A retrospective study: Long term prognosis in adults with PA-VSD-MAPCAs.

BACKGROUND: Pulmonary Atresia, Ventricular Deptal Defect, and Major Aortopulmonary Collateral Arteries (PA-VSD-MAPCAs) is a congenital cyanotic heart defect with poor prognosis. Due to its complex and highly variable anatomy, the best treatment plan is not clear. We aimed (1) to investigate the survival of PA-VSD-MAPCAs patients according to the underlying original anatomy and treatment strategy, and (2) to evaluate life expectancy between patients with or without severe hypoplastic native pulmonary arteries(s) after surgical versus non-surgical treatment. METHODS: A prospectively established database of 169 PA-VSD-MAPCAs patients treated and followed up at University Hospitals Leuven was accessed. Patients were divided into three groups according to the treatment strategy. Kaplan-Meier survival curves were plotted, and Log Rank tests were used for comparison. RESULTS: The overall mean survival for patients with PA-VSD-MAPCAs was 38.5 years (95%-CI: 33.1-43.9). Patients with complete intracardiac repair had the longest mean survival of 43.8 years (95%-CI: 38.1-49.6) versus the other groups (p < 0.001). A longer mean event-free survival time was found in patients with normal, well-developed NPAs (p = 0.047). Finally, patients with poorly developed or absent NPAs had worse survival rates when a surgical approach was followed. Systemic-pulmonary shunt placement or unifocalisation had limited effect on prognosis in the absence of total repair (p = 0.167). CONCLUSIONS: Patients with PA-VSD-MAPCAs who underwent complete intracardiac repair and/or with well-developed native pulmonary arteries had the best prognosis. Our analyzed data suggest that incomplete surgical repair resulted in survival rates comparable to those seen with a non-surgical approach.

Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial.

BACKGROUND: Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. METHODS: We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. FINDINGS: A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). INTERPRETATION: Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. FUNDING: XVIVO Perfusion.

Innovations in transplant techniques for complex anomalies.

PURPOSE OF REVIEW: With advances in the field of congenital cardiac surgery and in the management of congenital heart defects in early life, the population of adult congenital heart disease (ACHD) patients is increasing. End-stage heart failure is currently the main cause of cardiovascular mortality and is expected to increase in the coming years. This review summarizes recent innovations in transplant techniques, with special attention to what is known in the population of ACHD recipients. RECENT FINDINGS: The use of machine perfusion for heart preservation enables longer preservation times. Normothermic (organ care system - OCS) and hypothermic (hypothermic oxygenated perfusion - HOPE) machine perfusion will alleviate the time pressure associated with heart transplantation in the ACHD population, may allow for expansion of the geographical range in which donors can be matched and may improve graft quality. Donation after circulatory death (DCD) heart transplantation, either through direct procurement-machine perfusion (DP-MP) or thoraco-abdominal normothermic regional perfusion (TA-NRP) is a viable strategy to further expand the donor pool. SUMMARY: The use of machine perfusion and DCD donors in ACHD is feasible and shows promise. Time pressure and shortage of donors is even more critical in ACHD than in other patient populations, making these innovations particularly relevant. Further clinical experience and research is needed to elucidate their impact.

Long-term outcome after the Ross procedure in 173 adults with up to 25 years of follow-up.

OBJECTIVES: The potential risk of autograft dilatation and homograft stenosis after the Ross procedure mandates lifelong follow-up. This retrospective cohort study aimed to determine long-term outcome of the Ross procedure, investigating autograft and homograft failure patterns leading to reintervention. METHODS: All adults who underwent the Ross procedure between 1991 and 2018 at the University Hospitals Leuven were included, with follow-up data collected retrospectively. Autograft implantation was performed using the full root replacement technique. The primary end-point was long-term survival. Secondary end-points were survival free from any reintervention, autograft or homograft reintervention-free survival, and evolution of autograft diameter, homograft gradient and aortic regurgitation grade over time. RESULTS: A total of 173 adult patients (66% male) with a median age of 32 years (range 18-58 years) were included. External support at both the annulus and sinotubular junction was used in 38.7% (67/173). Median follow-up duration was 11.1 years (IQR, 6.4-15.9; 2065 patient-years) with 95% follow-up completeness. There was one (0.6%) perioperative death. Kaplan-Meier estimate for 15-year survival was 91.1% and Ross-related reintervention-free survival was 75.7% (autograft: 83.5%, homograft: 85%). Regression analyses demonstrated progressive neoaortic root dilatation (0.56 mm/year) and increase in homograft gradient (0.72 mmHg/year). CONCLUSIONS: The Ross procedure has the potential to offer excellent long-term survival and reintervention-free survival. These long-term data further confirm that the Ross procedure is a suitable option in young adults with aortic valve disease which should be considered on an individual basis.

Validating the Concept of Mechanical Circulatory Support with a Rotary Blood Pump in the Inferior Vena Cava in an Ovine Fontan Model.

Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary arteries. Our purpose was to investigate whether increasing inferior vena cava (IVC) flow with a rotary blood pump in the IVC only in an ovine animal model of Fontan would lead to acceptable superior vena cava (SVC) pressure. To achieve this, a Fontan circulation was established in four female sheep by anastomosing the SVC to the main pulmonary artery (MPA) and by interposing a Dacron graft between the IVC and the MPA. A rotary blood pump was then introduced in the graft, and the effect of incremental flows was observed at increasing flow regimen. Additionally, to stimulate increased pulmonary resistance, the experience was repeated in each animal with the placement of a restrictive band on the MPA distally to the SVC and Dacron graft anastomosis. Circulatory support of IVC flow alone increased the systemic cardiac output significantly, both with and without banding, indicating the feasibility of mechanical support of the Fontan circulation by increasing the flow only in the inferior vena cava. The increase in SVC pressure remained within acceptable limits, indicating the potential effectiveness of this mode of support. The findings suggest that increasing the flow only in the inferior vena cava is a feasible method for mechanical support of the Fontan circulation, potentially leading to an increase in cardiac output with acceptable increases in superior vena cava pressure.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale. The cell-scale model consists of a network model, that includes important signaling pathways and relations between relevant transcription factors and their target genes. The resulting gene activity leads to changes in the mechanical properties of the tissue, modeled as a constrained mixture of collagen, elastin and smooth muscle. The multiscale model is calibrated with findings from experiments in which seven sheep underwent the Ross procedure. The model is then validated against a different set of sheep experiments, for which a qualitative agreement between model and experiment is found. Model outcomes at the cell scale, including the activity of genes and transcription factors, also match experimentally obtained transcriptomics data.

Anesthesia for Combined Heart-Liver Transplantation: A Narrative Review.

In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years.

Hemodynamics and wall shear metrics in a pulmonary autograft: Comparing a fluid-structure interaction and computational fluid dynamics approach.

OBJECTIVE: In young patients, aortic valve disease is often treated by placement of a pulmonary autograft (PA) which adapts to its new environment through growth and remodeling. To better understand the hemodynamic forces acting on the highly distensible PA in the acute phase after surgery, we developed a fluid-structure interaction (FSI) framework and comprehensively compared hemodynamics and wall shear-stress (WSS) metrics with a computational fluid dynamic (CFD) simulation. METHODS: The FSI framework couples a prestressed non-linear hyperelastic arterial tissue model with a fluid model using the in-house coupling code CoCoNuT. Geometry, material parameters and boundary conditions are based on in-vivo measurements. Hemodynamics, time-averaged WSS (TAWSS), oscillatory shear index (OSI) and topological shear variation index (TSVI) are evaluated qualitatively and quantitatively for 3 different sheeps. RESULTS: Despite systolic-to-diastolic volumetric changes of the PA in the order of 20 %, the point-by-point correlation of TAWSS and OSI obtained through CFD and FSI remains high (r > 0.9, p < 0.01) for TAWSS and (r > 0.8, p < 0.01) for OSI). Instantaneous WSS divergence patterns qualitatively preserve similarities, but large deformations of the PA leads to a decrease of the correlation between FSI and CFD resolved TSVI (r < 0.7, p < 0.01). Moderate co-localization between FSI and CFD is observed for low thresholds of TAWSS and high thresholds of OSI and TSVI. CONCLUSION: FSI might be warranted if we were to use the TSVI as a mechano-biological driver for growth and remodeling of PA due to varying intra-vascular flow structures and near wall hemodynamics because of the large expansion of the PA.

Difference in coagulation systems of large animal species used in cardiovascular research: a systematic review.

Preclinical testing using animal models is indispensable in cardiovascular research. However, the translation to clinical practice of these animal models is questionable since it is not always clear how representative they are. This systematic review intends to summarize the interspecies differences in the coagulation profile of animal models used in cardiovascular research. It aims to guide future research in choosing the optimal animal species. A literature search of PubMed, Embase, Web of Science (Core Collection) and Cochrane Library was performed using a search string that was well defined and not modified during the study. An overview of the search terms used in each database can be found in the appendix. Articles describing coagulation systems in large animals were included. We identified 30 eligible studies of which 15 were included. Compared to humans, sheep demonstrated a less active external pathway of coagulation. Sheep had a higher platelet count but the platelet activatability and response to biomaterials were lower. Both sheep and pigs displayed no big differences in the internal coagulation system compared to humans. Pigs showed results very similar to those of humans, with the exception of a higher platelet count and stronger platelet aggregation in pigs. Coagulation profiles of different species used for preclinical testing show strong variation. Adequate knowledge of these differences is key in the selection of the appropriate species for preclinical cardiovascular research. Future thrombogenicity research should compare sheep to pig in an identical experimental setup.

Validation of large animal models in mechanical valve research: a histologic comparison.

OBJECTIVES: Mechanical valves still require life-long anticoagulation. Preclinical animal testing is a crucial step in the assessment of valves; however, the chosen animal model should be carefully considered, and a well-controlled animal model of mechanical valve thrombosis has not been established yet. In this study, a histopathologic comparison was performed to evaluate the representativity of pigs and sheep as large animal models in bileaflet mechanical valve thrombosis research. METHODS: 10 pigs and 8 sheep were implanted with a bileaflet mechanical valve in pulmonary position. During follow-up, no anticoagulative therapy was administered. Pigs were sacrificed between 14 and 38 days for explantation and assessment of the valve. Sheep were sacrificed between 71 and 155 days. Thrombus samples were processed and (immuno)histochemical stainings were applied. A pathologist evaluated the samples morphologically and semiquantitatively and compared these samples to available slides from 3 human patients who underwent redo surgery for acute bileaflet mechanical valve thrombosis, caused by insufficient anticoagulation. RESULTS: All pigs showed macroscopically evident thrombi on the mechanical valve surface at sacrifice. In contrast, none of the sheep showed any sign of thrombus formation. Histology showed a high fibrin content in thrombi of both human and porcine cases (3/3 vs 8/10). Porcine thrombi showed more cellular organization (0/3 vs 6/10), more calcification (0/3 vs 9/10) and more endothelialization (0/3 vs 6/10). Inflammatory cells were present in all samples and were considered physiological. CONCLUSIONS: Contrary to sheep, pigs develop thrombi on their mechanical valves in the short-term if no anticoagulation is administered. Histologic comparison of human and porcine thrombi shows comparable findings. The pig model might serve interestingly for further research on valve thrombosis, if it shows not to be an overly aggressive model.

Transcatheter versus surgical aortic valve replacement for severe aortic valve stenosis: Meta-analysis with trial sequential analysis.

OBJECTIVES: Randomized controlled trials comparing transcatheter aortic valve implantation with surgical aortic valve replacement demonstrate conflicting evidence, particularly in low-risk patients. We aim to reevaluate the evidence using trial sequential analysis, balancing type I and II errors, and compare with conventional meta-analysis. METHODS: Databases were searched for randomized controlled trials, which were divided into higher-risk and lower-risk randomized controlled trials according to a pragmatic risk classification. Primary outcomes were death and a composite end point of death or disabling stroke assessed at 1 year and maximum follow-up. Conventional meta-analysis and trial sequential analysis were performed, and the required information size was calculated considering a type I error of 5% and a power of 90%. RESULTS: Eight randomized controlled trials (n = 5274 higher-risk and 3661 lower-risk patients) were included. Higher-risk trials showed no significant reduction in death at 1 year with transcatheter aortic valve implantation (relative risk, 0.93, 95% CI, 0.81-1.08, P = .345). Lower-risk trials suggested lower death risk on conventional meta-analysis (relative risk, 0.67, 95% CI, 0.47-0.96, P = .031), but trial sequential analysis indicated potential spurious evidence (P = .116), necessitating more data for conclusive benefit (required information size = 5944 [59.8%]). For death or disabling stroke at 1 year, higher-risk trials lacked evidence (relative risk, 0.90, 95% CI, 0.79-1.02, P = .108). In lower-risk trials, transcatheter aortic valve implantation indicated lower risk in conventional meta-analysis (relative risk, 0.68, 95% CI, 0.50-0.93, P = .014), but trial sequential analysis suggested potential spurious evidence (P = .053), necessitating more data for conclusive benefit (required information size = 5122 [69.4%]). Follow-up results provided inconclusive evidence for both primary outcomes across risk categories. CONCLUSIONS: Conventional meta-analysis methods may have prematurely declared an early reduction of negative outcomes after transcatheter aortic valve implantation when compared with surgical aortic valve replacement.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.

Paediatric aortic valve replacement using decellularized allografts: a multicentre update following 143 implantations and five-year mean follow-up.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced in 2008 as a further option for paediatric aortic valve replacement (AVR). METHODS: Prospective, multicentre follow-up of all paediatric patients receiving DAH for AVR in 8 European centres. RESULTS: A total of 143 DAH were implanted between February 2008 and February 2023 in 137 children (106 male, 74%) with a median age of 10.8 years (interquartile range 6.6-14.6). Eighty-four (59%) had undergone previous cardiac operations and 24 (17%) had undergone previous AVR. The median implanted DAH diameter was 21 mm (interquartile range 19-23). The median operation duration was 348 min (227-439) with a median cardiopulmonary bypass time of 212 min (171-257) and a median cross-clamp time of 135 min (113-164). After a median follow-up of 5.3 years (3.3-7.2, max. 15.2 years), the primary efficacy end-points peak gradient (median 14 mmHg, 9-28) and regurgitation (median 0.5, interquartile range 0-1, grade 0-3) showed good results but an increase over time. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 5 years were 97.8 ± 1.2/88.7 ± 3.3/99.1 ± 0.9/100 and 99.2 ± 0.8%, respectively. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 10 years were 96.3 ± 1.9/67.1 ± 8.0/93.6 ± 3.9/98.6 ± 1.4 and 86.9 ± 11.6%, respectively. In total, 21 DAH were explanted. Seven were replaced by a mechanical AVR, 1 Ross operation was performed and a re-do DAH was implanted in 13 patients with no redo mortality. The calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.4 years), and in the same range as for Ross patients (9.2 years) and mechanical AVR (13.0 years). CONCLUSIONS: This large-scale prospective analysis demonstrates excellent mid-term survival using DAH with adverse event rates comparable to paediatric Ross procedures.

Mitral valve replacement in children: balancing durability and risk with mechanical and bioprosthetic valves.

OBJECTIVES: To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement. METHODS: We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases. The incidence rate of a 2nd replacement was calculated using the cumulative incidence function that considered death or transplantation as a competing risk. RESULTS: The median age at implantation was 3.6 years (interquartile range 0.8-7.9) for the bioprosthetic valve cohort (n = 28) and 3 years (interquartile range 1.3-7.8) for the mechanical valve cohort (n = 28). Seven years after bioprosthetic mitral valve replacement, the cumulative incidence of death or transplantation was 17.9% [95% confidence interval (CI) 6.3-34.1] and the cumulative incidence of a 2nd replacement was 63.6% (95% CI 39.9-80.1). Seven years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 28.6% (95% CI 13.3-46) and the cumulative incidence of a 2nd replacement was 10.7% (95% CI 2.6-25.5). Fifteen years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 33.6% (95% CI 16.2-52.1) and the cumulative incidence of a 2nd replacement was 41.1% (95% CI 18.4-62.7). The cumulative incidence curves for bioprosthetic and mechanical mitral valve replacement were statistically different for a 2nd valve replacement (P < 0.001) but not for death or transplantation (P = 0.33). CONCLUSIONS: There is no difference in transplant-free survival after bioprosthetic and mechanical mitral valve replacement in children. The lifespan of bioprosthetic mitral valves remains limited in children because of structural valve failure due to calcification. After 15 years, 40% of mechanical valves were replaced, primarily because of patient-prosthesis mismatch related to somatic growth.

Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function, and their interplay have accumulated, resulting in advanced knowledge on the complex functional characteristics of the aortic valve (AV) and root. This has shifted our vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved, with a similar shift towards treatments options that are more hemodynamically centered, such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress-related stimuli. Many of these physiological and hemodynamical processes are under-acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision making.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Complications related to extracorporeal life support in lung transplantation: single-center analysis.

Background: Extracorporeal life support (ECLS) is not routinely used at our center during sequential single-lung transplantation (LTx), but is restricted to anticipate and overcome hemodynamic and respiratory problems occurring peri-operatively. In this retrospective descriptive cohort study, we aim to describe our single-center experience with ECLS in LTx, analyzing ECLS-related complications. Methods: All transplantations with peri-operative ECLS use [2010-2020] were retrospectively analyzed. Multi-organ and heart-lung transplantation were excluded. Demographics, support type and indications are described. Complications are categorized according to the underlying nature and type. Data are presented as median [interquartile range (IQR)]. Kaplan-Meier was used for survival analysis. Results: The overall use of ECLS was 22% (156/703 patients) with a mean age of 52 years (IQR, 36-59 years). Transplant indications in ECLS cohort were interstitial lung disease (38%; n=60), chronic obstructive pulmonary disease (COPD) (19%; n=29), cystic fibrosis (17%; n=26) and others (26%; n=41). Per indication, 94% (15/16) of pulmonary arterial hypertension patients required ECLS, whereas only 8% (29/382) of COPD patients did. In 16% (25/156) of supported patients, veno-venous extracorporeal membrane oxygenation was initiated, while 77% (120/156) required veno-arterial support, and 7% (11/156) cardiopulmonary bypass. Thirty-day mortality was 6% (9/156). Sixteen percent (25/156) of patients were bridged to transplantation on ECLS and 24% (37/156) required post-operative support. Main reasons to use ECLS were intra-operative hemodynamic instability (53%; n=82), ventilation/oxygenation problems (22%; n=34) and reperfusion edema (17%; n=26). Overall incidence of patients with at least one ECLS-related complication was 67% (n=104). Most common complications were hemothorax (25%; n=39), need for continuous renal replacement therapy (19%; n=30), and thromboembolism (14%; n=22). Conclusions: ECLS was required in 22% of LTxs, with a reported ECLS-related complication rate of 67%, of which the most common was hemothorax. Larger databases are needed to further analyze complications and develop tailored deployment strategies for ECLS-use in LTx.