Symptom Distress Before and After Heart Transplantation - A Longitudinal 5-Year Follow-Up.

INTRODUCTION: Symptom distress after heart transplantation (HTx) is a significant problem causing uncertainty, low self-efficacy, and psychological distress. Few studies have addressed self-reported symptoms. The aim was to explore self-reported symptom distress from time on the waiting list to 5 years after HTx and its association with self-reported psychological well-being, chronic pain, and fatigue in order to identify possible predictors of psychological or transplant specific well-being. METHODS: This multicenter, longitudinal cohort study includes 48 heart recipients (HTRs), 12 women, and 36 men, with a median age of 57 years followed from pretransplant to 5 years post-transplant. Symptom distress was explored by means of four instruments measuring psychological general wellbeing, transplant specific wellbeing, pain, and fatigue. RESULTS: Transplant specific well-being for the whole improved in a stepwise manner during the first 5 years compared to pretransplant. Heart transplant recipients with poor psychological wellbeing were significantly more burdened by symptom distress, in particular sleep problems and fatigue, for up to 5 years after HTx, and their transplant-specific well-being never improved compared to baseline. The prevalence of pain varied from 40% to 60% and explained a significant proportion of the variance in transplant-specific well-being, while psychological general well-being was mainly predicted by overall symptom distress. CONCLUSION: The presence of distressing symptoms explains a significant proportion of poor psychological wellbeing both among HTRs reporting chronic pain and those without pain.

Reactive Oxygen Species Responsive Multifunctional Fusion Extracellular Nanovesicles: Prospective Treatments for Acute Heart Transplant Rejection.

Heart transplantation offers life-saving treatment for patients with end-stage heart failure; however, ischemia-reperfusion injury (IRI) and subsequent immune responses remain significant challenges. Current therapies primarily target adaptive immunity, with limited options available for addressing IRI and innate immune activation. Although plant-derived vesicle-like nanoparticles show promise in managing diseases, their application in organ transplantation complications is unexplored. Here, this work develops a novel reactive oxygen species (ROS)-responsive multifunctional fusion extracellular nanovesicles carrying rapamycin (FNVs@RAPA) to address early IRI and Ly6C+Ly6G- inflammatory macrophage-mediated rejection in heart transplantation. The FNVs comprise Exocarpium Citri grandis-derived extracellular nanovesicles with anti-inflammatory and antioxidant properties, and mesenchymal stem cell membrane-derived nanovesicles expressing calreticulin with macrophage-targeting ability. A novel ROS-responsive bio-orthogonal chemistry approach facilitates the active targeting delivery of FNVs@RAPA to the heart graft site, effectively alleviating IRI and promoting the polarization of Ly6C+Ly6G- inflammatory macrophages toward an anti-inflammatory phenotype. Hence, FNVs@RAPA represents a promising therapeutic approach for mitigating early transplantation complications and immune rejection. The fusion-targeted delivery strategy offers superior heart graft site enrichment and macrophage-specific targeting, promising improved transplant outcomes.

Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation.

BACKGROUND: Transplant recipients commonly harbor multidrug-resistant organisms (MDROs), as a result of frequent hospital admissions and increased exposure to antimicrobials and invasive procedures. AIM: To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition, as well as the impact of MDRO acquisition on intensive care unit (ICU) and hospital length of stay, and on ICU mortality and 1-year mortality post heart transplantation. METHODS: This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period (2013-2022) in a single transplantation center. Data was collected regarding MDROs commonly encountered in critical care. RESULTS: Among the 98 transplanted patients (70% male), about a third (32%) acquired or already harbored MDROs upon transplantation (MDRO group), while two thirds did not (MDRO-free group). The prevalent MDROs were Acinetobacter baumannii (14%), Pseudomonas aeruginosa (12%) and Klebsiella pneumoniae (11%). Compared to MDRO-free patients, the MDRO group was characterized by higher body mass index (P = 0.002), higher rates of renal failure (P = 0.017), primary graft dysfunction (10% vs 4.5%, P = 0.001), surgical re-exploration (34% vs 14%, P = 0.017), mechanical circulatory support (47% vs 26% P = 0.037) and renal replacement therapy (28% vs 9%, P = 0.014), as well as longer extracorporeal circulation time (median 210 vs 161 min, P = 0.003). The median length of stay was longer in the MDRO group, namely ICU stay was 16 vs 9 d in the MDRO-free group (P = 0.001), and hospital stay was 38 vs 28 d (P = 0.006), while 1-year mortality was higher (28% vs 7.6%, log-rank-χ 2: 7.34). CONCLUSION: Following heart transplantation, a predominance of Gram-negative MDROs was noted. MDRO acquisition was associated with higher complication rates, prolonged ICU and total hospital stay, and higher post-transplantation mortality.

Impact of Age of Heart Transplant Program on Patient Survival and Post-Transplant Outcomes.

BACKGROUND: The relationship between age of a heart transplant (HT) program and outcomes has not been explored. METHODS: We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. RESULTS: Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p < 0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p < 0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p < 0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p < 0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). CONCLUSION: Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.

European Society for Organ Transplantation (ESOT) Consensus Statement on the Use of Non-invasive Biomarkers for Cardiothoracic Transplant Rejection Surveillance.

While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.

Lipoprotein (a) and lipid-lowering treatment from the perspective of a cardiac surgeon. An impact on the prognosis in patients with aortic valve replacement and after heart transplantation.

Lipoprotein(a) is a recognized risk factor for ASCVD. There is still no targeted therapy for Lp(a), however, drugs such as pelacarsen, olpasiran, zerlasiran, lepodisiran and muvalaplin are in clinical trials and have been shown to be effective in significantly reducing Lp(a) levels. Moreover, elevated Lp(a) levels significantly affect the prognosis of patients after aortic valve replacement (AVR) and heart transplantation (HTx). Therefore, the assessment of Lp(a) concentration in these patients will allow for a more accurate stratification of their cardiovascular risk, and the possibility of lowering Lp(a) will allow for the optimization of this risk. In this article, we summarized the most important information regarding the role of Lp(a) and lipid-lowering treatment in patients after AVR and HTx.

Donation After Circulatory Death Heart Transplantation: A Narrative Review.

Heart transplantation is the definitive treatment for refractory, end-stage heart failure. The number of patients awaiting transplantation far exceeds available organs. In an effort to expand the donor pool, donation after circulatory death (DCD) heart transplantation has garnered renewed interest. Unlike donation after brain death, DCD donors do not meet the criteria for brain death and are dependent on life-sustaining therapies. Procurement can include a direct strategy or a normothermic regional perfusion, whereby there is restoration of perfusion to the organ before explantation. There are new developments in cold storage and ex vivo perfusion strategies. Since its inception, there has been a steady improvement in post-transplant outcomes, largely attributed to advancements in operative and procurement strategies. In this narrative review, the authors address the unique considerations of DCD heart transplantation, including withdrawal of care, the logistics of procuring and resuscitating organs, outcomes compared with standard donation after brain death, and ethical considerations.

Comparison of Cardiac Allograft Vasculopathy Incidence Between Simultaneous Multi-Organ and Isolated Heart Transplant Recipients in the United States.

BACKGROUND: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multi-organ transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multi-organ heart transplants in the contemporary era. METHODS: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary endpoint was the development of angiographic CAV within 5 years of follow-up. RESULTS: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multi-organ heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ) and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years and 74% were male. There were no significant between-group differences in cold ischemic time between the groups. The incidence of acute rejection during the first year after transplant was significantly lower in the multi-organ group (18% vs. 33%, p<0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multi-organ group (p<0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multi-organ heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio=0.76, 95% confidence interval: 0.66-0.88, p<0.01). CONCLUSIONS: Simultaneous multi-organ heart transplantation is associated with significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era.

Intra-operative Risk Factors Affecting Mortality after Heart Transplantation: A Referral Center Experience in Iran.

Background: Heart transplantation is the preferred treatment for end-stage heart failure. This study investigated the intra-operative risk factors affecting post-transplantation mortality. Methods: This single-center retrospective cohort study examined 239 heart transplant patients over eight years, from 2011-2019, at the oldest dedicated cardiovascular center, Shahid Rajaee Hospital (Tehran, Iran). The primary evaluated clinical outcomes were rejection, readmission, and mortality one month and one year after transplantation. For data analysis, univariate logistic regression analyses were conducted. Results: In this study, 107 patients (43.2%) were adults, and 132 patients (56.8%) were children. Notably, reoperation due to bleeding was a significant predictor of one-month mortality in both children (OR=7.47, P=0.006) and adults (OR=172.12, P<0.001). Moreover, the need for defibrillation significantly increased the risk of one-month mortality in both groups (children: OR=38.00, P<0.001; adults: OR=172.12, P<0.001). Interestingly, readmission had a protective effect against one-month mortality in both children (OR=0.02, P<0.001) and adults (OR=0.004, P<0.001). Regarding one-year mortality, the use of extracorporeal membrane oxygenation (ECMO) was associated with a higher risk in both children (OR=7.64, P=0.001) and adults (OR=12.10, P<0.001). For children, reoperation due to postoperative hemorrhage also increased the risk (OR=5.14, P=0.020), while defibrillation was a significant risk factor in both children and adults (children: OR=22.00, P<0.001; adults: OR=172.12, P<0.001). The median post-surgery survival was 22 months for children and 24 months for adults. Conclusion: There was no correlation between sex and poorer outcomes. Mortality at one month and one year after transplantation was associated with the following risk factors: the use of ECMO, reoperation for bleeding, defibrillation following cross-clamp removal, and Intensive Care Unit (ICU) stay. Readmission, on the other hand, had a weak protective effect.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus.

Prevention and rehabilitation after heart transplantation: A clinical consensus statement of the European Association of Preventive Cardiology, Heart Failure Association of the ESC, and the European Cardio Thoracic Transplant Association, a section of ESOT.

Little is known either about either physical activity patterns, or other lifestyle-related prevention measures in heart transplantation (HTx) recipients. The history of HTx started more than 50 years ago but there are still no guidelines or position papers highlighting the features of prevention and rehabilitation after HTx. The aims of this scientific statement are (i) to explain the importance of prevention and rehabilitation after HTx, and (ii) to promote the factors (modifiable/non-modifiable) that should be addressed after HTx to improve patients' physical capacity, quality of life and survival. All HTx team members have their role to play in the care of these patients and multidisciplinary prevention and rehabilitation programmes designed for transplant recipients. HTx recipients are clearly not healthy disease-free subjects yet they also significantly differ from heart failure patients or those who are supported with mechanical circulatory support. Therefore, prevention and rehabilitation after HTx both need to be specifically tailored to this patient population and be multidisciplinary in nature. Prevention and rehabilitation programmes should be initiated early after HTx and continued during the entire post-transplant journey. This clinical consensus statement focuses on the importance and the characteristics of prevention and rehabilitation designed for HTx recipients.

Application of nanomaterials in heart transplantation: a narrative review.

Background and Objective: Heart transplantation (HT) is a therapeutic option for end-stage heart disease. Still, it faces many challenges, especially the shortage of donor sources and the poor durability of grafts, which are the two critical issues. In this review, we generalize the application of existing nanomedicine technologies in donor management as well as prevention and diagnosis of post-transplantation complications, also including the current preclinical studies of nanomaterials in cardiac tissue engineering and gene-editing xeno-donor grafts. Finally, we discuss the remaining problems and future directions of nanomaterials in the field of HT. Methods: A narrative review using current search of the most recent literature on the topic. The terms "nanomaterials", "nano medicine'', "Heart transplantation (HT)", "Nano-drug delivery system (NDDS)" or their combination were searched in PubMed and Google Scholar. The specified timeframe began from 1990, and we prioritized publications mainly from the last 10 years. Key Content and Findings: Nano-systems integrating therapeutic and diagnostic functions have been applied to cardiovascular diseases (CVDs) with their unique advantages in multiple fields such as drug delivery, tissue engineering, gene editing, imaging, biomarker editing, and many other aspects. In terms of transplantation, the preservation, transportation, and pretreatment of donor hearts machine perfusion (MP) provide the possibility for nano-systems with unique features, and therapeutic and diagnostic functions to be directly and passively targeted in order to improve the functional status of the transplanted organs or to increase the ability to tolerate the graft of patients. The development of nano-imaging, nanosensor, and nano biomarker technologies are also being applied to monitor the status of transplant recipients for early prevention and treatment of post-transplantation-related complications. Nanomaterials combined with cardiac tissue engineering and gene editing technologies could also expand graft sources and alleviate donor shortages. Conclusions: Although the overall research on nanomaterial applications in the field of HT is in its infancy, its role in improving the prognosis of transplant recipients and breaking the current dilemma of HT is clear. However, before nanotechnologies can be translated into clinical applications in the future, they must be aimed at ensuring the drug delivery system's safety and pose a challenge in the direction of the ability to intervene with multiple drugs in combination.

Diagnosis and cardiac transplantation of a Carney syndrome-induced cardiac myxoma combined with dilated cardiomyopathy: a case report.

BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.

Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) mutations, an aging trait, has been associated with progression of cardiovascular disease and development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart transplantation outcomes. OBJECTIVES: To determine prevalence of CHIP mutations in heart transplantation and their association with long-term outcomes including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. METHODS: We conducted a mixed retrospective-prospective observational study of heart transplant recipients with targeted sequencing for CHIP mutations (Variant allele frequency (VAF) of ≥2%). The primary composite outcome was first occurrence of CAV grade ≥2, graft failure, malignancy, cardiac re-transplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. RESULTS: Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%) followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%) and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP was not associated with the primary outcome which occurred in 44 (46.3%) patients (HR=0.487; 95%CI:0.197-1.204; p=0.119), malignancy alone or death. CONCLUSION: We demonstrated no association between CHIP mutations and post-transplant outcomes including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence on the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after heart transplantation.

A challenging case of eosinophilic myocarditis leading to heart failure and transplantation.

The large spectrum of etiologies, severities, and histologic appearances of eosinophilic myocarditis (EoM) poses challenges to its diagnosis and management. Endomyocardial biopsy is the current gold standard for diagnosis. However, cardiovascular magnetic resonance imaging is becoming more frequently used to diagnose acute myocarditis because of enhanced sensitivity when compared to histopathologic examination, and its less invasive nature. We report a complicated case of EoM in a male in his mid-thirties that led to fulminant cardiogenic shock that required immunosuppressive therapy on day 5 of admission and implantation of a left ventricular assist device (LVAD) on day 30. EoM was diagnosed on histopathologic examination of the resected fragment of the left ventricular myocardium. Nine months after the initial presentation, the patient ultimately required heart transplantation. The explanted heart showed minimal residual interstitial inflammation with evidence of mildly active intimal arteritis and patchy areas of interstitial fibrosis. In this report, we describe our patient's clinical features and correlate them with imaging and histopathologic findings to illustrate the difficulty in diagnosing EoM, particularly in this complicated patient that ultimately required heart transplantation. The diagnosis can be challenging due to the variable histopathologic features, clinical presentation, and utilization of therapeutic medications and devices.

A Comprehensive Excursus of the Roles of Echocardiography in Heart Transplantation Follow-Up.

Current guidelines for the care of heart transplantation recipients recommend routine endomyocardial biopsy and invasive coronary angiography as the cornerstones in the surveillance for acute rejection (AR) and coronary allograft vasculopathy (CAV). Non-invasive tools, including coronary computed tomography angiography and cardiac magnetic resonance, have been introduced into guidelines without roles of their own as gold standards. These techniques also carry the risk of contrast-related kidney injury. There is a need to explore non-invasive approaches providing valuable information while minimizing risks and allowing their application independently of patient comorbidities. Echocardiographic examination can be performed at bedside, serially repeated, and does not carry the burden of contrast-related kidney injury and procedure-related risk. It provides comprehensive assessment of cardiac morphology and function. Advanced echocardiography techniques, including Doppler tissue imaging and strain imaging, may be sensitive tools for the detection of minor myocardial dysfunction, thus providing insight into early detection of AR and CAV. Stress echocardiography may offer a valuable tool in the detection of CAV, while the assessment of coronary flow reserve can unravel coronary microvascular impairment and add prognostic value to conventional stress echocardiography. The review highlights the role of Doppler echocardiography in heart transplantation follow-up, weighting advantages and limitations of the different techniques.

Trajectory of Diastolic Function after Heart Transplantation as Assessed by Left Atrial Deformation Analysis.

Diastolic dysfunction (DD) is a prevalent and clinically significant complication after heart transplantation (HTX). We aimed to characterize the diastolic function of HTX recipients with both short-term and long-term follow-ups by applying left atrial (LA) deformation analysis. We consecutively enrolled and followed up with 33 HTX patients. Three assessments were performed one month, 3-5 months, and 3-5 years after surgery. Beyond conventional echocardiographic measurements, apical four-chamber views optimized for speckle tracking analysis were acquired and post-processed by dedicated software solutions (TomTec AutoStrain LA and LV). Left atrial phasic functions were characterized by reservoir, conduit, and contraction strains. We categorized diastolic function according to current guidelines (normal diastolic function, indeterminate, DD). At the first assessment, nine (27%) patients were in the DD category, and eleven (33%) were indeterminate. At the second assessment, only one patient (3%) remained in the DD category and six (18%) were indeterminate. At the third assessment, 100% of patients were categorized as having normal diastolic function. LA reservoir strain gradually increased over time. LA contraction strain significantly improved from the second to the third assessment. We found a correlation between the LA reservoir strain and NT-proBNP (r = 0.40, p < 0.05). DD is prevalent immediately after HTX but rare until the end of the first postoperative quarter. Speckle tracking analysis enables the characterization of LA phasic functions that may reflect both short- and long-term changes in diastolic function and correlate with NT-proBNP.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. METHODS: We included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. RESULTS: Among 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. CONCLUSION: Cardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Donation After Circulatory Death Heart Transplant: Current State and Future Directions.

Orthotopic heart transplant is the gold standard therapeutic intervention for patients with end-stage heart failure. Conventionally, heart transplant has relied on donation after brain death for organ recovery. Donation after circulatory death (DCD) is the donation of the heart after confirming that circulatory function has irreversibly ceased. DCD-orthotopic heart transplant differs from donation after brain death-orthotopic heart transplant in ways that carry implications for widespread adoption, including differences in organ recovery, storage and ethical considerations surrounding normothermic regional perfusion with DCD. Despite these differences, DCD has shown promising early outcomes, augmenting the donor pool and allowing more individuals to benefit from orthotopic heart transplant. This review aims to present the current state and future trajectory of DCD-heart transplant, examine key differences between DCD and donation after brain death, including clinical experiences and innovations in methodologies, and address the ongoing ethical challenges surrounding the new frontier in heart transplant with DCD donors.