Adult heart retransplanlatton !-year survival by interval from first transplantation.. Figure 10 presents 5-year actuarial survival rates for those retransplantations done within and bey
Trang 196 J-D: Hosenpud et at
\A%
17.3%
7,2% 50.4%
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
Trang 2100
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
" " - 5 J J I » i m j j j „
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 = m i 9 5 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
Trang 398 J.D Hosenpudetal
3? 100
03
>
d
-:
rn
r
ID
TO
k_
to
0)
>
an
tjO
40
20
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
Trang 4Registry -oflnt 'I Soc for Heart <S Lung Tmnsplaniation: 15''^ Official Report '98 9 9
T a i l e 1 Risk factors, for I-year mortality aftcsr adult heart transplantation
Negative recipient factors
Ventilator 2.66
Repeat T x 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 i 4 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
Trang 51 0 0 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 ( U S 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
Trang 6Registry 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,
T a b l e 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
Trang 7102 / 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 • H o s p , NoiRei ,'Not liifect T H o s p , Rejection
• Hosp, Infection • H o s p , Rej +Infect
Figure 15 Rehospifabzation after heart transplantation
HTN
No
33.7%
Yes
66.3%
No
29.7»/
Yes
70.3%
Renal
Dysfyni o°*
• N o Rsnai •ZJysfunclion IHHenal Dysf iliJCreatnine >?.5mg/dl • C n r o n i c Datv'sss
Figure 16 Hyperten-iiot: and renal dysjunction after heart transplantation HTN hypertension
Trang 8Hyperiipder
Ni
64.1
D i a b e t e s
«
^"J
" ^ • ^ M "
-s , 1 ^ | P
Yes 45.6%
16 SK
r
F i g u r e 17 Hyperlipidemia and diabetes after heart transptantation
Malignancif
No
96.3»,-,
1 Year Foilowu,
^ ^ ^
No J I I M
92 4¥- IIIIIIJ^^
3 Year Foitowup i l l l l l P '
licA ?.(.•••
1 !1
Yes
3 7 % 0 ! • ••=; -••
2 5 ••••• •
Lynip'l NotRe-pora ' 5.0%
1 Ves
FigMi-e 18 Malignancy after heart transplantation
^WVear 1 llYiSar 3
^^^_
1
• ;
:i4.9%
1-1 51-1.7%
-\ -\ -\
r//
Trang 9104 J.D Ilosenpiid et at
M u i t i o • , •••••• •••••••• ••' ^^*^^'
Other.Cardiac
31 Days-1 Year
•• • • •.•• -• • ; a r d i a c
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
Trang 10Registryof Int'lSoc for Heart & Lung Transplantation: 15'^' Official Report '98 105
50
S
'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