REGALAD is an observational and multicenter study that retrospectively includes all dVAD procedures performed in Spain from 2007 to the date of registry activity initiation (November 30, 2018) and prospectively thereafter.

For the technical management of the registry, an external company was contracted by the registry management. The procedures used in the data collection, handling, and reporting are in line with the regulations established in the Spanish Data Protection Law, including informed consent. The protocol was approved by the ethics committees of the participating centers.

All Spanish hospitals performing dVAD implantation participated in this registry. In each center, a local physician and a surgeon undertook to introduce all dVAD procedures into the online database at least annually. They included both new cases and an update of the status and main complications of previous cases. All registry participants are listed in appendix 1 of the supplementary data.

REGALAD is restricted to the study of what are considered to be long-term devices. These devices are understood to be those that eventually allow patient autonomy and discharge.

Depending on the type of flow provided by the pump, the devices used comprised a paracorporeal pulsatile-flow dVAD model with the possibility of isolated left ventricular or biventricular support—EXCOR (Berlin Heart GmbH, Germany)—and various intracorporeal continuous-flow dVAD models for isolated left ventricular support: INCOR (Berlin Heart GmbH), HeartMate II (Abbott, United States), and Jarvik 2000 (Jarvik Heart Inc, United States), which provide axial flow, and HeartWare HVAD (Medtronic, United States) and HeartMate 3 (Abbott), the latest-generation pumps that provide centrifugal continuous flow. There was also a total artificial heart device that generates pulsatile flow in both circuits (systemic and pulmonary): SynCardia TAH-t (SynCardia Systems LLC, United States).

The patients analyzed in this work were all adults with advanced HF who underwent dVAD implantation in Spain between 2007 and 2020.

REGALAD includes most variables from the IMACS (International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support) and EUROMACS (European Registry for Patients with Mechanical Circulatory Support) registries, as well as additional variables considered pertinent by the registry founders. These variables include patients’ demographic, clinical, laboratory, echocardiographic, and hemodynamic characteristics, implantation data, and 3-month, 1-year, and annual follow-up data. Adverse events associated with the device were specifically recorded. A definition of all adverse events can be found in appendix 2 of the supplementary data.

HF severity at implantation was graded using the scale proposed by INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)5 (appendix 3 of the supplementary data).

Normally and nonnormally distributed numerical variables are expressed as mean ± standard deviation or median [interquartile range], respectively. Categorical variables are expressed as absolute and relative frequencies. Overall survival was estimated using the Kaplan-Meier method. Patients were followed up until death or study closure on December 31, 2020. For this survival analysis, patients were censored at transplantion or dVAD explantation. Patients’ clinical course was also examined using Fine-Gray competing risk analysis, which tracks multiple mutually exclusive outcomes (alive with device, death, transplantation, or explantation). At any time, the sum of the proportion (percentage) of patients in each outcome category was equal to 100%. To compare the clinical course in terms of implant characteristics and outcomes, the study time was divided into 3 periods (2007-2010, 2011-2015, and 2016-2020). All tests were 2-sided, and a P value less than .05 was considered statistically significant. The analyses were performed using IBM SPSS Statistics version 24.0 and R version 4.1.2 software. Survival and competing risk analyses were performed using the “survival” and “cmprsk” R libraries.

The 22 Spanish hospitals performing dVAD implantation between 2007 and 2020 participated in the registry; 15 had a HTx program. The number of devices per hospital was highly variable: in particular, 4 hospitals performed more than 20 implants per center, comprising more than half of all activity. The numbers of participating hospitals and of dVADs implanted in each center are shown in table 1.

Between 2007 and 2020, 263 dVADs were implanted in Spain. The device was a continuous-flow left ventricular device in 182 patients (69%), a pulsatile-flow device in 79 (30%) (58 left, 21 biventricular), and a total artificial heart in 2 (1%) (figure 1). The different dVAD models used are shown in table 2 by period.

Figure 1.

Central figure. Ventricular support in order of year of implantation and by type of device (2007-2020).

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Patients’ baseline characteristics are summarized in table 3.

The initial objective of the dVAD was BTT in 78 patients (30%), with a median time on the waiting list of 61 [21-228] days before device implantation. In 110 patients (42%), the dVAD was implanted as a bridge to candidacy; in these patients, the main contraindications to HTx were pulmonary hypertension (61 patients, 55%) and recent history of cancer (11 patients, 10%). In the 72 patients (27%) whose dVAD was implanted as destination therapy, the most commonly reported contraindications were advanced age (47 patients, 65%) and renal failure (22 patients, 31%). The device was implanted as bridge to recovery in only 3 patients (1%). The changes over time in the initial objective by implantation period are shown in figure 2.

Figure 2.

Initial objective of ventricular support by implantation period. HTx, heart transplantation.

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All patients met the criteria for advanced HF and most had an INTERMACS risk profile of 3 (44%) or 4 (27%) at implantation. The changes over time in the risk profile by implantation period are shown in figure 3.

Figure 3.

INTERMACS profile by device implantation period.

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In 250 patients (95%), the surgery was performed using cardiopulmonary bypass. The surgical approach was median sternotomy in 93% of the patients, minimally invasive surgery in 5%, and left thoracotomy in 2%. The surgery was associated with another cardiac surgery in 44 patients (17%); the most frequent was aortic valve surgery (figure 4).

Figure 4.

Additional surgery during ventricular assist device implantation. ASD, atrial septal defect; PFO, patent foramen ovale.

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Of the 263 patients treated, 190 (72%) were discharged after a median of 36 [20-64] days, 44 (17%) died, and 27 (10%) underwent a HTx during admission after 77 [33-121] days. In 23 of the 27 transplanted patients (85%), the devices were pulsatile pumps with events or other conditions that required that the patient be hospitalized until the HTx. Two patients (1%) developed dVAD-related complications that necessitated pump explantation.

Overall patient survival after a mean follow-up of 358 days (median, 173 [83-430] days) was 89%, 82%, 79%, 74%, and 69% at 1, 3, 6, 12, and 24 months (figure 5).

Figure 5.

Survival curve of implanted patients.

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Figure 6 shows survival by type of device and by the initial implant objective. The best survival was achieved with continuous-flow left ventricular devices (92%, 87%, 84%, 80%, and 75% at 1, 3, 6, 12, and 24 months) vs pulsatile-flow left ventricular devices (82%, 74%, 62%, and 31% at 1, 3, 6, and 12 months) and biventricular/total artificial heart devices (91%, 71%, and 56% at 1, 3, and 6 months).

Figure 6.

Survival curve by type of device and by implant objective. TAH, total artificial heart.

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During follow-up, 611 major ventricular assist device-related complications were recorded (2.3 events/patient) (table 4).

The most commonly reported complication was major bleeding. In the first postimplantation week, the most frequent bleeding events were related to the surgery itself; subsequently, they comprised gastrointestinal bleeding.

The second most common complication was major infection. Of the infections, 47% had no direct relationship with the device and most were respiratory or urinary. In addition, 43% were specific device infections, particularly infections of the percutaneous drive cable connecting the intracorporeal pump with the external controller or of the percutaneous cannulae in the case of paracorporeal pumps. The remaining 10% of infections were related to the device but were not specific to it (mediastinitis, bacteremias, and bacterial endocarditis).

Other less frequent, but more severe, complications were neurological, which were fatal in 26 patients (34% of cases): 12 patients died of ischemic stroke after a median of 15 [5-66] days and 12 patients died of hemorrhagic stroke after 162 [33-236] days. In another 10 patients (13%), the neurological complications had severe sequelae.

The most commonly detected dVAD dysfunction was pump thrombosis, which was seen on 26 occasions and affected 5% of patients with continuous-flow devices and 11% of those with pulsatile-flow devices. In most cases, the thrombosis was resolved by intensification of the antithrombotic therapy or by changing the paracorporeal ventricles. However, in 3 patients with severe thromboses and/or repeated thromboses, the pump was eventually explanted and the patients were connected to temporary circulatory support as a bridge to urgent HTx. Moreover, 21% of all device dysfunctions led to the patients being put on the urgent HTx waiting list.

After device implantation, 49 patients (19%) had some degree of right HF. In most patients, the HF was controlled with medical therapy, but 6 required temporary right circulatory support and 2 of these patients died of this condition.

Comparison of complication rates by type of dVAD (continuous left vs pulsatile left vs biventricular/artificial heart) revealed that, except for right HF, which was obviously prevented with biventricular devices, the other events were less frequent in the first group of patients (table 5).

On December 31, 2020, of the 263 patients included in the registry, 101 (38%) had received a HTx after a median of 159 [105-321] days, 90 (34%) were still alive with support after 173 [83-430] days, and 68 (26%) had died after 51 [18-178] days; in addition, the device had been explanted in 4 patients (2%) (3 due to pump dysfunction and 1 due to patient recovery from the heart disease).

Notably, of the subgroup of 110 patients initially implanted with a device as bridge to candidacy, 58 (53%) ultimately underwent transplant, 23 (21%) died, and 29 (26%) were still alive with a device at the end of follow-up; 15 (14%) of these were on the HTx waiting list.

Figure 7 shows the clinical course of patients during the first 2 postimplantation years. Figure 1 of the supplementary data shows the clinical course of patients by type of device implanted.

Figure 7.

Patients’ clinical course determined using competing risk analysis at 2 years. (The cumulative incidence of the events observed at any time always sums to 100%).

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The leading cause of death was a neurological complication (38% of deaths). The remaining causes of death are summarized in table 6.

The main limitations of this registry, in comparison with other international registries, are the small number of patients included and the relatively short follow-up. However, the registry is exhaustive, with the inclusion of all consecutive procedures performed since implantation of these devices began in Spain.