The Registry of the International Society for Heart and Lung Transplantation: Thirty-first Adult Lung and Heart–Lung Transplant Report—2014; Focus Theme: Retransplantation

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Data collection and statistical methods

Data are submitted to the ISHLT Registry by national and multinational organ/data exchange organizations, or by participating individual centers. Since the Registry’s inception, 416 heart transplant centers, 241 lung transplant centers and 168 heart–lung transplant centers have reported data. In our estimation, the data submissions to the Registry represent approximately two thirds of worldwide thoracic transplant activity.

This report used standard statistical methodology for analyses and

Centers and transplant activity

The Registry now contains data from 47,647 adult lung transplants performed through June 2013. Of these, 45,697 (95.9%) patients underwent primary lung transplantation and 1,950 underwent lung retransplantation. Data were submitted from 136 participating transplant centers for a total of 3,719 adult lung transplant procedures performed in 2012. For the Registry history, 2012 had the second highest reported annual activity, following the highest activity level in 2011 (Figure 1). The number of

Survival

Adults who underwent primary lung transplantation in the era January 1990 through June 2012 (n = 41,767) had a median survival of 5.7 years (Figure 7), with unadjusted survival rates of 88% at 3 months, 80% at 1 year, 65% at 3 years, 53% at 5 years and 32% at 10 years. The recipients who survived to 1 year post-transplant had a conditional median survival of 7.9 years.

Lung transplant recipient groups stratified by transplant type (single/unilateral vs double/bilateral) had markedly different

Causes of death

The major reported causes of mortality (January 1992 through June 2013) within the first 30 days after transplantation consisted of graft failure and non-CMV infections (Table 3). Other significant contributors to early post-transplant death included technical (i.e., related to the transplant procedure) and cardiovascular causes. During the remainder of the first post-transplant year, non-CMV infection became the most prominent cause of death. After the first post-transplant year, BO/chronic

Risk factors for mortality

For 16,785 adult lung transplants performed between January 2000 and June 2012, we conducted multivariable analyses to identify factors that had an independent association with risk of death during the first year post-transplant. After adjustment, the categorical risk factors significantly associated with mortality included type of underlying lung disease of the recipient, retransplantation, earlier era of transplant, increased severity of recipient illness at the time of transplantation (i.e.,

Retransplantation

As just described, lung retransplantation showed an independent association with risk of death in the non-conditional 1- and 5-year survival models. An analysis of risk factors for mortality within the first year after retransplantation for 731 adults transplanted between January 1995 through June 2012 found independent predictors of mortality, including earlier era of transplant, low transplant center volume, donor history of hypertension, shorter donor height, recipient severity of illness

Acute and chronic lung rejection

Based on follow-ups between July 2004 and June 2013, 3,307 of 11,443 (28.9%) adult primary lung transplant surviving recipients with known rejection status had at least 1 episode of treated acute rejection between discharge and 1-year follow-up (see website). BOS, conditional on surviving to 2 weeks after transplant (to avoid biases introduced by early mortality), remained a common long-term complication. For follow-ups performed between April 1994 and June 2013 (Figure 21), Kaplan–Meier

Complications and morbidities

Morbidities commonly caused or exacerbated by immunosuppressive medications (e.g., hypertension, renal dysfunction, diabetes, hyperlipidemia) occurred frequently after primary lung transplantation (Table 4), and the complication rates increased significantly over time (see website). Based on Kaplan–Meier estimates, lung transplant recipients had a high incidence of severe renal dysfunction. Within 5 years after transplantation, 24% of recipients had creatinine >2.5 mg/dl, dialysis or renal

Risk factors for retransplantation

An analysis of risk factors for retransplantation within 5 years of the primary lung transplantation (January 1995 through June 2008) for 13,778 adults found independent predictors that included single lung transplant, later transplant era, female gender, younger recipient age, older donor age, and greater recipient height (Figure 22). Registry analyses cannot fully explain the discrepant findings of later transplant era being an independent risk factor for retransplantation within 5 years of

Centers and transplant activity

The Registry now contains data from 3,755 adult heart–lung transplants (including retransplantation) prior to 2013. After a rapid rise in the 1980s and a peak at the end of that decade (226 heart–lung transplants in 1989), an overall decline in reported heart–lung transplantation occurred throughout the 1990s and into the first few years of the following decade (Figure 23). However, the number of reported adult heart–lung transplant procedures plateaued during the most recent decade and ranged

Indications and other recipient characteristics

For 3,767 heart–lung transplants that occurred between January 1982 through June 2013, approximately two thirds had an indication of congenital heart disease or IPAH (Table 5 and Figure 26). For decades, the proportion of adult transplants for diagnoses of congenital heart disease and IPAH remained largely unchanged, whereas the proportion for CF decreased and the proportion for acquired heart disease increased. Significant geographic differences in major indications existed (Figure 27) for

Survival

For 3,605 primary heart–lung transplants performed between January 1982 and June 2012, recipients had survival rates of 72% at 3 months, 63% at 1 year, 52% at 3 years, 45% at 5 years and 32% at 10 years (Figure 28). In comparison to lung-only transplantation (Figure 7), heart–lung transplantation had a more pronounced early mortality and better long-term survival. Recipients surviving the first year had a median survival of 10.3 years.

Survival for primary heart–lung transplants showed

Risk factors for mortality

Risk factors for 1-year mortality in adult heart–lung transplant recipients only consisted of advanced donor age and indications/diagnoses other than IPAH (Table 6). Transplant center volume showed borderline statistical significance, where lower volume had a trend toward a higher risk of mortality. The number of heart–lung retransplant recipients and recipient deaths was too small to allow for meaningful analyses of risk factors for mortality.

Causes of death

For heart–lung transplant recipients, based on reported deaths between January 1992 and June 2013, the most common identifiable causes of death in the first 30 days post-transplant were graft failure (lung or heart), technical complications and non-CMV infections (Table 7). After the first year, BOS/late graft failure (lung or heart) and non-CMV infections became the most common causes of mortality. Cardiovascular causes of death accounted for a smaller but important proportion of the deaths.

Heart–lung rejection

In primary heart–lung transplant recipients, BOS occurred more commonly than coronary artery vasculopathy (CAV) at all annual time-points, based on follow-up data from April 1994 to June 2013 (Figure 30). At 1, 3, 5 and 10 years after heart–lung transplantation, 9%, 28%, 42% and 57% of recipients developed BOS as compared with 3%, 7%, 10% and 30%, respectively, who developed CAV.

Complications and morbidities

Morbidities often associated with immunosuppressive therapy commonly occurred at both the 1- and 5-year time-points after heart–lung transplantation, and their rates increased over time (Table 8). Of all malignancies, lymphoma occurred most commonly, especially in the first year post-transplant.

Summary

During the past decade, the annual number of lung transplants has continued to increase, while the number heart–lung transplantation rates has plateaued. Survival for both transplant types has improved over time, mainly due to improved survival in the early post-transplant period. Morbidity rates after lung and heart–lung transplantation were high, and the main contributors to decreased long-term survival consisted of BOS of the lung and infections. Lung retransplant procedures increased

Disclosure statement

All relevant disclosures for the Registry Director, Executive Committee Members and authors are on file with the ISHLT and can be made available for review by contacting the Executive Director of the ISHLT.

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