heart OPTN/SRTR 2013 Annual Data Report:

Transcription

1 heart waiting list... deceased donation... transplant... donor-recipient matching outcomes... pediatric transplant... transplant center maps M. Colvin-Adams1,2, J. M. Smith1,3, B. M. Heubner1, M. A. Skeans1, L. B. Edwards4,, C. D. Waller4,, E. R. Callahan4,, J. J. Snyder1,6, A. K. Israni1,6,7, B. L. Kasiske1,7 1 Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN 2 Department of Medicine, Division of Cardiology, University of Minnesota, Minneapolis, MN 3 Department of Pediatrics, University of Washington, Seattle, WA 4 Organ Procurement and Transplantation Network, Richmond, VA United Network for Organ Sharing, Richmond, VA 6 Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 7 Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN OPTN/SRTR 213 Annual Data Report: 1 heart ABSTRACT The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 34.2% from 23 to 213. The heart transplant rate among active adult candidates peaked at 149. per 1 waitlist years in 27 and has been declining since then; in 213, the rate was 87.4 heart transplants per 1 active waitlist years. Increased waiting times do not appear to be correlated with an overall increase in waitlist mortality. Since 28, the proportion of patients on life support before transplant increased from 3.4% to 6.8% in 213. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately pediatric candidates are added to the waiting list each year; the number of pediatric transplants performed each year increased from 293 in 23 to 411 in 213. Patient survival among pediatric recipients continues to improve; -year patient survival for transplants performed from 21 through 28 was 7% to 8%. Medicare paid for some or all of the care for 42.2% of all heart transplant recipients in 212. KEY WORDS End-stage heart failure, heart transplant, transplant outcomes, ventricular assist device. It will be two years in September that our 19 year old daughter received her new heart. While camping two weeks ago she rode her bike: no breathlessness. I almost cried. Thank you to the donor families who make this possible for other families to experience moments like this. Jody, recipient mother

2 2 OPTN/SRTR 213 Annual Data Report Introduction Although 213 did not bring major changes in heart transplant, progress was made in perioperative management, patient selection, desensitization, management of rejection, and management of candidates with ventricular assist devices (VADs). Complications of VADs and their effect on candidacy and allocation policies remain major areas of concern, and defining a policy that further stratifies urgency remains of interest. The number of candidates listed for heart transplant continues to increase more rapidly than the number of donors suitable for heart donation. Since 22, the number of heart transplants performed also increased, but not at the same pace as the number of candidates being listed. The proportion of candidates with VADs remains high and continues to increase. Transplant rates and donation rates continue to show marked regional variability. Increasing proportions of older candidates and ethnic minorities are being listed, and the number of heart-kidney transplants has more than doubled since 23. The Organ Procurement and Transplantation Network/United Network for Organ Sharing Thoracic Committee is developing heart allocation policy that will better stratify risk of waitlist mortality. Adult Heart Transplant Waitlist Trends: New Listings, Time to Transplant, and Waitlist Mortality In 213, 3293 new candidates were listed for heart transplant, representing a 34.2% increase since 23 (Figure HR 1.1). The most notable waitlist trends include the following: The proportion of candidates aged 6 years or older continues to increase; in 213, 18.2% of candidates were aged 6 years or older, compared with 1.8% in 23. The proportion of black candidates has increased over the past decade by approximately 8%, to 22.8% of candidates in 213. The prevalence of cardiomyopathy as the reason for listing has increased to more than %, while prevalence of coronary artery disease as a reason for listing decreased to 3.8% in 213. Fewer candidates than in previous spend long times on the waiting list. In 23, 14.8% of candidates spent or more years on the waiting list, compared with only.4% in 213. The proportion of candidates with VADs at listing increased dramatically, from 7.% in 23 to 27.4% in 213. Over the past years alone, the prevalence of VADs at listing more than doubled. The distribution of medical urgency categories has shifted to a higher prevalence of status 1A and 1B. Over the past decade, the proportion of patients awaiting heart transplant as status 1A during the year increased from 21.6% to 43.9%, and the proportion awaiting heart transplant as status 1B increased from 1.8% to 27.4% (Figure HR 1.2). Heart transplant rates were highest among candidates aged 6 years or older, those with blood type AB, those listed as status 1A, and those with VADs (Figure HR 1.4). In general, few candidates died while awaiting a heart transplant (Figure HR 1.7). In the cohort of transplant candidates listed in 21, 66.4% underwent transplant within 3 years, 8.9% were still waiting, and 1.% had died. Some (14.7%) were removed from the list for other reasons, including improved or worsened condition (Figure HR 1.8). Half of all candidates listed in underwent transplant within 9.3 months, an increase from.3 months in 24-2 (Figure HR 1.9). Waiting time for candidates listed as status 1A increased slightly from 1.9 months to 2.6 months since 24-2; however, median waiting time for candidates listed as status 1B increased notably, from 2.7

3 heart 3 months to 8. months during the same period. The median waiting times for candidates with and without VADs at listing were essentially the same: 9.3 months and 9.4 months, respectively; however, the median waiting time for candidates with VADs increased sharply recently, from 6.2 months for candidates listed in to 9.3 months for candidates listed in (Figure HR 1.9). Waiting time to transplant varied notably by geographical area (Figure HR 1.6). When stratified by donation service area (DSA), the occurrence of heart transplant within 1 year of listing ranged from 28.9% to 1.%. This may reflect local practices in addition to donor availability; however, donor availability by state does not correspond to the trends in waiting times for the DSAs with the highest transplant rates (Figure HR 2.2). Death on the waiting list has steadily declined over the past decade, to 1.7 deaths per 1 waitlist years in from 14.8 deaths per 1 waitlist years in There were no major differences in waitlist mortality among subgroups in , but some trends are worth noting. Waitlist mortality declined by more than half for candidates aged 18 to 34 years; in , waitlist mortality for these candidates was the lowest (8.8 deaths per 1 waitlist years) among the age categories. Waitlist mortality declined in all race categories and for all etiologies except valvular cardiomyopathy, where variability was substantial and a large increase occurred in When compared by presence of VAD at listing, mortality for candidates with and without VADs was similar. Waitlist mortality was higher for candidates with blood type AB (17.1 deaths per 1 waitlist years) than for the other blood type groups, despite higher transplant rates, and lowest for candidates with blood type O (9.7 deaths per 1 waitlist years). Waitlist mortality remained substantial for the status 1A group, although it declined over the decade. Of note, waitlist mortality for the status 1B group was 4.9 deaths per 1 status 1B waitlist years, which is not substantially higher than mortality for the status 2 group. The mortality rate for inactive patients increased to 2. deaths per 1 inactive waitlist years in (Figure HR 1.1). Donor Trends In general, heart donation rates have been stable over the past decade; the rate was 3.49 per 1 patient deaths in 211. One notable exception is an increase in donation rates of 38.6% since 26 in the group aged 1 to 1 years. Donors aged years or older have become increasingly rare. Heart donation rates have either plateaued or decreased slightly in all race groups except black race, where rates have steadily increased (Figure HR 2.1). The overall donation rate was.94 hearts donated per 1 deaths in ; however, there was great regional variability, and donation rates were greater than. per 1 deaths in most states (Figure HR 2.2). Cerebrovascular accident/stroke was an increasing cause of death in donors aged years or older (data not shown), while head trauma remained the most prevalent cause of death in donors aged younger than years. In all age groups, anoxia was an increasingly prevalent cause of death (Figure HR 2.3). Trends in Heart Transplant The number of adult heart transplants has increased gradually over the past decade, by 22.4% since 23 (Figure HR 3.1). Among the age groups, the greatest increase in transplants was among recipients aged 6 years or older. The gradual growth in the number of heart transplants was seen for men and women and among race groups. The number of transplants due to cardiomyopathy and congenital heart disease continued to increase (Figure HR 3.2). Life support, including intravenous inotropes, intra-aortic balloon pumps, ventricular and circulator assist devices, ventilators, inhaled nitric oxide, and prostaglandins, is becoming more common before transplant. In 213, 6.8% of transplant recipients were on life support before transplant, compared with 3.4% in 28 (Figure HR 3.3). The major contributor to this trend is the increase in the prevalence of left VADs (LVADs) before transplant. In 213, 44.% of transplant recipients used LVADs and 34.3% were receiving intravenous inotropes. This is in striking contrast to 28, when 46.6% of transplant recipients were receiving inotropes and only 24.6% used LVADs. The number of candidates with a total artificial heart (TAH) before transplant has tripled over the past years, from 18 TAHs in 28 to 4 in 213, while ventilator support has decreased by nearly two-thirds (Figure HR 3.3). Recipient Characteristics The mean age of heart transplant recipients increased from 1.3 years in 23 to 3.2 years in 213. The proportion of recipients aged 6 years or older doubled to 2.9% during that same period. Most recipients were white men; however, 21.7% were black, which is a notable increase since 23. Women comprised 27.4% of recipients. The typical recipient had blood type A or O. The proportion of private payers declined by 1.6% to 48.% in 213, mirrored by an increase in Medicare as the primary payer to 3.1% of recipients. Although a waiting time to transplant of less than 31 days was most common, occurring for 23.8% of candidates in 213, waiting times between 3 months and 2 years became more frequent. Simultaneous heart-kidney and heart-liver transplants increased in frequency, while heart-lung transplants became even rarer; in 213, only 16 heart-lung transplants were performed (Figure HR 3.4). Since 23, status 1A and 1B listings (Figure HR 1.3) have increased markedly. This increase data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

4 4 OPTN/SRTR 213 Annual Data Report in higher urgency listings corresponded to an almost 2-fold increase in the proportion of status 1A recipients, to 6.1%. In contrast, status 1B transplants were less common in 213, occurring in 31.4% of recipients, and status 2 transplants declined from 26.4% in 23 to 3.% of transplants in 213 (Figure HR 3.4). Survival after Heart Transplant One-year survival in patients who underwent heart transplant from 26 through 28 was 88.1%; 3-year survival was 81.3% and -year survival 7.3%. Survival was slightly lower for women, particularly after year 3 posttransplant. Among the age groups, survival during year 1 was lowest for recipients aged 6 years or older; however, after year 1, survival was worst for recipients aged 18 to 34 years. At years, survival was only 67.4% for recipients aged 18 to 34 years, compared with 76.7%, 77.%, and 73.% for ages 3 to 49 years, to 64 years, and 6 years or older, respectively (Figure HR.1). Although the reason is difficult to determine, this difference may be a result of the etiology of heart failure, possibly immunologic complications (rejection), or psychosocial challenges that may be unique in the younger population. Early survival was similar in all race groups; however, curves diverged at 11 months, at which point survival for black recipients became lower. By year 3, survival was only 7.8% for blacks, compared with 82.7% for whites and 81.6% for other race groups. By year, survival was 68.8% for blacks, compared with 77.% for whites. Survival was slightly lower for recipients with prior VADs than for those without VADs. Survival did not differ meaningfully between the medical urgency categories at any time point (Figure HR.1). The number of heart transplant survivors continued to increase. On June 3, 213, 27,12 heart transplant recipients were alive with a functioning graft, most aged years or older (Figure HR.2). Posttransplant morbidity Rejection remains an important cause of morbidity after heart transplant; the cumulative incidence of rejection at 1 year was 23.6%. Rejection was most prevalent in recipients aged 18 to 34 years. As might be expected, the lowest occurrence of rejection was among the oldest age group, particularly those aged 6 years or older (Figure HR.3). Viral serologies were important risk factors for morbidity after transplant. Epstein-Barr virus (EBV) infection is associated with lymphoma and posttransplant lymphoproliferative disorder (PTLD), and cytomegalovirus (CMV) infection is strongly linked to cardiac allograft vasculopathy. Recipients who are EBV negative are more likely to have a positive (11.9% of all matches ) than a negative donor (.7%), due to the frequency of EBV in the general population (Figure HR 4.2). The risk of PTLD in EBV-negative recipients was more than twice that in EBV-positive recipients at years, 1.8% vs..7%, respectively (Figure HR.4). Overall, the incidence of PTLD was low in this population, only.9% at years (Figure HR.4). The leading causes of death during year 1 posttransplant were infection, cardiovascular/cerebrovascular disease, and graft failure. After year 1, however, cardiovascular/cerebrovascular disease became a more common cause of death, followed by infection and graft failure (Figure HR.7). Summary Current trends reflect the increasing use of mechanical circulatory support as a bridge to transplant. Listing as status 2 is becoming less common, as most patients are listed in a higher medical urgency category. VADs have had a great impact on the upward trend toward listing patients at higher urgency categories. Pediatric Heart Transplant Pediatric Waitlist Trends In 213, the number of new pediatric candidates added to the heart transplant waiting list increased to 89, with very few added as inactive status. At year-end 213, almost 3 candidates were awaiting heart transplant, with 64.% listed as active (Figure HR 6.1). The largest age group of children on the waiting list was 11 to 17 years (33.3%), followed by younger than 1 year (28.1%), 1 to years (24.1%), and 6 to 1 years (14.6%). Almost % of heart transplant candidates were white, 2.% were black, 19.9% were Hispanic, and less than % were Asian (Figure HR 6.2). The proportion of waitlist candidates aged younger than 1 year increased from 4.7% in 23 to 17.4% in 213 (Figure HR 6.3). Sex and race distribution remained relatively similar in 23 and 213. For candidates waiting on December 31, 213, congenital defect was the leading cause of heart disease (4.6%). Just over half of candidates (7.%) waiting for a heart transplant on December 31, 213, had been waiting for less than 1 year, compared with 38.2% in 23. Almost 3% of candidates were listed as status 1A in 213, compared with 8.8% in 23. Another notable change is the increase in the number candidates using VADs at the time of listing, from.9% in 23 to.1% in 213 (Figure HR 6.3). Among candidates removed from the waiting list in 213, 73.6% underwent transplant, 9.3% died, 8.6% were removed from the list because their condition improved, and.3% were considered too sick to undergo transplant (Figure HR 6.4). Almost 7% of patients newly listed in 21 underwent transplant within 3 years, 9.8% died, 1.8% were removed from the list, and.1% were still waiting (Figure HR 6.).

5 heart The rate of heart transplants among active pediatric waitlist candidates decreased from a peak of almost 3 per 1 waitlist years in 26 to 196 per 1 waitlist years in 213, likely attributable to a growing waiting list. Transplant rates varied by age, with the highest rates for candidates aged less than 1 year, at 317 transplants per 1 waitlist years, followed by candidates aged 11 to 17 years, at 212 transplants per 1 waitlist years. Transplant rates for candidates aged 1 to and 6 to 1 years were similar, at approximately 14 transplants per 1 waitlist years (Figure HR 6.6). Waitlist mortality continues to decrease; rates were almost half the rates observed a decade earlier. The waitlist mortality rate was highest for candidates aged younger than 1 year, at 42 deaths per 1 waitlist years in , almost 2. times higher than the rate for candidates aged 1 to years (Figure HR 6.7). Waitlist mortality among candidates with a VAD at the time of listing has declined over time and now almost equals that of candidates without a VAD. Looking at cause of disease, waitlist mortality was highest in candidates with congenital defects or dilated myopathy/myocarditis (Figure HR 6.7). Pediatric Transplant The number of pediatric heart transplants performed each year increased from 294 in 22 to 411 in 213, with the largest increase in candidates aged 11 to 17 years (Figure HR 6.8). Over the past decade, the age, sex, and race of pediatric heart transplant recipients changed little. Congenital defects remain the most common primary cause of disease, affecting 43.4% of recipients in The proportion of recipients undergoing retransplant has remained stable over the decade at 6% to 7%. The percentage of ABO-incompatible transplants in was 3.6%, increased from 1.3% a decade earlier. The proportion of recipients with private insurance decreased and Medicaid coverage increased. The proportion of patients who underwent transplant as status 1A increased from 67.9% in to 89.6% in VAD use increased from only 8.4% of transplant recipients in to 23.% in (Figure HR 6.9). Among pediatric heart transplant recipients from 29 to 213, 6.6% were CMV negative and 41.9% were EBV negative (Figure HR 6.1). The combination of a CMV-positive donor and CMV-negative recipient occurred in 28.8% of transplants; for EBV, this occurred in 31.1% of transplants (Figure HR 6.1). The incidence of PTLD among EBV-negative recipients was.9% at years after transplant, compared with 2.3% among EBV-positive recipients (Figure HR 6.11). Pediatric Immunosuppression and Outcomes Substantial changes in immunosuppression have occurred in heart transplantation. In 213, the most common induction therapy was T-cell depleting agents, used in almost half of heart transplant recipients, followed by interleukin-2 receptor antagonists in 2.2%. No induction therapy was reported in 3.% of recipients. The initial immunosuppression agents used most commonly in 213 were tacrolimus (86.%), mycophenolate mofetil (92.1%), and steroids (67.7%). Mammalian target of rapamycin inhibitors were used in only 1.% of recipients at the time of transplant but use increased to 8.6% at 1 year after transplant. Steroid use at 1 year after transplant was reported in 63.% of recipients (Figure HR 6.12). Patient survival was 96.9% at 3 days for transplants performed in 213, 92.7% at 1 year for transplants performed in 212, 87.1% at 3 years for transplants performed in 21, 76.% at years for transplants performed in 28, and 6.4% at 1 years for transplants performed in 23 (Figure HR 6.13). Among patients undergoing transplant in 21-28, 1-, 3-, and -year patient survival was 87.3%, 79.9%, and 74.1%, respectively (Figure HR 6.16). Patient survival was poorest for heart transplant recipients aged younger than 1 year. The leading identified causes of death were graft failure and cardio/cerebrovascular disease, with almost identical rates at 1 year and years after transplant (Figure HR 6.17). The rate of late graft failure is traditionally measured by the graft half-life conditional on 1-year survival, defined as the time to when half of grafts surviving at least 1 year are still functioning. For heart transplants performed in 211, the 1-year conditional graft half-life was 1.2 years (Figure HR 6.14). The incidence of first acute rejection increases over time after transplant. Interestingly, the age cohort with the highest incidence of acute rejection at all time points was aged 6 to 11 years, with almost half experiencing rejection by 2 years after transplant (Figure HR 6.1). data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

6 6 OPTN/SRTR 213 Annual Data Report waitinglist 4 3 New patients Patients on list on Dec 31 each year 4 Active Inactive 3 Patients 2 1 Active Inactive Patients HR 1.1 Adults waiting for heart transplant A new patient is one who first joined the list during the given year, without having been listed in a previous year. Previously listed candidates who underwent transplant and subsequently relisted are considered new. Candidates concurrently listed at multiple centers are counted once. Concurrently listed candidates who are active at any program are considered active; those who are inactive at all programs are considered inactive. HR 1.2 Distribution of adults waiting for heart transplant Candidates waiting for transplant any time in the given year. Candidates listed concurrently at multiple centers are counted once. Age is determined at the later of listing date or January 1 of the given year. Time on the waiting list is determined at the earlier of December 31 or removal from the waiting list. Medical urgency status is the most severe during the year. Active and inactive patients are included. VAD, ventricular assist device.

7 heart 7 waitinglist N % N % Age , , Sex Female Male 2, ,7 76. Race White 2, , Black Hispanic Asian Other/unknown Citizenship US citizen 3, , Non-citizen resident Non-citizen non-resident Other/unknown Primary diagnosis Coronary artery disease 1, , Cardiomyopathy 1, , Congenital disease Valvular disease Other/unknown Heart tx history First transplant 3, , Retransplant Blood type A 1, , B AB O 1, , Waiting time < 1 year 1, , < 2 years < 3 years < 4 years < years years Medical urgency 1A B , , Inactive 1, VAD at listing Multi-organ Heart only 3, , Heart-kidney Heart-lung Other candidates 3, , HR 1.3 Characteristics of adults on the heart transplant waiting list on December 31, 23, and December 31, 213 Patients waiting for transplant on December 31, 23, and December 31, 213, regardless of first listing date; active/inactive status is on this date, and multiple listings are not counted. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

8 8 OPTN/SRTR 213 Annual Data Report waitinglist Transplants per 1 wait-list years 1 Age Transplants per 1 wait-list years Blood type A B AB O Transplants per 1 wait-list years Medical urgency Status 1A Status 1B Status VAD at listing 1 HR 1.4 Heart transplant rates among active adult waitlist candidates Transplants per 1 wait-list years Yes No Transplant rates are computed as the number of deceased donor transplants per 1 patient-years of active waiting in a given year. VAD, ventricular assist device. No data No data HR 1. Deceased donor heart transplant rates per 1 waitlist years among active adult candidates, by DSA, Transplant rates by DSA of the listing center, limited to candidates with active time on the waiting list in 212 and 213; deceased donor transplants only. Maximum time per listing is 2 years. Candidates listed concurrently in a single DSA are counted separately. HR 1.6 Percentage of adult waitlisted candidates who underwent deceased donor heart transplant within 1 year, by DSA, 212 Candidates listed concurrently in a single DSA are counted once in that DSA; candidates listed in multiple DSAs are counted separately per DSA.

9 heart 9 waitinglist Patients at start of year 2,898 2,843 3,8 Patients added during year 2,811 3,2 3,293 Patients removed during year 2,862 2,8 3,19 Patients at end of year 2,847 3,63 3,332 Removal reason Deceased donor transplant 1,948 2, 2,116 Patient died Patient refused transplant Improved, tx not needed Too sick for transplant Other HR 1.7 Heart transplant waitlist activity among adults Candidates concurrently listed at more than one center are counted once, from the time of earliest listing to the time of latest removal. Candidates who are listed, undergo transplant, and are relisted are counted more than once. Candidates are not considered to be on the list on the day they are removed; counts on January 1 may differ from counts on December 31 of the prior year. Candidates listed for multi-organ transplants are included. HR 1.8 Three-year outcomes for adults waiting for heart transplant, new listings in 21 Adults waiting for heart transplant and first listed in 21. Candidates concurrently listed at more than one center are counted once, from the time of earliest listing to the time of latest removal. DD, deceased donor. Medical urgency at listing 2 VAD at listing 2 Median months to transplant 1 1 Status 1A Status 1B Status 2 Median months to transplant 1 1 No VAD VAD of listing of listing HR 1.9 Median months to heart transplant for waitlisted adults, by medical urgency and VAD status at listing Observations censored at earliest of December 31, 213, transfer to another center, or removal from waiting list due to improved condition; otherwise, candidates contribute waiting time until deceased donor transplant. Kaplan-Meier competing risks methods used to estimate time to transplant. Analysis performed per candidate not per listing. Only the first transplant is counted. VAD, ventricular assist device. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

10 1 OPTN/SRTR 213 Annual Data Report waitinglist 2 Age 2 Race Primary diagnosis 2 Deaths per 1 wait-list years Deaths per 1 wait-list years White Black Hispanic Asian Deaths per 1 wait-list years Coronary artery dis. Cardiomyopathy Congential dis. Valvular dis VAD at listing 12 Blood type 12 Medical urgency 12 Deaths per 1 wait-list years No Yes Deaths per 1 wait-list years A B AB O Deaths per 1 wait-list years Status 1A Status 1B Status 2 Inactive HR 1.1 Pretransplant mortality rates among adults waitlisted for heart transplant Mortality rates are computed as the number of deaths per 1 patient-years of waiting in the given year range. Candidates concurrently listed at multiple centers are counted once. Deaths after removal from the waiting list are not counted. Rates by status are calculated as the number of transplants for a given status divided by total waiting time in the year at that status. Age is determined at the later of listing date or January 1 of the given year. VAD, ventricular assist device.

11 heart 11 deceaseddonation Donations per 1, deaths Age < Donations per 1, deaths Race White Black Hispanic Asian Other/unknown HR 2.1 Deceased donor heart donation rates Numerator: Deceased donors aged younger than 7 years with hearts recovered for transplant. Denominator: US deaths per year, age younger than 7 years. Death data available only through 211. (Death data available at 1 Percent Anoxia Cerebrovascular/stroke Head trauma CNS tumor Other No data HR 2.2 Deceased donor heart donation rates (per 1 deaths), by state, Numerator: Deceased donors residing in the states whose hearts were recovered for transplant from 29 through 211. Denominator: US deaths, all ages, by state from 29 through 211 (death data available at cdc.gov/nchs/products/nvsr.htm) HR 2.3 Cause of death among deceased heart donors Deceased donors whose hearts were transplanted. CNS, central nervous system. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

12 12 OPTN/SRTR 213 Annual Data Report transplant Transplants Age < Transplants Sex Male Female Transplants Age< 18 Age HR 3.1 Total heart transplants heart transplant recipients, including adult and pediatric, retransplant, and multi-organ recipients. Transplants 2 Race White Black Hispanic Asian Other/unknown HR 3.2 Heart transplants Transplants Primary diagnosis 2 Coronary artery disease Cardiomyopathy Congenital disease 1 Valvular disease Other/unknown heart transplant recipients, including adult and pediatric, retransplant, and multi-organ recipients Support N % N % Any life support , Intravenous inotropes Left ventricular assist device Intra-aortic balloon pump Right ventricular assist device Ventilator Extra corporeal membrane oxygenation Total artificial heart Inhaled NO Prostaglandins HR 3.3 Adult heart recipients on circulatory support before transplant Patients may have more than one type of circulatory support.

13 heart 13 transplant N % N % Age , Sex Female Male 1, , Race White 1, , Black Hispanic Asian Other/unknown Primary diagnosis Coronary artery disease Cardiomyopathy ,21 6. Congenital disease Valvular disease Other/unknown Heart transplant history First transplant 1, , Retransplant Blood type A B AB O Insurance Private 1, ,4 48. Medicare Medicaid Other government Other/unknown Waiting time < 31 days days days < 6 months < 12 months < 2 years < 3 years years Medical urgency Status 1A , Status 1B Status Inactive 1.1. VAD status No VAD 1, , VAD , Multi-organ transplant Heart only 1, ,2 94. Heart-lung Heart-kidney Heart-liver Other HLA mismatches Unknown PRA < 1% 1, , < 2% < 8% < 98% % recipients 1, , HR 3.4 Characteristics of adult heart transplant recipients, 23 and 213 Adult heart transplant recipients, including retransplants. Ventricular assist device (VAD) information is from the OPTN Transplant Recipient Registration Form and includes left VAD, right VAD, total artificial heart, and left + right VAD. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

14 14 OPTN/SRTR 213 Annual Data Report transplant Percent Induction agents IL2-RA T-cell depleting None Calcineurin inhibitor Cyclosporine Tacrolimus Anti-metabolite Azathioprine Mycophenolate mtor inhibitors At transplant 1 year posttransplant Steroids At transplant 1 year posttransplant HR 3. Immunosuppression in adult heart transplant recipients One-year posttransplantdata arelimited topatients alivewith graft function at1 yearposttransplant. Mycophenolateincludes mycophenolatemofetil andmycophenolate sodium. IL2-RA, interleukin-2 receptor antagonist; mtor, mammalian target of rapamycin. % 1yr % 2-3yr Medication post-tx Medication post-tx Mycophenolate.1 Mycophenolate 74. Sulfamethoxazole-Trimethoprim 2.4 Prednisone 61.4 Tacrolimus 49.2 Pravastatin Sodium 4.3 Valganciclovir 4.1 Hydrocodone 38.6 Pravastatin Sodium 36.9 Amlodipine Besylate 36.7 Furosemide 3. Lisinopril 33. Nystatin 27.4 Amoxicillin 32.2 Amlodipine Besylate 27.3 Oxycodone 31.8 Oxycodone 26.6 Sulfamethoxazole-Trimethoprim 28.1 Hydrocodone 24.9 Azithromycin 26.9 Lisinopril 23.7 Furosemide 2. Potassium Chloride 22.7 Omeprazole 24.2 Magnesium Oxide 21.2 Potassium Chloride 21.2 Clotrimazole 2.7 Zolpidem Tartrate 2.7 HR 3.6 Top 1 medications filled by adult heart transplant recipients, 29 Adult heart transplant recipients, 29, who were matched to the IMS Health pharmacy claims database and had at least one medication filled during year 1 or year 2 or 3 posttransplant.

15 heart 1 donor-recipientmatching 4 3 Percent Unk. HLA mismatches HR 4.1 Total HLA A, B, and DR mismatches among adult heart transplant recipients, Donor and recipient antigen matching is based on OPTN antigen values and split equivalences policy as of 213. Recipient Recipient + Recipient unk. Donor D D+ D unk. D D+ D unk. D D+ D unk. CMV EBV HIV HR 4.2 Adult heart donor-recipient serology matching, Adult transplant cohort, Donor serology is reported on the OPTN Donor Registration Form and recipient serology on the OPTN Transplant Recipient Registration Form. Any evidence for a positive serology indicates positive for that serology. If all fields are unknown, incomplete, or pending, the person is categorized as "unknown'' for that serology; otherwise, serology is assumed negative. CMV, cytomegalovirus; EBV, Epstein-Barr virus; HIV, human immunodeficiency virus. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

16 16 OPTN/SRTR 213 Annual Data Report outcomes 1 Sex Age Race VAD Medical urgency 9 Percent Female Male White Black Hispanic Asian Other/unknown Months posttransplant Months posttransplant Months posttransplant Months posttransplant Months posttransplant HR.1 Patient survival among adult heart transplant recipients, No VAD VAD Status 1A Status 1B Status 2 Patient survival estimated using unadjusted Kaplan-Meier methods. For recipients of more than one transplant during the period, only the first is considered. Ventricular assist device (VAD) status at time of transplant. 3 4 Patients (in thousands) < Percent Percent EBV- EBV+ EBV Unknown HR.2 Recipients alive with a functioning heart graft on June 3 of the year, by age at transplant Recipients are assumed to be alive with function unless a death or graft failure is recorded. A recipient may experience a graft failure and be removed from the cohort, undergo retransplant, and reenter the cohort Months posttransplant HR.3 Incidence of first acute rejection among adult heart transplant recipients, by age, Acute rejection is defined as a record of acute or hyperacute rejection, or a record on the OPTN Transplant Recipient Registration or Transplant Recipient Follow-up Form of an anti-rejection drug being administered. Only the first rejection event is counted. Cumulative incidence is estimated using the Kaplan-Meier competing risk method Months posttransplant HR.4 Incidence of PTLD among adult heart transplant recipients, by recipient EBV status at transplant, Cumulative incidence is estimated using the Kaplan-Meier competing risk method. Posttransplant lymphoproliferative disorder (PTLD) is identified as a reported complication or cause of death on the OPTN Transplant Recipient Followup Form or the Posttransplant Malignancy Form as polymorphic PTLD, monomorphic PTLD, or Hodgkin disease. Only the earliest date of PTLD diagnosis is considered. EBV, Epstein-Barr virus.

17 heart 17 outcomes Rate per Cancer site Observed 1, PY Lower CI Upper CI Lip Mouth, tongue, other oral cavity and pharynx Salivary gland Oropharynx including tonsil Esophagus Stomach Small intestine Colorectum Anus, anal canal and anorectum Liver Intrahepatic bile duct Other biliary Pancreas Larynx Lung and bronchus Soft tissue including heart Melanoma of the skin Other non-epithelial skin Breast Cervix uteri Corpus uteri Ovary Vulva Prostate Testis Penis and other male genital organs Urinary bladder, ureter, and other urinary organs Kidney Eye and orbit Brain, cranial nerves, and other nervous system Thyroid Hodgkin lymphoma Non-Hodgkin lymphoma Myeloma Chronic lymphocytic leukemia Acute myeloid leukemia Acute monocytic leukemia Chronic myeloid leukemia Kaposi sarcoma Miscellaneous Tumors with poorly specified morphology HR. Posttransplant cancer among heart transplant recipients, 2-29 Reported cancer data linked to OPTN data from California, Colorado, Connecticut, Georgia, Hawaii, Illinois, Iowa, Michigan, New Jersey, New York, North Carolina, Texas, Florida, and Utah state cancer registries. Reported cancers are counted once per type per person posttransplant. Denominator: person-years posttransplant for residents of the above states who underwenttransplant2-29. Sex-specific denominators areusedtocomputeratesforsex-specific cancers. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

18 18 OPTN/SRTR 213 Annual Data Report outcomes Percent day 1-year 3-year -year 1-year HR.6 Patient death among adult heart transplant recipients adult recipients of deceased donor hearts, including multi-organ transplants. Patients are followed until the earliest of retransplant, death, or December 31, 213. Estimates computed with Cox proportional hazards models adjusted for age, sex, and race. Percent of recipients who died 1 year after transplant Graft failure Infection Cardio/cerebrovascular Malignancy Respiratory Months since transplant Percent of recipients who died years after transplant 7 Graft failure 6 Infection Cardio/cerebrovascular Malignancy 4 Respiratory s since transplant HR.7 Cumulative incidence of death by cause among adult heart recipients Primary cause of death is as reported on the OPTN Transplant Follow-up Form. Other causes of death include hemorrhage, trauma, noncompliance, unspecified other, unknown, etc. Cumulative incidence is estimated using Kaplan-Meier competing risk methods.

19 heart 19 pediatrictransplant New patients 6 Patients on list on Dec 31 each year 3 3 Patients 4 2 Active Inactive Patients 2 2 Active Inactive HR 6.1 Pediatric candidates waiting for heart transplant A new patient is one who first joined the list during the given year, without having been listed in a previous year. Previously listed candidates who underwent transplant and were subsequently relisted are considered new. Candidates concurrently listed at multiple centers are counted once. Concurrently listed candidates who are active at any program are considered active; those who are inactive at all programs are considered inactive. HR 6.2 Distribution of pediatric candidates waiting for heart transplant Candidates waiting for transplant any time in the given year. Candidates listed concurrently at multiple centers are counted once. Age is determined at the later of listing date or January 1 of the given year. Time on the waiting list is determined at the earlier of December 31 or removal from the waiting list. Medical urgency status is the most severe during the year. Ventricular assist device information is from the time of listing. Active and inactive patients are included. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

20 2 OPTN/SRTR 213 Annual Data Report pediatrictransplant N % N % Age < Sex Female Male Race White Black Hispanic Asian Other/unknown Citizenship US citizen Non-citizen resident 3.9. Non-citizen non-resident Other/unknown Primary diagnosis Congential defect Dilated myopathy: idiopathic Dilated myopathy: familial Restrictive myopathy: idiopathic Dilated myopathy: myocarditis Other/unknown Heart tx history First transplant Retransplant Blood type A B AB O Waiting time < 1 year < 2 years < 3 years < 4 years < years years Medical urgency 1A B Inactive VAD at listing Multi-organ Heart only Heart-kidney Heart-lung Other candidates Patients at start of year Patients added during year Patients removed during year Patients at end of year Removal reason Deceased donor transplant Patient died Patient refused transplant 2 Improved, tx not needed Too sick for transplant Other HR 6.4 Heart transplant waitlist activity among pediatric candidates Candidates concurrently listed at more than one center are counted once, from the time of earliest listing to the time of latest removal. Candidates who are listed, undergo transplant, and are relisted are counted more than once. Candidates are not considered to be on the list on the day they are removed; counts on January 1 may differ from counts on December 31 of the prior year. Candidates listed for multi-organ transplants are included. HR 6.3 Characteristics of pediatric candidates on the heart transplant waiting list on December 31, 23, and December 31, 213 Candidates waiting for transplant on December 31, 23, and December 31, 213, regardless of first listing date; active/inactive status is on this date, and multiple listings are not counted. VAD, ventricular assist device.

21 heart 21 pediatrictransplant HR 6. Three-year outcomes for pediatric candidates waiting for heart transplant among new listings, 21 Candidates waiting for any heart transplant and first listed in 21. Candidates concurrently listed at more than one center are counted once, from the time of earliest listing to the time of latest removal. DD, deceased donor. Transplants per 1 wait-list years < HR 6.6 Heart transplant rates among active pediatric waitlist candidates Transplant rates are computed as the number of deceased donor transplants per 1 patient-years of active waiting in a given year. Age is calculated on the first active listing date in a given year. 2 Age 2 Race Primary diagnosis 2 Deaths per 1 wait-list years 1 1 < Deaths per 1 wait-list years 1 1 White Black Hispanic Asian Other/unknown Deaths per 1 wait-list years 1 1 Congenital defect Dilated myopathy: idiopathic Restrictive myopathy: idiopathic Dilated myopathy: myocarditis Other/unknown VAD at listing Blood type Medical urgency 2 Deaths per 1 wait-list years 1 1 No Yes Deaths per 1 wait-list years 1 1 A B AB O Deaths per 1 wait-list years 1 1 Status 1A Status 1B Status 2 Inactive HR 6.7 Pretransplant mortality rates among pediatric heart transplant candidates, by age Mortality rates are computed as the number of deaths per 1 patient-years of waiting in the given year range. Candidates concurrently listed at multiple centers are counted once. Deaths after removal from the waiting list are not counted. Age is calculated on the later of listing date or January 1 of the given year. Rates by status are calculated as the number of transplants for a given status divided by total waiting time in the year at that status. VAD, ventricular assist device. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov

22 22 OPTN/SRTR 213 Annual Data Report pediatrictransplant Transplants < HR 6.8 Pediatric heart transplants, by age Recipients of heart or heart-lung transplant N % N % Age < Sex Female Male Race White Black Hispanic Asian Other/unknown Primary diagnosis Congenital defect Dilated myopathy: idiopathic Dilated myopathy: familial Restrictive myopathy: idiopathic Dilated myopathy: myocarditis Other/unknown Heart transplant history First transplant , Retransplant Blood type A B AB O ABO compatibility Comp./iden , Incompatible Insurance Private Medicaid Other government Other/unknown Waiting time < 31 days days days < 6 months < 12 months < 2 years < 3 years years Medical urgency Status 1A , Status 1B Status Inactive 1.1. VAD status No VAD VAD Multi-organ transplant Heart only , Heart-lung Heart-kidney Heart-liver. 3.3 PRA < 1% < 2% < 8% < 98% % recipients ,18 1. HR 6.9 Characteristics of pediatric heart transplant recipients, and Heart transplant recipients, including retransplants. VAD, ventricular assist device.

23 heart 23 pediatrictransplant Percent EBV- EBV+ EBV Unknown 2 Recipient Recipient + Recipient unk. Donor D D+ D unk. D D+ D unk. D D+ D unk. CMV EBV HR 6.1 Pediatric heart donor-recipient serology matching, Donor serology is reported on the OPTN Donor Registration Form and recipient serology on the OPTN Translant Recipient Registration Form. Any evidence for a positive serology indicates positive for that serology. If all fields are unknown, incomplete, or pending, the person is categorized as "unknown'' for that serology; otherwise, serology is assumed negative. CMV, cytomegalovirus; EBV, Epstein-Barr virus Months posttransplant HR 6.11 Incidence of PTLD among pediatric heart transplant recipients, by recipient EBV status at transplant, Cumulative incidence is estimated using the Kaplan-Meier competing risk method. Posttransplant lymphoproliferative disorder (PTLD) is identified as a reported complication or cause of death on the OPTN Transplant Recipient Follow-up Form or on the Posttransplant Malignancy Form as polymorphic PTLD, monomorphic PTLD, or Hodgkin disease. Only the earliest date of PTLD diagnosis is considered. EBV, Epstein-Barr virus. Percent Induction agents IL2-RA T-cell depleting None Calcineurin inhibitor Cyclosporine Tacrolimus Anti-metabolite Azathioprine Mycophenolate mtor inhibitors At transplant 1 year posttransplant Steroids At transplant 1 year posttransplant HR 6.12 Immunosuppression in pediatric heart transplant recipients One-year posttransplantdata arelimited topatients alivewith graft function at1 yearposttransplant. Mycophenolateincludes mycophenolatemofetil andmycophenolate sodium. IL2-RA, interleukin-2 receptor antagonist; mtor, mammalian target of rapamycin. data behind the figures can be downloaded from our website, at srtr.transplant.hrsa.gov