Heart transplantation has been considered the gold-standard treatment for patients with end-stage heart failure, provided that a careful selection process is followed to assess candidacy [1]. In addition, the increased survival rate and quality of life for patients undergoing transplantation during recent decades have contributed to the success of heart transplantation [2,3]. The annual number of heart transplants has remained steady at 3,500–4,500 worldwide and, notably, half were performed in the United States [4,5]. In 2018, only 100 heart transplants were performed in Iran, despite 2,500 patients on the waiting list. This significant difference in one year led to an increase in the wait time and in the mortality rate of patients on the waiting list [6]. According to Mandegar et al. [7], in Iran, the mean survival rate for heart transplant recipients was 6.6±0.87 years.

The major cause of brain death in potential organ donors in Iran is head trauma (including motor vehicle accidents), especially in the age range of 20 to 40 years. Based on reports from the Ministry of Health on the number of accidents and deaths due to trauma, the age of donors is increasing [8]. Concurrently, the number of patients on heart transplant waiting lists is growing due to the increased number of patients with cardiovascular diseases, dilated cardiomyopathy, and hypertension. Considering the limited number of brain death donors in the ideal age range with high-performance cardiovascular function, resources other than ideal donors should be considered for patients on the waiting list [9-11].

The age limit restrictions for organ donors vary slightly in different countries and medical centers, though these standards have expanded due to the increased need for organs and longer wait times. In addition to the age of the donor, other controversial eligibility issues such as smoking habits and communicable diseases (e.g., hepatitis C) have been addressed in different studies [12]. In Iran the upper age limit is usually between 40 and 50 years for donors. Marginal donors are defined as patients between 40 and 50 years or less than 40 years with risk factors such as drug abuse, a history of smoking, hypertension, diabetes mellitus, dyslipidemia, a family history of coronary artery disease, or high-dose inotrope treatment [13] indicating a potentially poor outcome based on follow-up echocardiography and coronary angiography. In recent years in Iran, harvests from marginal donors for heart transplants have been performed based on careful and complementary tests such as angiography at the Sina Hospital Organ Procurement Unit (OPU), a pioneer of procuring organs in the country.

Studies have shown that donations from older donors (>50 years) can be conducted for older (>60 years) recipients to avoid organ waste and to offer the patient a chance for survival [7,14-16]. An analysis by the United Network for Organ Sharing (UNOS) used a propensity score analysis to evaluate the postoperative outcomes of recipients of donor hearts with left ventricular ejection fractions <40% (reduced), 40%–50% (borderline), and ≥50% (normal) and the results showed equivalent odds of primary graft failure and death at 1 year in all three groups [17]. Several studies have demonstrated no significant difference in the survival rate of patients who received organs from older donors [1,18-21]. The characteristics of potential ideal donors in Iran are detailed in Table 1 [15].

The primary objective of the study was to determine whether patients who received a marginal donor heart had different outcomes in terms of survival compared with patients who received an ideal donor heart, with the goal of finding an appropriate solution to the shortage of donor organs and to reduce wait times for recipients.

This research was approved by the Tehran University of Medical Sciences ethics center (No. IR.TUMS.IKHC. REC.1399.359). Written consent was obtained from the families of deceased donors and the heart recipients before entering the study, and no organs were obtained from prisoners.

As heart transplantation progresses as an effective treatment for end-stage heart failure, physicians have considered relaxing the exclusion criteria and expanding the donor pool to meet the high demand for available organs [18-20]. Although heart transplantation from marginal donors is a relatively new topic in Iran, protocols regarding the suitability of potential cardiac donors have been modified over the years. Donors older than 40 to 50 years old or those with a positive history of drug abuse and smoking have recently been considered suitable. However, potential donors with chronic diseases like hepatitis B and C or high-grade tumors are not yet eligible candidate.

In our study, the most prevalent cause of brain death was head trauma, followed by non-traumatic ICH. In marginal donors, the most prevalent cause of brain death was also trauma and brain hemorrhage. These findings were similar to the study of Mizraji et al. [22]. Based on previous studies, age is one of the most important factors in choosing donors. Considering the organ shortage, the acceptable age range for organ harvest has increased [23]. According to Morgan et al. [24], older age is an independent risk factor for 1-year mortality, but the upper limit of the acceptable age range continues to increase as time progresses.

In our study, age as a continuous variable or as a categorical variable with a cutoff value of 50 years did not affect short and intermediate-term survival rates or the incidence of mechanical support. Although matching a young donor with a young recipient is a basic principle of donor selection, in this study there were 18 patients with an average age of 33.5 years who received hearts from donors 40.2 years or older.

According to the findings of previous studies, recipients of older donor hearts are exposed to the highest level of risk within the first postoperative month; therefore, precise care should be provided during that time [24]. However, Morgan et al. [24] did not report any significant difference between younger and older donor groups when assessing posttransplant complications such as sepsis and acute rejection. Moreover, they reported no difference in the first-year survival rates between the two groups. The findings of Drinkwater et al. [20] were similar to our study.

In a cohort study by Blanche et al. [25], two donor groups were compared who were similar to our cohort in all demographic data, except age (>50 years and <50 years), with recipient groups that were also similar. Their study recommended using donors older than 50 years and showed no difference in the survival rates of the two groups. According to the UNOS heart transplant registry, the donor-recipient predicted heart mass ratio, but not the weight or height ratio, is associated with survival [26]. Furthermore, sex matching between donors and recipients is very important. In our study, the sex was matched in 46 patients (61.3%) in group C and in 10 patients (55.56%) in group D. Considering the absence of a significant difference between the survival rates of the two groups, it can be concluded that sex match decreases the negative impacts of a marginal donor on survival.

Ayesta et al. [27] has shown that matched groups (female/female [F/F] and male/male [M/M]) were associated with higher recipient survival rates. In contrast, Antelmi et al. [28] suggested that a male donor organ for a female recipient is permissible. An analysis by the International Society for Heart and Lung Transplantation demonstrated that both mismatched groups (F/M and M/F) showed lower survival rates. A meta-analysis conducted by Ayesta et al. [27] and a retrospective cohort study by Reed et al. [26] assessed the relationship between sex mismatch and survival of heart recipients and concluded that sex mismatch increased 1-year mortality in men, but not in women. In our study, female recipients exhibited a higher mortality rate overall than male recipients. Wang et al. [29] demonstrated that female recipients of hearts from marginal donors may have lower survival rates than those who receive hearts from ideal donors.

Taking into consideration the limited number of subjects due to the novelty of the topic in Iran, our study showed no significant difference between the survival rates of the ideal and marginal groups. However, according to Felker et al. [30], a marginal donor heart graft is only acceptable when it offers a greater chance of survival than that achieved with existing conventional therapies. Based on prior experience and considering the limited availability of resources such as artificial devices for cardiac support, heart transplantation using appropriate marginal donors is a valuable treatment for end-stage heart failure patients in Iran. Although the use of marginal donors increases organ availability, it should be considered that the results may not replicate those obtained with ideal donors. Overall, due to the lack of organ availability in Iran, the use of marginal donors for marginal recipients can reduce the number of people on the waiting list. We also recommend establishing a national marginal donor system that is appropriate for Iranian patients and extends the donor pool. The small number of marginal cases in our study underscores the need for further studies that include data from other centers and have longer follow-up time frames.