To address the coronavirus (Covid-19) pandemic,¹ strict social containment measures have been adopted worldwide, and health care systems have been reorganized to cope with the enormous increase in the numbers of acutely ill patients.^2,3 During this same period, some changes in the pattern of hospital admissions for other conditions have been noted. The aim of the present analysis is to investigate the rate of hospital admissions for acute coronary syndrome (ACS) during the early days of the Covid-19 outbreak.

Ischemic diseases in an aging population pose a heavy social encumbrance. Moreover, current therapeutic approaches, which aimed to prevent or minimize ischemia-induced damage, are associated with relevant costs for healthcare systems. Early reperfusion by primary percutaneous coronary intervention (PPCI) has undoubtedly improved patient’s outcomes; however, the prevention of long-term complications is still an unmet need. To face these hurdles and improve patient’s outcomes, novel pharmacological and interventional approaches, alone or in combination, reducing myocardium oxygen consumption or supplying blood flow via collateral vessels have been proposed. A number of clinical trials are ongoing to validate their efficacy on patient’s outcomes. Alternative options, including stem cell-based therapies, have been evaluated to improve cardiac regeneration and prevent scar formation. However, due to the lack of long-term engraftment, more recently, great attention has been devoted to their paracrine mediators, including exosomes (Exo) and microvesicles (MV). Indeed, Exo and MV are both currently considered to be one of the most promising therapeutic strategies in regenerative medicine. As a matter of fact, MV and Exo that are released from stem cells of different origin have been evaluated for their healing properties in ischemia reperfusion (I/R) settings. Therefore, this review will first summarize mechanisms of cardiac damage and protection after I/R damage to track the paths through which more appropriate interventional and/or molecular-based targeted therapies should be addressed. Moreover, it will provide insights on novel non-invasive/invasive interventional strategies and on Exo-based therapies as a challenge for improving patient’s long-term complications. Finally, approaches for improving Exo healing properties, and topics still unsolved to move towards Exo clinical application will be discussed.

The relevance of extracellular vesicles (EV) as mediators of cardiac damage or recovery upon Ischemia Reperfusion Injury (IRI) and Remote Ischemic PreConditioning (RIPC) is controversial. This study aimed to investigate whether serum-derived EV, recovered from patients with Acute Coronary Syndrome (ACS) and subjected to the RIPC or sham procedures, may be a suitable therapeutic approach to prevent IRI during Percutaneous-Coronary-Intervention (PCI). A double-blind, randomized, sham-controlled study (NCT02195726) has been extended, and EV were recovered from 30 patients who were randomly assigned (1:1) to undergo the RIPC- (EV-RIPC) or sham-procedures (EV-naive) before PCI. Patient-derived EV were analyzed by TEM, FACS and western blot. We found that troponin (TnT) was enriched in EV, compared to healthy subjects, regardless of diagnosis. EV-naive induced protection against IRI, both in-vitro and in the rat heart, unlike EV-RIPC. We noticed that EV-naive led to STAT-3 phosphorylation, while EV-RIPC to Erk-1/2 activation in the rat heart. Pre-treatment of the rat heart with specific STAT-3 and Erk-1/2 inhibitors led us to demonstrate that STAT-3 is crucial for EV-naive-mediated protection. In the same model, Erk-1/2 inhibition rescued STAT-3 activation and protection upon EV-RIPC treatment. 84 Human Cardiovascular Disease mRNAs were screened and DUSP6 mRNA was found enriched in patient-derived EV-naive. Indeed, DUSP6 silencing in EV-naive prevented STAT-3 phosphorylation and cardio-protection in the rat heart. This analysis of ACS-patients' EV proved: (i) EV-naive cardio-protective activity and mechanism of action; (ii) the lack of EV-RIPC-mediated cardio-protection; (iii) the properness of the in-vitro assay to predict EV effectiveness in-vivo.

Artificial intelligence (AI) is transforming cardiovascular imaging by offering advancements across multiple modalities, including echocardiography, cardiac computed tomography (CCT), cardiovascular magnetic resonance (CMR), interventional cardiology, nuclear medicine, and electrophysiology. This review explores the clinical applications of AI within each of these areas, highlighting its ability to improve patient selection, reduce image acquisition time, enhance image optimization, facilitate the integration of data from different imaging modality and clinical sources, improve diagnosis and risk stratification. Moreover, we illustrate both the advantages and the limitations of AI across these modalities, acknowledging that while AI can significantly aid in diagnosis, risk stratification, and workflow efficiency, it cannot replace the expertise of cardiologists. Instead, AI serves as a powerful tool to streamline routine tasks, allowing clinicians to focus on complex cases where human judgement remains essential. By accelerating image interpretation and improving diagnostic accuracy, AI holds great potential to improve patient care and clinical decision-making in cardiovascular imaging.

Data regarding the best treatment for spontaneous coronary artery dissection (SCAD) are scarce. The aim of the present study was to compare the clinical outcomes of conservative versus invasive treatment in SCAD patients. We systematically searched the literature for studies evaluating the comparative efficacy and safety of invasive revascularization versus medical therapy for the treatment of SCAD from 1990 to 2020. The study endpoints were all-cause death, cardiovascular death, myocardial infarction, heart failure, SCAD recurrence and target vessel revascularization (TVR) rates. Random-effect meta-analysis was performed comparing the clinical outcomes between the two groups. A univariate meta-regression analysis was also performed. 24 observational studies with 1720 patients were included. After 28±14 months, a conservative approach was associated with lower TVR rate compared with invasive treatment (OR=0.50; 95%CI 0.28-0.90; P=0.02). No statistical difference was found regarding all-cause death (OR=0.81; 95%CI 0.31-2.08; P=0.66), cardiovascular death (OR=0.89; 95%CI 0.15-5.40; P=0.89), myocardial infarction (OR=0.95; 95%CI 0.50-1.81; P=0.87), heart failure (OR 0.96; 95%CI 0.41-2.22; P=0.92) and SCAD recurrence (OR=0.94; 95%CI 0.52-1.72; P=0.85). The meta-regression analysis suggested that male gender, diabetes mellitus, smoking habit, prior coronary artery disease, left main coronary artery involvement, lower ejection fraction and low TIMI flow at admission are related with higher overall mortality, whereas SCAD recurrence was higher among patients with fibromuscular dysplasia. A conservative approach was associated with similar clinical outcomes and lower TVR rates compared to with an invasive strategy in SCAD patients; future prospective studies are needed to confirm these results.

Aims: A 5-year survival of patients with unprotected left main (ULM) stenosis according to the choice of revascularization (percutaneous vs. surgical) remains to be defined. Methods and results: Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG) with a follow-up of at least 5 years were included. All-cause death was the primary endpoint. MACCE [a composite endpoint of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization] along with its single components and cardiovascular (CV) death were the secondary ones. Analyses were stratified according to the use of first- vs. last-generation coronary stents. Subgroup comparisons were performed according to SYNTAX score (below or above 33) and to age (using cut-offs of each trial’s subgroup analysis). Four RCTs with 4394 patients were identified: 2197 were treated with CABG, 657 with first generation, and 1540 with last-generation stents. At 5-year rates of all-cause death did not differ [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.71–1.21], as those of CV death and stroke. Coronary artery bypass graft reduced rates of MACCE (OR 0.69, 95% CI 0.60–0.79), mainly driven by MI (OR 0.48, 95% CI 0.36–0.65) and revascularization (OR 0.53, 95% CI 0.45–0.64). Benefit of CABG for MACCE was consistent, although with different extent, across values of SYNTAX score (OR 0.76, 95% CI 0.59–0.97 for values < 32 and OR 0.63, 95% CI 0.47–0.84 for values ≥ 33) while was not evident for ‘younger’ patients (OR 0.83, 95% CI 0.65–1.07 vs. OR 0.65, 95% CI 0.51–0.84 for ‘older’ patients). Conclusion: For patients with ULM disease followed-up for 5 years, no significant difference was observed in all-cause and cardiovascular death between PCI and CABG. Coronary artery bypass graft reduced risk of MI, revascularization, and MACCE especially in older patients and in those with complex coronary disease and a high SYNTAX score.