Extracorporeal life support (ECLS) through short-term ventricular assist devices (VADs) has enabled immediate mechanical circulatory support (MCS) for patients in cardiogenic shock, aiming to achieve rapid resuscitation and stabilization. When weaning from ECLS is not feasible and patients meet eligibility criteria, the sole survival options are durable MCS via long-term ventricular assist devices (LVADs) or cardiac transplantation.

In Spain, we are fortunate to have the world’s leading organ donation system, as demonstrated by the annual Spanish heart transplant records. Consequently, our use of durable ventricular assist devices (DVADs) is ten times lower than in the United States, as highlighted when analyzing the Spanish REGALAD registry. This results in the majority of critically ill patients on short-term support, for whom weaning is not possible, being referred for heart transplantation instead of DVAD implantation. Data from the ASIS-TC Registry, a multicenter Spanish database on the use of short-term mechanical circulatory support as a bridge to urgent heart transplantation, showed that from 2010 to 2020, 84.5% of urgent patients reached transplantation with an average support duration of six days under urgency level 0. This organizational advantage in transplantation, almost exclusive to Spain, would be unthinkable in most industrialized countries due to limited donor organ availability. For this reason, in much of Europe and the United States, durable MCS with DVAD remains the primary life-saving option for most ECLS patients.

The long-term ECLS registry is a multicenter study (13 European centers) that includes patients who transitioned from ECLS to a DVAD-based MCS system. Initiated in 2018, this registry encompasses patients with various DVAD types since 2010. Over the study period, several pump types were implanted, primarily Heartware™ in the initial phase and HeartMate 3™ (HM3) more recently. Abbott’s HM3™ is a new-generation, magnetically levitated centrifugal pump clinically introduced in Europe during the CE-mark trial in 2015. Interim results published at one and two years with HM3 demonstrated survival rates above 80%. However, the published trial data mainly included a less critically ill patient population compared to that of this registry. Therefore, the primary objective of this multicenter study was to evaluate the outcomes of patients who received HM3™ support after ECLS within the real-world context of a European multicenter registry involving different DVAD types, including HM3™.

To this end, patient data for those undergoing HM3™ implantation from January 2016 to April 2022 at 14 centers were collected and evaluated. The inclusion criteria encompassed patients with any type of ECLS, primarily veno-arterial extracorporeal membrane oxygenation (VA-ECMO), with or without intra-aortic balloon pump or Impella™ (Abiomed™), prior to HM3™ implantation. The obtained outcomes were reported and compared with those of patients receiving other types of DVAD.

A total of 337 patients were candidates for some form of DVAD following ECLS. Of these, 140 received HM3™ support. The other pump types included 170 Heartware™ (Medtronic™) (86%), 14 HeartMate II™ (7%), and 13 (7%) other pumps. Major postoperative complications included right heart failure, which required temporary right ventricular assist devices (RVAD) in 60 patients (47%). Postoperative stroke and pump thrombosis rates were significantly lower in HM3™ recipients compared to those receiving other DVADs, with stroke rates at 16% versus 28% (p = 0.01) and pump thrombosis at 3% versus 8% (p = 0.02). Thirty-day, one-year, and three-year survival rates for HM3™ recipients were 87%, 73%, and 65%, respectively, compared to survival rates of 81% at 30 days, 56% at one year, and 48% at three years among other DVAD recipients.

The authors conclude that, within this patient population supported by short-term VADs, the survival outcomes for patients transitioned to HM3™ are acceptable and superior to those observed with other DVADs.

COMMENTARY:

As medical technology advances, so do patient outcomes. This is evident in the study by Saeed et al., which demonstrates significantly improved outcomes in survival, stroke rates, and pump thrombosis with newer DVADs, specifically HeartMate 3™ (HM3), compared to its predecessor, Heartware™. The Heartware™ device was withdrawn from the market in 2021 due to safety concerns, primarily related to device failures.

The same research group previously published the largest series using the ECLS registry from 2010 to 2018, which included 531 patients. They reported a one-year survival rate of 53% in this specific patient cohort, which is lower than the survival rate observed in traditional DVAD candidates without ECLS. This survival rate aligns with that found in the current study (56%) when comparing the non-HM3™ group, mainly patients with Heartware™ DVADs. However, survival in patients with HM3™ was significantly better, reaching 73%, thereby demonstrating the superiority of this new device.

On the other hand, these excellent results with HM3™ allow us to compare them with those of heart transplantation in Spain under similar clinical conditions. According to the ASIS-TC multicenter registry, as previously discussed, the one-year survival rate among ECLS-supported patients prior to transplantation from 2010 to 2020 was consistently above 70%, varying depending on the support device used: 79.4% with intra-aortic balloon pump, 84.9% in patients with percutaneous devices, 79.9% in those with continuous flow surgical devices, 74.4% in patients supported with continuous flow BIVADs/RVADs, and 67.8% in ECMO patients. Therefore, we could suggest that the one-year survival rate of transplanted patients in this clinical context is comparable to that of patients with HM3™.

Without listing the well-known limitations of these studies, two aspects are worth noting: one related to the timing of DVAD implantation and the other concerning the high incidence of temporary right ventricular support use observed:

The average duration of VA-ECMO support before DVAD implantation was only five days, similar to previous reports from the same registry. Likewise, in Spain, according to the ASIS-TC registry, the median support time before heart transplantation is also short, at six days under urgency level 0. Thus, in this study, the wait time before DVAD implantation for ECLS patients was as brief as the wait time for transplants in Spain. This is significant because studies have shown that prolonged VA-ECMO duration is a negative predictor of survival, which this study could not demonstrate due to the limited support time.

Additionally, no algorithm was used in this study to suggest the ideal wait time before DVAD implantation based on etiology. Given that 55% of patients were ischemic, and these patients may sometimes recover or regain cardiac function, it is possible that a proportion of them could have recovered enough function to avoid durable MCS.

One of the major limitations of this study was the lack of a clear definition of right ventricular failure (RVF), as it did not adhere to the criteria established by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). This may explain why limited information is available on the use and dosage of inotropes. Likewise, there was no standardized protocol for RVAD use.

That said, the use of temporary right ventricular support in the HM3™ group was 47%, compared to 39% with other DVADs, reflecting a high incidence similar to that previously reported by the same group (42%). This frequent use of right ventricular support may be partially attributed to recent advancements in devices that facilitate its use. The Protek Duo™ dual-lumen cannula (LivaNova™), available since 2016, allows for a percutaneous right ventricular assist device (RVAD) implantation via the jugular vein in a simple and effective manner, avoiding direct cannulation of the pulmonary artery as previously required. Therefore, the high incidence of temporary RVAD use may result from a lower threshold for indication due to its prophylactic use and ease of implantation rather than strict criteria for right ventricular dysfunction. Moreover, the Protek Duo™ cannula allows for DVAD implantation while the right ventricular support is active, which stabilizes the patient during the procedure and facilitates RVAD weaning shortly after durable device implantation.

Studies like the one by Saeed et al. are a great advancement for science. At last, we can say that we have technology capable of achieving short- and mid-term outcomes comparable to heart transplantation in ECLS-supported patients, something that was previously unattainable.

In Spain, due to its unique infrastructure, most patients are quickly referred for transplantation without the need for DVAD. However, in dramatic cases where prolonged wait times are anticipated, an HM3™ bridge may be considered with supporting evidence.

Thanks to technological and scientific advances in this field, the near future—whether through transplantation (perhaps someday with xenograft options) or through the continued development of advanced devices like HM3—offers new hope where uncertainty once reigned.

REFERENCE:

Saeed D, Stark C, Otto W, Loforte A, Zimpfer D, et al. Outcome of patients supported with the HeartMate 3 after extracorporeal life support: On behalf of the Durable Mechanical Circulatory Support After Extracorporeal Life Support Study Group. J Thorac Cardiovasc Surg. 2024 Aug;168(2):569-578.e2. doi: 10.1016/j.jtcvs.2023.08.048.