Cathrine M Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Ersilia M DeFilippis, Salwa Rahman, Yonatan Mehlman, Elena M Donald, Dor Lotan, Edward Lin, Kyung T Oh, Sun H Lee, Jayant K Raikhelkar, Justin A Fried, David Majure, Farhana Latif, Gabriel T Sayer, Nir Uriel, Kevin J Clerkin
{"title":"供体来源的无细胞DNA水平升高与心肌血流量减少有关，但与血管造影心脏移植血管病变无关。","authors":"Cathrine M Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Ersilia M DeFilippis, Salwa Rahman, Yonatan Mehlman, Elena M Donald, Dor Lotan, Edward Lin, Kyung T Oh, Sun H Lee, Jayant K Raikhelkar, Justin A Fried, David Majure, Farhana Latif, Gabriel T Sayer, Nir Uriel, Kevin J Clerkin","doi":"10.1161/CIRCHEARTFAILURE.124.011756","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.</p><p><strong>Methods: </strong>A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.</p><p><strong>Results: </strong>Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; <i>P</i>=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; <i>P</i>=0.94; median, 0.31% [IQR, 0.17%-0.71%]; <i>P</i>=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; <i>P</i><0.001; median, 0.25% [IQR, 0.15%-0.52%]; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011756"},"PeriodicalIF":7.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753942/pdf/","citationCount":"0","resultStr":"{\"title\":\"Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.\",\"authors\":\"Cathrine M Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Ersilia M DeFilippis, Salwa Rahman, Yonatan Mehlman, Elena M Donald, Dor Lotan, Edward Lin, Kyung T Oh, Sun H Lee, Jayant K Raikhelkar, Justin A Fried, David Majure, Farhana Latif, Gabriel T Sayer, Nir Uriel, Kevin J Clerkin\",\"doi\":\"10.1161/CIRCHEARTFAILURE.124.011756\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.</p><p><strong>Methods: </strong>A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.</p><p><strong>Results: </strong>Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; <i>P</i>=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; <i>P</i>=0.94; median, 0.31% [IQR, 0.17%-0.71%]; <i>P</i>=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; <i>P</i><0.001; median, 0.25% [IQR, 0.15%-0.52%]; <i>P</i><0.001).</p><p><strong>Conclusions: </strong>HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.</p>\",\"PeriodicalId\":10196,\"journal\":{\"name\":\"Circulation: Heart Failure\",\"volume\":\" \",\"pages\":\"e011756\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753942/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Heart Failure\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011756\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Heart Failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011756","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.
Background: Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.
Methods: A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.
Results: Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001).
Conclusions: HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.
期刊介绍：
Circulation: Heart Failure focuses on content related to heart failure, mechanical circulatory support, and heart transplant science and medicine. It considers studies conducted in humans or analyses of human data, as well as preclinical studies with direct clinical correlation or relevance. While primarily a clinical journal, it may publish novel basic and preclinical studies that significantly advance the field of heart failure.
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