Of the 19 centers that have contributed data to the RETC, 18 are currently active (Table 1). Two centers are entirely dedicated to pediatric transplantation while another 3 perform both pediatric and adult transplantation. The numbers of procedures performed annually are summarized in Figure 1. The whole series comprises 7588 procedures. Data were lost on 12 patients, including follow-up information. These patients have been omitted from the analysis, giving a final sample size of 7576 patients. Of the 299 procedures performed in 2015, 22 (7.4%) were performed in pediatric patients (age<16 years). The types of procedures performed in 2015 and in the whole series are summarized in Table 2.

Figure 1.

Annual number of transplants (1984-2015), total and by age group.

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The database comprises 175 clinical variables, established by consensus among all the teams, and records data on recipients, donors, surgical techniques, immunosuppression, and follow-up. Since 2013, the data have been electronically introduced and updated in real time using a web-based program specifically designed for this purpose. The database support is a Microsoft Excel file. This procedure replaces the previous method, in which each center sent data to the registry director in Microsoft Access file format via email. An external CRO (contract research organization), currently ODDS S.L., performed database maintenance, quality control, and statistical analysis.

Ethics committee approval, auditing, and registration with the Ministry of Health were performed in accordance with the Spanish Organic Law on Data Protection 15/1999.

Continuous quantitative variables are presented as mean ± standard deviation; categorical variables are presented as percentages. The results are categorized according to the year of transplantation and the total sample has been divided into 4 time periods (1984-1993, 1994-2003, 2004-2013, and 2014-2015). Some variables were also analyzed according to the annual data from the whole series, such as donor age, emergency transplants, and ischemia time. Differences among groups were analyzed using a nonparametric test for temporal trends (Kendall τ) for categorical variables and analysis of variance test with polynomial fit for continuous variables. Survival curves were calculated using the Kaplan-Meier test and were compared using a log rank test. A P value <.05 was considered statistically significant.

In 2015, the recipients had a mean age of 49.5±16.5 years (range, 0.14-73 years); 76% were men, with the following underlying diagnoses: ischemic cardiomyopathy (21.4%), nonischemic dilated cardiomyopathy (30.4%), valvular heart disease (4.0%), and other etiologies (44.2%). Recipient characteristics by transplant period are summarized in Table 3. There were significant trends toward older recipients, female sex, atypical causes of underlying heart disease, and an increase in pretransplant conditions with known prognostic effects, such as insulin-dependent diabetes mellitus, infection, cardiac surgery, and mechanical ventilation prior to transplant. Although the difference was not statistically significant, the proportion of retransplants fell below 2% in 2014-2015, comprising 2.4% of the total series. In contrast, there was a significant decrease in pretransplant values of pulmonary vascular resistance and an almost significant decrease in pretransplant severe renal dysfunction throughout the time series.

Compared with 2014, there was a slight uptick in 2015 in emergency transplants, reaching almost half of all procedures. Thus, the use of emergency transplants has remained above 40% since 2013 (Figure 2). In 2015, there was another increase in the use of ventricular assist devices prior to transplantation, whose use was first recorded in 2009 (P<.001) (Figure 3). Moreover, there was increased use of continuous-flow left ventricular assist devices (33.9%) and reduction of almost one-half in the use of balloon pumps vs 2014 (Figure 4).

Figure 2.

Annual percentage of emergency transplants among the total population (1984-2015).

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Figure 3.

Distribution of the type of pretransplant circulatory support by time period (1984-2015). ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device.

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Figure 4.

Distribution of the type of pretransplant circulatory support by year (2009-2015). ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device.

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The characteristics of the donors in 2015 and according to time interval are summarized in Table 4. Donor age has been significantly increasing throughout the series, with 55% of donors considered suboptimal (age >45 years) in 2015 (Figure 5). There has been an increase in female donors and the percentage of female-to-male transplants (26.4%), as well as cardiac arrest prior to donation (21.8% in 2015). In addition, there was an increase in donors who died from stroke, with a consequent decrease in deaths from trauma (Figure 6).

Figure 5.

Annual changes in donor age and percentages of donors older than 45 years (1984-2015). 95%CI, 95% confidence interval.

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Figure 6.

Changes by time period in the causes of death of heart donors.

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Ischemia time has increased throughout the time series. In 2015, as in the previous decade, the ischemia time was greater than 240min in about a quarter of recipients (Table 4 and Figure 7).

Figure 7.

Annual changes in ischemia time and percentage with ischemia time >240min (1984-2015). 95%CI, 95% confidence interval.

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In 2015, 83.4% of recipients received some type of induction immunosuppressive therapy, mainly involving basiliximab (79.1%) (Figure 8), confirming the tendency observed since 2009.

Figure 8.

Drugs used in induction immunosuppression. ALG, antilymphocyte globulin; ATG, antithymocyte globulin.

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The drugs used in the initial immunosuppression and at the end of follow-up for the whole series are summarized in Figure 9. In a mean follow-up of 7.2 years, 63.1% of patients continued to receive corticoid therapy. At last follow-up, 30% of patients were under treatment with mTor inhibitors (everolimus or sirolimus).

Figure 9.

Initial and maintenance immunosuppression for the whole series (1984-2015). Progressive changes by type of drug: at time of transplant and at end of follow-up. MMF, mycophenolate mofetil; MPS, mycophenolate sodium.

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In 2015, initial immunosuppression predominantly consisted of tacrolimus (89.3%) as the calcineurin inhibitor, mycophenolate mofetil or mycophenolic acid (98.3%) as the antiproliferative agent, and steroids (98.3%). The annual changes in the use of the various calcineurin inhibitors and antimitotics are shown in Figure 10 and Figure 11, respectively. The annual changes in the use of the mTor inhibitors (sirolimus, everolimus) in the initial immunosuppression are shown in Figure 12.

Figure 10.

Annual changes in the use of calcineurin inhibitors (cyclosporine and tacrolimus) in initial immunosuppression in the total sample (1984-2015).

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Figure 11.

Annual changes in the use of antimitotics (azathioprine and mycophenolate mofetil/mycophenolic acid) in initial immunosuppression in the total sample (1984-2015). MMA, mycophenolic acid; MMF, mycophenolate mofetil.

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Figure 12.

Annual changes in the use of mTor inhibitors (sirolimus and everolimus) in initial immunosuppression in the total sample (1984-2015). The unlabeled points have a value of 0.

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With the most recent update from December 31, 2015, the 1-, 5-, 10-, 15-, and 20-year actuarial survivals in the entire time series are summarized in Figure 13. The survival curves indicate a mean annual mortality of about 2% to 3% after the first posttransplant year, with a median survival of 11.1 years. The 1-year conditional survival is shown in Figure 14. The conditional median survival after the first posttransplant year was 15.1 years. There were significant differences according to recipient age, donor age, type of procedure (isolated transplant, combined transplant, and retransplant), transplanturgency, and type of circulatory assistance at the time of transplant (without assistance, balloon pump, extracorporeal membrane oxygenation [ECMO], ventricular assist device). The most notable finding was the similar survival between elective transplants and transplants performed with balloon pump or ventricular assist devices. Transplants performed with prior ECMO showed significantly worse survival than those performed with no such device.

Figure 13.

Overall survival curve for the whole series (1984-2015).

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Figure 14.

Survival curve conditioned on survival to the first year in the whole series (1984-2015).

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The survival results have constantly improved throughout the time series (Figure 15). Compared with the 1984 to 1993 decade, there were highly significant differences with the second decade and the period 2014 to 2015. Compared with the first decade, there was improved survival in the first posttransplant year in the following 2 decades. Compared with procedures performed between 1993 and 2013, there was an additional improvement in 1-year survival in 2014 and 2015 (Table 5). The improved survival in the 2004 to 2013 decade vs 1994 to 2014 was observed at a longer term (from the second posttransplant year) (Figure 15). The median survival improvement is continuous: 9.1 years (1984-1993), 10.9 years (1994-2003), and 12.0 years (2004-2013). In addition, the 2014 to 2015 period shows a clear tendency for improved survival vs the previous decade (2004-2013), even if this result is not statistically significant due to the relatively small sample size of the later group.

Figure 15.

Survival curves by transplant period (10-year intervals, 1984-2013 and 2014-2015).

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In the total population, the most frequent cause of death was graft vascular disease/sudden death (18.7%), followed by infections (17.1%), primary graft failure (13.6%), and neoplasia (13.1%) (Figure 16). The causes of death depended on the time after transplant (Figure 16). In the first posttransplant month, almost 50% of deaths were due to primary graft failure. After the first month and until 1 year, acute rejection (15.3%) and, above all, infections (36.6%) were the main causes of death. After the first year, the main causes were various manifestations of graft vascular disease (30.2%) and tumors (22.0%). The main causes of death in the first year have changed significantly over time, with fewer deaths due to acute rejection and more deaths due to primary graft failure, even if the latter decreased in the 2014 to 2015 period (Figure 17). In deaths occurring between the first and fifth posttransplant years, there was a tendency for fewer deaths due to graft vascular disease/sudden death and significantly more deaths due to acute rejection (Figure 18).

Figure 16.

Causes of death by time from transplant and in the whole series (1984-2015). GVD, graft vascular disease; SD, sudden death.

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Figure 17.

Main causes of death in the first posttransplant year in the whole series (1984-2015).

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Figure 18.

Main causes of death occurring between the first year and fifth posttransplant years in the whole series (1984-2015). GVD, graft vascular disease; SD, sudden death.

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