Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction

Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF...

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Main Authors: Tetiana Berezina, Oleksandr O. Berezin, Michael Lichtenauer, Alexander E. Berezin
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Cardiogenetics
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Online Access:https://www.mdpi.com/2035-8148/14/4/14
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author Tetiana Berezina
Oleksandr O. Berezin
Michael Lichtenauer
Alexander E. Berezin
author_facet Tetiana Berezina
Oleksandr O. Berezin
Michael Lichtenauer
Alexander E. Berezin
author_sort Tetiana Berezina
collection DOAJ
description Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced ejection fraction (HFrEF). Cell-free nuclear (cf-nDNA) DNA is released from damaged cells and contributes to impaired cardiac structure and function and inflammation. The purpose of the study was to elucidate whether cf-nDNA is associated with HFimpEF. Methods: The study prescreened 1416 patients with HF using a local database. Between October 2021 and August 2022, we included 452 patients with chronic HFrEF after prescription of optimal guideline-based therapy and identified 177 HFimpEF individuals. Circulating biomarkers were measured at baseline and after 6 months. Detection of cf-nDNA was executed with real-time quantitative PCR (qPCR) using NADH dehydrogenase, ND2, and beta-2-microglobulin. Results: We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. The presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; <i>p</i> = 0.044), type 2 diabetes mellitus (OR = 0.77; <i>p</i> = 0.042), and digoxin administration (OR = 0.85; <i>p</i> = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤ 1940 pmol/mL (OR = 1.42, <i>p</i> = 0.001), relative decrease in NT-proBNP levels (>35% vs. ≤35%) from baseline (OR = 1.52; <i>p</i> = 0.001), and cf-nDNA ≤ 7.5 μmol/L (OR = 1.56; <i>p</i> = 0.001) were positive predictors for HFimpEF. Conclusions: We established that the levels of cf-nDNA ≤ 7.5 μmol/L independently predicted HFimpEF and improved the discriminative ability of ischemia-induced cardiomyopathy, IV NYHA class, and single-measured NT-proBNP and led to a relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF.
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spelling doaj-art-052c9ef5a0a34bd4a0cefd03a3e597932025-08-20T02:53:19ZengMDPI AGCardiogenetics2035-82532035-81482024-10-0114418319710.3390/cardiogenetics14040014Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection FractionTetiana Berezina0Oleksandr O. Berezin1Michael Lichtenauer2Alexander E. Berezin3Department of Internal Medicine and Nephrology, Vita Center, 69000 Zaporozhye, UkraineDepartment of Alter Psychiatrie, Luzerner Psychiatrie AG, 4915 St. Urban, SwitzerlandDivision of Cardiology, Department of Internal Medicine II, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaDivision of Cardiology, Department of Internal Medicine II, Paracelsus Medical University Salzburg, 5020 Salzburg, AustriaBackground: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced ejection fraction (HFrEF). Cell-free nuclear (cf-nDNA) DNA is released from damaged cells and contributes to impaired cardiac structure and function and inflammation. The purpose of the study was to elucidate whether cf-nDNA is associated with HFimpEF. Methods: The study prescreened 1416 patients with HF using a local database. Between October 2021 and August 2022, we included 452 patients with chronic HFrEF after prescription of optimal guideline-based therapy and identified 177 HFimpEF individuals. Circulating biomarkers were measured at baseline and after 6 months. Detection of cf-nDNA was executed with real-time quantitative PCR (qPCR) using NADH dehydrogenase, ND2, and beta-2-microglobulin. Results: We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. The presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; <i>p</i> = 0.044), type 2 diabetes mellitus (OR = 0.77; <i>p</i> = 0.042), and digoxin administration (OR = 0.85; <i>p</i> = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤ 1940 pmol/mL (OR = 1.42, <i>p</i> = 0.001), relative decrease in NT-proBNP levels (>35% vs. ≤35%) from baseline (OR = 1.52; <i>p</i> = 0.001), and cf-nDNA ≤ 7.5 μmol/L (OR = 1.56; <i>p</i> = 0.001) were positive predictors for HFimpEF. Conclusions: We established that the levels of cf-nDNA ≤ 7.5 μmol/L independently predicted HFimpEF and improved the discriminative ability of ischemia-induced cardiomyopathy, IV NYHA class, and single-measured NT-proBNP and led to a relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF.https://www.mdpi.com/2035-8148/14/4/14heart failure with improved ejection fractionheart failure with reduced ejection fractioncell-free nuclear DNAbiomarkers
spellingShingle Tetiana Berezina
Oleksandr O. Berezin
Michael Lichtenauer
Alexander E. Berezin
Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
Cardiogenetics
heart failure with improved ejection fraction
heart failure with reduced ejection fraction
cell-free nuclear DNA
biomarkers
title Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
title_full Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
title_fullStr Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
title_full_unstemmed Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
title_short Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction
title_sort circulating cell free nuclear dna predicted an improvement of systolic left ventricular function in individuals with chronic heart failure with reduced ejection fraction
topic heart failure with improved ejection fraction
heart failure with reduced ejection fraction
cell-free nuclear DNA
biomarkers
url https://www.mdpi.com/2035-8148/14/4/14
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AT oleksandroberezin circulatingcellfreenucleardnapredictedanimprovementofsystolicleftventricularfunctioninindividualswithchronicheartfailurewithreducedejectionfraction
AT michaellichtenauer circulatingcellfreenucleardnapredictedanimprovementofsystolicleftventricularfunctioninindividualswithchronicheartfailurewithreducedejectionfraction
AT alexandereberezin circulatingcellfreenucleardnapredictedanimprovementofsystolicleftventricularfunctioninindividualswithchronicheartfailurewithreducedejectionfraction