Enrico Coscioni

RNA modifications have recently gained great attention due to their extensive regulatory effects in a wide range of cellular networks and signaling pathways. In cardiovascular diseases (CVDs), several RNA changes, called “epitranscriptome” alterations, are found in all RNA molecules (tRNA, rRNA, mRNA, and ncRNAs). Unlike the epigenetic process, which influences the progression of atherosclerosis (AS), its transcriptional and post-transcriptional regulatory mechanisms are still unknown. Here, we described the main epitranscriptome signs to provide new insights into AS, including m6A, m5C, m1A, m7G, Ψ, and A-to-I editing. Moreover, we also included all current known RNAmodifier- targeting, including small molecular inhibitors or activators, mainly designed against m6A- and m5A-related enzymes, such as METTL3, FTO, and ALKBH5. Finally, since only a few drugs, such as azacitidine and tazemetostat, targeting the DNA epigenome, have been approved by the FDA, the next challenge would be to identify molecules for targeting the RNA epitranscriptome. To date, total Panax notoginseng total saponin could reduce vascular hyperplasia via Wilms’ tumor-associated protein-1 m6A-dependent. Indeed, a virtual screening allowed us to individuate a phytomolecule, the rhein, which acts as an FTO inhibitor by increasing mRNA m6A levels. In this review, we highlighted the RNA epitranscriptome pathways implicated in AS, describing their biological functions and their connections to the disease. The identification of epitranscriptome- sensitive pathways could provide novel opportunities to find predictive, diagnostic, and prognostic biomarkers for precision medicine.

Heart failure (HF) is a complex and progressive disease marked by substantial morbidity and mortality rates, frequent episodes of decompensation, and a reduced quality of life (QoL), with severe financial burden on healthcare systems. In recent years, several large-scale randomized clinical trials (RCTs) have widely expanded the therapeutic armamentarium, underlining additional benefits and the feasibility of rapid titration regimens. This notwithstanding, mortality is not declining, and hospitalizations are constantly increasing. It is widely acknowledged that even with guideline-directed medical therapy (GDMT) on board, HF patients have a prohibitive residual risk, which highlights the need for innovative treatment options. In this scenario, groundbreaking devices targeting valvular, structural, and autonomic abnormalities have become crucial tools in HF management. This has led to a full-fledged translational boost with several novel devices in development. Thus, the aim of this review is to provide an update on both approved and investigated devices.

In recent years, remarkable progress has been accomplished in the heart failure (HF) landscape, with novel drugs and groundbreaking device approaches

Medication adherence in chronic conditions is a long-term process. Modeling longitudinal trajectories using routinely collected prescription data is a promising method for describing adherence patterns and identifying at-risk groups. The study aimed to characterize distinct long-term sacubitril/valsartan adherence trajectories and factors associated with them in patients with heart failure (HF). Subjects with incident HF starting sac/val in 2017–2018 were identified from the Campania Regional Database for Medication Consumption. We estimated patients’ continuous medication availability (CMA9; R package AdhereR) during a 12-month period. We selected groups with similar CMA9 trajectories (Calinski-Harabasz criterion; R package kml). We performed multinomial regression analysis, assessing the relationship between demographic and clinical factors and adherence trajectory groups. The cohort included 4455 subjects, 70% male. Group-based trajectory modeling identified four distinct adherence trajectories: high adherence (42.6% of subjects; CMA mean 0.91 ± 0.08), partial drop-off (19.6%; CMA 0.63 ± 0.13), moderate adherence (19.3%; CMA 0.54 ± 0.11), and low adherence (18.4%; CMA 0.17 ± 0.12). Polypharmacy was associated with partial drop-off adherence (OR 1.194, 95%CI 1.175–1.214), while the occurrence of ≥1 HF hospitalization (OR 1.165, 95%CI 1.151–1.179) or other hospitalizations (OR 1.481, 95%CI 1.459–1.503) were associated with low adherence. This study found that tailoring patient education, providing support, and ongoing monitoring can boost adherence within different groups, potentially improving health outcomes.

Introduction: Real-world safety studies can provide important evidence on the thromboembolic risk associated with COVID-19 vaccines, considering that millions of people have been already vaccinated against COVID-19. In this study, we aimed to estimate the incidence of thromboembolic events after COVID-19 vaccination and to compare the Oxford–AstraZeneca vaccine with other COVID-19 vaccines. Methods: We conducted a retrospective real-world safety study using data from two different data sources: the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza, RNF) and the Campania Region Health system (Sistema INFOrmativo saNità CampanIA, SINFONIA). From the start date of the COVID-19 vaccination campaign (27 December 2021) to 27 September 2022, information on COVID-19 vaccinations and thromboembolic events were extracted from the two databases. The reporting rate (RR) and its 95% confidence interval (95%CI) of thromboembolic events for 10,000 doses was calculated for each COVID-19 vaccine. Moreover, the odds of being vaccinated with the Oxford–AstraZeneca vaccine vs. the other COVID-19 vaccines in cases with thromboembolic events vs. controls without thromboembolic events were computed. Results: A total of 12,692,852 vaccine doses were administered in the Campania Region, of which 6,509,475 (51.28%) were in females and mostly related to the Pfizer-BioNtech vaccine (65.05%), followed by Moderna (24.31%), Oxford–AstraZeneca (9.71%), Janssen (0.91%), and Novavax (0.02%) vaccines. A total of 641 ICSRs with COVID-19 vaccines and vascular events were retrieved from the RNF for the Campania Region, of which 453 (70.67%) were in females. Most ICSRs reported the Pfizer-BioNtech vaccine (65.05%), followed by Oxford–AstraZeneca (9.71%), Moderna (24.31%), and Janssen (0.91%). A total of 2451 events were reported in the ICSRs (3.8 events for ICSRs), of which 292 were thromboembolic events. The higher RRs of thromboembolic events were found with the Oxford–AstraZeneca vaccine (RR: 4.62, 95%CI: 3.50–5.99) and Janssen vaccine (RR: 3.45, 95%CI: 0.94–8.82). Thromboembolic events were associated with a higher likelihood of exposure to the Oxford–AstraZeneca vaccine compared to Pfizer-BioNtech (OR: 6.06; 95%CI: 4.22–8.68) and Moderna vaccines (OR: 6.46; 95%CI: 4.00–10.80). Conclusion: We observed a higher reporting of thromboembolic events with viral-vector-based vaccines (Oxford–AstraZeneca and Janssen) and an increased likelihood of being exposed to the Oxford–AstraZeneca vaccine compared to the mRNA vaccines (Pfizer-BioNtech and Moderna) among thromboembolic cases.

Introduction: Real-world safety studies can provide important evidence on the thromboembolic risk associated with COVID-19 vaccines, considering that millions of people have been already vaccinated against COVID-19. In this study, we aimed to estimate the incidence of thromboembolic events after COVID-19 vaccination and to compare the Oxford–AstraZeneca vaccine with other COVID-19 vaccines. Methods: We conducted a retrospective real-world safety study using data from two different data sources: the Italian Pharmacovigilance database (Rete Nazionale di Farmacovigilanza, RNF) and the Campania Region Health system (Sistema INFOrmativo saNità CampanIA, SINFONIA). From the start date of the COVID-19 vaccination campaign (December 27th, 2021) to September 27th, 2022, information on COVID-19 vaccinations and thromboembolic evets were extracted from the two databases. The reporting rate (RR) and its 95% confidence interval (95%CI) of thromboembolic events for 10,000 doses was calculated for each COVID-19 vaccine. Moreover, the odds of being vaccinated with the Oxford–AstraZeneca vaccine vs. the other COVID-19 vaccines in cases with thromboembolic events vs. controls without thromboembolic events were computed. Results: A total of 12,692,852 vaccine doses were administered in Campania Region, of which 6,509,475 (51.28%) were in female and mostly related to the Pfizer-BioNtech vaccine (65.05%), followed by Moderna (24.31%), Oxford–AstraZeneca (9.71%), Janssen (0.91%), and Novavax (0.02%) vaccines. A total of 641 ICSRs with a COVID-19 vaccines and a vascular events were retrieved from the RNF for the Campania Region, of which 453 (70.67%) were in female. Most ICSRs reported the Pfizer-BioNtech vaccine (65.05%), followed by Oxford–AstraZeneca (9.71%), Moderna (24.31%), and Janssen (0.91%). A total of 2,451 events were reported in the ICSRs (3.8 events for ICSRs) of which 292 were thromboembolic events. The highe RRs of thromboembolic events were found with the Oxford–AstraZeneca vaccine (RR: 4.62, 95%CI: 3.50-5.99) and Janssen vaccine (RR: 3.45, 95%CI: 0.94-8.82). Thromboembolic events were associated with a higher likelihood of exposure to the Oxford–AstraZeneca vaccine compared to Pfizer-BioNtech (OR: 6.06; 95%CI: 4.22-8.68) and Moderna vaccines (OR: 6.46; 95%CI: 4.00-10.80). Conclusion: We observed a higher reporting of thromboembolic events with viral-vector based vaccines (Oxford–AstraZeneca and Janssen) and an increased likelihood of being exposed to the Oxford–AstraZeneca vaccine compared to the mRNA vaccines (Pfizer-BioNtech and Moderna) among thromboembolic cases.

Laubry–Pezzi syndrome is a congenital heart disease characterized by the prolapse of an aortic valve cusp into a subjacent ventricular septal defect (VSD), mostly supracristal, leading to severe aortic regurgitation (AR). It has been reported nearly always in childhood, the Venturi effect is the predominant factor and onset symptoms may be variable. A 61–years–old male was admitted to our intensive case unit for chest pain radiated to interscapular region and exertional dyspnea. Hemodynamic parameters were normal. At ECG sinus rytm with heart rate 92 bpm and non–specific repolarization abnomalities were reported. Hs troponin I was 276 ng/L, myoglobin 30.2 ng/mL and BNP 325 pg/mL. Transthoracic echocardiography showed a dilated left ventricle (LV EDV 107 mL/m2) with normal ejection fraction (55%), severe AR without aortic root dilation and a suspicious shunt left to right at level of interventricular septum. Therefore, transesophageal echocardiography was performed and confirmed severe AR by probable bicuspid valve and right cusp prolapse, in absence of calcifications and/or vegetations by endocarditis, restrictive perimembranous VSD (maximum diameter 0.6 cm) and ostium secundum ASD with shunt L–R. Right chambers were not dilated and non invasive systolic pulmonary artery pressure was 43 mmHg. Coronary angiography was performed and showed a significant stenosis of distal left anterior descending (LAD) artery and of proximal circumflex artery. Right heart catetherization excluded significant high values of pulmonary pressures (mPAP=18 mmHg), of pulmonary capillary wedge pressure (9 mmHg), with a mild increase of pulmonary vascular resistances (1.16 HRU; nv < 96). Coronary artery bypass grafting (left internal mammary artery on LAD and Y–graft radial artery on obtuse marginal artery), aortic valve replacement with bioprothesis (Inspiris Resilia 23 mm), ASD closure by direct suture and VSD closure with pericardial patch were performed. No post–surgical complications were reported. Interestingly, during the replacement of aortic valve, it resulted tricuspid, confirming the suspicion of Laubry Pezzi syndrome.

Postinfarction ventricular septal defect is a rare mechanical complication of myocardial infarction, with difficult management, debated closure timing and high mortality rates. Standard repair techniques – infarcectomy and infarct exclusion through a left ventriculotomy – are surgically challenging and have high risk of operative mortality and frequently suboptimal results. We report the case of a 66–year–old patient with a 1.4 cm septal rupture developed after a sub–acute STEMI. At the admission, he had chest pain and moderate dyspnoea, EKG showed inferior STEMI with increased myocardial necrosis markers. Echocardiography showed a preserved ejection fraction, akinesia of the inferior, posterolateral walls and of the posterobasal septum, with septal rupture at this level and 1.5 Qp/Qs ratio. A total occlusion of proximal right main coronary artery was found at coronary angiography. After the heart team meeting, we performed a new modified closure, in urgent setting, using two hand–made composite patches (Fig. 1) parachuted through a transversal aortotomy and a right atriotomy, without left ventriculotomy (Fig. 2). In the 7th postoperative day a second septal rupture was detected at the echocardiographic control. After two weeks follow–up in optimized medical therapy, we decided to complete the closure of the later developed septal rupture percutaneously using an Amplatzer device. Six months after the event, the patient is still asymptomatic and echocardiography documents a 50% ejection fraction, with trivial residual left–to–right shunt and normal valve function. Computed tomography scans confirmed optimal surgical result. Timing, management and surgical strategy are still on debate. Our technique is effective, simple, reproducible and provides good result (Fig. 3) and can be perfectly integrated in a hybrid approach. Open in new tab Download slide Open in new tab Download slide Open in new tab Download slide

Mast cells are multifunctional immune cells with complex roles in tissue homeostasis and disease. Cardiac mast cells (HCMCs) are strategically located within the human myocardium, in atherosclerotic plaques, in proximity to nerves, and in the aortic valve. HCMCs express the high-affinity receptor (FcεRI) for IgE and can be activated by anti-IgE and anti-FcεRI. Autoantibodies to IgE and/or FcεRI have been found in the serum of patients with a variety of immune disorders. We have compared the effects of different preparations of IgG anti-IgE obtained from patients with atopic dermatitis (AD) with rabbit IgG anti-IgE on the release of preformed (histamine and tryptase) and lipid mediators [prostaglandin D₂ (PGD₂) and cysteinyl leukotriene C₄ (LTC₄)] from HCMCs. Functional human IgG anti-IgE from one out of six AD donors and rabbit IgG anti-IgE induced the release of preformed (histamine, tryptase) and de novo synthesized mediators (PGD₂ and LTC₄) from HCMCs. Human IgG anti-IgE was more potent than rabbit IgG anti-IgE in inducing proinflammatory mediators from HCMCs. Human monoclonal IgE was a competitive antagonist of both human and rabbit IgG anti-IgE. Although functional anti-IgE autoantibodies rarely occur in patients with AD, when present, they can powerfully activate the release of proinflammatory and vasoactive mediators from HCMCs.

SARS-CoV-2 infection after vaccination can occur because COVID-19 vaccines do not offer 100% protection. The study aim was to assess duration of vaccination coverage, disease symptoms and type of hospitalization among non-vaccinated and vaccinated subjects to evaluate the vaccination trend over time. A retrospective cohort study was carried out among people testing COVID-19 positive in Campania Region using information from the Health Information System of Campania Region (Sinfonia). Vaccination status was assessed considering: no vaccination, partial vaccination and effective vaccination. Univariate and multivariate logistic regression models were constructed to evaluate the association between ICU admissions caused by COVID-19 and gender, age groups and vaccine type. Vaccine coverage duration trends were investigated using segmented linear regression and breakpoint estimations. Vaccination coverage was assessed by analyzing COVID-19 positive subjects in the 9 months after an effective dose vaccination. A significant risk of hospitalization in the ICU was caused by vaccination status: subjects non-vaccinated (OR: 7.14) and partially vaccinated (OR: 3.68) were 3 and 7 times more at risk of hospitalization, respectively, than subjects effectively vaccinated. Regarding subjects with an effective vaccination, the vaccine’s ability to protect against infection in the months following vaccination decreased. The risk of contracting COVID-19 after vaccination was higher 5 months (β = 1441, p < 0.001) and 7 months (β = 3110, p < 0.001) after administration of an effective dose. COVID-19 vaccines were demonstrated to protect from symptomatic infection by significantly reducing hospitalization risk, and their full protection against SARS-CoV-2 was demonstrated to decrease after 5 months regardless of age, gender or vaccine type.