Background: Acute cellular rejection (ACR) after heart transplantation remains incompletely explained despite standardized immunosuppression. Environmental exposures may contribute to residual immune activation; however, prior studies have focused primarily on air pollution rather than residential land-use composition. Objectives: To determine whether buffer-specific residential environmental composition is associated with rejection risk and whether these associations are scale-dependent and domain-specific. Methods: In this retrospective single-center cohort study, 30 heart transplant recipients contributed 267 biopsy-linked observations. Residential land-use composition was quantified within 300 m, 500 m, 700 m, and 1000 m buffers and aggregated into five domains: trees, other green surroundings, roads, water, and industrial land. Associations with ACR were evaluated using clustered logistic regression models adjusted for time since transplantation. Results: The strongest and only statistically robust associations after FDR correction were observed within the 300 m buffer. Tree-dominant (OR 1.42, 95% CI 1.22-1.65, q = 0.010) and industrial land exposure (OR 1.50, 95% CI 1.28-1.76, q = 0.010) were independently associated with increased odds of ACR. At 500 m, the association with trees persisted nominally (OR 1.39, 95% CI 1.03-1.88, p = 0.034), but did not remain significant after FDR correction, whereas water exposure showed a non-significant trend (OR 1.28, p = 0.057), which did not reach statistical significance. No associations were observed beyond 700 m across all models. Conclusions: Residential environmental composition may be associated with acute cellular rejection after heart transplantation in a scale-dependent manner, with signals confined to the immediate residential environment. Tree-dominant exposure within 300 m showed an association in clustered models; however, this finding was attenuated in mixed-effects sensitivity analyses. These results should be considered exploratory and hypothesis-generating study.

Heart transplantation (HTx) remains the main long-term treatment for end-stage heart failure. Due to the high risk of acute cellular rejection (ACR), HTx recipients undergo multiple endomyocardial biopsies to monitor graft tolerance. This prospective, single-center study evaluated quantitative magnetic resonance imaging (MRI), particularly T1- and T2-mapping, as noninvasive tools for rejection monitoring. The study included 17 adult HTx recipients (men, 88

Background:Primary cardiac tumours are rare, and cardiac lipomas represent only 8.4% of these cases. Cardiac lipomas consist of two pathologically distinct types: lipomas, and lipomatous hypertrophy of the interatrial septum (LHIS). Both types can be challenging to differentiate through imaging and are often reported together in the literature, complicating an accurate count of each type. Cardiac lipomas can occur in all chambers of the heart, most commonly in the atrial septum and the right atrium, often presenting incidentally or during evaluation of non-specific symptoms. Case summary:This report presents a case of a 54-year-old female, who was incidentally found to have a large cardiac tumour during a routine abdominal ultrasound. Transthoracic and transoesophageal echocardiography revealed a 65 × 58 × 55 mm tumour occupying the right atrium. Initial suspicion pointed to a myxoma; however, surgical and pathological analysis confirmed the diagnosis of cardiac lipoma. The patient underwent complex cardiac surgery, which included tumour resection, atrial wall reconstruction, PFO closure, tricuspid ring implantation and left anterior descending artery (LAD) grafting using left internal mammary artery (LIMA). The patient recovered well however due to the perioperative complete atrioventricular (AV) block required permanent pacemaker implantation. The patient remains under regular echocardiographic follow-up to monitor for potential recurrence. Discussion:This case underscores the importance of surgical intervention for benign large intracavitary tumours to prevent mechanical and haemodynamic complications and improve long-term outcome. Carefully planning of surgical treatment should take into account the complexity of the procedure and potential conduction disturbances.

Giant cell myocarditis (GCM) is a rare, often fulminant inflammatory cardiomyopathy associated with rapid progression to advanced heart failure and high mortality. We report the case of a 52-year-old male with previously undiagnosed GCM who developed post-inflammatory cardiomyopathy leading to severe left ventricular dysfunction. Despite implantation of a cardiac resynchronization therapy defibrillator (CRT-D) and later a HeartMate III left ventricular assist device (LVAD) as a bridge to transplantation, the patient’s condition gradually worsened. Orthotopic heart transplantation was performed 5.5 years after diagnosis, with histopathological analysis of the explanted heart confirming GCM. Post-transplant follow-up over 16 months demonstrated preserved graft function, absence of recurrence, and stable clinical status. This case highlights the importance of histopathological evaluation of explanted hearts, the diagnostic challenges of atypical GCM, and the role of LVAD and heart transplantation in ensuring long-term survival. Video 1. Transthoracic echocardiography showing severely impaired left ventricular contractility with a left ventricular ejection fraction. Watch video

Background: In end-stage HF, interventional therapy is the treatment of choice, including mechanical circulatory support and heart organ transplantation. Acute cellular rejection is considered a major impediment to the long-term survival of cardiac allografts. The aim of this study is to point out a possible relationship underlying acute cellular rejection risk in heart organ recipients. Methods: A total of 30 (25 (83%) men and 5 (17%) women) heart organ recipients with a median (Q1–Q3) age of 49 (38–60) were enrolled in the analysis. The results from repeated hospitalizations due to protocolar endomyocardial biopsies performed between one and three months following the heart transplantation in relation air pollution exposure were taken into the analysis. Results: The median (Q1–Q3) observation time after organ transplantation was 92 (82–97) days. A significant difference in PM2.5 exposure between the rejection group (16.10 (14.24–17.61)) μg/m3 and the non-rejection group (11.97 (9.85–12.97)) μg/m3 was noticed (p < 0.001). The odds ratio (95% confidence interval) for acute rejection prediction related to PM2.5 was 1.79 (1.11–2.89), p = 0.018. The reviewer operator curve for acute cellular rejection related to PM2.5 exposure was performed, and the area under the curve (AUC) was 0.873, yielding a precision of 0.600 and an f-measure of 0.545. The predicted residual plots for PM2.5 indicated a 50% increased risk for PM2.5 above 16 μg/m3 and of 91% for PM2.5 above 20 μg/m3. Conclusions: The single-center study was performed on a limited number of heart organ recipients and was related to personalized individual calculations of PM2.5 exposure. The study represents a personalized approach and indicates possible links to the hypothesis, which should be verified on a higher volume of patients.

Thick struts and polymeric crystalline material are the potential mechanism of failure of the first generation bioresorbable scaffolds (BRS). We evaluated a novel fully amorphous bioresorbable scaffold (BRS) made of poly-L-lactide/poly-L-glycolide (PLLA/PLGA, Apollo, Biostent Consortium, Poland) in a porcine coronary restenosis model. Uncoated BRS (PLLA 120 μm, n = 7; PLLA 150 μm, n = 8; PLLA/PLGA 200 μm, n = 10) were implanted in 12 swine using OCT guidance and 110% overstretch. Follow-up included angiography, OCT, and histopathology at 30 and 90 days. At 30 days, OCT showed no significant differences in stenosis or neointimal hyperplasia between groups as represented by percent area stenosis (PLLA 120: 41% ± 17, PLLA 150: 52 ± 20%, PLLA/PLGA: 55 ± 6%; p = 0.07 ) and neointimal area (PLLA 120: 2.01 ± 0.8 mm2, PLLA 150: 2.57 ± 1.1 mm2, PLLA/PLGA: 2.02 ±0.8 mm2; p = 0.39). The average number and proportion of struts with no inflammation (score 0) was 7.2 fold higher in the PLLA/PLGA when compared to PLA 120 (p = 0,03). The endothelialization was nearly complete and comparable in all groups. At 90 days, PLLA/PLGA remained patent, covered, and free of restenosis, with positive remodeling and late lumen enlargement only in PLLA/PLGA group (lumen area 30 vs. 90 day: 1.86 vs. 3.40 mm², p = 0.02). The novel PLLA/PLGA BRS demonstrated improved healing, reduced inflammation and positive remodeling, supporting its potential for next-generation BRS.

Interactions of graphene oxide (GO) with an ex vivo rat heart and its coronary vessels have not been studied yet. Moreover, the conflicting data on the "structure-properties" relationships do not allow for biomedical applications of GO. Herein, we study the impact of GO on the ex vivo isolated rat heart, normotensive and hypertensive, under the working heart and the constant-pressure perfusion (Langendorff) regimes. Four structural GO variants of the following initial morphology were used: few-layer (below 10-layer) GO1, O < 49%; predominantly single-layer GO2, O = 41-50%; 15-20-layer GO3, O < 11%; and few-layer (below 10-layer) NH4+-functionalized GO4, O < 44%, N = 3-6%. The aqueous GO dispersions, sonicated and stabilized with bovine serum albumin in Krebs-Henseleit-like solution & horbar;uniformized in terms of the particle size & horbar;were eventually size-monodisperse as revealed by dynamic light scattering. To study the cardiotoxicity mechanisms of GO, histopathology, Raman spectroscopy, analysis of cardiac parameters (coronary and aortic flows, heart rate, aortic pressure), and nitric oxide (NO-)-dependent coronary flow response to bradykinin (blood-vessel-vasodilator) were used. GO1 (10 mg/L) exerted no effects on cardiac function and preserved an increase in coronary flow in response to bradykinin. GO2 (10 mg/L) reduced coronary flow, aortic pressure in normotensive hearts, and coronary flow in hypertensive hearts, and intensified the response to bradykinin in normal hearts. GO3 (10 mg/L) reduced all parameters in hypertensive hearts and coronary response to bradykinin in normal hearts. At higher concentrations (normotensive hearts, 30 mg/L), the coronary response to bradykinin was blocked. GO4 (10 mg/L) reduced the coronary flow in normal hearts, while for hypertensive hearts, all parameters, except the coronary flow, were reduced and the coronary response to bradykinin was blocked. The results showed that a low number of GO layers and high O-content were safer for normal and hypertensive rat hearts. Hypertensive hearts deteriorated easier upon perfusion with low-O-content GOs. Our findings support the necessity of strict control over the GO structure during organ perfusion and indicate the urgent need for personalized medicine in biomedical applications of GO.

CONTEXT.— Extracorporeal membrane oxygenation (ECMO) is increasingly used in the treatment of respiratory and cardiac failure, but data describing lung histopathology in ECMO recipients are limited. OBJECTIVE.— To examine pulmonary histopathologic findings in patients who underwent venovenous (VV) ECMO for pulmonary reasons, or venoarterial (VA) ECMO for cardiac indications shortly before death, and to determine if the pulmonary changes provided insights into therapy that may prevent complications and improve outcome. DESIGN.— We conducted a retrospective study of lung autopsies, from VV and VA ECMO recipients and patients with acute respiratory distress syndrome (ARDS) and non-ECMO treatment, between 2008 and 2020 in Silesia Center for Heart Diseases in Zabrze, Poland. RESULTS.— Among 83 ECMO patients (42-64 years; male, 57 [68.7%]), the most common histopathologic findings were bronchopneumonia (44 [53.0%]), interstitial edema (40 [48.2%]), diffuse alveolar damage (DAD; 32 [38.6%]), hemorrhagic infarct (28 [33.7%]), and pulmonary hemorrhage (25 [30.1%]). DAD was associated with longer ECMO treatment and longer hospital stay. The use of VV ECMO was a predictor of DAD in patients with ARDS and undergoing ECMO, but it also occurred in 21 of 65 patients (32.3%) in the VA ECMO group, even though VA ECMO was used for heart failure. CONCLUSIONS.— Although DAD was significantly more common in lung autopsies of VV ECMO patients, one-third of VA ECMO patients had histopathologic changes characteristic of ARDS. The presence of DAD in lung autopsies of patients treated with VA ECMO indicates that in these patients, protective lung ventilation should be considered.

Diagnosis of myocarditis as the cause of death in the forensic setting at post-mortem is currently determined by a forensic pathologist. There is no systematic method for diagnosis and thus the determination is subject to inter-observer variability and is often non-reproducible. The primary aim of this study was to investigate the differences in the amount of inflammation between cases where myocarditis was deemed the cause of death, compared to cases where myocardial inflammation was incidentally present at autopsy, but not determined to be the cause of death. Participants were sourced from the Victorian Institute of Forensic Medicine (VIFM) database, from full autopsies conducted on reportable death in Victoria, Australia between the years 2011 and 2021.Cases of fatal myocarditis were significantly more likely to experience infection-like symptoms prior to death, and to be in hospital at the time of death. Histopathological examination revealed fatal cases had a significantly higher inflammatory index compared to the incidental group. Lethal cases were also significantly more likely to have myocyte necrosis, and a diffuse pattern of inflammation.There are significant differences between cases where myocardial inflammation has been determined to be the cause of death and cases where inflammation in the myocardium was an incidental finding. These results could be used in the forensic autopsy to help pathologists determine if inflammation should be considered fatal or incidental.

Median sternotomy is the surgical method of choice for many procedures where one of the main problems is the long post-operative wound healing process leading to sternal dehiscence and the development of infection. This leads to prolonged hospital stay and increased mortality due to post-operative complications. A promising solution seems to be the use of allogeneic chondrocytes for wound treatment, whose properties in the field of cartilage reconstruction are widely used in medicine, mainly in orthopedics. In the present study, we investigated the effect of local delivery of allogeneic chondrocytes on the biological response and healing of the sternum after sternotomy. We optimized the culture conditions for the isolated chondrocytes, which were then applied to the sternal incision wound. Chondrocytes in the culture were assessed on the basis of the presence of chondrocyte-specific genes: Sox9, Aggrecan and Collagen II. In turn, the histopathological and immunohistochemical evaluation was used to assess the safety of implantation. In our work, we demonstrated the possibility of obtaining a viable culture of chondrocytes, which were successfully introduced into the sternal wound after sternotomy. Importantly, implantation of allogeneic chondrocytes showed no significant side effects. The obtained results open new possibilities for research on the use of allogeneic chondrocytes in the process of accelerating wound healing after median sternotomy.

BACKGROUND:The aim of the study was to evaluate bio-functionality of a novel, proprietary balloon-expandable biological transcatheter aortic valve implantation (TAVI) system (InFlow, CardValve Consortium, Poland) in an ovine model of aortic banding. METHODS:Surgical ascending aorta banding was created in 21 sheep. Two weeks later, 18 biological valves were implanted within the model using 15-16 F InFlow TAVI systems and carotid cut-down approach. Follow-up transthoracic echocardiography was performed at 30, 90, and 180-day. At designated time, animals were euthanized and valves harvested for analysis. RESULTS:All sheep survived the banding procedure. There were 4 (22%) procedure related deaths within a 7-day period. During the observation an additional 2 sheep died. In one, the valve dislocated after the procedure - the animal was excluded. Two animals completed 30-day follow up, five 90-day follow-up and four terminal follow-up of 180 days. Valves examined via transesophageal echocardiography showed proper hemodynamic parameters without evidence of structural valve deterioration. The maximum and average flow gradients at 180 days were 31.4 (23.3-37.7) and 17.5 (13.1-20.2) mmHg, respectively. There was one case of moderate insufficiency and no case of perivalvular leaks. By histopathology, there were no inflammation, thrombosis, nor calcifications in any tested valves at long-term follow-up. Neointimal coverage of stent struts increased with time from basal part in "early" groups to nearly 3/4 of stent length in the 180-day group. The pannus tissue showed maturation that increased with time with no stenotic "collar" visible in orthotopically implanted valves. CONCLUSIONS:The study showed good hemodynamic performance, durability and biocompatibility of the novel biological THV.

ObjectivesThe aim of the study is to evaluate the functionality, durability, and temporal biocompatibility of a novel, balloon-expandable polymeric transcatheter heart valve (ATHV) system (InFlow, CardValve Consortium, Poland). Along with expanding TAVI indications, the demand for new transcatheter valves is increasing.MethodsA surgical ascending aortic banding model was created in 20 sheep. Two weeks later, 16 sheep were implanted with ATHV systems (15–16F). Three animals were euthanized after a 30-day follow-up, four animals after a 90-day follow-up, and six animals after a 180-day follow-up. A follow-up transthoracic echocardiography (TTE) was performed.ResultsThere was one procedure-related (6,25%) and two model-related deaths (12,5%; banding site calcification with subsequent infection originating externally from banding). TTE revealed the flow gradients (max/average) of 30,75/17,91; 32,57/19,21; and 21,34/10,63 mmHg at 30, 90, and 180 days, respectively. There were two cases of low-degree regurgitation after 180 days with no perivalvular leak observed. Histopathological analysis showed no valve degeneration at terminal follow-up with optimal healing. Small thrombi were present at the aortic wall adjacent to the base of the leaflets, and between the aortic wall and the stent in most of the valves; however, leaflets remained free from thrombi in all cases. Scanty calcifications of leaflets were reported in three animals evaluated 180 days after implantation.ConclusionThis preclinical study in the aortic banding model showed good hemodynamic performance, durability, and biocompatibility of the novel ATHV. Furthermore, regulatory studies with longer follow-ups are warranted.

The consequences of myocardial infarction (MI) are an increasing problem worldwide. Despite spectacular progress in the invasive treatment of ischemic heart disease, the ability to limit the ischemia-reperfusion (I/R) injury remains largely unrealized. Recent studies have shown that stimulation of opioid receptors may confer a cardioprotective effect against I/R injury. Levosimendan, the inodilator, is indicated for the shortterm treatment of acutely decompensated heart failure. We tested the hypothesis that levosimendan may provide cardioprotection in the opioid-like mechanism in the human myocardium.

Cardiac stereotactic body radiotherapy is an emerging treatment method for recurrent ventricular tachycardia refractory to invasive treatment methods. The single-fraction delivery of 25 Gy was assumed to produce fibrosis, similar to a post-radiofrequency ablation scar. However, the dynamics of clinical response and recent preclinical findings suggest a possible different mechanism. The data on histopathological presentation of post-radiotherapy hearts is scarce, and the authors provide significantly different conclusions. In this article, we present unique data on histopathological examination of a heart explanted from a patient who had a persistent anti-arrhythmic response that lasted almost a year, until a heart failure exacerbation caused a necessity of a heart transplant. Despite a complete treatment response, there was no homogenous transmural fibrosis in the irradiated region, and the overall presentation of the heart was similar to other transplanted hearts of patients with advanced heart failure. In conclusion, our findings support the theorem of functional changes as a source of the anti-arrhythmic mechanism of radiotherapy and show that durable treatment response can be achieved in absence of transmural fibrosis of the irradiated myocardium.

freedom from NF-MACE, and 1-year rejection episodes.The severity of CAV observed in the donor coronary calcification group included: CAV1 = 13, CAV2 = 1, CAV3 = 0. Conclusion: Donor coronary artery calcification appears to be a marker for greater risk for developing CAV after heart transplantation.Caution must be taken to accept these organs and if accepted, early modification of immunosuppression with a proliferation signal inhibitor may be indicated. EndpointsHTx Patients with Coronary Calcification (n=31) HTx Patients without Coronary Calcification (n=192) P-value