Recipients Of Donor Hearts Research Articles

A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved with the SherpaPak System.

Traditional ice storage has been the historic standard for preserving donor's hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) (p = 0.03). When propensity matched, SCTS had improving 1-year survival (p = 0.10), significantly lower rates of severe PGD (p = 0.011), and lower overall post-transplant MCS utilization (p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization (p = 0.01), reduced incidence of severe PGD (p = 0.005), and improved 30-day survival (p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD (p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

The 2-year postoperative left heart function in marginal donor heart recipients assessing by speckle tracking echocardiography.

This study analyzed the differences and explored the donor/recipient factors between marginal and standard donor heart recipients after heart transplantation (HT) by speckle tracking echocardiography (STE). Seventy-two HT patients were enrolled: 25 standard and 47 marginal donor heart recipients. Thirty HT patients completed 2-year continuous follow-up (1, 6, 12, 24months). Thirty healthy volunteers were controls. STE was used to track the strain characteristics of the left ventricle and atrium for detecting early changes in marginal donor heart recipients, including left ventricular global longitudinal, circumferential and radial strain (LVGLS, LVGCS, LVGRS) and left atrial strain in systole (LAS-S) and late diastole (LAS-A). The perioperative parameters were similar between the standard and marginal groups. No significant differences were found in left heart size, systolic and diastolic function parameters. Left ventricular systolic strain (LVGLS, LVGCS, LVGRS) and systolic and late diastolic left atrial strain (LAS-S, LAS-A) were lower in the HT recipients than the control group (P < 0.05), but there was no difference between the marginal and standard groups (P > 0.05). LVGLS, LVGCS, and LAS-S were low in the marginal group 1month after surgery but recovered gradually at 6months. The patients with donor/recipient body weight ratio < 0.8 group had lower LVGLS and LAS-S. STE showed no significant difference between marginal and standard donor recipients. The LVGLS and LAS-S were lower in those with a smaller donor/recipient body weight ratio. The cardiac function of HT patients was lower in the early postoperative period but gradually recovered over time.

Renal replacement therapy in heart transplant recipients

Kidney injury in cardiac transplant recipients is one of the most severe complications affecting both short- and long-term transplant outcomes. The need for renal replacement therapy (RRT) is determined not only and not so much by the degree of renal dysfunction, as by the need for correction of fluid balance and metabolic disorders. These circumstances are associated with the specificity of extracorporeal renal replacement therapy in donor heart recipients. In this review, we discuss the problems of early versus delayed initiation of RRT, anticoagulation and vascular access, advantages and disadvantages of continuous and intermittent techniques. Special attention is paid to chronic kidney injury and peculiarities of kidney transplantation in heart recipients.

Donor Derived Cell Free DNA in Recipients of Hepatitis C Viremic Donors as a Possible Marker of a Pro-Inflammatory State Causing Graft Injury

Since the highly effective Direct-Acting Antiviral (DAA) therapies have been available for treatment of HCV, transplant centers have begun using organs from HCV infected donors followed by treatment with DAAs. Epidemiological studies have shown that HCV may be associated with an increase atherosclerosis and it has been hypothesized that this is caused by activation of an immunological or inflammatory response. HCV infection of endothelial cells may promote endothelial dysfunction and early atherogenesis. The question arises, could acute HCV that is treated expeditiously, cause an inflammatory response leading to rejection or CAV in the heart transplant population. We plan to compare all recipients at our institution enrolled in the Surveillance HeartCare Outcomes Registry (S.H.O.R.E.) for increased donor derived cell free DNA (dd-cf DNA). They will be placed in 3 population categories: 1) Recipients of Non HCV donors, 2)Recipients of NAT positive donors and 3) Recipients of Antibody positive, NAT negative donors. After solid organ transplantation, donor-derived cell-free DNA circulates in the recipient's blood, and accounts for only a small fraction of total cfDNA (recipient plus donor-derived). During graft injury high amounts of donor-derived cell-free DNA (dd-cfDNA) are shed into the blood stream. HeartCare assesses heart health by measuring both immune activity and dd-cfDNA. The recommended threshold for Cell injury is greater than 0.2 % dd-cf DNA. We will compare populations by episodes of rejection, type of rejection and CAV at one year. At our institution there are currently 6 recipients of donor hearts that were HCV NAT positive and 3 recipients of HCV antibody positive but NAT negative. Participants will receive HeartCare at routinely scheduled intervals of every other month starting at month 4 for the first year and then quarterly out to 5 years post-transplant. We will compare populations by episodes of rejection, type of rejection and CAV at one year.

Left ventricular dysfunction in potential heart donors and its influence on recipient outcomes

ObjectivesNew onset of left ventricular (LV) dysfunction in organ donors is frequent and considered as a contraindication for utilization of the heart. However, such dysfunction might be caused by sympathetic stress and could be transient (Takotsubo syndrome). In this study, we assessed the incidence, pattern, and predictors of LV dysfunction in potential heart donors and evaluated its influence on recipient outcomes. MethodsDonor records of consecutive organ donors in western Sweden between 2006 and 2016 were reviewed. Recipients of transplanted donor hearts were identified in the Scandiatransplant database. ResultsOf 641 potential heart donors who underwent echocardiographic assessment, LV dysfunction (ejection fraction <50% and/or regional hypokinesia) was found in 155 donors (24%). Regional hypokinesia was seen in 113 donors of whom 46 had a Takotsubo-like circumferential hypokinetic pattern. Independent donor variables associated with LV dysfunction were a younger age, cardiac arrest as a contributing factor to death, need for inotropic support, and a shorter time from admission to declaration of brain death. A total of 338 (54%) donor hearts were transplanted, of which 45 (14%) had LV dysfunction. LV dysfunction was a major determinant of not transplanting the heart (P < .001). After transplantation, LV function normalized in the recipients. Neither short-term outcomes nor the composite end point of death or retransplantation over time differed between recipients of donor hearts with versus without LV dysfunction (P = .587). ConclusionsLV dysfunction is common among potential heart donors. These hearts were safely transplanted in this study. The use of these hearts might significantly increase transplantation rates.

DCD Donor Hearts Recipients Compared to DBD Donor Heart Recipients Present with Comparable Systolic Left Ventricular Function and Better Myocardial Strain at 1 Year Follow Up

Purpose Cardiac transplantation from donation after circulatory death (DCD) has been implemented at Papworth hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. Methods We identified 26 DCD cardiac recipients who were transplanted from February 2015 to February 2017 and we matched them with 26 DBD cardiac recipients. Three and 2 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. Results DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function. LVEDV was similar in DCD and DBD patients (102+/-37 vs. 99+/-21 ml, respectively), as well as LVESV (44+/-12 vs. 43 +/- 18 ml, respectively) and LV mass (157+/-36 vs. 169+/-44 gr). LV ejection fraction was similar in two groups (57+/- 7 vs. 58+/-8 %), as well as GLS (-15.9+/-2.3 vs. 14.8+/- 1.9%, p=0.1) and GCS (-23.7+/-5.7 vs. -20.3+/-4.1, p=0.05). In both groups 3 patients presented with left ventricular dysfunction secondary either to primary graft dysfunction or cellular rejection. When we limited analysis to the patients who presented at 1 year follow up with LVEF>=50%, DCD and DBD cardiac recipients presented with similar LVEF (60+/-5 vs. 58+/-4%), but DCD cardiac recipients in comparison to DBD recipients had better GLS (-16.5+/-1.7% vs. -15.1+/-1.4%, p=0.04) and better GCS (-25.2+/-4% vs. 20.9+/-3.25, p=0.02). Conclusion DCD and DBD cardiac recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking in comparison to DBD cardiac recipients. Cardiac transplantation from donation after circulatory death (DCD) has been implemented at Papworth hospital since February 2015. Despite encouraging results some concerns may be raised about the impact of the warm ischemia and reperfusion injury on the myocardium status at longer follow-up. Therefore, we aimed to analyse systolic performance of the left ventricle at 1 year follow in DCD and donation after brain death (DBD) cardiac recipients, as assessed by echocardiography with myocardial deformation imaging. We identified 26 DCD cardiac recipients who were transplanted from February 2015 to February 2017 and we matched them with 26 DBD cardiac recipients. Three and 2 patients from DCD and DBD group, respectively, died in the first-year post transplant. In the remaining patients we have compared the classical echocardiographic measurements as well as global longitudinal strain (GLS) and global circumferential strain (GCS) at 1-year follow-up. DCD and DBD patients did not present with differences in terms of classical echocardiographic parameters of left ventricular (LV) structure and systolic function. LVEDV was similar in DCD and DBD patients (102+/-37 vs. 99+/-21 ml, respectively), as well as LVESV (44+/-12 vs. 43 +/- 18 ml, respectively) and LV mass (157+/-36 vs. 169+/-44 gr). LV ejection fraction was similar in two groups (57+/- 7 vs. 58+/-8 %), as well as GLS (-15.9+/-2.3 vs. 14.8+/- 1.9%, p=0.1) and GCS (-23.7+/-5.7 vs. -20.3+/-4.1, p=0.05). In both groups 3 patients presented with left ventricular dysfunction secondary either to primary graft dysfunction or cellular rejection. When we limited analysis to the patients who presented at 1 year follow up with LVEF>=50%, DCD and DBD cardiac recipients presented with similar LVEF (60+/-5 vs. 58+/-4%), but DCD cardiac recipients in comparison to DBD recipients had better GLS (-16.5+/-1.7% vs. -15.1+/-1.4%, p=0.04) and better GCS (-25.2+/-4% vs. 20.9+/-3.25, p=0.02). DCD and DBD cardiac recipients present with similar systolic LV function at 1-year follow, as assessed by classical echocardiographic parameters. DCD cardiac recipients have better myocardial deformation parameters as assessed by the speckle tracking in comparison to DBD cardiac recipients.

Heart Transplantation with Older Donors Age: Single Centre Experience

Purpose Heart transplantation (HTx) is the best therapeutic option for patients suffering from end-stage heart failure, but the shortage of donor hearts still represents a crucial problem. Methods Since 1985 to December 2017, a total of 611 HTx in 600 patients have been transplanted at our Centre. The aim of the study is to analyze the short- and long-term results of HTx in patients with older donor age, comparing the Results The mean age at HTx was 55±11.1 years. Of these, 561 (91%) received a donor heart Recipients transplanted with donors Conclusion In the older donor groups, the incidence mortality is highest in the first month from HTx; conversely, it appears similar at 1-year between donor

Long-term transplant outcomes of donor hearts with left ventricular dysfunction

ObjectiveDespite small single-center reports demonstrating acceptable outcomes using donor hearts with left ventricular dysfunction, 19% of potential donor hearts are currently unused exclusively because of left ventricular dysfunction. We investigated modern long-term survival of transplanted donor hearts with left ventricular dysfunction using a large, diverse cohort. MethodsUsing the United Network for Organ Sharing database, we reviewed all adult heart transplants between January 2000 and March 2016. Baseline and postoperative characteristics and Kaplan–Meier survival curves were compared. A covariates-adjusted Cox regression model was developed to estimate post-transplant mortality. To address observed variation in patient profile across donor ejection fraction, a propensity score was built using Cox predictors as covariates in a generalized multiple linear regression model. All the variables in the original Cox model were included. For each recipient, a predicted donor ejection fraction was generated and exported as a new balancing score that was used in a subsequent Cox model. Cubic spline analysis suggested that at most 3 and perhaps no ejection fraction categories were appropriate. Therefore, in 1 Cox model we added donor ejection fraction as a grouped variable (using the spline-directed categories) and in the other as a continuous variable. ResultsA total of 31,712 donor hearts were transplanted during the study period. A total of 742 donor hearts were excluded for no recorded left ventricular ejection fraction, and 20 donor hearts were excluded for left ventricular ejection fraction less than 20%. Donor hearts with reduced left ventricular ejection fraction were from younger donors, more commonly male donors, and donors with lower body mass index than normal donor hearts. Recipients of donor hearts with reduced left ventricular ejection fraction were more likely to be on mechanical ventilation. Kaplan–Meier curves revealed no significant differences in recipient survival up to 15 years of follow-up (P = .694 log-rank test). Cox regression analysis showed that after adjustment for propensity variation, transplant year, and region, ejection fraction had no statistically significant impact on mortality when analyzed as a categoric or continuous variable. Left ventricular ejection fraction at approximately 1 year after transplantation was normal for all groups. ConclusionsCarefully selected donor hearts with even markedly diminished left ventricular ejection fraction can be transplanted with long-term survival equivalent to normal donor hearts and therefore should not be excluded from consideration on the basis of depressed left ventricular ejection fraction alone. Functional recovery of even the most impaired donor hearts in this study suggests that studies of left ventricular function in the setting of brain death should be interpreted cautiously.

Donor Heart Selection: The Outcome of Cardiac Graft Received After at Least 6 Declines by a Candidate on Medical Grounds: A Single-Center Experience

The decline in the number of suitable donor hearts has led to an increasing interest in the use of previously unacceptable donors. In Japan, if one candidate declines a donor heart it may be offered to other candidates. Since 2015, we have started to proactively transplant donor hearts declined. This single-centre study aimed to evaluate the outcome of recipients of donor hearts considered medically unsuitable for transplantation by at least 6 candidates.

Outcomes After Transplantation of Donor Hearts With Improving Left Ventricular Systolic Dysfunction

BackgroundLeft ventricular systolic dysfunction (LVSD) accounts for almost 25% of nonacceptance of potential donor hearts. Previous smaller, single-center studies showed that LVSD following brain death may be transient, and such hearts can be successfully resuscitated with resolution of LVSD, then transplanted. ObjectivesThis study evaluated outcomes of donor hearts with LVSD on initial transthoracic echocardiogram (TTE) that resolved during donor management. MethodsWe reviewed echocardiograms of all cardiac donors in the United Network of Organ Sharing database that were transplanted from January 1, 2007, to September 30, 2015, and identified 472 donor hearts with LVSD (left ventricular ejection fraction [LVEF] ≤40%) on initial TTE that resolved (LVEF ≥50%) during donor management on a subsequent TTE. These patients comprised the improved donor LVEF group. These were compared with donor hearts with normal LVEF (LVEF ≥55%) on the initial TTE for recipient mortality, cardiac allograft vasculopathy (CAV), and primary graft failure (PGF). ResultsThere was no significant difference in recipient mortality at 30 days, 1 year, 3 years, and 5 years of follow-up, nor any difference in rates of PGF at 90 days and CAV at 5 years between recipients of donor hearts with improved LVEF and recipients of donor hearts with initially normal LVEF. Post-transplant length of stay was also similar between the 2 groups. Using propensity scores, 461 transplants in the improved-donor LVEF group were matched to 461 transplants in the normal-donor LVEF group. There was no significant difference in PGF at 90 days or recipient mortality after up to 5 years of follow-up. ConclusionsIn the largest analysis of donor hearts with transient LVSD, we found that such hearts can be successfully resuscitated and transplanted without increasing recipient mortality, CAV, or PGF. These results underscore the importance of appropriate donor management and should help to increase utilization of donor hearts with transient LVSD.

Outcomes of Early Adolescent Donor Hearts in Adult Transplant Recipients

ObjectivesThis study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts. BackgroundDespite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established. MethodsAll adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics. ResultsOf the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07). ConclusionsIn this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts.

Early Outcomes With Marginal Donor Hearts Compared With Left Ventricular Assist Device Support in Patients With Advanced Heart Failure

The shortage of donor hearts has limited cardiac transplantation for end-stage heart failure, leading to the increased use of left ventricular assist devices (LVADs) as bridge-to-transplant (BTT) and marginal donor hearts; however, outcomes have been mixed. This study examines differences in wait list survival of patients with continuous flow LVADs and post-transplantation survival of patients receiving a marginal donor heart. The United Network of Organ Sharing database was retrospectively queried from January 2005 to June 2013 to identify adult patients listed for heart transplant. Marginal donor criteria included age greater than 55 years, hepatitis C positive, cocaine use, ejection fraction less than 0.45, or donor to recipient body mass index mismatch of greater than 20%. The primary endpoint was wait list survival of patients with LVADs compared with post-transplant survival of marginal donor heart recipients using Kaplan-Meier analysis. A total of 2,561 and 4,737 patients received LVAD support or a marginal donor heart, respectively. The 30-day, 1-year, and 2-year survival was 96%, 89%, and 85%, for patients with LVAD support on the waiting list and 97%, 89%, and 85%, respectively, for recipients of marginal donor hearts (p= 0.213). Recipients of marginal hearts had worse survival than non-marginal heart recipients at 3 years (p= 0.011). There was no significant difference between waiting list survival of patients with LVAD support as BTT and post-transplant survival of recipients with marginal donor hearts. There could be clinical benefits for using LVAD support as BTT to allow time for better allocation of optimal donor hearts as opposed to transplantation with a marginal donor heart.

Outcome in Cardiac Recipients of Donor Hearts With Increased Left Ventricular Wall Thickness

The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT <or= 1.4 cm. By Cox regression, donor LVWT > 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients.

Donor heart selection: the outcome of "unacceptable" donors

BackgroundThe decline in the number of suitable donor hearts has led to an increasing interest in the use of previously unacceptable donors. In the United Kingdom, if one centre declines a donor heart on medical grounds it may be offered to other centres. This multi-centre study aimed to evaluate the outcome of recipients of donor hearts considered medically unsuitable for transplantation by one centre that were used in other centres.MethodsBetween April 1998 and March 2003, ninety-three donor hearts (group A) were transplanted, after being considered medically unsuitable for transplantation by another centre. During the same period, 723 hearts (group B) were transplanted in the UK using donors not previously rejected. Data on the donors and recipients was obtained from the UK transplant database. Comparative analysis on the two groups was performed using SPSS 11.5 for Windows.ResultsThe characteristics of recipients were similar in both groups. The main reasons for refusal of hearts are listed below. In most cases there was more than one reason for refusing the donor heart. We did not find significant differences in the post-operative mortality (up to 30 days), ICU and hospital stay and cardiac cause of death between the two groups. Kaplan-Meier survival curves showed no significant difference in the long-term survival, with Log Rank test = 0.30.ConclusionThis study demonstrates that some hearts declined on medical grounds by one centre can safely be transplanted and should be offered out nationally. The use of these hearts was useful to expand the scarce donor pool and there does not seem to be a justification for denying recipients this extra source of organs.

Does duration of donor brain injury affect outcome after orthotopic pediatric heart transplantation?

We tested the hypothesis that duration of donor brain injury and death would have an adverse effect on recipient rejection and mortality in pediatric heart transplantation. Ninety-three cardiac transplants were performed at our center from July 1, 1997, through June 30, 2003. The primary study end points were the number of rejection episodes and the time to first rejection. Secondary outcomes were early and late mortality. Among 88 recipients of 93 cardiac allografts, 5 (6%) and 1 (1%) received second and third allografts, respectively. Overall patient mortality (3 early and 2 late) was 6% (5/88), and overall graft loss was 6% (6/93). Median time from donor brain injury to declaration of brain death (brain injury interval), time from brain death to donor cardiectomy (brain death interval), and graft ischemia time were 38, 24, and 3.3 hours, respectively. Cox regression analysis (adjusting for United Network for Organ Sharing status, ventilator dependence, extracorporeal membrane oxygenation and ventricular-assist device status, diagnosis of congenital heart disease, sex and cytomegalovirus mismatches, and type of immunosuppression) demonstrated that recipients of donor hearts with relatively long periods from brain injury to death declaration or from death to organ removal had significantly improved rejection-free survival (hazard ratios 0.3, P = .01, and 0.5, P = .05, for brain injury and brain death times, respectively). Prolonged donor heart ischemia did not impact rejection rate. Increasing brain injury interval, brain death interval, and graft ischemia time had no significant effect on mortality. Longer brain injury and death intervals correlated with improved freedom from rejection but had no effect on mortality.

Donor Heart Selection: Wythenshawe Experience

Background The decline in the number of suitable donor hearts has led to an increasing interest in the use of previously unacceptable donors. This study aimed to evaluate the outcome of recipients of donor hearts considered medically unsuitable for transplantation at this center that were used in other centers in the United Kingdom. Methods Forty donor hearts (group 1) were declined by Wythenshawe Hospital and used in other units in the United Kingdom in the period extending from April 1998 to March 2003. One hundred four hearts (group 2) were transplanted at Wythenshawe Hospital during the same period. Donors and recipient data were obtained from the United Kingdom Cardiothoracic Transplant Audit database. Mortality in both groups was analyzed using SPSS software. Results Mortality in patients receiving grafts from group 1 donors was significantly higher than in group 2 ( P < .0009). Of the early deaths in this group 50% (6 of 12) were the result of graft failure. These donors were receiving high doses of inotropes, had ischemic time exceeding 3.5 hours, and the grafts were transplanted into high-risk patients. Conclusion Hearts declined on medical grounds by one center should be evaluated with caution before being considered suitable for transplantation, especially when more than one adverse factor is present.

Overexpression of human copper/zinc superoxide dismutase (SOD1) suppresses ischemia-reperfusion injury and subsequent development of graft coronary artery disease in murine cardiac grafts.

Ischemia-reperfusion injury is an important risk factor for graft coronary artery disease (GCAD). We hypothesized that overexpression of SOD1 in donor hearts would suppress ischemia-reperfusion injury and thereby reduce GCAD. In one series, donor hearts of C57BL/6 (H-2b) transgenic mice overexpressing human SOD1 or C57BL/6 wild-type mice were heterotopically transplanted into C57BL/6 recipients and procured after 4 hours of reperfusion (n=6 each). Superoxide, TNF-alpha, and MCP-1/CCL2 production were significantly reduced in the SOD1 transgenic donor heart recipients, and graft injury determined by serum CPK-MB levels was significantly decreased. Cardiomyocyte apoptosis and caspase-3 and caspase-9 activities were significantly decreased in these recipients; caspase-8 activity was unchanged. Fas ligand but not Fas expression was also reduced. In a second series, transgenic and wild-type hearts were transplanted into C-H-2bm12KhEg (H-2bm12) recipients, and then procured on day 56 (n=7 each). Cardiac graft beating was significantly better in the SOD1 transgenic donor heart recipients on days 28, 42, and 56 (but not day 14). Significant reduction in luminal narrowing, the intima/media ratio, and the percentage of diseased vessels was seen in the SOD1 transgenic donor heart recipients, and MCP-1/CCL2, ICAM-1, and VCAM-1 production were significantly reduced. Overexpression of SOD1 attenuates both apoptosis and the inflammatory response during ischemia-reperfusion injury and therefore mitigates against the subsequent development of GCAD.

Effect of older donor age on risk for mortality after heart transplantation

Background Despite the increasingly common use of donor hearts at least 50 years of age, controversy still remains regarding long-term outcome. Our goal was to determine if older donor age is associated with an increased risk of mortality and specifically if the use of donor hearts at least 50 years of age reduces survival. Methods We retrospectively studied records of all primary heart transplants performed between January 1990 and July 2002. Fifty-six patients who had received donor hearts at least 50 years of age were compared with 611 recipients of donor hearts less than 50 years of age. Clinicopathologic parameters were analyzed for their effect on mortality using the Cox proportional hazard model with calculation of hazard ratios (HR). Cut-point analysis of donor age was used to determine which donor age is associated with the greatest risk of mortality after transplant. Results Recipients of donor hearts at least 50 years of age were older (58.5 years ± 7.0 vs 53.2 ± 11.6; mean ± standard deviation [SD]; p < 0.0001), suffered more often from ischemic cardiomyopathy (69% vs 50%, p = 0.01), and experienced a longer waiting time (192.2 days ± 301.0 vs 138.6 ± 190.8, p < 0.0001). Donor hearts at least 50 years of age (age 54.1 ± 3.5 years) were more often female (50% vs 34%, p = 0.03), died less often of “head trauma” (9% vs 42%, p < 0.0001), and exhibited fewer cytomegalovirus (CMV) mismatches (29% vs 39%, p = 0.04) than donor hearts less than 50 years of age (age 26.8 ± 12.3 years). Multivariate predictors of mortality were rejection index (HR 1.90 per unit [rejections/100 survival days], p < 0.0001), donor age (HR 1.16 per 10-year increment, p = 0.002), and recipient age (HR 1.24 per 10-year increment, p = 0.04). Recipients of donor hearts at least 50 years of age had reduced 1-year and 5-year survival ([65.7% vs 81.7%, p < 0.05] and [48.3% vs 68.4%, p < 0.05], respectively), as well as a higher proportion of deaths occurring within 1 month of transplant (41% of total deaths vs 23%, p = 0.06). Cut-point analysis indicated the characteristic of donor age of at least 40 years (categorical variable) to predict mortality with the same degree of fit as age used as a continuous variable. Conclusions Although we observed a substantial reduction in survival among patients who were allocated donor hearts at least 50 years of age, this difference was not solely attributable to the categorical variable of donor age 50 in this group. Donor age as a continuous variable, however, was determined to be a notable predictor of survival and use of the donor age cut-point of 40 years (categorical variable) allowed risk stratification with similar accuracy. The use of a donor age cut-point of 40 years may be a useful clinical criterion for graft-related risk assessment.

Psychosocial problems of donor heart recipients adversely affecting quality of life.

Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them.