Author + information
- Published online November 27, 2017.
- Maria Rosa Costanzo, MD∗ ()
- ↵∗Address for correspondence:
Dr. Maria Rosa Costanzo, Advocate Heart Institute, 801 South Washington Street, Naperville, Illinois 60566.
As the story goes, the status of heart transplantation (HT) is excellent: the average half-life of HT for recipients surviving 12 months exceeds 13 years; the mortality rate on the HT wait list has declined by 17% since the 2006 change in organ allocation algorithm; and patients who earlier would have died while waiting for a suitable donor organ can now survive to HT with mechanical circulatory support (MCS) (1,2). Because of these tremendous advances, clinicians can be more discerning in the selection of donor hearts. For example, early adolescent (EA) donor hearts should be rejected for adult HT recipients, given concerns that the lack of hormonal activation until puberty may reduce the performance of these donor hearts and lead to poor outcomes (Online Ref. 1).
In this issue of JACC: Heart Failure, Madan et al. (3) disrupt this optimistic narrative with evidence-based data. A search of the United Network for Organ Sharing (UNOS) database identified 1,123 adults who received hearts from donors 10 to 14 years of age (EA). With propensity scoring, 944 recipients of EA donor hearts were matched with 944 recipients of adult donor hearts. Not only did the 2 groups have similar survival from 30 days to 5 years, but also transplant of EA hearts in adult recipients was associated with a trend toward a lower risk of cardiac allograft vasculopathy, the principal limiting factor to long-term survival after HT (1,3). In a landmark study evaluating predictors of heart size and growth during puberty, the ability of body size to predict heart growth and function decreased from childhood to puberty, and discrepancies between body and heart sizes began sooner in boys than in girls (Online Ref. 2). In fact, soon after menarche, girls have stagnation of heart growth, which catches up with that of boys after puberty (Online Ref. 3). These data diminish the importance of pubertal hormonal activation on heart size and function (Online Refs. 2 and 3).
Notably, in the study by Madan et al. (3), the EA hearts were offered to adults only after their rejection for pediatric HT candidates. Of 6,000 EA donor hearts registered in the UNOS database between 1987 and 2015, only 2,919 (48%) were transplanted. Tragically, most of the 3,081 EA hearts not used for HT were rejected for reasons other than organ quality. These figures should fuel very serious reflection because the number of nontransplanted EA donor hearts exceeds the number of adult HTs performed annually in the United States (≈2,400). Had these EA donor hearts been accepted, an additional 154 adult HTs could have been performed each year of the study period (3).
The rejection of young donor hearts is an inexcusable disservice both to adult HT candidates, as demonstrated by Madan et al. (3), and to children with end-stage heart disease who are awaiting HT. Indeed, another analysis from the UNOS database showed that between 2000 and 2015, 201 of 844 pediatric candidates (24%) never underwent HT, and 87 of them (43%) died or became too ill for HT (4). The 256 EA hearts refused for these 87 children were later accepted for adults, who had excellent outcomes. In other words, 1 in 10 pediatric candidates dies on the HT waiting list after refusal of EA donor hearts that are successfully transplanted in adults (5). The obligation to re-evaluate donor refusal criteria adopted by pediatric HT centers is further underscored by the finding that, in weight-matched pediatric HT recipients, donor older age reduces survival. This effect, primarily driven by recipients 11 to 17 years old who underwent HT with a donor older than 25 years of age, emphasizes that allocation of younger donor organs to adolescent recipients should be a priority for the HT community (Online Ref. 4).
Another fact challenging the overly positive story on the status of HT is that in the United States between 1995 and 2010, the donor heart acceptance rate declined from 44% to 32%. This means that, despite the alarming donor shortage, only 1 in 3 available donor hearts is currently accepted for HT (6). In addition, the use of donor hearts is highly variable among UNOS regions, consistently above average in some and below average in others, even after adjusting for donor characteristics (6). These regional differences underscore the crucial need for updated, evidence-based consensus criteria for the selection of donor hearts. For example, although reduced left ventricular ejection fraction (LVEF) in the donor heart has been a consistent predictor of graft nonuse, a propensity score matching analysis of the post-operative course of patients in the UNOS database who underwent HT between 1996 and 2015 showed that recipients of hearts with reduced LVEF (31 ± 6%) have equivalent survival compared with recipients of hearts with normal LVEF (62 ± 7%), most likely because donor hearts with reduced LVEF from brain injury or death experience significant functional recovery after HT (Online Ref. 5).
The “good story” also tells us that patients who would have previously died before the availability of a suitable donor heart can now survive to HT with MCS. It is unquestionable that MCS, used both as bridge to transplantation (BTT) and as destination therapy (DT), can prolong the lives of patients with advanced heart failure (7). However, the results of 2 recently published trials comparing the axial flow HeartMate II with 2 newer pumps (HeartMate III [Thoratec Pleasanton, California] and HeartWare [Framingham, Massachusetts] centrifugal flow devices) should make us pause and critically appraise the use of MCS in nearly one-half of HT candidates (1). Because the ENDURANCE study (A Clinical Trial to Evaluate the HeartWare Ventricular Assist System) included only patients receiving DT, the results of MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3), which included both BTT and DT groups, are more pertinent to the current discussion (Online Refs. 6 and 7). Although compared with the HeartMate II device, the HeartMate III had a higher percentage of patients with survival free of either disabling stroke or reoperation for device malfunction at 6 months (86.2% vs. 76.8%), all other common and potentially debilitating complications associated with MCS occurred with similar frequency with both pumps, including stroke (≈9%), bleeding (≈36%), sepsis (≈8%), driveline infection (≈9%), and right ventricular failure (≈27%) (Online Ref. 7).
Additional sobering data should cause us to reassess the role of MCS as BTT: 1) the average implant length of stay is approximately 18 days; 2) from implantation to 6 months, BTT recipients spend approximately 20% of the time in the hospital, and <10% of these patients undergo HT (Online Ref. 8); 3) competing outcome analyses from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database reveal that only 30% of BTT recipients listed at MCS implantation undergo HT in 1 year, and this percentage drops to 20% for patients listed later (7); and 4) sadly, up to 44% of BTT recipients are removed from the HT waiting list because of complications or clinical preference (Online Ref. 8).
Furthermore, the increased scrutiny of post-HT outcomes by national regulatory bodies, such as the U.S. Center for Medicare and Medicaid Services and the UNOS Membership Professional Standard Committee, that can result in loss of Medicare certification or even closure of HT centers deemed to be underperforming, may have had the unintended consequence of risk aversion in donor heart acceptance, thereby reducing HT rates (6).
These sobering observations are the “few facts” that ruin the “good story” and should spur the HT community to re-evaluate current donor acceptance guidelines critically and redouble their efforts to identify novel and improved methods of donor heart resuscitation and preservation.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Costanzo has reported that she has no relationships relevant to the contents of this paper to disclose.
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