Of the 19 centers that have contributed data to the RETC, 18 are now currently active (Table 1). Two centers are exclusively devoted to pediatric transplant procedures, whereas 4 others carry out transplants in both pediatric patients and adults. The number of procedures performed per year is shown in Figure 1. The total activity recorded in the Registry comprises 7869 procedures. Data were missing for 12 procedures, including follow-up information. These were omitted from the analysis, which left a final sample of 7857 transplant surgeries. Of 281 procedures carried out in 2016, 20 (7.1%) were performed in pediatric patients (age < 16 years). The types of procedures performed in 2016 and in the total recorded series are summarized in Table 2.

Figure 1.

Yearly number of transplant procedures performed (1984-2016), in the total series and by age groups.

(0.18MB).

The database includes 175 clinical variables established by consensus among all the transplant teams. The variables include data on the recipient, donor, surgical technique, immunosuppression used, and the follow-up. Since 2013, the data have been electronically recorded and updated in real time using a web-based program specifically designed for this purpose. The data are provided in a Microsoft Excel file. This system replaces the previous one, in which each center sent data to the Registry director by e-mail in a Microsoft Access file. An external contract research organization (CRO), currently ODDS S.L., carries out database maintenance, quality assurance, and the statistical analyses.

Ethics committee approval, auditing, and registration with the Spanish Ministry of Health were done in keeping with the requirements set down in the Organic Law on Data Protection 15/1999.

Continuous quantitative variables are expressed as the mean ± standard deviation and categorical variables as percentages. The results were categorized according to the year of transplant, with the overall sample being divided into 4 time periods (1984-1993, 1994-2003, 2004-2013, and 2014-2015). Certain variables were also analyzed according to the yearly data from the series, such as donor age, urgent transplant, and ischemia time. Differences between groups were analyzed using a nonparametric test for temporal trends (Kendall tau) for categorical variables and analysis of variance (ANOVA) with polynomial fitting for continuous variables. Survival curves were calculated with the Kaplan-Meier method and were compared using a log rank test. A P value < .05 was considered statistically significant in the comparisons.

In 2016, the mean age of the recipients was 49.5±17.5 (range, 0.18-72) years. Males accounted for 74.7%, and the main baseline diagnoses were ischemic cardiomyopathy (35.2%), nonischemic dilated cardiomyopathy (29.2%), valvular cardiomyopathy (3.9%), and other diagnoses (31.7%). The characteristics of the recipients by transplant period are summarized in Table 3. The age and sex of recipients has remained stable over the last 2 decades. Significant trends were seen toward an increase in unusual underlying heart disease and in pretransplant conditions having a recognized prognostic effect, such as insulin-dependent diabetes mellitus and infection, as well as cardiac surgery and mechanical ventilation prior to transplant. Although the differences did not reach statistical significance, the percentage of retransplants fell below 2% from 2014 to 2016, and accounted for 2.4% of the total series. In contrast, there was a significant decrease in pretransplant pulmonary vascular resistance values and a decrease approaching significance in severe pretransplant renal impairment over time in the total sample.

In 2016, urgent transplant accounted for more than 50% of the procedures. This maintains a trend observed since 2013, with urgent transplants being performed in more than 40% of patients (Figure 2). The increasing use of pretransplant ventricular assist devices detected since 2009 was also confirmed in 2016 (P < .001) (Figure 3). Furthermore, 2016 showed a predominance of continuous-flow ventricular assist devices (44.9%) and a reduction in the use of pretransplant balloon pumps (Figure 4).

Figure 2.

Percentage of urgent transplant procedures performed by year in the total series (1984-2016).

(0.18MB).

Figure 3.

Type of pretransplant circulatory support used by time period. ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device.

(0.13MB).

Figure 4.

Type of pretransplant circulatory support used by year (2009-2016). ECMO, extracorporeal membrane oxygenation; VAD, ventricular assist device.

(0.15MB).

The characteristics of the donors by time period and in 2016 are summarized in Table 4. Donor age has significantly increased throughout the total recorded series, and in 2016, 57% of donors were in the age range considered suboptimal (> 45 years) (Figure 5). The percentage of transplant surgeries performed with grafts from female donors to male recipients was somewhat lower in 2016 (24.1%) than in 2015 (26.4%). Furthermore, there was an increase in donors who died due to stroke and a decrease in those who died due to trauma (Figure 6).

Figure 5.

Yearly changes in donor age and percentage of donors older than 45 years (1984-2016). 95%CI, 95% confidence interval.

(0.19MB).

Figure 6.

Causes of death in heart donors, by time period.

(0.11MB).

The ischemia time has risen throughout the total recorded series. As in the previous decade, more than one-quarter of the patients underwent transplant with an ischemia time greater than 240minutes in 2016 (Table 4 and Figure 7).

Figure 7.

Yearly changes in ischemia time and percentage of procedures with ischemia time > 240minutes (1984-2016). 95%CI; 95% confidence interval.

(0.19MB).

In 2016, 82.4% of recipients received some type of induction immunosuppressive therapy, mainly basiliximab (78.4%) (Figure 8), confirming a trend described in previous reports and observed since 2009.

Figure 8.

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

(0.15MB).

A summary of the immunosuppressive drugs used initially and at completion of follow-up in the total recorded series is provided in Figure 9. At a mean follow-up of 7.3 years, 63.7% of patients continued receiving corticosteroid therapy, and at the last follow-up, 30% of patients were under treatment with mTOR inhibitors (everolimus or sirolimus).

Figure 9.

Initial and maintenance immunosuppression in the total series (1984-2015). Changes according to the type of drug at the start of transplant and at completion of follow-up. MMF, mycophenolate mofetil; MPS, mycophenolate sodium.

(0.11MB).

In 2016, the initial immunosuppressive regimen mainly consisted of tacrolimus (91.1%) as a calcineurin inhibitor, mycophenolate mofetil or mycophenolic acid (97.0%) as an antiproliferative agent, and steroids (98.9%). Yearly changes in the use of calcineurin inhibitors and antimitotic agents for initial immunosuppression are shown in Figure 10 and Figure 11, respectively, whereas changes in the use of mTOR inhibitors (sirolimus, everolimus) are shown in Figure 12.

Figure 10.

Yearly changes in the use of calcineurin inhibitors (cyclosporine and tacrolimus) for initial immunosuppression in the total sample (1984-2016).

(0.16MB).

Figure 11.

Yearly changes in the use of antimitotic drugs (azathioprine and mycophenolate mofetil/mycophenolic acid) for initial immunosuppression in the total series (1984-2016). MMF, mycophenolate mofetil, MPA, mycophenolic acid.

(0.19MB).

Figure 12.

Yearly changes in the use of mTor inhibitors (sirolimus and everolimus) for initial immunosuppression in the total series (1984-2016). Unlabeled points have a value of 0.

(0.15MB).

With the latest update on 31 December 2016, actuarial survival in the total recorded series at 1, 5, 10, 15, and 20 years is depicted in Figure 13. The findings indicate a mean yearly mortality rate of around 2% to 3% after the first year after transplant, with a median survival of 11.2 years. The 1-year conditional survival curve is shown in Figure 14. The conditional median survival after the first posttransplant year was 15.1 years. As shown in Table 5, there were significant differences in recipient age, donor age, type of procedure (single transplant, combined transplant, and retransplant), the urgency code for transplant, and the type of circulatory support at the time of transplant (no support, balloon pump, extracorporeal membrane oxygenation [ECMO], ventricular assist device), similar to the findings from the previous year. Of particular note, survival rates were comparable in patients undergoing elective transplant and those undergoing transplant with balloon pumps or ventricular assist devices. Survival was significantly lower in transplant procedures performed in patients with previous ECMO than in those with no devices.

Figure 13.

Survival curve for the total series (1984-2016).

(0.09MB).

Figure 14.

One-year conditional survival curve in the total series (1984-2016).

(0.08MB).

Survival rates have shown a steady increase throughout the total recorded series (Figure 15). Significant differences were found for the decade from 1984 to 1993 relative to later decades and for the period from 2014 to 2016. Compared with the first decade, the superior survival in later years was mainly attributable to increased survival in the first year after transplant. Nonetheless, starting from the decade from 2004 to 2013, survival rates after the second posttransplant year also showed an improvement. In the most recent period (2014-2016), a trend to greater early and longer-term survival was detected, although statistical significance was not reached because of the relatively small available sample size.

Figure 15.

Survival curves in the total series by transplant period (10-year intervals from 1984 to 2013, and the 2014-2016 period).

(0.11MB).

In the total series, the most common cause of death was graft vascular disease/cardiac arrest (20.3%), followed by infection (17.0%), neoplasm (13.5%), and primary graft failure (13.3%) (Figure 16). The causes of death varied according to the time considered following transplant (Figure 16). In the first posttransplant month, nearly half the deaths were due to primary graft failure. From the first month to the end of the first year, the main causes of death were acute rejection (15.1%) and particularly infections (36.8%). After the first year, the main causes were the various manifestations of graft vascular disease (29.9%) and tumors (22.5%). The main causes of death at 1 year have changed significantly over time, with a drop in cardiac arrests due to acute rejection and a rise in deaths caused by primary graft failure, although this latter event showed a decrease in the period from 2014 to 2016 (Figure 17). Analysis of mortality occurring between the first and fifth year following transplantshowed a significant decrease in deaths caused by graft vascular disease/cardiac arrest and a significant increase in deaths due to acute rejection (Figure 18).

Figure 16.

Main causes of death in the total series and by time since transplant (1984-2016). CA, cardiac arrest; GVD, graft vascular disease; RF, renal failure.

(0.22MB).

Figure 17.

Main causes of death occurring in the first year after transplant in the total series (1984-2016).

(0.11MB).

Figure 18.

Main causes of death occurring between the first and fifth years after transplant in the total series (1984-2013). CA, cardiac arrest; GVD, graft vascular disease.

(0.11MB).