The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients

Dhital, K.; Azeka, Estela; Colvin, Monica; DePasquale, E.C.; Farrero, Marta; Garcı́a-Guereta, Luis; Jamero, Gina; Khush, Kiran K.; Lavee, Jacob; Pouch, Stephanie M.; Michaud, Christopher J.; Shullo, M.; Schubert, Stephan; Angelini, Annalisa; Carlos, Lilibeth; Mirabet, Sònia; Patel, Jignesh; Pham, Michael; Urschel, Simon; Kim, Kyung‐Hee; Miyamoto, Shelly; Chih, Sharon; Daly, Kevin P.; Grossi, Paolo; Jennings, Doug; Kim, In Cheol; Lim, Hoong Sern; Miller, Tara; Potena, Luciano; Velleca, A.; Eisen, Howard J.; Bellumkonda, Lavanya; Danziger‐Isakov, Lara; Dobbels, Fabienne; Harkess, M.; Kim, Daniel; Lyster, Haifa; Peled, Yael; Reinhardt, Zdenka

doi:10.1016/j.healun.2022.10.015

Cited by 215 publications

(182 citation statements)

References 855 publications

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“…Collectively, our study is the first to show that dd-cfDNA correlates with both MMDx-based classifications of allograft rejection and tissue RAT profiles of the heart. Cardiac allograft injury and rejection remain one of the most important clinical concerns after heart transplantation (2).…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Donor Derived Cell-Free DNA and Tissue-Based Rejection-Related Transcripts In Heart Transplantation

Lee

Usmani

Ravichandran

et al. 2023

Preprint

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Introduction Endomyocardial biopsy (EMB)-based traditional microscopy remains the gold standard for the detection of cardiac allograft rejection, despite its limitation of inherent subjectivity leading to inter-reader variability. Alternative techniques now exist to surveil for allograft injury and classify rejection. Donor-derived cell-free DNA (dd-cfDNA) testing is now a validated blood-based assay used to surveil for allograft injury. The molecular microscope diagnostic system (MMDx) utilizes intragraft rejection-associated transcripts (RATs) to classify allograft rejection and identify injury. The use of dd-cfDNA and MMDx together provides objective molecular insight into allograft injury and rejection. The aim of this study was to measure the diagnostic agreement between dd-cfDNA and MMDx and assess the relationship between dd-cfDNA and MMDx-derived RATs which may provide further insight into the pathophysiology of allograft rejection and injury. Methods: This is a retrospective observational study of 186 endomyocardial biopsy (EMB) evaluated with traditional microscopy and MMDx. All samples were paired with dd-cfDNA from peripheral blood prior to EMB (up to 1 month). Diagnostic agreement between traditional microscopy, MMDx, and dd-cfDNA (threshold of 0.20%) were compared for assessment of allograft injury. In addition, the relationship between dd-cfDNA and individual RAT expression levels from MMDx was evaluated. Results MMDx characterized allograft tissue as no rejection (NR) (64.5%), antibody-mediated rejection (ABMR) (25.8%), T-cell-mediated rejection (TCMR) (4.8%), and mixed ABMR/ TCMR (4.8%). For the diagnosis of any type of rejection (TCMR, ABMR, and mixed rejection), there was substantial agreement between MMDx and dd-cfDNA (74.7% agreement). All transcript clusters (group of gene sets designated by MMDx) and individual transcripts considered abnormal from MMDx had significantly elevated dd-cfDNA. In addition, a positive correlation between dd-cfDNA levels and certain MMDx-derived RATs was observed. Tissue transcript clusters correlated with dd-cfDNA scores, including DSAST, GRIT, HT1, QCMAT and S4. For individual transcripts, tissue ROBO4 was significantly correlated with dd-cfDNA in both non-rejection and rejection as assessed by MMDx. Conclusion: Collectively, we have shown substantial diagnostic agreement between dd-cfDNA and MMDx. Furthermore, based on the findings presented, we postulate a common pathway between the release of dd-cfDNA and ROBO4 (a vascular endothelial-specific gene that stabilizes the vasculature) in the setting of AMR, which may provide a mechanistic rationale for observed elevations in dd-cfDNA in AMR, compared to ACR.

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Section: Discussionmentioning

confidence: 99%

Relationship Between Donor Derived Cell-Free DNA and Tissue-Based Rejection-Related Transcripts In Heart Transplantation

Lee

Usmani

Ravichandran

et al. 2023

Preprint

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“…Thus, conclusions from samples obtained further out from HTx cannot be confidently made. (3) The time difference between standard and expanded SNP testing may also be a confounding variable. However, the median time difference was only 1 day in our study and we found similar results in our sensitivity analysis…”

Section: Limitationsmentioning

confidence: 99%

Comparison of two donor‐derived cell‐free DNA tests and a blood gene‐expression profile test in heart transplantation

Rodgers

Gerding

Cusi

et al. 2023

Clinical Transplantation

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Background Donor‐derived cell‐free DNA (dd‐cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd‐cfDNA and gene‐expression profiling (GEP) testing in heart transplant (HTx) recipients. Methods This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd‐cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR. Results A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd‐cfDNA. Conclusion We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd‐cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd‐cfDNA testing into clinical practice are needed.

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“…Corticosteroids, calcineurin inhibitors (tacrolimus, cyclosporin) and azathioprine are considered safe during breastfeeding. Breastfeeding is not advised if HT recipients are on mTOR inhibitors (sirolimus and everolimus) or mycophenolate products [44]. Physicians can refer to the LactMed database, which provides comprehensive data on safety of drugs and acceptable drug levels during breastfeeding [45].…”

Section: Breast Feedingmentioning

confidence: 99%

Management of pregnancy in left ventricular assist device and heart transplant recipients: a concise review

Marek-Iannucci

Uber

Rajapreyar

2023

Current Opinion in Cardiology

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Purpose of reviewWomen of reproductive age are increasingly undergoing heart transplantation (HT) or left ventricular assist device (LVAD) implantation for advanced heart failure. This review is intended to give an overview of the current state of the art management of pregnancy in patients with LVAD or HT recipients.Recent findingsHeart transplant recipients are at increased risk for graft rejection, renal dysfunction, preeclampsia and worsening of comorbidities (hypertension and diabetes). Patients with LVAD are at higher risk of thromboembolic events, infections, right ventricular failure and require close surveillance during pregnancy. Preconception counseling must be offered to all women of reproductive age group with HT or LVAD to avoid unplanned pregnancies.SummaryA multidisciplinary approach with close antepartum and postpartum surveillance is recommended.

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The International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients

Cited by 215 publications

References 855 publications

Relationship Between Donor Derived Cell-Free DNA and Tissue-Based Rejection-Related Transcripts In Heart Transplantation

Relationship Between Donor Derived Cell-Free DNA and Tissue-Based Rejection-Related Transcripts In Heart Transplantation

Comparison of two donor‐derived cell‐free DNA tests and a blood gene‐expression profile test in heart transplantation

Management of pregnancy in left ventricular assist device and heart transplant recipients: a concise review

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