Patients with heart failure (HF) with improved LVEF (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. Identification 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 contribute to adverse cardiac remodeling, cardiac dysfunction and inflammation. The purpose of the study was to elucidate whether cf-nDNAs are associated with HFimpEF. 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 HFimpEF in 177 individuals from them according to the criteria of European Society of Cardiology. Measurements of circulating biomarkers were performed at baseline and in 6 months. Detection of cf-nDNA was executed with real time quantitative PCR (qPCR) using NADH dehydrogenase, ND2 and beta-2-microglobulin. 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. Presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; confidence interval [CI] = 0.62 – 0.88; p = 0.044), type 2 diabetes mellitus (OR = 0.77; CI = 0.71 – 0.82; p = 0.042) and digoxin administration (OR = 0.85; CI = 0.72-0.97; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤1940 pmol/mL (OR = 1.42; 95% CI = 1.19-1.98, p = 0.001), relative decrease in NT-proBNP levels (>35% vs. ≤35%) from baseline (OR = 1.52; 95% CI = 1.38-0.69, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.56; 95% CI = 1.07-2.94, p = 0.001) were positive predictors for HFimpEF. Multivariate logistic regression adjusted to ischemia-induced cardiomyopathy, IV HF NYHA class, and digoxin use yielded that NT-proBNP ≤1940 pmol/mL (OR = 1.43; 95% CI = 1.21-1.88, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.64; 95% CI = 1.19-2.15, p = 0.001) independently predicted HFimpEF. In conclusions: we established that the levels of cf-nDNA≤7.5 μmol/L independently predicted HFimpEF and improved discriminative ability of as single measured NT-proBNP as well as relative decrease in NT-proBNP levels ≤35% from baseline.

Abstract: (1) Background and Objective: MicroRNAs (miR) are biomarkers for assessing the extent of cardiac remodeling after myocardial infarction (MI) and important predictors of clinical outcome in heart failure. Overexpression of miR-30d appears to have a cardioprotective effect. The aim of the present study was to demonstrate whether miR-30d could be used as a potential therapeutic target to improve post-MI adverse remodeling. (2) Methods and Results: MiR profiling was performed by next generation sequencing to assess different expression patterns in ischemic vs. healthy myocardium in a rat model of MI. MiR-30d was significantly downregulated (p<0.001) in ischemic myocardium and was selected as promising target. A mimic of miR-30d was administered in the respective treatment group, whereas control group received non-functional, scrambled siRNA. To measure the effect of miR-30d on infarct area size of left ventricle, rats were randomized and treated with miR-30d or scrambled siRNA. Histological planimetry was performed 72 hours and 6 weeks after induction of MI. Infarct area was significantly reduced at 72 hours and at 6 weeks by using the miR-30d (72 hours: 22.89±7.66% vs. 35.96±9.27%, p=0.0136; 6 weeks: 6.93±4.58% vs. 12.48±7.09%; p=0.0172). To gain insight into infarct healing, scratch assays were used to obtain information on cell migration in human umbilical vein endothelial cells (HUVEC). Gap closure was significantly faster in the mimic-treated cells 20h post-scratching (12.4% more than scrambled control after 20h; p=0.013). To analyze anti-apoptotic quality of miR-30d, the ratio between phosphorylated p53 and total p53 was evaluated in human cardiomyocytes using ELISA. Under the influence of miR-30d mimic, cardiomyocytes demonstrated a decreased pp53/total p53 ratio (0.66±0.08 vs. 0.81±0.17), showing a distinct tendency (p=0.055) to decrease apoptosis rate compared to the control group. (3) Conclusion: Using a mimic of miR-30d underlines the cardioprotective effect of miR-30d in MI and could reduce the risk for development of ischemic cardiomyopathy.

Background: Cardiovascular risk in prediabetic patients is substantial yet it is often underestimated in everyday clinical practice. Objectives: This study examines the future cardiovascular risk in prediabetic patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: We conducted a retrospective analysis of 725 STEMI patients at a tertiary center in Austria between 2018 and 2020, categorized into groups of non-diabetic, prediabetic, and diabetic patients. Baseline characteristics, cardiovascular risk factors, and long-term survival outcomes were compared using Kaplan-Meier survival analysis along with other statistical tests. Results: Of the 725 patients, 407 (56.1%) were non-diabetic, 184 (25.4%) prediabetic, and 134 (18.5%) diabetic. Prediabetic patients exhibited significant additional cardiovascular risk factors, such as arterial hypertension (67.4%) and dyslipidemia (78.3%), with prevalence rates between those of non-diabetic and diabetic patients. Kaplan-Meier analysis revealed that at three-year follow-up, prediabetic patients faced a survival disadvantage with a significant decrease in survival rates compared to non-diabetic patients (log-rank p = 0.016); their survival outcomes approached those of diabetic patients (p = 0.125). Conclusions: Our findings underscore the critical need for early identification and aggressive management of prediabetes in cardiovascular care of patients after acute STEMI. In current clinical practice, prediabetic patients are often underdiagnosed and undertreated, putting them at disproportionate risk. Integrating rigorous cardiovascular risk management strategies for prediabetic individuals, including lifestyle interventions and potentially pharmacological treatments, could prevent the progression to diabetes and mitigate associated cardiovascular risks. This paradigm shift in treating prediabetes as seriously as diabetes may significantly improve long-term survival outcomes for this vulnerable population.

Background: Heart failure (HF) remains a challenging healthcare issue, necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, defining CRT-D responders lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions, encompassing functional, echocardiographic, and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria, including NYHA stage, LVEF increase, and proBNP decrease. Statistical analyses, such as Kaplan–Meier curves and Cox hazard regression, were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders, defined by NYHA decrease, LVEF increase, or proBNP decrease, exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction, and normal right ventricular, echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced, patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation, and renal function influence responses. The study enriches our understanding of CRT-D response, contributing to the foundation for personalized HF management.