Donor-derived cell-free DNA (dd-cfDNA) is a blood biomarker detecting graft injury with high negative predictive value. While non-invasive strategies for heart transplant (HTx) rejection surveillance are widely adopted in the United States with centralized testing, data on the feasibility of dd-cfDNA assay at the local level are lacking. Here, we report the first 6 months of experience with a local laboratory-run dd-cfDNA assay in the routine clinical surveillance setting. Twenty-six HTx patients with stable graft function were transitioned from endomyocardial biopsy-based (EMB) to dd-cfDNA-led rejection surveillance using a commercially available next-generation sequencing-based assay. In the 90 samples analyzed, dd-cfDNA fraction remained continuously low in most patients, thus 88% of surveillance EMBs could be safely avoided. In the case of ≥.25% dd-cfDNA, EMB was performed. There was no missed rejection. Our data show the feasibility to analyze dd-cfDNA at the local level and successful implementation of this non-invasive surveillance method into clinical practice, thus considerably reducing the frequency of invasive surveillance EMBs.

Background/Objectives: Donor-derived cell-free DNA (dd-cfDNA) is a marker of graft injury that increases in acute rejection and has excellent negative predictive value. Left ventricular global longitudinal strain (LVGLS) and strain-derived myocardial work indices are novel echocardiographic parameters with growing applications. Still, they have been poorly investigated in heart transplant (HTx) recipients so far. We sought to examine the diagnostic impact of left ventricular longitudinal strain-derived indices in diagnosing myocardial injury as assessed by dd-cfDNA after HTx. Methods: Since October 2022, HTx recipients have been shifted from our endomyocardial biopsy (EMB)-based rejection surveillance protocol to a monthly dd-cfDNA-led rejection assessment. We analysed the percentage of donor-derived to total cell-free DNA. For echocardiographic analysis, patient selection was restricted to those transplanted ≥ 6 months. We used 2D speckle-tracking echocardiography to assess LVGLS and strain-derived myocardial work parameters. Results: We analysed four hundred and forty-nine dd-cfDNA samples from seventy-one patients until November 2024. The mean dd-cfDNA fraction remained very low (0.13 ± 0.06%). Eighty-eight percent of surveillance EMBs that would have otherwise been performed were avoided. The mean LVGLS was lower than the literature reference values. We found no correlation between dd-cfDNA and LVGLS. Transplanted hearts had different myocardial work indices than the reference values reported in the literature. Conclusions: dd-cfDNA effectively rules out clinically significant acute rejection and decreases the need for invasive surveillance EMBs. LVGLS seems less sensitive than dd-cfDNA for the identification of myocardial injury in the early stages of HTx rejection in patients at low risk for rejection.

A szolidszerv-transzplantátum kilökődése a modern immunszuppresszív kezelés mellett is a graftdiszfunkció, a hospitalizáció és a halálozás egyik fő etiológiai tényezője. A rejekció diagnosztikájában ’gold standard’ invazív biopszia azonban a hospitalizáció mellett számos szövődménnyel járhat, interpretálását nagy interobszerver variabilitás jellemzi. A rejekció megítélésében a noninvazív módszerek ezért nagy klinikai jelentőséggel bírnak. A graftkárosodást jellemző donoreredetű sejtmentes DNS (dd-cfDNA) a recipiens szérumából mutatható ki, szintje már a biopszia által igazolt kilökődést megelőzően emelkedést mutat, és magas negatív prediktív értékkel bír. Munkánk során a dd-cfDNA-assay szolid szerv (vese, máj, szív, tüdő, hasnyálmirigy) transzplantációját követően betöltött szerepét vizsgáltuk az elérhető irodalom összefoglalásával, továbbá a szívtranszplantáltak körében a rutin klinikai gyakorlatba 2022. októberben bevezetett dd-cfDNA-alapú rejekció utánkövetése során nyert első hazai eredményeinket kívánjuk megosztani. Cardialis allograftrejekció utánkövetése során 46 szívtranszplantált beteg 264 dd-cfDNA-mintáját elemeztük. Az eredmény a keringő donoreredetű sejtmentes DNS és a plazma teljes (recipiens- és donoreredetű) sejtmentes DNS arányát mutatja: a ≥0,20% dd-cfDNA-érték károsodásra, míg a ≥0,35% dd-cfDNA-szint súlyos graftkárosodásra utal. A dd-cfDNA-minták 80%-a <0,20% értéket mutatott. Myocardium-károsodásra utaló dd-cfDNA-érték következtében összesen 20 szívizom-biopsziát végeztünk: kilökődés 6 esetben igazolódott. 16 hónap során 232, a reguláris surveillance-biopsziák 88%-a biztonságosan elhagyható volt a dd-cfDNA-értékek alapján. A korai graftkárosodás kimutatása által lehetőség nyílik az immunszuppresszív terápia korai és személyre szabott módosítására a súlyosabb fokú kilökődés és az irreverzibilis graftkárosodás megelőzése, illetve a gyógyszertoxicitás elkerülése érdekében. Orv Hetil. 2024; 165(33): 1275–1285.

Diastolic dysfunction (DD) is a prevalent and clinically significant complication after heart transplantation (HTX). We aimed to characterize the diastolic function of HTX recipients with both short-term and long-term follow-ups by applying left atrial (LA) deformation analysis. We consecutively enrolled and followed up with 33 HTX patients. Three assessments were performed one month, 3–5 months, and 3–5 years after surgery. Beyond conventional echocardiographic measurements, apical four-chamber views optimized for speckle tracking analysis were acquired and post-processed by dedicated software solutions (TomTec AutoStrain LA and LV). Left atrial phasic functions were characterized by reservoir, conduit, and contraction strains. We categorized diastolic function according to current guidelines (normal diastolic function, indeterminate, DD). At the first assessment, nine (27%) patients were in the DD category, and eleven (33%) were indeterminate. At the second assessment, only one patient (3%) remained in the DD category and six (18%) were indeterminate. At the third assessment, 100% of patients were categorized as having normal diastolic function. LA reservoir strain gradually increased over time. LA contraction strain significantly improved from the second to the third assessment. We found a correlation between the LA reservoir strain and NT-proBNP (r = 0.40, p < 0.05). DD is prevalent immediately after HTX but rare until the end of the first postoperative quarter. Speckle tracking analysis enables the characterization of LA phasic functions that may reflect both short- and long-term changes in diastolic function and correlate with NT-proBNP.

Funding Acknowledgements: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ÚNKP-19-3-I New National Excellence Program of the Ministry for Innovation and Technology; National Research, Development and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program) Background: The geometry and function of the left atrium (LA) change after orthotopic heart transplantation (HTX) with bicaval technique, as the LA has a recipient part around the pulmonary veins and a donor part, and these often contract separately. Because of this altered LA function, the recognition of left ventricular diastolic dysfunction can be challenging. The standard echocardiographic diastolic parameters are often in abnormal range in HTX patients despite of normal left ventricular diastolic function. Purpose: The aim of our prospective study was to investigate the LA volumes and function and their temporal changes after HTX using cardiac magnetic resonance (CMR). Method: To better understand the cardiac characteristics of HTX patients, we started a prospective trial in January 2018. CMR was performed at one, three and six months after HTX. Left atrial contour detection was performed in 2- and 4-chamber views. Patients who had ≥Grade II allograft rejection before the CMR examination, were excluded (n = 6). In the remaining HTX patients (n = 37, 52 ± 12y, 29 male) and in a control group (n = 20, 49 ± 5y, 15 male) LA ejection fraction (EF), BSA-corrected maximum and minimum LA volume (Vi), stroke volume (SVi) were evaluated using bi-plane mode. LA global longitudinal strain (GLS) was defined with CMR based deformation imaging, called feature tracking. Results: HTX patients had significantly higher LA volumes (maxLAVi 65 ± 22 vs. 46 ± 7 ml/m2, minLAVi 47 ± 21 vs. 18 ± 6 ml/m2) lower LASVi (19 ± 5 vs. 29 ± 4 ml/m2), LAEF (31 ± 10 vs. 62 ± 8%) and LA-GLS (10 ± 4 vs. 39 ± 11%) compared to the control group (p < 0.0001). Analysing the temporal changes in HTX patients, we found an increase in the LA-GLS already at three months (10 ± 4 vs. 12 ± 3%, p < 0.05). The LAEF improved significantly at six months (29 ± 10 vs. 33 ± 10%, p < 0.05). Conclusion: After HTX the LA volumes and function differ markedly from the normal population. The LA funcional parameters showed a moderate improvement after HTX. Better understanding the changes of left atrial function after HTX could help us to recognise pathological conditions. Abstract Figure. Strain analysis of the left atrium