Heart Transplant vs Left Ventricular Assist Device in Heart Transplant-Eligible Patients

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Theodora Watts
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1 Heart Transplant vs Left Ventricular Assist Device in Heart Transplant-Eligible Patients Matthew L. Williams, MD, Jaimin R. Trivedi, MD, MPH, Kelly C. McCants, MD, Sumanth D. Prabhu, MD, Emma J. Birks, MD, Laurie Oliver, RN, and Mark S. Slaughter, MD Division of Thoracic and Cardiovascular Surgery and Division of Cardiovascular Medicine, University of Louisville, and Jewish Hospital Transplant Center, Louisville, Kentucky Background. Patients listed for heart transplant have a prolonged wait time, with continued deterioration, poor quality of life, and 10% mortality. Although recent bridge to transplant (BTT) studies demonstrated 1-year survival similar to heart transplantation, doubt remains about overall effectiveness as a treatment strategy compared with waiting and implanting a left ventricular device (LVAD) only as a last resort. We evaluated 1-year outcome and effectiveness of LVAD vs heart transplantation. Methods. Patients on the heart transplantation list, either receiving an allograft or LVAD for BTT from January 2009 to December 2009 were evaluated. Of 43 patients treated, 1 received both LVAD and an allograft during same admission was removed from the analysis. All patients but one who received an allograft had prior LVAD. Descriptive and univariate (t test) statistics and Kaplan-Meier survival curve were used for analyses. Results. LVAD for BTT was used in 29 patients ( years, 6.9% women), and 13 ( years, 15.38% women) underwent heart transplantation. Initial hospital length of stay was days in BTT group and days in heart transplant group (p 0.44) At 1 year, the total number of days spent in the hospital (operation and related complications), including index hospitalization was days/100 days in BTT and days/100 days in heart transplantation (p 0.38). A total of 41% BTT and 46% heart transplant patients had one readmission within 3 months of the index hospitalization. Infection was the most common cause of readmission in both groups. The 1-year survival was similar for both groups (no hospital death in either group; 3 late deaths in the BTT group). Conclusions. One-year outcomes for patients eligible for heart transplantation were similar whether they received an allograft or LVAD for BTT. Heart transplant outcome for patients with LVAD were not adversely affected. Improving outcomes for patients treated with LVAD suggest that current decision models for patients eligible for heart transplantation may need to be reevaluated. (Ann Thorac Surg 2011;91:1330 4) 2011 by The Society of Thoracic Surgeons Continuous-flow left ventricular assist devices (LVADs) have been a major improvement over pulsatile-flow devices in patients with end-stage heart failure. Early outcomes are improved, and the durability of the devices has extended the period of time that patients can receive support. Previously published studies have described nearly 80% survival to heart transplantation, ongoing support, or explantation due to recovery in the most commonly used continuous-flow device [1]. Currently, attrition among patients awaiting an allograft remains high: 10% to 15% of patients die before a suitable donor organ becomes available, and another 10% to 15% are removed from the list each year because Accepted for publication Jan 12, Presented at the Fifty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 3 6, Address correspondence to Dr Slaughter, Division of Thoracic and Cardiovascular Surgery, University of Louisville, 201 Abraham Flexner Way, Ste 1200, Louisville KY 40202; mark.slaughter@ louisville.edu. they are no longer a suitable candidate for medical reasons [2]. Given the longer periods of device support and the improved quality of life with continuous-flow pumps, current strategies for bridging patients to transplantation (BTT) may need to be reviewed to evaluate how best to minimize death while waiting for a donor organ and also potentially improve the quality of life while waiting. We compared recent outcomes for heart transplantation vs continuous-flow LVADs as a BTT from a single center. Material and Methods This study was approved by The University of Louisville Institutional Review Board, and consent was obtained from all participants. Dr Birks discloses that she has a financial relationship with Thoratec Inc; Dr Slaughter with Thoratec Inc and Heartware Inc by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc doi: /j.athoracsur

Ann Thorac Surg WILLIAMS ET AL 2011;91:1330 4 HTX VS LVAD IN HTX-ELIGIBLE PATIENTS Table 1. Baseline Demographics Variables a BTT HTx p Value Female gender 2/29 (6.9) 2/13 (15.3) 0.38 Age, years 51.

2 Ann Thorac Surg WILLIAMS ET AL 2011;91: HTX VS LVAD IN HTX-ELIGIBLE PATIENTS Table 1. Baseline Demographics Variables a BTT HTx p Value Female gender 2/29 (6.9) 2/13 (15.3) 0.38 Age, years Reoperations 11/29 (37.9) 13/13 (100) Pre-op values BUN, mg/dl Creatinine, mg/dl PCWP, mm Hg a Data are presented as number (%) or mean standard deviation. BTT bridge to transplantation; BUN blood urea nitrogen; HTx heart transplantation; PCWP pulmonary capillary wedge pressure ADULT CARDIAC All patients listed for heart transplantation at a single center who underwent continuous-flow LVAD implantation (n 29) or heart transplantation (n 13) from January 2009 through December 2009 were included. One patient who underwent support with extracorporeal membrane oxygenation, LVAD implantation, and heart transplantation during the same admission was excluded. Prospectively acquired data entered into the Jewish Hospital LVAD/Heart Transplant database in Louisville, Kentucky, was reviewed. Statistical analyses were conducted using the t test, 2 test, and the log-rank test. All statistical analyses were performed with SAS 9.2 software (SAS Institute, Cary, NC). Charge information for all hospitalizations was acquired through the hospital billing department using the UB 04 forms. A standard cost/charge ratio (for 2009/ ) was used to calculate costs. Fig 1. (A) Index hospital length of stay. (B) Days in hospital during ventricular assist device as bridge to transplant (BTT) or for heart transplant (HTx) support. Results Baseline demographics can be found in Table 1. Characteristics between the two groups were similar. One notable difference included the high number of reoperations among the heart transplant recipients (100%) relative to the BTT patients (38%). This difference was because 12 transplant recipients (92%) were receiving LVAD support and the remaining patient had already had two prior operations for valve replacement. Overall, most of the heart transplant patients were at home, Table 2. In Hospital Outcomes During Index Hospitalization In-Hospital Adverse Events BTT (n 29) No. (%) HTx (n 13) No. (%) Stroke 0 (0) 0 (0) Re-operative bleeding 6 (20.7) 2 (15.3) Renal failure 0 (0) 1 (7.7) Infection deep sternum 0 (0) 0 (0) Septicemia 0 (0) 0 (0) Mortality 0 (0) 0 (0) BTT bridge to transplantation; HTx heart transplantation. ambulatory, with normal renal function and listed as UNOS status 1B. Also because of previously implanted VADs, the pulmonary capillary wedge pressure was much lower among the HTx patients, indicating improved hemodynamics in patients with VAD support. In-hospital outcomes are found in Table 2. No deaths or strokes occurred in either group. There was a significant rate of reexploration for bleeding in both groups, reflecting the complexity of both operations as well as the coagulopathy caused by the device itself. Length of stay for the index hospitalization can be found in Figure 1A. There was a nonsignificant increased length of stay of days for BTT patients vs days in heart transplant patients (p 0.44). Rates of rehospitalization after LVAD implantation and heart transplantation are high. To compare the rates of hospitalization, we determined the number of days spent in the hospital per 100 days of device support or graft support after transplantation, including the index hospitalization. The ratio of days hospitalized/100 days supported was days/100 days in BTT and days/100 days in transplantation, which was similar (p 0.38; Fig 1B). Additional days spent in the hospital due to surgical intervention or disease-related causes

3 1332 WILLIAMS ET AL Ann Thorac Surg HTX VS LVAD IN HTX-ELIGIBLE PATIENTS 2011;91: Table 3. Index Hospitalization and Rehospitalization Costs Variable Mean SD No. p Value Index hospitalization cost, a $ BTT 196,707 37, HTx 127,978 44, Presurgical hospital, days BTT HTx Post index hospitalization cost, b $ BTT 33,302 70, HTx c 38,437 48, a Index hospitalization cost adjusted using cost/charge ratio (CCR) for fiscal year charges. b Post index hospitalization cost within 10 months of implant or transplant (adjusted by CCR). c HTx post index hospitalization costs do not include right heart catheterization and immunosuppressive therapy costs. Note: One BTT patient required device replacement due to malfunction but was not removed from analyses. BTT bridge to transplantation; HTx heart transplantation; SD standard deviation. after the index hospitalization were similar: days/100 days in BTT and days/100 days in transplantation (p 0.92). Cost comparison between the two strategies demonstrated a higher cost of the index hospitalization due to the high cost of the device itself, which was $197,000 $38,000 for BTT and $128,000 $44, 000 for transplantation (p 0.001). Inpatient costs after the index hospitalization were similar, at $33,000 $70,000 for BTT and $38,000 $48,000 for transplantation (p 0.81). Outpatient costs for heart transplantation, including immunosuppressive drugs and right heart catheterization with biopsy, were not included but would be expected to increase the overall costs for transplantation relative to BTT. (Table 3). The 1-year survival data were similar between groups, with 3 late deaths in the BTT group and none in the heart transplant group (Fig 2). Our report compares 1-year outcomes of heart transplantation with continuous-flow LVAD implantation in transplant-eligible patients from a single center. Generally, outcomes for survival and hospitalization are similar. The numbers of patients in each group are small and are underpowered to detect subtle differences, but no striking divergence in 1-year outcomes was detected. United Network of Organ Sharing data demonstrate that there remains a significant rate of death while patients await a donor organ, and many patients are removed from the active list because they have medically deteriorated. To prevent adverse outcomes while awaiting heart transplantation, many centers have used continuous-flow LVADs as a BTT in patients listed for heart transplantation who are failing medical therapy with signs of deteriorating end-organ function. Decision making for timing of device implantation varies across centers. Most centers use continuous inotropic support for prolonged periods of time, despite diminished or worsening renal function and pulmonary vascular resistance. We believe that most patients who meet clinical criteria for listing for heart transplantation benefit from LVAD implantation to improve end-organ function, quality of life, and survival. The availability of a suitable donor heart is unpredictable and often delayed. Likewise, clinical deterioration of patients managed with inotropes is unpredictable. We believe that mechanical support with a continuous-flow LVAD provides better outcomes in transplant-eligible patients than other strategies in patients with left heart failure. Our report suggests that 1-year outcomes of VAD implantation are similar to heart transplantation, and the strategy of earlier VAD implantation for patients on the waiting list may prevent some of the attrition currently observed on the transplant waiting list and improve functional status as patients await a suitable donor organ. Our cost analysis demonstrated that initial therapy was more expensive for LVAD as BTT. This difference was due to preoperative days spent in the hospital for the BTT group as they were being managed before LVAD implantation and the cost of the device. Our cost for LVAD is approximately three times our current organ acquisition costs. With time, the cost of the device should decline, minimizing the initial cost difference. After the index Comment The initial report describing continuous-flow LVADs as a BTT described encouraging results, with 68% survival at 1 year [3]. Since that time, actuarial survival has improved, with the most recent follow-up data demonstrating 85% survival at 1 year [4]. Improved survival is not due to higher rates of transplantation, as this has decreased from 50% in the original trial to 34% in the most recent report, with a corresponding increase in the proportion of patients alive with ongoing device support. Outcomes with continuous-flow LVADs have improved due to multiple improvements in patient selection, the surgical procedure, patient management, and the new technology itself. Fig 2. Actuarial survival in patients who were bridged to transplantation (BTT) and who underwent heart transplantation (HTx). Causes of late death were system controller failure, diabetic ketoacidosis, or unknown.

4 Ann Thorac Surg WILLIAMS ET AL 2011;91: HTX VS LVAD IN HTX-ELIGIBLE PATIENTS hospitalization, the costs and the number of days spent in the hospital were the same for the two treatments. We have compared BTT with heart transplantation from a single center, with follow-up to 1 year. Overall survival, other adverse outcomes, and cost were similar between groups. These findings are similar to a recent report comparing LVAD destination therapy with extended criteria heart transplantation, which also found similar outcomes between groups [5]. Whether outcomes would remain similar with longer-term follow-up in the BTT population is unknown. Our findings raise questions about the current algorithm of heart transplantation with LVAD implantation as BTT until a suitable donor can be found. Currently, all patients who receive an LVAD as BTT receive 30 days of 1A status, to be used when they are medically stable and optimized for transplantation. Many patients who are listed at this point receive a donor organ and undergo transplantation, even while doing well at home with an excellent functional status and without device complication. Although all of the patients in our heart transplantation cohort survived operation, transplantation is associated with a significant periprocedural risk. In addition, the morbidity of the device is exchanged for the morbidity of immunosuppression. It is unclear if the risk of operation and immunosuppression is justified in the cohort of patients who are discharged home, in New York Heart Association functional class I without serious device complication. Notably, we have observed many patients who initially receive LVAD as a BTT have elected to be removed from the transplant list, preferring their current quality of life to the unknown of heart transplantation. An alternative strategy that could be considered would be to reserve heart transplantation in BTT patients who have a significant device-related complication. This strategy may allow for more donor hearts to be available for patients who have already had one or more sternotomies and who are receiving continuous inotropes and need a transplant as definitive therapy. Our single-center series does not provide enough data to support such a policy change, and even at our center, timing of transplantation is still largely based on the availability of a suitable donor heart. In patients with LVADs, we use the allotted 30 days of 1A status waiting time and also will request 1A status for patients with a device-related complication. Further investigations will describe longer-term LVAD outcomes, and define how frequently patients can be salvaged after serious device complications. If LVAD outcomes continue to improve, the best utilization for the scarce commodity of donor hearts may need to be reevaluated. As outcomes for continuous-flow LVADs and heart transplantation converge, the therapy of heart transplantation could emerge as salvage therapy for major device-related complications or dysfunction or progressive right heart failure as opposed to the default option for all patients who are eligible for transplant. References Pagani FD, Miller LW, Russell SD, et al. Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device. J Am Coll Cardiol 2009;54: Annual Report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: Transplant Data H.R.a.S.A. U.S. Department of Health and Human Services, Healthcare Systems Bureau, Division of Transplantation, Editor. 2009: Rockville, MD. 3. Miller LW, Pagani FD, Russell SD, et al. Use of a continuousflow device in patients awaiting heart transplantation. N Engl J Med 2007;57: Starling RC, Naka Y, Boyle AJ, Results of the post-fdaapproval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS Registry. J Am Coll Cardiol 2011; in press. 5. Daneshmand MA, Rajagopal K, Lima B, et al. Left ventricular assist device destination therapy versus extended criteria cardiac transplant. Ann Thorac Surg 2010;89:1205 9; discussion ADULT CARDIAC DISCUSSION DR WILLIAM L. HOLMAN (Birmingham, AL): Dr Slaughter is getting into a really interesting area in the evolution of this therapy. We have gone from the days when you were often doing cardiopulmonary resuscitation on the way to the operating room to having patients come into the hospital electively for a ventricular assist device (VAD) because their creatinine has bumped to 1.8; it is really quite remarkable. I was surprised that your transplant group had a 100% prevalence of secondary sternotomy. How many of those were because they were being transplanted off of a VAD? DR SLAUGHTER: Of the 13 that were transplanted, all but one were on a left ventricular assist device (LVAD). Unfortunately in the state of Kentucky, like other many other states, we have a limited number of donor hearts. We have tried to use prolonged out-patient inotropes, and all those patients came back with sepsis, renal failure, and subsequently died prior to even being able to receive a VAD. So we wait approximately 2 months on out-patient inotropes. If they have not received an organ offer, at that point we proceed to a device. The one patient that was not on a LVAD was already going to be a fourth-time redo. He had had three valve operations, all mechanical valves, and had severe biventricular failure, and we thought to do a fourth-time redo with a VAD, leaving him mechanical valves and go back a fifth time was prohibitive. He was hospitalized for 3 months on inotropes in an intensive care unit to get him transplanted. DR HOLMAN: Yes. It is remarkable that he survived. The one comment about this, the amount of information that we have now as opposed to, say, two years ago from the large cooperative efforts like Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) and the Transplant Cardiology Research Database (TCRD) has really changed the playing field, and I think a lot of institutions, ours included, have transformed us into a service line. We have at least weekly meetings to discuss how we

5 1334 WILLIAMS ET AL Ann Thorac Surg HTX VS LVAD IN HTX-ELIGIBLE PATIENTS 2011;91: are going to manage individual patients, and there is great consideration given to TCRD and INTERMACS data going forward. So we are really trying to avoid a waste of organs, because we have the same problem with diminishing donors, and are seeing this creep of more and more patients getting LVADs as what are called INTERMACS level 3 and 2, and the results in terms of the LVAD patient outcomes are pretty striking. The class 1 patients, and there are, of course, gradations of that, give us most of the problems. It is an interesting paper, Mark, and thank you very much for presenting it. DR SLAUGHTER: Thank you. Similar to you, we now have at least two meetings a week to discuss appropriate therapy for these patients, because it is not easy. DR FREDERICK GROVER (Denver, CO): That was a really great paper, and I think it just shows the balance of risk versus benefit and the tremendous advances in ventricular assist device therapy. I had one very short, simple question, and that is in terms of your cost analysis and your lengths of stay. Did you look at median as well as main and was there a lot of variation between the two? DR SLAUGHTER: We did, and there wasn t. We are sort of going back and forth, and we are probably going to report both in the paper and let the reviewers decide if we should include both or keep it to one. Requirements for Maintenance of Certification in 2011 Diplomates of the American Board of Thoracic Surgery (ABTS) who plan to participate in the 2011 Maintenance of Certification (MOC) process as Certified-Active must hold an unrestricted medical license in the locale of their practice and privileges in a hospital accredited by the JCAHO (or other organization recognized by the ABTS). In addition, a valid ABTS certificate is an absolute requirement for entrance into the Maintenance of Certification process. If your certificate has expired, the only pathway for renewal of a certificate is to take and pass the Part I (written) and the Part II (oral) certifying examinations. The CME requirements are 120 Category I credits earned since January 1, At least half of these CME hours need to be in the broad area of thoracic surgery. Category II credits are not allowed. Interested individuals should refer to the Board s website for a complete description of acceptable CME credits. Diplomates who hold certificates that end in 2011 will be required to complete all sections of SESATS after their applications have been approved. It is not necessary for Diplomates to purchase SESATS individually because it will be sent to them after their application has been approved. Diplomates who hold certificates that end in 2012 or 2013 will be required to take and pass a secured exam after their application has been approved. Taking SES- ATS in lieu of the secured exam is not an option. The secured exam will be given from September 12 to September 24, 2011 at a Pearson Vue Testing Centers, which are located nationwide. Diplomates will have the opportunity to select the day and location of their exam. Diplomates who wish to maintain a Certified-Active status will be required to submit a summary of cases and will be required to participate in an outcomes database. For more details about this requirement, please visit the Board s website at Diplomates may apply for Maintenance of Certification in the year their certificate expires, or if they wish to do so, they may apply up to two years before it expires. However, the new certificate will be dated 10 years from the date of expiration of their original certificate or most recent recertification certificate. In other words, going through the Maintenance of Certification process early does not alter the 10-year validation. Diplomates certified prior to 1976 (the year that time-limited certificates were initiated) are also required to participate in MOC if they wish to maintain valid certificates. The deadline for submitting an application for Maintenance of Certification is March 1, 2011; however, the Board will accept late applications by April 15, A brochure outlining the rules and requirements for Maintenance of Certification in thoracic surgery is available on the Board s website at For additional information, please contact the American Board of Thoracic Surgery, 633 N St. Clair St, Suite 2320, Chicago, IL 60611; telephone (312) ; fax (312) ; info@abts.org by The Society of Thoracic Surgeons Ann Thorac Surg 2011;91: /$36.00 Published by Elsevier Inc

Bridge to Heart Transplantation

Bridge to Heart Transplantation Ulf Kjellman MD, PhD Senior Consultant Surgeon Heart Centre KFSH&RC 1 Disclosure Appointed for Proctorship by Thoratec/St.Jude/Abbott 2 To run a full overall covering transplant