EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Heart transplant is the gold standard treatment for end-stage heart failure in appropriate patients.¹ Shortage of donor organs remains an ongoing problem, with many patients dying while on the wait list before they have received a donor heart.² Patients have good prognosis after heart transplant, with current median survival of more than 12 years.³ Mortality is highest in the first year after transplant, with reported rate of 11%.³ Several factors have been shown to influence mortality. On the recipient side, factors include age, congenital heart disease, diabetes, high serum creatinine, end-stage kidney failure requiring dialysis, preoperative mechanical ventilation, and preoperative mechanical circulatory support.^4,5 Older donors and donor-to-recipient sex mismatch are also associated with worse survival.^4,5 Effects of the allograft procurement procedure itself on mortality have been debated.

The effect of synchronous donor heart and lung procurement is one such area of debate. When donor hearts originate from donors whose lungs are also intended for transplant, procurement of both of these anatomically intertwined donor organs is obviously performed at the same time.⁶ This requires close collaboration and agreement on division of key anatomic structures, in particular division of the left atrium, between different surgical teams, each of which is likely striving for the best results for their respective donor organ.⁷ Given the added complexity, synchronous heart and lung procurement might be expected to negatively affect outcomes after heart transplant. So far, to our knowledge, no study has assessed the effects of synchronous heart and lung procurement from the experience of a European institution. The aim of our study was to fill this gap in the literature.

Materials and Methods

Patient inclusion and grouping
This single-center study included all adult patients who received a heart transplant at our institution from September 2010 to June 2022. These recipients and their corresponding donors were divided into 2 groups: (1) heart and lung procurement group and (2) heart-only procurement group.

Study design and data collection
The study was retrospective. Recipient baseline characteristics, peri- and postoperative course, complications at 1 year, and survival were obtained from electronic medical records from the transplant hospitalization and routine follow-up visits. Donor baseline characteristics were gathered from standardized donor reports. Outcomes were overall mortality and mortality at 30 days, 3 months, 1 year, and 3 years, as well as adverse events at 1 year. Adverse events included postoperative mechanical circulatory support, resternotomy, hemodialysis, neurovascular incidents, pacemaker implantation, transplant rejection (rejection grade 1R or more according to the International Society for Heart and Lung Transplantation 2004 grading scheme), clinically significant cytomegalovirus (CMV) viremia, and mycoses.⁸

Statistical analysis
Differences in baseline characteristics were analyzed with the t test for normally distributed variables, the chi-square test and the Mann-Whitney U test for non-normally distributed variables, and the Fisher exact test for small samples. Normal distribution of variables was checked by inspection of histograms and using the Shapiro-Wilk test. We analyzed overall mortality using Kaplan-Meier survival analysis with censoring at the end of follow-up. Differences in mortality at predefined timepoints and complications at 1 year were analyzed with logistic regression, adjusting for the following clinically relevant variables: recipient age, recipient preoperative creatinine levels, recipient diabetes, recipient preoperative mechanical ventilation, and donor age. P < .05 was considered significant. Statistical analysis was performed in IBM SPSS Statistics for Windows, version 27 (IBM Corp).

Ethics
This study followed the principles of the Declaration of Helsinki and was approved by the local university’s ethics committee. All patients gave their informed consent for the scientific use of anonymized patient data prior to inclusion in the study.

Study population
Our study included 253 recipients (72.3% male) with a mean age of 55.0 ± 11.1 years and 253 corres-ponding donors (50.0% male) with a mean age of 44.0 ± 12.4 years: 184 recipients (72.7%) received hearts from heart-and-lung donors and 69 recipients (27.3%) received hearts from heart-only donors. Mean follow-up was 3.2 years, and no patients were lost to follow-up as of November 2022.

Recipient baseline characteristics
Heart transplant recipients from both groups were comparable in terms of the recorded baseline variables (Table 1). More male heart transplant recipients were in the heart-and-lung donor group than in the heart-only donor group (75.0% vs 65.2%), but the difference was not statistically significant (P = .155). Recipients in both groups were at the lower end of being overweight, with body mass index of 25.8 for recipients of hearts from heart-and-lung donors and 25.7 for recipients of hearts from heart-only donors. Creatinine levels were higher in the heart-only group, with 7 heart transplant patients on dialysis (10.1%) compared with 8 heart transplant patients from the heart-and-lung group (4.3%). Both groups had normal preoperative hemoglobin and potassium levels. Nearly half of heart transplant recipients from the heart-and-lung group and one-third of heart transplant recipients from the heart-only group had high urgent listing on the wait list (P = .066). Underlying cardiac pathology was equally split between dilated and ischemic cardiomyopathy, which combined were present in almost 90% of patients in both groups.

Donor baseline characteristics
Heart-and-lung donors were significantly younger than heart-only donors (43.2 years vs 47.2 years; P = .017) but were otherwise comparable (Table 2). The youngest donor was aged 15 years, and the oldest was aged 68 years. At almost two-thirds in both groups, the proportion of ever-smokers in the donor population was high. Roughly one-third of donors had received cardiopulmonary resuscitation. The major cause of brain death was intracranial hemorrhage in both groups.

Cold and warm ischemic times
Despite the potential for added complexity of synchronous heart and lung procurement, there were no differences in ischemic times between the heart-and-lung and heart-only procurement groups. Mean cold ischemic time was 151 minutes in both groups (P = .959). Warm ischemic time was 64 minutes in the heart-and-lung procurement group and 62 minutes in the heart-only procurement group (P = .349).

Mortality and complication rates
There were no differences in overall mortality between heart transplant recipients from both donor groups (P = .33) (Figure 1). Mortality at 30 days was higher for heart transplant recipients from heart-only donors, at 15.9%, compared with 6.0% for heart transplant recipients from heart-and-lung donors (adjusted odds ratio for the heart-only group: 2.72; 95% CI, 1.06-6.95; P = .035). Refractory cardiogenic shock due to primary graft failure despite extracorporeal life support was the main cause of death within 30 days posttransplant and accounted for 91% of 30-day mortality in both groups. Of the 11 transplant recipients of hearts from heart-only donors who died within 30 days posttransplant, 1 patient had intraoperative aortic dissection with resulting global cerebral hypoxia and died on day 3. Of the 11 transplant recipients of hearts from heart-and-lung donors who died within the same time period, 1 had global abdominal ischemia that was fatal on day 27 despite broad surgical intervention. The trend toward lower mortality in the heart-and-lung donation group versus the heart-only donation group persisted at 3 months (10.1% vs 19.4%; P = .196), at 1 year (16.2% vs 27.6%; P = .348), and at 3 years (25.2% vs 33.3%; P = .375), but the difference was not significant. Donor age was independently associated with 30-day (P = .037) and 1-year mortality (P ≤ .01), with better survival in recipients of hearts from younger donors.

Hearts from heart-and-lung donors were not associated with more postoperative morbidity or overall morbidity within the first year of transplant compared with hearts from heart-only donors (Table 3). Recipients of hearts from heart-and-lung donors had numerically lower rates in all recorded complications except for transplant rejection and CMV viremia. Despite the potential for bradycardic arrhythmias from the left atrium incision site in recipients in the heart-and-lung donor group, rates of pacemaker implantation were not higher than shown for recipients in the heart-only donor group.

Synchronous donor heart and lung procurement is more complex than procurement of the donor heart without the lungs. Despite this added complexity, our study showed that synchronous procurement does not negatively affect the outcomes in heart transplant recipients. The literature on this topic to date is relatively limited, and the results have been conflicting. On the one hand, Russo and colleagues reported that recipients of heart-and-lung donor hearts have higher odds (odds ratio: 1.58) of developing primary graft failure than recipients of heart-only donor hearts, with primary graft failure defined as death or retransplant.⁹ Recipients of heart-and-lung donor hearts were also shown to have worse 10-year survival by Madden and colleagues, although perioperative survival was similar between the recipients of hearts from heart-and-lung and heart-only donors.¹⁰ On the other hand, Xia and colleagues found no difference in survival between their recipients.¹¹ In fact, their study showed a survival advantage for transplant recipients using hearts from heart-and-lung donors in univariate analysis, but this effect was not significant once adjusted for covariates.¹¹ Interestingly, looking at the topic from the donor lung perspective, Contreras and colleagues also found no effect of synchronous donor heart and lung procurement on mortality in lung transplant recipients.¹² The research to date on this topic has been based on data from the United Network of Organ Sharing. Although these data include large patient numbers, they cover a wide variety of institutions with differing practices and include only heart transplants performed in the United Status.

Our results support the findings by Xia and colleagues, with heart transplant recipients from heart-and-lung donors showing a trend toward better survival and lower morbidity. In our study, transplant recipients of hearts from heart-and-lung donors had received donor hearts from significantly younger donors and younger donor age is known to be associated with better outcomes in heart transplant recipients.¹³ However, the trend towards better outcomes in transplant recipients of hearts from heart-and-lung donors persisted once adjusted for donor age. Our findings dispute the hypothesis put forward by Madden and colleagues that hearts exposed to lungs suitable for transplant are not as well preconditioned to tolerate ischemic stress,¹⁰ and our results suggest that the opposite could be true. Heart-and-lung donations may be better quality donor organs, as lungs suitable for transplant may indicate better health state overall. The difference in suitability of lungs for organ donation was not explained by smoking in our study, as the prevalence of ever-smokers was comparable in both groups. Our study did not allow for further exploration of potential intrinsic differences between our 2 groups. Our results do not support the conclusion by Russo and colleagues that synchronous donor heart and lung procurement is associated with higher frequency of primary graft failure, a composite endpoint of death and retransplant. Comparability between our study and that of Russo and colleagues is limited given the very low rate of retransplant in our study: only 1 patient (0.4%) required a retransplant during follow-up. Previous research has shown an association between ischemic time and outcomes after heart transplant.¹³ Cold ischemic time was not higher in the heart-and-lung donor group in our study, suggesting that much of the important agreement between the cardiac and the thoracic surgical teams of where to divide and dissect important anatomic structures such as the left atrium and pulmonary artery likely occurs before aortic cross-clamping.

Limitations
There are several limitations to our study. First, limitations intrinsic to the retrospective design include potential bias; however, because we have closely followed all heart transplant recipients since 2010, we would consider this effect to be negligible. Second, donors were classified as heart-and-lung and heart-only based primarily on donor reports because the retrospective single-center design did not allow access to information from other centers. As a result, donors whose lungs were offered for transplant but ultimately not transplanted are included as heart-and-lung donors, likely overestimating the proportion of this group, and explaining the higher proportion of this group compared with previous studies. Third, we have a relatively small sample and different group sizes, with a much smaller number of patients in the heart-only donor group, making statistical significance more difficult to achieve.

Based on our study of heart transplant recipients at a European institution, despite its added complexity, the act of synchronous donor heart and lung procurement shows no negative effects on mortality or morbidity in heart transplant recipients. There may be a survival benefit associated with receiving a heart from a heart-and-lung donor, the mechanisms of which remain unknown.

Volume: 21 Issue: 8 August 2023

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