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Abstract Ischemia with non-obstructive coronary artery (INOCA) is a common cause of hospital admissions, leading to negative outcomes and reduced quality of life. Central to its pathophysiology is endothelial dysfunction, which contributes to myocardial ischemia despite the absence of significant coronary artery blockage. Addressing endothelial dysfunction is essential in managing INOCA to alleviate symptoms and prevent cardiovascular events. Recent studies have identified diabetes mellitus (DM) as a significant factor exacerbating INOCA complications by promoting endothelial impairment and coronary microvascular dysfunction. MicroRNAs (miRNAs) have emerged as potential biomarkers and therapeutic targets in various biological processes, including endothelial dysfunction and cardiovascular diseases. However, research on miRNA biomarkers in INOCA patients is sparse. In this study, we examined a panel of circulating miRNAs involved in the regulation of endothelial function in INOCA patients with and without DM. We analyzed miRNA expression using RT-qPCR in a cohort of consecutive INOCA patients undergoing percutaneous coronary intervention. We detected a significant dysregulation of miR-363-5p and miR-92a-3p in INOCA patients with DM compared to those without DM, indicating their role as biomarkers for predicting and monitoring endothelial dysfunction in INOCA patients with DM.

Abstract Background Sodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up. Methods In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis. Results At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p

Abstract Background No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not with sodium/glucose cotransporter 2 inhibitors (SGLT2i). Methods We recruited 377 patients with T2DM and AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 T2DM were treated with SGLT2 inhibitors before PCI. The primary outcome was major adverse cardiovascular events (MACE) defined as cardiac death, re-infarction, and heart failure related to ISR. In patients without ISR, minimal lumen area and minimal lumen diameter were assessed by coronary CT-angiography at 1-year follow-up. Results Glycemic control was similar in SGLT2i-treated patients and never SGLT2i-users. The incidence of ISR-related MACE was higher in never SGLT2i-users compared with SGLT2i-treated patients, an effect independent of glycemic status (HR = 0.418, 95% CI = 0.241–0.725, P = 0.002) and observed also in the subgroup of patients with HbA1c < 7% (HR = 0.393, 95% CI = 0.157–0.984, P = 0.027). In patients without the event, the stent patency was greater in SGLT2i-treated patients compared with never SGLT2i-users at 1-year follow-up. Conclusions SGLT2i treatment in T2DM is associated with a reduced incidence of ISR-related events, independently of glycemic control.

Abstract P‐Wave Dispersion (PWD) is an ECG parameter defined as the difference between the longest and the shortest P‐Wave duration. PWD has been associated with hypertension, a leading cause of age‐related cognitive decline. Moreover, hypertension is associated with vascular dementia and Alzheimer's Disease. Based on these considerations, we evaluated PWD and global cognitive function in frail hypertensive older adults with a previous diagnosis of cognitive decline. We evaluated consecutive frail hypertensive patients ≥65‐year‐old with a Mini‐Mental State Examination (MMSE) score

A 31-year-old male presented with sudden onset of chest pain and dyspnea after a COVID-19 infection. Initially labeled as a myopericarditis related to COVID-19, because of the young age and low risk profile, after a multiparametric evaluation was possible to diagnose and treat an unstable lesion on an intermediate branch of left coronary.

Abstract Background The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. Methods This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. Results In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p

Objective: We evaluated sodium-glucose co-transporter2 (SGLT2) expression and the effect of SGLT2 inhibitor (SGLT2i) therapies on carotid plaques of asymptomatic diabetic and non-diabetic patients. Methods: Plaques were obtained from 296 non-diabetic patients and 227 patients with type 2 diabetes undergoing carotid endarterectomy. 97 patients with type 2 diabetes were treated with SGLT2 inhibitors for 16 ± 4 months before endarterectomy. After propensity score matching analysis, patients with type 2 diabetes were categorized without (n = 87) and with SGLT2i therapy (n = 87). To investigate SGLT2 expression levels' effects on major adverse endpoints (MACE = stroke, transient ischemic attack, myocardial infarction, and death), we evaluated MACE outcomes at a 2-year follow-up. Results: Compared to plaques from patients without diabetes, plaques from patients with diabetes had higher SGLT2 expression, inflammation, and oxidative stress, along with lower SIRT6 expression and collagen content. Compared with plaques from patients with diabetes, SGLT2i-treated patients with type 2 diabetes presented increased SIRT6 expression and collagen content and lowered inflammation and ion and oxidative stress, thus indicating a more stable plaque phenotype. These results supported in vitro observations on human aorta endothelial cells (EC) (TeloHAEC-cells). Indeed, EC treated with high glucose (25 mM) in the presence of SGLT2i (100 nM canagliflozin) presented higher SIRT6 expression and decreased mRNA and protein SGLT2 levels, nuclear factor-kappa B (NF-B(NF-κB), and matrix metallopeptidase 9 (MMP-9) expression compared to cells treated only with high glucose. After two years following endarterectomy, a multivariable Cox regression analysis showed significantly higher 2-year overall survival from MACE in patients without diabetes (P

Objective: We evaluated the value of resting-state EEG source biomarkers to characterize mild cognitive impairment (MCI) subjects with an Alzheimer’s disease (AD)-like cerebrospinal fluid (CSF) profile and to track neurodegeneration throughout the AD continuum. We further applied a resting-state functional MRI (fMRI)-driven model of source reconstruction and tested its advantage in terms of AD diagnostic accuracy. Methods: Thirty-nine consecutive patients with AD dementia (ADD), 86 amnestic MCI, and 33 healthy subjects enter the EEG study. All ADD subjects, 37 out of 86 MCI patients and a distinct group of 53 healthy controls further entered the fMRI study. MCI subjects were divided according to the CSF phosphorylated tau/β amyloid-42 ratio (MCIpos: ≥ 0.13, MCIneg: < 0.13). Using Exact low-resolution brain electromagnetic tomography (eLORETA), EEG lobar current densities were estimated at fixed frequencies and analyzed. To combine the two imaging techniques, networks mostly affected by AD pathology were identified using Independent Component Analysis applied to fMRI data of ADD subjects. Current density EEG analysis within ICA-based networks at selected frequency bands was performed. Afterwards, graph analysis was applied to EEG and fMRI data at ICA-based network level. Results: ADD patients showed a widespread slowing of spectral density. At a lobar level, MCIpos subjects showed a widespread higher theta density than MCIneg and healthy subjects; a lower beta2 density than healthy subjects was also found in parietal and occipital lobes. Evaluating EEG sources within the ICA-based networks, alpha2 band distinguished MCIpos from MCIneg, ADD and healthy subjects with good accuracy. Graph analysis on EEG data showed an alteration of connectome configuration at theta frequency in ADD and MCIpos patients and a progressive disruption of connectivity at alpha2 frequency throughout the AD continuum. Conclusions: Theta frequency is the earliest and most sensitive EEG marker of AD pathology. Furthermore, EEG/fMRI integration highlighted the role of alpha2 band as potential neurodegeneration biomarker.

Abstract Objectives We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients. Background The management of hyperglycemic patients during STEMI is unclear. Methods We undertook an observational cohort study of 3166 first STEMI. Patients were grouped on the basis of whether they received TA or not. Moreover, among these patients we selected a subgroup of STEMI patients with hyperglycemia during the event (glycaemia > 140 mg/dl). The endpoint at 1 year included all-cause mortality, cardiac mortality and re-hospitalization for coronary disease, heart failure and stroke. Results One-thousand STEMI patients undergoing PPCI to plus TA (TA-group) and 1504 STEMI patients treated with PPCI alone (no-TA group) completed the study. In overall study-population, Kaplan–Meier-analysis demonstrated no significant difference in mortality rates between patients with and without TA (P = 0.065). After multivariate Cox-analysis (HR: 0.94, 95% CI 0.641–1.383) and the addition of propensity matching (HR: 0.86 95% CI 0.412–1.798) TA was still not associated with decreased mortality. By contrast, in hyperglycemic subgroup STEMI patients (TA-group, n = 331; no-TA group, n = 566), Kaplan–Meier-analysis demonstrated a significantly lower mortality (P = 0.019) in TA-group than the no-TA group. After multivariate Cox-analysis (HR: 0.64, 95% CI 0.379–0.963) and the addition of propensity matching (HR: 0.54, 95% CI 0.294–0.984) TA was still associated with decreased mortality. Conclusions TA was not associated with lower mortality in PPCI for STEMI when used in our large all-comer cohort. Conversely, TA during PPCI for STEMI reduces clinical outcomes in hyperglycemic patients. Trial registration NCT02817542. 25th, June 2016

Abstract Background No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exist. We evaluated the 12-months prognosis of Mv-NOCS-diabetics with first STEMI vs.to non-diabetics, and then Mv-NOCS-diabetics previously treated with incretin based therapy vs. a matched cohort of STEMI-Mv-NOCS never treated with such therapy. Methods 1088 Patients with first STEMI and Mv-NOCS were scheduled for the study. Patients included in the study were categorized in type 2 diabetics (n 292) and non-diabetics (n 796). Finally, we categorized diabetics in current-incretin-users (n 76), and never-incretin-users (n 180). The primary end point was all cause deaths, cardiac deaths, and major adverse cardiac events (MACE) at 12 months of follow up. Results The study results evidenced higher percentage of all cause deaths (2.2% vs. 1.1%, p value 0.05), cardiac deaths (1.6% vs. 0.5%, p value 0.045), and MACE (12.9% vs. n 5.9%), p value 0.001) in diabetic vs. no diabetic patients at 12 months follow up. Among diabetic patients, the current vs never-incretin-users, did not present a significant difference about all cause of deaths, and cardiac deaths through 12-months. The MACE rate at 1 year was 7.4% in diabetic incretin-users STEMI Mv-NOCS patients vs. 12.9% in diabetic never-incretin-users STEMI-Mv-NOCS patients (p value 0.04). In a risk-adjusted hazard analysis, MACE through 12 months were lower in diabetic STEMI-Mv NOCS incretin-users vs never-incretin-users patients (HR 0.513, CI [0.292–0.899], p 0.021). Consequently, lower levels of glucagon-like peptide 1(GLP-1) were predictive of MACE at follow up (HR 1.528, CI [1.059–2.204], p 0.024). Conclusion In type 2 diabetic patients with STEMI-Mv-NOCS, we observed higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared to non-diabetic STEMI-Mv-NOCS patients. In diabetic patients, never-incretin-users have worse prognosis as compared to current-incretin-users. Trail registration Clinical trial number: NCT03312179, name of registry: clinicaltrialgov, URL: clinicalltrialgov.com, date of registration: September 2017, date of enrollment first participant: September 2009

SUMMARY Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations – such as intractable epilepsy, mental retardation and autism – that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.

Following publication of the original article [1], the authors reported an error in Acknowledgment section. The last sentence should read as “All authors have read and approval the submission to Cardiovascular Diabetology.