Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress.

Introduction: The prognostic value of epicardial fat thickness (EFT) and inflammatory biomarkers such as hs-CRP have not been fully investigated in patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM). The study aim was to assess the correlation between the EFT, the persistence of elevated circulating levels of hs-CRP at 7 ± 2 days after an AMI and the amplitude of the left ventricular (LV) remodeling, in patients with type 2 DM. Methods: The study included 98 patients (45 with type 2 DM and 43 with no DM): Group 1 included 22 low-to-intermediate risk patients (hsCRP 3 mg/l) patients. EFT, LV function and remodeling were assessed at baseline and at six months after AMI in both groups. Results: In the diabetic population, the EFT was significantly higher in patients who developed ventricular remodeling as compared with those who did not (8.02 ± 1.80 mm vs. 6.65 ± 2.17 mm, p = 0.02) and significantly correlated with the circulating levels of hs-CRP (r = 0.6251, p <0.0001). The levels of circulating hs-CRP, at baseline, significantly correlated with the RI at six months (r = 0.39, p <0.001). Also, in the diabetic population, the epicardial fat thickness was significantly higher in patients who developed ventricular remodeling as compared with those who did not (8.02 ± 1.80 mm vs. 6.65 ± 2.17 mm, p = 0.02). The epicardial adipose tissue thickness significantly correlated with the circulating levels of hs-CRP (r = 0.6251, p <0.0001), while in the non-diabetic population, EFT was not significantly higher in patients who developed ventricular remodeling as compared with those who did not (71.38 ± 9.09 vs. 67.4 ± 10.17, p = 0.23). Multivariate analysis identified the hs-CRP values (OR: 4.09, p = 0.03) and the EFT (OR: 6.11, p = 0.01) as significant independent predictors for LV remodeling in diabetic population. Conclusions: A larger EFT is associated with a more severe remodeling and impairment of ventricular function in patients with type 2 DM and AMI.

Background: This systematic review seeks to evaluate the role of epicardial adipose tissue (EAT), quantified either by thickness, assessed by transthoracic echocardiography, or by volume, assessed by cardiac computed tomography (CT), in the follow-up of patients with acute coronary syndromes (ACS). Method: One-hundred forty-four articles were screened, from which 56 were reviewed in full-text. From those, 47 studies were excluded for the following reasons: they did not meet the inclusion criteria; they were either reviews or meta-analyses; the study cohorts included only stable coronary artery disease patients; they did not state a clear and concise study design, endpoints, or follow-up. The final draft included nine studies for systematic evaluation. Results: Of the 2,306 patients included in the review, 170 underwent cardiac CT while the remaining 2,136 underwent transthoracic echocardiography for the measurement of EAT. The analysis found that the EAT thickness was significantly associated with major adverse cardiovascular events (MACE) rates during hospitalization (OR: -1.3, 95% CI: 1.05-1.62, p = 0.020) and at three years (HR: 1.524, 95% CI: 1.0-2.2, p = 0.038). The included studies found that EAT was correlated with the following clinical and angiographic risk scores for ACS: GRACE (r = 0.438, p <0.001), TIMI risk score (r = 0.363, p = 0.001), SYNTAX score (r = 0.690, p <0.0001; r = 0.610, p <0.01), and Gensini score (r = 0.438, p = 0.001). There was an inverse correlation between ST-segment resolution of <70% after revascularization and EAT (r = −0.414, p = 0.01), and the myocardial blush grade (r = −0.549, p <0.001). The EF aggregation ranged between 2.65 mm and 4.7 mm within the included studies. Conclusions: EAT, evaluated either by echocardiography or cardiac CT, correlates with the severity of coronary lesions, with the clinical and angiographic risk scores for acute coronary syndromes, with indicators for coronary reperfusion, and with short- and long-term MACE rates. Further studies are required to fully elucidate the role of this extensively studied but still novel cardiovascular biomarker as part of a risk prediction tool.

While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree, on the extension of ventricular remodeling and scaring, has not been clarified yet. The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study. The main purpose of this trial is to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). One hundred patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms will be enrolled in the study. The level of systemic inflammation will be evaluated based on the serum biomarker levels (hs-CRP, matrix metalloproteinases, interleukin-6) in the acute phase of the myocardial infarction (MI) and at 1 month. Pan-coronary plaque vulnerability will be assessed based on serum biomarkers known to be associated with increased plaque vulnerability (V-CAM or I-CAM) and at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features of all coronary plaques. Myocardial viability and remodeling will be assessed based on 3D speckle tracking echocardiography associated with dobutamine infusion and LGE-CMR associated with post-processing imaging methods. The study population will be categorized in 2 subgroups: subgroup 1 - subjects with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl), and subgroup 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP < 3 mg/dl). Study outcomes will consist in the rate of post-infarction heart failure development and the major adverse events (MACE) rate. VIABILITY is the first prospective study designed to evaluate the influence of infarct-related inflammatory response on several major determinants of post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling.

Introduction: While the role of early mobilization in the immediate postinfarction period has been well demonstrated, little is known in present about the link between early mobilization and reduction of systemic inflammation. At the same time, the impact of early mobilization on regression of left ventricular remodeling has not been elucidated so far. Material and methods: Here we present the study protocol of the REHAB trial, a clinical descriptive, prospective study, conducted in a single-center, with the purpose to analyze the impact of early mobilization in reducing left ventricular remodeling, the complication rates and mortality in patients who had suffered a recent acute myocardial infarction (AMI). At the same time, the study aims to demonstrate the contribution of early mobilization to reduction of systemic inflammation, thus reducing the inflammation-mediated ventricular remodeling. 100 patients with AMI in the last 12 hours, and successful revascularization of the culprit artery within the first 12 hours after the onset of symptoms in ST-segment elevation acute myocardial infarction or within first 48 hours in non ST-segment elevation AMI will be enrolled in the study. Based on the moment of mobilization after AMI patients will be distributed in 2 groups: group 1 – patients with early mobilization (2 days after the onset of symptoms). Study outcomes will consist in the impact of early mobilization after AMI on the ventricular remodeling in the post-infarction period, as assessed by cardiac magnetic resonance imaging, the rate of in-hospital mortality, the rate of repeated revascularization or MACE and the effect of early mobilization on systemic inflammation in the immediate postinfarction phase. Conclusion: In conclusion, REHAB will be the first trial that will elucidate the impact of early mobilization in the first period after AMI, as a first step of a complex cardiac rehabilitation program, to reduce systemic inflammation and prevent deleterious ventricular remodeling in patients who suffered a recent AMI.

Background: The impact of nutritional status on the early outcome of subjects with acute myocardial infarction (AMI) is still not completely elucidated. This study aimed to assess the correlation between nutritional status, as expressed by the CONUT and PIN scores, and (1) clinical and laboratory characteristics, (2) complication rates, and (3) length of hospitalization, in patients with AMI. Materials and methods: We included 56 consecutive patients with AMI who underwent primary percutaneous intervention and stenting. Evaluation of the nutritional status was comprised in the calculation of the CONUT and PNI scores. The study population was divided into 2 groups according to the calculated CONUT score, as follows: group 1 – CONUT score <3 points (normal to mildly impaired nutritional status) and group 2 – CONUT score ≥3 points (moderate to severe malnutrition). The primary end-point of the study was the rate of in-hospital complications (left ventricular free wall rupture, hemodynamic instability requiring inotropic medication, high-degree atrioventricular block, the need for temporary cardiostimulation, supraventricular and ventricular arrhythmias and in-hospital cardiac arrest). The secondary end-points included the duration of hospitalization and the length of stay in the intensive cardiac care unit. Results: In total, 56 patients (44.64% with STEMI, 55.35% with NSTEMI) with a mean age of 61.96 ± 13.42 years, 58.92% males were included in the study. Group distribution was: group 1 – 76.78% (n = 43), group 2 – 23.21% (n = 23). There were no differences between the two groups regarding age, gender, cardiovascular risk factors, or comorbidities. PNI index in group 1 was 54.4 ± 10.4 and in group 2 41.1 ± 2.8, p <0.0001. Serum albumin was significantly lower in group 1 – 4.1 ± 0.3 vs. group 2 – 3.6 ± 0.3 (p <0.0001), similarly to total cholesterol levels (group 1 – 194.9 ± 41.5 vs. group 2 – 161.2 ± 58.2, p = 0.02). The complete blood cell count showed that group 2 presented lower levels of hematocrit (p = 0.003), hemoglobin (p = 0.002), and lymphocytes (p <0.0001) compared to group 1, but a significantly higher platelet count (p = 0.001), mean platelet volume (p = 0.03), neutrophil/lymphocyte (p <0.0001) and platelet/lymphocyte (p <0.0001) ratios, indicating enhanced blood thrombogenicity and inflammation. Regarding in-hospital complications, group 2 presented a higher rate of hemodynamic instability (group 1 – 11.6% vs. group 2 – 38.4%, p = 0.02). The overall hospitalization period was 7.7 ± 1.4 days in group 1 vs. 10.2 ± 4.8 days in group 2, p = 0.06; while the duration of stay in the intensive cardiac care unit was 2.6 ± 0.5 days in group 1 vs. 4.0 ± 2.5 days in group 2, p = 0.02. Conclusions: This study proved that nutritional deficit in acute myocardial patients who undergo revascularization is associated with an increased rate of in-hospital complications and with a longer observation time in a tertiary intensive cardiac care unit.