John Nguyen

National decline in donor heart utilization with regional variability: 1995-2010.

The severe shortage of donor hearts limits the availability of transplantation for the growing population of patients with end‐stage heart disease. We examined national trends in donor heart acceptance for transplant. OPTN data were analyzed for all potential adult cardiac organ donors between 1995 and 2010. Donor heart disposition was categorized as transplanted, declined for transplant or other. We studied changes in the probability of donor heart acceptance according to demographic and clinical characteristics, nationwide and by UNOS region. Of 82 053 potential donor hearts, 34% were accepted and 48% were declined (18% used for other purposes). There was a significant decrease in donor heart acceptance from 44% in 1995 to 29% in 2006, and subsequent increase to 32% in 2010. Older donor age, female sex and medical co‐morbidities predicted non‐acceptance. Donor age and co‐morbidities increased during the study period, with a concomitant decrease in acceptance of hearts from donors with undesirable characteristics. Overall, predictors of heart non‐use were similar across UNOS regions, although utilization varied between regions. Regional variation suggests a potential to improve heart acceptance rates in under‐performing regions, and supports research and policy efforts aimed at establishing evidence‐based criteria for donor heart evaluation and acceptance for transplantation.

Donor Predictors of Allograft Use and Recipient Outcomes After Heart Transplantation

Background—Despite a national organ-donor shortage and a growing population of patients with end-stage heart disease, the acceptance rate of donor hearts for transplantation is low. We sought to identify donor predictors of allograft nonuse, and to determine whether these predictors are in fact associated with adverse recipient post-transplant outcomes. Methods and Results—We studied a cohort of 1872 potential organ donors managed by the California Transplant Donor Network from 2001 to 2008. Forty-five percent of available allografts were accepted for heart transplantation. Donor predictors of allograft nonuse included age>50 years, female sex, death attributable to cerebrovascular accident, hypertension, diabetes mellitus, a positive troponin assay, left-ventricular dysfunction and regional wall motion abnormalities, and left-ventricular hypertrophy. For hearts that were transplanted, only donor cause of death was associated with prolonged recipient hospitalization post-transplant, and only donor diabetes mellitus was predictive of increased recipient mortality. Conclusions—Whereas there are many donor predictors of allograft discard in the current era, these characteristics seem to have little effect on recipient outcomes when the hearts are transplanted. Our results suggest that more liberal use of cardiac allografts with relative contraindications may be warranted.

Donor Predictors of Allograft Use and Recipient Outcomes After Heart TransplantationClinical Perspective

Background—Despite a national organ-donor shortage and a growing population of patients with end-stage heart disease, the acceptance rate of donor hearts for transplantation is low. We sought to identify donor predictors of allograft nonuse, and to determine whether these predictors are in fact associated with adverse recipient post-transplant outcomes. Methods and Results—We studied a cohort of 1872 potential organ donors managed by the California Transplant Donor Network from 2001 to 2008. Forty-five percent of available allografts were accepted for heart transplantation. Donor predictors of allograft nonuse included age>50 years, female sex, death attributable to cerebrovascular accident, hypertension, diabetes mellitus, a positive troponin assay, left-ventricular dysfunction and regional wall motion abnormalities, and left-ventricular hypertrophy. For hearts that were transplanted, only donor cause of death was associated with prolonged recipient hospitalization post-transplant, and only donor diabetes mellitus was predictive of increased recipient mortality. Conclusions—Whereas there are many donor predictors of allograft discard in the current era, these characteristics seem to have little effect on recipient outcomes when the hearts are transplanted. Our results suggest that more liberal use of cardiac allografts with relative contraindications may be warranted.

Electrocardiographic Characteristics of Potential Organ Donors and Associations With Cardiac Allograft Use

Background—Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results—A single experienced reviewer interpreted the first ECG obtained after brain stem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002 to 2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft use for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy, prolongation of the corrected QT interval, and repolarization changes (ST/T wave abnormalities). Fifty-seven percent of potential cardiac allografts in this cohort were accepted for transplantation. Left ventricular hypertrophy on ECG was a strong predictor of allograft nonuse. No significant associations were seen among corrected QT interval prolongation, repolarization changes, and allograft use for transplantation after adjusting for donor clinical variables and echocardiographic findings. Conclusions—We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brain stem herniation and are not associated with allograft use for transplantation.

Assessment of Heart Transplant Waitlist Time and Pre- and Post-transplant Failure: A Mixed Methods Approach

Background: Over the past two decades, there have been increasingly long waiting times for heart transplantation. We studied the relationship between heart transplant waiting time and transplant failure (removal from the waitlist, pretransplant death, or death or graft failure within 1 year) to determine the risk that conservative donor heart acceptance practices confer in terms of increasing the risk of failure among patients awaiting transplantation. Methods: We studied a cohort of 28,283 adults registered on the United Network for Organ Sharing heart transplant waiting list between 2000 and 2010. We used Kaplan–Meier methods with inverse probability censoring weights to examine the risk of transplant failure accumulated over time spent on the waiting list (pretransplant). In addition, we used transplant candidate blood type as an instrumental variable to assess the risk of transplant failure associated with increased wait time. Results: Our results show that those who wait longer for a transplant have greater odds of transplant failure. While on the waitlist, the greatest risk of failure is during the first 60 days. Doubling the amount of time on the waiting list was associated with a 10% (1.01, 1.20) increase in the odds of failure within 1 year after transplantation. Conclusions: Our findings suggest a relationship between time spent on the waiting list and transplant failure, thereby supporting research aimed at defining adequate donor heart quality and acceptance standards for heart transplantation.

Beta-Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors

Prior studies have demonstrated associations between beta‐adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction—an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001–2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52–4.57) and 2.70 (1.07–2.74) respectively for requiring >10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007–2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

Donor Predictors of Allograft Utilization and Recipient Outcomes after Heart Transplantation

Background—Despite a national organ-donor shortage and a growing population of patients with end-stage heart disease, the acceptance rate of donor hearts for transplantation is low. We sought to identify donor predictors of allograft nonuse, and to determine whether these predictors are in fact associated with adverse recipient post-transplant outcomes. Methods and Results—We studied a cohort of 1872 potential organ donors managed by the California Transplant Donor Network from 2001 to 2008. Forty-five percent of available allografts were accepted for heart transplantation. Donor predictors of allograft nonuse included age>50 years, female sex, death attributable to cerebrovascular accident, hypertension, diabetes mellitus, a positive troponin assay, left-ventricular dysfunction and regional wall motion abnormalities, and left-ventricular hypertrophy. For hearts that were transplanted, only donor cause of death was associated with prolonged recipient hospitalization post-transplant, and only donor diabetes mellitus was predictive of increased recipient mortality. Conclusions—Whereas there are many donor predictors of allograft discard in the current era, these characteristics seem to have little effect on recipient outcomes when the hearts are transplanted. Our results suggest that more liberal use of cardiac allografts with relative contraindications may be warranted.

RELIABILITY OF ECHOCARDIOGRAPHIC MEASUREMENTS OF LEFT VENTRICULAR SYSTOLIC FUNCTION IN POTENTIAL PEDIATRIC HEART TRANSPLANT DONORS

BACKGROUND Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory. METHODS We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed. RESULTS There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review. CONCLUSIONS Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.