Cardiaco
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The Registry of the International Society for Heart
and Lung transplantation: Fourteenth
Official Report - 1997*
DATA SET AND STATISTICAL METHODOLOGY
This report represents data on 40,738 heart transplantations reported from 297 heart transplantation programs, 2186 heart-lung transplantations reported from 114 programs, and 3939 single lung and 2543 double lung transplantations reported from a total of 145 lung transplant programs. For purposes of analysis, the data set was closed as of February 7, 1997. Survival was calculated actuarially (Harris and Albert, New York, Marcel Decker, 1991, pp 12-5, 53-62) and actuarial survival curves were contrasted using the Wilcoxon and log-rank tests. Logistic regression methods (Hosmer and Lemeshow, New York, John Wiley & Sons, 1989:1-134) were used to determine which variables were associated with survival after transplantation. A multivariate logistic regression analysis was then applied to a subset of the data (U.S. Centers, 10/1/87 to 2/7/97) to determine independent predictors of survival. Furthermore, the odds ratio of each variable was expressed as a comparison of survival between groups, with a value of 1.0 indicating no survival benefit, less than 1.0 indicating increased survival, and greater than 1.0 indicating decreased survival.
HEART TRANSPLANTATION
Figure 1 shows the number of heart transplantations reported to the Registry from the years 1982 to 1996 in the bars, with donor age as a line graph (Y2 axis). The reduced number of transplantations in 1996 reflects delayed reporting and mimics the 1995 numbers presented in last year's report. It is clear, however, that heart transplantation volume has plateaued, in spite of the practice of using older donors to "expand" the donor pool. Pediatric heart transplantations likewise have plateaued, and in the youngest populations (0 to 5 years), the number of procedures seems to be decreasing (Figure 2). Figure 3 demonstrates the indications for adult heart transplantation, with coronary artery disease and cardiomyopathy representing approximately equal numbers and both together representing the vast majority of cases. The percentage of cases for each of these two diagnoses has varied from year to year, with cardiomyopathy being the majority of cases in the early 1980s, supplanted by coronary artery disease in the late 1980s and early 1990s at a time when the age criteria for heart transplantation was being
*Compiled with the cooperation of the 306 cooperating Centers.
Presented at the Seventeenth Annual Meeting and Sejentifie Sessions of the International Society for Reart and Lung transplantation, London, England, April 2-5,1997.
Reprint requests: International Society for Heart and Lung Transplantation, 14673 Midway Rd., Suite 108, Dallas, TX 75244.
J Reart Lung Transplant 1997;16:691-712.
Copyright © 1997 by the International Society for Reart and Lung transplantation.
1053-2498/97/$5.00 + 0 14/1/82136
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The next series of figures represent actuarial survival for year of transplantation, recipient age and retransplantation. Figure 7 demonstrates 4-year actuarial survival over the past 16 years broken down in 3-year time blocks. There was a substantial increase in more recent patients, compared with those who underwent transplantation from I980 to l985. It is interesting to note, however, that no significant survival improvement has occurred from 1986 to the present time. Figure 8 deinonstrates actuarial survival broken down by recipient age group. There is a statistically significant decrease in
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Tables I and II show multivariate logistic regression analyses for adult cardiac allograft recipients performed on a subset of the Registry in which complete and verified data are available for a number of potential risk factors (U.S subset, see above). In this analysis, the end points are 1- and 5-year survival. 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
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time point as a result of their profound effects early on. Recipient risk factors that have a statistically significant impact include prior transplantation, requirement of ventilator support before transplantation, increasing age, and race. Center factors includvolume and ischemic time, and donor factors include donor race, sex, and age. In contrast to prior reports, both donor and recipient age were analyzed as continuous variables (linear and quadratic) and demonstrate a highly statistically significant merca increasing risk as age increases.
Figure 10 shows survival after pediatric heart transplantation overall and broken down by age groups. The older age pediatric group has survival nearly identical to the adult population, whereas those with the worst outcome are less than 1 year. Patients 1 to 5 years of age have intermediate survival rates. Tables III and VI demonstrate the multivariate logistic regression analysis of risk at 1 and 5 years for pediatric heart transplantation.
| Table IX Risk for 1-year mortality after pediatric heart-lung/lung transplantation | |||
| Variable | Odds ratio |
95% Confidence interval |
p Value |
| Ventilator | 13.1 | 4.49-38.21 | <0.0001 |
| Non-white recipient | 3.57 | 1.20-10.59 | 0.02 |
| Cold ischemic time | 1.7 | 1.23-2.34 | 0.001 |
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We have begun analyzing follow-up information collected over the past 2 years. This report will focus on U.S. centers (4/94 to 12/96) because of the data being more complete but will be expanded to the entire data set in subsequent years. Figures 11 and 12 demonstrate the activity levels and employment status of patients 1 and 2 years after transplantation. Most patients are considered to have no limitations in function, yet approximately 40% are not working (does not include those retired). Figure 13 demonstrates the percent of patients requiring hospitalization after the initial transplantation, with more than 20% requiring hospitalization in the second year. Figures 14 to 16 outline incidences of other morbid conditions in the first 2 years after transplantation, including drugtreated hypertension, renal dysfunction, drug-treated hyperlipidemia. drug-treated diabetes, and malignancy. Figure 17 demonstrates the maintenance immunosuppression in the population. Most patients continue to be maintained on corticosteroids, even in the second year after transplantation.
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HEART-LUNG transplantation
Figure 19 shows the number of heart-lung transplantations reported to the registry from 1982 to 1996 and the average donor age over this period. The number of heart-lung transplantations peaked in 1989 and has plateaued, whereas similarly to heart transplantation, donor age has continued to rise (excluding 1996). Figure 20 demonstrates the indications for heart-lung transplantation in the adult population. The three most common indications are pulmonary hypertension, congenital heart disease, and cystic fibrosis.
The 1-year actuarial survival for heart-lung transplantation is demonstrated in Figure 21. The 1-year survival rate is approximateiy 60%, whereas file 11-year survival rate is less than 20%. Thie survival ˝ life for file entire curve is 2.5 years because of the high first-year mortaltiy rate. The conditional ˝ life for those surviving the first year is more than 8 years. Tables V and VI demonstrate the multivariate logistic regression analysis of risk factors for 1- and 3-year mortality after adult heart - lung tramplantation. As shown in previous Regitry reports, being on a ventilator before transplantation and low center volume continue to be statistically significant risk factors. As was shown for heart transplantation, thle risk according to donor age increases as a continuous variable at bothl 1 and 3 year. Male donors also result in increased risk, as does donor race, but only at the latter time point. Furthermore, at the 3-year mark, underlying diagnosis other than pulmonary fibrosis is a significant risk factor. Figure 22 demonstrates the most common causes of death after heart-lung transplantation at three different postoperative intervals. Early after transplantation, nonspecific graft failure and hemorrhage account for a substantial majority of thle deaths. In thle intermediate time period, infection is the primary cause, and late after transplantation, bronchiolitis obliterans is the principal cause of death. CAV does account for an important minority of deaths (provide %) late after heart-lung transplantation.
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LUNG TRANSPLANTATION
Although lung transplantation had enjoyed continued growth through 1993, based on the past 3 years´data, this growth seems to be plateauing, again with the use of increasingly older donors (Figure 23). Figure 24 demonstrates the pediatric lung and heart-lung transplantation volumes over the past 12 years. Heart-lung transplantation seems to have been largely abandoned in this patient population, whereas pediatric lung transplantation continues to occur at low but steady rates.
The indications for adult single lung transplantation continue to be dominated principally by chronic obstructive pulmonary disease, whereas cystic fibrosis is the most common indication for double/bilateral lung transplantation as shown in Figure 25. Idiopathic pulmonary fibrosis and primary pulmonary hypertension are also important indications these procedures. The indications for pediatric lung and heart-lung transplantation are shown overall and over time in Figure 26 and by the two primary age groups in Figure 27.Congenital heart disease, cystic fibrosis, and primary pulmonary hypertension are the principal indications. Interestingly, retransplantation is used much more frequently in this age group than in adults.
The 6-year actuarial survival for all lung transplantation (adult and pediatric) is shown in Figure 28. There is no significant difference in actuarial survival comparing single lung to bilateral/double lung transplantation, with patient half times of 3.7 years and 4.5 years for single and double lung, respectively. For transplantation in adults there is a significant difference comparing lung transplantation performed from 1988 through 1990 compared with later years, but no improvement after 1991 (Figure 29). Figure 30 demonstrates the effect of recipient age on survival. Patients aged 55 and older had a significantly lawer survival than younger recipients.
Figures 31 and 32 show survival according to the different indications for single and bilatera/double lung trarisplantation, respectively. Patients with emphysema in both procedures fared well, whereas patients with interstitial pulmonary fibrosis and primary pulmonary hypertension had a significantly worse survival. Figures 33 and 34 show survival in patients with emphysema and primary pulmonary hypertension, respectively, by procedure. There are no differences in survival between single, bilateral/ double lung and, in the case of primary pulmonary hypertension, heart-lung transplantation for each of these indications. Adult lung and heart-lung retransplantation survival is presented in Figure 35. The 1-, 2-, and 3-year actuarial survival rates for lung retransplantation are 44%, 37%, and 30%, respectively. For heart-lung retransplantation the outcomes are even worse, with rates of 30%, 27%, and 24% for 1-, 2-, and 3-year survival, respectively.
Tables VII and VIII show the results of the multivariate logistic regression analyses for risk factors for 1- and 4-year mortality after lung transplantation, respectively, for the U.S. data. Several of the risk factors for 1-year survival, including preoperative ventilator support and patients with congenital heart disease or idiopathic pulmonary fibrosis, are no longer significant at 4 years. Other risk factors, including prior transplantation, donor race, and a recipient diagnosis of primary pulmonary hyperten sion, continue to predict worse long-terrn outcome. As with other organs, recipient age risk is a continuous variable. Of note is that in marked contrast to both heart and heart lung transplantation, donor age is not an independent risk factor for death in lung transplantation.
Actuarial survival for pediatric lung and heart-lung transplantation is shown to Figure 36. There are no significant differences in outcome between these three procedures; however, numbers in all groups are small. Survival rates for all repeat pediatric thoracic transplantations are shown in Figure 37. There is a substantial reduced survival for all organs compared with primary transplantation. Table IX shows the multivariate analysis for 1-year mortality after pediatric lung and heart-lung transplantation. Independent risk factors include ventilator assistance before transplantation (a thirteenfold risk), ischemic time (Continuous variable) aud recipient race.
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As with heart transplantation, we have analyzed follow-up information after lung transplantation collected over the past 2 years with U.S. data (4/94 to 12/96). Figures 38 and 39 show the activity levels and employment status of patients 1 and 2 years after transplantation. A slightly greater percentage of patients have some limitations compared with those after heart transplantation, although similar percentages of patients are used. Figure 40 shows that a significant percentage of patients continue to require repeat hospitalization after lung transplantation. Figures 41 to 43 show the prevalence of comorbid conditions in the first 2 years after transplantation, again including drug-treated hypertension, renal dysfunction, drug-treated hyperlipidemia, drug-treated diabetes, and malignancy. Figure 44 shows the maintenance immunosuppression in the population. There is a larger proportion of patients receiving tacrolimus after lung transplantation compared with heart transplantation.
Figure 45 shows the most common causes of death after lung transplantation (both adult and pediatric) at three different time points. Early after transplantation, nonspecific graft failure and infeetion predominate. In the intermediate time interval, infection is the most common cause of death. Late after transplantation, infection continues to be strongly represented, but bronchiolitis obliterans results in most deaths after 1 year.
CONCLUSIONS
As with the previous year the Registry report is increasingly focusing on late outcomes, because early outcomes have been well described. With the collection of more extensive follow-up information including posttransplantation activity levels, immunosuppression, graft function, and interim hospitalizations, the registry has begun and will continne to focus on morbidity after thoracic transplantation. We Will also begin correlating pretransplantation and posttransplantation variables to morbid events and death. We recognize the efforts of the contributing transplantation centers in submitting high quality data and thank these transplantation programs for their support and cooperation.
