Survival rates are significantly higher with the ventricular assist device (VAD) than with extracorporeal membrane oxygenation (ECMO), but serious adverse events, including infection, stroke and bleeding, occurred in a majority of study participants in both arms, according to the results of the prospective Berlin Heart Study, published Aug. 8 in the New England Journal of Medicine.

Heart failure (HF) is much less common among children than among adults, but it is highly lethal, with 46 percent of children with HF dying or undergoing transplantation within five years after diagnosis, according to one estimate (JAMA 2006;296:1867-1876). The survival rate among children after heart transplantation is estimated at 83 percent at three years (Circulation 2010;122:A13740-A13740), but the limited availability of donor hearts for children prolongs the waiting period, resulting in a high rate of death among children on waiting lists, according to the study authors.

The Excor Pediatric ventricular assist device (Berlin Heart) is a paracorporeal, pneumatically driven, pulsatile-flow mechanical circulatory-support device. The Berlin Heart Study Investigators conducted this study to evaluate the device as bridge therapy in children who were on waiting lists for orthotopic heart transplantation.

Charles D. Fraser, Jr., MD, surgeon-in-chief, chief of the department of congenital heart surgery and cardiac surgeon in-charge at Texas Children's Hospital, chief of the congenital heart surgery division at Baylor College of Medicine, both located in Houston, and colleagues conducted a trial of a VAD designed specifically for children as a bridge to heart transplantation.

The researchers divided patients 16 years of age or younger into two cohorts according to body-surface area (cohort 1, <0.7 m²; cohort 2, 0.7 to <1.5 m²), with 24 patients in each group between May 2007 and December 2010. In cohort 1, the median age was one year and the median weight was 9 kg. In cohort 2, the median age was nine years and the median weight was 31 kg. They compared survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing ECMO.

For participants in cohort 1, Fraser et al reported that the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days. For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively. Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42 percent and 50 percent of patients, respectively), infection (in 63 percent and 50 percent) and stroke (in 29 percent and 29 percent).

“Progress in developing pediatric devices has been much slower because of the proportionately greater variation in size among children,” the authors acknowledged. “Other reasons for the slow progress include biologic differences in the response to anticoagulant medicines, low levels of interest in the medical industry, and in particular, the size constraints in very small babies.”

In this study, Fraser and his colleagues found that the rate of survival to device explantation (owing to either transplantation or recovery) was “markedly higher” with the ventricular assist device than with ECMO. “The outcome comparison was particularly stringent because a successful outcome in the ventricular-assist group included an acceptable neurologic outcome, which could not be systematically analyzed in the ECMO group,” they wrote.

As with the use of a VAD for circulatory support in adults, serious adverse events, including bleeding, infection and stroke, occurred in a majority of the study participants, the study authors wrote. Although the occurrence of stroke is “troubling,” they said that the stroke rate in this cohort is similar to that reported during the use of ventricular assist devices in children who had a body-surface area greater than 1.2 m² and who were treated with adult-sized ventricular assist devices.

The prevalence of stroke in this trial did not preclude eligibility for transplantation in the majority of participants, and the stroke-related deficits were generally mild, according to study group investigators.

This study was supported by Berlin Heart and by a grant from the FDA’s Office of Orphan Product Development.