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Background: The brain and heart are strictly linked and the electrical physiologies of these organs share common pathways and genes. Epilepsy patients have a higher prevalence of electrocardiogram (ECG) abnormalities compared to healthy people. Furthermore, the relationship between epilepsy, genetic arrhythmic diseases and sudden death is well known. The association between epilepsy and myocardial channelopathies, although already proposed, has not yet been fully demonstrated. The aim of this prospective observational study is to assess the role of the ECG after a seizure. Materials and Methods: From September 2018 to August 2019, all patients admitted to the emergency department of San Raffaele Hospital with a seizure were enrolled in the study; for each patient, neurological, cardiological and ECG data were collected. The ECG was performed at the time of the admission (post-ictal ECG) and 48 h later (basal ECG) and analyzed by two blinded expert cardiologists looking for abnormalities known to indicate channelopathies or arrhythmic cardiomyopathies. In all patients with abnormal post-ictal ECG, next generation sequencing (NGS) analysis was performed. Results: One hundred and seventeen patients were enrolled (females: 45, median age: 48 ± 12 years). There were 52 abnormal post-ictal ECGs and 28 abnormal basal ECGs. All patients with an abnormal basal ECG also had an abnormal post-ictal ECG. In abnormal post-ictal ECG, a Brugada ECG pattern (BEP) was found in eight patients (of which two had BEP type I) and confirmed in two basal ECGs (of which zero had BEP type I). An abnormal QTc interval was identified in 20 patients (17%), an early repolarization pattern was found in 4 patients (3%) and right precordial abnormalities were found in 5 patients (4%). Any kind modification of post-ictal ECG was significantly more pronounced in comparison with an ECG recorded far from the seizure (p = 0.003). A 10:1 higher prevalence of a BEP of any type (particularly in post-ictal ECG, p = 0.04) was found in our population compared to general population. In three patients with post-ictal ECG alterations diagnostic for myocardial channelopathy (BrS and ERP), not confirmed at basal ECG, a pathogenic gene variant was identified (KCNJ8, PKP2 and TRMP4). Conclusion: The 12-lead ECG after an epileptic seizure may show disease-related alterations otherwise concealed in a population at a higher incidence of sudden death and channelopathies. Post-ictal BEP incidence was higher in cases of nocturnal seizure.

Healthy soil is critical to the growth of nutritious food and to farmers’ livelihoods. However, one-third of global soil is already affected by moderate to severe degradation by diverse processes. The reduction of soil degradation is one of the most important policy objectives, but policymakers and local planners require guidance in choosing the most effective interventions, both scientifically and economically, to reduce soil degradation. The complex interconnections between agriculture, the natural environment, and social well-being increase the need of researchers to access and use comprehensive soil data sets. Our ability to manage and support soil depends on the data we collect and the information and knowledge that we generate from them. Nevertheless, soil data accessibility and sharing are currently low and represent one of the major barriers to making better decisions in agriculture. A critical first step to capitalize on the opportunities offered by agriculture science and technologies is thus the standardization, organization, and the making of the multitude of specialty datasets generated by studies and projects publicly available to the global community. To address this challenge, Varda is creating an interactive soil digital platform that allows surfacing and comparing existing soil data across the globe in order to facilitate soil data sharing and interoperability. Moreover, the platform highlights soil data gaps across regions through a soil data gap index, and particularly soil health data gap through another ad hoc index developed by Varda and Aberdeen University. Such indexes will allow multilateral organizations, governments, and agribusiness stakeholders to fill some of these data gaps through ad-hoc soil sampling and data collection campaigns.

The management of our soils plays a crucial role in addressing some of our greatest challenges, such as food security and climate change. Working together across national borders is essential for securing the health and quality of our soil in the future. With multi-stakeholder processes, language and the use of language is very important since the capability of understanding each other is critical. Developing a common language facilitates learning together, trust-building, defining common viewpoints, resolving disagreements, and arriving at technically sound and practical solutions. This document represents the initial attempt to create a common soil domain ontology and data model to support the creation of a user-friendly infrastructure in accordance with FAIR (Findable, Accessible, Interoperable, and Reusable) data principles for uploading, managing, and providing comparable soil data at global scale. To meet these requirements, the review and application of accepted and widely used standards, conventions, and guidelines for the ingestion, organization, and sharing of soil data is necessary. The document should be regarded as a living document that evolves along with the progress of the project and in response to stakeholder feedback. This project began with the development of an ontology for the soil domain and the identification of representational terms. This was done by following a data-driven approach, which allowed the determination of relevant entities by making strategic decisions based on data analysis and organization, while facilitating a modular expansion of the knowledge base. Next, a standardized soil vocabulary was defined to facilitate data sharing and discovery. Furthermore, soil analytical information is collected and modelled across a variety of data sources, as well as SI units and non-SI units accepted for use with the International System of Units. Finally, a list of relevant conversion factors, regressions, and pedotransfer functions was collected to facilitate data comparison across different data bases.

Aims Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. Methods and results From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. Conclusions In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Background: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). Methods: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. Results: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). Conclusion: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.

Background To evaluate long-term efficacy of left atrial appendage occlusion with multiple devices. Methods All consecutive patients who underwent left atrial appendage occlusion (LAAO) with a follow-up of at least 4 years, were included in this single center, retrospective registry. No specific exclusion criteria were applied. LAA occlusion was performed with the Watchman, Watchman FLX, Amplatzer Cardiac plug or Amplatzer Amulet occluder devices. Results A total of 224 consecutive patients underwent LAAO occlusion. Mean age was 72.5 ± 9.0 years. A history of stroke was present in 29%, TIA in 8.5% and a previous episode of bleeding in 64.7% of patients. In 63% there was a contraindication to oral anticoagulants. The average CHADS-VASc was 4.0 ± 1.6 and the average HAS-BLED was 3.4 ± 1.3. There was a reduction of strokes of 72.9%, thromboembolic events of 59.7% and major bleeding events of 70.9% compared to historic data. During follow-up, 48.3% of the ischemic and major bleeding events occurred within the first year. The annual mortality rate of 7.5 deaths/ 100 patients years. There were no significant differences in terms of outcome between the devices used and there were no late events associated with any device. The main antithrombotic regimen in the long term was with single antiplatelet therapy and the second one was no therapy. Conclusion LAAO is a safe and effective procedure, that reduces ischemic and bleeding events in the long-term, regardless of the type of device used, in AF patients at high risk of ischemic stroke and major bleeding, without the need of anticoagulation.

Background Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods A total of 112 patients with suspected AM from 56963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty- one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Background Pentraxin 3 (PTX3) is an acute phase protein, which regulates the outcomes of inflammation. Currently, there are no myocarditis-typical biomarkers that allow a non-invasive diagnosis, and endomyocardial biopsy (EMB) is still the gold standard. Finally, risk stratification is often challenging in these patients. Aim To investigate whether PTX3 could be expressed in cardiomyocytes and released during myocarditis, serving as a novel and independent diagnostic indicator of myocardial inflammation, and contributing to prognosis prediction. Methods Fifty-five patients with a diagnosis of acute or chronic active myocarditis proven by cardiac magnetic resonance (CMR) and/or endomyocardial biopsy (EMB), were included. First, we evaluated tissue PTX3 expression by immunohistochemistry (IHC). Then, we assessed circulating blood PTX3 by ELISA technique. Results On cardiac tissue, PTX3 at IHC did not localize in the interstitium, and showed an inconstant expression in the vascular endothelium, but a marked staining by cardiomyocytes in all myocarditis patients. The only exception was represented by two patients with systemic COVID-19, with SARS-CoV-2 and PVB-19 intracardiac genomes, respectively, who showed a diffuse cardiac PTX3 expression. Remarkably, at semi-quantitative pixel analysis, viral aetiology showed higher levels of tissue expression, rather than the autoimmune one. Circulating PTX3 levels were significantly higher in myocarditis patients than controls, with pathologic values in 87% of myocarditis patients, and none among controls. Remarkably, plasma PTX3 proved to be more sensitive in myocarditis detection than CRP, ESR, troponin T, and NT-proBNP. As regards of prognosis, we observed that patients with heart failure (HF) presentation all had elevated PTX3 levels, as compared with chest pain or arrhythmia. Remarkably, patients with reduced LVEF ( Conclusions Tissue PTX3 is mostly expressed by cardiomyocytes in patients with active myocarditis on EMB samples. In addition, plasma PTX3 is a sensitive diagnostic and prognostic marker in patients with inflammatory cardiomyopathy.

Background MessengerRNA (mRNA) COVID-19 vaccination has been associated with a higher-than-expected occurrence of acute myocarditis. Scarce information is available on mid-term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Methods Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID-19 vaccination, with a confirmed myocarditis diagnosis based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin >99th upper reference limit or elevated creatine kinase myocardial band [CK-MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Results 77 patients (median age 25 years [IQR 20-35], 15% female) were included and followed-up for 147 days [IQR 74-215]. Follow-up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55-65]vs. 60%[57-64], p=0.507, right ventricular EF: 56%[52-62]vs. 57%[52-61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow-up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2-weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferior-lateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow-up (n=13 (68%) vs. n=4 (13%),p No differences in morpho-functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech®, n=36, 73.5%, m-RNA-1273 Moderna®, n=13, 26.5%). Among patients with available follow-up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusions At mid-term follow-up, patients who experienced an acute myocarditis after a mRNA COVID-19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID-19 vaccination.

Background Preclinical data support the rationale for targeting myocardial inflammation in genetic nonischemic cardiomyopathies. However, no consistent clinical reports have been provided so far. Methods We describe a series of patients (n=25) with genetic cardiomyopathy and active myocardial inflammation (AMI) proven by multimodal diagnostic workup. Patient-tailored immunosuppressive therapy was empirically started to target myocardial inflammation whenever feasible. Multiple outcomes were retrospectively assessed by a dedicated multidisciplinary disease unit. Results Patients carrying desmosomal (DGV), cytoskeletal (CGV) and membrane gene variants (MGV), were 12 (48%), 10 (40%), and 3 (12%), respectively. DGV carriers uniformly presented with myocarditis-like chest pain and ventricular arrhythmias, whereas heart failure symptoms were found only in CGV carriers. Dilated cardiomyopathy phenotype and ring-like pattern on cardiac magnetic resonance allowed the best discrimination among genotypes. AMI was proven by endomyocardial biopsy in all cases, and by noninvasive imaging in 21 (83%). IST was started in 17 patients (71%) with no safety issues. By the end of follow-up (median 69 months, range 21-182), signs of AMI were documented in 6/18 IST receivers (33%) and 4/7 untreated cases (57%). For most genotypes, paucity of adverse events was noted while on immunosuppression as compared to the off-treatment period. Conclusion Our preliminary data provide the clinical rationale for the research and targeting of AMI in a spectrum of genetic nonischemic cardiomyopathies.

Contrast, a simple Python framework for controlling beamline experiments, is presented. Contrast can be easily adapted to any beamline, or serve as inspiration for constructing new, suitable tools tailored to individual instruments., The emergence of fourth-generation synchrotrons is prompting the development of new systems for experimental control and data acquisition. However, as general control systems are designed to cover a wide set of instruments and techniques, they tend to become large and complicated, at the cost of experimental flexibility. Here we present Contrast, a simple Python framework for interacting with beamline components, orchestrating experiments and managing data acquisition. The system is presented and demonstrated via its application at the NanoMAX beamline of the MAX IV Laboratory.

Brugada syndrome (BrS) is an inherited autosomal dominant genetic disorder responsible for sudden cardiac death from malignant ventricular arrhythmia. The term “channelopathy” is nowadays used to classify BrS as a purely electrical disease, mainly occurring secondarily to loss-of-function mutations in the α subunit of the cardiac sodium channel protein Nav1.5. In this setting, arrhythmic manifestations of the disease have been reported in the absence of any apparent structural heart disease or cardiomyopathy. Over the last few years, however, a consistent amount of evidence has grown in support of myocardial structural and functional abnormalities in patients with BrS. In detail, abnormal ventricular dimensions, either systolic or diastolic dysfunctions, regional wall motion abnormalities, myocardial fibrosis, and active inflammatory foci have been frequently described, pointing to alternative mechanisms of arrhythmogenesis which challenge the definition of channelopathy. The present review aims to depict the status of the art of concealed arrhythmogenic substrates in BrS, often resulting from an advanced and multimodal diagnostic workup, to foster future preclinical and clinical research in support of the cardiomyopathic nature of the disease.

In myocarditis patients, persisting inflammation is associated with arrhythmias and unfavorable remodeling ([1][1]). Novel therapeutic strategies may counteract chronic myocardial inflammation, but their use is strictly dependent on the ability to detect and monitor myocardial inflammation.

Background Interest has grown in recent years in bipolar radiofrequency ablation (B-RFA). However, indications and outcome in patients with ventricular tachycardia (VT) are still to be defined. Objective The purpose of this study was to describe patient selection, safety and effectiveness of B-RFA, in a pilot cohort study of patients with nonischemic dilated cardiomyopathy (NIDCM) and drug-refractory VT. Methods We enrolled 21 patients with NIDCM (mean age 66±10 years; 18/21 (86%) men; left ventricular ejection fraction 35%±14%; 100% redo procedures) scheduled for a B-RFA procedure because of drug-refractory VT of suspected septal (interventricular septum [IVS]) origin. After electroanatomic mapping by using the CARTO®3 system, B-RFA was performed in all patients. Short- and long-term outcomes, including procedural success, major complications, and occurrence of major ventricular arrhythmias (MVAs), were evaluated at 25±8 months of follow-up (FU). Results Endocardial mapping showed IVS scar in all patients and extra-IVS in 7 patients (33%). B-RFA was performed at an average power of 33 W, for 60–90 seconds, over a 4.1 cm2 area, with 13±3 mm distance between catheters tips. The impedance drop was 27±4 Ω. The primary end point of noninducibility of the target clinical VT was obtained in 20 patients (95%). During FU, MVAs were documented in 7 patients (33%). FU MVAs occurred in all (100%) patients with extra-IVS localizations (7 of 7) or inflammatory nonischemic cardiomyopathy etiology (2 of 2). IVS thinning (tip-to-tip catheter distance Conclusion B-RFA is feasible in patients with NIDCM and drug-refractory VT of septal origin. Extra-IVS substrate and inflammatory NIDCM etiology were associated with an adverse outcome.

Abnormal ventricular signals (AVS) are the cornerstone of substrate-based ventricular tachycardia (VT) ablation in sinus rhythm. Signal characterization of AVS in ischemic and nonischemic cardiomyopathies has never been performed.The purpose of this study was to describe ventricular signal abnormalities in 3 different pathologies and examine their association with the diastolic component of VT circuits.A total of 45 patients (15 ischemic cardiomyopathy [ICM], 15 arrhythmogenic cardiomyopathy [ACM], 15 dilated cardiomyopathy [DCM]) who had undergone VT ablation with50% of the diastolic pathway of the VT circuit recorded were studied. AVS were classified into late potentials (LPs) and continuous fractionated ventricular signals (CFVS), and their characteristics and correlation with the diastolic pathway of VT circuits were analyzed.Seventy-five VT circuits were analyzed. Bipolar scars were greatest in ICM endocardially (53 cmThe nature of abnormal signals in different cardiomyopathies reflects underlying pathology. LPs rather than CFVS seem to be more linked to diastolic components of VT circuits, especially in ICM. LPs have greater sensitivity and specificity for VT; however, CFVS may be of more relevance in ACM.

Myocarditis Disease Unit (MDU) is a functional multidisciplinary network designed to offer multidisciplinary assistance to patients with myocarditis. More than 300 patients coming from the whole Country are currently followed at a specialized multidisciplinary outpatient clinics. Following the pandemic outbreak of the SARS-CoV-2 infection in Italy, we present how the MDU rapidly evolved to a “tele-MDU”, via a dedicated multitasking digital health platform., Graphical Abstract Unlabelled Image

Ptychographic X-ray computed tomography is a quantitative three-dimensional imaging technique offered to users of multiple synchrotron radiation sources. Its dependence on the coherent fraction of the available X-ray beam makes it perfectly suited to diffraction-limited storage rings. Although MAX IV is the first, and so far only, operating fourth-generation synchrotron light source, none of its experimental stations is currently set up to offer this technique to its users. The first ptychographic X-ray computed tomography experiment has therefore been performed on the NanoMAX beamline. From the results, information was gained about the current limitations of the experimental setup and where attention should be focused for improvement. The extracted parameters in terms of scanning speed, size of the imaged volume and achieved resolutions should provide a baseline for future users designing nano-tomography experiments on the NanoMAX beamline.

X-Ray Fluorescence (XRF) scanning is a widespread technique of high importance and impact since it provides chemical composition maps crucial for several scientific investigations. There are continuous requirements for larger, faster and highly resolved acquisitions in order to study complex structures. Among the scientific applications that benefit from it, some of them, such as wide scale brain imaging, are prohibitively difficult due to time constraints. However, typically the overall XRF imaging performance is improving through technological progress on XRF detectors and X-ray sources. This paper suggests an additional approach where XRF scanning is performed in a sparse way by skipping specific points or by varying dynamically acquisition time or other scan settings in a conditional manner. This paves the way for Compressive Sensing in XRF scans where data are acquired in a reduced manner allowing for challenging experiments, currently not feasible with the traditional scanning strategies. A series of different compressive sensing strategies for dynamic scans are presented here. A proof of principle experiment was performed at the TwinMic beamline of Elettra synchrotron. The outcome demonstrates the potential of Compressive Sensing for dynamic scans, suggesting its use in challenging scientific experiments while proposing a technical solution for beamline acquisition software., Comment: 16 pages, 7 figures, 1 table

Purpose To describe how a referral center for cardiac electrophysiology (EP) rapidly changed to comply with the ongoing COVID-19 healthcare emergency. Methods We present retrospective data about the modification of daily activities at our EP unit, following the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Italy. In particular, in the context of a pre-existing “hub-and-spoke” network, we describe how procedure types and volumes have changed in the last 3 months. Results Since our institution was selected as a COVID-19 referral center, the entire in-hospital activity was reorganized to assist more than 1000 COVID-positive cases. Only urgent EP procedures, including ventricular tachycardia ablation and extraction of infected devices, were both maintained and optimized to meet the needs of external hospitals. In addition, most of the non-urgent EP procedures were postponed. Finally, following prompt internal reorganization, both outpatient clinics and on-call services underwent significant modification, by integrating telemedicine support whenever applicable. Conclusion We presented the fast reorganization of an EP referral center during the ongoing COVID-19 healthcare emergency. Our hub-and-spoke model may be useful for other centers, aiming at a cost-effective management of resources in the context of a global crisis.

Background Ventricular arrhythmias (VAs) have never been systematically investigated in patients with myocarditis at different stages. Objectives The purpose of this study was to compare baseline and follow-up characteristics of VAs in patients with active myocarditis (AM) versus previous myocarditis (PM). Methods A total of 185 consecutive patients (69% males, age 44 ± 15 years, left ventricular ejection fraction 49 ± 14%) with myocarditis and VA at index hospitalization, including ventricular fibrillation, ventricular tachycardia (VT), nonsustained ventricular tachycardia (NSVT), and Lown’s grade ≥2 premature ventricular complexes, were enrolled. AM and PM groups were defined based on endomyocardial biopsy and cardiac magnetic resonance findings. A subset of patients (n = 46, 25%) also underwent electroanatomic mapping and VA transcatheter ablation. Results At presentation, AM patients (n = 123, 66%) more commonly had ventricular fibrillation (8 cases vs. 0 cases; p = 0.053), and both irregular (61% vs. 11%; p Conclusions In myocarditis patients, polymorphic and irregular VA are more common during the active inflammatory phase, whereas monomorphic and regular VA are associated with healed myocarditis.

INTRODUCTION No studies so far addressed the role of invasive programmed ventricular stimulation (PVS) in myocarditis patient's arrhythmic risk stratification. METHODS AND RESULTS We present a single-center prospective study on 96 consecutive adult patients (44 ± 13 years, 70.1% males) with myocarditis and ventricular arrhythmias (VA) at index hospitalization. Depending on baseline endomyocardial biopsy (EMB) and cardiac magnetic resonance, patients were divided into two groups: active (A) vs nonactive (NA) myocarditis. All of the patients underwent PVS at index hospitalization. Medical treatment and implantable cardioverter-defibrillator (ICD) implantation were clinically-driven. Malignant VA episodes (MVA = ventricular tachycardias [VT], ventricular fibrillation [VF], appropriate ICD therapy) were evaluated at 54 ± 18 months follow-up (FU). Patients who underwent VT ablation or with myocarditis recurrence (n = 9) were excluded. Of 87 patients, 41 (47.2%) were in group A. PVS was positive in 32 cases (36.8%), 16 A vs 16 NA (P = NS), with no associations with VA type at presentation. Before discharge, 55 patients (63.2%) underwent ICD implant. In FU, MVA occurred in 27 patients (31.0%), 13 A vs 14 NA (P = NS), 18 PVS+ vs 9 PVS- (P

Carbon nanotubes (CNTs) have been promoted as nanodevices in the biomedicine areas of diagnosis and therapy. In terms of drug delivery, CNTs could be useful in the case of hydrophobic drugs and multiple co-deliveries of therapeutic and imaging molecules. Epithelial cells, being specialized in absorption and secretion, are the first barrier to overcome. At the same time, several frequent tumors are of epithelial origin (cervix, ovarian, liver). Synchrotron-based imaging and spectroscopic techniques are suitable tools to follow the fate of nanodrugs in epithelial cells. We present an example of multi-microscopy approach combining soft X-ray spectromicroscopy at the TwinMic beamline (Elettra Synchrotron, Trieste, Italy) with light and Scanning Electron (SEM) microscopies. In particular, we show that 2–4 h exposure to SWCNTs is not toxic (no viability changes) to a model of cervical epithelial cells, even though it causes temporary perturbation in the membrane and intracellular structures of exposed cells.

Objective To outline the clinical, histological and prognostic features of systemic sclerosis (SSc) endomyocardial biopsy-proven myocarditis with respect to those of diverse endomyocardial biopsy-proven virus-negative myocarditis (VNM). Methods We retrospectively analysed data from three cohorts of endomyocardial biopsy-proven myocarditis: SSc-related VNM (SSc-VNM); isolated VNM (i-VNM); and VNM related to other systemic autoimmune diseases (a-VNM). The degree of myocardial fibrosis was expressed as relative percentage and fibrotic score (0–3). Clinical data, cardiac enzymes, echocardiogram, 24 h ECG Holter and cardiac magnetic resonance were obtained at baseline and during follow-up. Non-parametric tests were used. Results We enrolled 12 SSc-VNM [11 females, mean age 49.3 (14.2) years; seven diffuse-SSc, five early-SSc], 12 i-VNM [12 females, mean age 47.7 (10.8) years] and 10 a-VNM [four females, mean age 48.4 (16.3) years] patients. SSc patients had higher degrees of myocardial fibrosis as assessed by both percentage [SSc-VNM: 44.8 (18.8)%; a-VNM: 28.6 (16.5)%; i-VNM: 24.9 (10.3)%; P = 0.019] and score [SSc-VNM: 2.3 (0.8); a-VNM: 1.4 (1.1); i-VNM: 1.2 (0.7); P = 0.002]. Myocardial fibrosis directly correlated with skin score (r = 0.625, P = 0.03) and number of ventricular ectopic beats on 24 h ECG Holter in SSc patients (r = 0.756, P = 0.01). Dyspnoea class was higher at presentation in SSc-VNM patients (P = 0.041) and we found heart failure only in SSc patients (25%) (P = 0.05). At cardiac magnetic resonance, myocardial oedema was nearly undetectable in SSc-VNM patients compared with others (P = 0.02). All patients received immunosuppressive treatment. The number of patients who died during follow-up due to cardiac complications was significantly higher in SSc-VNM patients (50%), as compared with a-VNM (0%) and i-VNM (8.3%) patients (P = 0.006). Patients who died during follow-up had higher degrees of myocardial fibrosis [52.2 (11.6)% vs 27.5 (12.9)%, P = 0.024; fibrotic score: 2.83 (0.41) vs 1.4 (0.9), P Conclusion SSc has unique clinical and histological features, as it tends to present more frequently with heart failure and a higher dyspnoea class and to show higher degrees of myocardial fibrosis. These specific features are paralleled by a worse cardiac prognosis.

Little is known regarding the characterization of electrical substrate in both atria in patients with atrial fibrillation (AF).Eight consecutive patients undergoing AF ablation (five paroxysmal, three persistent) underwent electrical substrate characterization during sinus rhythm. Mapping of the left (LA) and right atrium (RA) was performed with the use of the HD Grid catheter (Abbott). Bipolar voltage maps were analyzed to search for low voltage areas (LVA), the following electrophysiological phenomena were assessed: (1) slow conduction corridors, and (2) lines of block. EGMs were characterized to search for fractionation. Electrical characteristics were compared between atria and between paroxysmal versus persistent AF patients.In the RA, LVAs were present in 60% of patients with paroxysmal AF and 100% of patients with persistent AF. In the LA, LVAs were present in 40% of patients with paroxysmal AF and 66% of patients with persistent AF. The areas of LVA in the RA and LA were 4.8±7.3 cmBi-atrial involvement is present in patients with paroxysmal and persistent AF. This is expressed by low voltage areas and slow conduction corridors whose extension progresses as the arrhythmia becomes persistent. This electrophysiological substrate demonstrates the important interplay with the pulmonary vein triggers to constitute the substrate for persistent arrhythmia.

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Aims In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. Methods and results Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients’ clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P Conclusion RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis.The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR).Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%).FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator-related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) (P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Aims Iron deficiency (ID) and associated anaemia (IDA) represent major comorbidities in chronic diseases. However, their prevalence and prognostic significance have never been investigated in chronic inflammatory cardiomyopathy (CIC). Methods and results This is a single-centre, prospective study, on consecutive adult patients with CIC (symptom onset > 3 months, endomyocardial biopsy-proven chronic myocarditis) undergoing iron status assessment (enrollment: January 2014–January 2019). ID was defined as either serum ferritin < 100 µg/l or transferrin saturation < 20%. IDA was defined as haemoglobin < 12 g/dl in women, < 13 g/dl in men. The primary endpoint was the occurrence of heart failure events (HFE) and/or arrhythmic events (AE). The study cohort is composed by 219 CIC patients (mean age 46 ± 15 y, 71% males, mean LVEF 50 ± 14%). Diagnosis was furtherly supported by cardiac magnetic resonance in 194 cases (89%). Baseline characteristics of patients with IDA (n = 48), ID (n = 70), and non-ID controls (n = 101) were largely comparable. We found that median in-hospital stay length was 13 days (IQR: 6–20) in IDA patients vs. 8 (IQR: 5–11) in the remaining groups (P = 0.002), and was inversely correlated with haemoglobin values on admission. By 3.9 ± 1.8 year prospective follow-up, events occurred in 86 patients (39%). For the composite endpoint, the only factors associated with events were ID status (HR: 6.3, 95% CI: 2.1–19.5, P = 0.001) and male gender (HR: 5.4, 95% CI: 1.2–24.9, P = 0.030). In detail, HFE occurred in 48 patients (40/118 IDA or ID vs. 8/101 controls, P Conclusions ID and IDA are common among CIC patients, and may bare a negative prognostic value. Our findings suggest a careful evaluation of haemoglobin levels and iron status, and call for further investigation on both pathophysiological and prognostic implications of ID and IDA among CIC patients.

Aims Although potentially life-threatening, arrhythmias in myocarditis are under-reported. To assess diagnostic yield and clinical impact of continuous arrhythmia monitoring (CAM) in patients with arrhythmic myocarditis. Methods and results We enrolled consecutive adult patients (n = 104; 71% males, age 47 ± 11 years, mean LVEF 50 ± 13%) with biopsy-proven active myocarditis and de novo ventricular arrhythmias (VA). All patients underwent prospective monitoring by both sequential 24-h Holter ECGs (4/y in the first year; 2/y in years 2–5; 1/y later) and CAM, including either ICD (n = 62; 60%) or loop recorder (n = 42; 40%). By 3.7 ± 1.6 year follow-up, 45 patients (43%) had VT, 67 (64%) NSVT, and 102 (98%) premature ventricular complexes (PVCs). As compared to Holter ECG (average 9.5 exams per patient), CAM identified more patients with VA (VT: 45 vs. 4; NSVT: 64 vs. 45; both P Conclusions In patients with arrhythmic myocarditis, CAM allowed accurate arrhythmia detection and showed a considerable clinical impact. As a complementary exam, VA characterization and PVC burden were better assessed by repeated Holter ECGs.

Aims Etiology identification and risk stratification represent major issues for patients presenting with undefined left ventricular arrhythmogenic cardiomyopathy (ULVACM). To investigate the role of genotyping and histology for ULVACM classification, management, and risk assessment. Methods and results We retrospectively analysed a multicentre cohort of patients (screened n = 1037) with ULVACM defined by ventricular arrhythmia (VA) onset, nonischaemic late gadolinium enhancement (LGE) limited to the LV, and no manifest dilated cardiomyopathy (LVEF ≥ 40%). We selected patients undergoing both next generation sequencing (NGS) genotyping and endomyocardial biopsy (EMB) for etiology definition. When feasible, immunosuppressive therapy (IST) was used to target active myocardial inflammation (AMI). The study endpoint was a composite of cardiac death, heart transplantation and malignant VAs (VT, VF, appropriate ICD treatment). The study cohort is composed by 135 ULVACM patients (age 43 ± 14 years, 63% males, LVEF 55 ± 7%). NGS identified pathogenic or likely-pathogenic variants (PVs/LPVs) consistent with ACM in 21 cases (16%), whereas EMB showed AMI in 78 patients (58%), including 13/21 PVs/LPVs + (62%). IST was started in 41/78 AMI patients (53%), including 9/13 PVs/LPVs + (69%). Twenty patients (15%) met the study endpoint by 12 months, and 36 (27%) by the end of the study (60 ± 27 months). Beyond malignant VT onset, AMI was the only predictor of events by 12 months (HR: 5.0, 95% CI: 1.4–18.1, P = 0.007). No prognostic role was found for PVs/LPVs, except for the subgroup (n = 77) with nonsustained VT onset. Among AMI patients, those treated by IST had a significantly lower occurrence of events, both by 12-months (1/41 vs. 16/37, P Conclusions Despite its limited diagnostic yield, the combined genetic and histological workup substantially contributed into ULVACM prognostic assessment. Furthermore, EMB identified suitable candidates for IST, who showed better outcomes irrespectively of their genotype.

Background: both myocarditis and mitral valve prolapse (MVP) are known uncommon causes of ventricular arrhythmias in young patients. Aim: to report the first clinical case of endomyocardial biopsy (EMB)-proven autoimmune myocarditis and associated arrhythmogenic MVP in a patient with recurrent ventricular fibrillation (VF) episodes. Methods: myocarditis was diagnosed both by cardiac magnetic resonance (CMR) and EMB. Arrhythmogenic MVP was documented by transthoracic echocardiogram, CMR, and electroanatomical mapping of the trigger premature ventricular contractions (PVCs). Results: a 22-year-old woman underwent immunosuppressive therapy after EMB-proven diagnosis of autoimmune myocarditis with VF onset and early implantable cardioverter defibrillator (ICD) placement. Three years later, she experienced two VF recurrences and persistent PVCs, despite no signs of myocarditis recurrence. An echocardiogram revealed bileaflet MVP with high arrhythmic risk features. Finally, electroanatomical mapping and ablation of the trigger PVC were successfully performed. Conclusion: in patients with recurrent VF episodes despite evidence-based medical treatment for myocarditis, MVP should be considered as an alternative arrhythmogenic substrate, and warrants early ICD implant and PVC-targeted therapy.