Valentina Parisi

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay.

Background: Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). Methods: A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle–Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger’s test and funnel plots. Results: Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = −0.143, 95% CI: −0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: −0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). Conclusion: This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1β which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) have emerged as novel therapeutic agents for T2DM, primarily aiming to reduce blood glucose levels. However, recent investigations have unveiled their multifaceted effects, extending beyond their glucose-lowering effect. SGLT2i operate by inhibiting the SGLT2 receptor in the kidneys, facilitating the excretion of glucose through urine, leading to reduced blood glucose levels, while GLP1-RA mimic the action of the GLP1 hormone, stimulating glucose-dependent insulin secretion from pancreatic islets. Both SGLT2i and GLP1-RA have shown remarkable benefits in reducing major cardiovascular events in patients with and without T2DM. This comprehensive review explores the expanding horizons of SGLT2i and GLP1-RA in improving cardiovascular health. It delves into the latest research, highlighting the effects of these drugs on heart physiology and metabolism. By elucidating their diverse mechanisms of action and emerging evidence, this review aims to recapitulate the potential of SGLT2i and GLP1-RA as therapeutic options for cardiovascular health beyond their traditional role in managing T2DM.

Purpose Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. Methods Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m². The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. Results A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m², a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m², DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. Conclusion DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.

Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its prevalence increases with age. AF is strongly associated with an increased risk of stroke, heart failure and cardiovascular mortality. Among the risk factors associated with AF onset and severity, obesity and inflammation play a prominent role. Numerous recent evidence suggested a role of epicardial adipose tissue (EAT), the visceral fat depot of the heart, in the development of AF. Several potential arrhythmogenic mechanisms have been attributed to EAT, including myocardial inflammation, fibrosis, oxidative stress, and fat infiltration. EAT is a local source of inflammatory mediators which potentially contribute to atrial collagen deposition and fibrosis, the anatomical substrate for AF. Moreover, the close proximity between EAT and myocardium allows the EAT to penetrate and generate atrial myocardium fat infiltrates that can alter atrial electrophysiological properties. These observations support the hypothesis of a strong implication of EAT in structural and electrical atrial remodeling, which underlies AF onset and burden. The measure of EAT, through different imaging methods, such as echocardiography, computed tomography and cardiac magnetic resonance, has been proposed as a useful prognostic tool to predict the presence, severity and recurrence of AF. Furthermore, EAT is increasingly emerging as a promising potential therapeutic target. This review aims to summarize the recent evidence exploring the potential role of EAT in the pathogenesis of AF, the main mechanisms by which EAT can promote structural and electrical atrial remodeling and the potential therapeutic strategies targeting the cardiac visceral fat.

Circulating microRNAs (miRNA) have been proposed as specific biomarkers for several diseases. Quantitative Real-Time PCR (RT-qPCR) is the gold standard technique currently used to evaluate miRNAs expression from different sources. In the last few years, digital PCR (dPCR) emerged as a complementary and accurate detection method. When dealing with gene expression, the first and most delicate step is nucleic-acid isolation. However, all currently available protocols for RNA extraction suffer from the variable loss of RNA species due to the chemicals and number of steps involved, from sample lysis to nucleic acid elution. Here, we evaluated a new process for the detection of circulating miRNAs, consisting of sample lysis followed by direct evaluation by dPCR in plasma from healthy donors and in the cardiovascular setting. Our results showed that dPCR is able to detect, with high accuracy, low-copy-number as well as highly expressed miRNAs in human plasma samples without the need for RNA extraction. Moreover, we assessed a known myocardial infarction-related miR-133a in acute myocardial infarct patients vs. healthy subjects. In conclusion, our results show the suitability of the extraction-free quantification of circulating miRNAs as disease markers by direct dPCR.

Background and aims: Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1β, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients.Methods: We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1β and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored in vitro by exposing human atrial fibroblasts to IL-1β and IL-18.Results: 40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1β and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1β secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The in vitro study showed that both IL-1β and IL-18 increase fibroblasts’ proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1β and transforming growth factor (TGF)-β.Conclusion: EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.

Introduction: Some abnormal electrocardiographic findings were independently associated with increased mortality in patients admitted for COVID‐19; however, no studies have focussed on the prognosis impact of the interatrial block (IAB) in this clinical setting. The aim of our study was to assess the prevalence and clinical implications of IAB, both partial and advanced, in hospitalized COVID‐19 patients.Materials: We retrospectively evaluated 300 consecutive COVID‐19 patients (63.22 ± 15.16 years; 70% males) admitted to eight Italian Hospitals from February 2020 to April 2020 who underwent twelve lead electrocardiographic recording at admission. The study population has been dichotomized into two groups according to the evidence of IAB at admission, both partial and advanced. The differences in terms of ARDS in need of intubation, in‐hospital mortality and thromboembolic events (a composite of myocardial infarction, stroke and transient ischaemic attack) have been evaluated.Results: The presence of IAB was noticed in 64 patients (21%). In the adjusted logistic regression model, the partial interatrial block was found to be an independent predictor of ARDS in need of intubation (HR: 1.92; p: .04) and in‐hospital mortality (HR: 2.65; p: .02); moreover, the advanced interatrial block was an independent predictor of thrombotic events (HR: 7.14; p < .001).Conclusions: Among COVID‐19 patients hospitalized in medical wards, the presence of interatrial block is more frequent than in the general population and it might be useful as an early predictor for increased risk of incident thrombotic events, ARDS in need of intubation and in‐hospital mortality.