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Background: Endomyocardial biopsy (EMB) is the gold standard in heart transplantation (HTx) followup, with samples commonly fixed with formalin, and then embedded in paraffin for histology analysis. Recently, EMB samples have been scanned with synchrotron X-ray phase-contrast imaging (X-PCI) to assess graft rejection.¹ We aim to compare imaging time efficiency and image quality between formalin-fixed and paraffin-embedded samples to determine the optimal scanning methodology. Methods: Three adult patients undergoing EMB after HTx were included. EMB samples were initially stored in formalin and imaged by X-PCI at the Paul Scherrer Institute TOMCAT beamline (Villigen, Switzerland). On site samples were scanned in glass tubes in deionised, degassed water, and then embedded in paraffin, positioned on a holder, and scanned again using a multi-scale beamline set-up. Imaging time efficiency was measured by on-site sample preparation and scan time, and image quality was assessed with signal-to-noise ratio (SNR) and pixel resolution. Post-processing comparison included fibrosis quantification (using Ilastik for segmentation and Fiji for calculating the average percentage of collagen in 3 selected areas) and graft-rejection grading (assessed by two blinded observers based on the ISHLT 2004. criteria)². Results: Scanning F1-F3 and P1-P3 samples produced the same imaging resolution, while F1-F3 samples exhibited higher SNR values (clearer sample visibility) (Table 1). On site preparation and scan time were shorter with P1-P3 samples. Fibrosis quantification produced similar results in all samples, with Embedding EMB samples in paraffin is more time efficient in terms of on-site sample preparation and imaging. Results showed similar fibrosis quantification regardless of preparation methods, whereas rejection grading did not differ in clinically meaningful way. In conclusion, in initial testing using small sample number, no significant difference was found between the preparation methods. [ABSTRACT FROM AUTHOR]

Background: Graft rejection remains the most important complication after heart transplantation (HTx). Endomyocardial biopsy (EMB) is the gold standard in HTx follow-up, however, conventional histopathological (HP) analysis is limited by tissue damage during preparation, 2-dimensional (2D) analysis, and low inter-observer agreement in rejection grading. X-ray phase contrast imaging (X-PCI) has shown potential for non-destructive imaging of the myocardium, enabling high-resolution 3-dimensional (3D) analysis with fibrosis and fibre orientation quantification.¹ Methods and Design: GRAFT-XPCI is a multi-centric, prospective observational study aiming to prove non-inferiority of X-PCI in graft rejection diagnosis, vs. conventional HP (Figure 1). It will include ap-proximately 400 patients in standard post-HTx follow-up at 3 clinical centres: University Hospital Centre Zagreb, Dubrava University Hospital and Hospital Clinic Barcelona. Collected data will include EMB samples, patient history, laboratory, electrocardiogram (ECG), coronarography and echocardiographic data. EMB specimens will be initially imaged by X-PCI at the Paul Scherrer Institute (Villigen, Switzerland), producing digital 3D imaging datasets (at 0.65 um pixel resolution) for computational analysis, and then prepared for HP microscopy at the University of Zagreb School of Medicine. Three datasets will be generated for analysis - 2D X-PCI dataset, 3D X-PCI dataset, and 2D HP images. Acquired X-PCI images and HP slides will be diagnostically graded (ISHLT 2004. grading system)², comparatively assessed by at least two observers in a blinded fashion, further analysed in conjunction with gathered clinical data. Computer methods for the automatic and semi-automatic analysis of digital image datasets will be developed as an additional output. Conclusion: GRAFT-XPCI will: 1) compare X-PCI and conventional HP in graft rejection analysis, 2) enable insight into structural and pathophysiological processes in graft rejection after HTx, 3) extend the amount of information gained by EMB analysis. The development of new research tools and imaging protocols should widen future research of EMB analysis in various cardiac conditions. This study has been fully supported by the Croatian Science Foundation under the trial registration no. UIP-2020-02-5572. [ABSTRACT FROM AUTHOR]

Introduction: Data on heart transplant (HTx) patients and infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are very limited. There is significant heterogeneity in the clinical presentation. Immunosuppression-related issues are of the main concern because of an increased risk for viral replication and superimposed infections. There is no evidence-based recommendation for the management of these patients. Some authors suggest modification in immunosuppression, i.e. discontinuation of mycophenolate mofetil (MMF) and calcineurin inhibitor (CNI) reduction in patients with more severe clinical presentation. Patients and Methods: This is a case series of 5 HTx recipients from our center who tested positive for COVID-19 infection and were treated in different COVID-19 specialized units. Results: There were 4 male and one female patients, 62-75 years old. Four of them were symptomatic and hospitalized, while one remained self-quarantined at home. The clinical presentation was mild to moderate, with symptoms including mild fever, dyspnea, and myalgia. X-ray signs of pneumonia were present in 3 patients, but none needed ICU care nor mechanical ventilation. Both a reduction of CNI dose with lower target serum concentration and MMF was discontinued in all patients. One patient was treated with hydroxychloroquine, one with remdesivir and one with steroid therapy. Antibiotics prophylaxis was administered in 2 patients. None of the patients experienced overt graft rejection and all patients have successfully recovered (Table 1). Conclusion: Lacking any evidence-based recommendation for the treatment of HTx patients infected with SARS-CoV-2, we are challenged to modify maintenance immunosuppression carefully balancing between the risk of uncontrolled viral replication with a superimposed infection on one side, and the increased risk of graft rejection on the other side. Further studies are needed to determine the optimal management of COVID-19 infection in these patients. [ABSTRACT FROM AUTHOR]

Background: Decrease in platelet count following the induction with polyclonal anti-thymocyte globulin (ATG) is deemed as an adverse event, while decrease in lymphocyte count represents a therapeutic goal1. Still, the effect on platelets may represent an important part of ATG anti-rejection mechanisms. Patients and Methods: This was a retrospective single-center study of consecutive HTx (heart transplantation) patients (pts) from February 2010 to February 2018 in University Hospital Centre Zagreb. All pts received rATG (Thymoglobulin®) 1.5 mg/kg daily during the first 5 days. Complete blood count with differential was assessed on days 0, 7 and 14 after HTx. The incidence of cellular-mediated rejection (ACR) was monitored for two years after HTx. ACR was classified according to ISHLT classification from 1990 and expressed as ACR of grade 1B or higher (≥1B). Results: A total of 159 pts were transplanted. Median age was 55 years (IQR, 47-62 years), 76% were male. A total of 27 pts (17 %) experienced ACR ≥1B during 24 months. Pts with ACR of grade ≥1B had higher platelet count on day 7 (145 vs 104 x 103/μL, p<0.001). They also had higher the absolute lymphocyte count (ALC) on the same day, but this did not reach statistical significance (162 vs 130 x 103/μL, p=0.19) and there was no correlation between ALC and platelet counts on day 7 (Pearson's correlation coefficient was 0.064, p=0.459). Conversely, more rejection was observed in pts with higher ALC on day 14 (326 vs 190 x 103/μL, p=0.035), with a trend towards statistical significance in the relationship with higher platelet count (210 vs 199 x 103/μL, P=0.076). In the univariate analysis, higher platelet count on day 7, younger recipient age and negative pre-transplant Cytomegalovirus (CMV) IgG serology were found as predictors of the ACR ≥1B in the first 2 years after HTx (Table 1). In multivariable model, platelet count on day 7 and pre-transplant CMV serostatus were independent predictors of rejection. ROC analysis of the aforementioned model showed a satisfying AUC of 0.75. Conclusion: Decrease in platelet count following the induction with rATG is strongly related to less graft rejection that is independent from the lymphodepleting effect. This indicates the importance of platelet involvement in anti-rejection mechanisms of ATG induction, and consequently a possible rationale for targeting platelets in future immunosuppressive regimens. [ABSTRACT FROM AUTHOR]

Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The number of transplant patients of childbearing age has increased. Decisions regarding the pregnancy management are challenging. Close monitoring includes screening for complications including rejection, graft dysfunction, and infection. First pregnancy in a post-cardiac transplant patient was reported in 1988 in a female patient who conceived less than 2 years post-transplant. Since then, there are many case reports that have demonstrated successful pregnancies in solid organ transplant recipients. Case report: We present a case of 42-years-old female patient who underwent heart transplant 2016. In 2018 the patient expressed wishes for pregnancy and childbirth. A multidisciplinary team of cardiologists and gynecologists was formed and preconception and genetic counseling given. Before pregnancy we adjusted standard immunosuppressant therapy – mycophenolate mofetil was excluded, prednisone was continued in dose of 5 mg daily, and tacrolimus titrated to achieve concentration of 10-15 ng/ml. One month later, myocardial biopsy excluded graft rejection and 6 months later patient conceived naturally. Graft function was assessed by regular monthly NT-proBNP check. Echocardiography performed at 4th and 35th week of pregnancy showed normal graft function. In 36th week of pregnancy patient was admitted to our Department due to renal failure and hyperkalemia and was treated conservatively. Due to labor contractions on the 7th day of hospitalization, urgent caesarean section was performed in general anesthesia. Our patient gave birth to a healthy male newborn, without postpartal complications. Standard immunosuppressant therapy with mycophenolate mofetil, tacrolimus and prednisone was introduced immediately after birth. Repeated myocardial biopsy performed in the follow-up showed no signs of graft rejection. Conclusion: Pregnancy and childbirth in post-cardiac transplant patient is feasible and should be managed by multidisciplinary team of healthcare providers [ABSTRACT FROM AUTHOR]

Supraventricular tachycardias (SVT) are increasingly recognized late complications after cardiac transplantation (CTX). The most commonly described arrhythmias include cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL), other macroreentrant atrial tachycardias (MRAT) and focal atrial tachycardias (AT). Although surgical substrate can be important, the effect of the surgical technique on the mechanism and the occurrence of arrhythmia remains unclear. We describe characteristics of CTX patients who presented with SVT for electrophysiological studies (EPS) at our centre from 2017 to 2020. Among 6 patients (mean age 48 ± 18 years, 4 of 6 were men), 2 presented during the first year after CTX, while 4 patients presented after a long follow-up (13.3 ± 2.8 years). Cardiac rejection was ruled out in all patients. In 3 patients significant graft vasculopathy was present. Initially, the conventional EPS was performed in all patients. In 5 cases, the initial diagnosis was CTI-dependent AFL and a successful radiofrequency ablation of CTI was performed. In one case, the arrhythmia was due to the non-CTIdependent MRAT and rate-control strategy was adopted. During the follow-up (29.2 ± 10.2 months), 3 patients remained without recurrences. In two patients early recurrence was noted (after 1 and 3 months) and a second EPS was performed (conventional or electroanatomical mapping) which demonstrated the multiple MRAT unsuitable for ablation. These patients were managed conservatively while one of them received second CTX due to advanced graft vasculopathy. During the follow-up one patient died due to graft rejection. In our group of patients typical AFL and other non-CTI-dependent MRAT were observed. In CTI-dependent AFL, conventional radiofrequency ablation was effective, while recurrences were more difficult to treat. Extensive scarring of the atria is the substrate for multiple MRAT circles that are not easily amenable with ablation. [ABSTRACT FROM AUTHOR]

Copyright of Cardiologia Croatica is the property of Croatian Cardiac Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: We investigated pretransplant and posttransplant factors that could influence survival and development of cardiac allograft vasculopathy (CAV) and graft cellular rejection (CR) in heart transplant patients (Pts). Methods: 120 study Pts in the follow-up 10 years, mean age 48,8±13,5. The patient characteristics (age, gender, blood type, diagnosis, pulmonary vascular resistance -- PVR), transpulmonary gradient, graft ischemic time and duration of extracorporeal circulation, ECC) and pretransplant comorbidities (diabetes mellitus, chronic renal failure, hypertension, hyperlipidaemia) were analysed. Postransplant complications (postHTx hypertension, chronic renal failure -- postHTx-RF, steroid diabetes mellitus -- SDM) were also correlated with CAV and mortality, as well as biomarkers such as NT-proBNP and troponin T. Immunosuppressive regimens and cellular rejection were also analyzed. For statistical analysis chi-square test, student t-test and ANOVA were used (SPSS vers.21). Results: Higher transpulmonary gradient (but not PVR) correlated significantly with higher mortality (p=0,003), as well as longer ischemic time (p=0.004) and ECC duration (p=0.043). PostHTx-RF (p=0.023) and SDM (p=0.042) also significantly contributed to mortality. Female gender had an insignificant trend toward longer survival (p=0.079). Higher NT- proBNP values (5,833 vs 2,721 pg/ml, p=0.025) significantly predicted all-cause mortality. There was a trend with higher standardized corticosteroid doses to correlate with lower CAV incidence (p=0.129). NT-proBNP cut-off value of >750 pg/ml has a trend to predict CR (p=0.084). Standardized cy- closporine A concentration (CyA) less than 10 0ng/ml (p=0.023) significantly correlated with CR and CyA between 100-150 ng/ml had the same trend (p=0.067). Other variables had no statistical significance. Conclusions: Patient pretransplant comorbidities did not have crucial impact on posttransplant survival, expected transpulmonary gradient which proved to be a very powerful parameter influencing survival (while PVR did not). Steroid diabetes and chronic renal failure (excluding early acutisa- tion of preexisting RF) are important postransplant comorbidities contributing to higher mortality. Immunosupression plays an important role for the CAV prevention and in our study more potent corticosteroid therapy proved to lower CAV incidence. CR rejection was not associated with higher CAV incidence, it could be predicted by higher NT- proBNP levels and prevented by higher CyA concentration. [ABSTRACT FROM AUTHOR]