragonfly Duo catheter)\u0026nbsp;and OCT images were analyzed by a blinded core laboratory according to 2012 consensus standards [4], measuring minimum lumen area (MLA) and minimum stent area (MSA) to guide optimal stent apposition and sizing.\u003c/p\u003e\n\u003cp\u003eCAG revealed diffuse long-segment stenosis in proximal/mid LAD (90% stenosis, TIMI 2–3 flow) and proximal/mid RCA (subtotal occlusion, TIMI 2 flow), with a normal left circumflex (TIMI 3 flow). Guided by SYNTAX I score 12, PCI with OCT optimization addressed diffuse fibrotic lesions: after non-compliant balloon pre-dilation (2.0×20 mm, 12 atm, 6 seconds) in LAD, OCT showed fibrotic plaques with neovessels (50–150 μm diameter, 3–5 vessels/mm²; MLA 0.65 mm², proximal/distal reference diameters 1.76/1.12 mm, no severe calcification), prompting sequential 2.5×38 mm and 3.0×26 mm SES implantation (3 mm overlap) with 13–15 atm post-dilation (10 seconds) for MSA 4.21 mm² (80% expansion) and final TIMI 3 flow/complete coverage; in RCA, after Miracle 3 guidewire passage and compliant balloon pre-dilation (2.0×20 mm, 10–12 atm, 6 seconds), OCT identified\u0026nbsp;fibrotic-lipidic plaques (MLA 1.79 mm², proximal/distal reference diameters 1.99/1.90 mm), leading to two 2.75×28 mm SES deployed at 13–15 atm (7 seconds) with high-pressure post-dilation (same pressure, 7 seconds) for MSA 5.61 mm² (85% expansion) and angiographic TIMI 3 flow/full coverage. Unfractionated heparin maintained ACT 250–300 seconds, and iso-osmolar contrast(250ml) minimized nephropathy risk\u003c/p\u003e\n\u003cp\u003eThe final diagnosis confirmed ISHLT Grade 3 CAV criteria, necessitating revascularization for ischemia and functional improvement. Postoperatively, NYHA class improved from III to II, with resolved dizziness/dyspnea and only mild exertional fatigue (CCS I). Post-procedural 24-hour serum creatinine was 159 μmol/L, eGFR 48.54 mL/min/1.73 m². DAPT included aspirin 100 mg + clopidogrel 75 mg daily for 12 months, followed by lifelong aspirin (100 mg) to balance risks; atorvastatin 20 mg daily targeted LDL-C \u0026lt;1.8mol/L, and tacrolimus trough levels were maintained at 6–7 ng/mL to minimize nephrotoxicity (no dose changes during PCI). At 6-month follow-up, CAG/OCT revealed a 5-mm Type B dissection in the proximal RCA with medial involvement, 30% residual stenosis, and TIMI 3 flow. Based on OCT-measured depth and stenosis, a 4.0×12 mm SES was implanted to cover the lesion, remain TIMI 3 flow and suppressing neointimal hyperplasia via local sirolimus release to avoid late stent failure from untreated dissections. 12-month outcomes showed stable HbA1c 8.3%, LDL-C 56 mg/dL, CKD stage 3b (eGFR 47.88 mL/min1.73 m²), CCTA-confirmed stent patency (no new stenosis), stable tacrolimus levels (6.6–6.9 ng/mL), and no major complications.\u003c/p\u003e"},{"header":"Discussion and conclusion","content":"\u003cp\u003eCAV, a leading cause of late graft failure, poses challenges in patients with complex comorbidities. This case demonstrates the feasibility of OCT-guided SES implantation in ISHLT Grade 3 CAV with stage 3b CKD, CHB, and severe hyperglycemia, achieving stable 1-year outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient’s comorbidities likely accelerated CAV via distinct mechanisms, shaping OCT-visible plaques. CKD drives vascular fibrosis as uremic toxins like asymmetric dimethylarginine activate mTOR, inducing coronary (e.g., LAD) smooth muscle fibrosis and 50–150 μm neovessels (3–5/mm²), worsened by oxidative stress, inflammation, and microRNA/EV signaling. SES target mTOR locally to suppress fibrosis and neovascularization in CKD-related vascular injury[5]. Severe hyperglycemia damages endothelial cells via mitochondrial stress (reactive oxygen species) and accumulation of advanced glycation end-products (AGEs), promoting the formation of RCA fibrous-lipidic plaques. Concurrently, transforming growth factor-β (TGF-β) upregulation drives smooth muscle cell migration, exacerbating intimal hyperplasia. This pathogenic cascade—mediated by mammalian target of mTOR pathway activation—is more effectively mitigated by SES, which locally inhibit mTOR to suppress both fibroproliferation and AGEs-induced oxidative stress, compared to PES, whose anti-migration effects are limited to smooth muscle cell kinetics without addressing the upstream mitochondrial/AGEs-mTOR axis.[6-7]. CHB promotes CAV via residual inflammation and metabolic dysfunction even with long-term entecavir suppression of HBV: persistent liver inflammation releases IL-6/TNF-α to damage endothelial cells, induce adhesion molecules, and facilitate immune cell infiltration[8], while Treg dysfunction and Th1 overactivation exacerbate chronic rejection-related vascular inflammation[9]. Meanwhile, lipid disorders drive smooth muscle cell proliferation through the mTOR pathway, and oxidative stress impairs endothelial repair by reducing nitric oxide (NO) and increasing endothelin-1 (ET-1), collectively accelerating CAV progression.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCAG remain standard for CAV assessment(Class Ia, Level C) [3], but its 2D imaging underestimates vessel wall disease (e.g., intimal hyperplasia), leading to poor stent sizing and higher in-stent restenosis(ISR) risk. In small vessels (≤2.5 mm, common in CAV), SES guided by CAG alone has a 39% ISR rate (vs. 17% in larger vessels, P=0.003)[10]. To address these limitations, IVUS and OCT serve as critical adjuncts to CAG. 2023 ISHLT guidelines recommend OCT combined with CAG for CAV assessment as Class IIa, level C, while IVUS combined with CAG is Class IIb, level C, but OCT’ s 10–20 μm resolution allows for better visualization of subtle CAV lesions such as intimal hyperplasia, neovascularization, and thrombus. A 2021 state-of-the-art review emphasized OCT’ s role in visualizing layered fibrotic plaques and neovessels, critical for tailoring stent dimensions in rigid, diffusely diseased vessels[11]. Besides, the ILUMIEN IV trial （NCT03507777） demonstrated that OCT-guided PCI achieved larger MSA(5.72 vs. 5.36 mm², P\u0026lt;0.001) and 64% lower stent thrombosis in complex CAD lesions [12], but direct evidence for CAV is lacking. Furthermore, in CKD patients, OCT’ s extra contrast use poses more contrast nephropathy risk without prophylaxis due to poor renal clearance. Besides, its shallow penetration (1–2 mm) requires IVUS for deep calcifications (≥500 μm), a contrast-free, CKD-safe tool. Combining OCT precision with IVUS safety in guiding coronary revascularization may balance accuracy and safety, critical for high-risk patients with CKD and complex lesions. Future research is warranted to determine their long-term efficacy and safety in this specific population.\u003c/p\u003e\n\u003cp\u003eCalcineurin inhibitors (CNIs) and MMF suppress immune cell activation but do not address CAV’ s key drivers: smooth muscle proliferation and neointimal hyperplasia. Guidelines recommend mTOR inhibitors (e.g., sirolimus) for their dual action: suppressing T-cell-mediated immunity while directly inhibiting vascular smooth muscle cell proliferation and neointimal formation but systemic mTOR inhibition was contraindicated here due to CKD and uncontrolled diabetes. When systemic mTOR inhibition was contraindicated, a SES offered a localized solution: a 2021 analysis showed SES had no binary restenosis at 6 months [0% vs. 4% with everolimus-eluting stents(EES), P＞0.05], aligning with SES’ s ability to inhibit neointimal hyperplasia at the lesion site—critical for CAV’ s diffuse intimal fibrotic and neovascular lesions [13]. This strategy avoids the systemic side `effects of oral mTOR inhibitors while capitalizing on the rapamycin analogue’ s proven efficacy in suppressing smooth muscle proliferation, as supported by comparable late lumen loss (0.14 ± 0.15 mm for SES vs. 0.19 ± 0.15 mm for EES). This leverages SES to deliver sirolimus directly to OCT-identified lesions, inhibiting local smooth muscle proliferation and avoiding systemic toxicity—critical for patients intolerant of oral mTOR inhibitors. By using localized rapamycin analogues, this approach balances guideline-recommended mTOR inhibition with patient comorbidities, offering a pragmatic CAV revascularization strategy.\u003c/p\u003e\n\u003cp\u003eConsidering the diffuse and progressive lesion patterns of CAV, both CABG and PCI are considered palliative therapies. \u003cstrong\u003eCABG\u003c/strong\u003eas a salvage strategy, especially when ISR cannot be controlled by medical therapy or repeat PCI,\u003cstrong\u003e\u0026nbsp;is limited by CAV’s diffuse distal small-vessel involvement (\u0026lt;2.0 mm), making anastomosis hard and revascularization incomplete; grafts (especially venous) develop accelerated intimal hyperplasia in the immunoinflammatory environment, with poor long-term patency.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Comorbidities like CKD and diabetes further raise surgery risks like acute kidney injury and wound issues.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Besides, a\u003c/strong\u003e meta-analysis of 1,520 patients showed higher overall mortality with CABG vs. PCI (42.3% vs. 21.4%, P=0.049), driven by 30-day mortality 8.5× higher in CABG (36.4% vs. 4.3%, P\u0026lt;0.001) [14], confirming PCI as the safer short-term choice. However, CAV’ s diffuse vascular involvement—affecting coronary arteries and distal branches—and limited suitable intervention segments complicate target lesion selection during PCI. This often causes incomplete revascularization due to lesions extending beyond stent length or mismatched vessel diameter. Additionally, PCI may mechanically injure the vessel wall, activating immune-driven smooth muscle cell growth and increasing in-stent restenosis (ISR) risk, forming a \"intervention-injury-restenosis\" cycle. Long-term data show CABG improves survival and reduces repeat revascularization in CAV versus PCI. Another meta-analysis reported a 5-year mortality rate of 17.0% with CABG vs. 14%–40.4% with PCI, reflecting its advantage in diffuse disease where PCI has higher restenosis and incomplete revascularization risks [15]. Despite the good short-term outcomes achieved with OCT-guided PCI in managing CAV lesions in this case, long-term follow-up is still needed to determine the value of this treatment modality.\u003c/p\u003e\n\u003cp\u003eThe proximal RCA Type B dissection likely results from CAV-specific fibro - lipidic plaques and 13–15 atm high - pressure dilation. When the OCT-detected plaques have uneven fibrous caps and stiff lipid cores, they are prone to medial tears under stress, which is a unique feature of CAV's fibrotic vessels. CAV’s rigid, fibrotic arteries concentrate stress at weak plaque areas or stent edges due to reduced elasticity. The 6-month-detected dissection probably originated from early micro-injuries worsened by tacrolimus, which delays endothelial repair. This complication shows OCT has a dual role. It can assess acute lesions and monitor chronic conditions. It detected the delayed healing and guided the bailout stenting. The patient’s CKD stage 3b combined with tacrolimus therapy likely made vascular repair worse.\u003c/p\u003e\n\u003cp\u003eAs a single-case, single-center report, findings may not apply broadly and could reflect individual variation or selection bias. While OCT-guided PCI showed short-term success, long-term risks like stent restenosis, late thrombosis, and progression of untreated CAV lesions need longer follow-up. OCT requires contrast dye, posing kidney injury risks in CKD, and its shallow imaging depth might miss deep vessel changes. Immunosuppressants may have affected healing, though their link to the 6-month dissection was unclear. Comorbidities’ (CHB, severe hyperglycemia) specific impacts on CAV weren’t confirmed with biomarker tests, and antiplatelet choices were based on theory, not personalized data. Larger studies are needed to validate long-term safety and efficacy in complex CAV patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAV: Cardiac allograft vasculopathy; CHB: Chronic hepatitis B; CKD: Chronic kidney disease; CCTA: Coronary computed tomography angiography; HbA1c: Hemoglobin A1c; ISHLT: International Society for Heart and Lung Transplantation; IVUS: Intravascular ultrasound; OCT: Optical coherence tomography; PCI: Percutaneous coronary intervention; SES: Sirolimus-eluting stents\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edeclaration\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuan Liang and Yan Wang were responsible for \u003cstrong\u003emanuscript writing and revision\u003c/strong\u003eChangyin Shen and Bei Shi contributed to the \u003cstrong\u003estudy design and\u003c/strong\u003e\u003cstrong\u003eimplementation\u003c/strong\u003e; Youcheng Shen and Zhijiang Liu conducted \u003cstrong\u003eimaging data analysis\u003c/strong\u003e. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank the patient for his consent to share his case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe anonymized patient data supporting the findings of this study are available from the corresponding author, Changyin Shen ([email protected]), upon reasonable request. The data are not publicly available due to ethical restrictions regarding patient privacy and institutional guidelines for handling clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient data were fully anonymized in this case report, with all identifiable information (name, hospital number, address, etc.) removed, and no characteristic markers included in imaging materials. In accordance with the guidelines of the Affiliated Hospital of Zunyi Medical University, ethical review and patient consent were not required for this study based on de-identified clinical data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient provided written informed consent for the publication of their clinical details, including demographic information, medical history, and imaging studies (CAG, CCTA and OCT images, shown in Figs. 1-3). All identifiable information was anonymized before submission, and the patient was informed that the images would be used in an academic context without revealing their identity.\u0026nbsp;The patient was fully informed of the purpose of publication, the nature of the data to be disclosed, and their right to withdraw consent at any stage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHsich E, Singh TP, Cherikh WS, Stehlik J. The International thoracic organtransplant registry of the International Society for Heart and Lung Transplantation: Thirty-ninth adult heart transplantation report-2022; focus on transplant for restrictive heart disease[J]. Journal of Heart and Lung Transplantation, 2022;41(10):1366-1375. DOI:10.1016/j.healun.2022.07.018.\u003c/li\u003e\n\u003cli\u003eVolleberg R, Mol JQ, van der Heijden D, et al. Optical coherence tomography and coronary revascularization: from indication to procedural optimization[J]. Trends in Cardiovascular Medicine, 2023;33(2):92-106. DOI:10.1016/j.tcm.2021.10.009.\u003c/li\u003e\n\u003cli\u003eVelleca A, Shullo MA, Dhital K, et al. The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients[J]. The Journal of Heart and Lung Transplantation, 2023;42(5):e1-e141. DOI:10.1016/j.healun.2022.10.015.\u003c/li\u003e\n\u003cli\u003eTearney GJ, Regar E, Akasaka T, et al. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation [published correction appears in J Am Coll Cardiol. 2012 May 1;59(18):1662. Dudeck, Darius [corrected to Dudek, Darius]; Falk, Erlin [corrected to Falk, Erling]; Garcia, Hector [corrected to Garcia-Garcia, Hector M]; Sonada, Shinjo [corrected to Sonoda, Shinjo]; Troels, Thim [corrected to Thim, Troels]; van Es, Gerrit-Ann [correct].]. J Am Coll Cardiol. 2012;59(12):1058-1072. DOI:10.1016/j.jacc.2011.09.079\u003c/li\u003e\n\u003cli\u003eCarracedo J, Alique M, Vida C, et al. Mechanisms of cardiovascular disorders in patients with chronic kidney disease: a process related to accelerated senescence[J]. Frontiers in Cell and Developmental Biology, 2020, 8: 185. DOI: 10.3389/fcell.2020.00185.\u003c/li\u003e\n\u003cli\u003eCostantino S, Paneni F, Cosentino F. Hyperglycemia: a bad signature on the vascular system[J]. Cardiovascular Diagnosis and Therapy, 2015, 5(5): 403-406. DOI: 10.3978/j.issn.2223-3652.2015.05.02.\u003c/li\u003e\n\u003cli\u003eBeckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II[J]. European Heart Journal, 2013, 34(31): 2444-2452. DOI: 10.1093/eurheartj/eht142.\u003c/li\u003e\n\u003cli\u003eDeng P, Tang N, Li L, et al. Diagnostic value of combined detection of IL-1\u0026beta;, IL-6, and TNF-\u0026alpha; for sepsis-induced cardiomyopathy[J]. Medical Clinic (Barcelona), 2022, 158(9): 413-417. DOI: 10.1016/j.medcli.2021.04.025.\u003c/li\u003e\n\u003cli\u003eKitz A, Dominguez-Villar M. Molecular mechanisms underlying Th1-like Treg generation and function[J]. Cellular and Molecular Life Sciences, 2017, 74(22): 4059-4075. DOI: 10.1007/s00018-017-2569-y.\u003c/li\u003e\n\u003cli\u003eElhage Hassan M, Khawaja M, Jaber WA, et al. Restenosis rates for drug-eluting stents used in treating small vessel cardiac allograft vasculopathy after orthotopic heart transplantation[J]. Cardiovascular Revascularization Medicine, 2025, 73: 64-69. DOI: 10.1016/j.carrev.2024.07.006.\u003c/li\u003e\n\u003cli\u003eAcharya D, Loyaga-Rendon RY, Chatterjee A, et al. Optical Coherence Tomography in Cardiac Allograft Vasculopathy: State-of-the-Art Review. Circ Heart Fail. 2021;14(9):e008416. doi:10.1161/CIRCHEARTFAILURE.121.008416\u003c/li\u003e\n\u003cli\u003eAli ZA, Landmesser U, Maehara A, et al. Optical coherence tomography-guided versus angiography-guided PCI[J]. The New England Journal of Medicine, 2023, 389(16): 1466-1476. DOI: 10.1056/NEJMoa2305861.\u003c/li\u003e\n\u003cli\u003eHawranek M, Pyka Ł, Szyguła-Jurkiewicz B, et al. Everolimus-eluting stents versus sirolimus-eluting stents in patients with cardiac allograft vasculopathy[J]. Postępy Kardiol Interwencyjnej, 2021, 17(4): 349-355. DOI: 10.5114/aic.2021.111891.\u003c/li\u003e\n\u003cli\u003eLuc JGY, Choi JH, Rizvi SA, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in heart transplant recipients with coronary allograft vasculopathy: a systematic review and meta-analysis of 1,520 patients. Ann Cardiothorac Surg. 2018;7(1):19-30. doi:10.21037/acs.2018.01.10\u003c/li\u003e\n\u003cli\u003eEl-Andari R, Bozso SJ, Fialka NM, et al. Coronary artery revascularization in heart transplant patients: a systematic review and meta-analysis.\u0026nbsp;\u003cem\u003eCardiology\u003c/em\u003e. 2022;147(3):348-363. doi:10.1159/000524781.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Cardiac allograft vasculopathy, Optical coherence tomography, Percutaneous coronary intervention","lastPublishedDoi":"10.21203/rs.3.rs-6644260/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6644260/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e International Society for Heart and Lung Transplantation (ISHLT) Grade 3 cardiac allograft vasculopathy (CAV) poses challenges for revascularization due to diffuse fibrotic lesions and neovascularization. While optical coherence tomography (OCT) enables high-resolution imaging, evidence for OCT-guided percutaneous coronary intervention (PCI) in high-risk patients with comorbidities like chronic kidney disease (CKD), chronic hepatitis B (CHB), or metabolic dysfunction remains limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation: \u003c/strong\u003eA 39-year-old male with ISHLT Grade 3 CAV, CKD stage 3b, (eGFR 42.5 mL/min/1.73 m²), CHB, and severe hyperglycemia (HbA1c 15.7%) underwent OCT-guided PCI. Coronary angiography(CAG) revealed diffuse stenosis in the left anterior descending (LAD) and right coronary artery (RCA). OCT identified fibrotic-neovascular plaques in the LAD and fibrotic-lipidic plaques in the RCA, prompting implantation of sirolimus-eluting stents (SES) to address CAV-specific neointimal hyperplasia. To mitigate CKD-related risks, iso-osmolar contrast, pre-procedural hydration, aspirin and clopidogrel were used for antiplatelet therapy. At 6-month follow-up, CAG/OCT showed patent stents with minimal neointimal hyperplasia and a Type B dissection in the proximal RCA, which was successfully managed with additional SES implantation. At 1-year, coronary computed tomography angiography (CCTA) confirmed sustained stent patency without new stenosis; renal function remained stable (eGFR 47.88 mL/min/1.73 m²), improved glycemic control(HbA1c 8.3%), and no major adverse events occurred.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis case shows OCT-guided SES implantation is feasible in high-risk CAV patients with complex conditions, highlighting OCT’ s role in precise lesion assessment and risk-adaptive strategies that led to stable outcomes at 1 year. Despite its single-case nature, it underscores the need for larger studies to confirm long-term benefits.\u003c/p\u003e","manuscriptTitle":"Optical Coherence Tomography-Guided PCI for ISHLT Grade 3 Cardiac Allograft Vasculopathy: A 1 -Year Follow-Up Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 09:41:06","doi":"10.21203/rs.3.rs-6644260/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":"345985a6-3a89-45b5-9238-b329f13e6fcb","owner":[],"postedDate":"June 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-17T07:40:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-25 09:41:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6644260","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6644260","identity":"rs-6644260","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}