Sudden cardiac arrest and death in the young is a critical public health issue. It occurs in children of any age, sex, racial or ethnic demographic, or socioeconomic status. Importantly, it can affect any individual-athlete and nonathlete alike. Prevention of sudden death in the young is of high importance not only because of the loss of a young life but also because of the substantial impact to families and to society at large. This White Paper summarizes the proceedings of a third national Think Tank on prevention of sudden cardiac death in the young. The Think Tank, which convened on January 11 to 12, 2024 at Duke University in Durham, NC, was organized and conducted by the Cardiac Safety Research Consortium in collaboration with a broad panel of US and international stakeholders including representatives from the United States Food and Drug Administration, medicine, academia, industry, the military, parents and sudden cardiac arrest/death prevention advocates, and the public. Primary and secondary prevention of sudden cardiac death in youth were discussed in depth with a goal of developing consensus on uniform approaches which could be applied nationally.

We report the case of a professional soccer athlete who died suddenly due to early arrhythmogenic cardiomyopathy that was not diagnosed at the time of preparticipation screening. Exercise testing had repeatedly shown effort-induced premature ventricular beats with normal echocardiography, a finding that was considered reassuring. However, there is emerging evidence that cardiac diseases characterized by focal ventricular scarring may not cause wall motion abnormalities and can be revealed only by tissue characterization with cardiac magnetic resonance. Modern interpretation of premature ventricular beats features is essential to select athletes who should undergo advanced cardiac imaging investigations to achieve a correct diagnosis and sport eligibility.

To evaluate the psychological reactions, perceptions and opinions of cardiovascular preparticipation screening (PPS) among young competitive athletes.

This convergent parallel mixed-methods study recruited 222 athletes (mean age: 18.7 years) who underwent PPS at a Canadian university. All athletes completed a cardiovascular history questionnaire, and a subgroup (n=165) additionally obtained an ECG and physical exam. On registering for PPS, athletes completed a psychological impact survey. Survey items were measured on a 5-point scale, ranging from -2 (strongly disagree) to 2 (strongly agree) and reported as means. After completing PPS, 18 athletes participated in focus groups or interviews to explore screening experiences. Qualitative data were analysed using reflexive thematic analysis, following an inductive and critical realist approach.

Athletes reported minimal symptoms of anxiety (-1.29), stress (-1.41) or worry (-1.12) concerning their participation in PPS and agreed that screening was beneficial for their safety (1.25). Psychological symptoms were higher in athletes who reported cardiovascular symptoms or a family history than those who did not. Athletes required to undergo an ECG and physical exam were less anxious, stressed and worried about PPS but more interested in learning about their results than those screened with only a history questionnaire. Three themes described athletes' responses to PPS: (1) importance of communication and service navigation; (2) distress surrounding the uncertainty of results and (3) screening as a non-disruptive and essential part of 'being an athlete'.

The PPS process does not lead to excessive distress among young competitive athletes before, during or after screening. Athletes identified solutions to enhance the PPS experience, including tailored educational resources and an integrated support system to manage psychological symptoms.

Sudden cardiac death is the leading medical cause of death among football players. Determining the optimal cardiac screening, the use of carefully selected medical assessments to detect underlying cardiovascular conditions associated with sudden cardiac arrest/death, is a desired objective of the Fédération Internationale de Football Association (FIFA) for football players of all ages. To date, cardiac screening recommendations in football have primarily focused on adult competitive players. Acknowledging its responsibility for player health worldwide, FIFA convened an international working group of cardiology and sports medicine experts to develop cardiac screening recommendations for youth football players. This group performed structured literature reviews and ultimately congregated in January of 2024, when recommendations were presented, scrutinised and judged using a systematic process. The final FIFA recommendations for youth cardiac screening include personal medical history, family medical history, focused physical examination and resting 12-lead electrocardiography. This document provides detailed rationale and clinical recommendations for youth cardiac screening and emphasises the importance of emergency action planning.

Premature deaths of bodybuilders have raised questions about the safety and associated risks of this discipline. The main objective of this study was to analyse mortality risk in a large international population of bodybuilders.

Male athletes who performed International Federation of Bodybuilding and Fitness (IFBB) competitions between 2005 and 2020 were identified and classified according to age, division and level. A standardized web-search, tailored to detect deaths, was performed for each athlete using specific keywords, with follow-up through July 2023. Mortality rates have been calculated both as the overall incidence rate during the monitored period as well as the annual incidence rate of those who participated in at least one competition within the previous year, i.e. currently competing athletes.

A total of 20 286 athletes competing in 730 IFBB events were identified with an average follow-up of 8.1 ± 3.8 years (i.e. 190 211 athlete-years of surveillance). During the study period, 121 deaths were identified: 73 were considered sudden deaths, of which 46 were classified as sudden cardiac deaths (SCD), including 11 currently competing athletes (mean age 34.7 ± 6.1 years). The incidence of SCD in currently competing athletes was 32.83 cases per 100 000 athlete-years. Available autopsies of SCD cases consistently showed cardiomegaly and ventricular hypertrophy. Professional bodybuilders had a higher risk of SCD than amateurs (HR 5.23 [3.58-7.64]).

The results of this study should alert the bodybuilding and medical communities to the need for improved preventive measures to promote safer sports participation.

In 2021, the American Academy of Pediatrics (AAP) recommended universal, history-based sudden cardiac death risk screening, representing an expansion from history- and exam-based screening for sports preparticipation. We studied the implementation of universal cardiac risk screening within a large pediatric primary care network to better understand optimal workflow design, screening positivity rate, and potential system-based effects that may arise from expanded screening.

We adapted the AAP guidelines to a three-question screener implemented into the electronic health record as a patient portal questionnaire with a back-up paper-based workflow. A non-interruptive alert provided clinical decision support. Screening positivity rates and rates of follow-up actions were measured. Screening rates were compared across patient demographics using a multivariable model.

Between March 1, 2024, and February 28, 2025, of 72,037 eligible patients, 41,433 (58%) were screened. Of these, 3,463 (8.4%) had a clinically actionable positive screen. Follow-up evaluation was ordered in 31% of cases. A multivariable model demonstrated that inactive patient portal status, teenage patient age, patient race of "Unknown," and public insurance were associated with lower screening rates.

Implementing universal history-based sudden cardiac death risk screening in a pediatric primary care network exhibited an 8.4% positivity rate after clinician review, representing a large potential burden of cardiology referrals. Over half of eligible patients were screened, and follow-up evaluation was ordered in a minority of positive cases, signaling a gap in adoption/adherence. This implementation was associated with lower screening rates in certain disadvantaged populations.

Olympic athletes represent a special subset of the athletic population and deserve a specialized medical approach. In view of the 2024 Paris Olympic Games, we developed and implemented a comprehensive medical protocol including (other than the standard screening with ECG, physical and history) cardiopulmonary exercise test, echocardiography and full blood and urine tests.

Our aim was to assess the prevalence and type of cardiovascular abnormalities in athletes candidate to Paris 2024 Olympic Games, after implementation of this Olympic medical program.

We enrolled 772 elite athletes, who underwent a comprehensive, multidisciplinary evaluation, including full panel of blood and urine tests, electrocardiography, trans-thoracic echocardiography (TTE) and a cardiopulmonary exercise test (CPET).

Of the 772 elite athletes, 363 (47%) were female. A substantial subset of 145 athletes (18.8%) showed one or more abnormalities. Specifically, either abnormal basal ECG findings (n = 26, 17.9%), abnormal TTE results (n = 45, 31%), high blood pressure (n = 2, 1.4%) or exercise induced arrhythmias (n = 49, 33.8%) were detected. 10 athletes (6.9%) showed both abnormal ECGs and exercise induced arrhythmias, and 13 athletes (9%) showed both ECG and echocardiographic abnormal findings. After further and more detailed investigations, of the 145 athletes showing cardiovascular abnormalities at the initial screening, in 4 of them were cardiac conditions implying potential risk of sudden cardiac death were identified and therefore they were withdrawn from competitive sport. Full blood test analysis identified metabolic abnormalities in 200 subjects. Of these, 165 (21%) showed hypercholesterolemia.

Olympic athletes, despite the highest level of physical performance, are not exempt from cardiovascular and metabolic diseases, including a small proportion of cardiac conditions at risk of SCD. More advanced diagnostic tools, including CPET, echocardiography and full blood tests, implemented in our protocol, were required to identify hidden cardiovascular abnormalities that could have jeopardized athlete's health and performance.

Fibro-fatty replacement of the myocardium plays a key role in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and may be associated with progressive heart failure (HF). We aimed to investigate the characteristic of the fibro-fatty tissues of ACM patients and the plasma chemokines levels according to HF burden.

The expression level of markers for brown, beige, and white fat of fibro-fatty tissues was determined using a quantitative real-time polymerase chain reaction. Lipidomics analysis of fibro-fatty tissues (n = 10 for normal control [NC]; n = 24 for ACM patients) was conducted using LC-MS. Single-cell RNA sequencing (n = 2 for NC; n = 6 for ACM patients) was used to compare the immune environment in the myocardium. Immunostaining and enzyme-linked immunosorbent assay were used to examine the expression of CCL3 in the myocardium and plasma samples, respectively.

The expression level of beige (TBX1 and TMEM26) and brown (TNFRSF9) fat markers were higher in the fibro-fatty tissues of ACM patients compared to NC. The fibro-fatty tissues revealed a significant increased level of saturated triglycerides (TGs) in ACM patients compared with NC. Single-cell RNA sequencing revealed the obvious accumulation of proinflammatory macrophages and a high expression level of proinflammatory markers in the myocardium of ACM patients compared to NC. The expression of CCL3 in the fibro-fatty tissues was positively correlated with HF progression in patients with ACM. Plasma CCL3 levels were significantly higher in patients with ACM compared to healthy volunteer. A total of 102 patients with ACM have been followed for a median of 7.8 years, indicating that plasma CCL3 levels could successfully predict the incidence of HF and heart transplantation (HTx)/death in patients with ACM (hazard ratio = 3.122 [95% confidence interval, 1.556-6.264]). The ROC curve analysis revealed the AUC value reached 0.814 for HF and 0.756 for HTx/death.

The increased level of saturated TGs and CCL3 in the fibro-fatty tissues might promote HF progression in ACM patients. Plasma CCL3 levels are useful for predicting HF-related adverse events in patients with ACM, but requiring further validation in larger and independent cohorts.

Medical clearance is often recommended for athletes prior to endurance exercise. The primary aim was to determine the percentage (%) of race entrants that sought medical clearance prior to participation in endurance running events, describe the diagnostic modalities used by doctors to assess entrants seeking medical clearance, and the clearance advice given. Secondary aims were to investigate the factors associated with seeking and outcome of clearance.

All consenting race entrants who completed an online screening questionnaire during registration to participate in the 21.1 km or 56 km Two Oceans marathon races from 2013-2015 (N.=60,609) were included. Runners were stratified into four risk categories: low risk (LR), intermediate risk (IR), high risk (HR) and very high risk (VHR). Runners were asked if they consulted with a medical doctor to obtain medical clearance. Follow-up questions enquired about what the doctor did when they sought medical clearance and what advice the doctor gave as an outcome of the medical clearance consultation. Prevalence (%, 95% CI) and Prevalence Ratios (PRs) are reported.

Over the 3-year period, 14.8% of entrants sought medical clearance. For clearance, doctors used history only (9.9%), history and physical examination (36.7%) and history, physical examination, and special investigations (53.0%). Most entrants seeking medical clearance were fully cleared to race (87.7% in 21.1 km and 85.9% in 56 km) (P=0.0156). Factors associated with seeking medical clearance include longer race distance, older age and a higher risk category (P<0.0001).

The methods doctors use when conducting medical clearance consultations vary greatly. Further research is suggested to develop a protocol that doctors can use for medical consultations.

Out-of-hospital cardiac arrest incidence in apparently healthy adults younger than 40 years ranges from 4 to 14 per 100 000 person-years worldwide. Of an estimated 350 000 to 450 000 total annual out-of-hospital cardiac arrests in the US, approximately 10% survive.

Among young adults who have had cardiac arrest outside of a hospital, approximately 60% die before reaching a hospital (presumed sudden cardiac death), approximately 40% survive to hospitalization (resuscitated sudden cardiac arrest), and 9% to 16% survive to hospital discharge (sudden cardiac arrest survivor), of whom approximately 90% have a good neurological status (Cerebral Performance Category 1 or 2). Autopsy-based studies demonstrate that 55% to 69% of young adults with presumed sudden cardiac death have underlying cardiac causes, including sudden arrhythmic death syndrome (normal heart by autopsy, most common in athletes) and structural heart disease such as coronary artery disease. Among young adults, noncardiac causes of cardiac arrest outside of a hospital may include drug overdose, pulmonary embolism, subarachnoid hemorrhage, seizure, anaphylaxis, and infection. More than half of young adults with presumed sudden cardiac death had identifiable cardiovascular risk factors such as hypertension and diabetes. Genetic cardiac disease such as long QT syndrome or dilated cardiomyopathy may be found in 2% to 22% of young adult survivors of cardiac arrest outside of the hospital, which is a lower yield than for nonsurvivors (13%-34%) with autopsy-confirmed sudden cardiac death. Persons resuscitated from sudden cardiac arrest should undergo evaluation with a basic metabolic profile and serum troponin; urine toxicology test; electrocardiogram; chest x-ray; head-to-pelvis computed tomography; and bedside ultrasound to assess for pericardial tamponade, aortic dissection, or hemorrhage. Underlying reversible causes, such as ST elevation myocardial infarction, coronary anomaly, and illicit drug or medication overdose (including QT-prolonging medicines) should be treated. If an initial evaluation does not reveal the cause of an out-of-hospital cardiac arrest, transthoracic echocardiography should be performed to screen for structural heart disease (eg, unsuspected cardiomyopathy) or valvular disease (eg, mitral valve prolapse) that can precipitate sudden cardiac death. Defibrillator implant is indicated for young adult sudden cardiac arrest survivors with nonreversible cardiac causes including structural heart disease and arrhythmia syndromes.

Cardiac arrest in apparently healthy adults younger than 40 years may be due to inherited or acquired cardiac disease or noncardiac causes. Among young adults who have had cardiac arrest outside of a hospital, only 9% to 16% survive to hospital discharge. Sudden cardiac arrest survivors require comprehensive evaluation for underlying causes of cardiac arrest and cardiac defibrillator should be implanted in those with nonreversible cardiac causes of out-of-hospital cardiac arrest.

Arrhythmogenic cardiomyopathy (AC) is a familial cardiac disease, mainly caused by mutations in desmosomal genes, which accounts for most cases of stress-related arrhythmic sudden death, in young and athletes. AC hearts display fibro-fatty lesions that generate the arrhythmic substrate and cause contractile dysfunction. A correlation between physical/emotional stresses and arrhythmias supports the involvement of sympathetic neurons (SNs) in the disease, but this has not been confirmed previously. Here, we combined molecular, in vitro and ex vivo analyses to determine the role of AC-linked DSG2 downregulation on SN biology and assess cardiac sympathetic innervation in desmoglein-2 mutant (Dsg2mut/mut) mice. Molecular assays showed that SNs express DSG2, implying that DSG2-mutation carriers would harbour the mutant protein in SNs. Confocal immunofluorescence of heart sections and 3-D reconstruction of SN network in clarified heart blocks revealed significant changes in the physiologialc SN topology, with massive hyperinnervation of the intact subepicardial layers and heterogeneous distribution of neurons in fibrotic areas. Cardiac SNs isolated from Dsg2mut/mut neonatal mice, prior to the establishment of cardiac innervation, show alterations in axonal sprouting, process development and distribution of varicosities. Consistently, virus-assisted DSG2 downregulation replicated, in PC12-derived SNs, the phenotypic alterations displayed by Dsg2mut/mut primary neurons, corroborating that AC-linked Dsg2 variants may affect SNs. Our results reveal that altered sympathetic innervation is an unrecognized feature of AC hearts, which may result from the combination of cell-autonomous and context-dependent factors implicated in myocardial remodelling. Our results favour the concept that AC is a disease of multiple cell types also hitting cardiac SNs. KEY POINTS: Arrhythmogenic cardiomyopathy is a genetically determined cardiac disease, which accounts for most cases of stress-related arrhythmic sudden death. Arrhythmogenic cardiomyopathy linked to mutations in desmoglein-2 (DSG2) is frequent and leads to a left-dominant form of the disease. Arrhythmogenic cardiomyopathy has been approached thus far as a disease of cardiomyocytes, but we here unveil that DSG2 is expressed, in addition to cardiomyocytes, by cardiac and extracardiac sympathetic neurons, although not organized into desmosomes. AC-linked DSG2 downregulation primarily affect sympathetic neurons, resulting in the significant increase in cardiac innervation density, accompanied by alterations in sympathetic neuron distribution. Our data supports the notion that AC develops with the contribution of several 'desmosomal protein-carrying' cell types and systems.

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital anomaly with a large spectrum of anatomical variations. Selective engagement of an AAOCA can present challenges during cardiac catheterization. A comprehensive understanding of the characteristics of major AAOCA can effectively assist operators for selecting and maneuvering catheters. This review outlines the recommended catheter manipulations based on the site of ectopic coronary origin. Identifying the initial course (prepulmonic, subpulmonic, interarterial or retroaortic course) is crucial for classifying each AAOCA. Besides invasive coronary angiography, coronary computed tomography angiography is frequently utilized to enhance the diagnostic assessment. Cardiac catheterization enables the use of intracoronary imaging and physiologic tools for accurately assessing the significance of AAOCA identified as at risk, mainly the anomalies associated with an interarterial course. Intravascular ultrasound is recognized as the gold standard for analyzing AAOCA with interarterial course. Optical tomography coherence imaging can be interesting to evaluate the rare AAOCA with a subpulmonic course, which are associated with ischemic symptoms or myocardial ischemia. Invasive physiological indices using pressure wires can be employed, with the caveat that their threshold values remain uncertain. Decision-making can be challenging for patients with AAOCA. Both non-invasive and invasive imaging tools are essential to support the final choice.

Although many studies have demonstrated a lower incidence of sudden cardiac arrest or death (SCA/D) in female athletes than in male, there is limited understanding of the specific underlying causes.

This systematic review aimed to assess the disparities in SCA/D incidence between male and female competitive athletes and explore the associated etiologies.

A comprehensive search was conducted for retrospective and prospective studies examining SCA/D incidence in male and female athletes. Incidence and incidence rate ratios (IRRs) according to sex were evaluated.

Among the 16 studies analyzed, 1797 cases of SCA/D were observed; 1578 occurred in males (87.81%). Ages ranged from adolescent to adult. The incidence was 1.42/100,000 athlete-years (AY) in males (95% CI 0.97-2.09), and 0.32/100,000 AY in females (95% CI 0.17-0.59), resulting in an IRR of 5.55. When considering athletes aged ≤ 35 years, the incidence was 1.46/100,000 AY in males (95% CI 0.91-2.34) and 0.30/100,000 AY in females (95% CI 0.14-0.66), with an IRR of 5.47. The IRR was 5.13 (95% CI 3.94-6.67) for the most recent studies with athletes enrolled only after the year 2000, versus 6.02 (95% CI 4.59-7.90) for the remaining studies covering all observed years. Hypertrophic cardiomyopathy (HCM) was the predominant cause among males (45.12%), while congenital coronary anomalies were more prevalent in females (33.04%).

The incidence of SCA/D in females was approximately 6 times lower than in males, with sex differences also in the leading causes of SCA/D. Understanding these discrepancies could lead to targeted strategies for the prevention of SCD in athletes.

(PROSPERO 2023 CRD42023432022)/05.07.2023.

Sports cardiologists specialize in the care of competitive athletes and highly active people by detecting and managing cardiovascular diseases that can impact sports participation and counseling on return to sports after cardiovascular events. Preparticipation evaluation of athletes includes history, physical examination, and electrocardiography (ECG), with exercise ECG added when screening master athletes. If the findings are abnormal or inconclusive, echocardiography is used for further evaluation. Further imaging with MRI, CT, or stress test is performed for establishing a diagnosis when echocardiography is indeterminate or discordant with clinical features and for risk stratification if echocardiography provides a definitive diagnosis. MRI can help distinguish athlete's heart from similar-appearing pathologic entities when echocardiography is inconclusive. Athlete's heart can manifest as left ventricular hypertrophy (LVH), left ventricle (LV) dilatation, prominent LV trabeculations, and right ventricular (RV) dilatation. Adaptive LVH in athletes is concentric and typically measures less than 16 mm, which distinguishes it from pathologic LV thickening of hypertrophic cardiomyopathy, hypertension, valvular disease, and infiltrative cardiomyopathies. Adaptive LV dilatation with normal or mildly reduced ejection fraction can be seen in endurance athletes. LV ejection fraction greater than 40%, augmentation of LV ejection fraction with exercise, and normal or supranormal diastolic function distinguishes it from dilated cardiomyopathy. Physiologic RV dilatation in athletes is distinguished from arrhythmogenic cardiomyopathy (RV type) by global involvement and absence of major regional wall motion abnormalities or late gadolinium enhancement. MRI is also useful in diagnosis and risk stratification of athletes with cardiovascular symptoms and after major cardiovascular events such as arrhythmias, myocardial infarction, and resuscitated sudden cardiac death or arrest. CT angiography provides accurate evaluation of coronary artery anomalies and coronary artery disease. ©RSNA, 2025 Supplemental material is available for this article.

While the exacerbating effect of physical exercise and its correlation with arrhythmic outcomes have been demonstrated for Arrhythmogenic Right Ventricular Cardiomyopathy, the impact of physical exercise on other forms of cardiomyopathies is poorly characterized. This study aimed to investigate the relationship between lifelong exercise intensity and the development of cardiac manifestations in subjects carrying a Likely Pathogenic (LP) or Pathogenic (P) truncating variant of titin (TTNtv).

TTNtv carriers - patients and family members - were interviewed regarding their exercise habits from birth until diagnosis (type of activity, hours/week, weeks/months, months/years, and number of years of exercise). Those engaging in ≥4 hours of vigorous exercise per week (equivalent to ≥1440 METs×minutes/week) for a minimum of 6 years were classified as Athletes. All others were classified as Non-athletes.The correlation between vigorous physical activity and the development of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction below 45% (LVEF <45%), was explored. Additionally, secondary endpoints included the occurrence of life-threatening ventricular arrhythmias (LTA - i.e., aborted cardiac arrest due to hyperkinetic arrhythmias, documented sustained ventricular tachycardia - SVT -, or appropriate implantable cardioverter-defibrillator therapy), non-LTA ventricular arrhythmias (i.e., >1000 premature ventricular complexes/24h and/or non-sustained ventricular tachycardia - NSVT), and the development of atrial fibrillation and/or atrial flutter (AF/AFL) during follow-up.

Among the 117 subjects (73% male, median age 45 - IQR 35-57 years), 38 (32%) were Athletes. Vigorous exercise was not associated with the development of LVEF <45% (adjusted OR 0.663, 95%CI 0.261-1.685, p 0.388), nor with the occurrence of LTA (p = 0.607), non-LTA (p = 0.648), and supraventricular arrhythmias (p = 0.701). Comparable results were obtained when considering the total amount of METs x hours/life burned by subjects as a continuous variable.

In carriers of TTNtv, vigorous physical activity was not associated with LVSD and LTA development.

Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1-35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD).

All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed.

During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42-4.20) annually, corresponding to a 49% (95% CI, 38.7-57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized -7.03% [95% CI, -8.57 to -5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized -0.09% [95% CI, -1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% (P<0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46-12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51-2.60]).

SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies.

Transverse aortic constriction (TAC) is one of the experimental mouse models that are designed to investigate cardiac hypertrophy and heart failure. Most of the studies with this model are devoted to the stage of developed heart failure. However, several studies of the early stages (hypertrophy after 1 week of TAC) of this disease found significant changes in the β-adrenergic system, electrical activity, and Ca2+ dynamics in mouse ventricular myocytes. To provide a quantitative description of cardiac hypertrophy, we developed a new compartmentalized mathematical model of hypertrophic mouse ventricular myocytes for the early stage after the TAC procedure. The model described the changes in cell geometry, action potentials, [Ca2+]i transients, and β1- and β2-adrenergic signaling systems. We also showed that the hypertrophic myocytes demonstrated early afterdepolarizations (EADs) upon stimulation with isoproterenol at relatively long stimulation periods. Simulation of the hypertrophic myocyte activities revealed that the synergistic effects of the late Na+ current, the L-type Ca2+ current, and the T-type Ca2+ current were responsible for the initiation of EADs. The mechanisms of EAD and its suppression were investigated and sensitivity analysis was performed. Simulation results obtained with the hypertrophic cell model were compared to those from the normal ventricular myocytes. The developed mathematical model can be used for the explanation of the existing experimental data, for the development of the models for other hypertrophic phenotypes, and to make experimentally testable predictions of a hypertrophic myocyte's behavior.

The first part of this Inter-Society Document describes the mechanisms involved in the development of cardiovascular diseases, particularly arterial hypertension, in adults and the elderly. It will also examine how consistent physical exercise during adolescence and adulthood can help maintain blood pressure levels and prevent progression to symptomatic heart failure. The discussion will include experimental and clinical evidence on the use of specific exercise programs for preventing and controlling cardiovascular diseases in adults and the elderly. In the second part, the clinical relevance of cardiac-specific biomarkers in assessing cardiovascular risk in the general adult population will be examined, with a focus on individuals engaged in sports activities. This section will review recent studies that suggest a significant role of biomarkers in assessing cardiovascular risk, particularly the presence of cardiac damage, in athletes who participate in high-intensity sports. Finally, the document will discuss the potential of using cardiac-specific biomarkers to monitor the effectiveness of personalized physical activity programs (Adapted Physical Activity, APA). These programs are prescribed for specific situations, such as chronic diseases or physical disabilities, including cardiovascular diseases. The purposes of this Inter-Society Document are the following: 1) to discuss the close pathophysiological relationship between physical activity levels (ranging from sedentary behavior to competitive sports), age categories (from adolescence to elderly age), and the development of cardiovascular diseases; 2) to review in detail the experimental and clinical evidences supporting the role of cardiac biomarkers in identifying athletes and individuals of general population at higher cardiovascular risk; 3) to stimulate scientific societies and organizations to develop specific multicenter studies that may take into account the role of cardiac biomarkers in subjects who follow specific exercise programs in order to monitor their cardiovascular risk.

Sport practice may elevate the risk of cardiovascular events, including sudden cardiac death, in athletes with undiagnosed heart conditions. In Italy, pre-participation screening includes a resting ECG and either the Harvard Step Test (HST) or maximal exercise testing (MET), but the relative efficacy of the latter two tests for detecting arrhythmias and heart conditions remains unclear.

This study examined 511 paediatric athletes (8-18 years, 76.3% male) without known cardiovascular, renal, or endocrine diseases. All athletes underwent both HST and MET within 30 days. Absolute data and data relative to theoretical peak heart rates, arrhythmias (supraventricular and ventricular) and cardiovascular diagnoses were collected.

HST resulted in a lower peak heart rate than MET (181.1 ± 9.8 vs. 187.5 ± 8.1 bpm, p < 0.001), but led to the detection of more supraventricular (18.6% vs. 13.1%, p < 0.001) and ventricular (30.5% vs. 22.7%, p < 0.001) arrhythmias, clustering during recovery (p = 0.014). This pattern was significant in males but not females. Among athletes diagnosed with cardiovascular diseases (22.3%), HST identified more ventricular arrhythmias (26.3% vs. 18.4%, p = 0.05), recovery-phase arrhythmias (20.2% vs. 14.0%, p = 0.035), and polymorphic arrhythmias (6.1% vs. 1.8%, p = 0.025).

HST detects arrhythmias more effectively than MET in young male athletes, especially during recovery. More ventricular arrhythmias were highlighted even in athletes with cardiovascular conditions.

Sudden cardiac death (SCD) in early adults aged 25 to 44 years represents an important and unexpected cause of death. We assessed trends in SCD-related mortality in the United States from 1999 to 2020 among early adults to determine differences by sex, ethnoracial groups, urbanization, and census region.

Mortality data were retrieved from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) data set from 1999 to 2020. Age-adjusted mortality rates were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change with relative 95% CIs. Trends in prevalence of coronary artery disease/myocardial infarction, heart failure, and stroke, which may have contributed to SCD-related mortality over the same period, were obtained from the National Health and Nutrition Examination Survey. From 1999 to 2020, 10 516 US early adults aged 25 to 44 years had SCD (7832 men and 2684 women), resulting in 3.72 deaths per 1000 population, or a mean of 478 deaths annually. The relative age-adjusted mortality rate increased linearly (average annual percentage change: +1.0% [95% CI, 0.3-1.8]), without sex differences. The age-adjusted mortality rate increase was more pronounced in Black patients, Hispanic/Latinx patients, and residents of rural areas. Higher absolute numbers of SCDs were clustered in the South (47.6%). During the same period, the prevalence of coronary artery disease/myocardial infarction, heart failure, and stroke plateaued. SCD-related mortality associated with opioids/stimulants overdose significantly increased over the entire study period.

SCD-related mortality among early adults has increased over the last 2 decades in the United States with notable racial and regional disparities.

Sudden cardiac arrest and death occur among competitive and recreational athletes across the entire spectrum of age, sex, and level of competition. These events are tragic, potentially preventable, and represent a global public health concern. Currently, the precise incidence of sudden cardiac arrest and death among all athletes is uncertain due to the lack of both mandatory case reporting and the infrastructure to process all cases that occur within the general population. Disparities in outcomes between Black and White athletes also exist without explanation. Causes of sudden cardiac arrest and death are age-dependent, with genetic heart conditions and unexplained cases (ie, normal autopsy) predominant among younger athletes, and coronary artery disease accounting for most cases among veteran Masters athletes. Determining best practices for prevention of primary sudden cardiac arrest and death, including preparticipation screening, remains controversial. However, secondary prevention grounded in an emergency action plan incontrovertibly represents a fundamental aspect of comprehensive cardiac care for all athletes.

Arrhythmogenic cardiomyopathy (ACM) is a nonischemic, familial heart disease with a high risk of sudden cardiac death (SCD) in the pediatric population and accounts for >20% of SCDs worldwide [...].

Sudden cardiac arrest (SCA) represents a major cause of premature mortality globally, with enormous impact and financial cost to victims, families, and communities. SCA prevention should be considered a health priority in Australia. National Cardiac Arrest Summits were held in June 2022 and March 2023, with inclusion from multi-faceted endeavours related to SCA prevention. It was agreed to establish a multidisciplinary Australian Sudden Cardiac Arrest Alliance (AuSCAA) working group charged with developing a national unified strategy, with clear and measurable quality indicators and standardised outcome measures, to amplify the goal of SCA prevention throughout Australia. A multi-faceted prevention strategy will include i) endeavours to progress community awareness, ii) improved fundamental mechanistic understanding, iii) implementation of best-practice resuscitation strategies for all demographics and locations, iv) secondary risk assessment directed to family members, and v) development of (near) real-time registry of cardiac arrest cases to inform areas of need and effectiveness of interventions. Together, we can and should reduce the impact of SCA in Australia.

The detection of myocardial scar tissue profoundly influences athletes care and prognostic categorization. Athletes appear to be at risk of developing fatal arrhythmias when harboring a quiescent cardiac disorder. Early identification of disease in asymptomatic individuals through preparticipation screening is means to prevent these events. We presented a male marathon runner master athlete who came at our Department of Sports Medicine for a preparticipation screening. Baseline 12-lead standard electrocardiogram was normal. A maximal cycle ergometer exercise test revealed exercise-induced premature ventricular contractions (PVCs) with uncommon morphology. Echocardiography revealed an hyperechogenic zone at mid-basal posterior segments of the left ventricle. Twenty-four-hours ECG Holter monitoring, with training session, showed some isolated polymorphic PVCs even during training session. Cardiac magnetic resonance (CMR) confirmed the presence of a non-ischemic left ventricular scar (subepicardial) into the mid-basal segment of the posterior wall. Echocardiography is a first-line, economic, and accessible diagnostic test for athletes and it can be useful, when abnormalities are detected, to indicate further investigations, such as CMR. Although non-ischemic left ventricular scarring is difficult to detect on echocardiography, this event is sometimes possible and require further investigation when observed.

Sports cardiology is an evolving field in cardiology, with several topics remaining controversial. Beyond the several well-known benefits of regular exercise practice, the occurrence of adverse clinical events during sports in apparently healthy individuals, especially sudden cardiac death, and the described long-term adverse cardiac adaptations associated to high volume of exercise, remain challenging. The early identification of athletes with increased risk is critical, but the most appropriate preparticipation screening protocols are also debatable and a more personalized evaluation, considering individual and sports-related characteristics, will potentially optimize this evaluation. As the risk of major clinical events during sports is not zero, independently of previous evaluation, ensuring the capacity for cardiopulmonary resuscitation, especially with availability of automated external defibrillators, in sports arenas, is crucial for its prevention and to improve outcomes. As in other areas of medicine, application of new digital technologies, including artificial intelligence, is promising and could improve in near future several aspects of sports cardiology. This paper aims to review the methodology of athletes' preparticipation screening, emphasizing current controversies and future challenges, in order to improve early diagnosis of conditions associated with sudden cardiac death.

Electrocardiogram modifications in athletes are common and usually reflect structural and electrical heart adaptations to regular physical training, known as the athlete's heart. However, these electrical modifications sometimes overlap with electrocardiogram findings that are characteristic of various heart diseases. A missed or incorrect diagnosis can significantly impact a young athlete's life and potentially have fatal consequences during exercise, such as sudden cardiac death, which is the leading cause of death in athletes. Therefore, it is crucial to correctly distinguish between expected exercise-related electrocardiogram changes in an athlete and several electrocardiogram abnormalities that may indicate underlying heart disease. This review aims to serve as a practical guide for cardiologists and sports clinicians, helping to define normal and physiology-induced electrocardiogram findings from those borderlines or pathological, and indicating when further investigations are necessary. Therefore, the possible athlete's electrocardiogram findings, including rhythm or myocardial adaptation, will be analyzed here, focusing mainly on the differentiation from pathological findings.

Youth and adult participation in sports continues to increase, and athletes may be diagnosed with potentially arrhythmogenic cardiac conditions. This international multidisciplinary document is intended to guide electrophysiologists, sports cardiologists, and associated health care team members in the diagnosis, treatment, and management of arrhythmic conditions in the athlete with the goal of facilitating return to sport and avoiding the harm caused by restriction. Expert, disease-specific risk assessment in the context of athlete symptoms and diagnoses is emphasized throughout the document. After appropriate risk assessment, management of arrhythmias geared toward return to play when possible is addressed. Other topics include shared decision-making and emergency action planning. The goal of this document is to provide evidence-based recommendations impacting all areas in the care of athletes with arrhythmic conditions. Areas in need of further study are also discussed.

The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood.

To investigate aetiology of SCD among different ethnicities in a large cohort of athletes.

Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes. All cases underwent detailed autopsy evaluation by expert cardiac pathologists. Clinical information was obtained from referring coroners. Most of athletes were white (n = 758; 89%). Black and Asian athletes were in number of 51 (6%) and 39 (5%), respectively. A structurally normal heart, indicative of sudden arrhythmic death syndrome (SADS) was the most common autopsy finding (n = 385; 45%), followed by myocardial diseases (n = 275; 32%), atherosclerotic coronary artery disease (CAD) (n = 58; 7%), and coronary artery anomalies (n = 29; 3%). In most of cases, death occurred during exercise (n = 737; 87%). Arrhythmogenic cardiomyopathy (ACM) was more common in black (n = 13; 25%) than in white (n = 109; 14%) and Asian (n = 3; 8%) athletes (P = 0.03 between black and white athletes; P = 0.04 between black and Asian athletes); in contrast, CAD was more common in Asians (n = 6; 15% vs. n = 51; 7% in whites vs. n = 1; 2%; in blacks, P = 0.02 between Asian and black athletes). Among white athletes, ACM was more common in individuals who died during exercise than in the ones who died at rest (P = 0.005). Such a difference was not observed in Asian and black athletes. In Asian athletes, CAD was the diagnosis at autopsy in 18% of individuals who died during exercise and in none of individuals who died at rest.

A structurally normal heart at autopsy and myocardial diseases are the most common findings in athletes who died suddenly. While ACM is more common in black athletes, atherosclerotic CAD is more common in Asian athletes, with a strong association with exercise-induced SCD. ACM appears to be a driver of exercise-induced SCD in white athletes, however this is not the case in black and Asian athletes.

Sudden cardiac death (SCD) in young individuals is often unexpected, provoking substantial emotional stress for family and friends of the deceased. Cardiac screening may identify individuals who harbour disorders linked to SCD. The feasibility and diagnostic yield of a nationwide cardiac screening programme in adolescents has never been explored.

All individuals eligible for cardiac screening (students aged 15 years) were systematically invited to enrol. Students were provided with a health questionnaire. ECGs were acquired at school. A physician led consultation was carried out on site. Participants with an abnormal screen were then referred for secondary evaluation to the nation's tertiary centre. Feasibility criteria included a) participation rate >60%, b) adherence to secondary evaluation >80%, and c) cost per individual screened equating to <€100. The diagnostic yield was also evaluated.

At the end of enrolment, 2708 students gave consent (mean 15 years, 50.4% male), equating to 67.9% of the eligible cohort. Overall, 109 participants (4.0%) were referred for further evaluation. An abnormal electrocardiogram (ECG) was the most common reason for referral (3.7%). Fifteen individuals (0.6%) were diagnosed with a cardiac condition. Nine (0.3%) had a condition linked to SCD (n = 1 Long-QT syndrome, n = 1 Hypertrophic Cardiomyopathy, n = 5 Wolff-Parkinson White, n = 2 coronary anomalies). The yield was similar in athletes and non-athletes (p = 0.324). The cost per cardiac individual screened equated to €51.15.

A nationwide systematic cardiac screening programme for adolescent athletes and non-athletes is feasible and cost-efficient, provided that responsible centres have the appropriate infrastructure.

For sporting organisations that conduct screening of athletes, there are very few consistent guidelines on the age at which to start. Our review found the total rate of sudden cardiac arrest or death is very low between the ages of 8-11 years (less than 1/100,000/year), increasing to 1-2/100,000/year in both elite athletes and community athletes aged 12-15 years and then steadily increases with age. The conditions associated with sudden cardiac death in paediatric athletes and young adult athletes are very similar with some evidence that death from coronary artery abnormalities occurs more frequently in athletes 10-14 years old. The decision when to begin a screening program involves a complex interplay between requirements and usual practices in a country, the rules of different leagues and programs, the age of entry into an elite program, the underlying risk of the population and the resources available. Given the incidence of sudden cardiac arrest or death in young people, we recommend beginning cardiac screening no earlier than 12 years (not later than 16 years). The risk increases with age, therefore, starting a program at any point after age 12 has added value. Importantly, anyone with concerning symptoms (e.g. collapse on exercise) or family history of an inherited cardiac condition should see a physician irrespective of age. Finally, no screening program can capture all abnormalities, and it is essential for organisations to implement a cardiac emergency plan including training on recognition and response to sudden cardiac arrest and prompt access to resuscitation, including defibrillators.

Sudden cardiac death is a rare but socially devastating event, especially if occurs in young people. Usually, this unexpected lethal event occurs during or just after exercise. One of the leading causes of sudden cardiac death is inherited arrhythmogenic syndromes, a group of genetic entities characterised by incomplete penetrance and variable expressivity. Exercise can be the trigger for malignant arrhythmias and even syncope in population with a genetic predisposition, being sudden cardiac death as the first symptom. Due to genetic origin, family members must be clinically assessed and genetically analysed after diagnosis or suspected diagnosis of a cardiac channelopathy. Early identification and adoption of personalised preventive measures is crucial to reduce risk of arrhythmias and avoid new lethal episodes. Despite exercise being recommended by the global population due to its beneficial effects on health, particular recommendations for these patients should be adopted considering the sport practised, level of demand, age, gender, arrhythmogenic syndrome diagnosed but also genetic diagnosis. Our review focuses on the role of genetic background in sudden cardiac death during exercise in child and young population.

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular genetic conditions. Although most patients with HCM typically do well clinically, there is a small but real incidence of sudden cardiac death. A diagnosis of HCM was previously a reason for complete exclusion in sports, particularly competitive sports.However, many of these recommendations are based on expert consensus, and much data has been published in the last decade furthering the scientific knowledge in this area, and allowing athletes who may have been previously excluded the potential to participate in strenuous activities and competitive sports.

With recent publications on participation in sports with HCM, as well as an emphasis on shared decision-making, more athletes with HCM are participating in competitive sports, even at a professional level. Even contact sports in the presence of an implantable cardioverter-defibrillator are no longer mutually exclusive in the current era.

Previous guidelines were likely overly restrictive for patients with HCM. Although there is a risk of sudden death that cannot be ignored, the potential for shared decision making as well as medical guidance are entering a new era in all aspects of medicine, particularly in sports participation.

The sudden death of a young or high-level athlete or adolescent during recreational sports is one of the events with the greatest impact on public opinion in modern society. Sudden cardiac death (SCD) is the principal medical cause of death in athletes and can be the first and last clinical presentation of underlying disease. To prevent such episodes, pre-participation screening has been introduced in many countries to guarantee cardiovascular safety during sports and has become a common target among medical sports/governing organizations. Different cardiac conditions may cause SCD, with incidence depending on definition, evaluation methods, and studied populations, and a prevalence and etiology changing according to the age of athletes, with CAD most frequent in master athletes, while coronary anomalies and non-ischemic causes prevalent in young. To detect silent underlying causes early would be of considerable clinical value. This review summarizes the pre-participation screening in athletes, the specialist agonistic suitability visit performed in Italy, the anatomical characteristics of malignant coronary anomalies, and finally, the role of coronary CT angiography in such arena. In particular, the anatomical conditions suggesting potential disqualification from sport, the post-treatment follow-up to reintegrate young athletes, the diagnostic workflow to rule-out CAD in master athletes, and their clinical management are analyzed.