Can Two Halves Make a Whole? Technical Feasibility of Isolated Parallel Circulation Heterotopic Cardiac Transplantation: A Pre-clinical Study in 3D and Porcine Models

Can Two Halves Make a Whole? Technical Feasibility of Isolated Parallel Circulation Heterotopic Cardiac Transplantation: A Pre-clinical Study in 3D and Porcine Models | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Can Two Halves Make a Whole? Technical Feasibility of Isolated Parallel Circulation Heterotopic Cardiac Transplantation: A Pre-clinical Study in 3D and Porcine Models Ayush Balaji, Rishab Makam, Akshay Balaji, Shantanu Bajaj, Natasha Bocchetta, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9123868/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Objectives: To explore a novel application of heterotopic cardiac transplantation for creating isolated parallel circulations in patients with univentricular pump failure, particularly those with Hypoplastic Left Heart Syndrome or severe one-sided ventricular dysfunction. Methods: The surgical technique was developed using 3D instructional anatomical modeling and subsequently performed in an ex-vivo porcine model (n=3). We assessed the anatomical feasibility of the "parallel" configuration, where the donor and native hearts function independently to support the systemic and pulmonary circuits. Results: Anatomical feasibility was demonstrated in all three porcine preparations. Key surgical maneuvers included extensive mobilization and anterior transposition of the branch pulmonary arteries and pulmonary vein (PV) rerouting to the donor left atrium. Anastomoses remained patent and leak-free under static fluid loading. Conclusions: Heterotopic cardiac transplantation with isolated parallel circulations may offer a novel therapeutic option for patients with complex congenital heart conditions or severe univentricular pump failure who are unsuitable for conventional orthotopic transplantation. This approach could potentially expand the pool of donor hearts available for transplantation and improve outcomes for this challenging patient population. However, further research, including clinical trials, is necessary to assess the safety, efficacy, and long-term outcomes of this innovative technique. This study lays the groundwork for future exploration and could represent a significant advancement in the field of cardiac transplantation. Central Message: This study introduces a pioneering surgical concept of utilizing heterotopic cardiac transplantation to establish isolated parallel circulations in patients with failing single ventricles. Supported by ex vivo simulations and novel anatomical reconstructions, it lays foundational work for potentially expanding donor heart availability and expanding therapeutic options in complex congenital heart disease. Further preclinical and clinical research is necessary to translate this innovative concept into practice. Transplant Fontan Univentricular Heterotopic HLHS Heart Failure Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background Heterotopic transplantation, often referred to as the "piggyback" procedure, is a unique surgical technique employed in the management of end-stage heart failure. Unlike orthotopic transplantation, where the recipient's heart is replaced with a donor heart, HHT involves the implantation of a donor heart alongside the recipient's existing heart. In this paper we introduce a novel approach where parallel pulmonary and systemic circulations can be established using two individual hearts. The philosophy being that two ‘half-hearts’ can achieve the same function as a bi-ventricular heart. This report overviews HHT's application in structurally and functionally univentricular hearts, detailing surgical methodology, post-operative care, and perioperative considerations. By evaluating the feasibility and implications of employing donor hearts which are typically not considered for OHT, we could potentially increase the availability of donor hearts( 1 ). By presenting a theoretical framework, this paper aims to contribute to cardiac transplantation discourse, especially for patients with complex congenital conditions and univentricular failure. Proposed Operative Techniques Two main techniques are explored, with four possible combinations based on the functionality of the recipient's and donor's ventricles. A donor RV acting as a pulmonary ventricle, A donor LV acting as a systemic ventricle, a donor RV acting as a systemic ventricle, and a donor LV acting as a pulmonary ventricle. The donor and recipients can both be either structurally biventricular or univentricular with modifications to the surgical approach. Utilising a Donor Right Ventricle as the Pulmonary Ventricle We propose a transplantation method for a structurally univentricular patients post-stage 1 procedure, adaptable for functionally univentricular hearts. (Fig. 1 ). To simplify the discussion moving forward, the native heart will be referred to as Heart A and the donor heart as Heart B. For the case of Heart B with a failing LV but preserved RV function, the harvest should be carried out with generous lengths retained of the SVC and IVC as well as the main PA. Ligation and oversewing of the aorta and PVs can be performed alongside. Care should be taken that the coronary ostia from Heart B are protected for connection to Heart A post-transplant. Heart A should be prepared following bi-caval cannulation with cannula placement very distal to the SVC-atrial junction and similarly for the IVC. Assessment of SA Node position through electrophysiological study prior to division of the SVC is crucial to avoid damaging the node. Following this, takedown of the BTT-shunt (if present) at the distal end can be performed if required and the branch PA can be opened for anastomosis of the PA from Heart B. Heart B is placed in a 'dextrocardiac' position, avoiding ascending PA kinking. Native SVC and IVC are anastomosed to Heart B, ensuring lumen is unobstructed. The ascending PA of Heart B is then anastomosed to the PA opening in the recipient. Different strategies for coronary perfusion are discussed later. The flow and connections are depicted in the box diagram (Fig. 2 ). Utilising a Donor Left Ventricle as the Systemic Ventricle This is a surgical technique where the donor heart is utilised as the systemic ventricle and receives pulmonary venous return (Fig. 3 ). Following initiation of CPB in the recipient pulmonary venous harvest is performed. Aortic cannulation is performed via the innominate artery or high ascending aorta for adequate mobilisation and anastomosis to Heart B. For the case of Heart B with a failing RV but preserved LV function, the harvest should be carried out with generous lengths retained of the ascending aorta. Ligation and oversewing of the SVC, IVC, and PA can be performed alongside. Following this, takedown of the BTT-shunt can be performed. The PV of Heart A are harvested, and the LA is oversewn. Heart B is introduced into the chest of the recipient in a ‘dextrocardiac’ position with care taken to avoid kinking of the ascending aorta. A window is created in the LA of Heart B for the anastomosis of the native PVs. The main PA can be opened for anastomosis of the native outflow tract. Extensive mobilization and anterior of the branch pulmonary arteries is performed to allow for the anastomosis to the PA. The distal aorta is reflected over the PA to reverse the displacement manoeuvre for the ascending aorta of Heart B to be anastomosed. The ascending aorta of the donor heart is anastomosed to the arch of the recipient. The aortic root stump is closed in the native heart after assessment of aortic valve competence. Alternatively, the native heart can be explanted, retaining the caval veins and LA wall, and the donor heart positioned orthotopically for anastomosis. The native heart can then be reintroduced in the heterotopic position where a caval vein anastomosis and PA to PA anastomosis can be conducted. There is also a potential for exploring a left atria to atria anastomosis with closure of the native mitral valve as an alternative to the mobilisation of pulmonary venous vasculature. The flow and connections are depicted in the box diagram (Fig. 2 ). Utilising a Donor Left Ventricle as the Pulmonary Ventricle Using left sided donor heart as a pulmonary ventricle is also a strategy that may be used in the case where only such hearts are available. However, it is important to anticipate any strain on the pulmonary vasculature from a ventricle that is used to maintaining systemic flow. Technically speaking, this would mean anastomosing native caval veins to the donor LA and anastomosing the donor aorta to the native pulmonary trunk. The coronary arterial blood flow would be the systemic venous blood. The coronary sinus return will need to be redirected to the donor LA. Utilising a Donor Right Ventricle as the Systemic Ventricle Using a right sided donor heart as a systemic ventricle is also a potential strategy however this would carry similar issues to a congenitally corrected transposition of the great arteries. The technique would be similar to the first outlined method where the donor aortic stump would need to be closed, and an alternative coronary perfusion strategy would need to be utilised. Methods Ex-Vivo porcine simulation was conducted using tissues acquired from an abattoir sourced according to UK laws. To assess anatomical feasibility, the proposed surgical technique was performed on three fresh porcine heart-lung blocks. All vascular connections were performed using standard 5 − 0 or 6 − 0 monofilament polypropylene (Prolene) sutures in a continuous fashion. Results Figure 4 depicts an ex-vivo reproduction of the first HHT technique outlined above in a porcine model. Using the experience from the ex-vivo simulation, 3-dimensional reconstructions (Fig. 5 ) were generated to showcase the technical aspects of the procedure. The operative flow went as described in the technique description above. Successful anatomical alignment was achieved in 100% of the porcine preparations (n = 3). Water testing showcased correct flow directions from the caval veins through donor heart into the pulmonary arteries and return through the pulmonary veins into the native heart through to the aorta and further through a graft to supply the donor aortic stump. The procedure was performed within the confines of the lung margins to emulate thoracic space constraints assuming opened pleura. Discussion Multiple approaches exist to create two half circulations with HHT, each with varying effectiveness. From a theoretical standpoint, the most effective approach would be application of the first method outlined where a donor heart with a functioning RV is used to support a failing right sided circulation due to easy anastomotic mobilisation and minimal inflow/outflow modifications. Managing coronary arterial supply and venous return are key challenges, with strategies outlined later. Ventricular offloading also has proven to show drastic reductions in myocardial oxygen requirement further allowing for more radical strategies in coronary perfusion of the donor heart (2, 3). Strategies for Coronary Perfusion when Utilising the Native Heart as the Systemic Ventricle and the right sided donor heart as the pulmonary ventricle : Free Graft The coronary ostium of Heart B is anastomosed to the ascending aorta of Heart A through a free graft end-to-end anastomosis extension to allow for any repeat delivery of cardioplegia to be given through the aortic root of Heart A. Pedicled Graft A Y graft or sequential anastomosis can be performed on Heart B after harvesting the right internal mammary of the patient. Utilisation of the BTT Shunt Following the final anastomosis, the distal end of the BTT shunt is anastomosed to the aortic root stump of Heart B to allow for coronary perfusion. The BTT shunt can be banded to reduce the flow rate if required. Venous Drainage In this strategy, the venous drainage remains through the coronary sinus in the RA of Heart B. Heart A sinus blood is mixed with the systemically ejected blood. In a non-structurally univentricular patient with an interatrial connection, a temporary ASD may need to be created in the native heart and a patch sutured to close this defect while encompassing the coronary sinus opening (Fig. 6). This is a similar technique to the intracardiac baffle that is used to manage unroofed coronary sinus. Another method would be to close the tricuspid valve and create a septostomy. Thebesian venous drainage is a potential consideration especially if significant return is seen when on bypass. Fenestration of the closed valve, similar to the Starnes procedure, may allow for management of any potential distention and enable atrophy of the RV (4). Atrial Septostomy Utilisation as a Novel Strategy of Coronary Perfusion: An atrial septostomy is performed in Heart B to allow for shunting of right atrial blood into the LA to leave the failing LV to perfuse the coronary ostium through the aortic root stump. At this stage, oxygen demand of the myocardium and saturations in the systemic venous blood need to be considered. The myocardial oxygen demand can be expressed by a modified Fick’s equation as outlined below(2): MVO2 is determined by the difference between the oxygen content in the blood entering and leaving the coronary circulation. In this equation, CO represents cardiac output, Hb stands for haemoglobin concentration, and the terms SvO2 and S'vO2 refer to oxygen saturation before and after blood has passed through the myocardium. There are also studies showing the use of Ranolazine to improve the efficiency of myocardial oxygen utilisation by shifting metabolic processes to more oxygen-economical glucose consumption compared to fatty acid oxidation(5). Further research regarding altitude medicine suggests that cardiac response and remodelling due to chronic hypoxia can be induced through the maintenance of elevated Hb and a lower left ventricular end diastolic volume (22). Populations that fail to adapt to the harsh conditions seem to have elevated pulmonary vascular resistance, which can be managed medically(6, 7). Strategies for Coronary Perfusion when Utilising a Left Sided Donor Heart as the Systemic Ventricle: Free Graft The coronary buttons harvested from the DKS of Heart A can be anastomosed to the ascending aorta of Heart B through a free graft end-to-end anastomosis extension to allow for any repeat delivery of cardioplegia to be given through the aortic root of Heart B. In the case where a DKS was not performed a free graft from the donor aorta to a closed aortic stump of the native heart can be performed and the PA is used as the outflow tract of the pulmonary ventricle. Pedicled Graft A Y-graft or sequential anastomosis can be performed on Heart A after harvesting the left internal mammary of the patient. Venous Drainage In this strategy, the venous drainage remains through the coronary sinus into the RA of Heart A. In Heart B the interatrial baffle can be used to reroute the coronary sinus to the LA. Considerations in the Fontan/TCPC Candidate In patients selected to undergo a Fontan procedure, we hypothesise that the HHT method may serve as a biological Fontan pump to help improve outcomes. This may not be limited to a patient who is yet to have a Fontan but can be applied to cases where a patient is beginning to exhibit signs of Fontan failure or is a candidate for transplant but unlikely to receive standard OHT. Further Operative Considerations Pulmonary Venous Mobilisation and Anastomosis: In the case of a donor heart being used as a systemic ventricle, the length of the left PVs may not be adequate for direct anastomosis to the LA. If needed, the PVs can be divided between the right and left sides, with the right PVs being directly anastomosed to the donor's LA and the left PVs connected using a conduit harvested from the donor (8, 9). An alternative strategy could be to anastomose the left PVs to the posterior pericardium and subsequently anastomose this pericardial well to the donor LA (Fig. 7), an adaptation of the technique for scimitar vein repair described by Lugones et al. (10). Otherwise, anastomosis of the LA back wall with the PVs to the posterior pericardium and routed to the donor heart (Fig. 7). Deairing Protocols: Previous HHT techniques have de-aired through the aortic root of the native heart, but with parallel circulation, we recommend that both hearts must be de-aired independently. Cardiopulmonary Bypass and Myocardial Protection: While there is a need for empirical studies on this, we believe that once the venous connections are ligated on the native heart, the cross-clamp may be removed to allow the heart to start beating, with care taken to ensure low myocardial oxygen demand. Once the venous connection sites are prepared for anastomosis, the donor heart can be anastomosed, and the venous return can be de-snared to allow the donor heart to fill. In the case of a donor heart being utilised as a RV, a cannula is inserted in the aortic stump to allow for continuous coronary perfusion. Once any obsolete openings are ligated or closed, the outflow tract anastomosis is conducted, taking care to prevent any air entry. In the preparation of the donor heart, myocardial protection is completed in the same manner as the standard explant protocol. Any modifications to the heart or further preparations should be performed while the heart is immersed in a cold saline bath to prevent the buildup of warm ischemic time. Pacing Considerations: With dyssynchrony being the largest expected challenge, we believe that it is key that when coming off bypass, pacing wires should be inserted, and where needed, pacing should be applied to synchronise the rhythm of the two hearts. Some studies have suggested that paced linkage or permanent pacemaker implantation could potentially improve outcomes further(11). In the initial Barnard HHT technique, where the donor heart was used as a biological LVAD, the challenges were fibrillation of the native ventricle and difficulty in diagnosis. Pacing may allow for the prevention of such an occurrence(12). The other key difference with both techniques outlined in our study is the complete isolation of both hearts from one another, excluding coronary supply. This can allow for potentially easier diagnostic methods, as the ‘pulmonary heart’ function can be monitored through monitoring of pulmonary vascular parameters, and the ‘systemic heart’ function can be monitored through systemic arterial monitoring. Electrocardiographic Considerations: Conventional ECG may have significant interference; therefore, we suggest the use of further lead placement in the right chest and utilise leads opposite to each other at the apices of both hearts to educate initial pacing decisions. Following guidance from the work by Barnard and colleagues, we also suggest marking the position of electrocardiographic leads such as V3, V4, V5, and V3R, V4R, V5R to prevent any confusion with postoperative ECG. It is also a key point to document that the LV of the transplanted heart may lie anterior to the RV and is therefore situated immediately behind the chest wall(13). Imaging Considerations: Intraoperatively, Transoesophageal Echocardiography may not provide the best images of both hearts; we would likely suggest the use of epicardial echocardiography and transthoracic echocardiography postoperatively. Routine CT and MRI may need modified contrast protocols for hearts without systemic venous return (14, 15). Managing Pulmonary Pressure: Based on the literature, Endothelin Receptor Antagonists (ERAs) like bosentan and ambrisentan, Phosphodiesterase Type 5 Inhibitors (PDE-5 Inhibitors) like Sildenafil and tadalafil that enhance nitric oxide-mediated vasodilation in the pulmonary vasculature, and Prostacyclin Analogues and Prostacyclin Receptor Agonists like epoprostenol, treprostinil, or iloprost that promote vasodilation and inhibit platelet aggregation could be used as a strategy to manage PA pressure post-operatively(16). Avoiding Coronary Steal: It is key in patients where a native heart-to-donor heart shunt is employed for coronary perfusion, to maintain control over the pulmonary pressures to prevent excessive stress on the pulmonary ventricle and to ensure that myocardial oxygen demand does not increase significantly. Domino Transplantation Approaches: Consider two patients: one with isolated left heart failure and the other with isolated right heart failure, who are suitable matches. If a single donor heart becomes available, a transplantation chain can be initiated: the higher-priority patient (Patient A) receives OHT, while the second patient (Patient B) receives Patient A’s heart in a HHT. This approach effectively increases donor heart availability by turning one donor heart into two transplants. It could also broaden the criteria for transplant assessment. Technically, HHT is feasible even if both patients have the same-sided ventricular failure, but patients with opposing failures are ideal to avoid complications related to a RV supporting systemic circulation. Patient and Donor Selection: It is key that the donor heart is smaller than the native heart to allow for space preservation in the thoracic cavity. 3D modelling can be used to evaluate this prior to surgery (Fig. 8). If necessary, the pleura may need to be opened to facilitate more space in the mediastinum, and the lung hilum mobilised (17). Studies translated from transplant patients who received size mismatched orthotopic heart transplants showed that while initial lung volume reduction is seen, there is an improvement over time with thoracic remodelling and adaptation by the lungs (18). A feasibility study in dogs from Elefteriades et al., showcased the potential for ventricular excision however the study admitted survival data is lacking therefore although a potential adjunct to our proposed method, survival studies are needed (19). A case series from the late 1900s showed that size matching led to a 4% greater survival rate among HHT patients compared to OHT patients (20, 21). Although this evidence may no longer reflect contemporary outcomes given the advancements in transplant techniques and postoperative care, it highlights the importance of size-matching. Moreover, this consideration may have an even greater role in the context of children and adolescent patients. Patients must be screened for comorbidities like valvular pathologies due to the additional hemodynamic burden they impose. Moreover, the presence of CAD must be thoroughly evaluated. Patients with significant CAD might face a higher risk of ischemic complications, particularly if the native coronary circulation is relied upon for myocardial perfusion in a heterotopic setup. Consequently, patients with severe or diffuse CAD that is not amenable to revascularisation may not be ideal candidates for this novel surgical approach. Because the donor heart is placed in a dextrocardiac position, the venous and arterial connections need to be carefully mobilized and appropriately fixed to avoid any torsion risk. Limitations: Our study is limited by the lack of dynamic hemodynamic data and the small sample size (n = 3). While anatomical feasibility was demonstrated ex-vivo, the physiological challenges of balancing two independent ventricles in a living system remain to be characterized in future in-vivo porcine trials. Although 3D instructional modeling was used to visualize the great vessel orientation, this study did not include a rigorous volumetric analysis of the pediatric thoracic cavity. The "two-heart" configuration inherently requires significant mediastinal and pleural space. While we propose a dextrocardiac position with pleural opening, the risk of mechanical compression of the donor heart, the native lungs, or the great vessels is a significant factor that requires future CT-based volumetric simulation in varied age groups. Promise from conventional heterotopic transplant procedures and intrathoracic ratio matching does alleviate some of these concerns. In an isolated parallel circulation, two independent hearts with potentially different intrinsic heart rates and responses to neurohumoral stimuli must function in tandem. This is something that needs further evaluation and animal studies are being planned. Conclusion HHT, as explored in this study, offers a potentially valuable alternative for patients with complex univentricular heart conditions or severe univentricular pump failure who are not suitable candidates for conventional OHT. By creating isolated parallel circulations, this technique may provide a novel way to support both systemic and pulmonary circulatory needs, thereby potentially broadening the range of donor hearts that can be utilised. However, this approach is still in the exploratory phase, and more research is needed to comprehensively understand its feasibility, safety, and long-term outcomes. The proposed strategies and techniques provide a framework for further investigation and clinical use. It is important to proceed cautiously, with thorough consideration of the complexities and potential risks involved. Future studies, including both experimental and clinical trials, will be crucial in refining these techniques, validating their benefits, and determining their place in the broader landscape of cardiac transplantation. We hope that this work encourages further exploration and discussion, contributing to the evolving field of cardiac surgery and offering new possibilities for patients facing significant cardiac failure. Abbreviations RA - Right Atrium LA - Left Atrium LV - Left Ventricle RV - Right Ventricle SVC - Superior Vena Cava IVC - Inferior Vena Cava PA - Pulmonary Artery PV - Pulmonary Veins HHT – Heterotopic Heart Transplant OHT – Orthotopic Heart Transplant CPB - Cardiopulmonary Bypass BTT - Blalock-Taussig-Thomas (Shunt) DKS - Damus-Kaye-Stansel (Procedure) ASD - Atrial Septal Defect MVO2 - Myocardial Oxygen Consumption CO - Cardiac Output Hb - Haemoglobin SvO2 - Venous Oxygen Saturation S'vO2 - Venous Oxygen Saturation Post Myocardium TCPC - Total Cavopulmonary Connection ERAs - Endothelin Receptor Antagonists PDE-5 Inhibitors - Phosphodiesterase Type 5 Inhibitors LVEDV - Left Ventricular End-Diastolic Volume ECG - Electrocardiogram MRI - Magnetic Resonance Imaging CT - Computed Tomography LVAD - Left Ventricular Assist Device CAD - Coronary Artery Disease ERA - Endothelin Receptor Antagonist VAD - Ventricular Assist Device EF - Ejection Fraction Declarations Author Contributions Statement Ayush Balaji, Rishab Makam: Conceptualisation, Methodology, Investigation, Writing - Original Draft, Review & Editing, Visualisation. Akshay Balaji, Shantanu Bajaj, Natasha Bocchetta: Methodology, Writing - Review & Editing. Mohammed Sherif, Nabil Hussein, Ignacio Lugones, Mahmoud Loubani: Supervision, Conceptualisation, Methodology, Resources, Writing - Review & Editing. Ethical Statement No ethical approval was required as the studies did not involve human or animal subjects. All tissues used were acquired from an abattoir sourced according to UK laws. Data Availability Statement There are no new data associated with this article. Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of Interest Statement The authors declare no conflicts of interest related to this study. References Yazji JH, Garg P, Wadiwala I, Alomari M, Alamouti-Fard E, Hussain MWA, et al. Expanding Selection Criteria to Repairable Diseased Hearts to Meet the Demand of Shortage of Donors in Heart Transplantation. Cureus [Internet]. 2022 May 30 [cited 2024 Aug 25];14(5). Available from: /pmc/articles/PMC9150717/ Kuzmiak-Glancy S, Jaimes R, Wengrowski AM, et al. Oxygen demand of perfused heart preparations: how electromechanical function and inadequate oxygenation affect physiology and optical measurements. 2015; 100: 603–616. Paolo Meani, Todaro S, Veronese G, et al. Science of left ventricular unloading. Perfusion. Epub ahead of print 26 July 2024. DOI: https://doi.org/10.1177/02676591241268389. Reemtsen BL, Polimenakos AC, Fagan BT, et al. Fate of the right ventricle after fenestrated right ventricular exclusion for severe neonatal Ebstein anomaly. The Journal of thoracic and cardiovascular surgery 2007; 134: 1406–10; discussion 1410-2. King J, Lowery DR. Physiology, Cardiac Output. StatPearls [Internet]. 2023 Jul 17 [cited 2024 Aug 25]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK470455/ McCormack JG, Stanley WC, Wolff AA. Ranolazine: A Novel Metabolic Modulator for the Treatment of Angina. General Pharmacology: The Vascular System. 1998 May 1;30(5):639–45. León-Velarde F, Villafuerte FC, Richalet JP. Chronic mountain sickness and the heart. Prog Cardiovasc Dis [Internet]. 2010 May [cited 2024 Aug 25];52(6):540–9. Available from: https://pubmed.ncbi.nlm.nih.gov/20417348/ Williams AM, Levine BD, Stembridge M. A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia. J Physiol [Internet]. 2022 Sep 1 [cited 2024 Aug 25];600(18):4089–104. Available from: https://onlinelibrary.wiley.com/doi/full/10.1113/JP281724 Zhao JY, Ganapathi AM, Whitson BA. Management of donor partial anomalous pulmonary veins during lung transplantation. JTCVS Tech [Internet]. 2023 Apr 1 [cited 2024 Aug 25];18:171. Available from: /pmc/articles/PMC10122138/ Fujiwara T, Okada K, Hirano Y, Maki Y, Saiki M, Yunoki K, et al. Pulmonary artery reconstruction using a pulmonary vein conduit in case having an imbalanced dissection length during double-sleeve lobectomy. General Thoracic and Cardiovascular Surgery Cases 2023 2:1 [Internet]. 2023 Mar 29 [cited 2024 Aug 25];2(1):1–7. Available from: https://gtcscases.biomedcentral.com/articles/10.1186/s44215-022-00027-w Lugones I, García R. A new surgical approach to scimitar syndrome. Ann Thorac Surg [Internet]. 2014 Jan [cited 2024 Aug 29];97(1):353–5. Available from: https://pubmed.ncbi.nlm.nih.gov/24384200/ Morris-Thurgood J, Cowell R, Paul V, Kalsi K, Seymour AM, Ilsley C, et al. Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation. Circulation [Internet]. 1994 [cited 2024 Aug 25];90(5):2342–7. Available from: https://pubmed.ncbi.nlm.nih.gov/7955192/ Kennelly BM, Corte P, Losman J, Barnard CN. Arrhythmias in two patients with left ventricular bypass transplants’. Br Heart J. 1976;38:725–31. Novitzky D, Cooper DKC, Barnard CN, Med M. The Surgical Technique of Heterotopic Heart Transplantation. 36:476–82. Lai H-Y, Chen J-H, Chiu K-M, et al. CT of Two Hearts Beating in One Chest. American Journal of Roentgenology 2008; 191: 1711–1716. Newcomb AE, Esmore DS, Rosenfeldt FL, Richardson M, Marasco SF. Heterotopic heart transplantation: An expanding role in the twenty-first century? Annals of Thoracic Surgery [Internet]. 2004 Oct 1 [cited 2024 Aug 25];78(4):1345–50. Available from: http://www.annalsthoracicsurgery.org/article/S000349750400743X/fulltext Shu T, Chen H, Wang L, Wang W, Feng P, Xiang R, et al. The Efficacy and Safety of Pulmonary Vasodilators in Pediatric Pulmonary Hypertension (PH): A Systematic Review and Meta-analysis. Front Pharmacol [Internet]. 2021 Apr 23 [cited 2024 Aug 25];12:668902. Available from: www.frontiersin.org Lloyd KS, Barnard P, Holland VA, et al. Pulmonary function after heart-lung transplantation using larger donor organs. The American review of respiratory disease 1990; 142: 1026–9. Elefteriades JA, Lovoulos CJ, Tellides G, et al. Right ventricle-sparing heart transplant: promising new technique for recipients with pulmonary hypertension. The Annals of Thoracic Surgery 2000; 69: 1858–1863. Khaghani A, Santini F, Dyke CM, Onuzu O, Radley-Smith R, Yacoub MH, et al. Heterotopic cardiac transplantation in infants and children. J Thorac Cardiovasc Surg. 1997 Jun 1;113(6):1042–9. Bleasdale RA, Banner NR, Anyanwu AC, Mitchell AG, Khaghani A, Yacoub MH. Determinants of outcome after heterotopic heart transplantation. The Journal of Heart and Lung Transplantation. 2002 Aug 1;21(8):867–73. Williams AM, Levine BD, Stembridge M. A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia. J Physiol. 2022 Sep;600(18):4089-4104. Table Table 1: Coronary Perfusion Strategies Strategy Oxygen Source Anticipated Advantages Technical Challenges / Risks Free Interposition Graft (e.g., SVB) Native Ascending Aorta Direct systemic oxygenation (High PO2). Requires two extra anastomoses; risk of graft kinking/thrombosis. Pedicled Arterial Graft Internal Thoracic Artery Native arterial conduit; potentially superior long-term patency. Limited length; risk of "steal" from cerebral circulation. Modified BTT Shunt Systemic-to-PA connection Simplifies procedure if shunt is already present; avoids new aortic puncture. Lower PO2 (venous blood in Fontan); risk of pulmonary over-circulation. Atrial Septostomy + Baffle Systemic Venous Return Eliminates need for extra-cardiac grafts; technically simpler "internal" plumbing. Chronic Myocardial Hypoxia; relies on venous blood to coronaries. Additional Declarations No competing interests reported. Supplementary Files GraphicalAbstract.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9123868","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606147108,"identity":"87d5319c-1ea5-459a-b453-f28622a10efd","order_by":0,"name":"Ayush Balaji","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIie3PsWrDMBCA4TMBZxFRR4FL8go2hUCH4FeRMXRSSKaQ0VC4rXT1e2TpKCOoFz+ABw/u4tklU7eeEjpGeCxE/3QIfegE4PP902YAGhYAUo80TCchkaq8kqCYSmDGphBeqqfzHrpVONdfZvPRpRC91r2LiFatoxKGBJmUZtsMWfH4mbkXI0L7mADBEjQShEqcZNXSYkRS5L00z2hSELtvJ4lbFUdEMhT0SoAmKIRyfz9phkPE4iFH0cvqDa19SUoXWdb56cyO3eadq3z8ocW4yPvRReBB2vXsxOTlIHRet3H9N8317Vs+n8931/0Co2ZQjHWYr3EAAAAASUVORK5CYII=","orcid":"","institution":"University of Hull","correspondingAuthor":true,"prefix":"","firstName":"Ayush","middleName":"","lastName":"Balaji","suffix":""},{"id":606147109,"identity":"d19ff0fd-d526-40d6-bedf-7921f80abd20","order_by":1,"name":"Rishab Makam","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Rishab","middleName":"","lastName":"Makam","suffix":""},{"id":606147110,"identity":"6fe5df85-7ecb-4b0e-a52f-b184b402b528","order_by":2,"name":"Akshay Balaji","email":"","orcid":"","institution":"University of Hull","correspondingAuthor":false,"prefix":"","firstName":"Akshay","middleName":"","lastName":"Balaji","suffix":""},{"id":606147111,"identity":"a4760b91-e9f0-4657-8cf5-03e4144d6eac","order_by":3,"name":"Shantanu Bajaj","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Shantanu","middleName":"","lastName":"Bajaj","suffix":""},{"id":606147112,"identity":"05e50b13-da66-4af8-893d-832cdc1dc835","order_by":4,"name":"Natasha Bocchetta","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Natasha","middleName":"","lastName":"Bocchetta","suffix":""},{"id":606147113,"identity":"5ad7ffda-cfac-4a44-aa3c-864ec07c4fac","order_by":5,"name":"Ujjawal Kumar","email":"","orcid":"","institution":"Papworth Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ujjawal","middleName":"","lastName":"Kumar","suffix":""},{"id":606147114,"identity":"3cd19649-9448-479b-a79c-0cd6fd498c18","order_by":6,"name":"Mohamed Sherif","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Sherif","suffix":""},{"id":606147115,"identity":"612bfb8d-f316-4a9e-8598-693848851797","order_by":7,"name":"Nabil Hussein","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Nabil","middleName":"","lastName":"Hussein","suffix":""},{"id":606147116,"identity":"1adc0a91-1b95-4cb1-b15d-9e309c0e9aea","order_by":8,"name":"Ignacio Lugones","email":"","orcid":"","institution":"Aspiring Congenital Heart Surgeons Association","correspondingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Lugones","suffix":""},{"id":606147117,"identity":"e8358a25-b906-47bb-b779-f360cedef3ef","order_by":9,"name":"Mahmoud Loubani","email":"","orcid":"","institution":"Hull University Teaching Hospitals Trust","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"","lastName":"Loubani","suffix":""}],"badges":[],"createdAt":"2026-03-14 16:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9123868/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9123868/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104795940,"identity":"407cd7f4-d0b9-41df-b360-b40dde85c2b9","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":580415,"visible":true,"origin":"","legend":"\u003cp\u003eStep By Step Schematic Illustration of the Surgical Technique for Donor Heart as the Pulmonary Ventricle. Panel 1 depicts the bicaval cannulation and the aortic cannulation. Panel 2 depicts takedown of the distal BTT shunt. Panel 3 and 4 shows harvest of the native caval veins. Panel 5 depicts anastomosis of the caval veins to the donor heart. Panel 6 shows the opening of the right PA. Panel 7 depicts the anastomosis of the donor PA to the native RPA.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/3e84147c66a4ebc7530fe3a5.png"},{"id":104795942,"identity":"601c22a1-7b33-41df-9846-946a4e222e0b","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120439,"visible":true,"origin":"","legend":"\u003cp\u003eBox diagram of the two completed procedures:\u003c/p\u003e\n\u003cp\u003e• Orange: Native heart\u003c/p\u003e\n\u003cp\u003e• Blue: Donor heart\u003c/p\u003e\n\u003cp\u003e• Purple: Inflow and outflow tracts\u003c/p\u003e\n\u003cp\u003e• Green Line: Anastomotic connections\u003c/p\u003e\n\u003cp\u003e• Grey Lines: Pre-existing connections\u003c/p\u003e\n\u003cp\u003e• Red Dashed Line: Ligated connections\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/e165a7586238988e47dc8002.png"},{"id":104795951,"identity":"0c0e994b-9b12-43cf-82ae-c1fa29e15d71","added_by":"auto","created_at":"2026-03-17 09:36:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":537169,"visible":true,"origin":"","legend":"\u003cp\u003eStep By Step Schematic Illustration of the Surgical Technique for Donor Heart as the Systemic Ventricle. Panel 1 depicts the bicaval cannulation and the high aortic cannulation. Panel 2 depicts harvest of the native PVs. Panel 3 shows the closure of the harvest site in the LA and ASD patch routing. Panel 4 depicts transection of the native aorta/systemic outflow. Panel 5 and 6 shows the Extensive mobilization and anterior displacement of the branch pulmonary arteries manoeuvre used to anastomose the native systemic outflow with the main PA. Panel 7 and 8 depicts the reversal of the anterior displacement manoeuvre and the introduction of the donor heart. Panel 9 depicts anastomosis of the PVs to the donor LA, and the anastomosis of the donor ascending aorta to the native aorta.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/27c7a514a1b6c97fbcaa48c1.png"},{"id":104808686,"identity":"797e183e-b8cb-460b-aa87-e536ae5902c0","added_by":"auto","created_at":"2026-03-17 12:39:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1076927,"visible":true,"origin":"","legend":"\u003cp\u003eEx-Vivo of the Surgical Technique for Donor Heart as the Pulmonary Ventricle in a patient with a DKS.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/91928d6021defd3b46f43966.png"},{"id":104795946,"identity":"e805df3a-334f-41ad-bbae-9c2bdfc1e89a","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":386870,"visible":true,"origin":"","legend":"\u003cp\u003e3D reconstruction of surgical techniques:\u003c/p\u003e\n\u003cp\u003e• Top Panel: Donor heart as the pulmonary ventricle.\u003c/p\u003e\n\u003cp\u003e• Bottom Panel: Donor heart as the systemic ventricle in a patient with DKS.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/dcdfce7dac0536f2605276e3.png"},{"id":104795944,"identity":"52263aa8-bac1-4620-8696-635033bee1a0","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":181784,"visible":true,"origin":"","legend":"\u003cp\u003eRerouting of the Coronary Sinus venous return through an ASD into the LA. Panel 1 shows the created ASD in relation to the sinus. Panel 2 shows the patch margins. Panel 3 Depicts the finished patch and the flow from the sinus through the baffle.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/a0772893d3173d8c9ba3ce36.png"},{"id":104795943,"identity":"9b979ff7-9269-4473-b57f-1385f3138e9e","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":379592,"visible":true,"origin":"","legend":"\u003cp\u003ePV rerouting for anastomosis to donor LA:\u003c/p\u003e\n\u003cp\u003e• Top Panel: Left PVs to posterior pericardium, forming a chamber for LA anastomosis.\u003c/p\u003e\n\u003cp\u003e• Bottom Panel: All PVs rerouted similarly to create a chamber for LA anastomosis.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/c8831da1f4ecb035dd437e78.png"},{"id":104795945,"identity":"69dcd7da-8e4b-4563-a400-64b4493f5816","added_by":"auto","created_at":"2026-03-17 09:36:03","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":501484,"visible":true,"origin":"","legend":"\u003cp\u003e3D rendering of the thorax with a simulated heterotopic transplant procedure\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/fc7a736ebe4d96c8835df0b4.png"},{"id":105035395,"identity":"55f48f42-1375-4ec9-99ff-50300aef248d","added_by":"auto","created_at":"2026-03-20 07:26:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5219244,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/0b12da46-bb5d-4d04-899c-39d292cc9b49.pdf"},{"id":104808764,"identity":"c5ae5e96-0d1f-4add-a1c4-847a18c1bc19","added_by":"auto","created_at":"2026-03-17 12:39:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":898345,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.docx","url":"https://assets-eu.researchsquare.com/files/rs-9123868/v1/24c0bc4c90a007046b6e8c5b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Can Two Halves Make a Whole? Technical Feasibility of Isolated Parallel Circulation Heterotopic Cardiac Transplantation: A Pre-clinical Study in 3D and Porcine Models","fulltext":[{"header":"Background","content":"\u003cp\u003eHeterotopic transplantation, often referred to as the \"piggyback\" procedure, is a unique surgical technique employed in the management of end-stage heart failure. Unlike orthotopic transplantation, where the recipient's heart is replaced with a donor heart, HHT involves the implantation of a donor heart alongside the recipient's existing heart. In this paper we introduce a novel approach where parallel pulmonary and systemic circulations can be established using two individual hearts. The philosophy being that two \u0026lsquo;half-hearts\u0026rsquo; can achieve the same function as a bi-ventricular heart.\u003c/p\u003e \u003cp\u003eThis report overviews HHT's application in structurally and functionally univentricular hearts, detailing surgical methodology, post-operative care, and perioperative considerations. By evaluating the feasibility and implications of employing donor hearts which are typically not considered for OHT, we could potentially increase the availability of donor hearts(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBy presenting a theoretical framework, this paper aims to contribute to cardiac transplantation discourse, especially for patients with complex congenital conditions and univentricular failure.\u003c/p\u003e\n\u003ch3\u003eProposed Operative Techniques\u003c/h3\u003e\n\u003cp\u003eTwo main techniques are explored, with four possible combinations based on the functionality of the recipient's and donor's ventricles. A donor RV acting as a pulmonary ventricle, A donor LV acting as a systemic ventricle, a donor RV acting as a systemic ventricle, and a donor LV acting as a pulmonary ventricle. The donor and recipients can both be either structurally biventricular or univentricular with modifications to the surgical approach.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eUtilising a Donor Right Ventricle as the Pulmonary Ventricle\u003c/h2\u003e \u003cp\u003eWe propose a transplantation method for a structurally univentricular patients post-stage 1 procedure, adaptable for functionally univentricular hearts. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). To simplify the discussion moving forward, the native heart will be referred to as Heart A and the donor heart as Heart B.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the case of Heart B with a failing LV but preserved RV function, the harvest should be carried out with generous lengths retained of the SVC and IVC as well as the main PA. Ligation and oversewing of the aorta and PVs can be performed alongside. Care should be taken that the coronary ostia from Heart B are protected for connection to Heart A post-transplant. Heart A should be prepared following bi-caval cannulation with cannula placement very distal to the SVC-atrial junction and similarly for the IVC. Assessment of SA Node position through electrophysiological study prior to division of the SVC is crucial to avoid damaging the node. Following this, takedown of the BTT-shunt (if present) at the distal end can be performed if required and the branch PA can be opened for anastomosis of the PA from Heart B. Heart B is placed in a 'dextrocardiac' position, avoiding ascending PA kinking. Native SVC and IVC are anastomosed to Heart B, ensuring lumen is unobstructed. The ascending PA of Heart B is then anastomosed to the PA opening in the recipient. Different strategies for coronary perfusion are discussed later. The flow and connections are depicted in the box diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eUtilising a Donor Left Ventricle as the Systemic Ventricle\u003c/h3\u003e\n\u003cp\u003eThis is a surgical technique where the donor heart is utilised as the systemic ventricle and receives pulmonary venous return (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Following initiation of CPB in the recipient pulmonary venous harvest is performed. Aortic cannulation is performed via the innominate artery or high ascending aorta for adequate mobilisation and anastomosis to Heart B. For the case of Heart B with a failing RV but preserved LV function, the harvest should be carried out with generous lengths retained of the ascending aorta. Ligation and oversewing of the SVC, IVC, and PA can be performed alongside. Following this, takedown of the BTT-shunt can be performed. The PV of Heart A are harvested, and the LA is oversewn. Heart B is introduced into the chest of the recipient in a \u0026lsquo;dextrocardiac\u0026rsquo; position with care taken to avoid kinking of the ascending aorta. A window is created in the LA of Heart B for the anastomosis of the native PVs. The main PA can be opened for anastomosis of the native outflow tract. Extensive mobilization and anterior of the branch pulmonary arteries is performed to allow for the anastomosis to the PA. The distal aorta is reflected over the PA to reverse the displacement manoeuvre for the ascending aorta of Heart B to be anastomosed. The ascending aorta of the donor heart is anastomosed to the arch of the recipient. The aortic root stump is closed in the native heart after assessment of aortic valve competence.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAlternatively, the native heart can be explanted, retaining the caval veins and LA wall, and the donor heart positioned orthotopically for anastomosis. The native heart can then be reintroduced in the heterotopic position where a caval vein anastomosis and PA to PA anastomosis can be conducted. There is also a potential for exploring a left atria to atria anastomosis with closure of the native mitral valve as an alternative to the mobilisation of pulmonary venous vasculature. The flow and connections are depicted in the box diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eUtilising a Donor Left Ventricle as the Pulmonary Ventricle\u003c/h3\u003e\n\u003cp\u003eUsing left sided donor heart as a pulmonary ventricle is also a strategy that may be used in the case where only such hearts are available. However, it is important to anticipate any strain on the pulmonary vasculature from a ventricle that is used to maintaining systemic flow. Technically speaking, this would mean anastomosing native caval veins to the donor LA and anastomosing the donor aorta to the native pulmonary trunk. The coronary arterial blood flow would be the systemic venous blood. The coronary sinus return will need to be redirected to the donor LA.\u003c/p\u003e\n\u003ch3\u003eUtilising a Donor Right Ventricle as the Systemic Ventricle\u003c/h3\u003e\n\u003cp\u003eUsing a right sided donor heart as a systemic ventricle is also a potential strategy however this would carry similar issues to a congenitally corrected transposition of the great arteries. The technique would be similar to the first outlined method where the donor aortic stump would need to be closed, and an alternative coronary perfusion strategy would need to be utilised.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEx-Vivo porcine simulation was conducted using tissues acquired from an abattoir sourced according to UK laws. To assess anatomical feasibility, the proposed surgical technique was performed on three fresh porcine heart-lung blocks. All vascular connections were performed using standard 5\u0026thinsp;\u0026minus;\u0026thinsp;0 or 6\u0026thinsp;\u0026minus;\u0026thinsp;0 monofilament polypropylene (Prolene) sutures in a continuous fashion.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e depicts an ex-vivo reproduction of the first HHT technique outlined above in a porcine model. Using the experience from the ex-vivo simulation, 3-dimensional reconstructions (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) were generated to showcase the technical aspects of the procedure. The operative flow went as described in the technique description above. Successful anatomical alignment was achieved in 100% of the porcine preparations (n\u0026thinsp;=\u0026thinsp;3). Water testing showcased correct flow directions from the caval veins through donor heart into the pulmonary arteries and return through the pulmonary veins into the native heart through to the aorta and further through a graft to supply the donor aortic stump. The procedure was performed within the confines of the lung margins to emulate thoracic space constraints assuming opened pleura.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMultiple approaches exist to create two half circulations with HHT, each with varying effectiveness. From a theoretical standpoint, the most effective approach would be application of the first method outlined where a donor heart with a functioning RV is used to support a failing right sided circulation due to easy anastomotic mobilisation and minimal inflow/outflow modifications. Managing coronary arterial supply and venous return are key challenges, with strategies outlined later. Ventricular offloading also has proven to show drastic reductions in myocardial oxygen requirement further allowing for more radical strategies in coronary perfusion of the donor heart (2, 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategies for Coronary Perfusion when Utilising the Native Heart as the Systemic Ventricle and the right sided donor heart as the pulmonary ventricle\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFree Graft\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe coronary ostium of Heart B is anastomosed to the ascending aorta of Heart A through a free graft end-to-end anastomosis extension to allow for any repeat delivery of cardioplegia to be given through the aortic root of Heart A.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePedicled Graft\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA Y graft or sequential anastomosis can be performed on Heart B after harvesting the right internal mammary of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUtilisation of the BTT Shunt\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFollowing the final anastomosis, the distal end of the BTT shunt is anastomosed to the aortic root stump of Heart B to allow for coronary perfusion. The BTT shunt can be banded to reduce the flow rate if required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVenous Drainage\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this strategy, the venous drainage remains through the coronary sinus in the RA of Heart B. Heart A sinus blood is mixed with the systemically ejected blood. In a non-structurally univentricular patient with an interatrial connection, a temporary ASD may need to be created in the native heart and a patch sutured to close this defect while encompassing the coronary sinus opening (Fig.\u0026nbsp;6). This is a similar technique to the intracardiac baffle that is used to manage unroofed coronary sinus. Another method would be to close the tricuspid valve and create a septostomy. Thebesian venous drainage is a potential consideration especially if significant return is seen when on bypass. Fenestration of the closed valve, similar to the Starnes procedure, may allow for management of any potential distention and enable atrophy of the RV (4).\u003c/p\u003e\n\u003ch3\u003eAtrial Septostomy Utilisation as a Novel Strategy of Coronary Perfusion:\u003c/h3\u003e\n\u003cp\u003eAn atrial septostomy is performed in Heart B to allow for shunting of right atrial blood into the LA to leave the failing LV to perfuse the coronary ostium through the aortic root stump. At this stage, oxygen demand of the myocardium and saturations in the systemic venous blood need to be considered. The myocardial oxygen demand can be expressed by a modified Fick\u0026rsquo;s equation as outlined below(2):\u003c/p\u003e\n\u003cdiv id=\"Equa\"\u003e\n \u003cdiv id=\"FileID_Equa\" name=\"EquationSource\"\u003e\u003cimg src=\"data:image/png;base64,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\"\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003eMVO2 is determined by the difference between the oxygen content in the blood entering and leaving the coronary circulation. In this equation, CO represents cardiac output, Hb stands for haemoglobin concentration, and the terms SvO2 and S\u0026apos;vO2 refer to oxygen saturation before and after blood has passed through the myocardium.\u003c/p\u003e\n\u003cp\u003eThere are also studies showing the use of Ranolazine to improve the efficiency of myocardial oxygen utilisation by shifting metabolic processes to more oxygen-economical glucose consumption compared to fatty acid oxidation(5). Further research regarding altitude medicine suggests that cardiac response and remodelling due to chronic hypoxia can be induced through the maintenance of elevated Hb and a lower left ventricular end diastolic volume (22). Populations that fail to adapt to the harsh conditions seem to have elevated pulmonary vascular resistance, which can be managed medically(6, 7).\u003c/p\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eStrategies for Coronary Perfusion when Utilising a Left Sided Donor Heart as the Systemic Ventricle:\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003eFree Graft\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe coronary buttons harvested from the DKS of Heart A can be anastomosed to the ascending aorta of Heart B through a free graft end-to-end anastomosis extension to allow for any repeat delivery of cardioplegia to be given through the aortic root of Heart B. In the case where a DKS was not performed a free graft from the donor aorta to a closed aortic stump of the native heart can be performed and the PA is used as the outflow tract of the pulmonary ventricle.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePedicled Graft\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eA Y-graft or sequential anastomosis can be performed on Heart A after harvesting the left internal mammary of the patient.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVenous Drainage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn this strategy, the venous drainage remains through the coronary sinus into the RA of Heart A. In Heart B the interatrial baffle can be used to reroute the coronary sinus to the LA.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eConsiderations in the Fontan/TCPC Candidate\u003c/h2\u003e\n \u003cp\u003eIn patients selected to undergo a Fontan procedure, we hypothesise that the HHT method may serve as a biological Fontan pump to help improve outcomes. This may not be limited to a patient who is yet to have a Fontan but can be applied to cases where a patient is beginning to exhibit signs of Fontan failure or is a candidate for transplant but unlikely to receive standard OHT.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eFurther Operative Considerations\u003c/h2\u003e\n \u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003ePulmonary Venous Mobilisation and Anastomosis:\u003c/h2\u003e\n \u003cp\u003eIn the case of a donor heart being used as a systemic ventricle, the length of the left PVs may not be adequate for direct anastomosis to the LA. If needed, the PVs can be divided between the right and left sides, with the right PVs being directly anastomosed to the donor\u0026apos;s LA and the left PVs connected using a conduit harvested from the donor (8, 9). An alternative strategy could be to anastomose the left PVs to the posterior pericardium and subsequently anastomose this pericardial well to the donor LA (Fig.\u0026nbsp;7), an adaptation of the technique for scimitar vein repair described by Lugones et al. (10). Otherwise, anastomosis of the LA back wall with the PVs to the posterior pericardium and routed to the donor heart (Fig.\u0026nbsp;7).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eDeairing Protocols:\u003c/h2\u003e\n \u003cp\u003ePrevious HHT techniques have de-aired through the aortic root of the native heart, but with parallel circulation, we recommend that both hearts must be de-aired independently.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003eCardiopulmonary Bypass and Myocardial Protection:\u003c/h2\u003e\n \u003cp\u003eWhile there is a need for empirical studies on this, we believe that once the venous connections are ligated on the native heart, the cross-clamp may be removed to allow the heart to start beating, with care taken to ensure low myocardial oxygen demand. Once the venous connection sites are prepared for anastomosis, the donor heart can be anastomosed, and the venous return can be de-snared to allow the donor heart to fill. In the case of a donor heart being utilised as a RV, a cannula is inserted in the aortic stump to allow for continuous coronary perfusion. Once any obsolete openings are ligated or closed, the outflow tract anastomosis is conducted, taking care to prevent any air entry.\u003c/p\u003e\n \u003cp\u003eIn the preparation of the donor heart, myocardial protection is completed in the same manner as the standard explant protocol. Any modifications to the heart or further preparations should be performed while the heart is immersed in a cold saline bath to prevent the buildup of warm ischemic time.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003ePacing Considerations:\u003c/h2\u003e\n \u003cp\u003eWith dyssynchrony being the largest expected challenge, we believe that it is key that when coming off bypass, pacing wires should be inserted, and where needed, pacing should be applied to synchronise the rhythm of the two hearts. Some studies have suggested that paced linkage or permanent pacemaker implantation could potentially improve outcomes further(11). In the initial Barnard HHT technique, where the donor heart was used as a biological LVAD, the challenges were fibrillation of the native ventricle and difficulty in diagnosis. Pacing may allow for the prevention of such an occurrence(12). The other key difference with both techniques outlined in our study is the complete isolation of both hearts from one another, excluding coronary supply. This can allow for potentially easier diagnostic methods, as the \u0026lsquo;pulmonary heart\u0026rsquo; function can be monitored through monitoring of pulmonary vascular parameters, and the \u0026lsquo;systemic heart\u0026rsquo; function can be monitored through systemic arterial monitoring.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003eElectrocardiographic Considerations:\u003c/h2\u003e\n \u003cp\u003eConventional ECG may have significant interference; therefore, we suggest the use of further lead placement in the right chest and utilise leads opposite to each other at the apices of both hearts to educate initial pacing decisions. Following guidance from the work by Barnard and colleagues, we also suggest marking the position of electrocardiographic leads such as V3, V4, V5, and V3R, V4R, V5R to prevent any confusion with postoperative ECG. It is also a key point to document that the LV of the transplanted heart may lie anterior to the RV and is therefore situated immediately behind the chest wall(13).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\"\u003e\n \u003ch2\u003eImaging Considerations:\u003c/h2\u003e\n \u003cp\u003eIntraoperatively, Transoesophageal Echocardiography may not provide the best images of both hearts; we would likely suggest the use of epicardial echocardiography and transthoracic echocardiography postoperatively. Routine CT and MRI may need modified contrast protocols for hearts without systemic venous return (14, 15).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec20\"\u003e\n \u003ch2\u003eManaging Pulmonary Pressure:\u003c/h2\u003e\n \u003cp\u003eBased on the literature, Endothelin Receptor Antagonists (ERAs) like bosentan and ambrisentan, Phosphodiesterase Type 5 Inhibitors (PDE-5 Inhibitors) like Sildenafil and tadalafil that enhance nitric oxide-mediated vasodilation in the pulmonary vasculature, and Prostacyclin Analogues and Prostacyclin Receptor Agonists like epoprostenol, treprostinil, or iloprost that promote vasodilation and inhibit platelet aggregation could be used as a strategy to manage PA pressure post-operatively(16).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\"\u003e\n \u003ch2\u003eAvoiding Coronary Steal:\u003c/h2\u003e\n \u003cp\u003eIt is key in patients where a native heart-to-donor heart shunt is employed for coronary perfusion, to maintain control over the pulmonary pressures to prevent excessive stress on the pulmonary ventricle and to ensure that myocardial oxygen demand does not increase significantly.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\"\u003e\n \u003ch2\u003eDomino Transplantation Approaches:\u003c/h2\u003e\n \u003cp\u003eConsider two patients: one with isolated left heart failure and the other with isolated right heart failure, who are suitable matches. If a single donor heart becomes available, a transplantation chain can be initiated: the higher-priority patient (Patient A) receives OHT, while the second patient (Patient B) receives Patient A\u0026rsquo;s heart in a HHT. This approach effectively increases donor heart availability by turning one donor heart into two transplants. It could also broaden the criteria for transplant assessment. Technically, HHT is feasible even if both patients have the same-sided ventricular failure, but patients with opposing failures are ideal to avoid complications related to a RV supporting systemic circulation.\u003c/p\u003e\n \u003cdiv id=\"Sec23\"\u003e\n \u003ch2\u003ePatient and Donor Selection:\u003c/h2\u003e\n \u003cp\u003eIt is key that the donor heart is smaller than the native heart to allow for space preservation in the thoracic cavity. 3D modelling can be used to evaluate this prior to surgery (Fig.\u0026nbsp;8). If necessary, the pleura may need to be opened to facilitate more space in the mediastinum, and the lung hilum mobilised (17). Studies translated from transplant patients who received size mismatched orthotopic heart transplants showed that while initial lung volume reduction is seen, there is an improvement over time with thoracic remodelling and adaptation by the lungs (18). A feasibility study in dogs from Elefteriades et al., showcased the potential for ventricular excision however the study admitted survival data is lacking therefore although a potential adjunct to our proposed method, survival studies are needed (19).\u003c/p\u003e\n \u003cp\u003eA case series from the late 1900s showed that size matching led to a 4% greater survival rate among HHT patients compared to OHT patients (20, 21). Although this evidence may no longer reflect contemporary outcomes given the advancements in transplant techniques and postoperative care, it highlights the importance of size-matching. Moreover, this consideration may have an even greater role in the context of children and adolescent patients.\u003c/p\u003e\n \u003cp\u003ePatients must be screened for comorbidities like valvular pathologies due to the additional hemodynamic burden they impose. Moreover, the presence of CAD must be thoroughly evaluated. Patients with significant CAD might face a higher risk of ischemic complications, particularly if the native coronary circulation is relied upon for myocardial perfusion in a heterotopic setup. Consequently, patients with severe or diffuse CAD that is not amenable to revascularisation may not be ideal candidates for this novel surgical approach.\u003c/p\u003e\n \u003cp\u003eBecause the donor heart is placed in a dextrocardiac position, the venous and arterial connections need to be carefully mobilized and appropriately fixed to avoid any torsion risk.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\"\u003e\n \u003ch2\u003eLimitations:\u003c/h2\u003e\n \u003cp\u003eOur study is limited by the lack of dynamic hemodynamic data and the small sample size (n\u0026thinsp;=\u0026thinsp;3). While anatomical feasibility was demonstrated ex-vivo, the physiological challenges of balancing two independent ventricles in a living system remain to be characterized in future in-vivo porcine trials. Although 3D instructional modeling was used to visualize the great vessel orientation, this study did not include a rigorous volumetric analysis of the pediatric thoracic cavity. The \u0026quot;two-heart\u0026quot; configuration inherently requires significant mediastinal and pleural space. While we propose a dextrocardiac position with pleural opening, the risk of mechanical compression of the donor heart, the native lungs, or the great vessels is a significant factor that requires future CT-based volumetric simulation in varied age groups. Promise from conventional heterotopic transplant procedures and intrathoracic ratio matching does alleviate some of these concerns. In an isolated parallel circulation, two independent hearts with potentially different intrinsic heart rates and responses to neurohumoral stimuli must function in tandem. This is something that needs further evaluation and animal studies are being planned.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eHHT, as explored in this study, offers a potentially valuable alternative for patients with complex univentricular heart conditions or severe univentricular pump failure who are not suitable candidates for conventional OHT. By creating isolated parallel circulations, this technique may provide a novel way to support both systemic and pulmonary circulatory needs, thereby potentially broadening the range of donor hearts that can be utilised. However, this approach is still in the exploratory phase, and more research is needed to comprehensively understand its feasibility, safety, and long-term outcomes.\u003c/p\u003e\n\u003cp\u003eThe proposed strategies and techniques provide a framework for further investigation and clinical use. It is important to proceed cautiously, with thorough consideration of the complexities and potential risks involved. Future studies, including both experimental and clinical trials, will be crucial in refining these techniques, validating their benefits, and determining their place in the broader landscape of cardiac transplantation. We hope that this work encourages further exploration and discussion, contributing to the evolving field of cardiac surgery and offering new possibilities for patients facing significant cardiac failure.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRA - Right Atrium\u003c/p\u003e\n\u003cp\u003eLA - Left Atrium\u003c/p\u003e\n\u003cp\u003eLV - Left Ventricle\u003c/p\u003e\n\u003cp\u003eRV - Right Ventricle\u003c/p\u003e\n\u003cp\u003eSVC - Superior Vena Cava\u003c/p\u003e\n\u003cp\u003eIVC - Inferior Vena Cava\u003c/p\u003e\n\u003cp\u003ePA - Pulmonary Artery\u003c/p\u003e\n\u003cp\u003ePV - Pulmonary Veins\u003c/p\u003e\n\u003cp\u003eHHT \u0026ndash; Heterotopic Heart Transplant\u003c/p\u003e\n\u003cp\u003eOHT \u0026ndash; Orthotopic Heart Transplant\u003c/p\u003e\n\u003cp\u003eCPB - Cardiopulmonary Bypass\u003c/p\u003e\n\u003cp\u003eBTT - Blalock-Taussig-Thomas (Shunt)\u003c/p\u003e\n\u003cp\u003eDKS - Damus-Kaye-Stansel (Procedure)\u003c/p\u003e\n\u003cp\u003eASD - Atrial Septal Defect\u003c/p\u003e\n\u003cp\u003eMVO2 - Myocardial Oxygen Consumption\u003c/p\u003e\n\u003cp\u003eCO - Cardiac Output\u003c/p\u003e\n\u003cp\u003eHb - Haemoglobin\u003c/p\u003e\n\u003cp\u003eSvO2 - Venous Oxygen Saturation\u003c/p\u003e\n\u003cp\u003eS\u0026apos;vO2 - Venous Oxygen Saturation Post Myocardium\u003c/p\u003e\n\u003cp\u003eTCPC - Total Cavopulmonary Connection\u003c/p\u003e\n\u003cp\u003eERAs - Endothelin Receptor Antagonists\u003c/p\u003e\n\u003cp\u003ePDE-5 Inhibitors - Phosphodiesterase Type 5 Inhibitors\u003c/p\u003e\n\u003cp\u003eLVEDV - Left Ventricular End-Diastolic Volume\u003c/p\u003e\n\u003cp\u003eECG - Electrocardiogram\u003c/p\u003e\n\u003cp\u003eMRI - Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eCT - Computed Tomography\u003c/p\u003e\n\u003cp\u003eLVAD - Left Ventricular Assist Device\u003c/p\u003e\n\u003cp\u003eCAD - Coronary Artery Disease\u003c/p\u003e\n\u003cp\u003eERA - Endothelin Receptor Antagonist\u003c/p\u003e\n\u003cp\u003eVAD - Ventricular Assist Device\u003c/p\u003e\n\u003cp\u003eEF - Ejection Fraction \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAyush Balaji, Rishab Makam: Conceptualisation, Methodology, Investigation, Writing - Original Draft, Review \u0026amp; Editing, Visualisation.\u003cbr\u003e\u0026nbsp;Akshay Balaji, Shantanu Bajaj, Natasha Bocchetta: Methodology, Writing - Review \u0026amp; Editing.\u003cbr\u003e Mohammed Sherif, Nabil Hussein, Ignacio Lugones, Mahmoud Loubani: Supervision, Conceptualisation, Methodology, Resources, Writing - Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo ethical approval was required as the studies did not involve human or animal subjects. All tissues used were acquired from an abattoir sourced according to UK laws.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no new data associated with this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest related to this study.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eYazji JH, Garg P, Wadiwala I, Alomari M, Alamouti-Fard E, Hussain MWA, et al. Expanding Selection Criteria to Repairable Diseased Hearts to Meet the Demand of Shortage of Donors in Heart Transplantation. Cureus [Internet]. 2022 May 30 [cited 2024 Aug 25];14(5). Available from: /pmc/articles/PMC9150717/\u003c/li\u003e\n \u003cli\u003eKuzmiak-Glancy S, Jaimes R, Wengrowski AM, et al. Oxygen demand of perfused heart preparations: how electromechanical function and inadequate oxygenation affect physiology and optical measurements. 2015; 100: 603\u0026ndash;616.\u003c/li\u003e\n \u003cli\u003ePaolo Meani, Todaro S, Veronese G, et al. Science of left ventricular unloading. Perfusion. Epub ahead of print 26 July 2024. DOI: https://doi.org/10.1177/02676591241268389.\u003c/li\u003e\n \u003cli\u003eReemtsen BL, Polimenakos AC, Fagan BT, et al. Fate of the right ventricle after fenestrated right ventricular exclusion for severe neonatal Ebstein anomaly. The Journal of thoracic and cardiovascular surgery 2007; 134: 1406\u0026ndash;10; discussion 1410-2.\u003c/li\u003e\n \u003cli\u003eKing J, Lowery DR. Physiology, Cardiac Output. StatPearls [Internet]. 2023 Jul 17 [cited 2024 Aug 25]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK470455/\u003c/li\u003e\n \u003cli\u003eMcCormack JG, Stanley WC, Wolff AA. Ranolazine: A Novel Metabolic Modulator for the Treatment of Angina. General Pharmacology: The Vascular System. 1998 May 1;30(5):639\u0026ndash;45.\u003c/li\u003e\n \u003cli\u003eLe\u0026oacute;n-Velarde F, Villafuerte FC, Richalet JP. Chronic mountain sickness and the heart. Prog Cardiovasc Dis [Internet]. 2010 May [cited 2024 Aug 25];52(6):540\u0026ndash;9. Available from: https://pubmed.ncbi.nlm.nih.gov/20417348/\u003c/li\u003e\n \u003cli\u003eWilliams AM, Levine BD, Stembridge M. A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia. J Physiol [Internet]. 2022 Sep 1 [cited 2024 Aug 25];600(18):4089\u0026ndash;104. Available from: https://onlinelibrary.wiley.com/doi/full/10.1113/JP281724\u003c/li\u003e\n \u003cli\u003eZhao JY, Ganapathi AM, Whitson BA. Management of donor partial anomalous pulmonary veins during lung transplantation. JTCVS Tech [Internet]. 2023 Apr 1 [cited 2024 Aug 25];18:171. Available from: /pmc/articles/PMC10122138/\u003c/li\u003e\n \u003cli\u003eFujiwara T, Okada K, Hirano Y, Maki Y, Saiki M, Yunoki K, et al. Pulmonary artery reconstruction using a pulmonary vein conduit in case having an imbalanced dissection length during double-sleeve lobectomy. General Thoracic and Cardiovascular Surgery Cases 2023 2:1 [Internet]. 2023 Mar 29 [cited 2024 Aug 25];2(1):1\u0026ndash;7. Available from: https://gtcscases.biomedcentral.com/articles/10.1186/s44215-022-00027-w\u003c/li\u003e\n \u003cli\u003eLugones I, Garc\u0026iacute;a R. A new surgical approach to scimitar syndrome. Ann Thorac Surg [Internet]. 2014 Jan [cited 2024 Aug 29];97(1):353\u0026ndash;5. Available from: https://pubmed.ncbi.nlm.nih.gov/24384200/\u003c/li\u003e\n \u003cli\u003eMorris-Thurgood J, Cowell R, Paul V, Kalsi K, Seymour AM, Ilsley C, et al. Hemodynamic and metabolic effects of paced linkage following heterotopic cardiac transplantation. Circulation [Internet]. 1994 [cited 2024 Aug 25];90(5):2342\u0026ndash;7. Available from: https://pubmed.ncbi.nlm.nih.gov/7955192/\u003c/li\u003e\n \u003cli\u003eKennelly BM, Corte P, Losman J, Barnard CN. Arrhythmias in two patients with left ventricular bypass transplants\u0026rsquo;. Br Heart J. 1976;38:725\u0026ndash;31.\u003c/li\u003e\n \u003cli\u003eNovitzky D, Cooper DKC, Barnard CN, Med M. The Surgical Technique of Heterotopic Heart Transplantation. 36:476\u0026ndash;82.\u003c/li\u003e\n \u003cli\u003eLai H-Y, Chen J-H, Chiu K-M, et al. CT of Two Hearts Beating in One Chest. American Journal of Roentgenology 2008; 191: 1711\u0026ndash;1716.\u003c/li\u003e\n \u003cli\u003eNewcomb AE, Esmore DS, Rosenfeldt FL, Richardson M, Marasco SF. Heterotopic heart transplantation: An expanding role in the twenty-first century? Annals of Thoracic Surgery [Internet]. 2004 Oct 1 [cited 2024 Aug 25];78(4):1345\u0026ndash;50. Available from: http://www.annalsthoracicsurgery.org/article/S000349750400743X/fulltext\u003c/li\u003e\n \u003cli\u003eShu T, Chen H, Wang L, Wang W, Feng P, Xiang R, et al. The Efficacy and Safety of Pulmonary Vasodilators in Pediatric Pulmonary Hypertension (PH): A Systematic Review and Meta-analysis. Front Pharmacol [Internet]. 2021 Apr 23 [cited 2024 Aug 25];12:668902. Available from: www.frontiersin.org\u003c/li\u003e\n \u003cli\u003eLloyd KS, Barnard P, Holland VA, et al. Pulmonary function after heart-lung transplantation using larger donor organs. The American review of respiratory disease 1990; 142: 1026\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eElefteriades JA, Lovoulos CJ, Tellides G, et al. Right ventricle-sparing heart transplant: promising new technique for recipients with pulmonary hypertension. The Annals of Thoracic Surgery 2000; 69: 1858\u0026ndash;1863.\u003c/li\u003e\n \u003cli\u003eKhaghani A, Santini F, Dyke CM, Onuzu O, Radley-Smith R, Yacoub MH, et al. Heterotopic cardiac transplantation in infants and children. J Thorac Cardiovasc Surg. 1997 Jun 1;113(6):1042\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eBleasdale RA, Banner NR, Anyanwu AC, Mitchell AG, Khaghani A, Yacoub MH. Determinants of outcome after heterotopic heart transplantation. The Journal of Heart and Lung Transplantation. 2002 Aug 1;21(8):867\u0026ndash;73.\u003c/li\u003e\n \u003cli\u003eWilliams AM, Levine BD, Stembridge M. A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia. J Physiol. 2022 Sep;600(18):4089-4104.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp\u003eTable 1: Coronary Perfusion Strategies\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eStrategy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOxygen Source\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAnticipated Advantages\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTechnical Challenges / Risks\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFree Interposition Graft (e.g., SVB)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNative Ascending Aorta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eDirect systemic oxygenation (High PO2).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRequires two extra anastomoses; risk of graft kinking/thrombosis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePedicled Arterial Graft\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eInternal Thoracic Artery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNative arterial conduit; potentially superior long-term patency.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eLimited length; risk of \u0026quot;steal\u0026quot; from cerebral circulation.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eModified BTT Shunt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSystemic-to-PA connection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSimplifies procedure if shunt is already present; avoids new aortic puncture.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eLower PO2 (venous blood in Fontan); risk of pulmonary over-circulation.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAtrial Septostomy + Baffle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSystemic Venous Return\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEliminates need for extra-cardiac grafts; technically simpler \u0026quot;internal\u0026quot; plumbing.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eChronic Myocardial Hypoxia; relies on venous blood to coronaries.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Transplant, Fontan, Univentricular, Heterotopic, HLHS, Heart Failure","lastPublishedDoi":"10.21203/rs.3.rs-9123868/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9123868/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Objectives:\u003c/strong\u003e\u003cbr\u003e\nTo explore a novel application of heterotopic cardiac transplantation for creating isolated parallel circulations in patients with univentricular pump failure, particularly those with Hypoplastic Left Heart Syndrome or severe one-sided ventricular dysfunction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe surgical technique was developed using 3D instructional anatomical modeling and subsequently performed in an ex-vivo porcine model (n=3). We assessed the anatomical feasibility of the \"parallel\" configuration, where the donor and native hearts function independently to support the systemic and pulmonary circuits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnatomical feasibility was demonstrated in all three porcine preparations. Key surgical maneuvers included extensive mobilization and anterior transposition of the branch pulmonary arteries and pulmonary vein (PV) rerouting to the donor left atrium. Anastomoses remained patent and leak-free under static fluid loading.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003cbr\u003e\nHeterotopic cardiac transplantation with isolated parallel circulations may offer a novel therapeutic option for patients with complex congenital heart conditions or severe univentricular pump failure who are unsuitable for conventional orthotopic transplantation. This approach could potentially expand the pool of donor hearts available for transplantation and improve outcomes for this challenging patient population. However, further research, including clinical trials, is necessary to assess the safety, efficacy, and long-term outcomes of this innovative technique. This study lays the groundwork for future exploration and could represent a significant advancement in the field of cardiac transplantation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCentral Message: \u003c/strong\u003eThis study introduces a pioneering surgical concept of utilizing heterotopic cardiac transplantation to establish isolated parallel circulations in patients with failing single ventricles. Supported by ex vivo simulations and novel anatomical reconstructions, it lays foundational work for potentially expanding donor heart availability and expanding therapeutic options in complex congenital heart disease. Further preclinical and clinical research is necessary to translate this innovative concept into practice.\u003c/p\u003e","manuscriptTitle":"Can Two Halves Make a Whole? Technical Feasibility of Isolated Parallel Circulation Heterotopic Cardiac Transplantation: A Pre-clinical Study in 3D and Porcine Models","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-17 09:35:58","doi":"10.21203/rs.3.rs-9123868/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"17b42eb4-5b18-48fb-80a0-d26fe20ba7f3","owner":[],"postedDate":"March 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-19T16:25:54+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-17 09:35:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9123868","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9123868","identity":"rs-9123868","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}