Abstract Background Patients with heart failure (HF) with improved LVEF (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. Iden-tification of predictors for HFimpEF may play a crucial role in individual management of HF with reduced EF (HFrEF). Cell-free nuclear (cf-nDNA) DNA are released from damaged cells and con-tribute to impaired cardiac structure and function, as well as inflammation. The purpose of the study was to elucidate whether cf-nDNAs are associated with HFimpEF. Methods It has been prescreened 1416 patients with HF using local database. Between October 2021 and August 2022 we included 452 patients chronic HFrEF after prescription of optimal guideline-based therapy and identified 177HFimpEF individuals (Figure 1). 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. ROC analysis revealed that that circulating levels of cf-nDNA 7.5 µmol/L (area under curve AUC = 0.875; 95% confidence interval CI = 0.795–0.950; sensitivity = 87.0%, specificity = 73.5%; likelihood ratio = 3.288; p = 0.001) were associated with HFimpEF. The presence of ischemia-induced cardiomyopathy (odds ration OR = 0.75; p = 0.044), type 2 diabetes mellitus (OR = 0.77; p = 0.042) and digoxin administration (OR = 0.85; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤1940 pmol/mL (OR = 1.42, p = 0.001), relative decrease in NT-proBNP levels (35% vs. ≤35%) from baseline (OR = 1.52; p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.56; p = 0.001) were positive predictors for HFimpEF. The combined model composed of relative decrease in NT-proBNP levels ≤35% from baseline + cf-nDNA demonstrated the best discriminative value on dependent variable when compared with a presence of ischemia-induced cardiomyopathy, IV NYHA class, NT-proBNP ≤1940 pmol/mL and relative decrease in NT-proBNP levels ≤35% from baseline alone. In conclusions we established that the levels of cf-nDNA≤7.5 μmol/L independently predicted HFimpEF and improved discriminative ability of as ischemia-induced cardiomyopathy, IV NYHA class, single measured NT-proBNP, as well as relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF.
Berezin et al. (Sun,) studied this question.