Early immune biomarkers and intermediate-term outcomes after heart transplantation: Results of Clinical Trials in Organ Transplantation-18

Stehlik, Josef; Baran, David A.; Bridges, Nancy D.; Chandraker, Anil; Gordon, Robert A.; Marco, Teresa De; Givertz, Michael M.; Heroux, Alain; Iklé, David; Hunt, Judson; Kfoury, Abdallah G.; Madsen, Joren C.; Morrison, Yvonne; Feller, Erika; Pinney, Sean; Tripathi, Sudipta; Heeger, Peter S.; Starling, Randall C.

doi:10.1111/ajt.15218

Cited by 14 publications

(7 citation statements)

References 32 publications

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“…In fact, both with regard to IVUS and angiographic evaluation we saw an overall trend toward more CAV in the no‐ACR group compared with the 1R group and the 2R/3R group. Prior studies have also examined PAV as a measure of CAV in HTx . We did not find excess rejection to result in excess CAV in terms of PAV measures.…”

Section: Discussionmentioning

confidence: 46%

Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy

et al. 2020

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ClinicalTrials.gov number: NCT01266148. SUMMARYTo evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Substudy of the SCHEDULE trial (n = 115), where de novo HTx recipients were randomized to (i) everolimus with early CNI elimination or (ii) CNI-based immunosuppression. Seventy-six patients (66%) were included based on matched intravascular ultrasound (IVUS) examinations at baseline and year 3 post-HTx. Biopsy-proven ACR within year 1 post-HTx was recorded and graded (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post-HTx. Median age was 53 years (45-61), and 71% were male. ACR was recorded in 67%, and patients were grouped by rejection profile: no ACR (33%), only 1R (42%), and ≥2R (25%). Median ΔMIT (maximal intimal thickness) was not significantly different between groups (P = 0.84). The incidence of CAV was 49% by IVUS and 26% by coronary angiography with no significant differences between groups. No correlation was found between number of 1R and ΔMIT BL-3Y (r = À0.025, P = 0.83). The number of 1R was not a significant predictor of ΔMIT BL-3Y (P = 0.58), and no significant interaction with treatment was found (P = 0.98). The burden of mild ACR was not associated with CAV development.

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Section: Discussionmentioning

confidence: 46%

Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy

et al. 2020

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“…45,48 There have also been evaluations of immune and angiogenesis biomarkers within the CTOT-5 and CTOT-18 studies (Clinical Trials in Organ Transplantation), showing an association between endothelial growth factor C and endothelin-1, with cardiac allograft vasculopathy, as well as anti-cardiac myosin antibody and vascular endothelial growth factors C and A, with adverse posttransplant outcomes. 49,50 Whether assays for circulating, targeted biomarkers can augment the accuracy of other -omics technologies for CAR remains an area of investigation.…”

Section: Protein Biomarkers and Exosomal Profilingmentioning

confidence: 99%

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

Goldberg,

Truby,

Agbor-Enoh

et al. 2023

Circulation

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The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The reference standard for diagnosis of acute cellular and antibody-mediated rejection includes histologic and immunofluorescence evaluation of endomyocardial biopsy samples, despite invasiveness and high interrater variability for grading histologic rejection. Circulating biomarkers and molecular diagnostics have shown substantial predictive value in rejection monitoring, and emerging data support their use in diagnosing other posttransplant complications. The use of genomic (cell-free DNA), transcriptomic (mRNA and microRNA profiling), and proteomic (protein expression quantitation) methodologies in diagnosis of these posttransplant outcomes has been evaluated with varying levels of evidence. In parallel, growing knowledge about the genetically mediated immune response leading to rejection (immunogenetics) has enhanced understanding of antibody-mediated rejection, associated graft dysfunction, and death. Antibodies to donor human leukocyte antigens and the technology available to evaluate these antibodies continues to evolve. This review aims to provide an overview of biomarker and immunologic tests used to diagnose posttransplant complications. This includes a discussion of pediatric heart transplantation and the disparate rates of rejection and death experienced by Black patients receiving a heart transplant. This review describes diagnostic modalities that are available and used after transplant and the landscape of future investigations needed to enhance patient outcomes after heart transplantation.

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“…In human cardiac allograft biopsy, the subendocardial inflammatory infiltrate is of recipient origin showing significant lymphangiogenesis [112]. In the context, serum level of VEGF-C may associate with risk of adverse events for providing useful information after heart transplantation [116].…”

Section: Lymphangiogenesis and Heart Transplantationmentioning

confidence: 99%

The role of lymphangiogenesis in cardiovascular diseases and heart transplantation

2021

Heart Fail Rev

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Cardiac lymphangiogenesis plays an important physiological role in the regulation of interstitial fluid homeostasis, inflammatory, and immune responses. Impaired or excessive cardiac lymphatic remodeling and insufficient lymph drainage have been implicated in several cardiovascular diseases including atherosclerosis and myocardial infarction (MI). Although the molecular mechanisms underlying the regulation of functional lymphatics are not fully understood, the interplay between lymphangiogenesis and immune regulation has recently been explored in relation to the initiation and development of these diseases. In this field, experimental therapeutic strategies targeting lymphangiogenesis have shown promise by reducing myocardial inflammation, edema and fibrosis, and improving cardiac function. On the other hand, however, whether lymphangiogenesis is beneficial or detrimental to cardiac transplant survival remains controversial. In the light of recent evidence, cardiac lymphangiogenesis, a thriving and challenging field has been summarized and discussed, which may improve our knowledge in the pathogenesis of cardiovascular diseases and transplant biology.

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Early immune biomarkers and intermediate-term outcomes after heart transplantation: Results of Clinical Trials in Organ Transplantation-18

Cited by 14 publications

References 32 publications

Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy

Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients—a SCHEDULE trial substudy

Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

The role of lymphangiogenesis in cardiovascular diseases and heart transplantation

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