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.