Third Paedi-EUROMACS report: more answers lead to more questions

In recent years, there has been an increasing population of children living with heart failure, in part due to improved recognition of cardiomyopathy in children as well as improved outcomes for patients with congenital heart disease (CHD) [1]. While the gold standard treatment in children is heart transplantation, limitations in paediatric donor pools limit its use. In adults, mechanical circulatory support (MCS) devices have become the standard of practice, with twelve Food and Drug Administration-approved devices. In contrast, fewer options exist for children [1, 2]. Over time the use of paediatric MCS devices has grown, but small numbers have made single-centre studies challenging and limited in scope. To aggregate data, the Paediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) and the Paediatric European Registry for Patients with Mechanical Circulatory Support (Paedi-EUROMACS) were created in 2012 and 2019, respectively [3].

In this issue of the journal, de By et al. [4] have published the third Paedi-EUROMACS report. We applaud the authors’ efforts to combine data from multiple centres across several countries, as these aggregate results give us a comprehensive overview of the state of paediatric durable MCS practice in Europe. In this update, the authors include data from 24 centres in 14 countries and examine 472 implants in 446 patients. Most patients fell between 11 and 19 years of age (41.9%) and were INTERMACS profile 2 (49.5%). The dominant aetiology of heart failure was dilated cardiomyopathy (53.6%). Over half of patients were supported by paracorporeal pulsatile (PP) devices (52.9%) with the Berlin Heart EXCOR being the most commonly used device. The most common intracorporeal (IC) device was the HeartWare HVAD (27.1%). Primary cause of death was cerebrovascular accident (CVA) followed by multi-organ failure.

The presentation of this data in a comprehensive registry form allows us to draw comparisons to the North American registry, Pedimacs. In 2020, Morales et al. [5] published the fourth Pedimacs report in which they studied 1031 device implants in 856 patients performed at 44 centres across North America. When comparing both registries, it may be useful to separate discussion into 3 broad categories—patient populations, device strategies and outcomes.

When looking at patient populations we see subtle differences in these cohorts. In both groups, the majority of patients tended to be older. However, while over 25% of children were younger than 1 year in North America, this younger group represented a smaller part of the European cohort (17% in more recent years). In addition, while dilated cardiomyopathy was the dominant aetiology in both cohorts, CHD was more prevalent in the North American registry (25% vs 15%). Both reports and previous literature demonstrate that younger patients, particularly those with CHD, represent a higher risk cohort, with greater baseline severity of illness and worse outcomes [2]. The fact that more of these patients undergo VAD implantation in North America may represent a more aggressive practice pattern compared to European centres.

In terms of device selection, both reports categorize devices as IC, PP or paracorporeal continuous. While IC devices were the most common device type in North America (43%), PP devices were the dominant device in Europe, though IC devices still represented a large proportion (38.3%). The Pedimacs report describes a general practice pattern of paracorporeal devices being used in children who are younger, weigh <20 kg, more frequently have CHD and are more ill (intubated, feeding tube or TPN dependent) compared to patients who receive IC devices. It can be assumed that a similar distribution is present in the European cohort, as these differences are largely due to patient size limitations for device selection.

With respect to survival, the EUROMACS registry demonstrated that 74% of patients survive to transplant, recovery or remain on MCS at 2 years. Comparing this to the 70% survival at 1 year seen in the Pedimacs registry is difficult given that baseline patient characteristics may not be similar as previously discussed. However, in both groups, risk factors for poor outcome were lower age, presence of CHD and paracorporeal device use. Given that these variables are all closely interrelated, it remains unclear to what degree device type, age or patient selection influences survival independently. Both registries cite adverse neurologic events as a major source of morbidity and mortality in this population. In the EUROMACS registry, about 1 in 4 deaths was attributed to CVA. In the Pedimacs cohort, the incidence of neurologic complications was 23%. However, we do see from the Pedimacs report that the overall incidence of CVA has decreased over time.

Combined, the Paedi-EUROMACS and Pedimacs registries contain over 1300 paediatric patients who underwent durable MCS implantation. This scale of data allows us to understand not only the current state of paediatric MCS practice but also where this field is headed in the coming years. First, the data clearly show that the number of children with heart failure who require durable VAD support continues to grow, stressing the importance of refining device technology and practice patterns. Reassuringly, outcomes have continued to improve over time. Even cohorts traditionally at highest risk, such as infants and CHD patients, have seen improvements in survival and reduction in adverse events. Neurologic events do remain a significant source of morbidity and mortality among this population, pointing towards a need to optimize anticoagulation protocols while on device support.

These data, while very revealing, undoubtedly lend itself to further questions. With the recent withdrawal of the HeartWare HVAD implantable device, which was the primary IC device in both registries, it remains to be seen whether newer implantable devices such as the HeartMate 3 will fill this gap. How will this affect outcomes in smaller patients who traditionally have not been candidates for the HeartMate 3 device? In a field with obvious inter-centre variability in volume and outcomes, how can we use collaborative registries such as the ones described here to standardize and improve practices? And as we continue to follow this cohort of patients into the future, how can we tailor MCS therapy to optimize outcomes after transplantation? As we often find, sometimes looking for more answers leads to more questions. Nevertheless, we will continue to rely on databases such as Paedi-EUROMACS and Pedimacs to help answer these questions and evolve future practices in this growing field.

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