Author + information
- Jon A. Kobashigawa, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Jon A. Kobashigawa, Cedars-Sinai Heart Institute, 127 South San Vicente Boulevard, Los Angeles, California 90048.
In this issue of JACC: Heart Failure, Hsich et al. (1) review the Scientific Registry of Transplant Recipients (SRTR) database between 2000 and 2010 and find a greater waitlist mortality for women than for men for status 1A patients. They conclude that the United Network for Organ Sharing (UNOS) donor heart allocation system favors men over women for status 1A patients with an unclear explanation for the difference.
The authors performed a detailed analysis of the SRTR database, including more than 30 risk factors that might be involved in waitlist mortality. They found that female gender is an independent risk factor for mortality for critically ill status 1A patients. The authors implicated the UNOS donor heart allocation policy as a possible cause favoring men over women for status 1A patients. Over the course of the past 2 decades, UNOS donor heart allocation policy revisions have occurred in 1999 and 2006. This most recent policy change, in 2006, allocated donor hearts to the sickest patients (status 1A and 1B), first locally then to zone A (500-mile radius from the donor hospital) and then to zone B (1,000-mile radius), and has demonstrated a reduction in waitlist mortality (2). However, it is clear that there still exists donor heart allocation disparity in certain subgroups such as patients with restrictive cardiomyopathy, sensitized patients, and patients with intractable angina or ventricular arrhythmias. Whether women should now be placed among these disadvantaged groups is not clear.
The authors searched for a cause for increased female waitlist mortality by assessing several risk factors. However, they failed to include the important risk factor of sensitization. It has been established that multiparous women are more prone to become sensitized (3), which results in increased time on the waitlist due to a reduced number of compatible donors (4). For status 1A patients, extra time on the waitlist may result in increased mortality. In addition to sensitization, women in this database appeared to be sicker. The authors noted that compared to status 1A men, status 1A women had various high-risk characteristics that may disadvantage them on the waitlist and lead to more severe illness and risk for mortality. Compared to men, women were reported to have more pre-transplant diagnoses of congenital heart disease and hypertrophic and restrictive cardiomyopathy while having fewer implantable cardioverter defibrillators placed. In addition, women were more likely than men to be on a ventilator and require inotrope or extracorporeal membrane oxygenation support and less likely to receive placement of a total artificial heart (TAH), a left ventricular assist device (LVAD), or an intra-aortic balloon pump (IABP). Finally, women were more likely than men to have a history of malignancy. All these factors put together, including sensitization, suggests that women were sicker than men in the status 1A group and/or had higher risk for mortality while waiting. Indeed, the authors found that women were significantly more likely than men to have characteristics of a UNOS status 1A patient (22.2% vs. 20.9%, respectively; p < 0.001).
If status 1A women are sicker than status 1A men and may have more difficulty finding a compatible donor due to sensitization, then the approach should center on addressing these problems. Should we be more aware of listing women sooner and be more aggressive in the placement of defibrillators or mechanical circulatory support devices (MCSD)? It seems clear that the increase in MCSD placement is having an impact on the management of patients on the heart transplant waitlist. The emergence of MCSDs in addition to advances in heart failure medical therapy have had the most impact in lowering waitlist mortality (2). For reasons possibly related to women's smaller sizes, there appear to be fewer LVADs and TAHs being placed in women than in men.
In the general population, there is contention as to whether gender plays a role in heart failure morbidity and mortality. A U.S.-based retrospective analysis of >100,000 patients (5) found a greater proportion of women were hospitalized with acute decompensated heart failure than men (52% vs. 48%, respectively). One explanation is that women are generally treated less aggressively with heart failure therapy (24% vs. 31% in terms of vasoactive therapy, respectively). Continuing the theme that women are treated less aggressively, a recent review found most of the evidence suggests that guideline-recommended drugs are given less often to female patients (6). Contrary to these studies, a retrospective analysis of >50,000 patients shows no differences by gender in terms of in-hospital mortality for acute decompensated heart failure (7). A European meta-analysis of more than 40,000 patients found survival for women with heart failure was better than for men, regardless of left ventricular function (8). The studies above may not necessarily represent female patients with advanced heart disease who are awaiting heart transplantation. Nonetheless, more aggressive heart failure therapy may be needed to reduce mortality in our status 1A female patients to realize parity with status 1A male patients.
In addition to possibly less aggressive heart failure therapy, status 1A women may have characteristics that place them in the previously mentioned disadvantaged subgroups. In this SRTR dataset, women also appeared to have more pre-transplant restrictive cardiomyopathy, in which case they might have become sicker to warrant eventual status 1A listing. These patients may not have systolic dysfunction and, in general, do not benefit from inotropic therapy or from the left ventricular assist devices, which are currently criteria for status 1A listing. These patients usually have severe biventricular diastolic heart failure and would require a TAH for support if needed. Unfortunately, the current TAH is suitable only for larger patients, thus excluding smaller patients, many of whom are women. A smaller total artificial heart will soon become available and provide smaller patients (e.g., women) with more durable biventricular support. Those patients who are highly sensitized are another disadvantaged subgroup. They have been noted to have a longer waitlist time due to a smaller donor pool, as many potential donors are not compatible. In Canada, highly sensitized patients have been given priority in one of their highest categories (9).
Currently, changes in the UNOS donor heart allocation policy are being formulated. To address these disadvantaged groups, more tiers will likely be added to the existing allocation system. A heart allocation score is desirable, but it will take much time (years) to validate the variables involved in such a score. Paramount with lowering status 1A waitlist mortality in women is the need to prevent the apparent sicker course of these patients at the time of heart transplant listing and to address prioritization of disadvantaged subgroups (which include many women) in future donor heart allocation policy.
↵∗ 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. Kobashigawa has reported that he has no relationships relevant to the contents of this paper to disclose.
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