Discussion
In this analysis, we found FtoM donation to be associated with the
lowest rate of 30-day and one-year survival in comparison of all
sex-match pairs, and female donation (both FtoF and FtoM) to be
associated with increased risk adjusted hazards for one-year mortality.
There was incremental risk of mortality with incremental degree of donor
heart undersizing using all three donor-to-recipient sizing metrics
within the FtoM cohort. However, based on prior sizing thresholds, only
pHM was found to have significant impacts on mortality. With large
degrees of undersizing, pHM was found to have the strongest associations
with mortality. Additionally, we found that approximately half of FtoM
recipients receive a donor heart with a donor-recipient pHM ratio that
is < 0.85.
Existing analyses investigating the impacts of donor undersizing based
on weight (donor-recipient weight ratio < 0.8) have had mixed
conclusions7,8,14. Jayarajan and colleagues did not
find associations with use of weight-undersized donors and survival in
either sex-matched or MtoF recipients. However, in FtoM recipients,
undersizing using weight metrics was associated with decreased median
posttransplant survival (435 days, P=0.0241) and risk adjusted hazards
for mortality (HR 1.201, P=0.0383)14. Bergenfeldt and
colleagues found weight undersizing to be associated with increased
mortality, but these findings did not apply to obese
recipients2. Other studies have identified undersizing
based on weight to be associated with increased mortality in UNOS status
1 patients7 and patients with increased pulmonary
vascular resistance15. Other groups have suggested
undersizing based on weight metrics to be associated with early graft
failure16,17. In our analysis, we did not find
donor-recipient weight ratio < 0.8 to be significantly
associated with survival in the FtoM transplant cohort.
Other groups have advocated the use of pHM as a better means of
donor-recipient heart sizing3,6. Kransdorf et
al studied the use of pHM in the general OHT
population6. In their analysis, undersizing based on
pHM (donor-recipient ratio < 0.86) was associated with
increased hazards for one-year mortality (HR 1.34, 95% CI 1.13 to 1.59,
P<0.001). In this analysis, undersizing based on weight, BMI
height, or body surface area metrics were not found to have significant
impacts on posttransplant survival in the general OHT population. They
concluded that a minimum donor-recipient pHM ratio of 0.86 was required
to sustain optimal cardiac output18. When analyzing
the FtoM cohort, we found increased risk adjusted mortality risk in
those who were undersized using pHM metrics, all while no associations
were found using either weight or BMI.
Prior report has suggested increased mortality following sex-mismatched
transplants, but only when the recipient is male10.
This decreased survival in the FtoM cohort was observed at one year, but
longer-term impacts are not as well understood. A possible explanation
for increased mortality in this cohort may be that there is a higher
propensity for female donors to be undersized in relation to their male
recipients. Previous study has suggested that an undersized donor heart
may be able to increase left ventricular mass over time to adapt to
increases in systemic demand19. If true, the impacts
of donor undersizing may be greatest within the first year following
transplantation.
The relationship between sex-pairing and donor sizing has proven rather
complex. When evaluating female donors for male recipients, our study
found this sex-paired combination to have the lowest rates of
undersizing when using weight or BMI metrics. Furthermore, Bergenfeldt
and colleagues have found no associations with FtoM donation and
inappropriate weight matched donors (donor-recipient weight ratio
<0.7)2. It is possible that this propensity
for undersizing and possibility for decreased survival to be known by
transplanting surgeons, and that precaution is taken to not
“undersize” a female donor to a male recipient when using BMI or
weight-based metrics. However, when analyzing this population with the
pHM metric, nearly half of the FtoM recipients were undersized
(donor-recipient pHM ratio < 0.85). Reed and colleagues found
that pHM discrepancies of > 10-15% to be associated with
increased mortality3. Such findings may account for
decreased survival in the FtoM OHT population. It is possible that
differences in distributions of body fat between males and females may
result in differential relationships between body weight/BMI and heart
size. Therefore, weight or BMI-based sizing in sex-mismatched pairs may
ultimately be inaccurate. It is possible that pHM sizing may result in
more appropriate sizing calculations when evaluating sex-mismatched
donor pairs.