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Competing Interests: Conflict of interest: none declared.

The knowledge of pericardial diseases has now improved, including prospective and retrospective cohort studies focusing on the pathogenesis, diagnosis, treatment, and outcomes. The complex interplay between genetic predisposition (especially for autoinflammatory conditions), inflammation, and autoimmunity is now known to trigger recurrences of pericarditis. Moreover, diagnostic capabilities have improved with the implementation of multimodality imaging, particularly cardiac magnetic resonance (CMR), to detect and monitor pericardial inflammation, to allow diagnosis in more complicated cases, and tailor the duration of therapy based on objective parameters. A new class of drugs, the anti-IL-1 agents, have been introduced for patients with an inflammatory phenotype of presentation, and not responding to conventional anti-inflammatory therapies, including NSAID, colchicine, and corticosteroids. At present, the clinical management of pericardial diseases is definitely on the road of evidence-based medicine with new ongoing European guidelines focusing on the spectrum of inflammatory myocardial and pericardial syndromes., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Competing Interests: Conflict of interest: none declared.

Nearly 35 years after its initial publication in 1989, the Italian Society of Sports Cardiology and the Italian Federation of Sports Medicine (FMSI), in collaboration with other leading Italian Cardiological Scientific Associations (ANCE - National Association of Outpatient Cardiology, ANMCO - National Association of Inpatient Cardiology, SIC - Italian Society of Cardiology), proudly present the 2023 version of the Cardiological Guidelines for Competitive Sports Eligibility. This publication is an update of the previous guidelines, offering a comprehensive and detailed guide for the participation of athletes with heart disease in sports. This edition incorporates the latest advances in cardiology and sports medicine, providing current information and recommendations. It addresses various topics, including the details of the pre-participation screening in Italy and recommendations for sports eligibility and disqualification in competitive athletes with various heart conditions. This revised version of the Cardiological Guidelines for Competitive Sports Eligibility, recorded in the Italian Guidelines Registry of the Italian Minister of Health, stands as a crucial resource for sports medicine professionals, cardiologists, and healthcare providers, marked by its completeness, reliability, and scientific thoroughness. It is an indispensable tool for those involved in the care, management and eligibility process of competitive athletes with heart conditions.

The knowledge of pericardial diseases has now improved, including prospective and retrospective cohort studies focusing on the pathogenesis, diagnosis, treatment, and outcomes. The complex interplay between genetic predisposition (especially for autoinflammatory conditions), inflammation, and autoimmunity is now known to trigger recurrences of pericarditis. Moreover, diagnostic capabilities have improved with the implementation of multimodality imaging, particularly cardiac magnetic resonance (CMR), to detect and monitor pericardial inflammation, to allow diagnosis in more complicated cases, and tailor the duration of therapy based on objective parameters. A new class of drugs, the anti-IL-1 agents, have been introduced for patients with an inflammatory phenotype of presentation, and not responding to conventional anti-inflammatory therapies, including NSAID, colchicine, and corticosteroids. At present, the clinical management of pericardial diseases is definitely on the road of evidence-based medicine with new ongoing European guidelines focusing on the spectrum of inflammatory myocardial and pericardial syndromes., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Transthoracic echocardiography (TTE) is routinely required during pre-participation screening in the presence of symptoms, family history of sudden cardiac death or cardiomyopathies <40-year-old, murmurs, abnormal ECG findings or in the follow-up of athletes with a history of cardiovascular disease (CVD). TTE is a cost-effective first-line imaging modality to evaluate the cardiac remodeling due to long-term, intense training, previously known as the athlete's heart, and to rule out the presence of conditions at risk of sudden cardiac death, including cardiomyopathies, coronary artery anomalies, congenital, aortic and heart valve diseases. Moreover, TTE is useful for distinguishing physiological cardiac adaptations during intense exercise from pathological behavior due to an underlying CVD. In this expert opinion statement endorsed by the Italian Society of Sports Cardiology, we discussed common clinical scenarios where a TTE is required and conditions falling in the grey zone between the athlete's heart and underlying cardiomyopathies or other CVD. In addition, we propose a minimum dataset that should be included in the report for the most common indications of TTE in sports cardiology clinical practice., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest. All authors have seen and approved the manuscript being submitted, have contributed significantly to the work, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission to the International Journal of Cardiology., (Copyright © 2024. Published by Elsevier B.V.)

Mobile health (mHealth) solutions have the potential to improve self-management and clinical care. For successful integration into routine clinical practice, healthcare professionals (HCPs) need accepted criteria helping the mHealth solutions' selection, while patients require transparency to trust their use. Information about their evidence, safety and security may be hard to obtain and consensus is lacking on the level of required evidence. The new Medical Device Regulation is more stringent than its predecessor, yet its scope does not span all intended uses and several difficulties remain. The European Society of Cardiology Regulatory Affairs Committee set up a Task Force to explore existing assessment frameworks and clinical and cost-effectiveness evidence. This knowledge was used to propose criteria with which HCPs could evaluate mHealth solutions spanning diagnostic support, therapeutics, remote follow-up and education, specifically for cardiac rhythm management, heart failure and preventive cardiology. While curated national libraries of health apps may be helpful, their requirements and rigour in initial and follow-up assessments may vary significantly. The recently developed CEN-ISO/TS 82304-2 health app quality assessment framework has the potential to address this issue and to become a widely used and efficient tool to help drive decision-making internationally. The Task Force would like to stress the importance of co-development of solutions with relevant stakeholders, and maintenance of health information in apps to ensure these remain evidence-based and consistent with best practice. Several general and domain-specific criteria are advised to assist HCPs in their assessment of clinical evidence to provide informed advice to patients about mHealth utilization., Competing Interests: Conflict of interest: G.B. declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Boston, Boehringer Ingelheim, Daiichi-Sankyo, Janssen, Sanofi. L.N. reports grants or contracts through her institution from Daiichi Sankyo; under 1000 USD personal honoraria from Pfizer-BMS. A.G.F. reports grant support from the European Union Horizon Europe programme for the CORE MD project (agreement 965246); being the Chairman, Regulatory Affairs Committee, Biomedical Alliance in Europe. F.D. Reports being a task force member for the European Society of Cardiology; support for attending meetings and/or travel by the BSI/TeamNB as a technical specialist; fiduciary role in Team NB as a technical specialist from BSI. A.B. reports Abiomed scientific grant (76445733); royalties or licences from Seerling Ltd; Support for attending meetings and/or travel from Pfizer for the ESC congress 2023; being a member of the Librexia ACS trial steering committee. E.G.C. reports a grant in the form of a <1K€ payment to his institution from the Advisory Board on digital Health of Medtronic USA; honoraria for presentations or educational events (total <10k€) from Servier, Summeet Srl, Dynamicom Education Srl, UVET GBT Spa, Sanofi; support for attending meetings and/or travel from the European Society of Cardiology. R.C. declares personal payments for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Servier, Novartis, BerlinChemie, Zentiva, Viatris, Pfizer, Astra Zeneca; support for attending meetings and/or travel from Novartis Berlin-Chemie, Astra Zeneca, Boehringer Ingelheim; participation on a Data Safety Monitoring Board or Advisory Board for Boehringer Ingelheim; receipt of drug samples from Astra Zeneca and Boehringer Ingelheim. D.A.L. declares grants or contracts to her institution from Bristol-Myers Squibb and Pfizer; consulting fees from Bristol-Myers Squibb (BMS) and Boehringer Ingelheim; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, BMS-Pfizer, Boehringer Ingelheim. G.R. declares consulting fees paid to the University no value transfer from Astra Zeneca, Bayer, Boehringer Ingelheim, Vifor, Menarini; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events to the university no value transfer from Astra Zeneca, Bayer, Boehringer Ingelheim, Vifor, Menarini; support for attending meetings and/or travel from Fondazione Menarini, Servier, Astra Zeneca. P.H declares Horizon Europe Label2Enable project payments to the Leiden University Medical center and to be the lead expert of CEN-ISO/TS 82304-2 with no financial ties or royalties for CEN TC251; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events covered by Label2Enable project; payment for expert testimony for the Advanced and Active Living project for project reviews; support for attending meetings and/or travel from, the American Society of Clinical Oncology in 2019 as a patient advocate; being the unpaid initiator and driver of two health apps in oncology (ReMind app and Goings-On app). R.A. reports <100 € of royalties or licences from Springer-Verlag GmbH; a 750 EUR payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from the Univers Formazione SRL Roma; participation on a Data Safety Monitoring Board or Advisory Board of Resilience Trial. H.P.B.LR. declares support for the present manuscript in the form of INTERREG-NWE project NWE702; PASSION-HF grants to his institution; grants or contracts from Dutch Heart Foundation CVON 2018-28, ZONMW IMDI 104022004, Vifor Pharma, and Roche Diagnostics to his institution; consulting fees from Novartis Pharma, Boehringer-Ingelheim, AstraZeneca, Roche Diagnostics, Vifor Pharma to his institution; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events to his institution from Novartis, Roche Diagnostics; payment for expert testimony to his institution from Novartis; being on Committee on pharmacological treatment of the Dutch Society of Cardiology. K.M.R. declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biosense Webster; support for attending meetings and/or travel to/from the European Heart Rhythm Association; being on the board of the European Heart Rhythm Association. E.T.L. declares a professional personal contract (2019–today) as a Senior Consultant with the IRCCS Policlinico San Donato and a professional personal contract (2003–today) as a Senior Consultant with the Italian National Health System—Lombardy Region, support for attending meetings and/or travel to/from the Japanese Heart Rhythm Society (July 2023). M.R.C. Reports having been the chair of the ESC Digital Health Committee in the period 2018–2022; being employed by AstraZeneca. G.P. declares honorariums for lectures from Omron Health Care and Somnomedics. P.S. declares payment or honorariums for educational events from Novartis and Polpharma. R.C.A. declares payment for lectures made to his institution by Abbot and Boston Scientific. CP declares honorariums for educational cardio-oncology presentations from Amgen and Beigene. P.D., S.C., A.S., C.O.M., B.B., M.S., H.K., declare no conflict of interest for this contribution., (© European Society of Cardiology 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: There is no acceptable maximum wall thickness (MWT) threshold for diagnosing apical hypertrophic cardiomyopathy (ApHCM), with guidelines referring to ≥15 mm MWT for all hypertrophic cardiomyopathy subtypes. A normal myocardium naturally tapers apically; a fixed diagnostic threshold fails to account for this. Using cardiac magnetic resonance, "relative" ApHCM has been described with typical electrocardiographic features, loss of apical tapering, and cavity obliteration but also with MWT <15 mm., Objectives: The authors aimed to define normal apical wall thickness thresholds in healthy subjects and use these to accurately identify ApHCM., Methods: The following healthy subjects were recruited: healthy UK Biobank imaging substudy subjects (n = 4,112) and an independent healthy volunteer group (n = 489). A clinically defined disease population of 104 ApHCM subjects was enrolled, with 72 overt (MWT ≥15 mm) and 32 relative (MWT <15 mm but typical electrocardiographic/imaging findings) ApHCM subjects. Cardiac magnetic resonance-derived MWT was measured in 16 segments using a published clinically validated machine learning algorithm. Segmental normal reference ranges were created and indexed (for age, sex, and body surface area), and diagnostic performance was assessed., Results: In healthy cohorts, there was no clinically significant age-related difference for apical wall thickness. There were sex-related differences, but these were not clinically significant after indexing to body surface area. Therefore, segmental reference ranges for apical hypertrophy required indexing to body surface area only (not age or sex). The upper limit of normal (the largest of the 4 apical segments measured) corresponded to a maximum apical MWT in healthy subjects of 5.2 to 5.6 mm/m 2 with an accuracy of 0.94 (the unindexed equivalent being 11 mm). This threshold was categorized as abnormal in 99% (71/72) of overt ApHCM patients, 78% (25/32) of relative ApHCM patients, 3% (122/4,112) of UK Biobank subjects, and 3% (13/489) of healthy volunteers., Conclusions: Per-segment indexed apical wall thickness thresholds are highly accurate for detecting apical hypertrophy, providing confidence to the reader to diagnose ApHCM in those not reaching current internationally recognized criteria., Competing Interests: Funding Support and Author Disclosures This research has been conducted using the UK Biobank Resource (project 71702). Dr Hughes is supported by the British Heart Foundation (grant number FS/17/82/33222). Dr Burke is supported by the British Heart Foundation (grant number FS/19/63/34902). Dr Jiang is funded by the British Heart Foundation (grant number FS/4yPhD/F/20/34134). Dr Davies is funded by the British Heart Foundation Accelerator Award (AA/18/6/34223). Dr Lopes is funded by a Medical Research Council Clinical Academic Research Partnership award. Dr Captur is supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC, #171603) and the National Institutes of Health University College London Hospitals Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The integration of artificial intelligence (AI) technologies is evolving in different fields of cardiology and in particular in sports cardiology. Artificial intelligence offers significant opportunities to enhance risk assessment, diagnosis, treatment planning, and monitoring of athletes. This article explores the application of AI in various aspects of sports cardiology, including imaging techniques, genetic testing, and wearable devices. The use of machine learning and deep neural networks enables improved analysis and interpretation of complex datasets. However, ethical and legal dilemmas must be addressed, including informed consent, algorithmic fairness, data privacy, and intellectual property issues. The integration of AI technologies should complement the expertise of physicians, allowing for a balanced approach that optimizes patient care and outcomes. Ongoing research and collaborations are vital to harness the full potential of AI in sports cardiology and advance our management of cardiovascular health in athletes., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Coronavirus-19 disease (COVID-19) related pandemic have deeply impacted human health, economy, psychology and sociality. Possible serious cardiac involvement in the infection has been described, raising doubts about complete healing after the disease in many clinical settings. Moreover, there is the suspicion that the vaccines, especially those based on mRNA technology, can induce myopericarditis. Myocarditis or pericarditis related scars can represent the substrate for life-threatening arrhythmias, triggered by physical activity. A crucial point is how to evaluate an athlete after a COVID-19 infection ensuring a safe return to play without increasing the number of unnecessary disqualifications from sports competitions. The lack of conclusive scientific data significantly increases the difficulty to propose recommendations and guidelines on this topic. At the same time, the psychological and physical negative consequences of unnecessary sports restriction must be taken into account. The present document aims to provide an updated brief review of the current knowledge about the COVID-19 cardiac involvement and how to recognize it and to offer a roadmap for the management of the athletes after a COVID-19 infections, including subsequent impact on exercise recommendations. Our document exclusively refers to cardiovascular implications of the disease, but pulmonary consequences are also considered.

Aims: Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL and the mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM., Methods and Results: Cardiovascular magnetic resonance imaging using a 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G+LVH-), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G+LVH+), and 53 age-, sex-, and body surface area-matched healthy volunteers. Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held three-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROIs) were tracked: ROIPMVL: hinge point of the posterior mitral valve leaflet; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; and ROIAAO: anterior aortic annulus. Compared with controls, normalized two-dimensional displacement-vs.-time plots in G+LVH- revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with the burden of left ventricular fibrosis (P < 0.028). As expected, SAM was observed in G+LVH+ together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008)., Conclusion: Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM before the development of LVH or left atrial enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO predisposition in HCM., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The characteristics and risk factor profile of young patients presenting with non-ST segment elevation acute coronary syndrome (NSTEACS) and how they may have changed over time is not well reported., Methods: We identified 26,708 NSTEACS patients aged under 50 presenting to United Kingdom (UK) hospitals between 2010 and 2017 from Myocardial Ischaemia National Audit Project (MINAP). We calculated incidence of NSTEACS per 100,000 UK population, using Office of National Statistics (ONS) population estimates, prevalence of comorbidities, ethnicity, and in-hospital mortality. We formed biennial groups to enable comparison, 2010-2011, 2012-2013, 2014-2015 and 2016-2017., Results: The incidence of NSTEACS per 100,000 population showed minimal change between 2010 and 2017 (2010: 5.4 per 100,000 and 2017; 4.9 per 100,000). Rates of smoking (2010-11; 58% and 2016-17; 53%), and family history of coronary artery disease (CAD) (2010-11; 51% and 2016-17; 44%) fell, but the proportion of patients from an ethnic minority background (2010-11; 12% and 2016-17; 20%), with diabetes mellitus (DM) (2010-11; 14%, and 2016-17; 18%) and female patients (2010-11; 22% and 2016-17; 24%) increased over the study period. Mortality from NSTEACS remained unchanged (2010-11; 1% and 2016-17; 1%)., Conclusions: The incidence of NSTEACS in patients aged under fifty has not reduced despite reduction in prevalence of risk factors such as smoking hypercholesterolaemia in those admitted to UK hospitals. Despite improved rates of early invasive coronary angiography and percutaneous coronary intervention in 'young' NSTEACS patients, in-hospital mortality remains unchanged., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Premature ventricular beats (PVBs) are recorded in a sizeable proportion of athletes during pre-participation screening, especially if the evaluation includes both resting and exercise ECG. While in the majority of cases no underlying heart disease is present, in others PVBs may be the sign of a condition at risk of sudden cardiac death, including cardiomyopathies, congenital, coronary artery, heart valves and ion channels diseases. In this expert opinion document of the Italian Society of Sports Cardiology, we propose a multiparametric interpretation approach to PVBs in athletes and a stepwise diagnostic algorithm. The clinical work-up should include the assessment of the probable site of origin based on the ECG pattern of the ectopic QRS and of the arrhythmia behavior (including the number of different PVB morphologies, complexity, response to exercise and reproducibility), as well as first-line tests such as echocardiography. Based on this initial evaluation, most athletes can be reassured of the benign nature of PVBs and cleared for competition under periodical follow-up. However, when the clinical suspicion is high, further investigations with non-invasive (e.g. cardiac magnetic resonance, cardiac computed tomography, genetic testing) and, in very selected cases, invasive (e.g. endocardial voltage mapping and endomyocardial biopsy) tests should be carried out to rule out a high-risk condition. Importantly, such advanced tests should be performed in centers with a consolidated experience not only in the technique, but also in evaluation of athletes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Three-dimensional electroanatomical mapping (EAM) has the potential to identify the pathological substrate underlying ventricular arrhythmias (VAs) in different clinical settings by detecting myocardial areas with abnormally low voltages, which reflect the presence of different cardiomyopathic substrates. In athletes, the added value of EAM may be to enhance the efficacy of third-level diagnostic tests and cardiac magnetic resonance (CMR) in detecting concealed arrhythmogenic cardiomyopathies. Additional benefits of EAM in the athlete include the potential impact on disease risk stratification and the consequent implications for eligibility to competitive sports. This opinion paper of the Italian Society of Sports Cardiology aims to guide general sports medicine physicians and cardiologists on the clinical decision when to eventually perform an EAM study in the athlete, highlighting strengths and weaknesses for each cardiovascular disease at risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression, and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2023 Elsevier B.V. All rights reserved.)

"Athlete's heart" is a spectrum of morphological, functional, and regulatory changes that occur in people who practice regular and long-term intense physical activity. The morphological characteristics of the athlete's heart may overlap with some structural and electrical cardiac diseases that may predispose to sudden cardiac death, including inherited and acquired cardiomyopathies, aortopathies and channelopathies. Overdiagnosis should be avoided, while an early identification of underlying cardiac life-threatening disorders is essential to reduce the potential for sudden cardiac death. A step-by-step multimodality approach, including a first-line evaluation with personal and family history, clinical evaluation, 12-lead resting electrocardiography (ECG), followed by second and third-line investigations, as appropriate, including exercise testing, resting and exercise echocardiography, 24-hour ECG Holter monitoring, cardiac magnetic resonance, computed tomography, nuclear scintigraphy, or genetic testing, can be determinant to differentiate between extreme physiology adaptations and cardiac pathology. In this context, cardiovascular imaging plays a key role in detecting structural abnormalities in athletes who fall into the grey zone between physiological adaptations and a covert or early phenotype of cardiovascular disease., Competing Interests: The authors declare no conflict of interest. Elena Cavarretta is serving as one of the Guest editors and Giuseppe Limongelli is serving as one of the Editorial Board members of this journal. We declare that Elena Cavarretta and Giuseppe Limongelli had no involvement in the peer review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Zhonghua Sun., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Cardiomyopathies are disease of the cardiac muscle largely due to genetic alterations of proteins with 'structural' or 'functional' roles within the cardiomyocyte, going from the regulation of contraction-relaxation, metabolic and energetic processes to ionic fluxes. Modifications occurring to these proteins are responsible, in the vast majority of cases, for the phenotypic manifestations of the disease, including hypertrophic, dilated, arrhythmogenic and restrictive cardiomyopathies. Secondary nonhereditary causes to be excluded include infections, toxicity from drugs or alcohol or medications, hormonal imbalance and so on. Obtaining a phenotypic definition and an etiological diagnosis is becoming increasingly relevant and feasible, thanks to the availability of new tailored treatments and the diagnostic advancements made particularly in the field of genetics. This is, for example, the case for transthyretin cardiac amyloidosis, Fabry disease or dilated cardiomyopathies due to laminopathies. For these diseases, specific medications have been developed, and a more tailored arrhythmic risk stratification guides the implantation of a defibrillator. In addition, new medications directly targeting the altered protein responsible for the phenotype are becoming available (including the myosin inhibitors mavacantem and aficamten, monoclonal antibodies against Ras-MAPK, genetic therapies for sarcoglycanopathies), thus making a precision medicine approach less unrealistic even in the field of cardiomyopathies. For these reasons, a contemporary approach to cardiomyopathies must consider diagnostic algorithms founded on the clinical suspicion of the disease and developed towards a more precise phenotypic definition and etiological diagnosis, based on a multidisciplinary methodology putting together specialists from different disciplines, facilities for advanced imaging testing and genetic and anatomopathological competencies., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease associated with an increased risk of life-threatening arrhythmias. The aim of the present study was to evaluate the association of ventricular arrhythmias (VA) with circadian and seasonal variation in ARVC. One hundred two ARVC patients with an implantable cardioverter defibrillator (ICD) were enrolled in the study. Arrhythmic events included (a) any initial ventricular tachycardia (VT) or fibrillation (VF) prompting ICD implantation, (b) any VT or non-sustained VT (NSVT) recorded by the ICD, and (c) appropriate ICD shocks/therapy. Differences in the annual incidence of events across seasons (winter, spring, summer, autumn) and period of the day (night, morning, afternoon, evening) were assessed both for all cardiac events and major arrhythmic events. In total, 67 events prior to implantation and 263 ICD events were recorded. These included 135 major (58 ICD therapies, 57 self-terminating VT, 20 sustained VT) and 148 minor (NSVT) events. A significant increase in the frequency of events was observed in the afternoon versus in the nights and mornings ( p = 0.016). The lowest number of events was registered in the summer, with a peak in the winter ( p < 0.001). Results were also confirmed when excluding NSVT. Arrhythmic events in ARVC follow a seasonal variation and a circadian rhythm. They are more prevalent in the late afternoon, the most active period of the day, and in the winter, supporting the role of physical activity and inflammation as triggers of events.

Cardiac magnetic resonance (CMR) has become an essential tool for the evaluation of patients affected or at risk of developing cardiomyopathies (CMPs). In fact, CMR not only provides precise data on cardiac volumes, wall thickness, mass and systolic function but it also a non-invasive characterization of myocardial tissue, thus helping the early diagnosis and the precise phenotyping of the different CMPs, which is essential for early and individualized treatment of patients. Furthermore, several CMR characteristics, such as the presence of extensive LGE or abnormal mapping values, are emerging as prognostic markers, therefore helping to define patients' risk. Lastly new experimental CMR techniques are under investigation and might contribute to widen our knowledge in the field of CMPs. In this perspective, CMR appears an essential tool to be systematically applied in the diagnostic and prognostic work-up of CMPs in clinical practice. This review provides a deep overview of clinical applicability of standard and emerging CMR techniques in the management of CMPs., (© 2022. The Author(s).)

The use of social media (SoMe) has spread worldwide among doctors, scientific societies, and researchers. SoMe offer a powerful platform to accelerate or create new contacts, spread scientific news, and increase visibility. A social media promotion strategy for cardiovascular medicine papers seems to be associated with increased online visibility and a higher number of citations. This effect is independent of the type of article and the total number of followers of the authors. Indeed, SoMe are democratic and even non-senior researchers may be popular on Twitter: your title is not as important as what you do on Twitter. Nevertheless, some physicians may be over-celebrated due to their presence on SoMe. This is why a new author index, the K-index, has been proposed. The K-index correlates the citations of a scientist with the number of Twitter followers. Even scientific journals and societies have recognized the importance of SoMe and in the last years they have appeared on SoMe with official accounts. Therefore, besides the classic impact factor, publishers now pay more and more attention to other parameters, such as the Altmetric score, which takes into account the number of citations, but also the number of downloads, mentions on SoMe, newspapers and tv news, web sites, and blogs. The COVID-19 pandemic has boosted the importance of SoMe for scientific content distribution, particularly for congresses. For all these reasons, it is important to understand the pros and cons of SoMe. It is also possible that SoMe will become a new education medium for continuing medical education.

Cardiac sequelae after COVID-19 have been described in athletes, prompting the need to establish a return-to-play (RTP) protocol to guarantee a safe return to sports practice. Sports participation is strongly associated with multiple short- and long-term health benefits in children and adolescents and plays a crucial role in counteracting the psychological and physical effects of the current pandemic. Therefore, RTP protocols should be balanced to promote safe sports practice, particularly after an asymptomatic SARS-CoV-2 infection that represents the common manifestation in children. The present consensus document aims to summarize the current evidence on the cardiac sequelae of COVID-19 in children and young athletes, providing key messages for conducting the RTP protocol in paediatric athletes to promote a safe sports practice during the COVID-19 era., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Molecular genetic testing is an increasingly available test to support the clinical diagnosis of inherited cardiovascular diseases through identification of pathogenic gene variants and to make a preclinical genetic diagnosis among proband's family members (so-called "cascade family screening"). In athletes, the added value of molecular genetic testing is to assist in discriminating between physiological adaptive changes of the athlete's heart and inherited cardiovascular diseases, in the presence of overlapping phenotypic features such as ECG changes, imaging abnormalities or arrhythmias ("grey zone"). Additional benefits of molecular genetic testing in the athlete include the potential impact on the disease risk stratification and the implications for eligibility to competitive sports. This position statement of the Italian Society of Sports Cardiology aims to guide general sports medical physicians and sports cardiologists on clinical decision as why and when to perform a molecular genetic testing in the athlete, highlighting strengths and weaknesses for each inherited cardiovascular disease at-risk of sudden cardiac death during sport. The importance of early (preclinical) diagnosis to prevent the negative effects of exercise on phenotypic expression, disease progression and worsening of the arrhythmogenic substrate is also addressed., (Copyright © 2022. Published by Elsevier B.V.)

Sports Cardiology practice commonly involves the evaluation of athletes for genetically determined cardiac conditions that may predispose to malignant arrhythmias, heart failure, and sudden cardiac death. High-level exercise can lead to electrical and structural cardiac remodelling which mimics inherited cardiac conditions (ICCs). Differentiation between 'athlete's heart' and pathology can be challenging and often requires the whole armamentarium of available investigations. Genetic studies over the last 30 years have identified many of the genetic variants that underpin ICCs and technological advances have transformed genetic testing to a more readily available and affordable clinical tool which may aid diagnosis, management, and prognosis. The role of genetic testing in the evaluation and management of athletes with suspected cardiac conditions is often unclear beyond the context of specialist cardio-genetics centres. This document is aimed at physicians, nurses, and allied health professionals involved in the athlete's care. With the expanding role and availability of genetic testing in mind, this document was created to address the needs of the broader sports cardiology community, most of whom work outside specialized cardio-genetics centres, when faced with the evaluation and management of athletes with suspected ICC. The first part of the document provides an overview of basic terminology and principles and offers guidance on the appropriate use of genetic testing in the assessment of such athletes. It outlines key considerations when contemplating genetic testing, highlighting the potential benefits and pitfalls, and offers a roadmap to genetic testing. The second part of the document presents common clinical scenarios in Sports Cardiology practice, outlining the diagnostic, prognostic, and therapeutic implications of genetic testing, including impact on exercise recommendations. The scope of this document does not extend to a comprehensive description of the genetic basis, investigation, or management of ICCs., Competing Interests: Conflicts of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiomyopathies (CMPs) are myocardial diseases in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Thought for a long time to be rare diseases, it is now clear that most of the CMPs can be easily observed in clinical practice. However, there is a group of specific heart muscle diseases that are rare in nature whose clinical/echocardiographic phenotypes resemble those of the four classical morphological subgroups of hypertrophic, dilated, restrictive, arrhythmogenic CMPs. These rare CMPs, often but not solely diagnosed in infants and paediatric patients, should be more properly labelled as specific CMPs. Emerging consensus exists that these conditions require tailored investigation and management. Indeed, an appropriate understanding of these conditions is mandatory for early treatment and counselling. At present, however, the multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a significant concern. The aim of this paper is to define practical recommendations for diagnosis and management of the rare CMPs in paediatric or adult age. A modified Delphi method was adopted to grade the recommendations proposed by each member of the writing committee., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study sought to report our single-center experience with left cardiac sympathetic denervation (LCSD) for long QT syndrome (LQTS) since 1973., Background: LCSD is still underutilized because clinicians are often uncertain whether to use it versus an implantable cardioverter-defibrillator (ICD)., Methods: We performed LCSD in 125 patients with LQTS (58% women, mean QT interval corrected for frequency [QTc] 527 ± 60 ms, 90% on beta blockers) with a follow-up of 12.9 ± 10.3 years. They were retrospectively divided into 4 groups according to the clinical/genetic status: very high risk (n = 18, symptomatic in the first year of life or with highly malignant genetics), with aborted cardiac arrest (ACA) (n = 31), with syncope and/or ICD shocks on beta blockers (n = 45), in primary prevention (n = 31)., Results: After LCSD, 17% in the very high risk group remained asymptomatic, compared with 52%, 47%, and 97% in the other 3 groups (P < 0.0001), with an overall 86% decrease in the mean yearly cardiac event rate (P < 0.0001). Among 45 patients with only syncope/ICD shocks before LCSD, none had ACA/sudden death as first symptom after LCSD and a 6-month post-LCSD QTc <500 ms predicted excellent outcome. Patients with a QTc ≥500 ms have a 50% chance of shortening it by an average of 60 ms. LCSD results are not affected by common genotypes., Conclusions: We provide definitive evidence for the long-term efficacy of LCSD in LQTS. The degree of antiarrhythmic protection is influenced by patient's specificity and amount of QTc shortening. This novel approach to the analysis of the outcome allows cardiologists to rationally decide and tailor their management strategies to the individual features of their patients., Competing Interests: Funding Support and Author Disclosures Drs Schwartz and Crotti were partially supported by Leducq Foundation for Cardiovascular Research, grant 18CVD05, “Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies.” All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na V 1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na V 1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background Women continue to be underrepresented in cardiology and even more so in leadership positions. We evaluated the trends and gender differences in the guideline writing groups of the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC) guidelines from 2006 to 2020. Methods and Results We extracted all guidelines authors from 2006 to 2020, assessed their gender from publicly available profiles, and compared differences based on subspecialties and specific societies. Stratified and trend analyses were performed using χ 2 and average annual percentage change/average 5 year percentage change. A total of 80 ACC/AHA (1288 authors [28% women]), 64 CCS (988 authors [26% women]), and 59 ESC (1157 authors [16% women]) guidelines were analyzed. A significant increase in inclusion of women was seen in ACC/AHA (12.6% [2006] to 42.6% [2020]; average annual percentage change, 6.6% [2.3% to 11.1%]; P =0.005) and ESC (7.1% [2006] to 25.8% [2020]; average annual percentage change, 6.6% [0.2% to 13.5%]; P =0.04), but the trend remained similar in CCS (20.6% [2006] to 36.3% [2020]; average annual percentage change, -0.1% (-3.7% to 3.5%); P =0.94), guideline authors. More women were coauthors in the ACC/AHA and ESC guidelines when women were chairs of guidelines. There was a persistent disparity of women among guideline authors for general cardiology and all subspecialties, except for pediatric cardiology and heart failure guidelines. The appointment of women authors as a chair was significantly low in all societies (22.4% [ACC/AHA], 16.9% [CCS], and 7.2% [ESC]; P =0.008). Conclusions There is a significant disparity in the inclusion of women on all national guideline committees, in addition to serving as a chair of cardiology guidelines. Further advocacy is required to promote equity, diversity, and inclusion in our cardiology guidelines globally.

Background Long scanning times impede cardiac magnetic resonance (CMR) clinical uptake. A "one-size-fits-all" shortened, focused protocol (eg, only function and late-gadolinium enhancement) reduces scanning time and costs, but provides less information. We developed 2 question-driven CMR and stress-CMR protocols, including tailored advanced tissue characterization, and tested their effectiveness in reducing scanning time while retaining the diagnostic performances of standard protocols. Methods and Results Eighty three consecutive patients with cardiomyopathy or ischemic heart disease underwent the tailored CMR. Each scan consisted of standard cines, late-gadolinium enhancement imaging, native T1-mapping, and extracellular volume. Fat/edema modules, right ventricle cine, and in-line quantitative perfusion mapping were performed as clinically required. Workflow was optimized to avoid gaps. Time target was <30 minutes for a CMR and <35 minutes for a stress-CMR. CMR was considered impactful when its results drove changes in diagnosis or management. Advanced tissue characterization was considered impactful when it changed the confidence level in the diagnosis. The quality of the images was assessed. A control group of 137 patients was identified among scans performed before February 2020. Compared with standard protocols, the average scan duration dropped by >30% (CMR: from 42±8 to 28±6 minutes; stress-CMR: from 50±10 to 34±6 minutes, both P <0.0001). Independent on the protocol, CMR was impactful in ≈60% cases, and advanced tissue characterization was impactful in >45% of cases. Quality grading was similar between the 2 protocols. Tailored protocols did not require additional staff. Conclusions Tailored CMR and stress-CMR protocols including advanced tissue characterization are accurate and time-effective for cardiomyopathies and ischemic heart disease.

"Sudden unexplained death (SUD) is a tragic event for both the family and community, particularly when it occurs in young individuals. Sudden cardiac death (SCD) represents the leading form of SUD and is defined as an unexpected event without an obvious extracardiac cause, occurring within 1 hour after the onset of symptoms. In children, the main causes of SCD are inherited cardiac disorders, whereas coronary artery diseases (congenital or acquired), congenital heart diseases, and myocarditis are rare. The present review examines the current state of knowledge regarding SCD in children, discussing the epidemiology, clinical causes, and prevention strategies.", (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Mutation type, location, dominant-negative IKs reduction, and possibly loss of cyclic adenosine monophosphate (cAMP)-dependent IKs stimulation via protein kinase A (PKA) influence the clinical severity of long QT syndrome type 1 (LQT1). Given the malignancy of KCNQ1-p.A341V, we assessed whether mutations neighbouring p.A341V in the S6 channel segment could also increase arrhythmic risk., Methods and Results: Clinical and genetic data were obtained from 1316 LQT1 patients [450 families, 166 unique KCNQ1 mutations, including 277 p.A341V-positive subjects, 139 patients with p.A341-neighbouring mutations (91 missense, 48 non-missense), and 900 other LQT1 subjects]. A first cardiac event represented the primary endpoint. S6 segment missense variant characteristics, particularly cAMP stimulation responses, were analysed by cellular electrophysiology. p.A341-neighbouring mutation carriers had a QTc shorter than p.A341V carriers (477 ± 33 vs. 490 ± 44 ms) but longer than the remaining LQT1 patient population (467 ± 41 ms) (P < 0.05 for both). Similarly, the frequency of symptomatic subjects in the p.A341-neighbouring subgroup was intermediate between the other two groups (43% vs. 73% vs. 20%; P < 0.001). These differences in clinical severity can be explained, for p.A341V vs. p.A341-neighbouring mutations, by the p.A341V-specific impairment of IKs regulation. The differences between the p.A341-neighbouring subgroup and the rest of LQT1 mutations may be explained by the functional importance of the S6 segment for channel activation., Conclusion: KCNQ1 S6 segment mutations surrounding p.A341 increase arrhythmic risk. p.A341V-specific loss of PKA-dependent IKs enhancement correlates with its phenotypic severity. Cellular studies providing further insights into IKs-channel regulation and knowledge of structure-function relationships could improve risk stratification. These findings impact on clinical management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The number of female athletes taking part in elite and amateur sport is ever increasing. In contrast with male athletes, few studies have focused on cardiovascular adaptations to exercise in women, the effects of lifelong exercise on heart muscle and electrical tissue, the risk of exerciserelated sudden cardiac death and the management of cardiovascular disease. Women have a lower prevalence of large QRS complexes, repolarisation changes including inferior and lateral T-wave inversion, and cardiac dimensions exceeding predicted limits compared with men. The risk of exercise-related sudden cardiac death is significantly lower in women than men. Also, women who have engaged in lifelong exercise do not have a higher prevalence of AF, coronary artery calcification or myocardial fibrosis than their sedentary counterparts. Apart from providing an overview of the existing literature relating to cardiac adaptations, this review explores possible reasons for the sex differences and focuses on the management of cardiovascular disorders that affect female athletes., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2021, Radcliffe Cardiology.)

Aims: Systematic pre-participation screening of subjects practicing sports activity has the potential to identify athletes at risk of sudden cardiac death. However, limited evidence are present concerning the yield of echocardiography as a second-line exam in athletes with abnormal pre-participation screening., Methods: Consecutive athletes were screened (2011-2017) in a community-based sports medicine center in Tuscany, with familial history, physical examination and ECG. Patients with abnormal/>1 borderline ECG findings, symptoms/signs of cardiovascular diseases, cardiovascular risk factors or family history of juvenile/genetic cardiac disease underwent echocardiography., Results: A total of 30109 athletes (age 21 [15;31]) were evaluated. Of these, 6234 (21%) were aged 8-11 years, 18309 (61%) 12-18 years, 4442 (15%) 19-35 years, 1124 (4%) >35 years. A total of 2569 (9%) athletes were addressed to echocardiography. Referral rates increased significantly with age (5% in preadolescents to 38% in master athletes, P< 0.01). Subclinical heart diseases were found in 290/30109 (0.8%) and were common >35 years (135/1124, 11%), but rare at 19-35 years (91/4442, 2%), very rare <18 years (64/24 543, 0.2%; P< 0.01). Seventy-four (0.3%) athletes were disqualified because of the structural alterations identified, 29 (0.1%) with cardiac structural diseases at risk for sudden death., Conclusions: Italian community-based pre-participation screening showed an age-dependent yield, with a three-fold increase in referral in athletes >35 years. Subclinical structural abnormalities potentially predisposing to sudden death were rare (0.01%), mostly in post-pubertal and senior athletes. Age-specific pre-participation screening protocols may help optimize resources and improve specificity., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

QT interval prolongation is a marker of increased risk for life-threatening arrhythmias, and needs to be promptly recognized. Many effective drugs, however, prolong QTc (QT interval corrected for heart rate) in genetically predisposed subjects. The possibility of remote monitoring and QTc measurement for up to 2 weeks, continuously providing physicians with real time data, allows life-saving interventions or changes in drug therapy. This applies especially to patients with the long QT syndrome and to those taking drugs blocking the IKr current and prolonging the QT interval. Patch monitors recording ECG traces continuously are available and contribute to effective arrhythmic prevention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose of Review: This review aims to assess the global impact of the COVID-19 pandemic on the cardiovascular diseases (CVDs), trying to assess the possible future trajectory of the CVDs and their management., Recent Findings: The COVID-19 pandemic has had a deleterious impact on the CV risk factors, with an increase in both sedentary and unhealthy food habits. The fear of contagion has decreased the access to the emergency systems with an increase in out-of-hospital-cardiac-arrests and late presentation of acute myocardial infarctions. The closure of the non-urgent services has delayed cardiac rehabilitation programmes and chronic clinical care. As a result of the COVID-19 pandemic impact on the population habits and on the management of CVDs, we will probably face an increase in CVD and heart failure cases. It is crucial to use all the non-traditional approaches, such as telemonitoring systems, in order to overcome the difficulties raised by the pandemic., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The proliferation of genetic profiling has revealed many associations between genetic variations and disease. However, large-scale phenotyping efforts in largely healthy populations, coupled with DNA sequencing, suggest variants currently annotated as pathogenic are more common in healthy populations than previously thought. In addition, novel and rare variants are frequently observed in genes associated with disease both in healthy individuals and those under suspicion of disease. This raises the question of whether these variants can be useful predictors of disease. To answer this question, we assessed the degree to which the presence of a variant in the cardiac potassium channel gene KCNH2 was diagnostically predictive for the autosomal dominant long QT syndrome., Methods: We estimated the probability of a long QT diagnosis given the presence of each KCNH2 variant using Bayesian methods that incorporated variant features such as changes in variant function, protein structure, and in silico predictions. We call this estimate the posttest probability of disease. Our method was applied to over 4000 individuals heterozygous for 871 missense or in-frame insertion/deletion variants in KCNH2 and validated against a separate international cohort of 933 individuals heterozygous for 266 missense or in-frame insertion/deletion variants., Results: Our method was well-calibrated for the observed fraction of heterozygotes diagnosed with long QT syndrome. Heuristically, we found that the innate diagnostic information one learns about a variant from 3-dimensional variant location, in vitro functional data, and in silico predictors is equivalent to the diagnostic information one learns about that same variant by clinically phenotyping 10 heterozygotes. Most importantly, these data can be obtained in the absence of any clinical observations., Conclusions: We show how variant-specific features can inform a prior probability of disease for rare variants even in the absence of clinically phenotyped heterozygotes.

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Cardiac magnetic resonance (CMR) has emerged as new mainstream technique for the evaluation of patients with cardiac diseases, providing unique information to support clinical decision-making. This document has been developed by a joined group of experts of the Italian Society of Cardiology and Italian society of Radiology and aims to produce an updated consensus statement about the current state of technology and clinical applications of CMR. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac radiology. Part 1 of the document will cover ischemic heart disease, congenital heart disease, cardio-oncology, cardiac masses and heart transplant.

Objectives: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS)., Background: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence., Methods: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation., Results: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country., Conclusions: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription., Competing Interests: Funding Support and Author Disclosures Dr. Lambiase is supported by the Stephen Lyness Memorial Fund, UCLH Biomedicine National Institutes of Health Research, Barts Biomedical Research Centre; and has obtained research grants and speaker fees from Medtronic, Abbott, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper belongs to a series of recommendation documents for participation in leisure-time physical activity and competitive sports by the European Association of Preventive Cardiology (EAPC). Together with an accompanying paper on supraventricular arrhythmias, this second text deals specifically with those participants in whom some form of ventricular rhythm disorder is documented, who are diagnosed with an inherited arrhythmogenic condition, and/or who have an implanted pacemaker or cardioverter defibrillator. A companion text on recommendations in athletes with supraventricular arrhythmias is published in the European Journal of Preventive Cardiology. Since both texts focus on arrhythmias, they are the result of a collaboration between EAPC and the European Heart Rhythm Association (EHRA). The documents provide a framework for evaluating eligibility to perform sports, based on three elements, i.e. the prognostic risk of the arrhythmias when performing sports, the symptomatic impact of arrhythmias while performing sports, and the potential progression of underlying structural problems as the result of sports., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate., Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants., Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10 -18 ) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10 -13 ). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency., Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Background: The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects who, over time, resulted as not affected. These individuals were all actively practicing sports-an observation that helped in the design of our study., Methods: We focused on subjects referred to our center by sports medicine doctors on suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening., Results: There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases, or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc, 482±35 ms). Genetic testing was negative in 78 subjects, but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc, 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms [ P <0.001]; their Schwartz score went from 3.0 to 0.06) after detraining. They were considered not affected by congenital LQTS and are henceforth referred to as "cases." Furthermore, among them, those who resumed similarly heavy physical training showed reappearance of the repolarization abnormalities., Conclusion: It is not uncommon to suspect LQTS among individuals actively practicing sports based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG after detraining, but the abnormalities tend to recur with resumption of training. These individuals are not affected by congenital LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.