DNA hypermethylation of MED1 and MED23 as early diagnostic biomarkers for unsolved issues in atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Much effort was spent to identify biomarkers useful to stratify AF patients. Mediator complex (MED) is an ancestral regulator of transcriptional mechanisms.

COMPArison of Multi-Point Pacing and ConvenTional Cardiac Resynchronization Therapy Through Noninvasive Hemodynamics Measurement: Short- and Long-Term Results of the COMPACT-MPP Study.

Invasive hemodynamic studies have shown improved left ventricular (LV) performances when cardiac resynchronization therapy/defibrillator is delivered through multipoint pacing (MPP). Nowadays, strategies have become available that allow studying the same hemodynamic parameters at a noninvasive level. The aim of the present study was to evaluate the clinical implication of using a patient-tailored approach for cardiac resynchronization therapy programming based on noninvasively assessed LV hemodynamics to identify the best biventricular pacing modality between standard single-site pacing (STD) and MPP for each patient.

CDK5R1, GSE1, HSPG2 and WDFY3 as indirect epigenetic-sensitive genes in atrial fibrillation.

Background: Although mounting evidence supports that aberrant DNA methylation occurs in the hearts of patients with atrial fibrillation (AF), noninvasive epigenetic characterization of AF has not yet been defined.

Methods: We investigated DNA methylome changes in peripheral blood CD4 T cells isolated from 10 patients with AF relative to 11 healthy subjects (HS) who were enrolled in the DIANA clinical trial (NCT04371809) via reduced-representation bisulfite sequencing (RRBS).

Results: An atrial-specific PPI network revealed 18 hub differentially methylated genes (DMGs), wherein ROC curve analysis revealed reasonable diagnostic performance of DNA methylation levels found within CDK5R1 (AUC = 0.

Endothelial Dysfunction Drives CRTd Outcome at 1-Year Follow-Up: A Novel Role as Biomarker for miR-130a-5p.

Endothelial dysfunction (ED) causes worse prognoses in heart failure (HF) patients treated with cardiac resynchronization therapy (CRTd). ED triggers the downregulation of microRNA-130 (miR-130a-5p), which targets endothelin-1 (ET-1). Thus, we evaluated ED and the response to CRTd by assessing miR-130a-5p and ET-1 serum levels.

De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients.

Background And Aims: DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications.

Angiotensin receptor/Neprilysin inhibitor effects in CRTd non-responders: From epigenetic to clinical beside.

Objectives: We evaluated whether Angiotensin receptor/Neprilysin inhibitors (ARNI) reduce heart failure (HF) hospitalizations and deaths in cardiac resynchronization therapy with defibrillator (CRTd) non-responders patients at 12 months of follow-up, modulating microRNAs (miRs) implied in adverse cardiac remodeling.

Background: adverse cardiac remodeling characterized by left ventricle ejection fraction (LVEF) reduction, left ventricular end-systolic volume (LVESv) increase, and the 6-minute walking test (6MWT) reduction are relevant pathological mechanisms in CRTd non-responders and could be linked to changes in miRNAs (miRs), regulating cardiac fibrosis, apoptosis, and hypertrophy.

Methods: miRs levels and clinical outcomes (LVEF, cardiac deaths, and 6MWT) were evaluated at baseline and one year of follow-up in CRTd non-responders divided into ARNI-users and Non-ARNI users.

and DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome network analysis.

Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease.We performed an epigenome-wide analysis of circulating CD4 and CD8 T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4 T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients HS.

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators.

Objectives: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach.

Background: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response.

Arrhythmogenic syncope leading to cardiac rhythm management procedures during COVID-19 lockdown.

: Following the coronavirus disease (COVID-19) outbreak, the Italian government adopted strict rules of lockdown and social distancing. The aim of our study was to assess admission rate for syncope leading to cardiac rhythm management (CRM) procedures in Campania, the third-most-populous region of Italy, during COVID-19 lockdown. : Data were sourced from 14 referral hospitals in Campania from 10 March to 4 May 2020 (lockdown period) and during the same period in 2019.

Integrated analysis of DNA methylation profile of HLA-G gene and imaging in coronary heart disease: Pilot study.

Aims: Immune endothelial inflammation, underlying coronary heart disease (CHD) related phenotypes, could provide new insight into the pathobiology of the disease. We investigated DNA methylation level of the unique CpG island of HLA-G gene in CHD patients and evaluated the correlation with cardiac computed tomography angiography (CCTA) features.

Methods: Thirty-two patients that underwent CCTA for suspected CHD were enrolled for this study.

Cardiac resynchronization therapy with a defibrillator (CRTd) in failing heart patients with type 2 diabetes mellitus and treated by glucagon-like peptide 1 receptor agonists (GLP-1 RA) therapy vs. conventional hypoglycemic drugs: arrhythmic burden, hospitalizations for heart failure, and CRTd responders rate.

Objectives: To evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs.

Background: Patients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%.

Automatic atrial capture device control in real-life practice: A multicenter experience.

Background: Device-based fully automatic pacing capture detection is useful in clinical practice and important in the era of remote care management. The main objective of this study was to verify the effectiveness of the new ACAP Confirm® algorithm in managing atrial capture in the medium term in comparison with early post-implantation testing.

Methods: Data were collected from 318 patients (66% male; mean age, 73±10 years); 237 of these patients underwent device implantation and 81 box changes in 31 Italian hospitals.

Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study.

Background: Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring.

Methods And Results: 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group.

Evaluation of synergistic effects of resynchronization therapy and a β-blocker up-titration strategy based on a predefined patient-management program: the RESTORE study.

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome.

Combined effects of PI3K and SRC kinase inhibitors with imatinib on intracellular calcium levels, autophagy, and apoptosis in CML-PBL cells.

Imatinib induces a complete cytogenetic regression in a large percentage of patients affected by chronic myeloid leukemia (CML) until mutations in the kinase domain of BCR-ABL appear. Alternative strategies for CML patients include the inhibition of phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway, which is constitutively activated in leukemia cells and seems important for the regulation of cell proliferation, viability, and autophagy. In this study, we verified the effect of imatinib mesylate (IM), alone or in association with LY294002 (LY) (a specific PI3K protein tyrosine kinase inhibitor) or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) (a Src tyrosine kinase inhibitor), on viability, intracellular calcium mobilization, apoptosis, and autophagy, in order to verify possible mechanisms of interaction.

Peri-procedural tight glycemic control during early percutaneous coronary intervention is associated with a lower rate of in-stent restenosis in patients with acute ST-elevation myocardial infarction.

Objective: We examined the effects of peri-procedural intensive glycemic control (IGC) during early percutaneous coronary intervention (PCI) on restenosis rate in hyperglycemic patients with ST-segment elevation myocardial infarction (STEMI).

Research Design And Methods: A total of 165 hyperglycemic patients (glucose ≥ 140 mg/dl) with first STEMI undergoing PCI were studied. Patients were randomized to IGC for almost 24 h after PCI (n = 82; glucose, 80-140 mg/dl) followed by multidose sc insulin during the hospital stay or conventional glycemic control (CGC; n = 83; glucose, 180-200 mg/dl) followed by conventional therapy.

Farnesyl transferase inhibitors induce neuroprotection by inhibiting Ha-Ras signalling pathway.

In previous studies we found that the GTPase p21 Harvey-Ras (Ha-Ras) stimulates the production of reactive oxygen species and induces apoptosis by oxidative stress; this effect was reversed by farnesyl transferase inhibitors (FTIs). In this study we investigated whether FTIs reduce rat brain damage induced by an excitotoxic stimulus, and the signalling pathway(s) underlying the neuroprotection by FTIs. In brain tissue, protein levels of Ha-Ras and farnesylation inhibition were assayed by Western blot, and superoxide production was measured by hydroethidine.

2,7-Bis-(4-amidinobenzylidene)-cycloheptan-1-one dihydrochloride, tPA stop, prevents tPA-enhanced excitotoxicity both in vitro and in vivo.

Tissue-type plasminogen activator (tPA) is available for the treatment of thromboembolic stroke in humans. However, adverse effects of tPA have been observed in animal models of ischemic brain injuries. In the present study, we have used a synthetic tPA inhibitor, named 2,7-bis-(4-amidino-benzylidene)-cycloheptan-1-one dihydrochloride (tPA stop), to investigate the role of endogenous tPA in the cerebral parenchyma.

Reconstituted high-density lipoprotein exhibits neuroprotection in two rat models of stroke.

Background: Reconstituted high-density lipoprotein (rHDL) is prepared from apolipoprotein A-I, isolated from human plasma, and soybean-derived phosphatidylcholine and exhibits biochemical and functional characteristics similar to endogenous nascent high-density lipoprotein (HDL). This study tested the hypothesis that pretreatment with rHDL may reduce neuronal damage in 2 experimental rat models of stroke.

Methods: In the first model, an excitotoxic lesion was induced by unilateral injection of N-methyl-D-aspartate (NMDA) in the right striatum (excitotoxic lesion model).

Hydrocortisone has a protective effect on CyclosporinA-induced cardiotoxicity.

CyclosporinA (CsA) is an immunosuppressive drug which induces severe adverse effects such as cardiotoxicity and nephrotoxicity. In several therapeutic protocols CsA is used in association with corticosteroids to obtain better therapeutic results. Recently, our studies showed that CsA increases blood pressure while inhibit Nitric Oxide (NO) production in vivo.

Protection of human endothelial cells from oxidative stress: role of Ras-ERK1/2 signaling.

Background: Reactive oxygen species play a critical role in inducing apoptosis. The small GTPase p21 Ras and the ERK1/2 MAPK have been proposed as key regulators of the signaling cascade triggered by oxidative stress (H2O2). Harvey-Ras (Ha-Ras) and Kirsten-Ras (Ki-Ras) isoforms are so far functionally indistinguishable, because they activate the same downstream effectors, including ERK1/2.