The ASIS-TC (Empleo de los dispositivos de asistencia circulatoria de corta duración como puente a trasplante cardiaco urgente en España) study was a retrospective, multicenter, registry that included all patients aged 18 years or older who were listed from 1 January 2010 to 31 December 2015 for first, single-organ, urgent HT within the Spanish national network for organ sharing—known as the Organización Nacional de Trasplantes—while being supported with short-term mechanical devices—IABP, extracorporeal membrane oxygenation or temporary ventricular assist devices (VAD). All 16 adult HT centers in the country participated in the registry.

The study protocol was approved by the Committee for Ethics in Clinical Investigation of the Autonomous Community of Galicia, and was ratified by the institutional review boards of participating hospitals.

During the study period, the highest waiting list priority level for HT within the Spanish organ donor allocation system—known as urgency status 0—was reserved exclusively for patients listed under extracorporeal membrane oxygenators or temporary VADs, or for patients with malfunctioning durable VADs. Status 0 conferred nationwide priority for receiving the first suitable organ donor available in the system. A recent study has reported the clinical outcomes of status 0 candidates.6

Candidates listed for HT under IABP support were included in a lower level of priority—known as urgency status 1—, which itself conferred advantage over medically managed candidates listed in the status 2 level—ie, the elective or nonurgent level— to receive a suitable cardiac donor, provided that no status 0 candidate could benefit from it. Before June 2014, priority of status 1 candidates over status 2 candidates applied to any organ retrieved within the whole nation, but beyond this date only to organs retrieved within the referral area of the transplant center where the candidate was hospitalized.

In this study, we report the clinical outcomes of patients listed for HT on IABP therapy as their unique MCS device, and therefore classified as urgency status 1. In the case of patients who were listed for HT as status 1 more than once during the study period, only the most recent episode of listing was included. The decision to implant an IABP and, subsequently, to include the patient on the waiting list for HT as urgency status 1 was adopted by each transplant team according to local protocols and clinical experience, but was not based on a prespecified protocol defined for the study.

Baseline clinical characteristics, outcomes and complications of IABP support, waiting times and post-transplant outcomes were analyzed. Specific definitions of study outcomes are presented in the supplementary material.

Continuous variables are presented as mean±standard deviation and categorical variables are presented as proportions. The Student t test and chi-squared test were used for statistical comparisons among groups, as required. The Clopper-Pearson exact method was used to estimate 95% confidence intervals (95%CI) of incidence rates of study outcomes. One-way analysis of variance with a lineal polynomial contrast was used to analyze the trend of waiting list times for HT over the study period.

Post-listing and post-transplant survival curves were depicted by means of the Kaplan-Meier method, and compared by means of the log-rank test. Multivariable Coxs regression was used to estimate the hazard ratio for 1-year mortality after urgent listing in patients with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles 1-2 vs 3-4, as adjusted by age, sex, and the etiology of heart failure—ischemic or nonischemic. Statistical significance was set as a P value <.05 for all comparisons. Statistical analyses were performed with SPSS 20 and Epidat 4.1.

From January 2010 to December 2015, 281 patients were listed for HT under IABP support, and therefore had a priority level of urgency status 1, in 16 Spanish hospitals. A total of 138 (49.1%) of these candidates had been already included in the waiting list for HT before IABP implantation, and had been upgraded to urgency status 1 after insertion of the device. Three patients were listed for status 1 HT under IABP support on more than 1 occasion during the study period.

An IABP was inserted through the femoral artery in all patients except 2 (0.7%), in which a brachial access was selected. The calibre of the device was 7-Fr in 89 (32%) patients, 8-Fr in 159 (57%) patients, and 9-Fr in 23 (8%) patients; this information was not reported in 10 patients. Mean time elapsed from IABP implantation to status 1 listing was 1.7±3.6 days.

Table 1 shows the most relevant baseline clinical characteristics of study patients, as considered at the time of status 1 listing.

Mean duration of IABP support was 10.9±9.7 days (range, 0-58 days). During this period, programmed—ie, not due to complications—device replacement was performed once in 5 patients and twice in 2 patients. A flow chart of study patients and outcomes of IABP support is presented in Figure 1.

Figure 1.

Flowchart of patients and outcomes of IABP support. IABP, intra-aortic balloon pump; MCS, mechanical circulatory support.

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Overall, 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI, 4.4-10.8) patients died during IABP support. Mean waiting time for HT was 9.6±10 days, increasing steadily over the study period, from 5.9±6.3 days in 2010 to 15±11.7 days in 2015 (Figure 2, P for lineal trend=.001).

Figure 2.

Trends of mean waiting list time for status 1 heart transplant and mean duration of IABP support over the study period. IABP, Intra-aortic balloon pump.

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Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full-support mechanical devices before an organ donor became available. Devices implanted were venoarterial extracorporeal membrane oxygenators (n=14), Levitronix Centrimag (n=13), Impella Recover (n=4), Abiomed BVS 5000 (n=3), and BerlinHeart Excor (n=1). Among these individuals, 11 patients died during MCS and 23 were subsequently transplanted as status 0 candidates—8 died during the early postoperative period after HT. One patient who underwent BerlinHeart Excor implantation was discharged from hospital on this device and was successfully transplanted 3 months later.

Intra-aortic balloon pump support was withdrawn before an organ donor became available in 32 (11.4%, 95%CI, 7.9-15.7) patients, who were subsequently managed medically. The reasons for cessation of IABP support were complications in 19 patients, clinical improvement in 10 patients, and futility in 3 patients. During their in-hospital stay after the cessation of IABP support, 18 patients underwent HT—all survived surgery—and 7 patients died without having been transplanted.

Overall, 235 (83.6%, 95%CI, 78.9-87.8) patients underwent HT during the in-hospital follow-up period after status 1 listing. Thirty-nine (13.9%, 95%CI, 10.1-18.5) patients died during hospital admission without having been transplanted.

Figure 3 represents the occurrence of the competing events HT during IABP support, death during IABP support, transition to full-support mechanical devices, or IABP removal (and transition to medical management) in the study population over a 28-day follow-up period after status 1 listing.

Figure 3.

Depiction of the competing outcomes analysis for death, weaning from IABP support, transition to full-support mechanical devices or transplantation during a 28-day follow-up period after status 1 listing. At any given time point, the sum of the proportion of patients experiencing each outcome equals 100%. IABP, intra-aortic balloon pump; MCS, mechanical circulatory support.

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The incidence rate of adverse clinical events during IABP support was 38.7 (95%CI, 32.1-46.3) episodes per 1000 patient-days; the incidence rate of major adverse clinical events–major bleeding, stroke, infection or IABP dysfunction–was 26.0 (95%CI, 20.6-32.4) episodes per 1000 patient-days. Table 2 shows the incidence rate of all individual adverse clinical events reported in the study.

Intra-aortic balloon pump explantation due to device-related complications was performed in 22 (7.8%) patients before an organ became available; in 3 of these individuals, a new IABP was reinserted. Causes for IABP explantation were ischemia/arterial thromboembolism (n=11), device dysfunction (n=5), infection (n=4), and refractory pain (n=2). The incidence rate of IABP explantation due to device-related complications was 7.2 (95%CI, 4.5-10.8) cases per 1000 patient-days.

Among 194 patients who underwent urgent HT while on IABP support, 36 (18.6%, 95%CI, 13.3-24.7) died within the in-hospital postoperative period. Table 3 shows the incidence rates of other relevant in-hospital postoperative outcomes after HT. Mean cold ischemic time of these procedures was 213±52min. Mean age of the donors was 42±12.6 years. Donors aged ≥ 45 years and donors with ischemic time ≥ 240minutes were used in 93 (47.9%) and 66 (34%) recipients, respectively.

Causes of in-hospital postoperative death after HT were early graft failure (n=17), infection (n=7), surgical bleeding (n=5), rejection (n=3), sudden death (n=1), and nonspecified multiorgan failure (n=3).

By means of the Kaplan-Meier method, estimated 30-day, 1-year, and 5-year survival rates after HT were 88.1% (95%CI, 85.7-90.5), 76% (95%CI, 72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively (Figure 4).

Figure 4.

Long-term postoperative survival of 194 patients who underwent heart transplant under intra-aortic balloon pump support.

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Overall 1-year survival after status 1 listing, considering both on-support and either post-transplant (if transplanted) or postsupport (if not transplanted) periods, was 66.7% (95%CI, 63.9-69.5). Adjusted hazard ratio for 1-year all-cause mortality after status 1 listing in patients with INTERMACS profiles 1-2 vs 3-4, as adjusted by age, sex and the etiology of heart failure was 2.17 (95%CI, 1.32-3.58, P=.005, Figure 5A). INTERMACS 1-2 candidates showed higher rates of transition to full-support devices (16.9% vs 4.1%; P=.002) and lower rates of transplantation (65% vs 78.6%; P=.019) during IABP support than INTERMACS 3-4 candidates.

Figure 5.

A: survival over the first year after status 1 listing according to INTERMACS status. B: survival over the first year after status 1 listing according to the endpoint of intra-aortic balloon pump support. IABP, intra-aortic balloon pump; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support.

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One-year survival after status 1 listing varied significantly according to the clinical endpoint of IABP support (Figure 5B, P=.001). Patients who transitioned from IABP to full-support mechanical devices showed the worst outcomes, with an estimated 1-year survival after status 1 listing of 42.9% (95%CI, 34.5-51.3). Estimated 1-year survival after status 1 listing was 78.1% (95%CI, 70.8-85.4) in patients in whom IABP support was stopped and who were subsequently managed medically; this was comparable to survival of candidates transplanted directly on IABP support. Specific 1-year post-transplant survival curves in these 3 subgroups of patients are presented in the Figure of the supplementary material.

This study has a few limitations. First, as an observational study, it is exposed to potential information, selection, observation and confusion biases. Second, the nature of this investigation is essentially descriptive, rather than analytic; the lack of a parallel control group of matched medically managed HT candidates prevented us from drawing consistent conclusions about an independent effect of IABP on pre- or post-transplant survival. Third, the study population was heterogeneous, as patients from 16 different institutions with variable center-specific protocols and clinical experience were included. Fourth, all patients were treated in the setting of the Spanish national organ sharing network, which is historically characterized by extremely short waiting times for urgent HT indications; consequently, the external validity of our observations is questionable, and our results might not be directly extrapolated to other countries. Finally, it must be recognized that the study focused on a recent—but, to some extent, also past—period of the evolution of the field; in view of the recent changes in clinical criteria required for urgent HT listing in Spain, it is presumable that the use of IABP as a direct bridge to HT will become less frequent in future years.