Cardiovascular diseases (CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction (AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cells that can generate new myocardial tissue to replace the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosome-based therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

Introduction:Interventional ablation has been demonstrated to represent an effective therapy in patients with atrial fibrillation (AF), leading to restoration and maintenance of sinus rhythm in the majority of cases. However, recurrence of AF is encountered in 35% to 40% of cases, and the causes for this frequent complication have not been elucidated so far.Material and methods:Here we present the study protocol of the FIBRO-RISK trial, a prospective, single-center, cohort study which aims to investigate the impact of inflammatory-mediated myocardial fibrosis on the risk of recurrence after successful catheter ablation of atrial fibrillation. The level of systemic inflammation in the pre-ablation and immediate post-ablation period will be assessed on the basis of serum levels of inflammatory biomarkers (hsCRP, matrix metalloproteases, interleukin-6), while the level of cardiac fibrosis will be determined based on cardiac magnetic resonance imaging associated with complex post-processing techniques for mapping myocardial fibrosis at the level of left atrium and left ventricle. At the same time, the amount of epicardial fat will serve as an indirect marker of localized inflammation and will be determined at different levels in the heart (surrounding left atrium, right atrium or the entire heart), while ventricular function will be assessed on the basis of serum levels of NT-proBNP prior to the procedure. All these parameters will be investigated in patients with successful ablation of AF, who will be divided into 2 groups: group 1 – patients who develop AF recurrence at 1-year, and group 2 – patients with no recurrence of AF at 1-year. In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers and NT-proBNP at 24 hours and 1-year post procedure, the amount of myocardial fibrosis at the level of left atrium and left ventricle at baseline +/− 7 days, and the amount of epicardial fat surrounding left atrium, right atrium and the entire heart at baseline +/− 7 days.The primary endpoint of the study will be represented by the rate of AF recurrence at 1-year post ablation, documented by either ECG or Holter monitoring. The secondary endpoints of the study will consist in:the rate of re-hospitalization,the rate of survival without relapse, andthe rate of major adverse cardiovascular events (MACE rate, including cardiovascular death or stroke).In conclusion, FIBRO-RISK will be the first CMR-based study that will investigate the impact of inflammation-mediated myocardial fibrosis and ventricular remodeling on the risk of recurrence after successful ablation of AF, aiming to validate inflammatory biomarkers and myocardial fibrosis as predictors for AF recurrence.

Introduction: In patients with out-of-hospital cardiac arrest (OHCA) complicating an ST-segment elevation myocardial infarction (STEMI), the survival depends largely on the restoration of coronary flow in the infarct related artery. The aim of this study was to determine clinical and angiographic predictors of in-hospital mortality in patients with OHCA and STEMI, successfully resuscitated and undergoing primary percutaneous intervention (PCI). Methods: From January 2013 to July 2015, 78 patients with STEMI presenting OHCA, successfully resuscitated, transferred immediately to the catheterization unit and treated with primary PCI, were analyzed. Clinical, laboratory and angiographic data were compared in 28 non-survivors and 50 survivors. Results:The clinical baseline characteristics of the study population showed no significant differences between the survivors and non-survivors in respect to age (p=0.06), gender (p=0.8), the presence of hypertension (p=0.4), dyslipidemia (p=0.09) obesity (p=1), smoking status (p=0.2), presence of diabetes (p=0.2), a clinical history of acute myocardial infarction (p=0.7) or stroke (p=0.17). Compared to survivors, the non-survivor group exhibited a significantly higher incidence of cardiogenic shock (50% vs 24%, p=0.02), renal failure (64.3% vs 30.0%, p=0.004) and anaemia (35.7% vs 12.0%, p=0.02). Three-vessel disease was significantly higher in the non-survivor group (42.8% vs. 20.0%, p=0.03), while there was a significantly higher percentage of TIMI 3 flow postPCI in the infarct-related artery in the survivor group (80.% vs. 57.1%, p=0.03). The time from the onset of symptoms to revascularization was significantly higher in patients who died compared to those who survived (387.5 +/-211.3 minutes vs 300.8 +/-166.1 minutes, p=0.04), as was the time from the onset of cardiac arrest to revascularization (103.0 +/-56.34 minutes vs 67.0 +/-44.4 minutes, p=0.002). Multivariate analysis identified the presence of cardiogenic shock (odds ratio [OR]: 3.17, p=0.02), multivessel disease (OR: 3.0, p=0.03), renal failure (OR: 4.2, p=0.004), anaemia (OR: 4.07, p=0.02), need for mechanical ventilation >48 hours (OR: 8.07, p=0.0002) and a duration of stay in the ICU longer than 5 days (OR: 9.96, p=0.0002) as the most significant independent predictors for mortality in patients with OHCA and STEMI. Conclusion: In patients surviving an OHCA in the early phase of a myocardial infarction, the presence of cardiogenic shock, renal failure, anaemia or multivessel disease, as well as a longer time from the onset of symptoms or of cardiac arrest to revascularization, are independent predictors of mortality. However, the most powerful predictor of death is the duration of stay in the ICU and the requirement of mechanical ventilation for more than forty-eight hours.

Atrial fibrillation (AF) is the most frequent form of supraventricular arrhythmia in medical practice. It is characterized by chaotic electrical activity in the atria, which often leads to irregular and fast ventricular contractions. Pulmonary veins (PV) play an essential part in the genesis of AF. There are a series of risk factors that trigger the development and recurrence of AF after PV isolation. Despite advanced medical technology, the success rate of AF ablation is not satisfactory. The purpose of this study is to assess the preprocedural imaging and serum biomarkers linked to an increased recurrence of AF after PV isolation. The primary endpoint is represented by AF recurrence after PV isolation. In addition, the rate of cardiovascular death and the rate of major adverse cardiovascular events will be assessed in relation to the enlargement of the left atrium and the volume of epicardial adipose tissue surrounding the heart.

The aim of this study was to investigate the association between left ventricular remodeling, atrial fibrillation (AF), and the severity of ventricular tachycardia (VT) in patients with ventricular rhythm disturbances admitted in a level 3 facility of acute cardiac care. Material and Methods: The RHYTHM-ACC registry was a single-center observational study, including 150 consecutive patients with sustained or non-sustained ventricular tachycardia (sVT and nsVT, respectively) admitted in an intensive cardiac care unit (ICCU), separated in: group 1 -29 patients (21.01%) with dilated cardiomyopathy (DCM), and group 2 -109 patients (78.99%) with normal ventricular performance. We investigated the difference between clinical characteristics of patients with sVT versus those with nsVT in each study group, and the association between AF and different forms of ventricular arrhythmia in 38 (25.33%) patients with AF and 112 (74.66%) patients in sinus rhythm. Results: There were no significant differences between the study groups with respect to type of ventricular arrhythmia: sVT (46.87% vs. 36.44%, p = 0.2), nsVT (43.75% vs. 55.93%, p = 0.2), or ventricular fibrillation (VF) (9.37% vs. 7.62%, p = 0.7). However, patients with DCM presented a significantly higher incidence of AF (43.75% vs. 20.33%, p = 0.01) and bundle branch block (37.5% vs. 11.86%, p = 0.0007). VF occurred more frequently in patients with AF compared to those in sinus rhythm (18.42% vs. 4.46%, p = 0.006). Multivariate analysis identified the co-existence of AF (OR = 4.8, p = 0.01) and the presence of a bundle branch block (BBB) (OR = 3.9, p = 0.03) as the most powerful predictors for the degeneration of VT into VF in patients admitted with sVT or nsVT in an ICCU unit. Conclusions: In patients with any type of VT admitted in an ICCU, the presence of ventricular remodeling is associated with a higher incidence of AF and conduction abnormalities, but not with a more severe pattern of ventricular arrhythmia. At the same time, AF and BBB seem to represent the most powerful predictors for degeneration of VT into VF, independent of the type of VT.