Heart transplantation is the treatment of choice for advanced heart failure in the pediatric population. The universal shortage of organs has driven the use of ventricular assist devices (VADs) as a bridge to transplantation. Over the last decade, the use of VADs has increased to the extent that they are employed in up to half of transplanted patients. Currently, the Berlin Heart EXCOR® (BHE) is one of the few paracorporeal VADs specifically approved for the pediatric population. Its use is indicated in INTERMACS 1 and 2 patients and allows for transplantation rates of up to 70%. However, a significant proportion of children experience cardiac function recovery after receiving this therapy. 

Successful explantation implies cardiac function recovery, avoiding the use of immunosuppressive medications and the uncertainties surrounding graft durability. The benefits extend beyond the individual patient, positively impacting the collective of patients awaiting a heart by reducing demand, increasing organ availability, and shortening waiting times. So, which patients might be expected to recover? 

Today’s article is a systematic review that aims to answer this question. A systematic search was conducted in five databases: PubMed, Medline, OVID, Web of Science, Cochrane Central, and CINAHL Complete, for articles about successful BHE VAD explantation in pediatric patients. Articles mixing pediatric and adult patient outcomes, studies with fewer than 10 patients, and those with no successful BHE explants were excluded. Successful explantation was defined as withdrawal of VAD support without mortality or severe neurological complications. The primary objective was to identify the characteristics of patients who achieved successful explantation, with a secondary aim to analyze the different published weaning protocols. 

Out of 42,000 potential studies, 14 were analyzed, including data from 58 hospitals across four continents during the 1990–2020 period. A total of 984 patients with BHE were analyzed. The most common primary diagnosis was dilated cardiomyopathy (33% of patients), followed by congenital heart disease (25%). Successful explantation of BHE was achieved in 85 children (8.6%). The primary diagnosis was identified in half of these cases (n=44): 14 of 166 cardiomyopathies (8.4%), 17 of 35 myocarditis cases (48.6%), and 12 of 72 congenital heart disease cases (16.7%). Most patients with successful explantation had left VADs, while successful explantation in biventricular VAD patients was exceedingly rare. 

The authors concluded that successful explantation of a BHE is not an uncommon milestone, occurring in up to 8% of cases with this type of VAD. Patients diagnosed with myocarditis and those with left VADs are more likely to achieve successful explantation. The authors emphasize the need to standardize BHE-related publications and initiate prospective registries to better identify such patients and unify weaning protocols. 

COMMENTARY: 

There is a myriad of publications on the BHE, but this is the first article focused on identifying patients in whom this therapy served as a bridge to recovery. Typically, a BHE is implanted as a bridge to transplantation, but this review shows that cardiac recovery in this patient profile can occur in up to 8% of cases—a surprisingly high figure to consider it anecdotal. In fact, according to the authors, nearly half of myocarditis cases and 17% of congenital heart disease cases might achieve successful explantation. Unsurprisingly, patients with left VADs had higher weaning rates compared to biventricular ones, given the severity of cardiac dysfunction. Curiously, more successful BHE explantations have been reported in Europe and Asia compared to the United States and Australia. Another notable observation is that the U.S. transplants more congenital heart disease patients, while Europe transplants more dilated cardiomyopathy cases. 

Unfortunately, very little has been published on weaning protocols, and among the studies that do mention them, few define the clinical parameters they use. Some cases involve cardiac catheterization with the device turned off to obtain baseline hemodynamic measurements, followed by a volume test to assess tolerance. Others, after observing clinical, echocardiographic, and laboratory recovery, perform weaning trials in the operating room. Some studies mention stress echocardiograms, while others refer to specific explant protocols without providing a citation for reference. In short, each institution has its own approach to BHE weaning and explantation, making it difficult for readers to benefit from this information. 

We must not overlook the limitations of such studies. They rely on single-center studies, show significant heterogeneity in diagnoses, and differ in how data is presented. Duplicate publications from the same hospital were excluded, potentially leading to the loss of relevant information. Additionally, this study’s selection criteria—including only studies with more than 10 pediatric patients and at least one successful BHE explant—may overestimate explantation rates. There is also no follow-up data on these patients, so we do not know if those with successful explantation eventually required a transplant or continued living with their recovered heart. 

In conclusion, despite the important limitations of this study, we cannot ignore the possibility of cardiac recovery after BHE implantation. We still don’t know exactly who the possible candidates could be. To do this, we would have to strive to collaborate on a common prospective multicenter registry of all BBB patients. In the end, with pathologies so rare, unity is strength. 

REFERENCE: 

Mikulski MF, Iyer S, Well A, Mery CM, Owens WR, Glass LD, el al. Successful explantation of children from the Berlin Heart EXCOR® ventricular assist device: A systematic review. Artif Organs. 2024 May;48(5):444-455. doi: 10.1111/aor.14727.