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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.

Heart failure is a progressive disease, representing a growing cause of morbidity, hospitalization, and mortality. An increasingly common type of heart failure with preserved ejection fraction (HFpEF) is an immunoglobulin light chain and transthyretin cardiac amyloidosis, in the pathophysiology of which oxidative damage appears to exert a strong impact. Reactive oxygen and nitrogen species have physiological signaling functions, but their overaccumulation, as in cardiac amyloidosis, leads to cardiomyocyte damage and apoptosis, and to cardiac hypertrophy and fibrosis. Moreover, such pathological processes worsen the redox damage with the perpetuation of an inflammatory state, in a vicious cycle. Here, the role of oxidative damage in the transthyretin and immunoglobulin light chain cardiac amyloidosis, the underlying pathogenic mechanisms, the therapeutic implications, and possible future strategies are reviewed.

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.

Abstract Background The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies. Methods To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle. Results 180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively. Conclusions Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure. Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020

Background and Objectives: Percutaneous left-atrial appendage (LAA) occlusion is an important therapeutic option for preventing cardioembolic stroke in patients with non-valvular atrial fibrillation (AF) at high risk of thromboembolic events and with contraindications for oral anticoagulation (OAC). It is usually performed with transesophageal echocardiography (TOE) guidance under general anesthesia (GA). In this retrospective study, we present a multicenter experience of LAA occlusion performed with conscious sedation (CS) without an anesthesiologist on site. Materials and Methods: All the patients on the waiting list for LAA occlusion procedure at Infermi Hospital, Rivoli, and San Luigi Gonzaga University Hospital, Orbassano, from October 2018 to October 2022 were analyzed. All the procedures were performed with a Watchman/FLX LAA closure device under TOE and fluoroscopic guidance without an anesthesiologist on site. CS was performed with a combination of midazolam and fentanyl as needed. Results: One-hundred fifteen patients were included (age 76.4 ± 7.6 years, median CHA2DS2Vasc 4.4 ± 1.4). CS was performed using midazolam (mean dose 5.9 ± 2.1 mg), adding fentanyl for thirty-nine (33.9%) patients in case of poor tolerance for the procedure despite midazolam. The acute procedural success rate was 99.1%. We observed seven acute severe complications. No patients needed anesthesiological assistance during the procedure, and no cases of respiratory failure necessitating ventilation were reported. In a follow-up after 10 ± 9 months, one case of stroke (0.9%) and one case (0.9%) of transient ischemic attack (TIA) occurred. Conclusions: LAA occlusion performed under CS and without the presence of an anesthesiologist on site appears to be safe and effective. It can be an attractive alternative to general anesthesia (GA), as fewer resources are required.

Introduction: 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. Methods: 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. Results: 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). Conclusions: 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. Keywords: Novel P2Y12 inhibitors, Switching, Clopidogrel, Ticagrelor, Prasugrel, Acute coronary syndrome

This text is intended as a contribution to the study of the profound mutual relations between architecture and psychoanalysis. Architecture creates representations that conceal unconscious forms of thought; psychoanalysis helps to explain the meanings of these representations - forms of construction and forms of the psyche. The multifaceted work of psychoanalyst Christopher Bollas - his thoughts on the relationships between psychoanalysis and architecture, on the vitality of objects, on the creative implications of the Oedipal relationship - serves as a critical and decisive instrument for the authors’ inquiry. The issue of the “vitality of objects” as described by Bollas also concerns - but only in part - the architectural “object.” One modern form of architecture with an inordinate capacity empathy has to be Louis Kahn’s. Kahn’s youngest son, Nathaniel, lost his father when he was still a child and hardly had a chance to get to know him. After becoming an adult and an established film-maker, he managed to recover his father in two ways: by discovering him in his works, with their powerful affective impact; and by drawing from those very works of his father to enhance his own creative process in his filmic art. As it turns out, it is this very process that has allowed for an emblematically positive resolution of the Oedipal relationship. [ABSTRACT FROM AUTHOR]