Abstract
We investigated clinical significance of cell-free DNA (cfDNA) in heart failure. This
study enrolled 32 heart failure patients and 28 control subjects. Total cfDNA levels
were not different between groups (P = 0.343). Bisulfite-digital polymerase chain reaction using the unmethylated FAM101A
locus demonstrated that cardiomyocyte-specific cfDNA was significantly elevated in
heart failure patients compared with control subjects (median 0.99 [interquartile
range 0.77-1.98] vs 0 [0-0.91] copies/mL; P = 0.003). Cardiomyocyte-specific cfDNA significantly discriminated heart failure
patients from control subjects (area under the receiver operating characteristic curve,
0.716; P = 0.003) and was positively correlated with troponin I (r = 0.438; P = 0.003) but not with B-type natriuretic peptide (r = 0.275; P = 0.058). cfDNA may be a novel biomarker to measure cardiomyocyte death in heart
failure.
Résumé
Nous avons étudié l’importance clinique de l’ADN acellulaire (ADNa) dans l’insuffisance
cardiaque chez 32 patients présentant une insuffisance cardiaque et 28 sujets témoins.
Les concentrations totales en ADNa ne différaient pas entre les groupes (p = 0,343). L’analyse par réaction de polymérisation en chaîne (PCR) numérique au bisulfite
ciblant le locus non méthylé FAM101A a démontré que l’ADNa issu de cardiomyocytes
était significativement plus élevé chez les patients présentant une insuffisance cardiaque
que chez les sujets témoins (médiane de 0,99 [intervalle écart : 0,77-1,98] vs 0 [0-0,91]
copies/ml; p = 0,003). L’ADNa de cardiomyocytes a permis de différencier de manière significative
les patients présentant une insuffisance cardiaque des sujets témoins (aire sous la
courbe ROC [receiver operating characteristic] : 0,716; p = 0,003) et était corrélé positivement avec le taux de troponine I (r = 0,438; p = 0,003), mais pas avec le taux du peptide natriurétique de type B (r = 0,275; p = 0,058). L’ADNa pourrait servir de nouveau biomarqueur pour mesurer la mort des
cardiomyocytes chez les patients présentant une insuffisance cardiaque.
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References
- A mechanistic role for cardiac myocyte apoptosis in heart failure.J Clin Invest. 2003; 111: 1497-1504
- Circulating cardiac troponin I in severe congestive heart failure.Circulation. 1997; 96: 2953-2958
- Free DNA in the serum of cancer patients and the effect of therapy.Cancer Res. 1977; 37: 646-650
- Application of cell-free DNA analysis to cancer treatment.N Engl J Med. 2018; 379: 1754-1765
- Identification of tissue-specific cell death using methylation patterns of circulating DNA.Proc Natl Acad Sci U S A. 2016; 113: E1826-E1834
- Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing.Proc Natl Acad Sci U S A. 2013; 110: 18761-18768
- Exhaled acetone concentration is related to hemodynamic severity in patients with non-ischemic chronic heart failure.Circ J. 2016; 80: 1178-1186
- Copy-number analysis of topoisomerase and thymidylate synthase genes in frozen and FFPE DNAs of colorectal cancers.Pharmacogenomics. 2008; 9: 1459-1466
- Noninvasive detection of human cardiomyocyte death using methylation patterns of circulating DNA.Nat Commun. 2018; 9: 1443
- Plasma levels of melatonin in dilated cardiomyopathy.J Pineal Res. 2019; 66 (e12564)
- Myocytes die by multiple mechanisms in failing human hearts.Circulation research. 2003; 92: 715-724
- Levosimendan reduces plasma cell-free DNA levels in patients with ischemic cardiomyopathy.J Thromb Thrombolysis. 2011; 31: 180-187
- Elevated cell-free serum DNA detected in patients with myocardial infarction.Clin Chim Acta. 2003; 327: 95-101
- Ongoing myocardial injury in stable severe heart failure: value of cardiac troponin T monitoring for high-risk patient identification.Circulation. 2004; 110: 2376-2382
- Diagnostic performance of high-sensitive troponin T in patients with renal insufficiency.Am J Cardiol. 2013; 112: 1968-1972
- “Paradox” of troponin elevations after noncardiac surgery.Br J Anaesth. 2015; 114: 863-865
- Blood clearance kinetics and liver uptake of mononucleosomes in mice.J Immunol. 1996; 156: 1151-1156
- Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature.Future Sci OA. 2018; 4: FSO295
- Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo.Nat Commun. 2018; 9: 391
Article info
Publication history
Published online: October 19, 2019
Accepted:
October 14,
2019
Received:
August 28,
2019
Footnotes
See editorial by Devaux, pages 807-808 of this issue.
See page 934 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Cardiomyocyte-Specific Cell-Free DNA as a Heart Failure Biomarker?Canadian Journal of CardiologyVol. 36Issue 6
- PreviewDespite significant advances in the management of heart failure, this disease remains a main cause of mortality and disability. Heart failure affects 1%-2% of the adult population in developed countries and this prevalence rises to more than 10% after 70 years of age.1 Owing to the ageing of the population, the prevalence of heart failure is expected to continue to increase. The health care costs of heart failure also show a continuing rise and represent a significant burden for society.2 Overall, heart failure is a serious public health issue which requires efforts from the research community to develop new drugs and biomarkers to allow movement toward personalized health care.
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