Animal models for partial heart transplantation.

BACKGROUND: Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression. AIMS: Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non-human primates. MATERIALS & METHODS: This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon. RESULTS: Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non-human primate partial heart xenotransplantation. DISCUSSION: Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open-heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open-heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation. CONCLUSIONS: Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants.

Combined en bloc heart and liver organ procurement.

A combined heart+liver transplant is the only option for survival in some patients with end-stage combined cardiac and hepatic disease. These patients may suffer from congenital or acquired cardiac disease. The potential aetiologies of the associated hepatic disease are heterogeneous and include systemic disease that impacts the liver as well as venous congestion in patients with functionally univentricular circulation. In the latter scenario, patients with functionally univentricular circulation often require complex cardiac reconstruction in the setting of a cardiac transplant after staged palliation. During cardiac procurement, our approach is to dissect the entire ascending aorta and aortic arch in continuity; the entire superior caval vein and innominate vein in continuity; and the pulmonary arteries from hilum to hilum if the donor is not a candidate for recovery of the lungs. The cardiac and abdominal organ procurement teams work in parallel during dissection and combined en bloc cardio-hepatectomy. This technique minimizes exposure of both organs to cold ischaemia. This video tutorial demonstrates the key steps for combined en bloc heart+liver organ procurement.

Heart Transplantation in a Patient With Rheumatic Heart Disease and Severe Left Atrial Calcification.

A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

In vivo mitral valve repair for the transplanted donor heart in orthotopic heart transplantation.

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation. Because of the difficulty in weaning from cardiopulmonary bypass, a second aortic cross-clamp was applied, and we detached the inferior vena cava and the right side of the left atrial anastomosis to approach the mitral valve, obtaining a satisfactory exposure. No abnormalities were observed in the mitral valve leaflets, annulus or subvalvular apparatus. Subsequent in vivo mitral annuloplasty using prosthetic full ring successfully controlled the regurgitation, and the patient was easily weaned from cardiopulmonary bypass. She discharged to home with good mitral valve and cardiac functions. And the patient has been doing well without any recurrence of MR or heart failure for over a year after surgery.

Noteworthy in Cardiothoracic Surgery 2023.

Noteworthy in Cardiothoracic Surgery 2023 summarizes a few of the most high-impact trials and provocative trends in cardiothoracic surgery and transplantation this past year. Transplantation using organs procured from donation after circulatory death (DCD) continues to increase, and the American Society of Transplant Surgeons released recommendations on best practices in 2023. We review a summary of data on the impact of DCD on heart and lung transplantation. There has been increased interest in extracorporeal life support (ECLS), particularly after the COVID-19 pandemic, and we review the results of the highly discussed ECLS-SHOCK trial, which randomized patients in cardiogenic shock with planned revascularization to ECLS vs usual care. With improving survival outcomes in complex aortic surgery, there is a need for higher-quality evidence to guide which cooling and cerebral perfusion strategies may optimize cognitive outcomes in these patients. We review the short-term outcomes of the GOT ICE trial (Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest), a multicenter, randomized controlled trial of three different nadir temperatures, evaluating outcomes in cognition and associated changes in functional magnetic resonance imaging. Finally, both the Society of Thoracic Surgeons (STS) and the American College of Cardiology, American Heart Association, American College of Chest Physicians and Heart Rhythm Society (ACC/AHA/ACCP/HRS) updated atrial fibrillation guidelines in 2023, and we review surgically relevant updates to the guidelines and the evidence behind them.

Macrophage-derived extracellular vesicles alter cardiac recovery and metabolism in a rat heart model of donation after circulatory death.

Conditions to which the cardiac graft is exposed during transplantation with donation after circulatory death (DCD) can trigger the recruitment of macrophages that are either unpolarized (M0) or pro-inflammatory (M1) as well as the release of extracellular vesicles (EV). We aimed to characterize the effects of M0 and M1 macrophage-derived EV administration on post-ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20 min aerobic perfusion, followed by 27 min global, warm ischaemia or continued aerobic perfusion and 60 min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0-macrophage-dervied EV; (4) ischaemia with M1-macrophage-derived EV. Post-ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1-EV hearts, but not in M0-EV hearts, compared to non-ischaemic hearts (p < 0.05). In parallel with the reduced functional recovery in M1-EV versus M0-EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0- and M1-macrophages differentially affect post-ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD.

Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death.

BACKGROUND: Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. METHODS AND RESULTS: Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. CONCLUSIONS: HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.

Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation.

Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.

Role of Radiology in Assessment of Postoperative Complications of Heart Transplantation.

Heart transplantation is a pivotal treatment of end-stage heart failure, and recent advancements have extended median posttransplant life expectancy. However, despite the progress in surgical techniques and medical treatment, heart transplant patients still face complications such as rejection, infections, and drug toxicity. CT is a reliable tool for detecting most of these complications, whereas MR imaging is particularly adept at identifying pericardial pathologies and signs of rejection. Awareness of these nuances by radiologists, cardiologists, and surgeons is desired to optimize care, reduce morbidities, and enhance survival.

Financial impact of donation after circulatory death heart transplantation: A single-center analysis.

INTRODUCTION: Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain-dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. METHODS: We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex-situ machine perfusion to in-situ organ perfusion employed during DCD recovery. RESULTS: We performed 58 DBD and 22 DCD heart-alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA-NRP) and six with direct procurement followed by normothermic machine perfusion (DP-NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P = .72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P = .49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA-NRP was $155,955 in comparison to $223,399 for DP-NMP (P = .21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA-NRP ($242, 657 vs. $175,768; P = .34). CONCLUSIONS: Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation.

Sex-Linked Differences in Cardiac Atrophy After Mechanical Unloading Induced by Heterotopic Heart Transplantation.

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.

Year in Review 2023: Noteworthy Literature in Cardiothoracic Transplantation.

This review highlights key studies examining perioperative management of cardiothoracic transplantation published in 2023. Articles were manually screened after searching Scopus, PubMed, and Google Scholar databases for manuscripts related to cardiothoracic transplantation, which yielded 343 papers with 15 qualitatively selected as the most salient for readers. Overarching themes include differences in outcomes across the various etiologies of end-stage lung disease, novel developments to expand the donor pool, and multi-organ transplantation.

HeartMate 3 implantation with an emphasis on the biventricular configuration.

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.

Successful explantation of children from the Berlin Heart EXCOR® ventricular assist device: A systematic review.

BACKGROUND: The Berlin Heart EXCOR® (BHE) can bridge children with severe heart failure to transplantation, but some are successfully weaned and spared transplantation. This study seeks to identify characteristics of children amenable to successful explantation with BHE support. METHODS: Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines were used. Five databases were screened for original, English articles measuring BHE support in patients <18 years old based on title and abstract. Exclusion criteria were applied: full-text availability, <10 total pediatric BHE patients, zero successful explantations from BHE, nonprimary literature, adult and pediatric results that could not be separated, and studies with overlapping patient information. Studies were analyzed with descriptive statistics. RESULTS: From 41 857 potential studies, 14 were analyzed with data from 58 hospitals on four continents from 1990 to 2020. There were 984 BHE patients. The most common diagnosis was dilated cardiomyopathy (n = 318, 32.3%), followed by congenital heart disease (n = 249, 25.3%). There were 85 (8.6%) children explanted with favorable outcomes. The underlying diagnosis was known in 44 (51.8%) cases: 14 (8.4%) of 166 cardiomyopathies, 17 (48.6%) of 35 myocarditis, and 12 (16.7%) of 72 with congenital heart disease were explanted. When the type of support was known, the rate of LVAD patients explanted was 21.3% (n = 19/89) and 2.4% (n = 1/42) of BiVAD patients were explanted. CONCLUSION: Explantation from BHE is not uncommon at 8.6%, but significant variation exists in the explantation data reported. Myocarditis and LVAD support may be populations suitable for weaning. Standardization of reporting measures and prospective registries may help identify patients suitable for this alternative to transplant and help develop weaning protocols.

The future of partial heart transplantation.

Heart valve replacement in children is an unsolved problem in congenital cardiac surgery because state-of-the-art heart valve implants do not grow. This leads to serial repeat operations to replace outgrown heart valve implants. Partial heart transplantation is a new transplant that helps alleviate this problem by delivering growing heart valve implants. In the future, partial heart transplantation has the potential to complement conventional heart transplantation for treating children with congenital cardiac disease primarily affecting the heart valves.