Conservative Management of Hemolytic Anemia Following Percutaneous Mitral Valve Clip Procedure: A Successful Case Report

Conservative Management of Hemolytic Anemia Following Percutaneous Mitral Valve Clip Procedure: A Successful 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 Conservative Management of Hemolytic Anemia Following Percutaneous Mitral Valve Clip Procedure: A Successful Case Report Yaxin Liao, zhenfei Fang, yingwang liu, fan xiang, zhihua bian, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8948456/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background:This report describes an 82-year-old female patient who developed secondary hemolysis following transcatheter edge-to-edge mitral valve repair (teer) for severe mitral regurgitation. Case presentation:On the day of the procedure, upon returning to the ward, the urinary catheter drainage bag showed tea-colored urine accompanied by oliguria. Subsequent evaluation revealed decreased hemoglobin, elevated lactate dehydrogenase, reduced haptoglobin, and acute renal failure, with the final diagnosis of device-related hemolysis. Following high-dose hydration and diuresis, the patient avoided hemodialysis, and renal function recovered. After discontinuation of antiplatelet therapy, hemolysis symptoms were controlled, and hemoglobin levels gradually improved. Conclusions:In selected patients, temporary discontinuation of antiplatelet therapy may ameliorate symptoms, but the attendant thrombotic risk necessitates intensified surveillance and individualized management. Teer procedure hemolytic anemia severe mitral valve regurgitation postoperative complications device-related hemolysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background Transcatheter edge‑to‑edge repair (teer) is a widely adopted, minimally invasive option for treating severe mitral regurgitation in high‑risk patients with suitable valve anatomy [ 1 ] 。Despite its overall safety and efficacy, teer can be complicated by adverse events, including the uncommon but potentially serious occurrence of hemolytic anemia. Case presentation An 82‑year‑old woman presented with a 5‑year history of intermittent dizziness and progressive dyspnea for two weeks.the patient's past medical history included hypertension, coronary artery disease, and prior thyroidectomy. On admission she was orthopneic with respiratory distress. Vital signs: Heart rate 79 beats/min, blood pressure 125/72 mmhg. Cardiac examination revealed leftward cardiac enlargement and a coarse grade 3/6 holosystolic blowing murmur at the apex. Comprehensive transthoracic and transesophageal echocardiography (Fig. 1 ) demonstrated posterior mitral leaflet prolapse (predominantly p2 with partial basal p1 involvement), multiple ruptured chordae tendineae, and severe (4+) mitral regurgitation. Imaging findings met criteria for transcatheter edge‑to‑edge mitral repair (teer). The patient underwent transcatheter edge‑to‑edge mitral valve repair (teer) under general anesthesia. Two transcatheter mitral valve clips (lc-8-12, lc-6-12) were deployed at the a2-3/p2-3 and a2/p2 positions, respectively. The procedure was uneventful, and no significant murmur was auscultated in the cardiac valve area postoperatively. Follow‑up echocardiography showed marked reduction of mitral regurgitation with a small residual jet (Fig. 2 ), and bedside chest radiography confirmed correct clip positioning (Fig. 3 ). The procedure was performed in the morning; the patient was safely returned to the ward at noon and extubated, reporting marked improvement in dyspnea. Vital signs immediately post‑procedure were hr 81 bpm and bp 116/68 mmhg, and cardiac auscultation revealed substantially reduced murmurs. That afternoon, tea‑colored urine was noted in the urinary catheter bag with associated nausea and a 24‑hour urine output < 100 ml. Laboratory tests demonstrated a drop in hemoglobin from baseline with an elevated reticulocyte count (Fig. 4 ), and concurrent rises in serum creatinine, blood urea nitrogen, total bilirubin, and lactate dehydrogenase, while platelet count remained stable (Fig. 5 ). The patient received theophylline for membrane stabilization, urine alkalinization, and aggressive intravenous hydration. After ~ 20 hours of hydration, a torasemide infusion was started. Following approximately 4,000 ml of fluid replacement, urine output improved ~ 24 hours post‑procedure and urine cleared by the second postoperative night (Fig. 6 ). After the initial treatment the patient’s symptoms resolved—no dyspnea or nausea—and mental status improved. On postoperative day 3, however, transient tea‑colored urine recurred after a red blood cell transfusion, accompanied by nausea and vomiting; following repeat hydration the urine cleared the next day, and this episode was markedly shorter than the first. Hemolysis workup showed a positive direct antiglobulin (coombs) test, low serum haptoglobin, persistently elevated lactate dehydrogenase, and schistocytes on peripheral smear (Fig. 7 ), consistent with intravascular hemolysis. On postoperative day 10 the patient had another brief episode of tea‑colored urine without significant symptoms, which may have been associated with a higher blood pressure that day (154/73 mmhg). The patient experienced recurrent tea‑colored urine consistent with device‑related hemolysis. Cardiothoracic surgery recommended mitral valve replacement, but given the patient’s advanced age, high operative risk, good mental status, absence of distress, and family reluctance for thoracotomy, clopidogrel was held and hemolysis was monitored conservatively. After stopping antiplatelet therapy, hemoglobin stabilized, lactate dehydrogenase began to decline, renal function recovered, and no further tea‑colored urine occurred. The patient was discharged uneventfully. At 1‑month follow‑up hemoglobin remained stable and heart‑failure symptoms were markedly improved. Because of in‑hospital paroxysmal atrial fibrillation and a cha2ds2‑vasc score of 6, oral anticoagulation with edoxaban 15 mg was resumed. At 2 months post‑procedure echocardiography showed satisfactory mitral valve function with persistent mild–moderate regurgitation (Fig. 8 ); the patient remained largely asymptomatic, but ldh had not shown a further significant decline. Discussion This report is the first to highlight the bold approach of discontinuing antiplatelet therapy to alleviate hemolysis after transcatheter edge-to-edge repair (teer). Previous literature has documented [ 11 ] cases of hemolytic anemia occurring after atrial septal defect (asd) closure, where discontinuing antiplatelet therapy resulted in significant improvement of hemolytic symptoms. This suggests that antiplatelet agents may contribute to exacerbating or sustaining hemolysis in certain patients. In the present case, a review of the treatment process revealed that hemolytic manifestations gradually improved after cessation of antiplatelet medication, accompanied by a marked increase in hemoglobin levels.this clinical observation suggests that for patients who experience hemolysis following teer, a conservative treatment approach may be considered, particularly when mitral regurgitation is mild and vital signs remain stable. After ruling out serious complications such as infection or device dislocation, temporary discontinuation of antiplatelet or anticoagulant therapy may be a reasonable strategy. This approach allows for optimal adaptation between the valve and the implanted clip, as well as for local tissue healing.simultaneously, active supportive care is essential. This includes aggressive intravenous hydration to prevent renal injury from hemoglobinuria and avoid tubular obstruction, blood pressure and heart rate control, renal protection, and measures to stabilize erythrocyte membranes. As hemolysis resolves, cautious reintroduction of anticoagulant therapy at low doses may be considered. Throughout this process, close monitoring of hemolysis indices, renal and cardiac function, and overall clinical status is crucial. Therapy should be promptly modified, and surgical intervention should be considered if conservative measures fail.mechanical intravascular hemolysis (mih) is the pathological process in which red blood cells are mechanically damaged and fragmented within the vascular lumen. [ 9 ] 。This complication is uncommon after conventional surgical valve replacement and even rarer following teer; published reports are limited, and no consensus exists on diagnostic criteria or management. Barrett et al. [ 2 ] reported intravascular hemolysis after mitraclip in which conservative measures failed and the patient ultimately required mitral valve replacement, implicating persistent postoperative mitral regurgitation as a potential cause. Yokoyama et al. [ 10 ] described a case of subacute hemolytic anemia after teer in which the patient remained on anti-platelet therapy and received only transfusion support, achieving a favorable outcome. The authors noted several factors that may have contributed to the good prognosis: Absence of underlying cardiac dysfunction (preoperative lvef 72.5%), later onset of hemolysis (2 weeks postprocedure), and other clinical variables. The mechanism of device-related hemolysis following mitral valve surgery remains incompletely understood; but several hypotheses have been proposed. Mechanical direct injury is a principal mechanism: Erythrocytes exposed to excessive shear stress or physical trauma from contact with native cardiac structures, prosthetic/repair devices, or abnormal flow jets can undergo membrane disruption and fragmentation, resulting in intravascular hemolysis [ 3 ].secondly, device‑related structural abnormalities are important precipitants of hemolysis. Features such as annular rupture, device malposition or migration, and exposed sutures or clips can create turbulent flow and focal high‑shear zones, increasing mechanical trauma to erythrocytes and exacerbating hemolysis [ 3 – 5 ] .furthermore, residual or recurrent mitral regurgitation must be considered, as high‑velocity regurgitant jets generate focal high‑shear forces that markedly increase erythrocyte trauma and exacerbate hemolysis [ 6 ] .in the first reported case of hemolysis after mitraclip, yokoyama et al. [ 10 ] attributed red‑cell fragmentation to high‑velocity flow through a narrow gap between the device surface and the coaptation line, causing repeated collisions with the device. This mechanism parallels our case: Serial postoperative echocardiography demonstrated persistent mild–moderate eccentric mitral regurgitation. High‑velocity jets traversing a narrow orifice generate substantial shear stress and focal impact forces, promoting erythrocyte membrane disruption and intravascular hemolysis. These observations reinforce residual regurgitation as a plausible and important contributor to post‑teer hemolysis. For device‑related hemolysis after mitral valve interventions, current evidence indicates that reoperation is an effective option to eliminate the mechanical source of hemolysis in patients who are suitable surgical candidates—particularly for severe paravalvular leaks or hemolysis refractory to conservative measures. [ 7 – 8 ] regarding pharmacotherapy, several agents have been reported to ameliorate symptoms of mechanical postoperative hemolysis, including beta‑blockers, erythropoietin, iron supplementation, folic acid, vitamins b12 and b6, and theophylline. [ 9 ] therefore, in this case, timely, individualized adjustment of pharmacotherapy may represent an effective strategy for managing post‑procedural hemolytic anemia. Conclusion Transcatheter edge‑to‑edge repair (teer) is an important therapeutic option for elderly patients with mitral regurgitation who are poor surgical candidates; therefore, thoracotomy should be avoided when feasible. Although hemolytic anemia after percutaneous mitral clip placement is uncommon, it carries substantial clinical implications and is frequently associated with residual postprocedural regurgitation. Early recognition and targeted intervention can control hemolysis; in selected patients, temporary discontinuation of antiplatelet therapy may ameliorate symptoms, but the attendant thrombotic risk necessitates intensified surveillance and individualized management. Combined pharmacologic and supportive measures offer effective non‑surgical treatment alternatives that can relieve symptoms while minimizing operative risk. Declarations Ethics approval and consent to participate: This study has obtained ethical approval from the Consent for publication: All authors consent to submit this manuscript for publication in bmc cardiovascular disorders and confirm that all co-authors are aware of and agree with the content of the manuscript. Funding this study did not receive any external funding support. Author Contribution YXL is responsible for manuscript writing and revision; ZFF and YWL are responsible for surgery and treatment guidance; FX is responsible for providing and analyzing the researchers' imaging; ZHB and QYZ are responsible for data collection; JJT and QYZ are responsible for providing guidance on research direction and ensuring the overall quality and academic standards of the manuscript. Acknowledgement Special thanks to the Second Xiangya Hospital of Central South University for the assistance and support provided in this study. Data Availability No datasets were generated or analyzed during this study; therefore, data sharing is not applicable to this manuscript. References Otto cm. nishimura ra, bonow ro, carabello ba, erwin jp 3rd, gentile f, jneid h, krieger ev, mack m, mcleod c, o'gara pt, rigolin vh, sundt tm 3rd, thompson a, toly c. 2020 acc/aha guideline for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation. 2021 feb 2;143(5):E72-e227. Barrett. cd, cerbin l, desai a, carroll jd. Red blood cell fragmentation syndrome after placement of mitraclip. Jacc case rep. 2020 jun 17;2(7):1084–1088. Lam. bk, cosgrove dm, bhudia sk, gillinov am. Hemolysis after mitral valve repair: Mechanisms and treatment. Ann thorac surg. 2004 jan;77(1):191-5. Rabbani. m, hafiz a, algadheeb m, thain a, kiaii bb. A case of systolic anterior motion after mitral valve repair causing hemolytic anemia: Mechanism and treatment. Can j cardiol. 2020 dec;36(12):1977.e5-1977.e8. Inoue m. kaku b, kanaya h, ohka t, ueda m, masahiro s, shimizu m, mabuchi h. Reduction of hemolysis without reoperation following mitral valve repair. Circ j. 2003 sep;67(9):799–801. Baudo m. cuko b, ternacle j, sicouri s, busuttil o, denti p, godino c, de vincentiis c, ramlawi b, leroux l, modine t, palloshi a, maisano f. Transcatheter management of residual mitral regurgitation after transcatheter edge-to-edge repair: A systematic review. Cardiovasc interv ther. 2025 apr;40(2):255–67. Nishimura ra. otto cm, bonow ro, carabello ba, erwin jp 3rd, fleisher la, jneid h, mack mj, mcleod cj, o'gara pt, rigolin vh, sundt tm 3rd, thompson a. 2017 aha/acc focused update of the 2014 aha/acc guideline for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association task force on clinical practice guidelines. Circulation. 2017 jun 20;135(25):E1159-e1195. Huang jb. wen zk, lu wj, lu cc, tang xm. Diagnosis and treatment of mechanical hemolysis after mitral repair in adult. Heart surg forum 2021 feb 16;24(1):E165–9. Cannata a. cantoni s, sciortino a, bruschi g, russo cf. Mechanical hemolysis complicating transcatheter interventions for valvular heart disease: Jacc state-of-the-art review. J am coll cardiol. 2021 may 11;77(18):2323–2334. Yokoyama h. mizuno s, saito s. Subacute hemolytic anemia after transcatheter edge-to-edge mitral valve repair: A case report. Catheter cardiovasc interv. 2020 may 1;95(6):1230–1234. Xie. x, hanx, ye h, Hemolysis after transcatheter closure of atrial septal defect: A case report.chin j intervent cardiol, 2019 october , 27(10):599–600. 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-8948456","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":618447985,"identity":"56123294-5faa-4cfe-aef9-82d3220f4ada","order_by":0,"name":"Yaxin Liao","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"Yaxin","middleName":"","lastName":"Liao","suffix":""},{"id":618447986,"identity":"cae74689-a65b-4e5a-8b9f-5bb6e99fd2d2","order_by":1,"name":"zhenfei Fang","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"zhenfei","middleName":"","lastName":"Fang","suffix":""},{"id":618447987,"identity":"ee0da7cf-99d6-4766-ad2f-1e76fba59b29","order_by":2,"name":"yingwang liu","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"yingwang","middleName":"","lastName":"liu","suffix":""},{"id":618447988,"identity":"d9a54844-daab-402b-b33e-dbd86ca5225f","order_by":3,"name":"fan xiang","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"fan","middleName":"","lastName":"xiang","suffix":""},{"id":618447989,"identity":"8c7434f0-e1ef-4ed8-a927-253d6da4066c","order_by":4,"name":"zhihua bian","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"zhihua","middleName":"","lastName":"bian","suffix":""},{"id":618447990,"identity":"85c2b9ca-10fc-4e17-aa99-4a599540e0e2","order_by":5,"name":"qingyun zheng","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"qingyun","middleName":"","lastName":"zheng","suffix":""},{"id":618447991,"identity":"9f973347-7f07-4772-a377-7ea5af110cf2","order_by":6,"name":"Qing yi Zhu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYDACCSBOAGI29gYwn7GBeC08B0jRAmEkEKlFfnaP4Y2HO2oT+yQfP/7Mw2Aju+EA87MH+LQwzjljbJF45nhim3SamTQPQ5rxhgNs5gb4tDBL5JhJJLYdA2rJYWPmYTicuOEAD5sEPi1scC2SZ5iBDvtPWAsPREtNYpsEDwPQYQcIa5GQSCu2SGw7YNzGk2YmOccg2XjmYTYzvFrkZyRvvPmzrU52fvvhxx/eVNjJ9h1vfoZXC9gmBobDjg1gJiiomAmph2ipsydC3SgYBaNgFIxUAADPTUSPC+at7QAAAABJRU5ErkJggg==","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":true,"prefix":"","firstName":"Qing","middleName":"yi","lastName":"Zhu","suffix":""},{"id":618447992,"identity":"ec7ee79c-a40a-4ded-b673-7f4031af2dcd","order_by":7,"name":"Jianjun Tang","email":"","orcid":"","institution":"中南大学湘雅二医院","correspondingAuthor":false,"prefix":"","firstName":"Jianjun","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2026-02-23 15:08:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8948456/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8948456/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106469023,"identity":"0f47b817-5215-4f98-989f-d978874c0aae","added_by":"auto","created_at":"2026-04-09 00:45:26","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":82887,"visible":true,"origin":"","legend":"\u003cp\u003eThe imagea isa transthoracic echocardiogram, which indicatesthat the maximum flow velocity of the mitral regurgitation jet can reach 4 m/s. Image b shows a transesophageal ultrasound, where the mitral valve leaflets fail to completely close during systole, suggesting mitral valve insufficiency.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/b6c1823edd43ee24b19de3ad.jpg"},{"id":106469025,"identity":"c7ad1ddd-cb85-4145-bc4f-d23eca2c54f8","added_by":"auto","created_at":"2026-04-09 00:45:26","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":132272,"visible":true,"origin":"","legend":"\u003cp\u003eThe images show preoperativeand postoperative conventional ultrasound and colordoppler flow imaging.image a depicts a preoperative apicalfour-chamber view, revealing mitral valve insufficiency and a large, high-velocity regurgitant jet.image b is a postoperative follow-up echocardiogram, showing the clip fixedin place with reduced mitral regurgitation compared to before.images c and d are follow-up echocardiograms at 2 and 3 weeks post-surgery, respectively, both indicating stable clip position, though a small residual shunt remains.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/449b248ac14217b32f97cd6d.jpg"},{"id":106724535,"identity":"9638acab-d71a-41f1-a766-4db06f5b728d","added_by":"auto","created_at":"2026-04-12 18:28:30","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96087,"visible":true,"origin":"","legend":"\u003cp\u003ePanel a shows the preoperative chest radiograph. Panel b displays the patient's postoperative follow-up chest radiograph; arrows indicate the clip fixation sites.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/af73857d8501556b051acb73.jpg"},{"id":106469027,"identity":"b4623ed0-c00f-4d96-8cf1-38a9ecaef47f","added_by":"auto","created_at":"2026-04-09 00:45:26","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":46411,"visible":true,"origin":"","legend":"\u003cp\u003eReticulocyte count as shown, with absolute reticulocyte levels persistently above the reference range, indicating active bone marrow proliferation\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/74436cdf6d2fb13a92974a45.jpg"},{"id":106724434,"identity":"10974143-3551-44ac-8ba1-23132e8763c1","added_by":"auto","created_at":"2026-04-12 18:28:03","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":82074,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in hemolysis-related parameters: Hb: Hemoglobin, plt: Platelets, cr: Serum creatinine, tb: Total bilirubin, ldh: Lactate dehydrogenase\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/53087b3dad2672a11d017c7c.jpg"},{"id":106469029,"identity":"e671a927-f79b-4850-80b4-def44c62867b","added_by":"auto","created_at":"2026-04-09 00:45:26","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":82146,"visible":true,"origin":"","legend":"\u003cp\u003eThe urine color ofthe patient became clear on the second day after surgery\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/7c7dbed1f9c6c3b349746b87.jpg"},{"id":106724303,"identity":"85cb57fb-a6fe-46d5-905c-6e3940011cd9","added_by":"auto","created_at":"2026-04-12 18:27:21","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":39791,"visible":true,"origin":"","legend":"\u003cp\u003ePeripheral blood smear showing fragmented red blood cells\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/ba44ff2bdb504fc891bff8c3.jpg"},{"id":106469031,"identity":"e072c5c7-e23e-4e3c-aab4-5192a4c16cf8","added_by":"auto","created_at":"2026-04-09 00:45:26","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":64555,"visible":true,"origin":"","legend":"\u003cp\u003eThis image shows the four-chamber view on echocardiography at 2 months postoperatively, with the arrow indicating persistent regurgitation and stability at the clip site.\u003c/p\u003e","description":"","filename":"Picture8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/59d06217c60acb25cade0bf8.jpg"},{"id":106726678,"identity":"0e421a29-3d42-404d-9766-55f5e7d951e1","added_by":"auto","created_at":"2026-04-12 18:37:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1011599,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/3ab5562f-81fe-4c8d-b4d9-2fd95d75c7a0.pdf"},{"id":106724612,"identity":"c4a7ea8e-6c3f-4abc-8710-9e2666048e9b","added_by":"auto","created_at":"2026-04-12 18:28:55","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":240527,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8948456/v1/cefe2e6bbfc8478e44ebedc6.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Conservative Management of Hemolytic Anemia Following Percutaneous Mitral Valve Clip Procedure: A Successful Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eTranscatheter edge‑to‑edge repair (teer) is a widely adopted, minimally invasive option for treating severe mitral regurgitation in high‑risk patients with suitable valve anatomy\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e。Despite its overall safety and efficacy, teer can be complicated by adverse events, including the uncommon but potentially serious occurrence of hemolytic anemia.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eAn 82‑year‑old woman presented with a 5‑year history of intermittent dizziness and progressive dyspnea for two weeks.the patient's past medical history included hypertension, coronary artery disease, and prior thyroidectomy. On admission she was orthopneic with respiratory distress. Vital signs: Heart rate 79 beats/min, blood pressure 125/72 mmhg. Cardiac examination revealed leftward cardiac enlargement and a coarse grade 3/6 holosystolic blowing murmur at the apex. Comprehensive transthoracic and transesophageal echocardiography (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) demonstrated posterior mitral leaflet prolapse (predominantly p2 with partial basal p1 involvement), multiple ruptured chordae tendineae, and severe (4+) mitral regurgitation. Imaging findings met criteria for transcatheter edge‑to‑edge mitral repair (teer).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient underwent transcatheter edge‑to‑edge mitral valve repair (teer) under general anesthesia. Two transcatheter mitral valve clips (lc-8-12, lc-6-12) were deployed at the a2-3/p2-3 and a2/p2 positions, respectively. The procedure was uneventful, and no significant murmur was auscultated in the cardiac valve area postoperatively. Follow‑up echocardiography showed marked reduction of mitral regurgitation with a small residual jet (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and bedside chest radiography confirmed correct clip positioning (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe procedure was performed in the morning; the patient was safely returned to the ward at noon and extubated, reporting marked improvement in dyspnea. Vital signs immediately post‑procedure were hr 81 bpm and bp 116/68 mmhg, and cardiac auscultation revealed substantially reduced murmurs. That afternoon, tea‑colored urine was noted in the urinary catheter bag with associated nausea and a 24‑hour urine output\u0026thinsp;\u0026lt;\u0026thinsp;100 ml. Laboratory tests demonstrated a drop in hemoglobin from baseline with an elevated reticulocyte count (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), and concurrent rises in serum creatinine, blood urea nitrogen, total bilirubin, and lactate dehydrogenase, while platelet count remained stable (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The patient received theophylline for membrane stabilization, urine alkalinization, and aggressive intravenous hydration. After ~\u0026thinsp;20 hours of hydration, a torasemide infusion was started. Following approximately 4,000 ml of fluid replacement, urine output improved\u0026thinsp;~\u0026thinsp;24 hours post‑procedure and urine cleared by the second postoperative night (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter the initial treatment the patient\u0026rsquo;s symptoms resolved\u0026mdash;no dyspnea or nausea\u0026mdash;and mental status improved. On postoperative day 3, however, transient tea‑colored urine recurred after a red blood cell transfusion, accompanied by nausea and vomiting; following repeat hydration the urine cleared the next day, and this episode was markedly shorter than the first. Hemolysis workup showed a positive direct antiglobulin (coombs) test, low serum haptoglobin, persistently elevated lactate dehydrogenase, and schistocytes on peripheral smear (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e), consistent with intravascular hemolysis. On postoperative day 10 the patient had another brief episode of tea‑colored urine without significant symptoms, which may have been associated with a higher blood pressure that day (154/73 mmhg).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient experienced recurrent tea‑colored urine consistent with device‑related hemolysis. Cardiothoracic surgery recommended mitral valve replacement, but given the patient\u0026rsquo;s advanced age, high operative risk, good mental status, absence of distress, and family reluctance for thoracotomy, clopidogrel was held and hemolysis was monitored conservatively. After stopping antiplatelet therapy, hemoglobin stabilized, lactate dehydrogenase began to decline, renal function recovered, and no further tea‑colored urine occurred. The patient was discharged uneventfully. At 1‑month follow‑up hemoglobin remained stable and heart‑failure symptoms were markedly improved. Because of in‑hospital paroxysmal atrial fibrillation and a cha2ds2‑vasc score of 6, oral anticoagulation with edoxaban 15 mg was resumed. At 2 months post‑procedure echocardiography showed satisfactory mitral valve function with persistent mild\u0026ndash;moderate regurgitation (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e); the patient remained largely asymptomatic, but ldh had not shown a further significant decline.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis report is the first to highlight the bold approach of discontinuing antiplatelet therapy to alleviate hemolysis after transcatheter edge-to-edge repair (teer). Previous literature has documented \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003ecases of hemolytic anemia occurring after atrial septal defect (asd) closure, where discontinuing antiplatelet therapy resulted in significant improvement of hemolytic symptoms. This suggests that antiplatelet agents may contribute to exacerbating or sustaining hemolysis in certain patients. In the present case, a review of the treatment process revealed that hemolytic manifestations gradually improved after cessation of antiplatelet medication, accompanied by a marked increase in hemoglobin levels.this clinical observation suggests that for patients who experience hemolysis following teer, a conservative treatment approach may be considered, particularly when mitral regurgitation is mild and vital signs remain stable. After ruling out serious complications such as infection or device dislocation, temporary discontinuation of antiplatelet or anticoagulant therapy may be a reasonable strategy. This approach allows for optimal adaptation between the valve and the implanted clip, as well as for local tissue healing.simultaneously, active supportive care is essential. This includes aggressive intravenous hydration to prevent renal injury from hemoglobinuria and avoid tubular obstruction, blood pressure and heart rate control, renal protection, and measures to stabilize erythrocyte membranes. As hemolysis resolves, cautious reintroduction of anticoagulant therapy at low doses may be considered. Throughout this process, close monitoring of hemolysis indices, renal and cardiac function, and overall clinical status is crucial. Therapy should be promptly modified, and surgical intervention should be considered if conservative measures fail.mechanical intravascular hemolysis (mih) is the pathological process in which red blood cells are mechanically damaged and fragmented within the vascular lumen.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e。This complication is uncommon after conventional surgical valve replacement and even rarer following teer; published reports are limited, and no consensus exists on diagnostic criteria or management. Barrett et al. \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003ereported intravascular hemolysis after mitraclip in which conservative measures failed and the patient ultimately required mitral valve replacement, implicating persistent postoperative mitral regurgitation as a potential cause. Yokoyama et al.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e described a case of subacute hemolytic anemia after teer in which the patient remained on anti-platelet therapy and received only transfusion support, achieving a favorable outcome. The authors noted several factors that may have contributed to the good prognosis: Absence of underlying cardiac dysfunction (preoperative lvef 72.5%), later onset of hemolysis (2 weeks postprocedure), and other clinical variables.\u003c/p\u003e \u003cp\u003eThe mechanism of device-related hemolysis following mitral valve surgery remains incompletely understood; but several hypotheses have been proposed. Mechanical direct injury is a principal mechanism: Erythrocytes exposed to excessive shear stress or physical trauma from contact with native cardiac structures, prosthetic/repair devices, or abnormal flow jets can undergo membrane disruption and fragmentation, resulting in intravascular hemolysis\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e].secondly, device‑related structural abnormalities are important precipitants of hemolysis. Features such as annular rupture, device malposition or migration, and exposed sutures or clips can create turbulent flow and focal high‑shear zones, increasing mechanical trauma to erythrocytes and exacerbating hemolysis\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.furthermore, residual or recurrent mitral regurgitation must be considered, as high‑velocity regurgitant jets generate focal high‑shear forces that markedly increase erythrocyte trauma and exacerbate hemolysis\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.in the first reported case of hemolysis after mitraclip, yokoyama et al. \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e attributed red‑cell fragmentation to high‑velocity flow through a narrow gap between the device surface and the coaptation line, causing repeated collisions with the device. This mechanism parallels our case: Serial postoperative echocardiography demonstrated persistent mild\u0026ndash;moderate eccentric mitral regurgitation. High‑velocity jets traversing a narrow orifice generate substantial shear stress and focal impact forces, promoting erythrocyte membrane disruption and intravascular hemolysis. These observations reinforce residual regurgitation as a plausible and important contributor to post‑teer hemolysis.\u003c/p\u003e \u003cp\u003eFor device‑related hemolysis after mitral valve interventions, current evidence indicates that reoperation is an effective option to eliminate the mechanical source of hemolysis in patients who are suitable surgical candidates\u0026mdash;particularly for severe paravalvular leaks or hemolysis refractory to conservative measures. \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e regarding pharmacotherapy, several agents have been reported to ameliorate symptoms of mechanical postoperative hemolysis, including beta‑blockers, erythropoietin, iron supplementation, folic acid, vitamins b12 and b6, and theophylline.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e therefore, in this case, timely, individualized adjustment of pharmacotherapy may represent an effective strategy for managing post‑procedural hemolytic anemia.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTranscatheter edge‑to‑edge repair (teer) is an important therapeutic option for elderly patients with mitral regurgitation who are poor surgical candidates; therefore, thoracotomy should be avoided when feasible. Although hemolytic anemia after percutaneous mitral clip placement is uncommon, it carries substantial clinical implications and is frequently associated with residual postprocedural regurgitation. Early recognition and targeted intervention can control hemolysis; in selected patients, temporary discontinuation of antiplatelet therapy may ameliorate symptoms, but the attendant thrombotic risk necessitates intensified surveillance and individualized management. Combined pharmacologic and supportive measures offer effective non‑surgical treatment alternatives that can relieve symptoms while minimizing operative risk.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003eThis study has obtained ethical approval from the\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent for publication:\u003c/h2\u003e \u003cp\u003eAll authors consent to submit this manuscript for publication in bmc cardiovascular disorders and confirm that all co-authors are aware of and agree with the content of the manuscript.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003ethis study did not receive any external funding support.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYXL is responsible for manuscript writing and revision; ZFF and YWL are responsible for surgery and treatment guidance; FX is responsible for providing and analyzing the researchers' imaging; ZHB and QYZ are responsible for data collection; JJT and QYZ are responsible for providing guidance on research direction and ensuring the overall quality and academic standards of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eSpecial thanks to the Second Xiangya Hospital of Central South University for the assistance and support provided in this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analyzed during this study; therefore, data sharing is not applicable to this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOtto cm. nishimura ra, bonow ro, carabello ba, erwin jp 3rd, gentile f, jneid h, krieger ev, mack m, mcleod c, o'gara pt, rigolin vh, sundt tm 3rd, thompson a, toly c. 2020 acc/aha guideline for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation. 2021 feb 2;143(5):E72-e227.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarrett. cd, cerbin l, desai a, carroll jd. Red blood cell fragmentation syndrome after placement of mitraclip. Jacc case rep. 2020 jun 17;2(7):1084\u0026ndash;1088.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLam. bk, cosgrove dm, bhudia sk, gillinov am. Hemolysis after mitral valve repair: Mechanisms and treatment. Ann thorac surg. 2004 jan;77(1):191-5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRabbani. m, hafiz a, algadheeb m, thain a, kiaii bb. A case of systolic anterior motion after mitral valve repair causing hemolytic anemia: Mechanism and treatment. Can j cardiol. 2020 dec;36(12):1977.e5-1977.e8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInoue m. kaku b, kanaya h, ohka t, ueda m, masahiro s, shimizu m, mabuchi h. Reduction of hemolysis without reoperation following mitral valve repair. Circ j. 2003 sep;67(9):799\u0026ndash;801.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaudo m. cuko b, ternacle j, sicouri s, busuttil o, denti p, godino c, de vincentiis c, ramlawi b, leroux l, modine t, palloshi a, maisano f. Transcatheter management of residual mitral regurgitation after transcatheter edge-to-edge repair: A systematic review. Cardiovasc interv ther. 2025 apr;40(2):255\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishimura ra. otto cm, bonow ro, carabello ba, erwin jp 3rd, fleisher la, jneid h, mack mj, mcleod cj, o'gara pt, rigolin vh, sundt tm 3rd, thompson a. 2017 aha/acc focused update of the 2014 aha/acc guideline for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association task force on clinical practice guidelines. Circulation. 2017 jun 20;135(25):E1159-e1195.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang jb. wen zk, lu wj, lu cc, tang xm. Diagnosis and treatment of mechanical hemolysis after mitral repair in adult. Heart surg forum 2021 feb 16;24(1):E165\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCannata a. cantoni s, sciortino a, bruschi g, russo cf. Mechanical hemolysis complicating transcatheter interventions for valvular heart disease: Jacc state-of-the-art review. J am coll cardiol. 2021 may 11;77(18):2323\u0026ndash;2334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYokoyama h. mizuno s, saito s. Subacute hemolytic anemia after transcatheter edge-to-edge mitral valve repair: A case report. Catheter cardiovasc interv. 2020 may 1;95(6):1230\u0026ndash;1234.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie. x, hanx, ye h, Hemolysis after transcatheter closure of atrial septal defect: A case report.chin j intervent cardiol, 2019 october , 27(10):599\u0026ndash;600.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Teer procedure, hemolytic anemia, severe mitral valve regurgitation, postoperative complications, device-related hemolysis","lastPublishedDoi":"10.21203/rs.3.rs-8948456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8948456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:This report describes an 82-year-old female patient who developed secondary hemolysis following transcatheter edge-to-edge mitral valve repair (teer) for severe mitral regurgitation.\u003c/p\u003e\n\u003cp\u003eCase presentation:On the day of the procedure, upon returning to the ward, the urinary catheter drainage bag showed tea-colored urine accompanied by oliguria. Subsequent evaluation revealed decreased hemoglobin, elevated lactate dehydrogenase, reduced haptoglobin, and acute renal failure, with the final diagnosis of device-related hemolysis. Following high-dose hydration and diuresis, the patient avoided hemodialysis, and renal function recovered. After discontinuation of antiplatelet therapy, hemolysis symptoms were controlled, and hemoglobin levels gradually improved.\u003c/p\u003e\n\u003cp\u003eConclusions:In selected patients, temporary discontinuation of antiplatelet therapy may ameliorate symptoms, but the attendant thrombotic risk necessitates intensified surveillance and individualized management.\u003c/p\u003e","manuscriptTitle":"Conservative Management of Hemolytic Anemia Following Percutaneous Mitral Valve Clip Procedure: A Successful Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-09 00:45:21","doi":"10.21203/rs.3.rs-8948456/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-14T04:48:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137265907256701225992540066006051374571","date":"2026-04-14T04:19:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-06T20:14:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174042714751119819897117357321906201771","date":"2026-04-02T12:56:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-02T08:37:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T05:01:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-13T16:53:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T20:53:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-03-11T13:43:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b07a0f54-15dd-4802-b5aa-792b7b2dfb8c","owner":[],"postedDate":"April 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-09T00:45:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-09 00:45:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8948456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8948456","identity":"rs-8948456","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}