Percutaneous Mitral Valve Repair in Pediatric Patients

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Scott Lim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3711501/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Dec, 2023 Read the published version in Pediatric Cardiology → Version 1 posted 7 You are reading this latest preprint version Abstract Rigorous clinical trials have demonstrated the safety and efficacy of Transcatheter Edge-to-Edge Repair (TEER) to treat severe secondary mitral regurgitation in adults with primary cardiomyopathy who have failed guideline directed medical therapy, as well as those with primary mitral regurgitation at high surgical risk. To date, there have only been three case reports describing this procedure in the pediatric population. We report a case series of four pediatric patients, including the youngest and smallest reported, who underwent this procedure. Figures Figure 1 Figure 2 Introduction Therapeutic options for congestive heart failure (CHF) in the pediatric population remain limited, with very few studies assessing the benefit of novel medications or devices approved for adults. Dilated cardiomyopathy (DCM) can be associated with secondary mitral regurgitation (MR) contributing to the patient’s burden of CHF. Similarly, patients with primary mitral valve disease can also present with CHF. For patients with secondary MR, guideline directed medical therapy (GDMT) is considered the first step in treatment. Mitral valve surgery has previously been considered, and surgical replacement has found value over repair 1 . However, more recently, surgery has been supplanted in the guidelines and in practice by transcatheter approaches to severe secondary MR. In cases with advanced left ventricular dysfunction, ventricular assist devices (VAD), and/or cardiac transplantation are the standard of care, albeit limited in availability. However, these options are not available for all children for various reasons. Fairly rigorous clinical trials have demonstrated the safety and efficacy of Transcatheter Edge-to-Edge Repair (TEER) to treat severe secondary MR in adults with primary cardiomyopathy who have failed GDMT, as well as those with primary MR at high surgical risk 2 – 6 . While over 150,000 adult patients have been treated with TEER, only three case reports exist describing this procedure in pediatric patients with CHF unresponsive to medical treatment 7 – 9 . We report our recent experience with TEER for severe MR in four pediatric patients. Case Series Patient 1 was a 17 year old (y/o) who underwent heart transplant in infancy for failed single ventricle palliation and presented with CHF exacerbation secondary to severe mixed etiology MR (anterior leaflet prolapse in the transplanted heart with progressive restriction of the posterior leaflet) with decreased ventricular function. His post-transplant course was notable for ventricular tachycardia requiring implantable cardioverter defibrillator placement, post-transplant lymphoproliferative disorder, stage III chronic kidney disease, and a history of both cellular mediated rejection and cardiac allograft vasculopathy. Despite GDMT his heart failure progressed to requiring inpatient care with inotropic support. He was deemed to not be a re-transplant or surgical candidate due to comorbidities and psychosocial concerns, so he was transferred to our institution for transcatheter mitral valve repair with the MitraClip device (Abbott Vascular, Santa Clara, California). Intraprocedural transesophageal echocardiography (TEE) confirmed degenerative mitral valve disease with anterior leaflet prolapse. He underwent TEER of the mitral valve with placement of one MitraClip, with reduction in MR from severe to mild (Fig. 1 ). At last follow up, his MR was moderate by transthoracic echocardiography (TTE) and he was without symptoms or physical limitations. He continues to be free from re-hospitalization 10 years after his TEER procedure. Patient 2 was a 17 y/o male with a history of Graves’ disease who developed thyrotoxicosis-induced DCM with moderately decreased bi-ventricular function and severe secondary MR and tricuspid regurgitation requiring inpatient care with intravenous inotropes. He was unable to wean off inotropic support despite GDMT. Several psychosocial concerns discovered during the heart transplant evaluation process precluded him from transplant consideration. His right ventricular dysfunction with severe tricuspid insufficiency were prohibitive risk factors for surgical repair of his MR, so transcatheter mitral valve repair was pursued. He underwent TEER with placement of two MitraClips with reduction in MR from severe to mild, and improvement in cardiac index from 1.0 to 2.9 L/min/m 2 . Inotropic support was discontinued two days later and he was discharged ten days later. Over a two year follow-up period, he has been without readmission with improved symptoms. Patient 3 was a 6 y/o referred to our center for congenital mitral valve dysplasia with severe degenerative MR, severe LV dilation with mild dysfunction, and worsening heart failure symptoms. He was a poor surgical candidate due to multiple comorbidities including hepatic cirrhosis. He underwent TEER with reduction in MR from severe to mild-moderate. At follow up evaluation two years later, his family reported that he maintained his improved exercise tolerance, his MR remained moderate, and he has been free from hospitalization. Patient 4 was a 12 y/o with DCM with severe LV dysfunction and severe secondary MR had recurrent heart failure admissions and progressive end-organ injury. Despite being placed on optimal GDMT, he deteriorated further requiring intubation and inotropic support. Transplant evaluation was initiated but he was felt to be a poor candidate secondary to medication non-compliance throughout his multiple hospital admissions, as well as other psychosocial concerns. For similar reasons, a VAD was not a suitable option, so he underwent TEER of the mitral valve with placement of one MitraClip with reduction in MR from severe to mild. He was extubated and weaned off all vasoactive medications within ten days and discharged home. After demonstrating improved compliance in the outpatient setting, he was later readmitted and underwent LVAD placement and subsequently heart transplantation five months after TEER procedure. Discussion TEER of the mitral valve is an established treatment option for adult patients with primary MR who are at high or prohibitive surgical risk and for those with secondary MR who remain symptomatic despite GDMT, regardless of the surgical risk. These treatment strategies are supported by data from the EVEREST II and COAPT randomized controlled trials, as well as from large international registries. However, the patients enrolled in these trials were predominately an elderly cohort 2 – 4 , 6 , 10 – 14 . To our knowledge, this constitutes the first case series on TEER use in pediatric patients. In TEER using the MitraClip, the delivery system consists of a large bore steerable guide catheter sized 24 French at the skin, and 22 French as it crosses the interatrial septum, which likely limits its utility in pediatric patients under 15–20 kilograms (Fig. 2 A). Following common femoral venous access, the delivery system is introduced into the right atrium and across the inter-atrial septum to bring the MitraClip device to the mitral valve (Fig. 2 C). The anterior and posterior mitral valve leaflets are grasped between the clip arms and frictional gripper elements of the device and brought together to reduce the regurgitant orifice area. Although TEER has been proven safe, and durable out to 5 years, there remains a paucity of longer-term data on the durability of its efficacy - an especially important consideration in younger patients who are surgical candidates. Currently in younger adult patients at low surgical risk, there are multiple trials with rigorous follow-up to ten-years that are currently in progress -- PRIMARY (Percutaneous or Surgical Mitral Valve Repair, ClinicalTrials.gov: NCT05051033) and REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve REpair in PAtients with PrImaRy MItral Regurgitation Who Are Candidates for Surgery, ClinicalTrials.gov: NCT04198870). This procedure has value in certain clinical scenarios. As we have shown, patients with MR in cardiogenic shock or refractory heart failure who are at prohibitive risk for surgery can be stabilized by TEER to allow further evaluation, mitral valve surgery, or serve as definitive therapy. Furthermore, in patients with advanced heart failure and secondary MR despite GDMT, TEER can serve as definitive therapy, decrease the need for LVAD or heart transplant, or serve as a bridge to those advanced therapies. As shown in our series, TEER can improve heart failure symptoms such that more advanced therapies such as heart transplantation may no longer be required. This benefit was observed in the MitraBridge registry for which 119 adult heart transplant candidates with advanced heart failure and at least moderate-to-severe MR underwent TEER with MitraClip as a bridging therapy. Nearly one-quarter (23.5%) of patients were removed from the heart transplant list due to clinical improvement and two-thirds (64%) remained free from major adverse events at 1 year (death, urgent heart transplant or LVAD implantation, re-hospitalization for heart failure) 15 . There are technical considerations for TEER specific to the pediatric population. Pre-procedural planning is paramount with careful consideration of the overall size, height, and weight of the patient. The MitraClip steerable guide catheter comes in a single size of 24 French at skin entry. If there is a concern of an inadequate iliofemoral venous system to accommodate the guide catheter, a computed tomography scan, with venous phase, is useful to evaluate the vascular anatomy with more precision. In those with a small left atrium, maneuvering the device can be challenging. Slow, controlled steering under constant echocardiographic visualization is important to avoid structural injury, as serious procedural complications can occur despite a cautious approach. There are currently two different types of TEER devices (MitraClip and Pascal), that also come in various sizes with different lengths and widths, allowing physicians to choose a device size best suited to each patient’s mitral valve anatomy for optimal MR reduction without introducing significant mitral stenosis. The third patient in our series is the youngest and smallest patient to have undergone this procedure at 6 years of age, weighing 19 kilograms. Randomized clinical trials in adult patients with CHF and moderate to severe MR demonstrate a reduction in all-cause mortality, need for transplant, and re-hospitalization following TEER, as well as symptomatic improvement. Although not as well studied in younger patients, our case series adds to the limited existing pediatric data to suggest this may be a therapeutic option in select patients with prohibitive surgical risk for primary MR, and for those with symptomatic secondary MR despite GDMT. Declarations Ethics declarations: Dr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures. This study was approved by the institutional review board (IRB) of the University of Virginia Competing Interests Dr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures. Author Contribution MM and SL conceived of this review. FH and NW performed literature review, data collection, and writing of the manuscript. All authors edited and reviewed the mansuscript. References Acker MA, Dagenais F, Goldstein D, Kron IL (2015) Perrault, L. P. Severe ischemic mitral regurgitation: Repair or replace? J Thorac Cardiovasc Surg 150:1425–1427 Feldman T et al (2005) Percutaneous mitral valve repair using the edge-to-edge technique: Six-month results of the EVEREST phase I clinical trial. J Am Coll Cardiol 46:2134–2140 Feldman T et al (2015) Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation 5-Year Results of EVEREST II. J Am Coll Cardiol 66:2844–2854 Stone GW et al (2018) Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 379:2307–2318 Lim DS et al (2022) Randomized Comparison of Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients. JACC Cardiovasc Interv 15, Glower DD et al (2014) Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: Results of the EVEREST II study. J Am Coll Cardiol 64:172–181 Gorenflo M, Katus HA, Bekeredjian R (2013) Successful MitraClipTM implantation in a 15-year-old patient with multiple prior cardiac surgeries. Cardiol Young 23:620–622 Joffe DC et al (2016) Not for adults only: MitraClip use in a paediatric patient. EuroIntervention 12:e1065–e1070 Saji M et al (2022) Successful transcatheter mitral valve repair with the MitraClip system in a patient with Duchenne muscular dystrophy. J Cardiol Cases 26:59–61 Obadia J-F et al (2018) Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med 379:2297–2306 Maisano F et al (2013) Percutaneous mitral valve interventions in the real world: Early and 1-year results from the ACCESS-EU, A prospective, multicenter, nonrandomized post-approval study of the Mitraclip therapy in Europe. J Am Coll Cardiol 62:1052–1061 Nickenig G et al (2014) Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011–2012 pilot European Sentinel Registry. J Am Coll Cardiol 64:875–884 Baldus S et al (2012) Mitra Clip therapy in daily clinical practice: Initial results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail 14:1050–1055 Sorajja P et al (2017) Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT Registry Report. J Am Coll Cardiol 70:2315–2327 Godino C et al (2020) MitraClip in secondary mitral regurgitation as a bridge to heart transplantation: 1-year outcomes from the International MitraBridge Registry. J Hear Lung Transplant 39:1353–1362 Additional Declarations Competing interest reported. Dr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures. Cite Share Download PDF Status: Published Journal Publication published 27 Dec, 2023 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Accepted 18 Dec, 2023 Reviews received at journal 18 Dec, 2023 Reviewers agreed at journal 18 Dec, 2023 Reviewers invited by journal 10 Dec, 2023 Submission checks completed at journal 06 Dec, 2023 Editor assigned by journal 06 Dec, 2023 First submitted to journal 05 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-3711501","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":256830923,"identity":"eab3e4fb-8292-423c-b476-661bc6921b86","order_by":0,"name":"Firezer Haregu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBAC9hnsByQ+ABkGDAyMBxgbiNDCc4MnQXIGRAvDgYPEaWEwkOYhTYt0Q+Jt27bD8ubszQ8Of9zBIGfev4CAFpmDh61z2w4b7uw5ZnDg4BkGY5kbD/BrsZdISJPObUtj3HAjAailjSFxhsQBArZIJJhJW7al2W+4//wDCVoY22wSN9zggdrC30BIS06yZc85m+QNZ3IKDpxtkzCWkMCvA6gl/eCNH2USthuOH9/4oLLNRk6Cn4DD0AHQCokE0rQAAam2jIJRMApGwbAHAEk0S5qUO3XbAAAAAElFTkSuQmCC","orcid":"","institution":"University of Virginia Children's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Firezer","middleName":"","lastName":"Haregu","suffix":""},{"id":256830925,"identity":"54eeebd9-0113-4f3c-a538-e23effa23886","order_by":1,"name":"Ningyan Wong","email":"","orcid":"","institution":"University of Virginia","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ningyan","middleName":"","lastName":"Wong","suffix":""},{"id":256830926,"identity":"6d54093a-7e42-4c45-9747-cda89c190282","order_by":2,"name":"Michael McCulloch","email":"","orcid":"","institution":"University of Virginia Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"McCulloch","suffix":""},{"id":256830927,"identity":"5bcd04c8-3f77-4ac9-aa3e-6f3d2334b495","order_by":3,"name":"D. Scott Lim","email":"","orcid":"","institution":"University of Virginia Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"D.","middleName":"Scott","lastName":"Lim","suffix":""}],"badges":[],"createdAt":"2023-12-05 19:14:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3711501/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3711501/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-023-03387-4","type":"published","date":"2023-12-27T15:00:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":47813356,"identity":"50d6a6dd-5d8e-42c6-ae06-2eaf71135d70","added_by":"auto","created_at":"2023-12-07 19:31:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":373794,"visible":true,"origin":"","legend":"\u003cp\u003eTransesophageal echocardiographic (TEE) images showing reduction of mitral regurgitation severity from severe (A) to mild (B) after a single MitraClip (red arrow). (C) TEE 3D en-face view of the mitral valve showing the MitraClip implanted centrally, coapting the A2/P2 segments of the mitral valve leaflets. (D) Fluoroscopic image of MitraClip implantation.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-3711501/v1/5c0cb43f623d268085de4e20.png"},{"id":47813357,"identity":"2c64cc76-9b78-4b87-a171-9d324b784983","added_by":"auto","created_at":"2023-12-07 19:31:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":348611,"visible":true,"origin":"","legend":"\u003cp\u003e(A) MitraClip system consisting of MitraClip device, steerable guide catheter and clip delivery system. (B) MitraClip device showing the grippers and clip arms for which the mitral valve leaflets will be grasped between. (C) Diagram showing the transvenous and transseptal route for the MitraClip procedure. Images with approval from Abbott.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3711501/v1/3d7f1e8a90e26832f5d37cb5.png"},{"id":49028242,"identity":"5de0296e-10af-4f6e-9d06-34aba417ea2e","added_by":"auto","created_at":"2024-01-01 15:05:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1131779,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3711501/v1/4c06c9ee-a0b7-4c4d-ae3b-93f8f175a292.pdf"}],"financialInterests":"Competing interest reported. Dr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures.","formattedTitle":"Percutaneous Mitral Valve Repair in Pediatric Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTherapeutic options for congestive heart failure (CHF) in the pediatric population remain limited, with very few studies assessing the benefit of novel medications or devices approved for adults. Dilated cardiomyopathy (DCM) can be associated with secondary mitral regurgitation (MR) contributing to the patient\u0026rsquo;s burden of CHF. Similarly, patients with primary mitral valve disease can also present with CHF. For patients with secondary MR, guideline directed medical therapy (GDMT) is considered the first step in treatment. Mitral valve surgery has previously been considered, and surgical replacement has found value over repair\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. However, more recently, surgery has been supplanted in the guidelines and in practice by transcatheter approaches to severe secondary MR. In cases with advanced left ventricular dysfunction, ventricular assist devices (VAD), and/or cardiac transplantation are the standard of care, albeit limited in availability. However, these options are not available for all children for various reasons. Fairly rigorous clinical trials have demonstrated the safety and efficacy of Transcatheter Edge-to-Edge Repair (TEER) to treat severe secondary MR in adults with primary cardiomyopathy who have failed GDMT, as well as those with primary MR at high surgical risk\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. While over 150,000 adult patients have been treated with TEER, only three case reports exist describing this procedure in pediatric patients with CHF unresponsive to medical treatment\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. We report our recent experience with TEER for severe MR in four pediatric patients.\u003c/p\u003e"},{"header":"Case Series","content":"\u003cp\u003ePatient 1 was a 17 year old (y/o) who underwent heart transplant in infancy for failed single ventricle palliation and presented with CHF exacerbation secondary to severe mixed etiology MR (anterior leaflet prolapse in the transplanted heart with progressive restriction of the posterior leaflet) with decreased ventricular function. His post-transplant course was notable for ventricular tachycardia requiring implantable cardioverter defibrillator placement, post-transplant lymphoproliferative disorder, stage III chronic kidney disease, and a history of both cellular mediated rejection and cardiac allograft vasculopathy. Despite GDMT his heart failure progressed to requiring inpatient care with inotropic support. He was deemed to not be a re-transplant or surgical candidate due to comorbidities and psychosocial concerns, so he was transferred to our institution for transcatheter mitral valve repair with the MitraClip device (Abbott Vascular, Santa Clara, California). Intraprocedural transesophageal echocardiography (TEE) confirmed degenerative mitral valve disease with anterior leaflet prolapse. He underwent TEER of the mitral valve with placement of one MitraClip, with reduction in MR from severe to mild (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At last follow up, his MR was moderate by transthoracic echocardiography (TTE) and he was without symptoms or physical limitations. He continues to be free from re-hospitalization 10 years after his TEER procedure.\u003c/p\u003e \u003cp\u003ePatient 2 was a 17 y/o male with a history of Graves\u0026rsquo; disease who developed thyrotoxicosis-induced DCM with moderately decreased bi-ventricular function and severe secondary MR and tricuspid regurgitation requiring inpatient care with intravenous inotropes. He was unable to wean off inotropic support despite GDMT. Several psychosocial concerns discovered during the heart transplant evaluation process precluded him from transplant consideration. His right ventricular dysfunction with severe tricuspid insufficiency were prohibitive risk factors for surgical repair of his MR, so transcatheter mitral valve repair was pursued. He underwent TEER with placement of two MitraClips with reduction in MR from severe to mild, and improvement in cardiac index from 1.0 to 2.9 L/min/m\u003csup\u003e2\u003c/sup\u003e. Inotropic support was discontinued two days later and he was discharged ten days later. Over a two year follow-up period, he has been without readmission with improved symptoms.\u003c/p\u003e \u003cp\u003ePatient 3 was a 6 y/o referred to our center for congenital mitral valve dysplasia with severe degenerative MR, severe LV dilation with mild dysfunction, and worsening heart failure symptoms. He was a poor surgical candidate due to multiple comorbidities including hepatic cirrhosis. He underwent TEER with reduction in MR from severe to mild-moderate. At follow up evaluation two years later, his family reported that he maintained his improved exercise tolerance, his MR remained moderate, and he has been free from hospitalization.\u003c/p\u003e \u003cp\u003ePatient 4 was a 12 y/o with DCM with severe LV dysfunction and severe secondary MR had recurrent heart failure admissions and progressive end-organ injury. Despite being placed on optimal GDMT, he deteriorated further requiring intubation and inotropic support. Transplant evaluation was initiated but he was felt to be a poor candidate secondary to medication non-compliance throughout his multiple hospital admissions, as well as other psychosocial concerns. For similar reasons, a VAD was not a suitable option, so he underwent TEER of the mitral valve with placement of one MitraClip with reduction in MR from severe to mild. He was extubated and weaned off all vasoactive medications within ten days and discharged home. After demonstrating improved compliance in the outpatient setting, he was later readmitted and underwent LVAD placement and subsequently heart transplantation five months after TEER procedure.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTEER of the mitral valve is an established treatment option for adult patients with primary MR who are at high or prohibitive surgical risk and for those with secondary MR who remain symptomatic despite GDMT, regardless of the surgical risk. These treatment strategies are supported by data from the EVEREST II and COAPT randomized controlled trials, as well as from large international registries. However, the patients enrolled in these trials were predominately an elderly cohort\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. To our knowledge, this constitutes the first case series on TEER use in pediatric patients.\u003c/p\u003e \u003cp\u003eIn TEER using the MitraClip, the delivery system consists of a large bore steerable guide catheter sized 24 French at the skin, and 22 French as it crosses the interatrial septum, which likely limits its utility in pediatric patients under 15\u0026ndash;20 kilograms (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). Following common femoral venous access, the delivery system is introduced into the right atrium and across the inter-atrial septum to bring the MitraClip device to the mitral valve (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). The anterior and posterior mitral valve leaflets are grasped between the clip arms and frictional gripper elements of the device and brought together to reduce the regurgitant orifice area. Although TEER has been proven safe, and durable out to 5 years, there remains a paucity of longer-term data on the durability of its efficacy - an especially important consideration in younger patients who are surgical candidates. Currently in younger adult patients at low surgical risk, there are multiple trials with rigorous follow-up to ten-years that are currently in progress -- PRIMARY (Percutaneous or Surgical Mitral Valve Repair, ClinicalTrials.gov: NCT05051033) and REPAIR MR (Percutaneous MitraClip Device or Surgical Mitral Valve REpair in PAtients with PrImaRy MItral Regurgitation Who Are Candidates for Surgery, ClinicalTrials.gov: NCT04198870).\u003c/p\u003e \u003cp\u003eThis procedure has value in certain clinical scenarios. As we have shown, patients with MR in cardiogenic shock or refractory heart failure who are at prohibitive risk for surgery can be stabilized by TEER to allow further evaluation, mitral valve surgery, or serve as definitive therapy. Furthermore, in patients with advanced heart failure and secondary MR despite GDMT, TEER can serve as definitive therapy, decrease the need for LVAD or heart transplant, or serve as a bridge to those advanced therapies. As shown in our series, TEER can improve heart failure symptoms such that more advanced therapies such as heart transplantation may no longer be required. This benefit was observed in the MitraBridge registry for which 119 adult heart transplant candidates with advanced heart failure and at least moderate-to-severe MR underwent TEER with MitraClip as a bridging therapy. Nearly one-quarter (23.5%) of patients were removed from the heart transplant list due to clinical improvement and two-thirds (64%) remained free from major adverse events at 1 year (death, urgent heart transplant or LVAD implantation, re-hospitalization for heart failure)\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere are technical considerations for TEER specific to the pediatric population. Pre-procedural planning is paramount with careful consideration of the overall size, height, and weight of the patient. The MitraClip steerable guide catheter comes in a single size of 24 French at skin entry. If there is a concern of an inadequate iliofemoral venous system to accommodate the guide catheter, a computed tomography scan, with venous phase, is useful to evaluate the vascular anatomy with more precision. In those with a small left atrium, maneuvering the device can be challenging. Slow, controlled steering under constant echocardiographic visualization is important to avoid structural injury, as serious procedural complications can occur despite a cautious approach. There are currently two different types of TEER devices (MitraClip and Pascal), that also come in various sizes with different lengths and widths, allowing physicians to choose a device size best suited to each patient\u0026rsquo;s mitral valve anatomy for optimal MR reduction without introducing significant mitral stenosis. The third patient in our series is the youngest and smallest patient to have undergone this procedure at 6 years of age, weighing 19 kilograms.\u003c/p\u003e \u003cp\u003eRandomized clinical trials in adult patients with CHF and moderate to severe MR demonstrate a reduction in all-cause mortality, need for transplant, and re-hospitalization following TEER, as well as symptomatic improvement. Although not as well studied in younger patients, our case series adds to the limited existing pediatric data to suggest this may be a therapeutic option in select patients with prohibitive surgical risk for primary MR, and for those with symptomatic secondary MR despite GDMT.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics declarations:\u003c/h2\u003e\n\u003cp\u003e\u0026nbsp;Dr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures.\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional review board (IRB) of the University of Virginia\u003c/p\u003e\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eDr. Scott Lim reports that his institution receives research grants on his behalf from Abbott, Boston Scientific, Corvia, Edwards, Medtronic, V Wave, and WL Gore, and personal consulting fees from LagunaTech, Philips, Valgen, and Venus. All other authors do not have relevant disclosures.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMM and SL conceived of this review. FH and NW performed literature review, data collection, and writing of the manuscript. All authors edited and reviewed the mansuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAcker MA, Dagenais F, Goldstein D, Kron IL (2015) Perrault, L. P. Severe ischemic mitral regurgitation: Repair or replace? J Thorac Cardiovasc Surg 150:1425\u0026ndash;1427\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeldman T et al (2005) Percutaneous mitral valve repair using the edge-to-edge technique: Six-month results of the EVEREST phase I clinical trial. J Am Coll Cardiol 46:2134\u0026ndash;2140\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeldman T et al (2015) Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation 5-Year Results of EVEREST II. J Am Coll Cardiol 66:2844\u0026ndash;2854\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone GW et al (2018) Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 379:2307\u0026ndash;2318\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim DS et al (2022) Randomized Comparison of Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients. JACC Cardiovasc Interv 15,\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlower DD et al (2014) Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: Results of the EVEREST II study. J Am Coll Cardiol 64:172\u0026ndash;181\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGorenflo M, Katus HA, Bekeredjian R (2013) Successful MitraClipTM implantation in a 15-year-old patient with multiple prior cardiac surgeries. Cardiol Young 23:620\u0026ndash;622\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoffe DC et al (2016) Not for adults only: MitraClip use in a paediatric patient. EuroIntervention 12:e1065\u0026ndash;e1070\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaji M et al (2022) Successful transcatheter mitral valve repair with the MitraClip system in a patient with Duchenne muscular dystrophy. J Cardiol Cases 26:59\u0026ndash;61\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObadia J-F et al (2018) Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation. N Engl J Med 379:2297\u0026ndash;2306\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaisano F et al (2013) Percutaneous mitral valve interventions in the real world: Early and 1-year results from the ACCESS-EU, A prospective, multicenter, nonrandomized post-approval study of the Mitraclip therapy in Europe. J Am Coll Cardiol 62:1052\u0026ndash;1061\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNickenig G et al (2014) Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011\u0026ndash;2012 pilot European Sentinel Registry. J Am Coll Cardiol 64:875\u0026ndash;884\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaldus S et al (2012) Mitra Clip therapy in daily clinical practice: Initial results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail 14:1050\u0026ndash;1055\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSorajja P et al (2017) Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT Registry Report. J Am Coll Cardiol 70:2315\u0026ndash;2327\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGodino C et al (2020) MitraClip in secondary mitral regurgitation as a bridge to heart transplantation: 1-year outcomes from the International MitraBridge Registry. J Hear Lung Transplant 39:1353\u0026ndash;1362\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":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3711501/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3711501/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRigorous clinical trials have demonstrated the safety and efficacy of Transcatheter Edge-to-Edge Repair (TEER) to treat severe secondary mitral regurgitation in adults with primary cardiomyopathy who have failed guideline directed medical therapy, as well as those with primary mitral regurgitation at high surgical risk. To date, there have only been three case reports describing this procedure in the pediatric population. We report a case series of four pediatric patients, including the youngest and smallest reported, who underwent this procedure.\u003c/p\u003e","manuscriptTitle":"Percutaneous Mitral Valve Repair in Pediatric Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-12-07 19:31:52","doi":"10.21203/rs.3.rs-3711501/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2023-12-18T16:26:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-18T15:20:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6381f118-4789-4293-8dfa-3d38f3999d59","date":"2023-12-18T13:24:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-12-10T16:57:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-06T06:39:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-06T06:39:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2023-12-05T19:00:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"775acc6f-eaee-43cf-adee-85126a85d0f9","owner":[],"postedDate":"December 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-01-01T15:03:24+00:00","versionOfRecord":{"articleIdentity":"rs-3711501","link":"https://doi.org/10.1007/s00246-023-03387-4","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2023-12-27 15:00:51","publishedOnDateReadable":"December 27th, 2023"},"versionCreatedAt":"2023-12-07 19:31:52","video":"","vorDoi":"10.1007/s00246-023-03387-4","vorDoiUrl":"https://doi.org/10.1007/s00246-023-03387-4","workflowStages":[]},"version":"v1","identity":"rs-3711501","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3711501","identity":"rs-3711501","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}