96 J-D: Hosenpud et at 74.0% 41 A% \A% 17.3% 7,2% 50.4% 3,6% 3,7% 61- <1 Ys 1-5 Years i45Years •CongBnital BOlhet •Myopathy OReTK Figure 6. Pediatric heart transplantation indications by age. Rett = Retransplantation. cardiomyopatliy and patisnts with coronarv' lulery disease. Figures 5 and 6 present tlie indications for pedia.tnc heart tra.nspIantation (age < 16 years), first a.s overall uidications, indications by yeai- for the two major indications, and finally indications by age of Ihc recipient. Congenital heait disea-se is the most common indication for transplantation in. the pediatric population and has been since 1989, As anticipated, congenital heart disease makes up close to 75% of the transplan^iations in the less than 1 year age group, 3'et less than 30% m the older aged children. Figure 7 presents tie actuarial suri'ival rate after heart transplantation over a 13^yeai- penod. 'Die overall 1-ycar siu-^ival rate for heart transplantation is 79%. The patient V2 lite (time to 50% sim'ival) is 8.7 years and m those surviving tlie firet year, the patient V2 He is 11.4 years. The falloff in sur\'ival is almost a straight luie firom year 1 through 14. witli a constant mortality rate of 4% per year. The next .series of figiu'es represent actumal sur>;ival rates for yeai" of transplantation, recipient age, and retransplantation. Figure 8 demonstjates 5-year actuarial son-ival rates over the past ] 7 yeai's broken down m ,3-ycar time blocks. There was a substantial increase in more recent patients, compared with those who underwent transplantation fi^oin 1980 to 1985. There is a marginal but statisticahy significant fuitlier increase in survival rates comparmg tic last 5 years of the 1980s with patients who imdeweiit transplantation from Haif-lif8=8,7 yrs Ccnd, tialf-llfe=11,4yre 7 8 8 10 11 12 13 14 Years Post Transplantation Hgnre 7. Total heart transplantation actuarial survival. Registry ofint 1 Soc. for Heart & Lung Transplantation: 15'" Official Report '98 97 100 90 80 70 60 50 40 •'^'Sj- 1980-1985 Ha)f4ife=5.3 yrs 1986-1990 ttalfnife=8.8yrs 1991-1997 Half-life=9.4yrs ""-5JJI»imjjj„ i80-85vs 86-90: p=<,0001 •'-" *' "• p=<.OI)Of p=<.0001 i80-85vs 91-97: 86-90 «s 91-97: 0 5 10 15 20 25 30 35 40 45 50 55 60 Months Post Transplantation • 1980-1985 » 1986-1990 » 1991-1997 N=2,207 N=-,2,80! N=2:,97-; Figure 8. Aduh hean transplantation actuarial f-annval by era Monttis Post Transplantation • <45 Years u 4S-54 Years -+ 55-64 Years •» >=65 Years N=mi95 N-12 769 N=12.J86 N=1 291 Figure f. Adult heart transplantation actuarial survival by age. 0 6 12 18 24 30 36 42 48 54 60 ivionths Post Transplantation + Retransplant < 9 MO » Retransplant > 9 MO o Overall Retransplants N=484 N=415 N=899 Figure IS. Adult heart retransplanlation actuarial survival 98 J.D. Hosenpudetal. 3? 100 03 > d -: rn r ID TO k_ to 0) > an tjO 40 20 I 40-^ T + I4±n 3^ 7-12 13-24 25-36 37-48 4a«) 61-84 85+ Inter-transplart interval (months) Figure 11. Adult heart retransplanlatton !-year survival by interval from first transplantation. 1991 onward. Figure 9 demonstrates actuarial survival rates broken down by recipient age group. There is a statistically significant decrease in survival for each increase in decade of life, with a clinically significant decrease in those patients over age 65 years The actuarial survival rate for adult retransplantation is displayed in Figures 10 and 11. Figure 10 presents 5-year actuarial survival rates for those retransplantations done within and beyond 9 months after the initial transplantation. Figure 11 presents the average (± 95% confidence intervals) 1 -year survival rate depending on the interval between first and second transplantation. As can be seen, there is a progressive increase in survival rates with increased time between operations. Those patients who underwent transplantation after 2 years have 1-year survival rates of approximately 70%, still lower than priman transplantation. Tables I and 11 show multivariate logistic regression analyses for adult cardiac allogratt recipients perfonned on all patients in the Registry having complete data. In this analysis, the end points are 1 - and 5-years survival rates. As has been previously shown in prior Registry reports, the vast majority of risk factors known to affect 1 -year mortality persist at the 5-year time point as a result of their profound effects early on. Recipient factors that have a statistically significant negative impact include prior transplantation, requiring a venU-icular assist device or ventilator support before transplantation, and increasing age Recipient factors that have a positive impact include diagnosis of either coronan artery disease or cardiomyopathy and ABO blood group A. Center factors that are negative include low volume, and donor factors include increasing ischemic time, donor sex, iuid age In this report (as with last year's report) donor and recipient age, as well as ischemic time, were analyzed as a)ntinuous variables and dcTnonstrate a highly statisticalh significant increasing risk with increasing values. Figure 12 demonstrates survival rates after pediatnc heart transplantation overall and IS broken down by age groups. The older age pediatric group has sur\ival rates nearly identical to the adult population, whereas those with the worst outcome are less than 1 year of age. Patients 1 to 5 years of age have intermediate survival rates Registry -oflnt 'I Soc. for Heart <S Lung Tmnsplaniation: 15''^ Official Report '98 99 Taile 1. Risk factors, for I-year mortality aftcsr adult heart transplantation. Variable Odds ratio 95%'Confidenes iniervat p Value Negative recipient factors Ventilator 2.66 Repeat Tx 2.33 VAD IA<J Ctrvol" :9TX/YR 1.3 Female, donor 1.2'!^ Positive reeipiettt factors AEO.iypsA -0,9 CAD 0.79 CM 0.71 Isctieiiiic time linear lschefnic'time:(0} QJS Ischeniictlme (2)'' .0.93 Ischemic time (4)- 1.1 S rseliemic time (6)' 1. .43 rscliemic4'i!ae:(.S) .1 7S Recip age (linear) Recip age. 20 0.S5 KecipageSO' O.XS: Recip.agc.40 0.8?: Reeip age 50 1 Recip age 50 1,19 Recip age 70 1,5' Donor age (linear) Donor age JO- 0\t9 'Donor age \10 .0,9.9- Donor age 4.0' 1.18. Donor age 50 1 48: Donor age'6Q 1.99 ,2.20-3.2! 1,80-3.01 1.23-1,SO 1 15-1.47 1.11-1,33 0,83.0:9S fl.8-8-0.93 0.:60-0.83 0.67-0.83: 0.90-0 95 1.09-1.22 1.25-1.64 1.43-2.22 0.'69-1.06: 0.76-0.94 0.85-0.93 LOW.OO .1.11-1.27 •1.26-1,?<)• 0.84-0:95 0.99-1,00 1 14-1.22 1.34-1.64 159-2.48 0 0001 0 01^01 onooi 0 0001 0 OOOI OOl 0 005 (.IHIiIl 0 CIIJOI <a.ooo;l •<0.0001 T%^Jransplantation'^ VAB, V^asmlar CM, •cnrdiomyffpaihy^ Recip, mapient. device; Ctr viA,.Gmter volsira^,.CAD, comnnry-artery dh^me. l<1 vs6 15 p='f»00! 1. 18 i4 30 3o 42 4'J Months Post Trahsplantalion, -•••<1Yea.r -u .1-5 Tears ©:.S 15Yea«. »-Overall N-=1.01-0- N=71-8 N=!,2» l<J=3.,1319 Figure 12. Pediatric heart (rampkmtalkm 'actuarial 'mtvivai by age 100 J. D. Hosenpud et al. Table 2. Risk factors for 5 year mortality after adult heart transplantation Variable Repeal Tx Ventilator Ctr vol 9 Tx,yr Female donor Ischemic time (linear) Ischemic lime (0) Ischemic time (2) Ischemic time (4) Ischemic time (6) Ischemic time (8) Recip age (linear) Recip age 20 Recip age 30 Recip age 40 Recip age 50 Recip age 60 Recip age 70 Donor age (linear) Donor age 20 Donor age 30 Donor age 40 Donor age 50 Donor age 60 l>onor age 60 Odds ratio 3.08 1.78 1.29 1.15 0.77 0.94 1.13 1.37 1.66 1.21 0.99 0.93 1 1.22 1.71 0.89 0.99 1.19 1.53 2.21 2.21 95% Confidence interval p Value 2.34-4.05 1.40-2,27 1.14-1.47 1 04-1.28 0.68-0.88 0.91-0.97 1.06-1.21 1.17-1.60 1.29-2.13 0.97-1.51 0.89-1.10 0.89-0.97 1.00-1.00 1.10-1.31 1.40-2.09 0.83-0.94 0.99-1,00 1.14-1.25 1.34-1.76 1.57-2.82 1.78-2.75 0.0001 • 0.0001 0.0001 0.006 0.0001 0.0001 0.0001 Tx. Transplanlatwn. Ctr vol. center volume. Recip, recipient ' 9.536 Tables III and IV demonstrate the multivariate logistic regression analysis of risk at 1 and 5 years for pediatric heart transplantation. Similar to the adult population, repeat transplantation, ventricular assist device, and ventilator mechanical support carry the greatest risks. Other risk factors include very young age, congenital heart disease, low center volume, and donor age Interestingly, recipient age risk m the pediatric population is also linear, but in this ca.se, the risk is inversely correlated to age At 5 years, recipient age is no longer a nsk factor, but recipient se.x (female) becomes one In this year's report, morbidity' data at both 1 and 3 years are presented The data set for these analyses include worldwide data from 1994 onward (US data only for employment status). Figures 13 and 14 demonstrate the acti\ity levels and employment status of paticiits 1 iind 3 years after transplantation. Most of the patients are considered to have no limitations in function, yet less than 40% are working (does not include those retired). Figure 15 demonstrates the percent of patients requiring hospitalization alter the initial transplantation, with approximately 18% still requiring a hospitalization between the second and third years after tran.splantation Figures 16 to 18 outline incidences of other morbid conditions in the first 3 years after tran.splantation, including drug-treated hypertension, renal dysfunction, drug-treated Registry of bit 1 Soafor Heart A Lung Transplantation: 15'" Official Report '98 101 Table 3. Risk factors for 1 year mortality in pediatric heart transplantation Variable Odds ratio 95% Confidence interval p Value Retransplmt lABP/VAD Ventilator Congenital Ctr vol <9 Tx,'>T Becip age (linear) Recip age 0 Recip age 3 Recip age 6 Recip age 12 Recip age 17 Donor age (quadratic) Donor age 0 Donor age 10 Donor age 20 Donor age 30 Donor age 40 Donor age 50 2.55 2.54 1.5 1.41 1.36 1.39 1.2 1.03 0.75 0.58 1.08 1 1.07 1.33 1.89 3.11 1.44-4.51 1.17-5.51 1.24-2.0C 1.10-2.80 1.08-1.71 1.21-1.61 1.11-1.29 1.01-1.04 0.67-0.85 0.46-0.73 1.03-1.13 1.00-1.00 1.02-1.12 1.10-1.60 1.24-2.87 0.87-7.86 <0.0001 0.02 0.0003 0.006 0.009 <0.0001 0.003 lAWjMraaomc balloon pump; VAD, vmcular assist device-, Ctr vol, cenler volume; Tx, transplantation; Recip, recipient II = 20113, Table 4, Risk factors for 5 year mortality after pediatric heart transplantation. Variable Odds ratio 95% Confidence interval p Value Retranisplant Ventilator Diagnosis-cong Female recipient Donor age (quadratic) Donor age 0 Donor age 10 Donor age 20 Donor age 30 Donor age 40 Donor age 50 3.21 1.47 1.36 1.31 1.08 1 1.08 1.34 1,95 3,28 1.40-7.35 1.08-2.01 1.03-1.79 1.00-1.71 1.01-1.15 1.00-1.00 1.01-1.15 1.04-1.7.1 1.10-3.45 1.19-9.0S 0.006 0.02 0.03 0.05 0.03 , congemtal; n~ i 063. 93.5% 1.4% 8.5% O.B% 5 8% 1 Year Followup 3 Year Follovjup • No Activity Limitations nPerforms witli Assistance •Total Assistance Figure 13. Heart transplant recipient functional status. 102 /. D. Ilosenpud et al. 47.1 39J ^-'A 1 Year Followup 3 Year Followup •Working Full Time S Working Part Time a Not Working HI Retired Figure 14. Heart transplant recipient work status. 5- i :::•:• . • 1 Year Followup mi'/- • 7.1% 4.8% "if:. ;::iE" •••:::••••::•}?::: 3 Year Followup • No Hospitalization •Hosp., NoiRei ,'Not liifect. THosp, Rejection • Hosp, Infection •Hosp, Rej +Infect Figure 15. Rehospifabzation after heart transplantation. HTN No 33.7% Yes 66.3% No 29.7»/. Yes 70.3% Renal Dysfyni o°* •No Rsnai •ZJysfunclion IHHenal Dysf iliJCreatnine >?.5mg/dl •Cnronic Datv'sss Figure 16. Hyperten-iiot: and renal dysjunction after heart transplantation. HTN. hypertension Registry of Im'l Soc. for Heart & Lung Tmmplantaimn: 15* Official Report '98 103 Hyperiipder Ni 64.1 Diabetes « ^"J "^ •^M"- s,1.^| P Yes 45.6% 16 SK r Figure 17. Hyperlipidemia and diabetes after heart transptantation. Malignancif No 96.3»,-, 1 Year Foilowu, ^^^ No JIIM 92 4¥ IIIIIIJ^^ 3 Year Foitowup illlllP' licA ?.(.••• . 1 !1 Yes 3 7% 0! • ••=; •• 25 ••••• • Lynip'l NotRe-pora ' 5.0% 1 Ves FigMi-e 18. Malignancy after heart transplantation. ^WVear 1 llYiSar 3 ^^^_ 1 • ; :i4.9% 1- 1 51.7% - \ \ \ r// Hgure 19. Maintenance immunosuppression after heart transplantation. 104 J.D. Ilosenpiid et at Muitio • , •••••• •••••••• ••' ^^*^^' Other.Cardiac 31 Days-1 Year •• • • •.•• • •.;ardiac CAl Lymphom Malig, C - 1+ Year Figure 20. Heart transplantation cause of death by time after tramplantation. CMV, Cytomegalovirus, CAV, cardiac allograft myopathy. hyperlipidemia, drag-treated diabetes, and malignancy. Figure 19 demonstrates the inaiBtenance itninimosuppression in the population. An increasing number of patients are being treated willi tacrolimus or mycophcnolatc mofetil, and more than 75% of patients arc still on corticosteroids at 3 years after transplantation. Figure 20 demonstrates the causes of death after heart transplantation (both adult and pediatnc) at three different time points with the entire data set. Early after transplantation, nonspecific graft failure accounts for the largest proportion of deaths. In the mtennediate penod, there is an approximately equal representation by aeute rejection and infection. Late after transplantation the most common causes of death are cardiac allograft vasculopathy, malipancy, and, interestingly, acute rejection. The other categoiy is made up of listed diagnoses not fitting into die more common categories. > Figure 21. Heart-lung transplantation volumes and donor age hyyear. Registryof Int'lSoc. for Heart & Lung Transplantation: 15'^' Official Report '98 105 50 S I 40 'a. £ 30 H 20 ^^ O ^ 10 0 >1 1-5 6-10 11-17 18-34 35-49 50-64 Age Figure 22. Age distribution of heart-lung transplant recipients. Heart-Lung Tranplantatioii Figure 21 shows tlie number of heart-lung trasnplantations reported to the registrv' from 1982 to 1997 and the average donor age over this period. The number of heart-lung transplantations peaked in 1989 and has dechned thereafter. Similar to heart, transplantation, donor age has continued to ri.se. Figure 22 demonstrates the age distribution for heart-lung transplantation, with clustering between 18 and 49 years. Figure 23 demonstrates the indications for heart-lung Iran.splantation in the adull population. The three most common indications are pulmonar}' hypertension, congenital heart disease, and cystic fibrosis. The 11-year actuanal survival rate for heart-keg transplantation is demonstrated m Figure 24. The 1 -year siir\'ival rate is approxmiately 60%, whereas tlie 11 -year .survival rate IS 21%. The survival Vi life for the entire curve is 2.6 years because of the high first-year mortality rate. The conditional Yi life for those sun-iving the first year is more than 8.4 years. Tables V and VI demonstrate the multivariate logistic regression analysis of lital 27,7% PPH 25,9' ,1A 2,3% ipp 2.' nnphysema 3,8% ReTx 2.8"/ X., 15.6% Misc 19.2% Figure 23. Heart-lung transplant indications. PPH, Primary pulmonary hypertension; AI,4, alpha,, antitrypsin: C¥. cystic fibrosis, MeTx, reinmsplantation, IPF, idiopathic pulmonary fibrosis. [...]... Donor age 50 Donor age 60 Odds ratio 95% Confidence interval p Value 2.39 1.88 1 .6 5-3 .47 1.2 5-2 .84 '%;%'%% % - % \ % ^ % % fniBiiateral'l'-jubie Lung fisSingle Lung Figure 26 Ijing tran;iplcmiaikm volumes and donor age hy year 50 40 30 20 10 >1 I-5 6 0 1 1-1 7 1 3-3 4 3 5-4 9 5 0 -6 4 >6E Age Figure 27 Age distnbuiion of lung recipiems 20 0) X JJJIIIJJJJ^ \%%%%%%%%%\%%% Figure 2Ji ''cdirjinc hcai >-haig-hiny^ iroh^iptai'iiaiiim mLmber:', by age undyear Registry ofint 1 Soc for Heart. .. 36 'fhcrc arc no significaii! differences in outcomes between tliesc three procedures; h.owcver, numbers in all groups are small Table IX displays the multivariate analysis for 1 -year mortality after pediatric lung and heart- lung transplantation 100 £ I \ BO b • • , _ * - - ; -' " ^- •' -' - -^ :•;?•;;«-i^^^., 20 - • 33 36 a • 0 ' 3 6 9 12 15 18 21 24 27 30 tvlonths Post Transplantation ^ • Lyng » Heart- Lung... through 1993, on the basis of tlie past 3 years' data, this growth has clearly ceased, again m spite of the use of increasingly older donors (Figure 26) The age distribution for lung transplantation is younger than for heart or heart- lung transplant recipients, priraanly because of its use in the cystic fibrosis population (Figure 27) Figure 28 demonstrates the pediatric lung and heart- lung transplantation... Registry' of hit'I Soc for Heart & Lung Tramplantation: 15'^' Official Report '98 111 0 6 12 18 24 30 36 42 48 54 60 Months Post Transplantation • =65 Years i lii=2,158 N-l,832 N=1,«S N=125 Figure M,.iduH huig iran.ipiamslion acmanai sun'jval by age Adult I'jng and hcaii-Iurig ti";iiiSj3lantation survivai rates are presented m Figure liS- I'lie 1-, 2-, ami 3-yeiirs... alpha,-antitrypsin deficiency Recip, recipient n = 4237 Table 8 Risk factors for 5-year mortality after adult lung transplantation Variable Repeat Tx IPF AlA Recip age (linear) Recip age 20 Recip age 30 Recip age 40 Recip age 50 Recip age 60 Recip age 70 Odds ratio 95% Confidence 2.12 1 .68 0 .67 p Value 0.007 0.01 0.002 1.1 1-4 . 06 1.1 6- 2 .43 0.4 8-0 .92 1.07 0.91 0.92 1.11 1 .6 2.74 interval 0 .6 8-1 .68 0.7 6- 1 .10... 1.2 5-2 060 1,2 7-2 .85 0.85 1.09 1.39 1.79 2.29 p Value 0.7 6- 0 .95 1.0 3-1 .15 1 1 1-1 .74 1.2 0-2 .65 1,3 0-4 .02 0.02 0.002 0.004 Tx tratviplantation: Ctr vol, center volume n '.:7 Table 6 Risk factors for 3 year mortality in adult heart- lung transplantation Variable Ventilator Ctr vol 5 l \ \T Donor age (linear) Donor age 20 Donor age 30 Donor age 40 Donor age 50 Donor age 60 Odds ratio 432 interval 9 1.7 1.2 5-2 0 .60 ... 1.2 5-2 0 .60 1.2 7-2 .85 0.87 1.07 1 31 1 .61 1.98 0.7 7-0 .99 I.0 0-1 .I4 1.0 2-1 .69 1.0 3-2 .51 1.0 5-3 .73 !antdtu^n, agi'ii inc!>tduii_' dpig-tieaicJ h\ri-ri''nsi -t jenai i!\"lanelii!n, (H»j;-luMtedhvfalil'jdentw itm^-tiearci! Jiibt-t^j atdmaliguanc} i s g t a c J ; Jeniouvtialc-' ihr rwirk-njnLC inimiuioMippressinn . 1 .6 5-3 .47 1.2 5-2 .84 1.3 7-3 .12 1.0 1-1 .71 0.5 8-0 .94 0.4 0-0 .59 0 .6 6-0 .89 0.5 1-0 ,72 0 .6 6-0 .82 0.8 6- 0 .93 1.0 6- 1 .13 1.2 1-1 .47 1.3 7-1 .92 1.0 2-1 .11 1.0 0-1 .00 1.0 3-1 .12 1.1 1-1 .58 1.2 7-2 . 76. 0. :6 0-0 .83 0 .6 7-0 .83: 0.9 0-0 95 1.0 9-1 .22 1.2 5-1 .64 1.4 3-2 .22 0.&apos ;6 9-1 . 06: 0.7 6- 0 .94 0.8 5-0 .93 LOW.OO .1.1 1-1 .27 •1.2 6- 1 ,?<)• 0.8 4-0 :95 0.9 9-1 ,00 1 1 4-1 .22 1.3 4-1 .64 15 9-2 .48. 3.11 1.4 4-4 .51 1.1 7-5 .51 1.2 4-2 .0C 1.1 0-2 .80 1.0 8-1 .71 1.2 1-1 .61 1.1 1-1 .29 1.0 1-1 .04 0 .6 7-0 .85 0.4 6- 0 .73 1.0 3-1 .13 1.0 0-1 .00 1.0 2-1 .12 1.1 0-1 .60 1.2 4-2 .87 0.8 7-7 . 86 <0.0001