The Long and Winding Road to an Effective Left Ventricular Assist Device: The Demise of Medtronic’s HVAD
2021; Lippincott Williams & Wilkins; Volume: 144; Issue: 7 Linguagem: Inglês
10.1161/circulationaha.121.056027
ISSN1524-4539
AutoresJosef Stehlik, James K. Kirklin,
Tópico(s)Cardiac Structural Anomalies and Repair
ResumoHomeCirculationVol. 144, No. 7The Long and Winding Road to an Effective Left Ventricular Assist Device: The Demise of Medtronic's HVAD Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessArticle CommentaryPDF/EPUBThe Long and Winding Road to an Effective Left Ventricular Assist Device: The Demise of Medtronic's HVAD Josef Stehlik, MD, MPH and James K. Kirklin, MD Josef StehlikJosef Stehlik Correspondence to: Josef Stehlik, MD, MPH, Division of Cardiovascular Medicine, Cardiac Transplant Program, University of Utah Health, 50 N Medical Dr, 4A100 SOM, Salt Lake City, UT 84132. Email E-mail Address: [email protected] https://orcid.org/0000-0002-7362-0513 Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City (J.S.). and James K. KirklinJames K. Kirklin Division of Cardiothoracic Surgery, University of Alabama at Birmingham (J.K.K.). Originally published9 Jun 2021https://doi.org/10.1161/CIRCULATIONAHA.121.056027Circulation. 2021;144:509–511Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 9, 2021: Ahead of Print In 1968, Paul McCartney composed the famous "The Long and Winding Road," a mournful song that embodied the sad end to The Beatles' run. On June 3, 2021, the Medtronic Corporation announced that the durable left ventricular assist device HVAD, currently approved by the US Food and Drug Administration (FDA) for bridge-to-transplant therapy and permanent or destination therapy, will be removed from the global market for new implants, effective immediately.1 This seminal event in the dynamic field of mechanical circulatory support (MCS) justifies a contemplation of the advances in the MCS field and the likely effect of this decision on future innovation.The first durable left ventricular assist devices (LVADs) were pulsatile pumps with high adverse event rate and insufficient durability. Engineering innovation resulted in the introduction of continuous-flow LVADs, which afforded a smaller size and fewer moving parts, promising a more favorable adverse event profile. A number of continuous-flow devices entered preclinical or clinical testing (Figure), but only 2 companies have prevailed as the dominant manufacturers of durable LVADs: Thoratec Corporation and HeartWare International. Prospective clinical trials eventually lead to FDA approval of the HeartMate II device (Thoratec, Pleasanton, CA) and the HVAD device (HeartWare, Framingham, MA).Download figureDownload PowerPointFigure. Overview of clinical testing timeline and approval for select durable continuous-flow LVADs. Orange highlight indicates the approximate period of clinical testing; green highlight indicates year of approval for clinical use by the US Food and Drug Administration. BTT indicates bridge-to-transplant indication; DT, destination therapy indication; LT, long-term therapy indication; and LVAD, left ventricular assist device.Favorable results of the clinical trials, along with FDA device approvals and expanded clinical experience with the 2 dominant devices fueled the rapid pace of progress; thousands of patients received durable LVAD therapy, and many centers started new LVAD programs. As the experience in patient selection grew and protocolized multidisciplinary care was implemented, survival became more predictable. In fact, the improved survival of bridge-to-transplant therapy patients supported by continuous-flow LVADs resulted in a downgrading of LVAD patient priority for heart transplantation in the United States in 2018. Yet, the adverse event profile of durable LVAD therapy remained a significant challenge with morbid and potentially fatal complications such as stroke, device-related infection, gastrointestinal bleeding, and pump thrombosis.The evolution of durable LVAD therapy as a mainstream treatment for advanced heart disease naturally influenced corporate investments. In 2009, Thoratec Corporation announced their intent to acquire HeartWare International, but the merger was blocked by the US Federal Trade Commission, which was concerned with substantially reduced competition in the market for LVADs. Global medical device manufacturers subsequently entered the space of durable MCS. Thoratec Corporation was acquired by St Jude Medical in 2015, which was, in turn, acquired by Abbott in 2017. HeartWare International was acquired by Medtronic in 2016. These acquisitions were viewed with an anticipation of further investment in research and development and provided to relatively small device companies an avenue for access to a substantial infrastructure that could foster further evolution of the ventricular assist device technology and its clinical applications. Abbott sponsored a randomized study of 1026 patients that showed its newly developed, fully magnetically levitated LVAD HeartMate 3 device was superior to the HeartMate II.2 Medtronic completed the FDA destination therapy approval process for its newly acquired HVAD LVAD and improved device peripherals.The HeartMate 3 LVAD was FDA-approved for bridge-to-transplant therapy in 2017 and for long-term therapy in 2018, followed by an almost immediate divestment of clinicians from the HeartMate II device in favor of HeartMate 3. Meanwhile, in the absence of head-to-head comparison of HeartMate 3 and HVAD in clinical trials, clinicians started to reevaluate patient selection for the 2 FDA-approved devices. Investigators also turned to the Society of Thoracic Surgeons' INTERMACS (Interagency Registry for Mechanically-Assisted Circulatory Support), comparing clinical outcomes of LVADs with centrifugal flow and hybrid levitation with clinical outcomes of LVADs with centrifugal flow and full magnetic levitation (representing mostly HVAD and HeartMate 3, respectively).3,4 The reports suggested that HeartMate 3 was associated with superior outcomes, including freedom from stroke, gastrointestinal bleed, infection, and survival. A study using Medicare claims files further confirmed these results.5The findings supported an ongoing trend in the United States toward increased use of the HeartMate 3 and decreased application of the HVAD. Medtronic would have to determine whether improvements to identified shortcomings of the HVAD would improve clinical outcomes to approximate the results seen with HeartMate 3. The FDA would have to decide whether changes to device labeling or other actions were needed. This occurred in the context of 2 recent FDA class I HVAD recalls for unexpected power source switching, and instances where the pump failed to initially start, restart, or had a delay in restarting after it was stopped.The key decisions have now been made: Medtronic moved to discontinue the availability of HVAD for future implants. Clinical management of the ≈4000 patients with HVAD is to follow the current clinical practice, and Medtronic has committed to ongoing product support. As the full details are communicated, lessons can be learned from yet another dramatic turn of events in the durable MCS field:While clinical trials provide us with robust evidence, the results address only the specific questions they are designed to answer. Postapproval registries that are well planned and well funded can—and should, be used to generate information directly impacting patient care decisions—especially in areas of rapidly evolving treatment approaches.The goal and modus operandi in our professional lives is to seek solutions for problems. Sometimes the right solution is not to remedy but to stop or abandon a process after disciplined and informed deliberations.Regulatory oversight, often viewed as overbearing, provides a needed guidance in complex therapies. The Independent Practitioner Quality Panel, established by Medtronic on the basis of an FDA recommendation, assisted the company in defining the appropriate response and its implementation.1 The FDA will continue to play an important role in supporting clinicians and patients in this transition and into the future, where many patients will be supported by a device that is no longer manufactured.There is no doubt that the departure of the HVAD from the durable MCS field will have some unwelcome consequences. While most patients will receive an alternate durable LVAD for their treatment, some patients will be disadvantaged. In particular, pediatric patients and petite adults with a body size that accommodates HVAD, but not the larger HeartMate 3, will not have a feasible option for durable intracorporeal support. For patients with an HVAD who may need LVAD replacement in the future, the LVAD replacement surgery may be more technically challenging because a different LVAD will be required.The degree to which the decision to stop HVAD distribution was financially driven will be argued. It is clear, though, that the massive commercial cost of a failed device with such global recognition, coupled with the presence now of a single dominant manufacturer, may discourage investment, innovation, and novel device development.The departure of HVAD concludes one era of durable LVAD therapy. HVAD has helped thousands of patients emerge from advanced symptoms of heart failure, reenter active lifestyle, or reach transplant. Although the barriers to entry into the durable LVAD field are real, as witnessed by the number of devices that did not advance from clinical testing to FDA approval (Figure) and are highlighted by recent events, we look forward to major advances in the current technologies as well as new disruptive innovations that improve and extend the lives of our patients. However, the challenges of the long and winding road of durable MCS have suddenly become much more formidable.Sources of FundingNone.Disclosures Dr Stehlik reports receiving consulting fees from Medtronic for serving on the Independent Practitioner Quality Panel, and he serves as Medical Director of the International Society for Heart and Lung Transplantation International Thoracic Organ Transplant Registry. Dr Kirklin serves as Director of Society of Thoracic Surgeons INTERMACS (Interagency Registry for Mechanically-Assisted Circulatory Support) Data Coordinating Center.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 511.https://www.ahajournals.org/journal/circCorrespondence to: Josef Stehlik, MD, MPH, Division of Cardiovascular Medicine, Cardiac Transplant Program, University of Utah Health, 50 N Medical Dr, 4A100 SOM, Salt Lake City, UT 84132. Email josef.[email protected]utah.eduReferences1. Urgent medical device communication notification letter Medtronic HVAD System. Mounds View, MN: Medtronic; June 3, 2021. https://www.medtronic.com/content/dam/medtronic-com/global/HCP/Documents/hvad-urgent-medical-device-notice-june-2021.pdf. Accessed June 7, 2021.Google Scholar2. Mehra MR, Uriel N, Naka Y, Cleveland JC, Yuzefpolskaya M, Salerno CT, Walsh MN, Milano CA, Patel CB, Hutchins SW, et al.; MOMENTUM 3 Investigators. A fully magnetically levitated left ventricular assist device - final report.N Engl J Med. 2019; 380:1618–1627. doi: 10.1056/NEJMoa1900486CrossrefMedlineGoogle Scholar3. Teuteberg JJ, Cleveland JC, Cowger J, Higgins RS, Goldstein DJ, Keebler M, Kirklin JK, Myers SL, Salerno CT, Stehlik J, et al.. The Society of Thoracic Surgeons Intermacs 2019 Annual Report: the changing landscape of devices and indications.Ann Thorac Surg. 2020; 109:649–660. doi: 10.1016/j.athoracsur.2019.12.005CrossrefMedlineGoogle Scholar4. Pagani FD, Cantor R, Cowger J, Goldstein D, Teuteberg J, Mahr C, Atluri P, Kilic A, Maozami N, Habib R, et al.. Concordance of treatment effect: an analysis of the Society of Thoracic Surgeons Intermacs database [published online June 1, 2021].Ann Thorac Surg. doi: 10.1016/j.athoracsur.2021.05.017.Google Scholar5. Pagani FD, Mehra MR, Cowger JA, Horstmanshof DA, Silvestry SC, Atluri P, Cleveland JC, Lindenfeld J, Roberts GJ, Bharmi R, et al.. Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - the CLEAR-LVAD study.J Heart Lung Transplant. 2021; 40:323–333. doi: 10.1016/j.healun.2021.02.010CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ibeh C, Melmed K, Yuzefpolskaya M, Colombo P and Willey J (2022) Stroke epidemiology and outcomes in the modern era of left ventricular assist devices, Heart Failure Reviews, 10.1007/s10741-021-10201-x, 27:2, (393-398), Online publication date: 1-Mar-2022. Amarelli C and Trivedi J (2022) Patient-centered real-world registry analysis of cfLVAD recipients: From survival to freedom from hospitalization and beyond, The Journal of Heart and Lung Transplantation, 10.1016/j.healun.2021.10.011, 41:2, (171-173), Online publication date: 1-Feb-2022. August 17, 2021Vol 144, Issue 7Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.056027PMID: 34106733 Originally publishedJune 9, 2021 Keywordsdevice approvalheart failureheart-assist deviceUnited States Food and Drug AdministrationPDF download Advertisement SubjectsHeart Failure
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