Predicted heart mass (PHM) ratio has become the standard donor-recipient size matching method in heart transplantation. Although use of small PHM ratio hearts is associated with increased 1-year mortality, the underlying mechanisms and time horizon of mortality remain uncertain.

A single-institution analysis of 334 isolated heart transplant recipients (January 2019-July 2022) was performed. Patients were stratified by PHM ratio: undersized (<0.86; n = 106), matched (0.86-1.15; n = 175), and oversized (>1.15; n = 53). Survival within PHM ratio groups was further stratified by complex transplant group (preoperative left ventricular assist device, adult congenital, or preoperative extracorporeal membrane oxygenation) and noncomplex transplant group (all others).

Donor and recipient variables were similar. However, undersized patients were more likely to have a durable left ventricular assist device (P = .022). Although postoperative primary graft dysfunction and inotrope score were similar between groups, there was a trend toward increased need for postoperative dialysis with undersized hearts (P = .056). Overall, 30-day (P = .012) and 1-year survival (P = .002) was significantly worse in the undersized group compared with the matched or oversized groups. However, subset analysis showed these differences only remained among the complex transplant recipients (P = .013) but not the noncomplex transplant recipients (P = .428). Median mixed venous oxygen saturations at serial time points were maintained between 65% and 70% in all heart size groups, with cardiac indices between 2.4 and 2.8 L/min/m2.

Small PHM ratio hearts are associated with increased 1-year mortality, driven by complex transplant operations. Recipients who received undersized PHM ratio hearts from noncomplex transplant operations had a similar hemodynamic profile and survival as those who received matched and oversized hearts. Small PHM ratio hearts may be selectively safe for transplantation.

The Organ Care System and Non-ischemic Heart Preservation methods have emerged as significant advancements in heart transplantation, designed to mitigate ischemic injury and extend preservation times. However, their high costs and logistical complexities necessitate strategic utilization.

We evaluated data from 83,761 heart transplants registered in the International Society for Heart and Lung Transplantation registry from 1988 to 2018. Utilizing a Cox proportional hazards model, we explored the influence of donor age and ischemic time on transplant survival. A key innovation of our study is the development of a nomogram to predict post-transplant survival, incorporating both traditional and advanced statistical methods.

The median age of recipients was 52 years (22% female) and 33 years (31% female) for donors. Analysis revealed a median ischemic time of 3 hours and median survival of 11.5 years across the cohort. The nomogram showed a decline in survival probabilities with increasing donor age, notably from age 40 and more significantly with ischemic times >4 hours. Ischemic times ≥4 hours versus <2 hours were associated with hazard ratio (HR) of 1.2 (95% CI, 1.1-1.3) for donors aged 40-59, a disparity that escalated for donors aged ≥60 (HR: 2.0; 95% CI, 1.5-2.7).

This study highlights the importance of careful donor selection and indicates that certain groups, particularly older donors with prolonged ischemic times, might benefit from ex-vivo preservation techniques. The developed nomogram offers a practical tool for clinicians, enhancing decision-making by providing detailed insights into the relationship between donor age, ischemic time, and post-transplant mortality.

The number of candidates on the waiting list for heart transplantation (HT) continues to far outweigh the number of available organs, and the donor heart nonuse rate in the United States remains significantly higher than that of other regions such as Europe. Although predicting outcomes in HT remains challenging, our overall understanding of the factors that play a role in post-HT outcomes continues to grow. We observe that many donor risk factors that are deemed "high-risk" do not necessarily always adversely affect post-HT outcomes, but are in fact nuanced and interact with other donor and recipient risk factors. The field of HT continues to evolve, with ongoing development of technologies for organ preservation during transport, expansion of the practice of donation after circulatory death, and proposed changes to organ allocation policy. As such, the field must continue to refine its processes for donor selection and risk prediction in HT.

Donor-recipient size matching is a key factor in donor selection for heart transplantation (HT). One approach uses predicted heart mass (PHM), derived from the Multi-Ethnic Study of Atherosclerosis (MESA). We sought to examine whether predicted left ventricular mass (PLVM) derived from the Dallas Heart Study (DHS) is associated with post-transplant outcomes.

The study cohort included participants without pre-existing cardiac disease in the DHS who had cardiac MRIs (n = 1746). A PLVM model was derived by linear regression. The DHS PLVM and MESA PHM were tested for correlation. The associations of the DHS PLVM and the MESA PHM with 1-year mortality post-HT were assessed in the United Network for Organ Sharing Registry in 3 eras: era 1: 1/1/2011-12/31/2014; era 2: 1/1/2015-10/17/2018; and era 3: 10/18/2018-12/31/2021). A pre-specified threshold for low donor-to-recipient mass ratio (< 0.86) was used in Kaplan-Meier survival estimation and univariate and multivariable Cox proportional hazard models.

The DHS cohort had a median age of 43 (IQR 36-52) years, 49% male, 40% Black, and 18% Hispanic ethnicity. The DHS PLVM was highly correlated with the MESA PHM: r = 0.96; P < 0.001. In era 1, a low donor-to-recipient mass ratio according to the DHS PLVM was associated with increased 1-year mortality rates (log-rank P < 0.001) as was the MESA PHM (log rank P = 0.002). However, in eras 2 and 3, a low donor-to-recipient mass ratio by either the DHS PLVM or MESA PHM was not associated with increased 1-year mortality rates.

PLVM was highly correlated with PHM. A low donor-to-recipient mass ratio, whether assessed by PLVM or PHM, was associated with 1-year mortality post-HT in a historical era but not in the current era under the new allocation system. These findings suggest that other factors may be contributing to donor selection and mortality risk in the modern era.

Donor-recipient heart size matching is crucial in heart transplantation; however, the often-used predicted heart mass (PHM) ratio may be inaccurate in the setting of obesity.

In this study, the authors sought to investigate the association between echocardiographically measured donor left ventricular mass (LVM) for heart size matching and the risk of the primary 1-year composite outcome of death or retransplantation.

The Donor Heart Study was a prospective, multicenter, observational cohort study that collected echocardiograms from brain-dead donors. The measured LVM ratio (donor measured LVM/recipient predicted LVM) was defined as the exposure variable, and the association with the primary outcome was analyzed with Cox proportional hazard modeling. Secondary analyses evaluated the association of the PHM and predicted LVM (donor predicted LVM/recipient predicted LVM) ratios with the primary outcome.

In 2,015 heart transplants, the measured LVM ratio demonstrated that undersized matches (<0.80) had a 47% higher risk (adjusted HR [aHR]: 1.47; 95% CI: 1.01-2.15) and oversized (>1.20) matches had a 58% increased risk (aHR: 1.58; 95% CI: 1.05-2.37) of the 1-year composite outcome compared with ideally matched transplants. However, the PHM and predicted LVM ratios were not associated with the primary outcome. Nonlinear modeling demonstrated a U-shaped relationship between the measured LVM ratio and composite outcome. The measured LVM ratio had superior predictive power for poor post-transplantation outcomes in obese recipients.

Measuring donor LVM with the use of echocardiography may provide a more accurate method for donor-recipient heart size matching that could improve heart transplant outcomes, especially in obese recipients.

Currently, there are no standardized guidelines for graft allocation in heart transplants (HTxs), particularly when considering organs from marginal donors and donors after cardiocirculatory arrest. This complexity highlights the need for an effective risk analysis tool for primary graft dysfunction (PGD), a severe complication in HTx. Existing score systems for predicting PGD lack superior predictive capability and are often too complex for routine clinical use. This study sought to develop a user-friendly score integrating variables from these systems to enhance the efficacy of the organ allocation process.

Severe PGD was defined as the need for mechanical circulatory support and/or death from an unknown etiology within the first 24 hours following HTx. We used a meta-analytical approach to create a derivation cohort to identify risk factors. We then applied a logistic regression analysis to generate an equation predicting severe PGD risk. We used our previous experience in HTx to create a validation cohort. Subsequently, we implemented the formula in a smartphone application.

The meta-analysis comprising six studies revealed a 10.5% ( 95% confidence interval (CI): 5.3-12.4) incidence rate of severe PGD and related 30-day mortality of 38.6%. Eleven risk factors were identified: female donors, female donor to male recipient, undersized donor, donor age, recipient on ventricular assist device support, recipient on amiodarone treatment, recipient with diabetes and renal dysfunction, re-sternotomy, graft ischemic time, and bypass time. An equation to predict the risk, including the 11 parameters (GREF-11), was created using logistic regression models and validated based on our experience involving 116 patients. In our series, 29 recipients (25%) required extracorporeal membrane oxygenation support within 24 hours post-HTx. The overall 30-day mortality was 4.3%, 3.4%, and 6.8% in the non-PGD and severe PGD groups, respectively. The area under the receiver operating characteristic (AU-ROC) curve of the model in the validation cohort was 0.804.

The GREF-11 application should offer HTx teams several benefits, including standardized risk assessment and bedside clinical decision support, thereby helping minimize the risk of severe PGD post-HTx.

The gut microbiome plays a crucial role in human health by influencing various physiological functions through complex interactions with the endocrine system. These interactions involve the production of metabolites, signaling molecules, and direct communication with endocrine cells, which modulate hormone secretion and activity. As a result, the microbiome can exert neuroendocrine effects and contribute to metabolic regulation, adiposity, and appetite control. Additionally, the gut microbiome influences reproductive health by altering levels of sex hormones such as estrogen and testosterone, potentially contributing to conditions like polycystic ovary syndrome (PCOS) and hypogonadism. Given these roles, targeting the gut microbiome offers researchers and clinicians novel opportunities to improve overall health and well-being. Probiotics, such as Lactobacillus and Bifidobacterium, are live beneficial microbes that help maintain gut health by balancing the microbiota. Prebiotics, non-digestible fibers, nourish these beneficial bacteria, promoting their growth and activity. When combined, probiotics and prebiotics form synbiotics, which work synergistically to enhance the gut microbiota balance and improve metabolic, immune, and hormonal health. This integrated approach shows promising potential for managing conditions related to hormonal imbalances, though further research is needed to fully understand their specific mechanisms and therapeutic potential.

An association between predicted heart mass (PHM) and post heart transplantation outcomes has been well established; however, there is limited data on the effect of donor PHM on recipients bridged with a durable left ventricular assist device (LVAD). This retrospective observational study seeks to challenge the theoretical benefit of oversizing donor hearts for recipients bridged with LVADs.

Analysis of the United Network for Organ Sharing database revealed 10,806 adult patients with 1 of 3 durable LVADs (HeartMate 2, HeartMate 3 [HM3], HeartWare Ventricular Assist Device) between January 1, 2015 and December 31, 2021. Baseline characteristics were compared between 7 equally sized groups based on donor-to-recipient PHM. Univariable and multivariable Cox regression analyses were constructed to evaluate the effect of PHM size-matching on the primary outcome of 1-year post-transplant survival. Further analyses were performed specifically on HM3 patients and with PHM as a continuous variable.

Multivariable analysis revealed that severely undersized donor hearts (PHM ratio <0.86) resulted in worse outcomes with respect to 1-year mortality (hazard ratio 1.30; confidence interval 1.03-1.64, p = 0.03). There was no significant benefit to oversizing donor hearts. Similar results were found in patients bridged to transplant with HM3.

Similar to prior studies on heart transplant recipients, recipients bridged with durable LVAD had worse outcomes when using severely undersized donor hearts. Oversized donor hearts did not significantly improve 1-year mortality, compared to size-matched references. These results were consistent in a subgroup analysis of patients bridged only with HM3 LVADs.

For heart transplantation, optimal donor-recipient matching is an important factor in the ongoing development of the United Network for Organ Sharing (UNOS) continuous distribution framework. Donor-recipient sex-mismatch has decreased since the 1990s, but this may be related to the risk posed by size mismatching, particularly when donor hearts are undersized. Thus, the impact of sex-mismatching, controlling for other factors including size mismatch, is uncertain.

Adult first-time, isolated heart transplant patients from the UNOS database between October 1, 1987 and December 31, 2022 were analyzed. Cohorts were separated into male and female recipients. Propensity score matching on known preoperative risk factors was performed. Equivalence testing via Two One-Sided Testing (TOST) was performed to assess between-arm equivalence in postoperative outcomes. Survival differences were measured by the between-arm ratio of restricted mean survival time and binary outcome differences by the odds ratio.

In the propensity-matched cohort, we found significant equivalence between arms in both male (TOST p < 0.001) and female (TOST p < 0.001) recipients for overall survival at all temporal end-points, postoperative treatment for rejection within 1 year, and predischarge dialysis.

Sex-mismatch in isolated heart transplantation confers no additional risk to postoperative outcomes when controlling for other factors, including size mismatch. Consequently, sex-mismatch should not factor into individual assessments of organ acceptance or be incorporated into any national organ allocation policy. Increasing the acceptance of sex-mismatched donors has the potential to expand the donor pool and increase female donor utilization.

This study evaluates the effects of pre-transplant transpulmonary gradient (TPG) and donor right ventricular mass (RVM) on outcomes following heart transplantation.

UNOS registry was queried to analyze adult recipients who underwent primary isolated heart transplantation from 1/1/2010 to 12/31/2018. The recipients were dichotomized into 2 groups based on their TPG at the time of transplantation, < 12 and ≥ 12 mmHg. The outcomes included 5-year survival and post-transplant complications. Propensity score-matching was performed. Subanalysis was performed to evaluate the effects of donor-recipient RVM matching, where a ratio < 0.85 was classified as undersized, 0.85-1.15 as size-matched, and > 1.15 as oversized.

We analyzed 17,898 isolated heart transplant recipients, and 5129 (28.7%) recipients had TPG ≥ 12 mmHg at the time of transplantation. The recipients with TPG ≥ 12 mmHg experienced significantly lower 5-year survival rates (78.4% vs 81.2%; P < 0.001) compared to the recipients with TPG < 12 mmHg, and this finding persisted in the propensity score-matched comparison. The recipients with TPG ≥ 12 mmHg experienced a higher rate of post-transplant dialysis and a longer duration of hospitalization. Oversizing the donor RVM considerably improved the 5-year survival among the recipients with TPG ≥ 12 mmHg, comparable to those with TPG < 12 mmHg.

Elevated pre-transplant TPG is associated with significantly reduced post-transplant survival. However, oversizing the donor RVM is associated with improved survival rates in recipients with elevated TPG, resulting in improved survival that is comparable to that of recipients with normal TPG. Therefore, careful risk stratification and donor matching among recipients with elevated TPG is essential to improve outcomes in this vulnerable population.

Cardiac fibrosis is increasingly recognized as a marker of worse outcomes in long-term follow-up after heart transplantation (HTX). We investigated the clinical determinants and biomarkers of focal and interstitial cardiac fibrosis as assessed with cardiac magnetic resonance (CMR).

Consecutive HTX recipients underwent CMR with late gadolinium enhancement for focal myocardial fibrosis and T1 mapping for interstitial fibrosis. We calculated the correlations of these findings with clinical parameters, history, biomarkers of fibrosis (B-type natriuretic peptide (BNP), growth differentiation factor-15, galectin-3 and soluble ligand ST2) and echocardiography.

Forty-eight HTX patients were included: median age 63 ± 13 years, 11 ± 6 years after heart transplantation. Only donor weight (p 0.044) and the rate of a > 30 % mismatch between donor and recipient weight (p 0.02) were significantly different in patients with vs. without late LGE. Extracellular volume (ECV) was correlated with the weight mismatch between donor and recipient (r = 0.32, p 0.04), resulting in a higher ECV for oversized donors. BNP was the only biomarker of the four studied that was correlated with interstitial fibrosis as assessed by ECV (r = 0.35, p 0.04). T1 relaxation time was correlated with treated acute cellular rejection grade ≥ 2 (ISHLT grading) (r = 0.34, p 0.02).

Both focal and interstitial fibrosis, as determined by CMR, after heart transplantation are correlated with donor and recipient weight mismatch. BNP was the only biomarker clinically relevant to interstitial cardiac fibrosis.

Cardiac volume-based estimation offers an alternative to donor-recipient weight ratio (DRWR) in pediatric heart transplantation (HT) but has not been correlated to posttransplant outcomes. We sought to determine whether estimated total cardiac volume (eTCV) ratio is associated with HT survival in infants.

The United Network for Organ Sharing database was used to identify infants (aged <1 year) who received HT in 1987-2020. Donor and recipient eTCV were calculated from weight using previously published data. Patient cohort was divided acc ording to the significant range of eTCV ratio; characteristics and survival were compared.

A total of 2845 infants were identified. Hazard ratio with cubic spline showed prognostic relationship of eTCV ratio and DRWR with the overall survival. The cut point method determined an optimal eTCV ratio range predictive of infant survival was 1.05 to 1.85, whereas no range for DRWR was predictive. Overall, 75.6% of patients had an optimal total cardiac volume ratio, while 18.1% were in the lower (LR) and 6.3% in the higher (HR) group. Kaplan-Meier analysis showed better survival for patients within the optimal vs LR (p = 0.0017) and a similar significantly better survival when compared to HR (p = 0.0053). The optimal eTCV ratio group (n = 2,151) had DRWR, ranging from 1.09 to 5; 34.3% had DRWR of 2% to 3%, and 5.0% had DRWR of >3.

Currently, an upper DRWR limit has not been established in infants. Therefore, determining the optimal eTCV range is important to identify an upper limit that significantly predicts survival benefit. This finding suggests a potential increase in donor pool for infant recipients since over 40% of donors in the optimal eTCV range include DRWR values >2 that are traditionally not considered for candidate listing.

Limited research has been conducted on sex disparities in heart transplant (HT). The aim of this review is to analyse the available evidence on the influence of sex and gender-related determinants in the entire HT process, as well as to identify areas for further investigation.

Although women make up half of the population affected by heart failure and related mortality, they account for less than a third of HT recipients. Reasons for this inequality include differences in disease course, psychosocial factors, concerns about allosensitisation, and selection or referral bias in female patients. Women are more often listed for HT due to non-ischaemic cardiomyopathy and have a lower burden of cardiovascular risk factors. Although long-term prognosis appears to be similar for both sexes, there are significant disparities in post-HT morbidity and causes of mortality (noting a higher incidence of rejection in women and of malignancy and cardiac allograft vasculopathy in men). Additional research is required to gain a better understanding of the reasons behind gender disparities in eligibility and outcomes following HT. This would enable the fair allocation of resources and enhance patient care.

Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized.

Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression.

Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation.

Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

 Predicted cardiac mass (PCM) has been well validated for size matching donor hearts to heart transplantation recipients. We hypothesized that cardiothoracic ratio (CTR) could be reflective of recipient-specific limits of oversizing, and sought to determine the utility of donor to recipient PCM ratio (PCMR) and CTR in predicting delayed chest closure after heart transplantation.

 A retrospective review of prospectively collected data on 38 consecutive heart transplantations performed at our institution from 2017 to 2020 was performed. Donor and recipient PCM were estimated using Multi-Ethnic Study of Atherosclerosis predictive models. Receiver operating characteristic analysis was performed to determine the discriminatory power of the ratio of PCMR to CTR in predicting delayed sternal closure.

 Of the 38 patients, 71.1% (27/38) were male and the median age at transplantation was 58 (interquartile range [IQR]: 47-62) years. Ischemic cardiomyopathy was present in 31.6% of recipients (12/38). Median recipient CTR was 0.63 [IQR: 0.59-0.66]. Median donor to recipient PCMR was 1.07 [IQR: 0.96-1.19], which indicated 7% oversizing. Thirteen out of 38 (34.2%) underwent delayed sternal closure. Primary graft dysfunction occurred in 15.8% (6/38). PCMR/CTR showed good discriminatory power in predicting delayed sternal closure [area under the curve: 80.4% (65.3-95.6%)]. PCMR/CTR cut-off of 1.7 offered the best trade-off between the sensitivity (69.6%) and specificity (91.7%).

 CTR could be helpful in guiding the recipient-specific extent of oversizing donor hearts. Maintaining the ratio of PCMR to CTR below 1.7 could avoid excessive oversizing of the donor heart.

Preoperative size matching is essential for both allogeneic and xenogeneic heart transplantation. In preclinical pig-to-baboon xenotransplantation experiments, porcine donor organs are usually matched to recipients by using indirect parameters, such as age and total body weight. For clinical use of xenotransplantation, a more precise method of size measurement would be desirable to guarantee a "perfect match." Here, we investigated the use of transthoracic echocardiography (TTE) and described a new method to estimate organ size prior to xenotransplantation.

Hearts from n = 17 genetically modified piglets were analyzed by TTE and total heart weight (THW) was measured prior to xenotransplantation into baboons between March 2018 and April 2022. Left ventricular (LV) mass was calculated according to the previously published method by Devereux et al. and a newly adapted formula. Hearts from n = 5 sibling piglets served as controls for the determination of relative LV and right ventricular (RV) mass. After explantation, THW and LV and RV mass were measured.

THW correlated significantly with donor age and total body weight. The strongest correlation was found between THW and LV mass calculated by TTE. Compared to necropsy data of the control piglets, the Devereux formula underestimated both absolute and relative LV mass, whereas the adapted formula yielded better results. Combining the adapted formula and the relative LV mass data, THW can be predicted with TTE.

We demonstrate reliable LV mass estimation by TTE for size matching prior to xenotransplantation. An adapted formula provides more accurate results of LV mass estimation than the generally used Devereux formula in the xenotransplantation setting. TTE measurement of LV mass is superior for the prediction of porcine heart sizes compared to conventional parameters such as age and total body weight.

In the last decades, outcomes significantly improved for both heart transplantation and LVAD. Heart transplantation remains the gold standard for the treatment of end stage heart failure and will remain for many years to come. The most relevant limitations are the lack of grafts and the effects of long-term immunosuppressive therapy that involve infectious, cancerous and metabolic complications despite advances in immunosuppression management. Mechanical circulatory support has an irreplaceable role in the treatment of end-staged heart failure, as bridge to transplant or as definitive implantation in non-transplant candidates. Although clinical results do not overcome those of HTx, improvement in the new generation of devices may help to reach the equipoise between the two therapies. This review will go through the evolution, current status and perspectives of both therapeutics.

(1) Background: Heart failure is an extremely impactful health issue from both a social and quality-of-life point of view and the rate of patients with this condition is destined to rise in the next few years. Transplantation remains the mainstay of treatment for end-stage heart failure, but a shortage of organs represents a significant problem that prolongs time spent on the waiting list. In view of this, the selection of donor and recipient must be extremely meticulous, considering all factors that could predispose to organ failure. One of the main considerations regarding heart transplants is the risk of graft rejection and the need for immunosuppression therapy to mitigate that risk. In this study, we aimed to assess the characteristics of patients who need immunosuppression treatment for rejection within one year of heart transplantation and its impact on mid-term and long-term mortality. (2) Methods: The United Network for Organ Sharing (UNOS) Registry was queried to identify patients who solely underwent a heart transplant in the US between 2000 and 2021. Patients were divided into two groups according to the need for anti-rejection treatment within one year of heart transplantation. Patients' characteristics in the two groups were assessed, and 1 year and 10 year mortality rates were compared. (3) Results: A total of 43,763 patients underwent isolated heart transplantation in the study period, and 9946 (22.7%) needed anti-rejection treatment in the first year. Patients who required treatment for rejection within one year after transplant were more frequently younger (49 ± 14 vs. 52 ± 14 years, p < 0.001), women (31% vs. 23%, p < 0.001), and had a higher CPRA value (14 ± 26 vs. 11 ± 23, p < 0.001). Also, the rate of prior cardiac surgery was more than double in this group (27% vs. 12%, p < 0.001), while prior LVAD (12% vs. 11%, p < 0.001) and IABP (10% vs. 9%, p < 0.01) were more frequent in patients who did not receive anti-rejection treatment in the first year. Finally, pre-transplantation creatinine was significantly higher in patients who did not need treatment for rejection in the first year (1.4 vs. 1.3, p < 0.01). Most patients who did not require anti-rejection treatment underwent heart transplantation during the new allocation era, while less than half of the patients who required treatment underwent transplantation after the new allocation policy implementation (65% vs. 49%, p < 0.001). Patients who needed rejection treatment in the first year had a higher risk of unadjusted 1 year (HR: 2.25; 95% CI: 1.88-2.70; p < 0.001), 5 year (HR: 1.69; 95% CI: 1.60-1.79; p < 0.001), and 10 year (HR: 1.47; 95% CI: 1.41-1.54, p < 0.001) mortality, and this was confirmed at the adjusted analysis at all three time-points. (4) Conclusions: Medical treatment of acute rejection was associated with significantly increased 1 year mortality compared to patients who did not require anti-rejection therapy. The higher risk of mortality was confirmed at a 10 year follow-up. Further studies and newer follow-up data are required to investigate the role of anti-rejection therapy in the heart transplant population.

The goal of this review was to summarize contemporary evidence surrounding sex differences in heart transplantation (HT).

Women have steadily comprised approximately 25% of waitlist candidates and HT recipients. This disparity is likely multifactorial with possible explanations including barriers in referral to advanced heart failure providers, implicit bias, and concerns surrounding sensitization. Women continue to experience higher waitlist mortality at the highest priority tiers. After HT, there are differences in post-transplant complications and outcomes. Future areas of study should include sex differences in noninvasive surveillance, renal outcomes after transplantation, and patient-reported outcomes. There are important sex-specific considerations that impact candidate selection, donor matching, waitlist and post-transplant outcomes. Concerted efforts are needed to improve referral patterns to ensure transplantation is allocated equally.

The predicted heart mass (PHM) ratio has recently emerged as a better metric for donor-to-recipient size-matching than weight ratios. It is unknown whether this applies to transplant candidates on left ventricular assist device (LVAD) support. Our study examines if PHM ratio is optimal for size-matching specifically in the LVAD patient population. Patients with LVAD who received a heart transplant from January 1997 to December 2020 in the Scientific Registry of Transplant Recipients database were studied. We compared 5 size-matching metrics, including donor-recipient ratios of weight, height, body mass index, body surface area, and PHM. Single and multivariable Cox proportional hazards models for 1-year mortality were calculated. Our sample consisted of 11,891 patients. In our multivariate analysis, we found that patients in the undersized group with PHM ratios <0.83 had a hazard ratio for 1-year mortality of 1.34 (95% confidence interval 1.08 to 1.65, p = 0.007) suggestive of increased mortality with the use of undersized donors. There was no statistical difference in mortality between the matched (PHM ratio 0.83 to 1.2) and oversized group (PHM ratio ≥1.2). In heart transplant recipients on LVAD support, the PHM ratio provides better risk stratification than other metrics. Use of undersized donor hearts with PHM ratio <0.83 confers higher 1-year mortality. Using oversized donor hearts for transplantation in recipients on LVAD support has no benefit.

Predicted heart mass ratio (PHMr) has been proposed as an optimal size metric in the selection of a donor heart for transplant; however, it is not known if the same size matching criteria pertains uniformly to all types of cardiomyopathies. Heart transplant recipients in the United Network for Organ Sharing registry database were categorized into 6 groups based on the type of cardiomyopathy, dilated, coronary artery disease, hypertrophic, restrictive, valvular and adult congenital heart disease. Patients in each group of etiology were stratified based on the PHMr into 5 groups: severely undersized <0.86, moderately undersized 0.86 to 0.94, matched 0.95 to 1.04, moderately oversized 1.05 to 1.24, and severely oversized >1.25. The survival and cause of death of patients in each etiology group were reviewed. The United Network for Organ Sharing registry database from January 1987 to July 2021 included 53,573 patients who received a heart transplant. Compared with patients with size matched hearts, recipients with dilated (hazard ratio 1.17, p = 0.001) and valvular (hazard ratio 1.79, p = 0.032) cardiomyopathy who had an undersized heart with PHMr <0.86 had decreased survival. In addition, the survival of patients with hypertrophic or restrictive cardiomyopathy and adult congenital heart disease was not affected by size matching based on the PHMr (0.601 and 0.079, respectively, p = 0.873). In conclusion, our analysis suggests that the size matching criteria based on PHMr may not be uniform to all patients across various etiologies of cardiomyopathy. Therefore, the data can be used to increase the acceptance rate of donor hearts, particularly, for patients with hypertrophic, restrictive cardiomyopathy and congenital heart disease in which size matching is less significant for survival outcome.

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.

Donor/recipient size matching is paramount in heart transplantation. Body weight, height, body mass index, body surface area, and predicted heart mass (PHM) ratios are generally used in size matching. Precise size matching is important to achieve better clinical outcomes. This study aims to determine the donor/recipient ascending aortic diameter (AAoD) ratio as a metric for donor selection and its effect on postoperative clinical outcomes in heart transplant patients.

We retrospectively reviewed all consecutive patients who underwent heart transplantation from January 2015 to December 2018. A cutoff value of 0.8032 for the donor/recipient AAoD ratio (independent variable for the primary endpoint during unmatched cohort analysis) was determined for predicting in-hospital mortality. The patients were divided into two groups based on the cutoff value. Group A, AAoD < 0.8032 (n = 96), and Group B, AAoD > 0.8032 (n = 265). A propensity score-matched (PSM) study was performed to equalize the two groups comprising 77 patients each in terms of risk. A Cox regression model was developed to identify the independent preoperative variables affecting the primary end-point. The primary endpoint was all-cause in-hospital mortality.

A total of 361 patients underwent heart transplantation during the given period. On the multivariate analysis, donor/recipient PHM ratio [HR 16.907, 95% confidence interval (CI) 1.535-186.246, P = 0.021], donor/recipient AAoD ratio < 0.8032 (HR 5.398, 95% CI 1.181-24.681, P = 0.030), and diabetes (HR 3.138, 95% CI 1.017-9.689, P = 0.047) were found to be independent predictors of in-hospital mortality. Group A had higher 3-year mortality than Group B (P = 0.022). The surgery time was longer and postoperative RBC, plasma, and platelets transfusion were higher in Group A (P < 0.05). Although not statistically significant the use of continuous renal replacement therapy (P = 0.054), and extracorporeal membrane oxygenation (P = 0.086), was realatively higher, and ventilation time (P = 0.079) was relatively longer in Group A.

The donor/recipient AAoD ratio is a potential metric for patient matching and postoperative outcomes in heart transplantation. A donor/recipient AAoD ratio > 0.8032 could improve post-heart transplantation outcomes and donor heart utilization.

Current donor-recipient size matching guidelines rely primarily on body weight, with no specified oversizing cutoff values. Recent literature has explored predicted total ventricular mass matching over body weight matching. We aim to explore the impact of total ventricular mass oversizing on heart transplant outcomes.

The United Network for Organ Sharing database was queried for adults who underwent primary heart transplant from 1997 to 2017. By using validated equations, donor-recipient total ventricular mass mismatch was calculated. Donor-recipient pairs were divided into 3 groups by total ventricular mass mismatch. Post-heart transplant 1-year survival was analyzed using the Kaplan-Meier method and Cox proportional hazards models. We also investigated post-heart transplant complications, independent predictors for mortality, donor-recipient sex mismatch, and donor-recipient body habitus in total ventricular mass mismatch greater than +50%.

A total of 34,455 donor-recipient pairs were included. Fractional polynomial regression demonstrated increased the risk of mortality with higher total ventricular mass mismatch. Total ventricular mass mismatch of +48.3% maximized the Youden Index. Donor-recipient pairs were subsequently grouped by total ventricular mass mismatch as -20% to +30%, +30% to +50%, and greater than +50%. Total ventricular mass mismatch greater than +50% was an independent risk factor for 1-year mortality (hazard ratio, 1.40, P = .004) and was associated with increased postoperative stroke (P = .002). Some 80.3% of these recipients were smaller female patients with male donors. Total ventricular mass mismatch from +30% to +50% was not associated with worse survival (P = .17).

Total ventricular mass mismatch greater than +50% is associated with worse 1-year survival, although this group comprises a small portion of heart transplant. total ventricular mass mismatch from +30% to +50% is not associated with worse survival. These outcomes should be considered in selecting donors and in efforts to expand the potential donor pool.

Implantation of an appropriately sized donor heart is critical for optimal outcomes after heart transplantation. Although predicted heart mass has recently gained consideration, there remains a need for improved granularity in size matching, particularly among small donor hearts. We sought to determine if indexed donor cardiac output is a sensitive metric to assess the adequacy of a donor heart for a given recipient.

A retrospective analysis was performed (2003-2021) in isolated orthotopic heart transplant recipients from the United Network for Organ Sharing database. Donor cardiac output was divided by recipient body surface area to compute cardiac index (donor cardiac index). Predicted heart mass ratio was computed as donor/recipient predicted heart mass. The primary outcome was mortality 1 year after transplant.

Among transplant recipients, median donor cardiac output was 7.3 (5.8-9.0) liters per minute and donor cardiac index was 3.7 (3.0-4.6) liters per minute/m2. Predicted heart mass ratio was 1.01 (0.91-1.13). After multivariable adjustment, higher donor cardiac index was associated with lower 1-year mortality risk (odds ratio, 0.92, P = .042). Recipients with predicted heart mass ratio less than 0.80 (n = 255) had a lower median donor cardiac index than those with a predicted heart mass ratio of 0.80 or greater (3.2 vs 3.7, P < .001). As predicted, heart mass ratio became smaller and the association between donor cardiac index and 1-year mortality became progressively stronger.

Higher donor cardiac index was associated with a lower probability of 1-year mortality among patients undergoing heart transplantation and served to further quantify mortality risk among those with a small predicted heart mass ratio. Donor cardiac index appears to be an effective tool for size matching and may serve as an adjunctive strategy among small donor hearts with a low predicted heart mass ratio.

Total predicted heart mass (PHM) is the recommended metric to assess donor-recipient size matching in patients undergoing heart transplantation. Separately measuring right ventricular (RV) and left ventricular (LV) PHM may improve risk prediction of 1-year graft failure.

Adult heart transplant recipients from the UNOS database from 2000 to 2018 were included in the study. LV and RV PHM were modeled as restricted cubic splines. The association with 1-year graft failure was determined using adjusted Cox regression. The risk reclassification of using both LV and RV PHM versus total PHM was assessed using the net reclassification index.

A total of 34 976 recipients were included. We observed a U-shaped association between total PHM and 1-year graft failure, such that risk increased for hearts undersized by >15% and those oversized by more than 27%. Graft failure incrementally increased when LV PHM was undersized by more than 5% and when RV was oversized by >20%. There was 1.5-fold greater risk of graft failure for an LV undersized by >26% or an RV oversized by more than 40%. Using LV and RV PHM risk-assessment separately led to a net reclassification index=8.5% ([95% CI, 5.3%-11.7%], nonevent net reclassification index=9.1%, event net reclassification index=-0.6%).

The association between donor-recipient PHM match and the risk of graft failure after heart transplantation can be further understood as risk attributable to LV undersizing and RV oversizing. Assessing LV and RV PHM separately instead of total PHM could further refine the methods used to match donors and recipients for heart transplantation, minimize the risk of 1-year graft failure, and increase the use of donor organs.

Extended criteria donors (ECD) hearts have demonstrated acceptable outcomes in select populations. However, their use in patients undergoing simultaneous heart-kidney transplantation (SHKT) has not been explored. This study is assessed the effect of ECD hearts in patients undergoing SHKT vs isolated heart transplants (IHT).

The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing IHT and SHKT. Patients were stratified by receipt of ECD heart, defined as donor hearts failing to meet established acceptable use criteria. Interaction effects between ECDs and simultaneous kidney transplants were generated. Postoperative outcomes, risk factors, and patient/graft survival were compared across cohorts using Fine-Gray, Kaplan Meier, and Cox Proportional Hazards analyses.

Among 26,207 patients included, 1,766 (7%) underwent SHKT. ECD hearts were used in 25% of both IHT and SHKT cohorts. Five-year survival among SHKT/ECD patients (67.3%) was reduced (p < 0.01) compared to SHKT/SDC (80.3%), IHT/ECD (78.1%) and IHT/SCD (80.0%) groups. Among SHKT patients, use of ECD hearts was associated with increased risk (SHR: 1.48; p < 0.01) of renal graft failure compared to SCD hearts. Among SHKT patients, receipt of an ECD heart, and individual ECD criteria (coronary disease and size mismatch >20%), predicted mortality. The interaction effect of receiving both ECD and SHKT predicted mortality and graft failure (HR 1.43; p < 0.01).

Patients undergoing SHKT with an ECD heart face greater risks of mortality and graft failure in comparison to those undergoing IHT with ECD hearts. Careful selection of donor organs should be applied to this high-risk cohort.

Pretransplant obesity and higher pulmonary vascular resistance (PVR) are risk factors for death after heart transplant. However, it remains unclear whether appropriate donor-to-recipient size matching using predicted heart mass (PHM) is associated with lower risk.

To investigate the association of size matching using PHM with risk of death posttransplant among patients with obesity and/or higher PVR.

All adult patients (>18 years) who underwent heart transplant between 2003 and 2022 with available information using the United Network for Organ Sharing cohort database. Multivariable Cox models and multivariable-adjusted spline curves were used to examine the risk of death posttransplant with PHM matching. Data were analyzed from October 2022 to March 2023.

Recipient's body mass index (BMI) in categories (<18.0 [underweight], 18.1-24.9 [normal weight, reference], 25.0-29.9 [overweight], 30.0-34.9 [obese 1], 35-39.9 [obese 2], and ≥40.0 [obese 3]) and recipient's pretransplant PVR in categories of less than 4 (29 061 participants), 4 to 6 (2842 participants), and more than 6 Wood units (968 participants); and less than 3 (24 950 participants), 3 to 5 (6115 participants), and 5 or more (1806 participants) Wood units.

All-cause death posttransplant on follow-up.

The mean (SD) age of the cohort of 37 712 was 52.8 (12.8) years, 27 976 (74%) were male, 25 342 were non-Hispanic White (68.0%), 7664 were Black (20.4%), and 3139 were Hispanic or Latino (8.5%). A total of 12 413 recipients (32.9%) had a normal BMI, 13 849 (36.7%) had overweight, and 10 814 (28.7%) had obesity. On follow-up (median [IQR] 5.05 [0-19.4] years), 12 785 recipients (3046 female) died. For patients with normal weight, overweight, or obese 2, receiving a PHM-undermatched heart was associated with an increased risk of death (normal weight hazard ratio [HR], 1.20; 95% CI, 1.07-1.34; overweight HR, 1.12; 95% CI, 1.02-1.23; and obese 2 HR, 1.07; 95% CI, 1.01-1.14). Moreover, patients with higher pretransplant PVR who received an undermatched heart had a higher risk of death posttransplant in multivariable-adjusted spline curves in graded fashion until appropriately matched. In contrast, risk of death among patients receiving a PHM-overmatched heart did not differ from the appropriately matched group, including in recipients with an elevated pretransplant PVR.

In this cohort study, undermatching donor-to-recipient size according to PHM was associated with higher posttransplant mortality, specifically in patients with normal weight, overweight, or class II obesity and in patients with elevated pretransplant PVR. Overmatching donor-to-recipient size was not associated with posttransplant survival.

Historically, transplantation of a female donor heart to male recipient has been viewed with caution given evidence of suboptimal outcomes, particularly in special populations such as patients with pulmonary hypertension or those supported by ventricular assist devices. However, the use of predicted heart mass ratio for donor-recipient size matching demonstrated that the size of the organ rather than sex of the donor was most responsible for the outcomes. With the advent of the predicted heart mass ratio, avoiding female donor hearts for male recipients is no longer justified and may result in unnecessary waste of available organs. In this review, we highlight the value of donor-recipient sizing by predicted heart mass ratio and summarize the evidence of different approaches to the donor-to-recipient size and sex matching. We conclude that the utilization of predicted heart mass is currently considered a preferred method of matching heart donors and recipients.