The efficacy and safety of switching P2Y12 receptor antagonists in patients admitted for acute coronary syndrome (ACS) remain unclear. We assessed the short-term clinical outcomes (in-hospital and within 30 days) of switching P2Y12 inhibitor (P2Y12I) drugs versus maintaining the same regimen by performing a comprehensive review and meta-analysis of available data. MEDLINE/PubMed/SCOPUS/Cochrane databases were screened for studies regarding switching of P2Y12I in patients with ACS that reported 30 days follow-up. Major cardiac events (MACE) and bleeding were compared between patients who were switched/not switched. 22,500 patients from 14 studies were included. Unstable angina/non-ST elevation myocardial infarction (62.0%, interquartile range, 52.8%-68.0%) was the most common clinical presentation. The total number switched was 4294 (19.1%); escalation in 3416 (79.5%) patients (from clopidogrel to prasugrel, 62.9%) and de-escalation in 18.5%. Pooled analysis revealed no significant differences in MACE for any comparison; risk of bleeding was significantly increased among switched patients overall (odds ratio [OR], 1.60; 95% confidence interval [CI] 1.22-2.10) and increased in the escalation group (OR, 1.51; 95% CI, 1.06-2.16). Among patients presenting with ACS, switching from one P2Y12I agent to another in the acute phase seems associated with a short-term increased risk of bleeding. Accurate upfront selection and prescription of a P2Y12I based on ischemic and bleeding risks is paramount to avoid adverse events switching-related during hospitalization and in the first 30 days.

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet’s function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.

Cardiomyopathies have evolved from being considered rare and idiopathic to being increasingly linked to genetic factors. This shift was enabled by advancements in understanding genetic variants and the widespread use of next generation sequencing (NGS). Current guidelines emphasize the importance of evidence-based gene panels that can offer “clinically actionable results”, which provide diagnostic and prognostic insights. They also advise against indiscriminate family screening after finding variants of uncertain significance (VUS) and recommend collaboration among multidisciplinary teams for an accurate variant pathogenicity assessment. This article presents an innovative “cardiogenetic clinic” approach involving cardiologists and medical geneticists to provide genetic testing and family screening. This study attempts to improve the diagnostic process for suspected genetic cardiomyopathies; this includes direct patient recruitment during cardiology appointments, NGS analysis, and combined consultations with cardiologists and geneticists to assess the results and screen the families. The study cohort of 170 patients underwent genetic testing, which identified 78 gene variants. Positive results (C4 or C5 variants) occurred in 20 (19.8%) cases, with rates varying by cardiomyopathy phenotype, while 57 (73.1%) of the variants found were classified as C3-VUS, causing a significant management issue. This model shortened the time to results, increased patient adherence, and improved patients’ diagnoses. Family screening was pondered depending on the relevance of the detected variants, showing this method’s potential to impact patient management.

Razionale. Il trapianto di cuore (TxC) è il trattamento cardiochirurgico di riferimento nello scompenso cardiaco (SC) avanzato. Il grado e la tipologia di coinvolgimento delle cardiologie nella filiera organizzativa dei centri TxC italiani per realizzare i programmi TxC rimane sostanzialmente poco nota. Materiali e metodi. L’Associazione Nazionale Medici Cardiologia Ospedalieri (ANMCO) e la Società Italiana dei Trapianti d’Organo e di Tessuti (SITO) hanno collaborato per sviluppare un questionario mirato a valutare: 1) i modelli organizzativi dei centri TxC e le relazioni istituzionali di questi ultimi con le cardiologie; 2) il volume e la tipologia delle attività delle cardiologie nei percorsi assistenziali assicurati dai centri TxC in merito alla selezione dei pazienti candidati a TxC, il follow-up in coloro che sono in lista d’attesa per TxC, la gestione della riacutizzazione dello SC e dello shock cardiogeno, la valutazione ed allocazione degli organi a riceventi, il follow-up post-trapianto, ed in particolare la gestione di eventuale rigetto d’organo. Risultati. Dei 14 direttori dei programmi TxC, 13 hanno risposto al questionario, di cui il 46% dichiarava di aver effettuato fino a 15 trapianti/anno nel triennio 2017-2019, ed un ulteriore 46% dichiarava di aver effettuato tra 16 e 30 trapianti/anno. La maggioranza (62%) dei centri TxC era collocata in dipartimenti di cardiochirurgia che non includevano unità complesse di cardiologia; il 54% dei centri TxC non era incluso in reti per la gestione integrata dello SC; solo una minoranza dei centri (15%) aveva al suo interno un team multidisciplinare che comprendeva cardiologi per la gestione dei pazienti del centro. In prevalenza, le cardiologie erogavano sevizi clinici e diagnostici a favore del TxC senza partecipare direttamente ed attivamente alla fase di selezione dei pazienti per TxC; il follow-up dei pazienti inseriti in lista per TxC veniva effettuato direttamente dai chirurghi nel 38%, così come un 33% dei centri TxC dichiarava di avere posti letto dedicati per la gestione diretta della riacutizzazione dello SC. La fase di selezione ed allocazione degli organi coinvolgeva marginalmente le cardiologie, così come il follow-up post-chirurgico e la gestione di eventuali rigetti d’organo avveniva prevalentemente per risorse cardiochirurgiche interne al centro TxC. Nell’85% i centri TxC dichiaravano di ricevere pazienti inviati internamente dalle cardiologie. Il coinvolgimento dei centri TxC nella rete formativa cardiologica risultava prevalente (69%). Nel follow-up post-trapianto e nella gestione del rigetto d’organo, il coinvolgimento delle cardiologie era infrequente (25% dei rispondenti). Conclusioni. I modelli organizzativi dei centri TxC sono risultati piuttosto vari, come alquanto variabile è risultato il coinvolgimento quantitativo e qualitativo delle cardiologie nell’articolazione dei percorsi assistenziali assicurati dai centri TxC nello SC avanzato.

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) yields variable positivity rates. Identifying clinical predictors of positive genetic tests could improve pre-test counseling and refine expectations about diagnostic yield. Methods: We analyzed consecutive genotyped HCM probands from a contemporary multicenter cohort across four Italian tertiary centers. Genotype positivity was defined as the presence of ≥1 pathogenic or likely pathogenic variant (ACMG classes 4–5). Multivariable logistic regression identified predictors of genotype positivity. Sensitivity analyses assessed the incremental value of left atrial volume index (LAVI) ≥ 34 mL/m² and the mode of first clinical presentation. Results: Among 274 genotyped probands (median age at diagnosis 54 years; 62% male), 86 (31%) were genotype-positive (38% MYBPC3, 29% MYH7). Age at diagnosis 20 mm and gender were not predictive of genotype positivity. Inclusion of LAVI modestly improved the model performance (AUC 0.769, p = 0.016, ΔAUC +0.024; DeLong p = 0.016) but without leading to meaningful patient reclassification. Conclusions: Genotype positivity in HCM links to earlier onset and family history; traditional severity markers and initial presentation may not independently suggest genetic causality. These findings may help shape a personalized approach to genetic counseling in HCM.

The role of beta blockers (BB) post–myocardial infarction (MI) in patients without reduced ejection fraction in the era of invasive management is controversial results from observational studies have led to opposite results. REBOOT is an independent multinational pragmatic, controlled, randomized, open–label, with blinded endpoint adjudication clinical trial. The study is testing the benefits of BB maintenance therapy in post–MI patients (either with or without ST segment elevation) discharged with LVEF >40%. Patients ≥18 years old undergoing invasive management during admission and without history of heart failure (HF) are eligible to participate. At discharge, they are 1:1 randomized to either receive BB (agent and dose chosen by the treating physician) or no BB therapy. The primary endpoint is a composite of all–cause death, nonfatal re–MI, or heart failure hospitalization over a minimum follow–up period of 2.75 years (minimum 2 years, maximum 3 years). Events are adjudicated by a blinded committee. Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) is the sponsor of the trial and the coordinator of Spanish Centers while Istituto di Ricerche Farmacologiche Mario Negri IRCCS coordinates the Italian participating network. Hospital admission for COVID–19 were also recorded since June 2020. The study is currently ongoing and 29 Italian centers are still actively recruiting. A sample size of 8468 pts (728 events) was estimated to provide a power of 85% to detect a RRR of 20% (incidence of primary endpoint in control 10%) and assuming 5% withdrawals. More than 75 Spanish and 35 Italian centers recruited patients. The first patients have been included in Spain in October 2018, in Italy in January 2019. On December 31st 2022, the number of enrolled patients by Italian centers was 1685. The top three Italian enrollers at the moment are: Ospedale G. da Saliceto –Piacenza (483 pts), Ospedale S. Luigi Gonzaga – Orbassano (183 pts) and A.O San’Anna and San Sebastiano – Caserta (170 pts). The patient enrollment rate was almost stable during all the study periods with a slight decrease during COVID pandemic outbreaks. The Italian REBOOT Network goal is to include 1800 patients by April 2023. The first results will become available by the end of 2025. The REBOOT, with other ongoing trials, will provide robust evidence to guide the prescription of BB to patients discharged after MI without reduced LVEF.