The good, the bad, the ugly: Optimal left ventricular assist device duration in bridge to transplantation

Abstract

Central MessageOptimal duration of durable LVAD support before transplant is a nuanced decision process that weighs the advantages of functional, organ, and psychologic recovery versus the risk of adverse events.See Commentary on page 121. Optimal duration of durable LVAD support before transplant is a nuanced decision process that weighs the advantages of functional, organ, and psychologic recovery versus the risk of adverse events. See Commentary on page 121. Left ventricular assist devices (LVADs) are an important treatment option for patients with end-stage heart failure refractory to optimal medical management. Compared with medical therapy, LVADs improve quality of life and survival.1Rose E.A. Gelijns A.C. Moskowitz A.J. Heitjan D.F. Stevenson L.W. Dembitsky W. et al.Long-term use of a left ventricular assist device for end-stage heart failure.N Engl J Med. 2001; 345: 1435-1443Crossref PubMed Scopus (3423) Google Scholar,2Starling R.C. Estep J.D. Horstmanshof D.A. Milano C.A. Stehlik J. Shah K.B. et al.Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: the ROADMAP study 2-year results.JACC Heart Fail. 2017; 5: 518-527Crossref PubMed Scopus (138) Google Scholar Over the past decade, approximately 50% of patients received an LVAD as destination therapy (DT), whereas close to 25% received a device as a either a bridge to transplant (BTT) or bridge to candidacy (BTC).3Molina E.J. Shah P. Kiernan M.S. Cornwell III, W.K. Copeland H. Takeda K. et al.The Society of Thoracic Surgeons Intermacs 2020 annual report.Ann Thorac Surg. 2021; 111: 778-792Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar In 2018, the US heart allocation system was modified in such a way that priority of patients who are stable with an LVAD was less emphasized. Since that time, there has been an increase in DT LVADs to 70% of all implants, and a decrease in the use of LVADs in the pretransplant setting. Despite this trend, the number of patients with an LVAD, regardless of implant strategy, who ultimately receive a heart transplant remains significant: BTT (60%), BTC (40%), and DT (17%).3Molina E.J. Shah P. Kiernan M.S. Cornwell III, W.K. Copeland H. Takeda K. et al.The Society of Thoracic Surgeons Intermacs 2020 annual report.Ann Thorac Surg. 2021; 111: 778-792Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar These observations not only call into question the role for categorization of implant strategy, but also suggest that advanced heart failure programs need to view patients with an LVAD within the spectrum of transplantation. Indeed, the common goal of prolonging survival and improving quality of life will often head down the transplant pathway independent of one's a priori LVAD designation.4Goldstein D.J. Naka Y. Horstmanshof D. Ravichandran A.K. Schroder J. Ransom J. et al.Association of clinical outcomes with left ventricular assist device use by bridge to transplant or destination therapy intent: The multicenter study of MagLev technology in patients undergoing mechanical circulatory support therapy with HeartMate 3 (MOMENTUM 3) randomized clinical trial.JAMA Cardiol. 2020; 5: 411-419Crossref PubMed Scopus (74) Google Scholar Within the paradigm that a large proportion of patients with LVAD will be considered for transplant, providers are routinely faced with questions regarding when to list for transplant. Unfortunately, this issue is poorly defined, dependent on multiple variables, and lacking guidance from contemporary data. Patients with LVAD receive comprehensive, multidisciplinary evaluations that often identify definitive and relative barriers to heart transplantation and influence duration of LVAD support. Ultimately, mechanical circulatory support programs must balance the benefits of circulatory support with the known complications associated with LVADs. This Commentary highlights the good, the bad, and the ugly facets of durable LVAD support that are utilized to determine the optimal timing of LVAD support in patients moving toward heart transplantation. Decisions regarding the optimal time to remove an LVAD or list a patient for transplant are complex and multifactorial. A key question remains largely unanswered in the modern era: Does the timing of transplant in patients bridged with an LVAD make a difference on posttransplant outcomes? Historically, several groups have reported excellent posttransplant outcomes in patients bridged with an LVAD. The multicenter, axial-flow HeartMate II (Thoratec Corp, Pleasanton, Calif) data showed equivalent survival in LVAD patients at 30 days and 1 year compared with de novo transplant recipients.5John R. Pagani F.D. Naka Y. Boyle A. Conte J.V. Russell S.D. et al.Post-cardiac transplant survival after support with a continuous-flow left ventricular assist device: impact of duration of left ventricular assist device support and other variables.J Thorac Cardiovasc Surg. 2010; 140: 174-181Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar In this study, 33% of patients were transplanted with a mean support duration of 151 days. No difference in mortality was seen when comparing LVAD support <30 days, 30 to 90 days, 90 to 180 days, and >180 days. Patients who received 2 or more units of packed red blood cells in 24 hours after LVAD implantation showed worse survival compared with those who received <2 U transfused blood (82% vs 94%).5John R. Pagani F.D. Naka Y. Boyle A. Conte J.V. Russell S.D. et al.Post-cardiac transplant survival after support with a continuous-flow left ventricular assist device: impact of duration of left ventricular assist device support and other variables.J Thorac Cardiovasc Surg. 2010; 140: 174-181Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Similarly, in a larger registry study using the United Network for Organ Sharing (UNOS) database, 1332 patients were identified during 2011-2012 as having received a continuous-flow LVAD as BTT.6Grimm J.C. Magruder J.T. Crawford T.C. Fraser III, C.D. Plum W.G. Sciortino C.M. et al.Duration of left ventricular assist device support does not impact survival after US heart transplantation.Ann Thorac Surg. 2016; 102: 1206-1212Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Patients were stratified into LVAD duration cohorts <90 days, 90 days to 365 days, and >365 days with no difference in posttransplant morbidity or mortality. In subgroup analysis, LVAD support >90 days was associated with improvement in pretransplant functional performance in these patients.6Grimm J.C. Magruder J.T. Crawford T.C. Fraser III, C.D. Plum W.G. Sciortino C.M. et al.Duration of left ventricular assist device support does not impact survival after US heart transplantation.Ann Thorac Surg. 2016; 102: 1206-1212Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Using Medicare data, 1186 (45%) of patients were identified as BTT compared with 1453 (55%) who went directly to heart transplantation without a durable device. The patients with LVAD patients were stratified into ≤31 days, 31 days to 365 days, and >365 days. Patients receiving a heart transplant within 31 days of LVAD support had significantly worse survival compared with the other cohorts.7Brown C.R. Khurshan F. Chen Z. Groeneveld P.W. McCarthy F. Acker M. et al.Optimal timing for heart transplantation in patients bridged with left ventricular assist devices: is timing of the essence?.J Thorac Cardiovasc Surg. 2019; 157: 2315-2324.e4Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Alternatively, other studies suggest a negative influence on posttransplant outcomes in patients bridged with a durable LVAD.8Patlolla V. Patten R.D. Denofrio D. Konstam M.A. Krishnamani R. The effect of ventricular assist devices on post-transplant mortality an analysis of the United Network for Organ Sharing thoracic registry.J Am Coll Cardiol. 2009; 53: 264-271Crossref PubMed Scopus (84) Google Scholar, 9Robertson J.O. Lober C. Smedira N.G. Navia J.L. Sopko N. Gonzalez-Stawinski G.V. One hundred days or more bridged on a ventricular assist device and effects on outcomes following heart transplantation.Eur J Cardiothorac Surg. 2008; 34: 295-300Crossref PubMed Scopus (12) Google Scholar, 10Takeda K. Takayama H. Kalesan B. Uriel N. Colombo P.C. Jorde U.P. et al.Outcome of cardiac transplantation in patients requiring prolonged continuous-flow left ventricular assist device support.J Heart Lung Transplant. 2015; 34: 89-99Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 11Truby L.K. Farr M.A. Garan A.R. Givens R. Restaino S.W. Latif F. et al.Impact of bridge to transplantation with continuous-flow left ventricular assist devices on posttransplantation mortality.Circulation. 2019; 140: 459-469Crossref PubMed Scopus (40) Google Scholar In another UNOS database study from 2008 to 2015, propensity-matched analysis of 5486 patients with and without an LVAD undergoing heart transplantation demonstrated a higher 1-year mortality in bridged patients (9.5% vs 7.2%; P < .001).11Truby L.K. Farr M.A. Garan A.R. Givens R. Restaino S.W. Latif F. et al.Impact of bridge to transplantation with continuous-flow left ventricular assist devices on posttransplantation mortality.Circulation. 2019; 140: 459-469Crossref PubMed Scopus (40) Google Scholar Logistic regression identified reduced glomerular filtration rate and obesity as risk factors for increased mortality in transplanted LVAD patients.11Truby L.K. Farr M.A. Garan A.R. Givens R. Restaino S.W. Latif F. et al.Impact of bridge to transplantation with continuous-flow left ventricular assist devices on posttransplantation mortality.Circulation. 2019; 140: 459-469Crossref PubMed Scopus (40) Google Scholar With single-center and registry studies, it is difficult to determine the influence of LVAD duration on posttransplant outcomes. It seems that early transplantation after LVAD, within the first month, confers a negative influence on transplant outcomes, and that certain post-LVAD adverse events and patient factors may increase the mortality of patients with an LVAD who move on to transplant. However, these studies lack the granularity and insight to the clinical decisions on when to transplant patients with an LVAD. To answer these questions, one must consider why the LVAD was implanted in the first place. As stated, the goal of LVAD therapy is to improve survival and quality of life in patients with end-stage heart failure. Duration of LVAD support may not affect posttransplant outcomes beyond the early postoperative period, with the obligatory morbidity of a major heart operation. Conversely, a longer duration of LVAD support subjects patients to a defined risk of serious complications. Often, during the pre-LVAD evaluation period, a patient's severity of illness and definitive and relative contraindications to heart transplant dictate the decision-making process in offering LVAD therapy. Many of these variables persist after LVAD implantation and influence the duration of LVAD support. Patients being considered for LVAD present with a spectrum of scenarios that are categorized by the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support profiles of clinical presentation, ranging from cardiogenic shock to mildly symptomatic. The allocation of organs to patients in profiles 1 and 2 challenges utilization of a scarce resource. Sicker patients often have additional organ failure that precludes transplant listing. Durable LVAD has traditionally been an option for these patients to allow for other organ recovery and improve conditioning and functional status. An increasing percentage of profile 1 and 2 patients are being supported with temporary mechanical circulatory support because of the change in the US heart allocation system.12Ton V.K. Xie R. Hernandez-Montfort J.A. Meyns B. Nakatani T. Yanase M. et al.Short- and long-term adverse events in patients on temporary circulatory support before durable ventricular assist device: an IMACS registry analysis.J Heart Lung Transplant. 2020; 39: 342-352Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Furthermore, with the heart allocation system change, the number of patients listed with LVAD at the time of transplant has markedly decreased.13Mullan C.W. Chouairi F. Sen S. Mori M. Clark K.A.A. Reinhardt S.W. et al.Changes in use of left ventricular assist devices as bridge to transplantation with new heart allocation policy.JACC Heart Fail. 2021; 9: 420-429Crossref PubMed Scopus (51) Google Scholar In a recent UNOS registry study, transplanted patients with LVAD decreased to 14% compared with 47% before the allocation change, with significant decrease in 1-year survival estimate and more graft failure.13Mullan C.W. Chouairi F. Sen S. Mori M. Clark K.A.A. Reinhardt S.W. et al.Changes in use of left ventricular assist devices as bridge to transplantation with new heart allocation policy.JACC Heart Fail. 2021; 9: 420-429Crossref PubMed Scopus (51) Google Scholar These patients are foregoing durable LVAD in some circumstances while awaiting transplant with temporary mechanical circulatory.14Cogswell R. John R. Estep J.D. Duval S. Tedford R.J. Pagani F.D. et al.An early investigation of outcomes with the new 2018 donor heart allocation system in the United States.J Heart Lung Transplant. 2020; 39: 1-4Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar In patients who fail to secure a suitable donor in a timely fashion on temporary mechanical circulatory, transitioning to durable LVAD remains an option. In addition to severity of illness, some patients with advanced heart failure have myriad contraindications to transplant—some modifiable, others not. These include multiorgan dysfunction, obesity, infection, malignancy, financial barriers, and psychosocial issues. The good part of LVAD therapy is the time it allows patients and care providers to address modifiable risk factors to heart transplantation, especially organ dysfunction. In patients with chronic heart failure, approximately 50% will have coexisting chronic kidney disease.15Damman K. Valente M.A. Voors A.A. O'Connor C.M. van Veldhuisen D.J. Hillege H.L. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.Eur Heart J. 2014; 35: 455-469Crossref PubMed Scopus (616) Google Scholar Chronic kidney disease stages 4 and 5 are relative contraindications to heart transplant listing.16Mehra M.R. Kobashigawa J. Starling R. Russell S. Uber P.A. Parameshwar J. et al.Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates–2006.J Heart Lung Transplant. 2006; 25: 1024-1042Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar The support provided by LVAD therapy transiently improves renal function in many patients who did not affect overall survival when compared with medically managed patients awaiting transplant.17Zittermann A. Schramm R. Becker T. von Rössing E. Hinse D. Wlost S. et al.Renal function in patients with or without a left ventricular assist device implant during for a heart Transplant. 2020; 25: PubMed Scopus Google Scholar However, LVAD implantation is also associated with a negative influence on renal function, with LVAD patients who a postoperative kidney having higher mortality and renal function at 1-year and R. K. S. K. A.A. et kidney and 1-year mortality after left ventricular assist device Heart Lung Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar A influence has been in patients with dysfunction. LVAD therapy has been to improve failure as early as 1 post-LVAD implantation with survival A. A. D. C. et left ventricular assist device therapy in patients with failure: are the 2015; 39: PubMed Scopus (15) Google Scholar as seen in patients who postoperative kidney the of postoperative is associated with increased early and morbidity and K. R.J. K. et al.Impact of postoperative on survival after left ventricular assist device Thorac Surg. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar LVAD therapy have postoperative effects on patients with as a to transplant. may be present in to of patients with advanced heart J. D. T. of on clinical outcomes in advanced heart failure: analysis of the evaluation study of heart failure and effectiveness Heart J. 2009; 157: PubMed Scopus Google Scholar LVAD support has been to improve in these patients and heart transplant candidacy in patients M. Takayama H. Takeda K. J. Colombo P.C. M. et of before left ventricular assist device implantation on and long-term post-transplant Thorac Cardiovasc Surg. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar Despite early in is often or in patients with and associated with increased posttransplant M. Takayama H. Takeda K. J. Colombo P.C. M. et of before left ventricular assist device implantation on and long-term post-transplant Thorac Cardiovasc Surg. 2015; Full Text Full Text PDF PubMed Scopus Google C.A. but in advanced heart failure is the of cardiac Thorac Cardiovasc Surg. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar A of LVAD therapy is the improvement in function to allow of transplant The influence of LVAD therapy in recovery to early during the postoperative within the first 1 to 3 after influence the duration of LVAD support and timing of listing. to LVAD therapy is associated with recovery and functional LVAD therapy has been to significantly improve and when compared with the heart failure in patients with advanced heart failure implanted with a left ventricular assist 2019; 34: PubMed Scopus Google Scholar In patients supported with LVAD, significantly to regardless of Intermacs profile or heart failure van L.W. et year improvement of in patients with mechanical circulatory support as bridge to Heart Fail. 2021; PubMed Scopus Google Scholar in function, and functional improvement the good of LVAD therapy and to quality of life for these D. Stevenson M.A. Pagani F.D. et quality of life improves to after mechanical circulatory support regardless of severity of heart failure before Heart Lung Transplant. 2014; Full Text Full Text PDF PubMed Scopus Google C. in quality of life by implant from the registry for circulatory support.J Heart Lung Transplant. 2020; 39: Full Text Full Text PDF PubMed Scopus Google Scholar Despite the many of LVAD therapy, the part of LVAD support is the of the device with an of adverse events. LVADs have profiles that include infection, and The number and rate of these complications increase to the duration of LVAD support. an patients are often in transplant and mortality is significantly M. et and mortality in heart transplant supported with mechanical circulatory is of the United Network for Organ Sharing thoracic organ allocation PubMed Scopus Google Scholar Furthermore, a to be with increased and mortality Stehlik J. of ventricular assist device complications on posttransplant an analysis of the United Network for Organ Sharing Thorac Surg. Full Text Full Text PDF PubMed Scopus Google Scholar The more studies with contemporary that the for and associated outcomes. The HeartMate 3 LVAD is the durable device and has an adverse profile compared with axial-flow significant in ventricular and M.R. Uriel N. Naka Y. J.C. M. et left ventricular assist device Engl J Med. 2019; PubMed Scopus Google Scholar The reduced complications associated with this device may the number of for complications in LVAD patients awaiting and influence optimal timing of transplant, and posttransplant outcomes. In more utilization and of the HeartMate 3 the that one must transplant a patient with an LVAD before adverse events The effect of LVADs with with the heart allocation remains to be seen because data are In the of an the of an LVAD in patients bridged to transplant has been associated with increased risk of graft and prolonged posttransplant T. D. J. S. et graft failure is more common in patients bridged to heart transplant with role of early Heart Lung Transplant. Full Text Full Text PDF PubMed Google L.K. Takeda K. V.K. Takayama H. Garan A.R. M. et al.Risk of graft in patients bridged to heart transplantation with continuous-flow left ventricular assist Heart Lung Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar complications associated with LVAD therapy is to improve posttransplant outcomes. To the duration of LVAD support seems and R.J. Smedira N.G. et al.Optimal timing of heart transplant after HeartMate II left ventricular assist device Thorac Surg. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar the optimal timing of transplant in patients supported with continuous-flow LVADs from to In this study of posttransplant survival was when within of LVAD R.J. Smedira N.G. et al.Optimal timing of heart transplant after HeartMate II left ventricular assist device Thorac Surg. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar decreased as the duration of support R.J. Smedira N.G. et al.Optimal timing of heart transplant after HeartMate II left ventricular assist device Thorac Surg. 2017; Full Text Full Text PDF PubMed Scopus Google Scholar Heart transplant before the of complications is to transplant The ugly to LVAD support and the optimal duration of support before transplant are the many variables that are difficult to or and often These include psychosocial common in patients with advanced heart failure such as or and financial in patients with an LVAD has been associated with increased mortality and overall R. E. A. A. Duval S. et at the time of left ventricular assist device implantation is associated with increased Heart Lung Transplant. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar past or use is not to survival and the of transplant A.K. A. S. A.C. S. et and left ventricular assist device does a and of use Heart Lung Transplant. 2015; 34: Full Text Full Text PDF Google Scholar not a risk for increased has been associated with increased and post-LVAD D. S.D. S. and outcomes in patients with left ventricular assist device implanted as destination Heart J. 2015; PubMed Scopus Google Scholar Many of these variables mechanical circulatory support programs when patients for transplant and influence the duration of LVAD there is no defined time for of these variables to move to transplant. a of patients may recovery after LVAD of recovery include renal function, and a duration of heart failure. These make this of patients for heart transplantation other et recovery during long-term left ventricular assist device support.J Am Coll Cardiol. 2016; PubMed Scopus Google Scholar with LVAD support with a LVAD with chronic heart E.J. Starling R.C. et multicenter study of recovery using left ventricular assist devices from heart and 2020; PubMed Scopus Google Scholar there a duration of LVAD support that be to recovery patients before transplant Using and heart showed that early improvement in and ventricular function often within the first to after LVAD implant and was in a of R. et and time of by continuous-flow left ventricular assist device in chronic heart failure: into cardiac Am Coll Cardiol. PubMed Scopus Google Scholar This for recovery with that of organ barriers to transplant, as as complications of LVAD. the optimal duration of LVAD support as BTT is balance these good, bad, and ugly variables that also must consider and an LVAD is a major with significant morbidity and mortality. It is to allow these patients to from because the recovery process patients and is often by a patient before and <30 days LVAD will to outcomes. The LVAD allows time for functional and modifiable contraindications to transplant to be while the patient is the duration of LVAD support will the of adverse events. before to as early as post-LVAD complications and improve posttransplant outcomes. patients with the of recovery often within a to time there are many psychosocial variables that are and affect duration of LVAD support before transplant. is no defined or optimal time for of these variables that affect duration of support and for transplant listing.

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