Value of screening for the risk of sudden cardiac death in young competitive athletes.

AIMS: This study aimed to report the long-term findings of the Italian programme of cardiovascular preparticipation screening (PPS) in young, competitive athletes. METHODS AND RESULTS: The study assessed the diagnostic yield for diseases at risk of sudden cardiac death (SCD), the costs of serial evaluations, and the long-term outcomes of PPS in a large population of Italian children (age range, 7-18 years). The PPS was repeated annually and included medical history, physical examination, resting electrocardiogram, and stress testing; additional tests were reserved for athletes with abnormal findings. Over an 11-year study period, 22 324 consecutive children [62% males; mean age, 12 (interquartile range, 10-14) years at first screening] underwent a total of 65 397 annual evaluations (median 2.9/child). Cardiovascular diseases at risk of SCD were identified in 69 children (0.3%) and included congenital heart diseases (n = 17), channelopathies (n = 14), cardiomyopathies (n = 15), non-ischaemic left ventricular scar with ventricular arrhythmias (n = 18), and others (n = 5). At-risk cardiovascular diseases were identified over the entire age range and more frequently in children ≥12 years old (n = 63, 91%) and on repeat evaluation (n = 44, 64%). The estimated cost per diagnosis was 73 312€. During a follow-up of 7.5 ± 3.7 years, one child with normal PPS findings experienced an episode of resuscitated cardiac arrest during sports activity (event rate of 0.6/100.000 athletes/year). CONCLUSION: The PPS programme led to the identification of cardiovascular diseases at risk of SCD over the whole study age range of children and more often on repeat evaluations. Among screened children, the incidence of sport-related cardiac arrest during long-term follow-up was low.

A Comprehensive Analysis of Non-Desmosomal Rare Genetic Variants in Arrhythmogenic Cardiomyopathy: Integrating in Padua Cohort Literature-Derived Data.

Arrhythmogenic cardiomyopathy (ACM) is an inherited myocardial disease at risk of sudden death. Genetic testing impacts greatly in ACM diagnosis, but gene-disease associations have yet to be determined for the increasing number of genes included in clinical panels. Genetic variants evaluation was undertaken for the most relevant non-desmosomal disease genes. We retrospectively studied 320 unrelated Italian ACM patients, including 243 cases with predominant right-ventricular (ARVC) and 77 cases with predominant left-ventricular (ALVC) involvement, who did not carry pathogenic/likely pathogenic (P/LP) variants in desmosome-coding genes. The aim was to assess rare genetic variants in transmembrane protein 43 (TMEM43), desmin (DES), phospholamban (PLN), filamin c (FLNC), cadherin 2 (CDH2), and tight junction protein 1 (TJP1), based on current adjudication guidelines and reappraisal on reported literature data. Thirty-five rare genetic variants, including 23 (64%) P/LP, were identified in 39 patients (16/243 ARVC; 23/77 ALVC): 22 FLNC, 9 DES, 2 TMEM43, and 2 CDH2. No P/LP variants were found in PLN and TJP1 genes. Gene-based burden analysis, including P/LP variants reported in literature, showed significant enrichment for TMEM43 (3.79-fold), DES (10.31-fold), PLN (117.8-fold) and FLNC (107-fold). A non-desmosomal rare genetic variant is found in a minority of ARVC patients but in about one third of ALVC patients; as such, clinical decision-making should be driven by genes with robust evidence. More than two thirds of non-desmosomal P/LP variants occur in FLNC.

Is Congenital Muscular Mitral-Aortic Discontinuity Another Feature of Obstructive Hypertrophic Cardiomyopathy? A Pathology Validation Study.

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease at risk of sudden cardiac death and heart failure, even requiring heart transplantation. A "muscular mitral-aortic discontinuity" has been reported during surgery in the obstructive form. We aimed to validate these findings through pathological analysis of HCM heart specimens from the cardiovascular pathology tissue registry. Hearts with septal asymmetric HCM from sudden cardiac death, other causes of death, or heart transplantation were included. Sex-matched and age-matched patients without HCM served as controls. Gross and histologic analysis of the mitral valve (MV) apparatus and the mitral-aortic continuity were performed. Thirty HCM hearts (median age, 29.5 years; 15 men) and 30 controls (median age, 30.5 years; 15 men) were studied. In HCM hearts, a septal bulging was present in 80%, an endocardial fibrous plaque in 63%, a thickening of the anterior MV leaflet in 56.7%, and an anomalous insertion of papillary muscle in 10%. All cases but 1 (97%) revealed a myocardial layer overlapping the mitral-aortic fibrous continuity on the posterior side, corresponding to the left atrial myocardium. A negative correlation between the length of this myocardial layer and the age and the anterior MV leaflet length was found. The length did not differ between HCM and controls. Pathologic study of obstructive HCM hearts does not confirm the existence of a "muscular mitral-aortic discontinuity". An extension of left atrial myocardium, overlapping posteriorly the intervalvular fibrosa, is rather visible, and its length decreases with age, possibly as a consequence of left atrial remodeling. Our study highlights the fundamental role of thorough gross examination and the value of organ retention for further analysis in order to validate new surgical and imaging findings.

Cardiac magnetic resonance imaging of arrhythmogenic cardiomyopathy: evolving diagnostic perspectives.

Arrhythmogenic cardiomyopathy (ACM) is a genetically determined heart muscle disease characterized by fibro-fatty myocardial replacement, clinically associated with malignant ventricular arrhythmias and sudden cardiac death. Originally described a disease with a prevalent right ventricular (RV) involvement, subsequently two other phenotypes have been recognized, such as the left dominant and the biventricular phenotypes, for which a recent International Expert consensus document provided upgrade diagnostic criteria (the 2020 "Padua Criteria"). In this novel workup for the diagnosis of the entire spectrum of phenotypic variants of ACM, including left ventricular (LV) variants, cardiac magnetic resonance (CMR) has emerged as the cardiac imaging technique of choice, due to its capability of detailed morpho-functional and tissue characterization evaluation of both RV and LV. In this review, the key role of CMR in the diagnosis of ACM is outlined, including the supplemental value for the characterization of the disease variants. An ACM-specific CMR study protocol, as well as strengths and weaknesses of each imaging technique, is also provided. KEY POINTS: • Arrhythmogenic cardiomyopathy includes three different phenotypes: dominant right, biventricular, and dominant left. • In 2020, diagnostic criteria have been updated and cardiac magnetic resonance has emerged as the cardiac imaging technique of choice. • This aim of this review is to provide an update of the current state of art regarding the use of CMR in ACM, with a particular focus on novel diagnostic criteria, CMR protocols, and prognostic significance of CMR findings in ACM.

Ventricular arrhythmias recorded on 12-lead ambulatory electrocardiogram monitoring in healthy volunteer athletes and controls: what is common and what is not.

AIMS: Premature ventricular beats (PVBs) in athletes are often benign, but sometimes they may be a sign of an underlying disease. We evaluated the prevalence, burden, and morphology of PVBs in healthy voluntary athletes and controls with the main purpose of defining if certain PVB patterns are 'common' and 'training related' and, as such, are more likely benign. METHODS AND RESULTS: We studied 433 healthy competitive athletes [median age 27 (18-43) years, 74% males] and 261 age- and sex-matched sedentary subjects who volunteered to undergo 12-lead 24 h ambulatory electrocardiogram (ECG) monitoring (24H ECG), with a training session in athletes. Ventricular arrhythmias (VAs) were evaluated in terms of their number, complexity [i.e. couplet, triplet, or non-sustained ventricular tachycardia (NSVT)], exercise inducibility, and morphology. Eighty-six percent of athletes and controls exhibited a total of ≤10 PVBs/24 h, and >90% did not show any couplets, triplets, or runs of NSVT > 3 beats. An higher number of PVBs correlated with increasing age (P < 0.01) but not with sex and level of training. The most frequent morphologies among the 36 athletes with >50 PVBs were the infundibular (44%) and fascicular (22%) ones. In a comparison between athletes and sedentary individuals, and male and female athletes, no statistically significant differences were found in PVBs morphologies. CONCLUSION: The prevalence and complexity of VAs at 24H ECG did not differ between athletes and sedentary controls and were not related to the type and amount of sport or sex. Age was the only variable associated with an increased PVB burden. Thus, no PVB pattern in the athlete can be considered 'common' or 'training related'.

Electrocardiographic characteristics of right-bundle-branch-block premature ventricular complexes predicting absence of left ventricular scar in athletes with apparently structural normal heart.

AIMS: Left ventricular scar is an arrhythmic substrate that may be missed by echocardiography and diagnosed only by cardiac magnetic resonance (CMR), which is a time-consuming and expensive imaging modality. Premature ventricular complexes (PVCs) with a right-bundle-branch-block (RBBB) pattern are independent predictors of late gadolinium enhancement (LGE) but their positive predictive value is low. We studied which electrocardiographic features of PVCs with an RBBB pattern are associated with a higher probability of the absence of an underlying LGE. METHODS: The study included 121 athletes (36 ± 16 years; 48.8% men) with monomorphic PVCs with an RBBB configuration and normal standard clinical investigations who underwent CMR. LGE was identified in 35 patients (29%), predominantly in those with PVCs with a superior/intermediate axis (SA-IntA) compared to inferior axis (IA) (38% vs. 10%, P = 0.002). Among patients with SA-IntA morphology, the contemporary presence of qR pattern in lead aVR and V1 was exclusively found in patients without LGE at CMR (51.0% vs. 0%, P < 0.0001). Among patients with IA, the absence of LGE correlated to a narrow ectopic QRS (145 ± 16 vs. 184 ± 27 msec, P < 0.001). CONCLUSIONS: Among athletes with apparently idiopathic PVCs with a RBBB configuration, the presence of a concealed LGE at CMR was documented in 29% of cases, mostly in those with a SA-IntA. In our experience, the contemporary presence of qR pattern in lead aVR and V1 in PVCs with RBBB/SA-IntA morphology or, on the other hand, a relatively narrow QRS in PVCs with an IA, predicted absence of LGE.

Scarring/arrhythmogenic cardiomyopathy.

The designation of 'arrhythmogenic cardiomyopathy' reflects the evolving concept of a heart muscle disease affecting not only the right ventricle (ARVC) but also the left ventricle (LV), with phenotypic variants characterized by a biventricular (BIV) or predominant LV involvement (ALVC). Herein, we use the term 'scarring/arrhythmogenic cardiomyopathy (S/ACM)' to emphasize that the disease phenotype is distinctively characterized by loss of ventricular myocardium due to myocyte death with subsequent fibrous or fibro-fatty scar tissue replacement. The myocardial scarring predisposes to potentially lethal ventricular arrhythmias and underlies the impairment of systolic ventricular function. S/ACM is an 'umbrella term' which includes a variety of conditions, either genetic or acquired (mostly post-inflammatory), sharing the typical 'scarring' phenotypic features of the disease. Differential diagnoses include 'non-scarring' heart diseases leading to either RV dilatation from left-to-right shunt or LV dilatation/dysfunction from a dilated cardiomyopathy. The development of 2020 upgraded criteria ('Padua criteria') for diagnosis of S/ACM reflected the evolving clinical experience with the expanding spectrum of S/ACM phenotypes and the advances in cardiac magnetic resonance (CMR) imaging. The Padua criteria aimed to improve the diagnosis of S/ACM by incorporation of CMR myocardial tissue characterization findings. Risk stratification of S/ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other ECG or imaging parameters may have a role. Medical therapy is crucial for treatment of ventricular arrhythmias and heart failure. Implantable cardioverter defibrillator (ICD) is the only proven life-saving treatment, despite its significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice.

Implantable defibrillators in primary prevention of genetic arrhythmias. A shocking choice?

Many previously unexplained life-threatening ventricular arrhythmias and sudden cardiac deaths (SCDs) in young individuals are now recognized to be genetic in nature and are ascribed to a growing number of distinct inherited arrhythmogenic diseases. These include hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (VT), and short QT syndrome. Because of their lower frequency compared to coronary disease, risk factors for SCD are not very precise in patients with inherited arrhythmogenic diseases. As randomized studies are generally non-feasible and may even be ethically unjustifiable, especially in the presence of effective therapies, the risk assessment of malignant arrhythmic events such as SCD, cardiac arrest due to ventricular fibrillation (VF), appropriate implantable cardioverter defibrillator (ICD) interventions, or ICD therapy on fast VT/VF to guide ICD implantation is based on observational data and expert consensus. In this document, we review risk factors for SCD and indications for ICD implantation and additional therapies. What emerges is that, allowing for some important differences between cardiomyopathies and channelopathies, there is a growing and disquieting trend to create, and then use, semi-automated systems (risk scores, risk calculators, and, to some extent, even guidelines) which then dictate therapeutic choices. Their common denominator is a tendency to favour ICD implantation, sometime with reason, sometime without it. This contrasts with the time-honoured approach of selecting, among the available therapies, the best option (ICDs included) based on the clinical judgement for the specific patient and after having assessed the protection provided by optimal medical treatment.

Prevalence and clinical significance of isolated low QRS voltages in young athletes.

AIMS: Low QRS voltages (peak to peak <0.5 mV) in limb leads (LQRSV) on the athlete's electrocardiogram (ECG) may reflect an underlying cardiomyopathy, mostly arrhythmogenic cardiomyopathy (ACM) or non-ischaemic left ventricular scar (NILVS). We studied the prevalence and clinical meaning of isolated LQRSV in a large cohort of competitive athletes. METHODS AND RESULTS: The index group included 2229 Italian competitive athletes [median age 18 years (16-25), 67% males, 97% Caucasian] without major ECG abnormalities at pre-participation screening. Three control groups included Black athletes (N = 1115), general population (N = 1115), and patients with ACM or NILVS (N = 58). Echocardiogram was performed in all athletes with isolated LQRSV and cardiac magnetic resonance (CMR) in those with ventricular arrhythmias or echocardiographic abnormalities. The isolated LQRSV pattern was found in 1.1% index athletes and was associated with increasing age (median age 28 vs. 18 years; P < 0.001), elite status (71% vs. 34%; P < 0.001), body surface area, and body mass index but not with sex, type of sport, and echocardiographic left ventricular mass. The prevalence of isolated LQRSV was 0.2% in Black athletes and 0.3% in young individuals from the general population. Cardiomyopathy patients had a significantly greater prevalence of isolated LQRSV (12%) than index athletes, Black athletes, and general population. Five index athletes with isolated LQSRV and exercise-induced ventricular arrhythmias underwent CMR showing biventricular ACM in 1 and idiopathic NILVS in 1. CONCLUSIONS: Unlike cardiomyopathy patients, the ECG pattern of isolated LQRSV was rarely observed in athletes. This ECG sign should prompt clinical work-up for exclusion of an underlying cardiomyopathy.

'Hot phase' clinical presentation in arrhythmogenic cardiomyopathy.

AIMS: The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries ('hot phase'). METHODS AND RESULTS: We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the 'hot phase'. CONCLUSION: 'Hot phase' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part 2: ventricular arrhythmias, channelopathies, and implantable defibrillators.

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.

"Apical sparing" T-wave inversion in a case of mid-ventricular takotsubo syndrome.

Previous studies showed that myocardial edema correlates with dynamic T-wave inversion and QTc prolongation in a variety of acute cardiovascular diseases including takotsubo syndrome (TTS). We reported the case of a patient with "atypical" (mid-ventricular) TTS showing a unique pattern of diffuse T-wave inversion that spared only the apical precordial leads V3-V4. Cardiac magnetic resonance (CMR) showed myocardial edema involving all mid-ventricular segments but not the apex. Both ECG and CMR normalized at follow-up evaluation. This case further reinforces the theory of an association between presence and regional distribution of acute myocardial inflammation and dynamic repolarization changes.

Role of Exercise as a Modulating Factor in Arrhythmogenic Cardiomyopathy.

PURPOSE OF REVIEW: The review addresses the role of exercise in triggering ventricular arrhythmias and promoting disease progression in arrhythmogenic cardiomyopathy (AC) patients and gene-mutation carriers, the differential diagnosis between AC and athlete's heart and current recommendations on exercise activity in AC. RECENT FINDINGS: AC is an inherited heart muscle disease caused by genetically defective cell-to-cell adhesion structures (mainly desmosomes). The pathophysiological hallmark of the disease is progressive myocyte loss and replacement by fibro-fatty tissue, which creates the substrates for ventricular arrhythmias. Animal and human studies demonstrated that intense exercise, but not moderate physical activity, may increase disease penetrance, worsen the phenotype, and favor life-threatening ventricular arrhythmias. It has been proposed that in some individuals prolonged endurance sports activity may in itself cause AC (so-called exercise-induced AC). The studies agree that intense physical activity should be avoided in patients with AC and healthy gene-mutation carriers. However, low-to-moderate intensity exercise does not appear detrimental and these patients should not be entirely deprived from the many health benefits of physical activity.

Recommendations for participation in competitive sport in adolescent and adult athletes with Congenital Heart Disease (CHD): position statement of the Sports Cardiology & Exercise Section of the European Association of Preventive Cardiology (EAPC), the European Society of Cardiology (ESC) Working Group on Adult Congenital Heart Disease and the Sports Cardiology, Physical Activity and Prevention Working Group of the Association for European Paediatric and Congenital Cardiology (AEPC).

Improved clinical care has led to an increase in the number of adults with congenital heart disease (CHD) engaging in leisure time and competitive sports activities. Although the benefits of exercise in patients with CHD are well established, there is a low but appreciable risk of exercise-related complications. Published exercise recommendations for individuals with CHD are predominantly centred on anatomic lesions, hampering an individualized approach to exercise advice in this heterogeneous population. This document presents an update of the recommendations for competitive sports participation in athletes with cardiovascular disease published by the Sports Cardiology & Exercise section of the European Association of Preventive Cardiology (EAPC) in 2005. It introduces an approach which is based on the assessment of haemodynamic, electrophysiological and functional parameters, rather than anatomic lesions. The recommendations provide a comprehensive assessment algorithm which allows for patient-specific assessment and risk stratification of athletes with CHD who wish to participate in competitive sports.

Current challenges in sudden cardiac death prevention.

Ischemic heart disease and non-ischemic dilated cardiomyopathy are the most common causes of arrhythmic sudden cardiac death (SCD). Implantable cardioverter defibrillator (ICD) therapy is the only strategy that proved to be effective in preventing SCD in high-risk individuals while the role of antiarrhythmic drugs is limited to symptoms relief. Current guidelines recommend selecting candidates to ICD implantation based on etiology, symptoms of heart failure (NYHA class), and severely depressed left ventricular ejection fraction, but these parameters are neither sensitive nor specific. The review addresses the mechanisms of SCD in patients with heart failure of either ischemic or non-ischemic etiology, risk stratification, and strategies for prevention of SCD in the clinical practice (including optimization of heart failure therapy, avoidance of triggering factors, antiarrhythmic drugs, ICD therapy, early resuscitation, and public access defibrillators).

CardioMEMS, the real progress in heart failure home monitoring.

The burden of hospitalizations driven by exacerbation of acute heart failure remains unacceptably high. The associated use of hospital resources drives increasing patient, caregiver, and economic costs. Noninvasive telemedical systems investigated in randomized controlled trials have failed to demonstrate to reduce hospitalization rates probably because of the indirect (non-linear) relationship of the measured biological signals with the patient congestion status. Instead, there is increasing evidence that direct measure of intracardiac and pulmonary artery pressure can effectively guide heart failure management and reduce hospitalizations. Early studies adopting implantable hemodynamic monitors in the right heart unveiled the potential of pressure-based heart failure management, whereas subsequent investigations showed the powerful preemptive approach for heart failure exacerbations. One large randomized trial (CHAMPION) proved that a direct pulmonary pressure monitor system (CardioMEMS) substantially reduced heart failure hospitalizations in subjects randomized to active pulmonary pressure-guided management. The system monitoring safety and efficacy were also excellent. The study proved that early management in response to increased pulmonary pressure is able to provide the most effective therapeutic intervention to prevent heart failure exacerbations.

Criteria for interpretation of the athlete's ECG: A critical appraisal.

The electrocardiogram (ECG) is cheap and widely available but its use as a screening tool for early identification of athletes with a cardiac disease at risk of sudden cardiac death is controversial because of presumed low specificity. In the last decade, several efforts have been made to improve the distinction between physiological and pathological ECG findings in the athlete, leading to continuous evolution of the interpretation criteria. The most recent 2017 International criteria grouped ECG changes into three categories: normal, borderline, and abnormal. Borderline findings warrant further investigations only when two or more are present while abnormal changes should always be considered as the sign of a possible underlying disease. This review encompasses the evolution of the athlete's ECG interpretation criteria and highlights areas of uncertainty that will need to be addressed by further studies.

How to evaluate premature ventricular beats in the athlete: critical review and proposal of a diagnostic algorithm.

Although premature ventricular beats (PVBs) in young people and athletes are usually benign, they may rarely mark underlying heart disease and risk of sudden cardiac death during sport. This review addresses the prevalence, clinical meaning and diagnostic/prognostic assessment of PVBs in the athlete. The article focuses on the characteristics of PVBs, such as the morphological pattern of the ectopic QRS and the response to exercise, which accurately stratify risk. We propose an algorithm to help the sport and exercise physician manage the athlete with PVBs. We also address (1) which athletes need more indepth investigation, including cardiac MRI to exclude an underlying pathological myocardial substrate, and (2) which athletes can remain eligible to competitive sports and who needs to be excluded.

The Italian preparticipation evaluation programme: diagnostic yield, rate of disqualification and cost analysis.

INTRODUCTION: Italian law mandates that every competitive athlete must undergo annual preparticipation evaluation (PPE) to identify cardiovascular (CV) diseases that pose a risk of sudden death (SD) during sport and other conditions that may threaten the athlete's health. We investigated the diagnostic yield, rate of disqualification and costs of our PPE. METHODS: We included 5910 consecutive apparently healthy athletes (61% males, mean age 15±4 years) who underwent annual PPE performed by a sports medicine specialist. The PPE included history, physical examination, weight, height and blood pressure measurement, test of visual acuity, spirometry, urine chemistry, resting 12-lead ECG and exercise testing with ECG monitoring. In cases of abnormal findings, we carried out second-line investigations. RESULTS: During a 12-month study period, 5.326 (90.2%) athletes were cleared for competition after a normal first-line evaluation and 584 (9.8%) underwent one or more further examinations. Of those, 88 (1.5%) were diagnosed to have a CV disease (including 18 (0.3%) at-risk of SD) and 31 (0.5%) had a non-CV diagnosis. A total of 32 (0.5%) athletes were temporarily (n=15) or permanently (n=17) disqualified from competitive sports. The average cost per athlete was €79, which consisted of €64 (80%) for first-line evaluations and €15 (20%) for additional investigations. CONCLUSION: PPE according to the Italian model identified a range of diseases in 2.0% of apparently healthy athletes at an average cost of €79.